1Psychiatry Res 2000 Aug 99: 93-110
PMID10963985
TitleEvidence of a smaller left hippocampus and left temporal horn in both patients with first episode schizophrenia and normal control subjects.
AbstractFindings from cerebral magnetic resonance imaging (MRI) studies in schizophrenia indicating temporal lobe involvement have been inconsistent and controversial. In a prospective study, we quantified the volumes of temporal lobe structures in 20 male patients with first episode schizophrenia (FES; mean+/-S.D.=27.4+/-4. 8 years) and 20 healthy age-matched male control subjects (27.7+/-3. 1 years). Measurements were performed on contiguous 2.2-mm coronal MRI slices, which included, as well as the temporal lobe, the amygdala, the hippocampal formation, and the temporal horn of the lateral ventricle. The definition of the borders of the structures relied on measurement guidelines derived from mutual comparisons of MRI and histological data. The definition of the hippocampus-amygdala interface was also validated in a correlated triplanar display. We did not detect any significant volume reductions of the measured structures in the FES group, as compared with healthy control subjects, on either side. Comparisons within groups, however, revealed that in both the patients and the healthy volunteers the hippocampal formations showed a significant right-sided bias (+9%, P=0.004, in the FES group; +12%, P=0.0003 in the control subjects). A significant volume difference in favor of the right hemisphere was also observed in the temporal horns of the lateral ventricles (+17%, P=0.02 in the patients with FES; +34%, P=0. 003, in the control group). There was only a nonsignificant trend for a larger temporal horn on the left side in patients with schizophrenia as compared with the control subjects. Our findings do not indicate a loss or reversal of the normal volume asymmetry pattern in the FES group.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
2Neuroreport 2001 Sep 12: 2801-6
PMID11588580
TitleImpaired P600 in neuroleptic naive patients with first-episode schizophrenia.
AbstractDeficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
3Neuroreport 2001 Sep 12: 2801-6
PMID11588580
TitleImpaired P600 in neuroleptic naive patients with first-episode schizophrenia.
AbstractDeficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
4Neuroreport 2001 Sep 12: 2801-6
PMID11588580
TitleImpaired P600 in neuroleptic naive patients with first-episode schizophrenia.
AbstractDeficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
5J Int Neuropsychol Soc 2003 Mar 9: 384-93
PMID12666763
TitleCategory fluency in first-episode schizophrenia.
AbstractAnimal word list generation (ANWLG) was administered to 47 first-episode schizophrenia (FES) participants and 31 controls. Fifty-nine left temporal lobe epilepsy (LTLE) participants were included as a comparison group with known temporal lobe damage and expected semantic deficits. Semantic knowledge was assessed with the Association Index (AI), a measure of the semantic relatedness of all consecutive ANWLG responses. Neuropsychological tests of language and executive functioning were also administered. Results showed that both FES and LTLE groups generated fewer ANWLG responses than controls, but only the LTLE participants obtained a lower AI relative to controls. FES participants did not differ from controls on the AI. FES and LTLE groups produced fewer semantic subcategories (clusters), however, only the LTLE group produced fewer words per subcategory compared to controls (cluster size). FES participants produced a higher rate of perseverative responses compared to the other groups. Finally, correlation analyses showed that for FES participants both executive and language tests significantly correlated with ANWLG total responses, while the correlation between ANWLG and only 1 language test was significant for LTLE participants. Taken together, the results suggest that reduced ANWLG output in FES participants may be best conceptualized as a deficit in the executive component of word list generation (i.e., semantic search/access, response monitoring) or global cognitive impairment.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
6Schizophr. Res. 2004 Dec 71: 323-30
PMID15474902
TitleNeuropsychological correlates of symptom profiles in first episode schizophrenia.
AbstractThis paper aimed to examine the relationship between the trichotomous symptom structure of psychopathology and neuropsychological functioning in young people with first episode schizophrenia (FES), most of whom were receiving atypical antipsychotic medication. This was with a view to providing insight into the underlying pathophysiology of the clinical symptoms of schizophrenia. Fifty-three young people (aged 13-25 years) with FES participated in the study. Subjects completed a comprehensive clinical and neuropsychological examination. Cognitive domain scores were correlated with composite scores relating to Disorganisation, Psychomotor Poverty and Reality Distortion. A significant association was identified between Disorganisation and Verbal Acquisition, Verbal Recall and Cognitive Flexibility. There were no significant associations between cognitive domains and either Reality Distortion or Psychomotor Poverty, nor with measures of depressive symptomatology. The present study provides preliminary evidence that symptoms associated with the Disorganisation factor are significantly associated with cognitive deficits suggesting impaired frontal-temporal functioning. Differences between the current findings and those of similar research may reflect the effects of different medication regimes, as well as the absence of illness chronicity.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
7Psychiatry Res 2004 Jan 121: 303-7
PMID14675749
TitleAcademic deterioration prior to first episode schizophrenia in young Singaporean males.
AbstractThere has been relatively little study of the longitudinal course of cognitive functioning before the onset of schizophrenia. We report scores from standardized academic examinations at ages 12 and 16 years of 30 male patients with a first episode of schizophrenia (FES) and a normal control group balanced for gender, age, parental socio-economic class and academic scores at age 12. The FES group had greater deterioration in mathematics scores and poorer educational outcome, possibly reflecting neurocognitive changes that preceded the onset of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
8Psychiatry Res 2005 Aug 139: 229-38
PMID16055311
TitleGrey matter deficits and symptom profile in first episode schizophrenia.
AbstractSeveral studies have investigated grey matter reductions in first episode schizophrenia (FES), but few have examined the relationship between grey matter reduction and clinical profile. A group of 31 patients with strictly defined FES and 30 healthy controls underwent T1-weighted magnetic resonance imaging (MRI) scan. Voxel-based morphometry in SPM99 was used to identify four distinct regions of grey matter reduction in the FES subjects. The regions of interest (ROIs) were in the left ventral prefrontal cortex (ROI 1), left parietal and temporal cortices (ROI 2), right cerebellum (ROI 3), and right frontal and parietal cortices (ROI 4). These regions of reduction were transformed into binary masks, which were convolved with patients' pre-processed grey matter images. Patients' grey matter volumes in these regions were correlated with their composite scores on the following three symptom dimensions: Psychomotor Poverty, Disorganization and Reality Distortion. The volumes of ROIs 1, 2 and 4 were found to be significantly correlated with the Reality Distortion syndrome score. Our findings indicate that distinct, widespread grey matter reductions are present very early in the course of schizophrenia. The results also suggest a possible structural underpinning for the abnormal brain activity typically associated with symptoms of Reality Distortion.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
9Prog. Neuropsychopharmacol. Biol. Psychiatry 2006 Dec 30: 1426-34
PMID16828218
TitleNovelty P3 and P3b in first-episode schizophrenia and chronic schizophrenia.
AbstractThe objective of this study was to evaluate P3b and novelty P3 responses in patients with first-episode schizophrenia (FES) and chronic schizophrenia (CS). P3b is consistently reported to be reduced in CS. However, novelty P3 results in CS are controversial. Novelty P3 is not studied, and there are only a few P3b studies in patients with FES. Subject groups comprised 31 patients with FES and 36 younger control subjects, and 26 patients with CS and 35 older control subjects. Automatically elicited auditory novelty P3 and effortfully elicited auditory P3b potentials were assessed. P3b amplitudes were reduced in both patients with FES and CS relative to their controls. CS and FES patients did not differ in P3b amplitude. Novelty P3 amplitude was reduced in patients with CS. Novelty P3 amplitude in patients with FES did not differ from their controls. P3b amplitude reduction may be a trait marker of schizophrenia and may not progress over the course of illness, although this can only be definitively determined by longitudinal studies. Novelty P3 amplitude reduction present in patients with CS, is not found at the onset of illness. Novelty P3 seems unaffected early in the disease process.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
10Schizophr. Res. 2006 Dec 88: 82-9
PMID16904871
TitlePhysical comorbidity, insight, quality of life and global functioning in first episode schizophrenia: a 24-month, longitudinal outcome study.
AbstractThis prospective study sought to determine the clinical impact of physical comorbidity on patients with first episode schizophrenia (FES) and we tested the hypothesis that patients with physical comorbidity were associated with poorer clinical and functional outcomes. The severity of psychopathology, insight, social/occupational functioning and quality of life were evaluated using Positive And Negative Syndrome Scale (PANSS), Scale to assess Unawareness of Mental Disorder, Global Assessment of Functioning Scale (GAF), and World Health Organisation Quality of Life-Bref Scale (WHOQOL-Bref) respectively at baseline and at 6, 12, 18 and 24 months. Out of 142 patients, physical comorbidity was present in 21.8% (n=31) of the patients, and they were mainly related to the cardiovascular, respiratory and endocrine systems. Compared to baseline measurements, patients with physical comorbidity had greater awareness into the consequences of their psychiatric illness at 12 months, the need for treatment at 12 and 18 months, and better improvement of PANSS total and general psychopathology subscale scores at 24 months. FES patients with physical comorbidity also had less reduction in their WHOQOL-Bref scores in the physical health domain at 12 and 18 months and greater increase in the GAF scores at 18 and 24 months, indicating better subjective rating of quality of life and objective measure of their global functioning prospectively. Clinicians need to be aware of the substantial rates of physical comorbidity in FES patients which may not be necessarily associated with worse longitudinal outcomes and the findings should encourage even greater efforts at early identification and management of these physical conditions.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
11J Psychiatr Res 2006 Oct 40: 656-63
PMID16904688
TitlePsychiatric comorbidity in first episode schizophrenia: a 2 year, longitudinal outcome study.
AbstractWe have previously documented a high prevalence of Axis I psychiatric comorbidity in our patients with first episode psychosis. This study sought to determine the longitudinal impact of Axis I psychiatric comorbidity on patients with first episode schizophrenia (FES) and we hypothesised that patients with psychiatric comorbidity were associated with poorer clinical and functional outcomes.
One hundred and forty two consecutively hospitalized FES patients were included. Socio-demographic information was obtained and the PANSS, SUMD, GAF, WHOQOL-Bref were used to assess psychopathology, insight, social/occupational functioning and quality of life respectively at baseline and at 6, 12, 18 and 24 months after discharge.
Over time and compared with baseline scores, patients with Axis I psychiatric comorbidity (n=46, 32.4%) had significantly less reduction of their PANSS total and subscale scores, less improvement in their awareness of their psychiatric illnesses and symptoms at 12, 18 and 24 months and poorer insight into the consequences of their illness at 18 and 24 months. Poor insight at baseline was correlated positively with PANSS negative symptom subdomain, and negatively with GAF at 24 months.
Axis I Psychiatric comorbidity was associated with worse prospective outcomes in hospitalized patients with first episode schizophrenia, and this highlights a greater need towards the early recognition and management of these conditions.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
12Neuroimage 2006 Aug 32: 511-9
PMID16677830
TitleProgressive grey matter atrophy over the first 2-3 years of illness in first-episode schizophrenia: a tensor-based morphometry study.
AbstractLittle is known about the structural brain changes that occur over the first few years of schizophrenia, or how these changes differ from those associated with healthy brain development in adolescence and early adulthood. In this study, we aimed to identify regional differences in grey matter (GM) volume between patients with first-episode schizophrenia (FES) and matched healthy controls, both at the time of the patients' first psychotic episode (baseline condition) and 2-3 years subsequently (follow-up condition). Forty-one patients with FES and 47 matched healthy controls underwent a T1-weighted structural MRI scan. Of these participants, 25 FES patients and 26 controls returned 2-3 years later for a follow-up scan. Voxel-based morphometry in SPM2 was used to identify the regions of GM difference between the groups in the baseline condition, while tensor-based morphometry was used to identify the longitudinal change within subject over the follow-up interval. The FES patients exhibited widespread GM reductions in the frontal, parietal, and temporal cortices and cerebellum in the baseline condition, as well as more circumscribed regions of GM increase, particularly in the occipital lobe. Furthermore, the FES subjects were observed to lose considerably more GM over the follow-up interval than the controls, especially in the parietal and temporal cortices. We argue that the progressive GM atrophy we have found to be associated with the onset of schizophrenia arises from a dysfunction in the dramatic period of healthy brain development typically associated with adolescence.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
13Neurosci. Lett. 2007 May 417: 297-302
PMID17399900
TitleFunctional dysconnectivity of the dorsolateral prefrontal cortex in first-episode schizophrenia using resting-state fMRI.
AbstractThe known regional abnormality of the dorsolateral prefrontal cortex (DLPFC) and its role in various neural circuits in schizophrenia has given prominence to its importance in studies on the dysconnection associated with schizophrenia. Abnormal functional connectivities of the DLPFC have been found during various goal-directed tasks; however, the occurrence of the abnormality during rest in patients with schizophrenia has rarely been reported. In the present study, we selected bilateral Brodmann's area 46 as region of interest and analyzed the differences in the DLPFC functional connectivity pattern between 17 patients with first-episode schizophrenia (FES) and 17 matched controls using resting-state fMRI. We found that the bilateral DLPFC showed reduced functional connectivities to the parietal lobe, posterior cingulate cortex, thalamus and striatum in FES patients. We also found enhanced functional connectivity between the left DLPFC and the left mid-posterior temporal lobe and the paralimbic regions in FES patients. Our results suggest that functional dysconnectivity associated with the DLPFC exists in schizophrenia during rest. This may be partially related to disturbance in the intrinsic brain activity.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
14Prog. Neuropsychopharmacol. Biol. Psychiatry 2008 Dec 32: 1952-6
PMID18929611
TitleP50 gating at acute and post-acute phases of first-episode schizophrenia.
AbstractDeficit in P50 sensory gating has repeatedly been shown in schizophrenia. In order to determine the contribution of trait and/or state features to P50 gating deficit in schizophrenia we evaluated the P50 gating in patients with first-episode schizophrenia (FES) at acute and post-acute phases. Subject groups comprised 16 patients with FES and 24 healthy controls. Patients were tested at the acute phase of the illness and retested at the post-acute phase when their positive symptoms improved. During the testing at the acute phase five patients were neuroleptic-naive and the others were taking atypical antipsychotics which were started recently in order to control the acute excitation. Patients were receiving risperidone, olanzapine or quetiapine treatment at the post-acute phase. P50 gating was impaired in patients at the acute phase compared to controls. However, at the post-acute phase P50 gating was increased compared to the acute phase, reaching to the gating values of controls. P50 gating improvement might be emerged from atypical antipsychotic medication, although this can only be definitively determined by randomized studies including different antipsychotics.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
15Schizophr. Res. 2008 Feb 99: 1-6
PMID18248793
TitleCannabis use and brain structural alterations in first episode schizophrenia--a region of interest, voxel based morphometric study.
AbstractStructural alterations of the brain in schizophrenia have been associated with genetic and environmental factors. Among the environmental factors, cannabis use has been associated with increased risk for patients with schizophrenia, but the effect of cannabis on their brain structure is unclear. We examined gray matter alterations in first episode schizophrenia patients (FES) with cannabis use (FES+C; n=15) compared to FES without cannabis use (FES-C; n=24) and 42 healthy controls who did not use cannabis. We conducted a voxel based morphometric analysis of a priori determined regions of interest consisting of the CB1 receptor rich brain regions. We observed a decrease in gray matter density in the right posterior cingulate cortex (PCC) in FES+C when compared with FES-C. The results suggest that cannabis use may be associated with altered brain structure, in particular regions rich in CB1 receptors. These findings need to be confirmed by larger, prospective studies.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
16J. Nerv. Ment. Dis. 2008 Jan 196: 67-70
PMID18195644
TitlePreserved orbitofrontal function in first-episode schizophrenia: further evidence from the object alternation paradigm.
AbstractNeuropsychological literature indicates that performance on Object Alternation Task (OAT) can be linked to the orbitofrontal cortex (OFC). Patients with chronic schizophrenia perform poorly on behavioral and neuropsychological tasks related to OFC functions. In a previous study using the Iowa Gambling Task, we found unimpaired performance in a sample of individuals with first-episode schizophrenia (FES) spectrum disorders. In this study, we aimed to extend our study of OFC functions by using the OAT paradigm, to determine whether there are abnormalities in the early phases of schizophrenia. We examined the performance of 70 patients with FES and 21 healthy controls on a computerized version of OAT. There were no significant differences between patients and control subjects with respect to the OAT. This finding suggests that the OFC function, as measured by decision-making tasks, is preserved in the early phases of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
17Schizophr. Res. 2008 Sep 104: 44-60
PMID18703313
TitleStructural brain alterations at different stages of schizophrenia: a voxel-based morphometric study.
AbstractStructural alterations in schizophrenia have mainly been regarded as the result of neurodevelopmental processes. However, it remains unresolved whether the pattern of morphological brain changes differs between different stages of disease. We examined structural brain changes in 93 first-episode (FES) and 72 recurrently ill (REZ) patients with schizophrenia (SZ) and 175 matched healthy control subjects (HC) using cross-sectional and conjunctional voxel-based morphometry (VBM) of whole-brain MRI data in a three-step approach. We found significant grey matter density (GMD) reductions in FES compared to HC bilaterally in the temporal and prefrontal areas, including the anterior cingulate gyrus, as well as in both thalami. Hippocampus and amygdala were affected on the left side (P<0.05, corrected). In REZ patients this pattern was spatially extended. The basal ganglia were exclusively reduced in the recurrently ill group compared to controls. Common to both disease groups were reductions in the bilateral perisylvian regions, the opercular region, the insula, prefrontal cortex, left inferior temporal gyrus, limbic system including hippocampus and amygdala, and the thalami. In FES patients there were no regions affected that were not also affected in REZ patients. In contrast, REZ patients showed extended alterations within the frontal and temporal regions, the hippocampus, amygdala and exclusively in the basal ganglia relative to the FES patients. Our findings suggest a system-specific involvement of neuronal networks in schizophrenia. Furthermore, our data suggest that in the advanced stages of schizophrenia additional cortical and subcortical brain areas become involved in the disease process. Longitudinal data will be required to further test this hypothesis.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
18Prog. Neuropsychopharmacol. Biol. Psychiatry 2008 Feb 32: 531-8
PMID18061326
TitleInvestigating the neuropsychological and neuroanatomical changes that occur over the first 2-3 years of illness in patients with first-episode schizophrenia.
AbstractThis study explored the concurrent courses of the neuroanatomical and neuropsychological changes that occurred over the first 2-3 years of illness in patients with first-episode schizophrenia (FES).
Fifty-two patients with FES underwent neuropsychological testing and a structural magnetic resonance imaging (sMRI) scan within three months of their first presentation to mental health services with psychotic symptoms (time1). Patients' cognitive performance was evaluated via an extensive neuropsychological test battery, which assessed 9 cognitive domains. Of the 52 patients at time1, 32 returned 2-3 years later (time2) for follow-up neuropsychological testing, and 20 of these also underwent follow-up sMRI. MR images were preprocessed in SPM99. Grey matter volumes of patients' whole-brain, frontal lobes and temporal lobes were calculated by convolving the preprocessed images with manually-drawn binary masks.
Patients exhibited longitudinal improvements in full-scale IQ, performance IQ and visual memory. In contrast, concurrent reductions in grey matter were observed for the whole-brain (3% reduction) and the frontal lobe (3.65% reduction). Furthermore, the extent of patients' whole-brain and frontal-lobe grey matter changes were positively correlated with longitudinal changes in verbal learning and memory.
The results of this study suggest that while the early stages of schizophrenia are associated with a mild improvement in patients' overall cognitive functioning, they are also associated with progressive grey matter atrophy.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
19Schizophr. Res. 2008 Feb 99: 182-91
PMID18053688
TitleGeneral and social cognition in first episode schizophrenia: identification of separable factors and prediction of functional outcome using the IntegNeuro test battery.
AbstractIt is increasingly recognized that cognitive assessments, unlike symptom ratings, provide a reliable predictor of functional outcome in schizophrenia. This study evaluated the utility of the 'IntegNeuro' computerized test battery for assessing cognition in first episode schizophrenia. We determined the presence of separable factors of general and social cognition, their equivalence to the consensus domains identified by the NIMH MATRICS project, and their effectiveness in predicting real world functional outcomes.
Fifty six first episode schizophrenia (FES) patients and 112 matched healthy controls were assessed on the touchscreen-based 'IntegNeuro' cognitive test battery and FES patients for social functioning (SOFAS) and quality of life (WHOQOL-BREF).
Principal components analysis identified i) six factors corresponding to MATRICS domains of general cognition ('Information Processing Speed', 'Verbal Recall', 'Working Memory Capacity', 'Sustained Attention/Vigilance', 'Verbal Processing', 'Executive Function'), ii) an 'Emotional Intelligence' factor corresponding to the MATRICS social cognition domain, and iii) an additional 'Sensori-Motor Function' factor of general cognition and 'Negativity' factor of social cognition. Patients showed impairments relative to controls across all factors, but especially for Working Memory Capacity, followed by Verbal Memory, Sustained Attention/Vigilance and Negativity. These factors strongly predicted poorer social functioning in FES, along with poorer quality of life in psychological, social, and health satisfaction facets.
The IntegNeuro battery has utility for assessing separable domains of general and social cognition in FES, which are predictive of real world outcomes. Thus, it may be appropriate for clinical application, including in multi-center trials targeting new treatments for cognition in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
20Schizophr. Res. 2009 Dec 115: 163-72
PMID19837566
TitleGrey and white matter abnormalities are associated with impaired spatial working memory ability in first-episode schizophrenia.
AbstractSpatial working memory (SWM) dysfunction has been suggested as a trait marker of schizophrenia and implicates a diffuse network involving prefrontal, temporal and parietal cortices. However, structural abnormalities in both grey and white matter in relation to SWM deficits are largely unexplored. The current magnetic resonance imaging (MRI) study examined this relationship in a sample of young first-episode schizophrenia (FES) patients using a whole-brain voxel-based method. SWM ability of 21 FES patients and 41 comparable controls was assessed by the CANTAB SWM task. Using an automated morphometric analysis of brain MRI scans, we assessed the relationship between SWM abilities and both grey matter volume and white matter density in both groups. Our findings demonstrated the different directionality of the association between SWM errors and grey matter volume in left frontal regions and white matter tracts connecting these regions with temporal and occipital areas between FES patients and controls. This suggests that the substrate underpinning the normal variability in SWM function in healthy individuals may be abnormal in FES, and that the normal neurodevelopmental processes that drive the development of SWM networks are disrupted in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
21Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Nov 33: 1438-46
PMID19647777
TitleGray matter morphology and the level of functioning in one-year follow-up of first-episode schizophrenia patients.
Abstractschizophrenia is a condition with a highly variable course that is hard to predict. The aim of the present study was to investigate if local gray matter volume (GMV) can differentiate poor (PF) and good (GF) functioning patients using voxel-wise analysis in a group of first-episode schizophrenia subjects (FES).
32 FES male patients were assessed twice: at the time of the first episode of schizophrenia and one year later. 18 healthy controls matched for age, gender, and handedness were also included. Local gray matter volume was analyzed using voxel-wise full-factorial design with factors group (GF, PF) and time.
FES subjects had bilateral gray matter reduction in the lateral prefrontal cortex as compared with healthy controls. PF subjects had smaller GMV in the left orbitofrontal and frontopolar cortex.
GMV in the left prefrontal cortex differentiates later poor and good functioning schizophrenia patients. Morphological analysis might be considered a candidate for a biological marker in outcome prediction. However, the small sample size, and the lack of female subjects limit generalization of results. Moreover, studies analyzing the predictive value of brain morphology on a single-subject level should be performed to assess its real usefulness in outcome prediction.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
22Clin Neurophysiol 2009 Sep 120: 1667-82
PMID19646922
TitleSpatio-temporal EEG waves in first episode schizophrenia.
Abstractschizophrenia is characterized by a deficit in context processing, with physiological correlates of hypofrontality and reduced amplitude P3b event-related potentials. We hypothesized an additional physiological correlate: differences in the spatio-temporal dynamics of cortical activity along the anterior-posterior axis of the scalp.
This study assessed latency topographies of spatio-temporal waves under task conditions that elicit the P3b. EEG was recorded during separate auditory and visual tasks. Event-related spatio-temporal waves were quantified from scalp EEG of subjects with first episode schizophrenia (FES) and matched controls.
The P3b-related task conditions elicited a peak in spatio-temporal waves in the delta band at a similar latency to the P3b event-related potential. Subjects with FES had fewer episodes of anterior to posterior waves in the 2-4 Hz band compared to controls. Within the FES group, a tendency for fewer episodes of anterior to posterior waves was associated with high Psychomotor Poverty symptom factor scores.
Subjects with FES had altered global EEG dynamics along the anterior-posterior axis during task conditions involving context update.
The directional nature of this finding and its association with Psychomotor Poverty suggest this result is related to findings of hypofrontality in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
23Psychiatry Res 2009 Jun 172: 175-9
PMID19395244
TitleDelusions and dorso-medial frontal cortex volume in first-episode schizophrenia: a voxel-based morphometry study.
AbstractOf the few studies that have directly investigated the neuroanatomical correlates of delusions in patients with recent-onset schizophrenia, a number have paradoxically reported a positive correlation between delusion severity and regional grey matter volume. In order to explore this relationship, 31 patients with first-episode schizophrenia (FES) underwent a clinical interview and a T1-weighted structural MRI scan. Patients' scores on the Delusions subscale of the Positive and Negative Syndrome Scale were correlated with the volume of every voxel in their grey matter images in SPM99. Patients' delusion scores were found to correlate with the volume of a cluster of voxels located in the dorso-medial frontal cortex, centred on the medial frontal gyrus. Post-hoc analysis revealed that this 'region-of-correlation' was volumetrically reduced in the FES patients relative to a group of 21 matched healthy controls. The results of this study support the hypothesis that while a certain level of structural brain atrophy is necessary for delusion formation in patients with FES, excessive structural atrophy may in fact preclude the formation of highly systematized delusions.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
24Neuroimage 2009 Oct 47: 1163-71
PMID19375511
TitleCombined analyses of thalamic volume, shape and white matter integrity in first-episode schizophrenia.
AbstractThe thalamus has been considered to be integral to the pathophysiology of schizophrenia. To determine whether its anatomical abnormalities may be associated with cognitive deficits in the onset of schizophrenia, we assessed thalamic volume, shape, white matter integrity, and their correlations with cognition in patients with first-episode schizophrenia. T1-weighted magnetic resonance and diffusion tensor (DT) images were collected in 49 healthy comparison controls (CON) and 32 patients with FES (FES). Large deformation diffeomorphic metric mapping (LDDMM) algorithms were used to delineate and assess the thalamic shape from MRI scans. The thalamic white matter integrity was quantified by fractional anisotropy (FA) and mean diffusivity (MD) averaged over the thalamus using DTI. Our analysis revealed that FES did not differ from CON in FA and MD but did differ markedly from them in the thalamic volume and shape. Patients with FES also performed poorly in spatial working memory and executive tasks. The correlation study found that regional thalamic shapes highly correlate with the two cognitive scores in the entire sample and healthy comparison controls but not in patients with FES even though no correlation was found between the thalamic volumes with the two cognitive scores in any group. Left thalamic FA was correlated with spatial working memory deficits in FES. Our findings suggest that thalamic volume and shape abnormalities are evident at the onset of FES prior to thalamic abnormal white matter integrity. Altered microstructural white matter integrity assessed using DTI may not be apparent in FES but may be observed as the disease progresses. Cognitive deficits related to spatial working memory and executive functioning in FES were observed in the context of loss of their normal relationship with the thalamic shapes, that is, regionally-specific thalamic shape compression is associated with poor performance in executive functioning and spatial working memory.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
25Zhonghua Yi Xue Za Zhi 2010 Aug 90: 2026-9
PMID21029637
Title[N400 changes elicited by Chinese sentences in first episode schizophrenia].
AbstractTo explore N400 changes elicited by Chinese sentences ending with matching (congruent) or mismatching (incongruent) words in first episode schizophrenia.
ERP (event-related potentials) component N400 were recorded by an ERP device in 56 first episode schizophrenia (FES) and 62 normal controls (NC) according to a paradigm of Chinese sentences ending with matching or mismatching words.
(1) Latencies: compared with NC, FES showed prolonged N400 latencies in five areas at pre-treatment: in Cz. The latencies were (358 ms ± 32 ms vs 394 ms ± 45 ms, P < 0.01) in congruent and (410 ms ± 29 ms vs 446 ms ± 35 ms, P < 0.01) in incongruent situation. And so did in Fz, Pz, C3 and C4; (2) amplitudes: compared with NC, FES also showed smaller N400 amplitudes in five areas at pre-treatment. The amplitudes were (8.6 µV ± 5.1 µV vs 5.2 µV ± 4.6 µV, P < 0.01) in congruent and (13.4 µV ± 6.7 µV vs 8.5 µV ± 5.9 µV, P < 0.01) in incongruent situation. And so did in Fz, Pz, C3 and C4; (3) the prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS.
With clear priming effect in first episode schizophrenia, Chinese sentences are suitable stimuli in N400 experiment. They may be used for further study of neural mechanism and early diagnosis of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
26Schizophr. Res. 2010 Jun 119: 61-4
PMID20409692
TitleDisrupted integrity of the fornix in first-episode schizophrenia.
AbstractAlterations of the fornix in chronic patients with psychosis are well established, but its integrity in the early stage of schizophrenia remains unknown. Thirty-two patients experiencing first-episode schizophrenia (FES) and 25 matched controls completed a DTI scan. DTI-tractography was used to estimate fractional anisotropy (FA) in bilateral fornices. The analysis showed significant overall FA reductions in the fornix in FES patients relative to controls. No significant correlations were found between FA values and clinical and sociodemographic data in FES patients. These findings revealed slight alterations along the fornix in early stage of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
27Neuroimage 2010 Feb 49: 2901-6
PMID19963069
TitleLocalization of cerebral functional deficits in treatment-naive, first-episode schizophrenia using resting-state fMRI.
AbstractSpontaneous low-frequency fluctuations (LFF) in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal have been shown to reflect cerebral spontaneous neural activity, and the present study attempts to explore the functional changes in the regional brain in patients with schizophrenia using the amplitude of the BOLD signals.
A total of 66 treatment-naïve, first-episode schizophrenia (FES) patients and 66 normal age- and sex-matched controls were recruited. Resting-state fMRIs were obtained using a gradient-echo echo-planar imaging sequence. The amplitude of LFF (ALFF) was calculated using REST software. Voxel-based analysis of the ALFF maps between control and patient groups was performed with twos-sample t-tests using SPM2.
Compared to the controls, the FES group showed significantly decreased ALFF in the medial prefrontal lobe (MPFC) and significant increases in the ALFF in the left and right putamen. Significant positive correlations were observed between ALFF values in the bilateral putamen in both the patient and control groups.
Alterations of the ALFF in the MPFC and putamen in FES observed in the present study suggest that the functional abnormalities of those areas are at an early stage of the disease.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
28Psychol Med 2010 Jun 40: 935-44
PMID19751542
TitlePrognostic value of cognitive functioning for global functional recovery in first-episode schizophrenia.
AbstractIt has become widely accepted that cognitive deficits in schizophrenia are related to functional outcome. However, it remains to be seen whether these associations are relevant for predicting which cases will have a global functional recovery. In this study, we attempt to determine whether global functional recovery (integrating social and occupational outcomes) after first-episode schizophrenia (FES) can be predicted by cognitive variables.
A total of 131 FES patients with functional deficits (n=97) and functional recovery (n=34) as determined at 1-year follow-up were examined. Neuropsychological, sociodemographic, pre-morbid and clinical data at baseline were analysed using independent groups comparisons and a logistic regression method.
Sustained attention and negative symptoms emerged as significant predictors of good global functional outcome. Although the model revealed a high accuracy (91%) in the classification of patients with functional deficits, it was unacceptably low (26%) in the classification of patients with global functional recovery.
The limitations found in the prediction of a favourable global functional outcome may well be an indication for a need to address the role of other factors not commonly included in longitudinal studies of long-term outcomes in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
29Early Interv Psychiatry 2010 Aug 4: 243-50
PMID20712730
TitleReshaping an enduring sense of self: the process of recovery from a first episode of schizophrenia.
AbstractAlthough advances in the treatment of schizophrenia have been made, little is known about the process of recovery from first episode of schizophrenia (FES). To date, the study of recovery in the field of mental health has focused on long-term mental illness. This qualitative study addresses ways in which individuals with FES describe their process of recovery and how identified individuals (e.g. family members) describe their perceptions of and roles in the participant's process of recovery.
Charmaz's constructivist grounded theory methodology was used to interview 10 young adults twice who self-identified as recovering from FES. In addition, 10 individuals were identified who had influenced their recovery and were interviewed once, for a total of 30 interviews. Data collection sources included in-depth semi-structured interviews. Data analysis methods were consistent with Charmaz's methodology and included coding, and constant comparison of data.
The results provide a substantive theory of the process of recovery from FES that is comprised of the following phases: 'Who they were prior to the illness', 'Lives interrupted: Encountering the illness', 'Engaging in services and supports', 'Re-engaging in life', 'Envisioning the future'; and the core category, 'Re-shaping an enduring sense of self', that occurred throughout all phases. A prominent feature of this model is that participants' enduring sense of self were reshaped rather than reconstructed throughout their recovery.
This model of recovery from FES is unique, and as such, provides implications for clinical care, research and policy development for these young adults and their families.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
30Psychopathology 2010 -1 43: 312-8
PMID20664307
TitleFamily environment and pediatric major depressive disorder.
AbstractThe risks for depression broadly include biological and environmental factors. Furthermore, having a family member suffering from major depression is also likely to have consequences for the family environment. Further research aimed at understanding the effects of having a child with major depression on family interaction patterns is warranted.
We studied 31 families with an 8- to 17-year-old child (mean age +/- SD = 12.9 +/- 2.7 years) who met the DSM-IV criteria for major depressive disorder (MDD) and 34 families with no mentally ill children (mean age +/- SD = 12.6 +/- 2.9 years) or parents. Children and their parents were assessed with the K-SADS-PL (Kiddie Schedule for Affective Disorders and schizophrenia--Present and Lifetime Version) interview. Parents completed the Moos Family Environment Scale (FES) to assess their perceptions of current family functioning. Data were analyzed using the nonparametric Wilcoxon-Mann-Whitney test.
Families of MDD children showed significantly different patterns of family functioning on FES subscales representing relationships and personal growth dimensions. The families with MDD children showed higher levels of conflict (p < 0.001) and lower levels of cohesion (p < 0.001), expressiveness (p = 0.003) and active-recreational orientation (p = 0.02) compared to the families without mentally ill children.
Families with MDD children show a lower degree of commitment, provide less support to one another, provide less encouragement to express feelings and have more conflicts compared to families with no mentally ill children or parents. Interventions aimed at improving family dynamics may be beneficial to MDD children and their families.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
31Schizophr. Res. 2010 Sep 122: 72-80
PMID20630708
TitleNeural markers of remission in first-episode schizophrenia: a volumetric neuroimaging study of the hippocampus and amygdala.
AbstractThe temporolimbic region has been implicated in the pathophysiology in schizophrenia. More specifically, significantly smaller hippocampal volumes but not amygdala volumes have been identified at onset in first-episode schizophrenia (FES) patients. However, volumetric differences (namely, in the hippocampus) exhibit an ambiguous relationship with long-term outcome. So, we examined the relationship between hippocampus and amygdala volumes and early remission status.
We compared hippocampus and amygdala volumes between 40 non-remitted and 17 remitted FES patients and 57 healthy controls. Amygdala and hippocampus were manually traced with the hippocampus additionally segmented into three parts: body, head, and tail. Remission was defined as mild or less on both positive and negative symptoms over a period of 6 consecutive months as per the 2005 Remission in schizophrenia Working Group criteria.
A significant [group x structure x side] interaction revealed outcome groups differed in hippocampus tail volumes; significantly on the left (non-remitted=694+/-175 mm(3); remitted=855+/-133 mm(3); p=0.001) with a trend difference on the right (non-remitted=723+/-162 mm(3); remitted=833+/-126 mm(3); p=0.023). Groups did not differ in body, head, or amygdala volumes bi-laterally.
A smaller hippocampal tail volume may represent a neural marker in FES patients who do not achieve early remission after the first 6 months of treatment. The early identification of patients with poor outcome with respect to the hippocampus tail may encourage the search for new, more target-specific, medications in hope of improving outcome and moving us towards a better understanding of the pathophysiology of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
32Schizophr. Res. 2010 Jun 119: 18-26
PMID20335007
TitleFirst-episode schizophrenia patients neuropsychologically within the normal limits: evidence of deterioration in speed of processing.
AbstractIn apparent contradiction to the notion of cognitive impairment as a core feature of schizophrenia, some studies have described a subgroup of patients neuropsychologically within normal limits. It remains to be determined whether this subgroup has intact cognitive functioning or a higher premorbid functioning that attenuates the evidence of deterioration. Out of a total of 111 patients with FES or schizophreniform disorder, 25 (23%) were classified as cognitive normal (CN) according to criteria based on performance in six basic cognitive dimensions and an overall composite score, and their cognitive profile was compared with that of 28 controls. The CN subgroup had better social premorbid adjustment and had a higher premorbid IQ than the cognitive impaired subgroup. There were no differences in the other pretreatment variables examined. The CN subgroup performed similarly to controls in the cognitive dimensions, including sustained attention, verbal memory and executive functions. These profiles remained mostly unaltered after controlling for premorbid IQ. The cognitive deterioration index, calculated by ratio of performance in general knowledge and vocabulary abilities to a measure of processing speed , showed that both patient subgroups had similar levels of deterioration and that this was significantly different to that of controls. Although FES patients performed within normal limits and better than cognitive impaired patients in a processing speed task, they did nevertheless display a pattern of deterioration in processing speed (in relation to their premorbid IQ) equivalent to that of those with marked impairments.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
33Psychiatry Res 2011 Aug 189: 33-7
PMID21196051
TitleRemission after first-episode schizophrenia: results of a long-term follow-up.
AbstractThe aim of this study was to identify the rate and predictors of remission after first episode of schizophrenia (FES). Ninety-three FES patients were followed for at least 12 months and up to 12 years (mean=58.4 months) including monthly assessments with the Brief Psychiatric Rating Scale-Expanded (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative Symptoms (SANS). We also administered the Premorbid Adjustment Scale (PAS). We used the remission criteria recently defined by Andreasen et al. (2005). Fifty-six (59.5%) patients met the remission criteria in the first 24 months of the follow-up period, but 40 (71.5%) of these patients could not maintain their status. However, 23 (57%) of these patients later met the remission criteria again. The remission group patients achieved a higher rate of employment both in the first year and overall. In the logistic regression analysis, lower negative and higher positive symptoms at admission, lower positive symptoms at month 3 of the follow-up, medication compliance in the first 6 months, and occupational status during the last month before admission were found related to remission status. Our findings suggest that the remission group has advantages in terms of occupational status and symptom severity compared with their counterparts who did not achieve or maintain a state of remission.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
34Zhonghua Yi Xue Za Zhi 2011 Nov 91: 3040-3
PMID22333055
Title[Preliminary study on variations and neural generators of error-related negativity in first episode schizophrenics].
AbstractTo explore the variations and their activated brain areas of error-related negativity (ERN) in first episode schizophrenics.
ERN was tested by an ERP device and their activated brain areas were compared in 58 first episode schizophrenics (FES) and 62 normal controls (NC) from March 2010 to February 2011.
(1) The ERN latencies in the FES group were significantly longer on Cz (58 ± 14 ms), Fz (60 ± 11 ms), C3 (57 ± 17 ms) and C4 (60 ± 13 ms) electrodes compared with those in the NC group (49 ± 13 ms, 47 ± 13 ms, 50 ± 14 ms, 51 ± 12 ms). And the ERN amplitudes were significantly lower than those in the controls in Cz (5.0 ± 2.8 µV; 7.5 ± 3.1 µV, P < 0.01), C3 (5.5 ± 4.0 µV; 8.0 ± 3.7 µV, P < 0.01), Fz (5.0 ± 3.1 µV; 7.7 ± 3.8 µV, P < 0.01) and Pz (4.5 ± 3.3 µV: 7.5 ± 3.0 µV, P < 0.01) electrodes.(2) The variations of ERN latencies and amplitudes showed an insignificant correlation with the positive symptom scores and total scores of PANSS. (3) The activation levels of insula, superior temporal gyrus, middle temporal gyrus and inferior parietal lobule were obviously lower in the FES group than those in the NC group.
The anomalies of ERN latencies and amplitudes in first episode schizophrenics may reflect the deficient error-monitoring functions. Further studies are warranted. And such brain areas as insular may contribute pathogenically to the dysfunctions of error-monitoring in schizophrenics.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
35Neurosci. Lett. 2011 Sep 502: 173-7
PMID21827833
TitleSemantic fluency and executive functions as candidate endophenotypes for the early diagnosis of schizophrenia in Han Chinese.
AbstractNeurocognitive de?cits are recognized as core features of schizophrenia. The aim of this study was to compare the cognitive performance of antipsychotic, drug-naive patients with first-episode schizophrenia (FES patients) to their healthy siblings and to healthy controls from the Han Chinese population for exploring potential endophenotypes for the early detection of schizophrenia. A battery of cognitive assessment tools was used to measure seven cognitive domains in matched groups consisting of 56 subjects each. Cognitive tests included the grooved pegboard test (GPT), the category fluency test (CFT), the trail making test A (TMT-A), the Wechsler memory scale-III spatial span test (WMS-III SST), the Hopkins verbal learning test-revised (HVLT-R), the brief visuospatial memory test-revised (BVMT-R), the paced auditory serial addition test (PASAT), and the Wisconsin card sorting test-64 cards version (WCST-64). The performances of FEP patients were inferior to normal controls on all neuropsychological tests, while siblings were lower than healthy controls in many of the same tasks. Patients' performances were lower than siblings' on all tests except for the CFT, the WMS-III SST backward test, and four subtests of the WCST-64. Our data suggest that FEP patients exhibited pronounced impairment of fine motor skills, speed of processing, attention, verbal memory, visual memory, and executive function, while siblings exhibited deficits intermediate between those of schizophrenic patients and the control group. Semantic fluency function and executive function may be potential endophenotypes for the early diagnosis of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
36Neurosci. Lett. 2011 Sep 502: 173-7
PMID21827833
TitleSemantic fluency and executive functions as candidate endophenotypes for the early diagnosis of schizophrenia in Han Chinese.
AbstractNeurocognitive de?cits are recognized as core features of schizophrenia. The aim of this study was to compare the cognitive performance of antipsychotic, drug-naive patients with first-episode schizophrenia (FES patients) to their healthy siblings and to healthy controls from the Han Chinese population for exploring potential endophenotypes for the early detection of schizophrenia. A battery of cognitive assessment tools was used to measure seven cognitive domains in matched groups consisting of 56 subjects each. Cognitive tests included the grooved pegboard test (GPT), the category fluency test (CFT), the trail making test A (TMT-A), the Wechsler memory scale-III spatial span test (WMS-III SST), the Hopkins verbal learning test-revised (HVLT-R), the brief visuospatial memory test-revised (BVMT-R), the paced auditory serial addition test (PASAT), and the Wisconsin card sorting test-64 cards version (WCST-64). The performances of FEP patients were inferior to normal controls on all neuropsychological tests, while siblings were lower than healthy controls in many of the same tasks. Patients' performances were lower than siblings' on all tests except for the CFT, the WMS-III SST backward test, and four subtests of the WCST-64. Our data suggest that FEP patients exhibited pronounced impairment of fine motor skills, speed of processing, attention, verbal memory, visual memory, and executive function, while siblings exhibited deficits intermediate between those of schizophrenic patients and the control group. Semantic fluency function and executive function may be potential endophenotypes for the early diagnosis of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
37Psychiatry Res 2011 Mar 191: 174-81
PMID21295452
TitleMaximum-uncertainty linear discrimination analysis of first-episode schizophrenia subjects.
AbstractRecent techniques of image analysis brought the possibility to recognize subjects based on discriminative image features. We performed a magnetic resonance imaging (MRI)-based classification study to assess its usefulness for outcome prediction of first-episode schizophrenia patients (FES). We included 39 FES patients and 39 healthy controls (HC) and performed the maximum-uncertainty linear discrimination analysis (MLDA) of MRI brain intensity images. The classification accuracy index (CA) was correlated with the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning scale (GAF) at 1-year follow-up. The rate of correct classifications of patients with poor and good outcomes was analyzed using chi-square tests. MLDA classification was significantly better than classification by chance. Leave-one-out accuracy was 72%. CA correlated significantly with PANSS and GAF scores at the 1-year follow-up. Moreover, significantly more patients with poor outcome than those with good outcome were classified correctly. MLDA of brain MR intensity features is, therefore, able to correctly classify a significant number of FES patients, and the discriminative features are clinically relevant for clinical presentation 1 year after the first episode of schizophrenia. The accuracy of the current approach is, however, insufficient to be used in clinical practice immediately. Several methodological issues need to be addressed to increase the usefulness of this classification approach.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
38Biol. Psychiatry 2011 May 69: 959-66
PMID21167475
TitlePrediction of psychosis by mismatch negativity.
AbstractTo develop risk-adapted prevention of psychosis, an accurate estimation of the individual risk of psychosis at a given time is needed. Inclusion of biological parameters into multilevel prediction models is thought to improve predictive accuracy of models on the basis of clinical variables. To this aim, mismatch negativity (MMN) was investigated in a sample clinically at high risk, comparing individuals with and without subsequent conversion to psychosis.
At baseline, an auditory oddball paradigm was used in 62 subjects meeting criteria of a late risk at-state who remained antipsychotic-naive throughout the study. Median follow-up period was 32 months (minimum of 24 months in nonconverters, n = 37). Repeated-measures analysis of covariance was employed to analyze the MMN recorded at frontocentral electrodes; additional comparisons with healthy controls (HC, n = 67) and first-episode schizophrenia patients (FES, n = 33) were performed. Predictive value was evaluated by a Cox regression model.
Compared with nonconverters, duration MMN in converters (n = 25) showed significantly reduced amplitudes across the six frontocentral electrodes; the same applied in comparison with HC, but not FES, whereas the duration MMN in in nonconverters was comparable to HC and larger than in FES. A prognostic score was calculated based on a Cox regression model and stratified into two risk classes, which showed significantly different survival curves.
Our findings demonstrate the duration MMN is significantly reduced in at-risk subjects converting to first-episode psychosis compared with nonconverters and may contribute not only to the prediction of conversion but also to a more individualized risk estimation and thus risk-adapted prevention.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
39World J. Biol. Psychiatry 2011 Dec 12: 598-607
PMID21143005
TitlePhospholipase A? activity in first episode schizophrenia: associations with symptom severity and outcome at week 12.
AbstractIntracellular phospholipases A? (inPLA?) are activated during monoaminergic neurotranismision and act as key enzymes in cell membrane repair and remodelling, neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes and neuroinflammation. Several independent studies found increased inPLA? activity in drug-naïve first episode and chronic schizophrenia. This study investigates if inPLA? activity is associated with symptoms severity and treatment response in first episode schizophrenia (FES).
InPLA? activity was measured in serum of 35 young FES patients (mean age: 19.36 ± 3.32, mean duration of illness: 7.53 ± 6.28 months, 16 neuroleptic-naïve) before and after 12 weeks of treatment with second-generation antipsychotic medications (olanzapine, quetiapine or risperidone), as well as in 22 healthy controls matched for age. Psychopathology and social functioning were assessed at the same time points.
Baseline inPLA? activity was significantly increased in drug-naïve and treated FES patients compared to healthy controls. Baseline inPLA? activity was also associated with severity of negative symptoms and lower functioning at baseline. Furthermore, baseline inPLA? activity was associated with improvement in negative symptoms and functioning within the first 12 weeks of treatment.
Intracellular PLA? activity is increased in first episode schizophrenia and associated with symptom severity and outcome after 12 weeks of treatment. Future studies should investigate the implications of inPLA? activity as a potential predictor of treatment response for different antipsychotic agents.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
40Schizophr Bull 2011 Jan 37: 199-211
PMID19759093
TitleGray matter in first-episode schizophrenia before and after antipsychotic drug treatment. Anatomical likelihood estimation meta-analyses with sample size weighting.
AbstractCerebral morphological abnormalities in schizophrenia may be modulated by treatment, chronicity, and duration of illness. Comparing brain imaging studies of individuals with first-episode schizophrenia and neuroleptic naive (NN-FES) with that of their neuroleptic-treated counterparts (NT-FES) can help to dissect out the effect of these potential confounders.
We used the anatomical likelihood estimation method to compare voxel-based morphometric studies of NN-FES (n = 162 patients) and NT-FES (n = 336 patients) studies. The analysis included a sample size weighting step based on the Liptak-Stouffer method to reflect the greater power of larger studies.
Patient samples were matched for age, gender, and duration of illness. An extensive network of gray matter deficits in frontal, temporal, insular, striatal, posterior cingulate, and cerebellar regions was detected in the NN-FES samples as compared with healthy controls. Major deficits were detected in the frontal, superior temporal, insular, and parahippocampal regions for the NT-FES group compared with the NN-FES group. In addition, the NT-FES group showed minor deficits in the caudate, cingulate, and inferior temporal regions compared with the NN-FES group. There were no regions with gray matter volumetric excess in the NT-FES group.
Frontal, striato-limbic, and temporal morphological abnormalities are present in the early stage of schizophrenia and are unrelated to the effects of neuroleptic treatment, chronicity, and duration of illness. There may be dynamic effects of treatment on striato-limbic and temporal, but not frontal, regional gray matter volumes of the brain.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
41Schizophr Bull 2011 Jan 37: 177-88
PMID19633214
TitleBrain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: an activation likelihood estimation meta-analysis of illness progression.
AbstractThe present study reviewed voxel-based morphometry (VBM) studies on high-risk individuals with schizophrenia, patients experiencing their first-episode schizophrenia (FES), and those with chronic schizophrenia. We predicted that gray matter abnormalities would show progressive changes, with most extensive abnormalities in the chronic group relative to FES and least in the high-risk group.
Forty-one VBM studies were reviewed. Eight high-risk studies, 14 FES studies, and 19 chronic studies were analyzed using anatomical likelihood estimation meta-analysis.
Less gray matter in the high-risk group relative to controls was observed in anterior cingulate regions, left amygdala, and right insula. Lower gray matter volumes in FES compared with controls were also found in the anterior cingulate and right insula but not the amygdala. Lower gray matter volumes in the chronic group were most extensive, incorporating similar regions to those found in FES and high-risk groups but extending to superior temporal gyri, thalamus, posterior cingulate, and parahippocampal gryus. Subtraction analysis revealed less frontotemporal, striatal, and cerebellar gray matter in FES than the high-risk group; the high-risk group had less gray matter in left subcallosal gyrus, left amygdala, and left inferior frontal gyrus compared with FES. Subtraction analysis confirmed lower gray matter volumes through ventral-dorsal anterior cingulate, right insula, left amygdala and thalamus in chronic schizophrenia relative to FES.
Frontotemporal brain structural abnormalities are evident in nonpsychotic individuals at high risk of developing schizophrenia. The present meta-analysis indicates that these gray matter abnormalities become more extensive through first-episode and chronic illness. Thus, schizophrenia appears to be a progressive cortico-striato-thalamic loop disorder.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
42Clin Psychopharmacol Neurosci 2012 Aug 10: 78-87
PMID23430971
TitleTreatment Response in First-episode Schizophrenia.
AbstractFirst episode schizophrenia (FES) patients tend to be more responsive to treatment. An adequate response has been associated with a favourable long-term course in FES patients. Yet, despite the generally very favourable response profile around one quarter of the patients shows persisting symptoms of psychosis. To improve the outcome and course of psychosis great effort has emerged in identifying biological and clinical variables associated with non-response in order to identify non-responders as early as possible and adopt specific treatment strategies improving illness outcome. Different antipsychotic treatment regimens have been evaluated in terms of their efficacy in reducing symptoms of FES with psychological interventions gaining increasing importance in the treatment concept of patients suffering from their first illness episode. Therefore, aim of this review is to summarize current evidence on the response patterns, the most important predictors of response/non-response as well as on effective treatment interventions in FES patients.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
43J Clin Psychopharmacol 2012 Oct 32: 694-8
PMID22926606
TitleAkathisia and suicidal ideation in first-episode schizophrenia.
AbstractPatients with first-episode schizophrenia (FES) are known to be notably sensitive for developing extrapyramidal adverse effects, but the relation of akathisia and suicidal ideation has rarely been studied. The current report is an ongoing analysis of an 8-week double-blind randomized controlled multicenter trial in 289 FES, comparing risperidone and haloperidol. Assessments were conducted weekly and included the Hillside Akathisia Scale and 21-item Hamilton Depression Rating Scale ratings. Suicidal ideation was significantly associated with clinician observed akathisia, depressed mood, younger age, and use of propranolol. The allocated treatment, anxiety, and nervousness had no influence. The present findings suggest a promoting effect of akathisia on suicidal ideation can not be ruled out in patients with FES.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
44BMC Psychiatry 2012 -1 12: 104
PMID22870896
TitleStructural brain changes in First Episode Schizophrenia compared with Fronto-Temporal Lobar Degeneration: a meta-analysis.
AbstractThe authors sought to compare gray matter changes in First Episode schizophrenia (FES) compared with Fronto-Temporal Lobar Degeneration (FTLD) using meta-analytic methods applied to neuro-imaging studies.
A systematic search was conducted for published, structural voxel-based morphometric MRI studies in patients with FES or FTLD. Data were combined using anatomical likelihood estimation (ALE) to determine the extent of gray matter decreases and analysed to ascertain the degree of overlap in the spatial distribution of brain changes in both diseases.
Data were extracted from 18 FES studies (including a total of 555 patients and 621 comparison subjects) and 20 studies of FTLD or related disorders (including a total of 311 patients and 431 comparison subjects). The similarity in spatial overlap of brain changes in the two disorders was significant (p?=?0.001). Gray matter deficits common to both disorders included bilateral caudate, left insula and bilateral uncus regions.
There is a significant overlap in the distribution of structural brain changes in First Episode schizophrenia and Fronto-Temporal Lobar Degeneration. This may reflect overlapping aetiologies, or a common vulnerability of these regions to the distinct aetio-pathological processes in the two disorders.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
45Conscious Cogn 2012 Sep 21: 1365-74
PMID22673373
TitleBodily self and schizophrenia: the loss of implicit self-body knowledge.
Abstractschizophrenia spectrum has been associated with a disruption of the basic sense of self, which pertains, among others, the representation of one's own body. We investigated the impact of either implicit or explicit access to the representation of one's own body-effectors on bodily self-awareness, in first-episode schizophrenia (FES) patients and healthy controls (HCs). We contrasted their performance in an implicit self-recognition task (visual matching) and in an explicit self/other discrimination task. Both tasks employed participant's own and others' body-effectors. Concerning the implicit task, HCs were more accurate with their own than with others' body-effectors, whereas patients did not show such self-advantage. Regarding the explicit task, both groups did not exhibit a self-advantage, and patients showed a higher percentage of self-misattribution errors. Neither self/other nor implicit/explicit effects were found in both groups when processing inanimate-objects. We propose that FES patients suffer of a disturbed implicit sense of bodily self.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
46Clin Psychopharmacol Neurosci 2012 Apr 10: 13-24
PMID23429992
TitleDiffusion tensor imaging findings of white matter changes in first episode schizophrenia: a systematic review.
AbstractEarlier structural magnetic resonance imaging in schizophrenia have noted smaller white matter volumes in diverse brain regions and recent diffusion tensor imaging (DTI) studies have allowed better elucidation of changes in brain white matter integrity within the illness. As white matter abnormalities have been reported to occur early in the course of schizophrenia, we systematically review extant DTI studies of anomalies of white matter integrity in first episode schizophrenia (FES) up till October 2011. Overall, disruptions of white matter integrity were found in the cortical, subcortical brain regions and white matter associative and commissural tracts, suggesting that changes of cortical-subcortical white matter integrity were found at an early stage of the disorder. These changes in white matter integrity were correlated with specific cognitive deficits (verbal and spatial working memory) as well as psychopathology (positive more than negative symptoms) in patients with FES. The correlation of these white matter integrity changes with cognitive and phenomenological factors may shed light on neurobiological substrates underlying these clinical maniFEStations. Future studies need to validate these findings in larger samples of subjects and in different populations as well as chart the progress of these cerebral white matter changes over time so as to better appreciate their trajectory with illness course, treatment and chronicity.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
47J Psychiatr Res 2012 Jun 46: 733-7
PMID22445279
TitleThe dopamine b-hydroxylase 19 bp insertion/deletion polymorphism was associated with first-episode but not medicated chronic schizophrenia.
AbstractNumerous studies report dysfunctional dopaminergic and noradrenergic neurotransmission in the pathogenesis of schizophrenia. Dopamine beta-hydroxylase (DBH) is an intracellular enzyme catalyzing the conversion of dopamine to noradrenaline. Functional polymorphisms have been reported in the promoter region of DBH gene, including a 19 bp insertion/deletion polymorphism. The purpose of this study was to investigate whether there was an association between the functional polymorphism (DBH5'-Ins/Del) and schizophrenia in a Han Chinese population.
This polymorphism was genotyped in 221 first-episode schizophrenics, 360 chronic schizophrenics and 318 healthy controls using a case-control design. We assessed their psychopathology using the Positive and Negative Syndrome Scale (PANSS).
We showed that the DBH5'-Ins/Del deletion (Del) allelic and genotypic frequencies were significantly lower in controls than first-episode of schizophrenics (FES) (both p < 0.001), but controls were not different from chronic schizophrenics. Furthermore, the PANSS positive symptom and total scores were significantly higher in FES with the Del/Del genotype than those with Ins/Del and Ins/Ins genotypes (all p < 0.05).
The DBH5'-Ins/Del polymorphism may play a role in susceptibility to the positive symptoms of FES and to these FES not progressing on to chronic schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
48J Psychiatr Res 2012 Jun 46: 733-7
PMID22445279
TitleThe dopamine b-hydroxylase 19 bp insertion/deletion polymorphism was associated with first-episode but not medicated chronic schizophrenia.
AbstractNumerous studies report dysfunctional dopaminergic and noradrenergic neurotransmission in the pathogenesis of schizophrenia. Dopamine beta-hydroxylase (DBH) is an intracellular enzyme catalyzing the conversion of dopamine to noradrenaline. Functional polymorphisms have been reported in the promoter region of DBH gene, including a 19 bp insertion/deletion polymorphism. The purpose of this study was to investigate whether there was an association between the functional polymorphism (DBH5'-Ins/Del) and schizophrenia in a Han Chinese population.
This polymorphism was genotyped in 221 first-episode schizophrenics, 360 chronic schizophrenics and 318 healthy controls using a case-control design. We assessed their psychopathology using the Positive and Negative Syndrome Scale (PANSS).
We showed that the DBH5'-Ins/Del deletion (Del) allelic and genotypic frequencies were significantly lower in controls than first-episode of schizophrenics (FES) (both p < 0.001), but controls were not different from chronic schizophrenics. Furthermore, the PANSS positive symptom and total scores were significantly higher in FES with the Del/Del genotype than those with Ins/Del and Ins/Ins genotypes (all p < 0.05).
The DBH5'-Ins/Del polymorphism may play a role in susceptibility to the positive symptoms of FES and to these FES not progressing on to chronic schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
49BMC Psychiatry 2012 -1 12: 154
PMID22998680
TitleExecutive attention impairment in first-episode schizophrenia.
AbstractWe compared the attention abilities of a group of first-episode schizophrenia (FES) patients and a group of healthy participants using the Attention Network Test (ANT), a standard procedure that estimates the functional state of three neural networks controlling the efficiency of three different attentional behaviors, i.e., alerting (achieving and maintaining a state of high sensitivity to incoming stimuli), orienting (ability to select information from sensory input), and executive attention (mechanisms for resolving conflict among thoughts, feelings, and actions).
We evaluated 22 FES patients from 17 to 29 years of age with a recent history of a single psychotic episode treated only with atypical neuroleptics, and 20 healthy persons matched with FES patients by sex, age, and educational level as the control group. Attention was estimated using the ANT in which participants indicate whether a central horizontal arrow is pointing to the left or the right. The central arrow may be preceded by spatial or temporal cues denoting where and when the arrow will appear, and may be flanked by other arrows (hereafter, flankers) pointing in the same or the opposite direction.
The efficiency of the alerting, orienting, and executive networks was estimated by measuring how reaction time was influenced by congruency between temporal, spatial, and flanker cues. We found that the control group only demonstrated significantly greater attention efficiency than FES patients in the executive attention network.
FES patients are impaired in executive attention but not in alerting or orienting attention, suggesting that executive attention deficit may be a primary impairment during the progression of the disease.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
50Indian J Psychiatry 2012 Jan 54: 15-22
PMID22556432
TitleAddition of home-based cognitive retraining to treatment as usual in first episode schizophrenia patients: a randomized controlled study.
AbstractWe examined the effectiveness of a 2-month-long home-based cognitive retraining program together with treatment as usual (TAU; psychoeducation and drug therapy) on neuropsychological functions, psychopathology, and global functioning in patients with first episode schizophrenia (FES) as well as on psychological health and perception of level of family distress in their caregivers.
Forty-five FES patients were randomly assigned to either treatment group receiving home-based cognitive retraining along with TAU (n=22) or to control group receiving TAU alone (n=23). Patients and caregivers received psychoeducation. Patients and one of their caregivers were assessed for the above parameters at baseline, post-assessment (2 months) and at 6-months follow-up assessment.
Of the 45 patients recruited, 12 in the treatment group and 11 in the control group completed post-intervention and follow-up assessments. Addition of home-based cognitive retraining along with TAU led to significant improvement in neuropsychological functions of divided attention, concept formation and set-shifting ability, and planning. Effect sizes were large, although the sample size was small.
Home-based cognitive retraining program has shown promise. However, further studies examining this program on a larger cohort with rigorous design involving independent raters are suggested.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
51Schizophr. Res. 2012 May 137: 124-31
PMID22425035
TitleLocalized gray matter volume reductions in the pars triangularis of the inferior frontal gyrus in individuals at clinical high-risk for psychosis and first episode for schizophrenia.
AbstractRecent studies have suggested an important role for Broca's region and its right hemisphere counterpart in the pathophysiology of schizophrenia, owing to its roles in language and interpersonal information processing. Broca's region consists of the pars opercularis (PO) and the pars triangularis (PT). Neuroimaging studies have suggested that they have differential functional roles in healthy individuals and contribute differentially to the pathogenesis of schizophrenic symptoms. However, volume changes in these regions in subjects with ultra-high risk for psychosis (UHR) or first-episode schizophrenia (FES) have not been clarified. In the present 3 Tesla magnetic resonance imaging study, we separately measured the gray matter volumes of the PO and PT using a reliable manual-tracing volumetry in 80 participants (20 with UHR, 20 with FES, and 40 matched controls). The controls constituted two groups: the first group was matched for age, sex, parental socioeconomic background, and intelligence quotient to UHR (n=20); the second was matched for those to FES (n=20). Compared with matched controls, the volume of the bilateral PT, but not that of the PO, was significantly reduced in the subjects with UHR and FES. The reduced right PT volume, which showed the largest effect size among regions-of-interest in the both UHR and FES groups, correlated with the severity of the positive symptoms also in the both groups. These results suggest that localized gray matter volume reductions of the bilateral PT represent a vulnerability to schizophrenia in contrast to the PO volume, which was previously found to be reduced in patients with chronic schizophrenia. The right PT might preferentially contribute to the pathogenesis of psychotic symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
52Schizophr. Res. 2012 May 137: 124-31
PMID22425035
TitleLocalized gray matter volume reductions in the pars triangularis of the inferior frontal gyrus in individuals at clinical high-risk for psychosis and first episode for schizophrenia.
AbstractRecent studies have suggested an important role for Broca's region and its right hemisphere counterpart in the pathophysiology of schizophrenia, owing to its roles in language and interpersonal information processing. Broca's region consists of the pars opercularis (PO) and the pars triangularis (PT). Neuroimaging studies have suggested that they have differential functional roles in healthy individuals and contribute differentially to the pathogenesis of schizophrenic symptoms. However, volume changes in these regions in subjects with ultra-high risk for psychosis (UHR) or first-episode schizophrenia (FES) have not been clarified. In the present 3 Tesla magnetic resonance imaging study, we separately measured the gray matter volumes of the PO and PT using a reliable manual-tracing volumetry in 80 participants (20 with UHR, 20 with FES, and 40 matched controls). The controls constituted two groups: the first group was matched for age, sex, parental socioeconomic background, and intelligence quotient to UHR (n=20); the second was matched for those to FES (n=20). Compared with matched controls, the volume of the bilateral PT, but not that of the PO, was significantly reduced in the subjects with UHR and FES. The reduced right PT volume, which showed the largest effect size among regions-of-interest in the both UHR and FES groups, correlated with the severity of the positive symptoms also in the both groups. These results suggest that localized gray matter volume reductions of the bilateral PT represent a vulnerability to schizophrenia in contrast to the PO volume, which was previously found to be reduced in patients with chronic schizophrenia. The right PT might preferentially contribute to the pathogenesis of psychotic symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
53Schizophr. Res. 2012 May 137: 85-90
PMID22377101
TitleMTR abnormalities in subjects at ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls.
AbstractNeuroimaging studies have suggested gray (GM) and white matter (WM) abnormalities in early stages of schizophrenia. We aimed at evaluating subtle parenchymal alterations in individuals at ultra-high risk (UHR) for transition into psychosis and first-episode schizophrenic (FES) patients by measuring the magnetization transfer ratio (MTR).
In a cross-sectional study magnetization transfer images and high-resolution volumetric T1-weighted images were acquired in 70 age- and gender-matched subjects (25 UHR subjects, 16 FES patients and 29 controls) in a 1.5Tesla scanner. Following normalization of MTR-maps the intensity histograms were analyzed by performing a Kruskal-Wallis-test.
Gray matter MTR decreases were depicted in UHR subjects solely, involving the cingulate gyrus and precentral cortex. WM MTR alterations were more pronounced in FES than in UHR patients and exclusively affected the frontal lobe bilaterally. In addition, UHR subjects showed bilateral MTR decreases at the stria terminalis though statistically significant only on the left side (p=0.018.)
Our results indicate GM affection earlier on during disease progression as well as cumulative WM affection within frontal lobes during transition from UHR to FES. MTR reductions at the stria terminalis of UHR patients points to the involvement of the extended amygdala in the prodromal disease stage.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
54Schizophr. Res. 2012 May 137: 85-90
PMID22377101
TitleMTR abnormalities in subjects at ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls.
AbstractNeuroimaging studies have suggested gray (GM) and white matter (WM) abnormalities in early stages of schizophrenia. We aimed at evaluating subtle parenchymal alterations in individuals at ultra-high risk (UHR) for transition into psychosis and first-episode schizophrenic (FES) patients by measuring the magnetization transfer ratio (MTR).
In a cross-sectional study magnetization transfer images and high-resolution volumetric T1-weighted images were acquired in 70 age- and gender-matched subjects (25 UHR subjects, 16 FES patients and 29 controls) in a 1.5Tesla scanner. Following normalization of MTR-maps the intensity histograms were analyzed by performing a Kruskal-Wallis-test.
Gray matter MTR decreases were depicted in UHR subjects solely, involving the cingulate gyrus and precentral cortex. WM MTR alterations were more pronounced in FES than in UHR patients and exclusively affected the frontal lobe bilaterally. In addition, UHR subjects showed bilateral MTR decreases at the stria terminalis though statistically significant only on the left side (p=0.018.)
Our results indicate GM affection earlier on during disease progression as well as cumulative WM affection within frontal lobes during transition from UHR to FES. MTR reductions at the stria terminalis of UHR patients points to the involvement of the extended amygdala in the prodromal disease stage.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
55Neuropsychologia 2012 Apr 50: 988-96
PMID22361253
TitleAction verb understanding in first-episode schizophrenia: is there evidence for a simulation deficit?
Abstractschizophrenia is often associated with deficits in the domain of language, which are thought to be closely related to deficits in the structure of semantic knowledge. The main aim of the present study was to behaviorally investigate whether semantic impairments in schizophrenia are present also at the very basic level of action verb processing, in particular at the level of motor simulation. We used a go-no go paradigm both for a semantic decision task (with either an early, EGD, or a delayed go-signal delivery, DGD) and for a lexical decision task (control task). Only the first task requires motor simulation to be solved. We found that first-episode schizophrenia (FES) patients, like healthy control (HC) participants, use motor simulation as a basic strategy to semantically judge action verbs. In the EGD condition, both motor simulation and action verb understanding seem to be preserved in FES. However, differently from HC participants, FES patients kept on using the simulation strategy also with the DGD condition, whereas, simultaneously, task performance during this condition appeared to be less efficient and sensitive. Voxel-based morphometry analysis suggested that this altered performance in FES patients could be related to structural brain abnormalities in the right dorsolateral prefrontal cortex. We propose that a prolonged motor simulation in FES may serve as a compensatory strategy for impairments in the selection of action representation and/or for memory deficits disclosed by the DGD condition during the semantic decision task investigated in the present study.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
56Psychiatry Res 2012 Jan 201: 40-7
PMID22285715
TitleNeural markers of early remission in first-episode schizophrenia: a volumetric neuroimaging study of the parahippocampus.
AbstractUsing voxel-based morphometry (VBM), our laboratory recently identified significantly lower grey matter concentration in the parahippocampal gyrus bilaterally in non-remitted patients with a first episode of psychosis (FEP) compared with remitted FEP patients. These results identified a localized difference but did not reveal which cortex (entorhinal, perirhinal, or parahippocampal), if any, was predominantly affected. So, the parahippocampal gyrus was manually segmented and grey matter volumes from the three cortices were compared between 42 non-remitted and 17 remitted patients with a first episode of schizophrenia (FES). Remission was defined as mild or less on eight key symptoms and maintained for 6 consecutive months following the 2005 consensus definition. The non-remitted patients displayed smaller volumes in the parahippocampal cortex - trend-level difference on the left [mm(3), mean (S.D.): non-remitted=2486 (413); remitted=2775 (593)] and significant difference on the right [mm(3), mean (S.D.): non-remitted=2546 (463); remitted=2926 (525)]. No notable differences were found in the entorhinal or perirhinal cortices. This result supported our VBM finding of reduced parahippocampal grey matter bilaterally in non-remitted patients and further suggested differences may be selectively limited to the parahippocampal cortex. A smaller parahippocampal cortex may represent a neural marker in FES patients who do not achieve remission after 1 year of treatment.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
57Schizophr. Res. 2012 Mar 135: 34-9
PMID22222379
TitleCharacteristics and clinical correlates of prospective memory performance in first-episode schizophrenia.
AbstractThe aim of this study was to examine prospective memory (PM) and its socio-demographic, clinical, and neurocognitive correlates in first episode schizophrenia (FES).
Fifty-one FES patients and 42 healthy controls formed the study sample. Time- and event-based PM (TBPM and EBPM) performance were measured with the Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT). A battery of neuropsychological tests was also administered. Patients' clinical symptoms were evaluated with the Positive and Negative Symptom Scale (PANSS).
Patients performed significantly worse in both TBPM (8.7 ± 5.3 vs. 14.8 ± 3.5) and EBPM (11.3 ± 4.7 vs. 15.7 ± 2.7) than the controls. After controlling for age, gender, education level and neurocognitive test score, the difference in performance on the two types of PM tasks between patients and controls was no longer present. In multiple linear regression analyses, longer duration of untreated psychosis (DUP), lower scores of the Hopkins Verbal Learning Test-Revised (HVLT-R) and the categories completed of the Wisconsin Card Sorting Test (WCST-CC) and higher score of the Color Trails Test-2 (CTT-2) contributed to poorer TBPM performance, while lower score of HVLT-R, higher score of the perseverative errors of the Wisconsin Card Sorting Test (WCST-PE) and longer DUP contributed to worse performance on EBPM.
Both subtypes of PM are impaired in first-episode schizophrenia suggesting that PM deficits are an integral part of the cognitive dysfunction in the disease process.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
58Early Interv Psychiatry 2012 May 6: 166-75
PMID21951785
TitleDetection of metabolites in the white matter of frontal lobes and hippocampus with proton in first-episode treatment-naïve schizophrenia patients.
AbstractThis study aimed to investigate the changes of the metabolites in the white matter of frontal lobes and hippocampus in schizophrenia by using proton magnetic resonance spectroscopy ((1) H-MRS).
Sixty-three first-episode treatment-naïve schizophrenia (FES) patients and 63 age-, gender- and education level-matched healthy controls were recruited. The relative levels of metabolites including N-acetylaspartate (NAA), choline-containing compounds (Cho), (Cr) and myo-inositol (MI) were detected with (1) H-MRS, and the laterality index (Li) was calculated. The severity of symptoms was assessed using the Positive and Negative Syndrome Scale.
Compared with controls, FES patients did not show significant differences in all metabolites. The severity of positive symptoms was negatively correlated with the NAA/Cho in the white matter of the left frontal lobe and positively correlated with the Cho/Cr in the right white matter of frontal lobes. A negative correlation was observed between the severity of negative symptoms and the NAA/Cr in the white matter of bilateral frontal lobes. No difference was shown in the Li of metabolites between FES patients and controls.
The metabolites such as NAA, Cho and MI in white matter of frontal lobes and hippocampus were not significantly altered in FES patients. The lower axonal integrity/number (NAA concentration) may be associated with more severe negative symptoms, and dysmetabolism in process of myelination in the white matter of frontal lobes associated with more severe positive symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
59Schizophr. Res. 2012 Jan 134: 20-6
PMID21937197
TitleDepressive symptoms in first episode schizophrenia spectrum disorder.
AbstractDepressive symptoms in 'non-affective' first episode schizophrenia spectrum disorders (FES) are common, but poorly understood, resulting in a range of conceptual and clinical management issues. This study had three aims: (i) to determine the prevalence of moderate to severe depressive symptoms (defined as a Clinical Global Impressions Scale-Bipolar Disorder (CGI-BP depression) score >3) in a large representative sample of FES patients; (ii) to compare the clinical and functional characteristics of FES patients with and without these depressive symptoms at service entry; and (iii) to compare the characteristics of FES patients with and without persistent depressive symptoms.
Medical file audit methodology was employed to collect information on 405 patients with FES treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia.
26.2% (n=106) of the patients had moderate to severe depression at service entry. At service entry and at discharge, those with depressive symptoms had greater insight into their illness but did not differ from those without depressive symptoms in terms of severity of overall psychopathology. Substance use was significantly less common in those with depressive symptoms at service entry and at discharge. Of those who were depressed at baseline, 14.2% (n=15) continued to have moderate to severe depressive symptoms at discharge.
Depressive symptoms are common in patients with FES. Understanding the nature and characteristics of depression in FES has important clinical implications for both early intervention and treatment.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
60Int. J. Neuropsychopharmacol. 2012 Apr 15: 297-307
PMID21557880
TitleCerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults.
AbstractEpidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to 'schizophrenia-like' cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter:total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
61Zhonghua Yi Xue Za Zhi 2013 Nov 93: 3261-4
PMID24401618
Title[Diagnostic P300 threshold based on the analysis of receiver operating characteristic curve].
AbstractTo explore the diagnostic application of receiver operating characteristic (ROC) curve of P300 amplitude and latency in schizophrenia.
ROC curve of P300 amplitude and latency was plotted from 91 first episode schizophrenia (FES) and 141 normal controls (NC). Youden's index and distance were calculated in ROC curve to determine the optimal cutoff point of P300 amplitude and latency for schizophrenic diagnosis. Then the subjects were layered by gender and age for improved diagnostic accuracy.
The area under ROC curve for P300 amplitude for predicting schizophrenia was 0.746 (P < 0.001), while P300 latency showed poor power in predicting schizophrenia (P = 0.373). The optimal cutoff point of P300 amplitude was 5.097 µV with a sensitivity of 80.14% and a specificity of 63.74%. After gender and age stratification, Youden' s index was enhanced in all 5 subgroups (from 1.8% to 14.88%) and the sensitivities of corresponding cutoff were enhanced obviously in subgroups of males (25.01%), ? 25 years (22.22%) and >40 years (28.80%) patients.
P300 amplitude has certain values in schizophrenic diagnosis. Gender and age stratification may enhance the diagnostic efficiency of ROC curve in the diagnosis of frequent schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
62Schizophr. Res. 2013 Dec 151: 265-9
PMID24262680
TitleCognitive deficits in clinical and familial high risk groups for psychosis are common as in first episode schizophrenia.
AbstractThe aim of this study is to compare the neurocognitive functions in individuals with clinical or genetic risk for psychosis, in patients with first-episode schizophrenia (FES) and in healthy controls. We compared cognitive functions of 52 individuals at ultra high risk (UHR) for psychosis, 53 patients with FES, their 30 healthy siblings (familial high risk group, FHR) and controls. FES group had worse neuropsychological performance than controls in all of the domains. UHR group had worse performance in verbal learning, attention, and working memory than controls. Additionally, individuals at UHR with familial risk had worse performance on executive functions than the control group. FES group had lower global composite score than UHR group, and worse sustained attention than FHR group. FHR group had worse performance on executive functions and attention than controls. We found no difference in cognitive performances of UHR and FHR groups. Cognitive deficits in UHR and FHR groups were largely similar to those with FES. These findings support that cognitive deficits may arise before the first episode of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
63J. Nerv. Ment. Dis. 2013 Mar 201: 229-33
PMID23407202
TitleRelationships between psychopathological variables and insight in psychosis risk syndrome and first-episode and multiepisode schizophrenia.
AbstractInsight may vary across psychosis risk syndrome (PRS), first-episode schizophrenia (FES), or multiepisode schizophrenia (MES). We aimed to compare insight domains (awareness, relabeling, and compliance) in PRS, FES, and MES groups and to correlate scores with psychopathological measures. Insight was assessed in 48 (14 PRS, 16 FES, and 18 MES) patients using the Schedule for the Assessment of Insight-Expanded Version. We conducted psychopathological assessment through the Brief Psychiatric Rating Scale (BPRS). In the whole group, the BPRS psychosis factor correlated with all insight domains. In the MES group, the more severe the anxiety/depression, the higher the insight score in the symptom relabeling domain. Insight did not differ significantly between the PRS, FES, and MES groups. Our results suggest that, across different phases of the illness, lack of insight behaves like a trait and is modulated by positive symptom severity. Anxiety and depression may be associated with increased insight in patients with chronic schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
64Schizophr. Res. 2013 Mar 144: 31-6
PMID23347949
TitleTheory of mind impairments in first-episode psychosis, individuals at ultra-high risk for psychosis and in first-degree relatives of schizophrenia: systematic review and meta-analysis.
AbstractTheory of mind (ToM) deficit is a well-established feature of schizophrenia and has been suggested as a vulnerability marker of this disorder. However, as most of this evidence is based on studies in chronic patients, it is less clear whether ToM is impaired prior to or following the onset of a first-episode and whether it is evident in unaffected relatives of patients. In this meta-analysis, ToM performance of 3005 individuals with first-episode psychosis (FEP), individuals at ultra-high risk for psychosis (UHR) and unaffected relatives were compared with 1351 healthy controls. ToM was substantially impaired in first-episode psychosis (Cohen d=1.0) and this deficit was comparable to findings in chronic patients. ToM was also impaired in unaffected relatives (d=0.37) and UHR subjects (d=0.45) and performances of these groups were intermediate between FES and healthy controls. Severity of ToM deficits in unaffected relatives and UHR subjects was similar to other cognitive deficits observed in these groups. Longitudinal studies of clinical and genetic high-risk subjects are necessary to investigate the trajectory of development of ToM deficits in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
65Zhonghua Yi Xue Za Zhi 2013 Nov 93: 3261-4
PMID24401618
Title[Diagnostic P300 threshold based on the analysis of receiver operating characteristic curve].
AbstractTo explore the diagnostic application of receiver operating characteristic (ROC) curve of P300 amplitude and latency in schizophrenia.
ROC curve of P300 amplitude and latency was plotted from 91 first episode schizophrenia (FES) and 141 normal controls (NC). Youden's index and distance were calculated in ROC curve to determine the optimal cutoff point of P300 amplitude and latency for schizophrenic diagnosis. Then the subjects were layered by gender and age for improved diagnostic accuracy.
The area under ROC curve for P300 amplitude for predicting schizophrenia was 0.746 (P < 0.001), while P300 latency showed poor power in predicting schizophrenia (P = 0.373). The optimal cutoff point of P300 amplitude was 5.097 µV with a sensitivity of 80.14% and a specificity of 63.74%. After gender and age stratification, Youden' s index was enhanced in all 5 subgroups (from 1.8% to 14.88%) and the sensitivities of corresponding cutoff were enhanced obviously in subgroups of males (25.01%), ? 25 years (22.22%) and >40 years (28.80%) patients.
P300 amplitude has certain values in schizophrenic diagnosis. Gender and age stratification may enhance the diagnostic efficiency of ROC curve in the diagnosis of frequent schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
66Psychol Med 2013 Jul 43: 1353-63
PMID23186886
TitleAmygdala-hippocampal shape and cortical thickness abnormalities in first-episode schizophrenia and mania.
AbstractAbnormalities in cortical thickness and subcortical structures have been studied in schizophrenia but little is known about corresponding changes in mania and brain structural differences between these two psychiatric conditions, especially early in the stage of the illness. In this study we aimed to compare cortical thickness and shape of the amygdala-hippocampal complex in first-episode schizophrenia (FES) and mania (FEM). Method Structural magnetic resonance imaging (MRI) was performed on 28 FES patients, 28 FEM patients and 28 healthy control subjects who were matched for age, gender and handedness.
Overall, the shape of the amygdala was deformed in both patient groups, relative to controls. Compared to FEM patients, FES patients had significant inward shape deformation in the left hippocampal tail, right hippocampal body and a small region in the right amygdala. Cortical thinning was more widespread in FES patients, with significant differences found in the temporal brain regions when compared with FEM and controls.
Significant differences were observed between the two groups of patients with FES and FEM in terms of the hippocampal shape and cortical thickness in the temporal region, highlighting that distinguishable brain structural changes are present early in the course of schizophrenia and mania.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
67Acta Neuropsychiatr 2013 Oct 25: 268-74
PMID25287726
TitleAspects of metabolic changes in first-episode drug-naïve schizophrenic patients.
AbstractAim The aim of the study was to investigate the state of parameters characterising different sites of metabolism and the degree of endogenous intoxication in first-episode drug-naïve schizophrenic [first episode of schizophrenia (FES)] patients. It is hypothesised that the FES is the initial step in the development of pathologically disturbed biochemical status that is characteristic of chronic schizophrenia.
Platelet monoamine oxidase (MAO) and serum semicarbazide-sensitive amine oxidase (SSAO) activities, serum concentrations of middle-mass endotoxic molecules (MMEM) and malondialdehyde and parameters of the serum albumin functional state were measured in 26 FES patients and 15 age-matched healthy controls.
Severity of disorder before the treatment was 75.5 ± 2.2, according to Positive and Negative Syndrome Scale score. FES patients were characterised by significant increase in MAO activity (99%) and MMEM concentration (124%) and significant decrease in SSAO activity (26%) as compared with controls. Changes of all other parameters were insignificant. Regression analysis has showed a significant relationship of three parameters - MAO, SSAO and MMEM, with values of PANNS score. Two methods of extraction of factor analysis revealed that MAO and SSAO belonged to Factor 1, whereas MMEM and albumin functional parameters belonged to Factor 2.
Comparing our earlier data on chronic schizophrenic patients with present data, we hypothesise that FES patients are at the stage that leads to a stable, pathological state of metabolism.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
68Front Behav Neurosci 2013 -1 7: 148
PMID24155700
TitleElectrophysiological and neuropsychological predictors of conversion to schizophrenia in at-risk subjects.
AbstractPatients with schizophrenia show neurophysiological and psychological disturbances before the onset of the illness. Mismatch negativity (MMN), an event-related potential, has been shown to be associated with cognitive function. Specifically, duration MMN (dMMN) amplitudes have been indicated to predict progression to overt schizophrenia in subjects with at-risk mental state. The aim of this article is to provide a hypothesis that a combined assessment of dMMN and neuropsychological performance would enhance accuracy for predicting conversion to schizophrenia in at-risk subjects. Data from these neurocognitive modalities in subjects with first-episode schizophrenia (FES) are also presented. There is accumulated evidence that converters to schizophrenia among at-risk subjects show significantly smaller dMMN amplitudes than those in healthy control (HC) subjects at the frontal lead before the onset. In fact, the amplitudes in these converters have been reported to be similar to those in FES to begin with. dMMN current source density, by means of low-resolution brain electromagnetic tomography, was significantly lower in FES than HC subjects, especially in some medial temporal regions which are implicated in the pathophysiology of schizophrenia. Importantly, dMMN current density in the frontal lobe was positively correlated with working memory performance in FES subjects. These findings indicate the utility of the combination of electrophysiological/neuropsychological assessments for early intervention into patients with schizophrenia and high-risk people.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
69Aust N Z J Psychiatry 2013 Nov 47: 1051-7
PMID24108060
TitleDysfunctional family environment in affected versus unaffected offspring of parents with bipolar disorder.
AbstractChildren of parents with bipolar disorder (BD) are at heightened risk for developing mood and other psychiatric disorders. We proposed to evaluate the environment of families with at least one parent with BD type I (BDF) with affected offspring (aBDF) and unaffected offspring (uBDF) compared with control families without a history of DSM-IV Axis I disorder (CF).
We used the Family Environment Scale (FES) to evaluate 47 BDF (aBDF + uBDF) and 30 CF. Parents were assessed through the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Diagnosis of the offspring was determined through the Schedule for Affective Disorders and schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL) interview.
There were statistically significant differences between aBDF, uBDF and CF in cohesion (p = 0.003), intellectual-cultural orientation (p = 0.01), active-recreational orientation (p = 0.007), conflict (p = 0.001), control (p = 0.01), moral-religious emphasis (p = 0.01) and organization (p = 0.001). The aBDF showed higher levels of control (p = 0.02) when compared to the uBDF.
Families with a BD parent presented more dysfunctional interactions among members. Moreover, the presence of BD or other psychiatric disorders in the offspring of parents with BD is associated with higher levels of control. These results highlight the relevance of psychosocial interventions to improve resilience and family interactions.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
70Schizophr. Res. 2013 Nov 150: 547-54
PMID24012461
TitleAuditory mismatch negativity and P3a in response to duration and frequency changes in the early stages of psychosis.
AbstractA shorter duration of untreated psychosis in patients with schizophrenia results in better symptomatic and functional outcomes. Therefore, identifying biological markers in the early stages of psychosis is an important step toward early detection and intervention. Mismatch negativity (MMN) and P3a are leading candidate biomarkers. MMN measures differ in their sensitivity to varying deviants. However, this has not been fully addressed in assessing the early stages of psychosis. In the current study, we examined MMN/P3a to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of psychosis. To our knowledge, this is the first study that examined both MMN/P3a to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of psychosis.
Participants consisted of 20 patients with first episode schizophrenia (FES), 21 ultra-high risk (UHR) individuals, and 22 healthy controls (HC). We measured dMMN/dP3a and fMMN/fP3a ERP components by means of a 64 electrodes-cap for EEG recording, and we used two-tone auditory oddball paradigms with 2000 stimuli.
The amplitude of dMMN was significantly reduced in FES and UHR compared to HC. The amplitude of fMMN showed no significant difference among the three groups. The amplitudes of dP3a and fP3a were significantly reduced in FES and UHR compared to HC.
These findings suggest that dMMN may have higher sensitivity than fMMN whereas dP3a and fP3a may have similar sensitivity in the early stages of psychosis.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
71Neuropsychiatr Dis Treat 2013 -1 9: 861-8
PMID23818786
TitleEfficacy of second-generation antipsychotics in patients at ultra-high risk and those with first-episode or multi-episode schizophrenia.
AbstractThe aim of this study was to examine the speed of response, doses, and safety of treatment with second-generation antipsychotics (SGAs) in patients at ultra-high risk (UHR) compared to those with schizophrenia.
A 12-week open-label, prospective study of SGAs was performed in UHR patients and those with first-episode schizophrenia (FES) and multi-episode schizophrenia (MES). The subjects were 14-30 years old and were recruited at Zikei Hospital, Okayama, Japan from December 1, 2006 to December 1, 2011. Treatment was carried out in a natural setting in an open-label format, but clinical evaluation was performed blind. The clinical rating scales include the Global Assessment of Functioning (GAF), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression-Severity scale (CGI-S).
UHR (n = 17), FES (n = 23), and MES (n = 21) patients all showed significant improvements on the GAF, PANSS, and CGI-S. However, the UHR patients showed significantly greater improvement on the GAF at weeks 4, 8, and 12 compared to the other groups, and a significantly lower modal dose of SGAs (chlorpromazine equivalent: 183 [201.1] mg/day, mean [SD]) was needed for improvement in the UHR group. Each group was also prescribed anticholinergic agents during the study period and the UHR group had significantly fewer extrapyramidal symptoms (only 6%) compared with the FES group.
Our findings suggest that UHR patients have a better response to SGAs compared to patients with schizophrenia, and that these drugs can be given safely by minimizing the dosage of SGAs and using anticholinergic agents.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
72Prog. Neuropsychopharmacol. Biol. Psychiatry 2013 Aug 45: 100-6
PMID23648972
TitleWhite matter deficits in first episode schizophrenia: an activation likelihood estimation meta-analysis.
AbstractDiffusion tensor imaging (DTI) has been widely used in psychiatric research and has provided evidence of white matter abnormalities in first episode schizophrenia (FES). The goal of the present meta-analysis was to identify white matter deficits by DTI in FES.
A systematic search was conducted to collect DTI studies with voxel-wised analysis of the fractional anisotropy (FA) in FES. The coordinates of regions with FA changes were meta-analyzed using the activation likelihood estimation (ALE) method which weighs each study on the basis of its sample size.
A total of 8 primary studies were selected, including 271 FES patients and 297 healthy controls. Among these studies, 52 regions showed reductions in the FA in FES while 2 regions had increased FA. Consistent FA reductions in the white matter of the right deep frontal and left deep temporal lobes were identified in all FES patients relative to healthy controls. Fiber tracking showed that the main tracts involved were the cingulum bundle, the left inferior longitudinal fasciculus, the left inferior fronto-occipital fasciculus and the interhemispheric fibers running through the corpus callosum.
The current findings provide evidence confirming the lack of connection in the fronto-limbic circuitry at the early stages of the schizophrenia. Because the coordinates reported in the primary literature were highly variable, future investigations with large samples would be required to support the identified white matter changes in FES.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
73Schizophr. Res. 2013 Jun 147: 169-74
PMID23528796
TitleDifferences between first episode schizophrenia and schizoaffective disorder.
AbstractThe diagnostic and clinical overlap between schizophrenia and schizoaffective disorder is an important nosological issue in psychiatry that is yet to be resolved. The aim of this study was to compare the clinical and functional characteristics of an epidemiological treated cohort of first episode patients with an 18-month discharge diagnosis of schizophrenia (FES) or schizoaffective disorder (FESA).
This study was part of the larger First Episode Psychosis Outcome Study (FEPOS) which involved a medical file audit study of all 786 patients treated at the Early Psychosis Prevention and Intervention Centre between 1998 and 2000. Of this cohort, 283 patients had an 18-month discharge diagnosis of FES and 64 had a diagnosis of FESA. DSM-IV diagnoses and clinical and functional ratings were derived and validated by two consultant psychiatrists.
Compared to FES patients, those with FESA were significantly more likely to have a later age of onset (p=.004), longer prodrome (p=.020), and a longer duration of untreated psychosis (p<.001). At service entry, FESA patients presented with a higher illness severity (p=.020), largely due to the presence of more severe manic symptoms (p<.001). FESA patients also had a greater number of subsequent inpatient admissions (p=.017), had more severe depressive symptoms (p=.011), and higher levels of functioning at discharge.
The findings support the notion that these might be considered two discernable disorders; however, further research is required to ascertain the ways and extent to which these disorders are discriminable at presentation and over time.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
74Schizophr. Res. 2013 Mar 144: 37-42
PMID23360727
TitleDecreased left middle temporal gyrus volume in antipsychotic drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings.
AbstractThe shared neuropathological characteristics of patients with schizophrenia and their siblings might represent intermediate phenotypes that could be used to investigate genetic susceptibility to the illness. We sought to discover gray matter volume differences in patients with schizophrenia and their unaffected siblings with voxel-based morphometry (VBM).
We recruited antipsychotic drug-naive, first-episode schizophrenia (FES) patients, their unaffected siblings and age-, sex- and handedness-matched healthy controls. We used VBM to investigate differences in gray matter volume among the 3 groups.
There were significant gray matter volumetric differences among the 3 groups in bilateral hippocampal and parahippocampal gyri, bilateral middle temporal gyri, and superior temporal gyri (FDR p<0.05). Patients had significant regional gray matter reduction in all regions listed above compared with healthy volunteers, and their gray matter volume in the right hippocampus and parahippocampus was also lower than the sibling group. The sibling group had significantly lower volumes compared to healthy individuals only in the left middle temporal gyrus, and volume of this region was not different between siblings and patients.
Our findings confirm and extend previous VBM analyses in schizophrenia and it indicate that schizophrenia may be characterized by an abnormal development of cerebral lateralization. Furthermore, these data argue that patients and their unaffected siblings might share decreases in the gray matter volume of the left middle temporal gyrus, and this regional reduction might be a potential endophenotype for schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
75Acta Neuropsychiatr 2013 Oct 25: 268-74
PMID25287726
TitleAspects of metabolic changes in first-episode drug-naïve schizophrenic patients.
AbstractAim The aim of the study was to investigate the state of parameters characterising different sites of metabolism and the degree of endogenous intoxication in first-episode drug-naïve schizophrenic [first episode of schizophrenia (FES)] patients. It is hypothesised that the FES is the initial step in the development of pathologically disturbed biochemical status that is characteristic of chronic schizophrenia.
Platelet monoamine oxidase (MAO) and serum semicarbazide-sensitive amine oxidase (SSAO) activities, serum concentrations of middle-mass endotoxic molecules (MMEM) and malondialdehyde and parameters of the serum albumin functional state were measured in 26 FES patients and 15 age-matched healthy controls.
Severity of disorder before the treatment was 75.5 ± 2.2, according to Positive and Negative Syndrome Scale score. FES patients were characterised by significant increase in MAO activity (99%) and MMEM concentration (124%) and significant decrease in SSAO activity (26%) as compared with controls. Changes of all other parameters were insignificant. Regression analysis has showed a significant relationship of three parameters - MAO, SSAO and MMEM, with values of PANNS score. Two methods of extraction of factor analysis revealed that MAO and SSAO belonged to Factor 1, whereas MMEM and albumin functional parameters belonged to Factor 2.
Comparing our earlier data on chronic schizophrenic patients with present data, we hypothesise that FES patients are at the stage that leads to a stable, pathological state of metabolism.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
76Early Interv Psychiatry 2013 Nov 7: 414-20
PMID23343404
TitleThe history of childhood trauma among individuals with ultra high risk for psychosis is as common as among patients with first-episode schizophrenia.
AbstractChildhood trauma (CT) is more common in patients with psychosis than in general population and is found to be related to the severity of symptoms. The objective of this study was to investigate the severity of CT, and its relationship with clinical features in two different groups: first-episode schizophrenia (FES) and ultra high risk for psychosis (UHR) groups.
In this cross-sectional study, 83 patients with FES, 41 individuals with UHR and 69 healthy controls were included. Clinical features were evaluated with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms (SAPS). We evaluated CT with the Childhood Trauma Questionnaire (CTQ). UHR group was also assessed with the Calgary Depression Scale for schizophrenia.
The emotional and physical abuse, physical and emotionalneglect subscale scores and CTQ total score of both the UHR group and FES group were higher than the control group. However, the CTQ total score and subscale scores did not differ between FES and UHR groups. UHR group had more Schneiderian symptoms in terms of both number and severity, and severity of sexual abuse was found to be correlated with SAPS scores especially for the 'commenting voices' item. The CTQ emotional abuse and neglect scores were correlated with the severity of depression. FES patients with higher CTQ scores obtained higher total scores on SAPS and higher total scores on Schneiderian items.
We found that CT is related to the severity of psychotic symptoms in both FES and UHR groups. Therefore, it is possible that interventions aimed at preventing CT in children would reduce the maniFEStation of psychosis among young people.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
77Acta Psychiatr Scand 2013 Oct 128: 261-70
PMID23216145
TitleAnatomical substrates of cognitive and clinical dimensions in first episode schizophrenia.
AbstractTo explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES).
Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively.
Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts.
These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
78Int. J. Neuropsychopharmacol. 2013 Jul 16: 1205-18
PMID23199972
TitleEfficacy and safety of individual second-generation vs. first-generation antipsychotics in first-episode psychosis: a systematic review and meta-analysis.
AbstractBecause early treatment choice is critical in first-episode schizophrenia-spectrum disorders (FES), this meta-analysis compared efficacy and tolerability of individual second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) in FES. We conducted systematic literature search (until 12 December 2010) and meta-analysis of acute, randomized trials with ?1 FGA vs. SGA comparison; patients in their first episode of psychosis and diagnosed with schizophrenia-spectrum disorders; available data for psychopathology change, treatment response, treatment discontinuation, adverse effects, or cognition. Across 13 trials (n = 2509), olanzapine (seven trials) and amisulpride (one trial) outperformed FGAs (haloperidol: 9/13 trials) in 9/13 and 8/13 efficacy outcomes, respectively, risperidone (eight trials) in 4/13, quetiapine (one trial) in 3/13 and clozapine (two trials) and ziprasidone (one trial) in 1/13, each. Compared to FGAs, extrapyramidal symptom (EPS)-related outcomes were less frequent with olanzapine, risperidone and clozapine, but weight gain was greater with clozapine, olanzapine and risperidone. Pooled SGAs were similar to FGAs regarding total psychopathology change, depression, treatment response and metabolic changes. SGAs significantly outperformed FGAs regarding lower treatment discontinuation, irrespective of cause, negative symptoms, global cognition and less EPS and akathisia, while SGAs increased weight more (p < 0.05-0.01). Results were not affected by FGA dose or publication bias, but industry-sponsored studies favoured SGAs more than federally funded studies. To summarize, in FES, olanzapine, amisulpride and, less so, risperidone and quetiapine showed superior efficacy, greater treatment persistence and less EPS than FGAs. However, weight increase with olanzapine, risperidone and clozapine and metabolic changes with olanzapine were greater. Additional FES studies including broader-based SGAs and FGAs are needed.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
79Psychol Med 2013 Aug 43: 1651-60
PMID23149169
TitleCigarette smoking, psychopathology and cognitive function in first-episode drug-naive patients with schizophrenia: a case-control study.
AbstractAlthough patients with chronic schizophrenia have substantially higher smoking rates than either the general population or patients with other mental illnesses, drug-naive patients with a first episode of schizophrenia have received little systemic study. This study examined smoking rates, the association between smoking and symptom severity and cognitive function in Chinese first-episode schizophrenia (FES) patients using cross-sectional and case-control designs.
Two hundred and forty-four drug-naive FES patients and 256 healthy controls matched for gender, age and education completed the Fagerström Test for Nicotine Dependence (FTND) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients were also rated on the Positive and Negative Symptom Scale (PANSS).
The rate and quantity of smoking were not significantly higher among FES patients compared to the general population. Among patients, smokers scored higher than non-smokers on the total PANSS and the positive symptom subscale scores. There were no significant associations between cognitive function and smoking in either FES patients or healthy controls.
In contrast to studies in patients with chronic schizophrenia, drug-naive FES patients did not smoke more frequently than the general population. Furthermore, patients with psychotic disorders who smoked did not exhibit significant cognitive differences compared with those who did not smoke. However, smoking may have other detrimental effects on physical and mental health, for example on positive symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
80Psychol Med 2013 Apr 43: 769-80
PMID22883428
TitleAberrant intrinsic brain activity and cognitive deficit in first-episode treatment-naive patients with schizophrenia.
AbstractGiven the important role of the default mode network (DMN) in cognitive function and the well-known neurocognitive deficit in schizophrenia, it is intriguing to examine systematically the relationship between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia. Method First-episode, treatment-naive patients with schizophrenia (FES) (n = 115) and healthy controls (n = 113) underwent resting-state functional magnetic resonance imaging (fMRI) scans and neurocognitive tests. Intrinsic neural activities evaluated by using the fragment amplitude of low-frequency fluctuations (fALFF) and the resting-state functional connectivity assessed by seed-based correlational analysis were compared between patients and controls. Aberrant intrinsic activities and DMN connectivity in patients were then correlated to neurocognitive performance and clinical symptoms.
Compared to controls, patients with FES showed decreased fALFF in the bilateral medial prefrontal cortex (MPFC) and the orbitofrontal cortex (OFC), and increased fALFF in the bilateral putamen. Increased functional connectivity with the DMN was observed in the left insula and bilateral dorsolateral PFC (DLPFC) in patients with FES. In patients, aberrant fALFF in the bilateral OFC were correlated with cognitive processing speed; fALFF in the left OFC and right putamen were correlated with the clinical factors excited/activation and disorganization; and increased DMN functional connectivity in the left insula was correlated with the clinical factors positive, excited/activation, disorganization and neurocognitive deficit in the domain of sustained attention.
These associations between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia may provide important insights into the neural mechanism of the disease.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
81Soc Cogn Affect Neurosci 2013 Apr 8: 394-403
PMID22275166
TitleOut of touch with reality? Social perception in first-episode schizophrenia.
AbstractSocial dysfunction has been recognized as an elementary feature of schizophrenia, but it remains a crucial issue whether social deficits in schizophrenia concern the inter-subjective domain or primarily have their roots in disturbances of self-experience. Social perception comprises vicarious processes grounding an experiential inter-relationship with others as well as self-regulation processes allowing to maintain a coherent sense of self. The present study investigated whether the functional neural basis underlying these processes is altered in first-episode schizophrenia (FES). Twenty-four FES patients and 22 healthy control participants underwent functional magnetic resonance imaging during a social perception task requiring them to watch videos depicting other individuals' inanimate and animate/social tactile stimulations, and a tactile localizer condition. Activation in ventral premotor cortex for observed bodily tactile stimulations was reduced in the FES group and negatively correlated with self-experience disturbances. Moreover, FES patients showed aberrant differential activation in posterior insula for first-person tactile experiences and observed affective tactile stimulations. These findings suggest that social perception in FES at a pre-reflective level is characterized by disturbances of self-experience, including impaired multisensory representations and self-other distinction. However, the results also show that social perception in FES involves more complex alterations of neural activation at multiple processing levels.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
82PLoS ONE 2014 -1 9: e97794
PMID24933577
TitleP300 aberration in first-episode schizophrenia patients: a meta-analysis.
AbstractDecreased P300 amplitude is one of the most consistent findings in patients with schizophrenia. However, whether prolonged P300 latency occurs in patients with schizophrenia, especially first-episode schizophrenia (FES) patients, remains controversial.
A meta-analyses of P300 aberration in FES patients and healthy control(HC) group was conducted. The meta-regression analysis was performed using a random effects model. The pooled standardized effect size (PSES) was calculated as the division of the difference between the means of the two groups by the common standard deviation.
A total of 569 FES patients and 747 HCs were included in this meta-analysis. P300 amplitude was significantly reduced (PSES?=?-0.83, 95% CI: -1.02-0.65, P?=?0.00001) and P300 latency was delayed significantly in FES patients (PSES?=?-0.48, 95% CI: 0.14-0.81, P?=?0.005). The meta-regression analysis showed that task difficulty was a source of heterogeneity.
The meta-analysis confirms that disrupted information processing is found in FES patients, which is maniFESted by smaller P300 amplitude and delayed P300 latency.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
83Perspect Psychiatr Care 2014 Apr 50: 102-10
PMID24308894
TitlePredictive value of prospective memory for remission in first-episode schizophrenia.
AbstractThe study examined the rate of remission in individuals experiencing a first episode of schizophrenia (FES) in China and explored predictors of remission in the acute phase of the illness.
Fifty-five FES patients were randomly treated with risperidone, olanzapine, or aripiprazole at therapeutic doses for 8 weeks, and their clinical profiles and cognition were assessed using standardized assessment instruments at entry and the end of the study.
Of the 55 patients, 30 (54.5%) remitted by the end of the 8-week study. In univariate analyses, shorter duration of untreated psychosis, higher scores on both the time-based prospective memory (TBPM) and event-based prospective memory tasks and the Hopkins Verbal Learning Test-revised, and less severe negative symptoms were significantly associated with remission. In stepwise multiple logistic regression analyses, only higher scores on the TBPM significantly predicted remission. Individuals having higher scores reflecting better TBPM at baseline were more likely to achieve remission after 8 weeks of optimized antipsychotic treatment.
TPBM may be useful in helping clinicians identify those FES patients most likely to achieve a favorable treatment response.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
84J Psychiatr Res 2014 Jan 48: 79-85
PMID24157247
TitleObstetrical complications and Apgar score in subjects at risk of psychosis.
AbstractThe objective of the study was to identify associations between a history of obstetrical complications (OCs) and the future development of symptoms indicating risk of psychosis (At Risk Mental State - ARMS). The frequency of OCs was assessed in 66 ARMS subjects, 50 subjects with the first episode of schizophrenia (FES) and 50 healthy controls. Obstetrical data was obtained from medical documentation and evaluated with the Lewis and Murray Scale. Definite OCs, according to the Lewis and Murray Scale, occurred significantly more frequently in the ARMS group compared to the controls (?(2) = 7.79, p = 0.005; OR = 4.20, 95% CI = 1.46-12.11), as well as in the FES subjects compared to the controls (?(2) = 8.39, p = 0.004; OR = 4.64, 95% CI = 1.56-13.20). Apgar scores in the first (Apgar 1) and the fifth minute after birth (Apgar 5) were significantly lower in the FES subjects compared to the controls (for Apgar 1 score Z = 4.439, p < 0.0001; for Apgar 5 score Z = 5.250, p < 0.0001). The ARMS subjects demonstrated significantly lower Apgar 5 scores compared to the healthy controls (Z = 3.458, p = 0.0016). The results indicate that OCs and low Apgar 5 score should be considered important factors in identifying subjects at risk of developing psychosis.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
85Schizophr. Res. 2014 Dec 160: 57-66
PMID25458859
TitleBoth volumetry and functional connectivity of Heschl's gyrus are associated with auditory P300 in first episode schizophrenia.
AbstractReduced gray matter volume in left superior temporal gyrus (STG) is considered to be associated with auditory P300 amplitude in schizophrenia. Little is known about possible pathological circuits regarding sub-regions of STG that contribute to auditory P300 abnormality in schizophrenia. The current study investigated gray matter volume in STG and functional connectivity of Heschl's gyrus in first-episode schizophrenia (FESZ), as well as their correlations with P300 amplitude.
Nineteen FESZ patients and 19 healthy controls contributed MRI scans. Eighteen patients and 17 controls underwent auditory P300 test within 1 week after MRI scanning. STG structural abnormalities were analyzed using voxel-based morphometry (VBM) analysis. Bilateral Heschl's gyri (HG) were selected as seeds for FC analysis in resting MRI data. Correlations of P300 amplitude with gray matter alterations in STG and HG-based FC were analyzed using Pearson correlation analysis within each group.
Compared to healthy controls, FESZ patients showed reduced gray matter in left STG and P300 amplitude. Gray matter volume of left Heschl's gyrus was positively correlated with P300 amplitude in FESZ patients. HG-based FC of resting fMRI was decreased in the inferior frontal gyrus (IFG), medial frontal gyrus (MFG), anterior cingulate cortex (ACC), and left temporal pole, whereas the same metric was increased in the lingual gyrus, precuneus and cerebellar tonsil among FESZ patients. FC between bilateral HG and precuneus was inversely correlated with P300 amplitude among healthy controls, and was absent among FES patients.
The findings point towards both decreased volume of Heschl's gyrus and its altered functional pathways may contribute to auditory P300 abnormality in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
86PLoS ONE 2014 -1 9: e111562
PMID25365028
TitleProspective memory performance in non-psychotic first-degree relatives of patients with schizophrenia: a controlled study.
AbstractWe aimed at investigating prospective memory and its socio-demographic and neurocognitive correlates in non-psychotic, first-degree relatives (FDRs) of patients with schizophrenia compared to patients with first episode schizophrenia (FES), and healthy controls (HCs).
Forty-seven FES patients, 50 non-psychotic FDRs (23 offspring and 27 siblings) of patients with chronic schizophrenia (unrelated to the FES group) and 51 HCs were studied. The Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT) was used to measure time-based prospective memory (TBPM) and event-based prospective memory (EBPM) performance. Other cognitive functions (involving respective memory and executive functions) were evaluated with standardized tests.
After controlling for basic demographic characteristics including age, gender and educational level, there was a significant difference between FDRs, FES and HCs with respect to both TBPM (F(2,142)?=?10.4, p<0.001) and EBPM (F(2,142)?=?10.8, p<0.001). Multiple linear regression analyses revealed that lower scores of the Hopkins Verbal Learning Test-Revised (HVLT-R) and the STROOP Word-Color Test (SWCT) contributed to TBPM impairment, while lower educational level and higher scores of the Color Trails Test-2 (CTT-2) contributed to EBPM deficit in FDRs.
FDRs share similar but attenuated prospective memory impairments with schizophrenia patients, suggesting that prospective memory deficits may represent an endophenotype of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
87JAMA Psychiatry 2014 Dec 71: 1350-63
PMID25321337
TitleCardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study.
AbstractThe fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear.
To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity.
Baseline results of the Recovery After an Initial schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment.
Prebaseline antipsychotic treatment was based on the community clinician's and/or patient's decision.
Body composition and fasting lipid, glucose, and insulin parameters.
In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P<.01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P=.04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P?.01). In multivariable analyses, olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P?.02).
In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy liFEStyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
88Eur. J. Clin. Pharmacol. 2014 Dec 70: 1433-41
PMID25291992
TitleEffects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients.
AbstractAlterations in one-carbon metabolism (OCM) have been repeatedly reported in schizophrenia. However, there is a scarcity of studies addressing the effects of antipsychotics on selected OCM markers in schizophrenia and provided results are inconsistent.
We recruited 39 first-episode schizophrenia (FES) patients and determined serum profile of total homocysteine (tHcy), folate, vitamin B12, lipoproteins and glucose at baseline and after 12 weeks of treatment with second-generation antipsychotics (SGA) including olanzapine and risperidone in monotherapy.
After 12 weeks of treatment, all patients had significantly higher body mass index (BMI), serum levels of total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG) and tHcy together with significantly lower levels of folate and vitamin B12. The analysis of differences between SGA revealed the same biochemical alterations in patients treated with olanzapine as in the whole group, while those receiving risperidone had no statistically significant changes in serum folate, vitamin B12 and TG. There was a significantly higher increase in BMI and TC in patients treated with olanzapine in comparison with those treated with risperidone. Patients receiving olanzapine had a higher decrease in vitamin B12 than those assigned to the treatment with risperidone. Changes in folate, vitamin B12, tHcy and TC levels were significant only in males, even after Bonferroni correction. Multiple regression analysis revealed that changes in tHcy levels are associated with gender and baseline metabolic parameters (BMI, glucose, TC, LDL and HDL) but not with selected SGA.
These results indicate that SGA may influence OCM, especially in first-episode schizophrenia (FES) males.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
89Schizophr. Res. 2014 Oct 159: 80-9
PMID25132644
TitleHyper-coupling between working memory task-evoked activations and amplitude of spontaneous fluctuations in first-episode schizophrenia.
AbstractWorking memory (WM) deficit is an important component of impaired cognition in schizophrenia. However, between-studies inconsistencies as to the specific functional substrate imply that inter-individual variability (IIV) in the WM performance is associated with IIV in brain activity in schizophrenia. To examine the neural substrate of this WM IIV, we studied whether the neural mechanisms that underlie individual differences in WM capacity are the same in schizophrenia patients and healthy people. We correlated the IIV of the task-evoked brain activity and task performance during an n-back WM task with the IIV of the moment-to-moment variability in intrinsic resting-state activity, as measured by the amplitude of low-frequency fluctuations (ALFFs) and further compared this relationship between 17 patients with first-episode schizophrenia (FES) and 18 healthy controls. Between-group comparisons of the correlation patterns indicated aberrant ALFF-WM activation correlations and ALFF-WM performance correlations in the FES patients, but no significant changes were detected in any single measurement of these three characteristics. Specifically, we found increased positive ALFF-WM activation correlations in the bilateral lateral prefrontal cortices, posterior parietal cortices and fusiform gyri in the FES patients. We also observed significant increases in positive ALFF-WM performance correlations in the bilateral ventromedial prefrontal cortices in the FES patients. This hyper-coupling between the ALFF and fMRI measures during a WM task may indicate that it was difficult for the patients to detach themselves from one state to transition to another and suggests that the inefficient cortical function in schizophrenia stems from the intrinsic functional architecture of the brain.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
90Schizophr. Res. 2014 Sep 158: 45-51
PMID24924404
TitleFrequency and pattern of childhood symptom onset reported by first episode schizophrenia and clinical high risk youth.
AbstractPsychosis prevention and early intervention efforts in schizophrenia have focused increasingly on sub-threshold psychotic symptoms in adolescents and young adults. Although many youth report symptom onset prior to adolescence, the childhood incidence of prodromal-level symptoms in those with schizophrenia or related psychoses is largely unknown.
This study reports on the retrospective recall of prodromal-level symptoms from 40 participants in a first-episode of schizophrenia (FES) and 40 participants at "clinical high risk" (CHR) for psychosis. Onset of positive and non-specific symptoms was captured using the Structured Interview for Prodromal Syndromes. Frequencies are reported according to onset during childhood (prior to age 13), adolescence (13-17), or adulthood (18+).
Childhood-onset of attenuated psychotic symptoms was not rare. At least 11% of FES and 23% of CHR reported specific recall of childhood-onset of unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most recalled experiencing non-specific symptoms prior to positive symptoms. CHR and FES did not differ significantly in the timing of positive and non-specific symptom onset. Other than being younger at assessment, those with childhood onset did not differ demographically from those with later onset.
Childhood-onset of initial psychotic-like symptoms may be more common than previous research has suggested. Improved characterization of these symptoms and a focus on their predictive value for subsequent schizophrenia and other major psychoses are needed to facilitate screening of children presenting with attenuated psychotic symptoms. Accurate detection of prodromal symptoms in children might facilitate even earlier intervention and the potential to alter pre-illness trajectories.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
91Neuropsychiatr Dis Treat 2014 -1 10: 687-93
PMID24812513
TitleIncreased serum dehydroepiandrosterone sulfate in the first episode but not in subsequent episodes in male patients with schizophrenia.
AbstractMany studies have investigated the relationship between blood levels of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEA-S), cortisol, progesterone, and testosterone and the onset, prognosis, symptom severity, and treatment response of schizophrenia. In the present study, we assessed potential differences in blood levels of neurosteroids between drug-naïve first-episode patients with schizophrenia (FES), and drug-free patients with schizophrenia who were not in the first episode but were in a phase of acute exacerbation (DFP).
The present study included 32 male FES, 28 male DFP, and 24 male healthy controls (HC). Groups were compared in terms of blood levels of adrenocorticotropic hormone (ACTH), cortisol, testosterone, progesterone, and DHEA-S.
Blood levels of ACTH, cortisol, testosterone, and progesterone were similar among the groups. The mean value of serum DHEA-S was significantly different among the groups (P<0.001). The value of serum DHEA-S was higher in the FES group than in the DFP and HC groups (both P<0.001). The mean values of serum DHEA-S in the HC and DFP groups were found to be similar (P=0.33).
We suggest that higher values of DHEA-S in the FES group compared with both the DFP and HC groups indicate that this neurosteroid response is unique to first-episode schizophrenia patients. Further studies are needed to investigate the difference in blood levels of neurosteroids in different groups in terms of age of diagnosis.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
92Chin. Med. J. 2014 -1 127: 1651-5
PMID24791869
TitleDifferences in P50 and prepulse inhibition of the startle reflex between male smokers and non-smokers with first episode schizophrenia without medical treatment.
AbstractNicotine may improve schizophrenia patient's cognitive deficit symptoms. This study was to explore the chronic effects of smoking on prepulse inhibition of the startle reflex (PPI) and P50 in the patients with first-episode schizophrenia (FES).
The event-related potentials (ERP) recording and analysis instrument made by Brain Products, Germany, was used to detect PPI and P50 in 49 male FES patients (FES group, n = 21 for smokers and n = 28 for non-smokers) and 43 normal male controls (control group, n = 19 for smokers and n = 24 for non-smokers).
Compared with normal controls, the FES group had prolonged PPI latency when elicited by single stronger stimulus (P < 0.05); the FES group had prolonged PPI latency and increased PPI amplitude (P < 0.05, 0.01) when elicited by weak and strong stimuli. The FES group had lower PPI inhibition rate than normal controls (P < 0.05). Compared with normal controls, the FES group had increased P50-S2 amplitude and increased amplitude ratio S2/S1 (both P <0.05). In the control group, the smokers had a tendency of increase in P50-S2 amplitude (P > 0.05) and shorter P50-S2 latency (P < 0.05) than the non-smokers. The smokers had higher PPI amplitude than the non-smokers (P < 0.05). In the FES group, the smokers had higher P50-S1 amplitude, shorter P50-S2 latency, and higher amplitude ratio S2/S1 than the non-smokers (P < 0.05, 0.01). The smokers had higher PPI amplitude than the non-smokers (P < 0.05).
There is obvious PPI and P50 deficits in schizophrenic patients. However, these deficits are relatively preserved in the smokers compared with the non-smokers, which suggests that long-term smoking might partially improve the sensory gating in schizophrenic patients. Whether this conclusion can be deduced to female patients requires further follow-ups.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
93Metab Brain Dis 2014 Sep 29: 661-70
PMID24682777
TitleElevated homocysteine level in first-episode schizophrenia patients--the relevance of family history of schizophrenia and lifetime diagnosis of cannabis abuse.
AbstractAccumulating evidence indicates that elevated homocysteine (Hcy) level occurs in first-episode schizophrenia (FES) patients. We included 56 FES patients and 53 healthy controls (HC). Plasma level of Hcy was significantly higher in FES patients than HC (p?=?0.044). In addition, plasma levels of high-density lipoproteins (HDL) and folate were significantly lower in FES than in HC (p?schizophrenia was associated with lower plasma HDL (p?=?0.041) and vitamin B12 (p?=?0.017), as well as higher level of Hcy (p?=?0.017). Patients with FES, who abused cannabis, had higher levels of Hcy (p?=?0.017), as well as lower levels of vitamin B12 (p?=?0.017) and HDL (p?=?0.041). Plasma Hcy negatively correlated with duration of untreated psychosis (r?=?-0.272, p?=?0.042). There was a positive correlation between Hcy level and the severity of negative symptoms (r?=?0.363, p?=?0.006) and general psychopathology (r?=?0.349, p?=?0.008) assessed using Positive and Negative Syndrome Scale (PANSS). Vitamin B12 level was negatively associated with the severity of negative symptoms (r?=?-0.406, p?=?0.002), while folate level negatively correlated with general psychopathology score (r?=?-0.365, p?=?0.006) in PANSS. These results indicate that the severity of one-carbon metabolism alterations and HDL deficiency might be associated with family history of schizophrenia and cannabis abuse. Lower vitamin B12 and folate along with elevated Hcy may influence the severity of FES psychopathology.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
94Compr Psychiatry 2014 May 55: 785-91
PMID24556516
TitleBasic symptoms and psychotic symptoms: their relationships in the at risk mental states, first episode and multi-episode schizophrenia.
AbstractIn the field of the early psychosis two main approaches attempt to develop rating tools, one investigating the basic symptoms domain, and the other the attenuated psychotic symptoms. To explore the relationship between basic symptoms (BSs) and other symptom domains in different phases of the psychotic illness 32 at ultra-high risk (UHR), 49 first episode schizophrenia (FES), 42 multiple episode schizophrenia (MES), and 28 generalized anxiety disorder (GAD) patients were enrolled. Participants were assessed using the SIPS/SOPS and the FCQ scales. Analyses of covariance taking into account socio-demographic and clinical variables significantly different between groups were applied to compare FCQ and SOPS scores. Finally FCQ and SOPS principal component analysis was carried out in the schizophrenia spectrum group. SOPS scores were higher in the UHR, FES and MES groups compared to the GAD control group. Concordantly, FES and MES groups had a higher number of basic symptoms in comparison with the GAD group, whereas UHR did not differ from the control group. The largest number of correlations between BSs and psychotic symptoms was found in the GAD group. According to the principal component analysis (PCA) five factors were extracted, with the BSs loading on a unique factor. Our findings imply that the boundary between psychotic and non-psychotic conditions cannot be outlined on the basis of the presence/absence of basic and psychotic symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
95Pharmacogenomics 2014 Feb 15: 189-99
PMID24444409
TitlePatterns of variation influencing antipsychotic treatment outcomes in South African first-episode schizophrenia patients.
AbstractMany antipsychotic pharmacogenetics studies have been performed examining candidate genes or known variation; however, our understanding of the genetic factors involved in antipsychotic pharmacogenetic traits remains limited.
A well-characterized cohort of first-episode schizophrenia (FES) patients was used to identify a subset of nonresponders and responders to antipsychotic treatment for exome sequencing (n = 11). The variation observed in the responders and nonresponders was subsequently compared and a prioritization strategy was employed to identify variants for genotyping in the entire FES cohort (n = 103) as well as an additional Xhosa schizophrenia cohort (n = 222).
Examination of coding variation revealed a potential role for rare loss-of-function variants in treatment response outcomes. One variant, rs11368509, was found to be weakly associated with better treatment outcomes in the FES cohort (p = 0.057) and the Xhosa schizophrenia cohort (p = 0.016). In addition, the majority of the loss-of-function variation that was considered likely to be involved in antipsychotic treatment response was either novel or rare in Asian and European populations.
This pilot study has highlighted the importance of exome sequencing for antipsychotic pharmacogenomics studies, particularly in African individuals. Furthermore, the results emphasize once again the complexity of antipsychotic pharmacogenomics and the need for future research.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
96Psychol Med 2014 Sep 44: 2489-501
PMID24443827
TitleExtensive brain structural network abnormality in first-episode treatment-naive patients with schizophrenia: morphometrical and covariation study.
AbstractAlterations in gray matter (GM) are commonly observed in schizophrenia. Accumulating studies suggest that the brain changes associated with schizophrenia are distributed rather than focal, involving interconnected networks of areas as opposed to single regions. In the current study we aimed to explore GM volume (GMV) changes in a relatively large sample of treatment-naive first-episode schizophrenia (FES) patients using optimized voxel-based morphometry (VBM) and covariation analysis.
High-resolution T1-weighted images were obtained using 3.0-T magnetic resonance imaging (MRI) from 86 first-episode drug-naive patients with schizophrenia and 86 age- and gender-matched healthy volunteers. Symptom severity was evaluated using the Positive and Negative Syndrome Scale (PANSS). GMV was assessed using optimized VBM and in 16 regions of interest (ROIs), selected on the basis of a previous meta-analysis. The relationships between GMVs in the ROIs were examined using an analysis of covariance (ANCOVA).
The VBM analysis revealed that first-episode patients showed reduced GMV in the hippocampus bilaterally. The ROI analysis identified reductions in GMV in the left inferior frontal gyrus, bilateral hippocampus and right thalamus. The ANCOVA revealed different patterns of regional GMV correlations in patients and controls, including of inter- and intra-insula, inter-amygdala and insula-postcentral gyrus connections.
schizophrenia involves regional reductions in GMV and changes in GMV covariance in the insula, amygdala and postcentral gyrus. These findings were evident at the onset of the disorder, before treatment, and therefore cannot be attributable to the effects of chronic illness progression or medication.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
97Schizophr Bull 2014 Sep 40: 1072-82
PMID24191160
TitleAltered brain long-range functional interactions underlying the link between aberrant self-experience and self-other relationship in first-episode schizophrenia.
AbstractSelf-experience anomalies are elementary features of schizophrenic pathology. Such deficits can have a profound impact on self-other relationship, but how they are related through aberrant brain function remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, we provide new evidence for a cortical link between aberrant self-experience and social cognition in first-episode schizophrenia (FES). As identified in previous studies, ventral premotor cortex (vPMC) and posterior insula (pIC) are candidate brain regions underlying disturbances in both self-experience and self-other relationship due to their processing of predominantly externally guided (vPMC; goal-oriented behavior) and internally guided (pIC; interoception) stimuli. Results from functional interaction analysis in a sample of 24 FES patients and 22 healthy controls show aberrant functional interactions (background/intrinsic connectivity) of right vPMC and bilateral pIC with posterior cingulate cortex (PCC), a midline region that has been shown central in mediating self-experience. More specifically, our results show increased functional coupling between vPMC and PCC, which positively correlated with basic symptoms (subjective self-experience disturbances). pIC showed reduced functional coupling with PCC and postcentral gyrus and increased functional interactions with anterior insula. Taken together, our results suggest an imbalance in the processing between internally and externally guided information and its abnormal integration with self-referential processing as mediated by PCC. Due to our correlation findings, we suggest this imbalance to be closely related to basic symptoms in FES and thus anomalous self-experience. The findings further disentangle the cortical basis of how self-experience anomalies may pervade the social domain.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
98MAGMA 2014 Aug 27: 283-90
PMID24100864
TitleAssociation of white matter deficits with clinical symptoms in antipsychotic-naive first-episode schizophrenia: an optimized VBM study using 3T.
AbstractTo examine the whole brain white matter morphology in antipsychotic-naive patients with first-episode schizophrenia (FES) and its correlations with symptom severity.
High-resolution T1-weighted images of 64 drug-naive FES patients and 64 matched healthy controls were acquired using a 3 T MR imaging system. Then, optimized voxel-based morphometry was performed to compare the group differences. Finally, correlation analyses were conducted between the white matter volume (WMV) changes and clinical symptoms.
The FES showed significantly decreased WMV in the bilateral posterior limb of the internal capsule (PLIC) and right subgyral frontal white matter. The volume of the bilateral PLIC was negatively correlated with the Positive and Negative Syndrome Scale positive scores. Positive correlations were observed between all of the changed WMV measures and the Global Assessment of Functioning scores.
The current findings provide further evidence to support internal capsule and subgyral frontal white matter deficits at the early stage of schizophrenia that are potentially related to the core pathophysiology of the disease. Furthermore, these anatomical alterations were related to the clinical symptoms but not the untreated illness duration, suggesting that these deficits are related to aberrations in the neurodevelopmental process and may be relatively stable during the early course of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
99Nord J Psychiatry 2014 Jul 68: 341-6
PMID24094029
TitleIncreased serum prolactin levels in drug-naive first-episode male patients with schizophrenia.
AbstractProlactin is a hormone receiving considerable attention in psychiatry. Increased serum prolactin level is frequently associated with dopamine blocking antipsychotics. Furthermore, decreased prolactin level was considered a reflector of the effect of antipsychotics. However, there is restricted numbers of investigations that researched baseline prolactin levels in first-episode patients with schizophrenia.
We purpose to investigate serum baseline prolactin levels in drug-naive first-episode patients with schizophrenia (FES) and to explore the differences in serum prolactin levels between FES, drug-free schizophrenic patients (DFS) and healthy controls (HC).
The study was conducted in the Departments of Psychiatry, Gölba?? Hasvak and K?rklareli State Hospitals, Turkey. Thirty male FES, 41 male DFS and 32 male HC were included in study. All participants were clinically examined and individually interviewed. Before initiating any pharmacological treatment, 5 ml of venous blood was collected to measure serum prolactin levels between 08:00 and 10:00 h, which was determined by radioimmunoassay (RIA). Prolactin levels were also collected from the consenting HC using the same assay.
The mean age was higher in the DFS group. The mean score of Brief Psychiatric Rating Scale was higher in the FES group and mean score of Scale for the Assessment of Negative Symptoms was higher in the DFS group. The mean value of prolactin was higher in the FES group (34.1 ± 19.9 ng/dl) compared with DFS (17.9 ± 6.5 ng/dl) and HC (9.7 ± 2.3 ng/dl) (F = 35.5, P < 0.001). Additionally, the mean value of serum prolactin is higher in the DFS group compared with HC (P < 0.001).
To our knowledge, this study is the first to demonstrate higher serum prolactin levels in male FES compared with male DFS and male HC. Prolactin might act as a protective factor while first episode of schizophrenia is experienced. Future studies are needed to provide the role of prolactin in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
100Schizophr Bull 2014 Sep 40: 1128-39
PMID24023251
TitleReduced frontal glutamate + glutamine and N-acetylaspartate levels in patients with chronic schizophrenia but not in those at clinical high risk for psychosis or with first-episode schizophrenia.
AbstractChanges in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy ((1)H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in (1)H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent (1)H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in (1)H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
101Schizophr. Res. 2014 Feb 152: 469-77
PMID23978776
TitleAre there clinically useful predictors and early warning signs for pending relapse?
AbstractDespite the availability of effective long-term treatment strategies in schizophrenia, relapse is still common. Relapse prevention is one of the major treatment objectives, because relapse represents burden and costs for patients, their environment, and society and seems to increase illness progression at the biological level. Valid predictors for relapse are urgently needed to enable more individualized recommendations and treatment decisions to be made.
Mainly recent evidence regarding predictors and early warning signs of relapse in schizophrenia was reviewed. In addition, data from the first-episode (long-term) study (FES; Gaebel et al., 2007, 2011) performed within the German Research Network on schizophrenia were analyzed.
On the basis of FES data, premorbid adjustment, residual symptoms and some side effects are significant predictors. Although a broad spectrum of potential parameters has been investigated in several other studies, only a few and rather general valid predictors were identified consistently. Data of the FES also indicated that predictive power could be enhanced by considering interacting conjunctions, as suggested by the Vulnerability-Stress-Coping model. Prospective studies, however, are rare. In addition, prodromal symptoms as course-related characteristics likewise investigated in the FES add substantially to early recognition of relapse and may serve as early warning signs, but prognosis nevertheless remains a challenge.
Comprehensive and well-designed studies are needed to identify and confirm valid predictors for relapse in schizophrenia. In this respect, broadly accepted and specifically defined criteria for relapse would greatly facilitate comparison of results across studies.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
102Chin. Med. J. 2014 -1 127: 1651-5
PMID24791869
TitleDifferences in P50 and prepulse inhibition of the startle reflex between male smokers and non-smokers with first episode schizophrenia without medical treatment.
AbstractNicotine may improve schizophrenia patient's cognitive deficit symptoms. This study was to explore the chronic effects of smoking on prepulse inhibition of the startle reflex (PPI) and P50 in the patients with first-episode schizophrenia (FES).
The event-related potentials (ERP) recording and analysis instrument made by Brain Products, Germany, was used to detect PPI and P50 in 49 male FES patients (FES group, n = 21 for smokers and n = 28 for non-smokers) and 43 normal male controls (control group, n = 19 for smokers and n = 24 for non-smokers).
Compared with normal controls, the FES group had prolonged PPI latency when elicited by single stronger stimulus (P < 0.05); the FES group had prolonged PPI latency and increased PPI amplitude (P < 0.05, 0.01) when elicited by weak and strong stimuli. The FES group had lower PPI inhibition rate than normal controls (P < 0.05). Compared with normal controls, the FES group had increased P50-S2 amplitude and increased amplitude ratio S2/S1 (both P <0.05). In the control group, the smokers had a tendency of increase in P50-S2 amplitude (P > 0.05) and shorter P50-S2 latency (P < 0.05) than the non-smokers. The smokers had higher PPI amplitude than the non-smokers (P < 0.05). In the FES group, the smokers had higher P50-S1 amplitude, shorter P50-S2 latency, and higher amplitude ratio S2/S1 than the non-smokers (P < 0.05, 0.01). The smokers had higher PPI amplitude than the non-smokers (P < 0.05).
There is obvious PPI and P50 deficits in schizophrenic patients. However, these deficits are relatively preserved in the smokers compared with the non-smokers, which suggests that long-term smoking might partially improve the sensory gating in schizophrenic patients. Whether this conclusion can be deduced to female patients requires further follow-ups.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
103Schizophr Bull 2014 Sep 40: 1072-82
PMID24191160
TitleAltered brain long-range functional interactions underlying the link between aberrant self-experience and self-other relationship in first-episode schizophrenia.
AbstractSelf-experience anomalies are elementary features of schizophrenic pathology. Such deficits can have a profound impact on self-other relationship, but how they are related through aberrant brain function remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, we provide new evidence for a cortical link between aberrant self-experience and social cognition in first-episode schizophrenia (FES). As identified in previous studies, ventral premotor cortex (vPMC) and posterior insula (pIC) are candidate brain regions underlying disturbances in both self-experience and self-other relationship due to their processing of predominantly externally guided (vPMC; goal-oriented behavior) and internally guided (pIC; interoception) stimuli. Results from functional interaction analysis in a sample of 24 FES patients and 22 healthy controls show aberrant functional interactions (background/intrinsic connectivity) of right vPMC and bilateral pIC with posterior cingulate cortex (PCC), a midline region that has been shown central in mediating self-experience. More specifically, our results show increased functional coupling between vPMC and PCC, which positively correlated with basic symptoms (subjective self-experience disturbances). pIC showed reduced functional coupling with PCC and postcentral gyrus and increased functional interactions with anterior insula. Taken together, our results suggest an imbalance in the processing between internally and externally guided information and its abnormal integration with self-referential processing as mediated by PCC. Due to our correlation findings, we suggest this imbalance to be closely related to basic symptoms in FES and thus anomalous self-experience. The findings further disentangle the cortical basis of how self-experience anomalies may pervade the social domain.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
104Nord J Psychiatry 2014 Jul 68: 341-6
PMID24094029
TitleIncreased serum prolactin levels in drug-naive first-episode male patients with schizophrenia.
AbstractProlactin is a hormone receiving considerable attention in psychiatry. Increased serum prolactin level is frequently associated with dopamine blocking antipsychotics. Furthermore, decreased prolactin level was considered a reflector of the effect of antipsychotics. However, there is restricted numbers of investigations that researched baseline prolactin levels in first-episode patients with schizophrenia.
We purpose to investigate serum baseline prolactin levels in drug-naive first-episode patients with schizophrenia (FES) and to explore the differences in serum prolactin levels between FES, drug-free schizophrenic patients (DFS) and healthy controls (HC).
The study was conducted in the Departments of Psychiatry, Gölba?? Hasvak and K?rklareli State Hospitals, Turkey. Thirty male FES, 41 male DFS and 32 male HC were included in study. All participants were clinically examined and individually interviewed. Before initiating any pharmacological treatment, 5 ml of venous blood was collected to measure serum prolactin levels between 08:00 and 10:00 h, which was determined by radioimmunoassay (RIA). Prolactin levels were also collected from the consenting HC using the same assay.
The mean age was higher in the DFS group. The mean score of Brief Psychiatric Rating Scale was higher in the FES group and mean score of Scale for the Assessment of Negative Symptoms was higher in the DFS group. The mean value of prolactin was higher in the FES group (34.1 ± 19.9 ng/dl) compared with DFS (17.9 ± 6.5 ng/dl) and HC (9.7 ± 2.3 ng/dl) (F = 35.5, P < 0.001). Additionally, the mean value of serum prolactin is higher in the DFS group compared with HC (P < 0.001).
To our knowledge, this study is the first to demonstrate higher serum prolactin levels in male FES compared with male DFS and male HC. Prolactin might act as a protective factor while first episode of schizophrenia is experienced. Future studies are needed to provide the role of prolactin in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
105Transl Psychiatry 2015 -1 5: e626
PMID26305477
TitleApoptotic markers in cultured fibroblasts correlate with brain metabolites and regional brain volume in antipsychotic-naive first-episode schizophrenia and healthy controls.
AbstractCultured fibroblasts from first-episode schizophrenia patients (FES) have shown increased susceptibility to apoptosis, which may be related to glutamate dysfunction and progressive neuroanatomical changes. Here we determine whether apoptotic markers obtained from cultured fibroblasts in FES and controls correlate with changes in brain glutamate and N-acetylaspartate (NAA) and regional brain volumes. Eleven antipsychotic-naive FES and seven age- and gender-matched controls underwent 3-Tesla magnetic resonance imaging scanning. Glutamate plus glutamine (Glx) and NAA levels were measured in the anterior cingulate (AC) and the left thalamus (LT). Hallmarks of apoptotic susceptibility (caspase-3-baseline activity, phosphatidylserine externalization and chromatin condensation) were measured in fibroblast cultures obtained from skin biopsies after inducing apoptosis with staurosporine (STS) at doses of 0.25 and 0.5 ?M. Apoptotic biomarkers were correlated to brain metabolites and regional brain volume. FES and controls showed a negative correlation in the AC between Glx levels and percentages of cells with condensed chromatin (CC) after both apoptosis inductions (STS 0.5 ?M: r = -0.90; P = 0.001; STS 0.25 ?M: r = -0.73; P = 0.003), and between NAA and cells with CC (STS 0.5 ?M induction r = -0.76; P = 0.002; STS 0.25 ?M r = -0.62; P = 0.01). In addition, we found a negative correlation between percentages of cells with CC and regional brain volume in the right supratemporal cortex and post-central region (STS 0.25 and 0.5 ?M; P < 0.05 family-wise error corrected (FWEc)). We reveal for the first time that peripheral markers of apoptotic susceptibility may correlate with brain metabolites, Glx and NAA, and regional brain volume in FES and controls, which is consistent with the neuroprogressive theories around the onset of the schizophrenia illness.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
106Epigenomics 2015 -1 7: 1275-85
PMID26212695
TitleLower LINE-1 methylation in first-episode schizophrenia patients with the history of childhood trauma.
AbstractWe investigated methylation of DNA repetitive sequences (LINE-1 and BAGE) in peripheral blood leukocytes from first-episode schizophrenia (FES) patients and healthy controls (HCs) with respect to childhood adversities.
Patients were divided into two subgroups based on the history of childhood trauma - FES(+) and FES(-) subjects. The majority of HCs had a negative history of childhood trauma - HCs(-) subjects.
FES(+) patients had significantly lower LINE-1 methylation in comparison with FES(-) patients or HC(-) subjects. Emotional abuse and total trauma score predicted lower LINE-1 methylation in FES patients, while general trauma score was associated with lower BAGE methylation in HCs.
Childhood adversities might be associated with global DNA hypomethylation in adult FES patients.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
107Chin. Med. J. 2015 Aug 128: 2215-9
PMID26265616
TitleFollow-up of N400 in the Rehabilitation of First-episode Schizophrenia.
AbstractThe N400 component of event-related potentials (ERP) has recently drawn widespread attention at home and abroad. This study was to explore the relationship between N400 changes and risperidone treatment and rehabilitation infirst-episode schizophrenia (FES).
ERP component N400 was recorded by Guangzhou Runjie WJ-1 ERP instruments, in 58 FES before and 6 months, 15 months after risperidone treatment, and in 62 normal controls. The patients' syndromes were assessed by Positive and Negative Syndrome Scale (PANSS). And the stimuli are Chinese sentences with matching (congruent) or mismatching (incongruent) ending words.
N400 latencies were prolonged, and amplitudes were decreased in Cz, Pz, Fz, C3, C4, in FES compared with in NC, before treatment. The prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS. There are significant differences of N400 amplitudes and latencies in 6 months and 15 months follow-up after treatment. Before treatment, 6 months and 15 months after treatment, N400 latencies are 446 ± 35 ms, 440 ± 37 ms, 414 ± 31 ms (F = 9.72, P < 0.01) in incongruent situation; N400 amplitudes are 5.2 ± 4.6 ?V, 5.7 ± 4.8 ?V, 7.3 ± 5.0 ?V (F = 2.06, P > 0.05) in congruent situation, and 8.5 ± 5.9 ?V, 10.1 ± 5.0 ?V, 11.9 ± 7.0 ?V (F = 3.697, P < 0.05) in incongruent situation.
N400 could be used to predict the effects of treatment of schizophrenia to some degree. The linguistic and cognitive impairment in schizophrenia can be improved by antipsychotic drugs.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
108Schizophr Bull 2015 Dec -1: -1
PMID26685867
TitleAltered Neural Correlate of the Self-Agency Experience in First-Episode Schizophrenia-Spectrum Patients: An fMRI Study.
AbstractThe phenomenology of the clinical symptoms indicates that disturbance of the sense of self be a core marker of schizophrenia.
To compare neural activity related to the self/other-agency judgment in patients with first-episode schizophrenia-spectrum disorders (FES, n = 35) and healthy controls (HC, n = 35).
A functional magnetic resonance imaging (fMRI) using motor task with temporal distortion of the visual feedback was employed. A task-related functional connectivity was analyzed with the use of independent component analysis (ICA).
(1) During self-agency experience, FES showed a deficit in cortical activation in medial frontal gyrus (BA 10) and posterior cingulate gyrus, (BA 31; P < .05, Family-Wise Error [FWE] corrected). (2) Pooled-sample task-related ICA revealed that the self/other-agency judgment was dependent upon anti-correlated default mode and central-executive networks (DMN/CEN) dynamic switching. This antagonistic mechanism was substantially impaired in FES during the task.
During self-agency experience, FES demonstrate deficit in engagement of cortical midline structures along with substantial attenuation of anti-correlated DMN/CEN activity underlying normal self/other-agency discriminative processes.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
109Eur Arch Psychiatry Clin Neurosci 2015 Oct -1: -1
PMID26499939
TitleDriving skills in unmedicated first- and recurrent-episode schizophrenic patients.
AbstractThe present study was designed to examine driving skills according to regulations of the German guidelines for road and traffic safety in unmedicated schizophrenic inpatients. A total of 13 first-episode (FES) and 13 recurrent-episode (RES) schizophrenic inpatients were included in the analysis and compared with a group of 20 healthy controls (HC). Data were collected with the computerised Wiener Testsystem measuring visual perception, reactivity and stress tolerance, concentration and vigilance. Analysis of data indicates that a great proportion (58 %) of schizophrenic patients were impaired in psychomotor functions related to driving skills. FES and RES significantly differed with respect to driving ability with a greater proportion in the FES (38 %) showing severe impairments when compared with RES (25 %). Differences with respect to HC performance were most pronounced in concentration and for the FES additionally in visual perception. Analysis of our data indicates that a great proportion of schizophrenic patients are impaired in psychomotor functions related to driving skills that cannot be attributed to adverse side effects of psychopharmacological treatment. Besides, we cannot confirm a chronical decline of psychomotor functions related to driving skills at least in the early course of schizophrenic illness.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
110Sci Rep 2015 -1 5: 14505
PMID26403064
TitleDecreased bilateral thalamic gray matter volume in first-episode schizophrenia with prominent hallucinatory symptoms: A volumetric MRI study.
AbstractStudies comparing gray matter (GM) volume of schizophrenic patients with or without auditory verbal hallucinations (AVHs) to that of normal controls remain controversial. This project aims to investigate changes of GM volumes of drug-naïve schizophrenic patients with and without AVHs. Eighteen first episode schizophrenic (FES) patients with AVHs, 18 FES patients without AVHs, and 18 healthy controls were scanned using structural MRI. Voxel-based morphometry (VBM) analysis was conducted to investigate changes of GM volume among the three groups. Patients with and without AVHs exhibited reduced GM volumes relative to normal controls in the left superior temporal gyrus, frontal regions, cerebellum and caudate. Further analysis of the GM of subcortical structures found that patients with AVHs had reduced thalamic volume than healthy controls. No significant difference was found between patients with and without AVHs. Significant correlation was found between the total scores of the Positive and Negative Syndrome Scale and bilateral thalamic volume. ROC analysis of thalamic volumes of the patients with AVHs and normal controls showed that the area under the curve was 0.698 (P = 0.043). The decreased thalamic volumes might serve as a biomarker for discriminating FES AVHs patients from normals.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
111BMC Psychiatry 2015 -1 15: 152
PMID26149490
TitleReduced cortical thickness in right Heschl's gyrus associated with auditory verbal hallucinations severity in first-episode schizophrenia.
AbstractAuditory verbal hallucinations (AVHs) represent one of the most intriguing phenomena in schizophrenia, however, brain abnormalities underlying AVHs remain unclear. The present study examined the association between cortical thickness and AVHs in first-episode schizophrenia.
High-resolution MR images were obtained in 49 first-episode schizophrenia (FES) patients and 50 well-matched healthy controls (HCs). Among the FES patients, 18 suffered persistent AVHs ("auditory hallucination" AH group), and 31 never experienced AVHs ("no hallucination" NH group). The severity of AVHs was rated by the Auditory Hallucinations Rating Scale (AHRS). Cortical thickness differences among the three groups and their association with AVHs severity were examined.
Compared to both HCs and NH patients, AH patients showed lower cortical thickness in the right Heschl's gyrus. The degree of reduction in the cortical thickness was correlated with AVH severity in the AH patients.
Abnormalities of cortical thickness in the Heschl's gyrus may be a physiological factor underlying auditory verbal hallucinations in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
112Schizophr. Res. 2015 Aug 166: 65-8
PMID26004692
TitleCognitive insight in first-episode schizophrenia: further evidence for a role of the ventrolateral prefrontal cortex.
AbstractIn people with psychoses, Self-Reflectiveness may rely on the right ventrolateral prefrontal cortex (VLPFC). We used functional magnetic resonance imaging (fMRI) and a novel virtual reality paradigm to evaluate the role of the VLPFC for Self-Reflectiveness in 25 first-episode of schizophrenia (FES) participants and 24 controls. Participants first viewed 20 characters each paired with a unique object/location, and later completed source memory judgements during fMRI scanning. Self-Reflectiveness, measured with the Beck Cognitive Insight Scale, was significantly and positively correlated to activation in bilateral VLPFC in FES, but not in controls, providing further evidence that the VLPFC supports Self-Reflectiveness in FES.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
113Psychiatry Res 2015 Mar 226: 383-8
PMID25618471
TitleHigher total cholesterol level is associated with suicidal ideation in first-episode schizophrenia females.
AbstractThere are inconsistent reports showing that the relationship between total cholesterol (TC) level and suicidality might be gender-specific. We compared 30 first-episode schizophrenia (FES) patients reporting suicidal ideation based on the Operational Criteria for Psychotic Illness (OPCRIT) checklist with 70 FES patients, who have never experienced suicidal ideation. After controlling for potential confounders, higher TC was associated with suicidal ideation only in FES females. Future studies should disentangle biological underpinnings of this gender-specific association.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
114Schizophr Bull 2015 Sep 41: 1095-104
PMID25616505
TitleMeta-analysis of Cognitive Impairment in First-Episode Bipolar Disorder: Comparison With First-Episode Schizophrenia and Healthy Controls.
AbstractNeurocognitive deficits are evident both in established schizophrenia and bipolar disorder (BP). However, it has been suggested that schizophrenia, but not BP, is characterized by neurodevelopmental abnormalities that can lead to cognitive deficits at the earliest stages of the illness. The aim of this meta-analytic review was to compare neurocognitive deficits in first-episode BP (FEBP) with healthy controls and first-episode schizophrenia (FES) patients. The current meta-analysis included a total of 22 adult studies and involved comparisons of 533 FEBP patients with 1417 healthy controls and 605 FEBP and 822 FES patients. FEBP patients were significantly impaired in all cognitive domains (d = 0.26-0.80) and individual tasks (d = 0.22-0.66) investigated. FES patients significantly underperformed FEBP patients in most cognitive domains (d = 0.05-0.63) and on individual tasks (d = 0.13-0.77). Neuropsychological impairment, which is comparable to chronic BP, was evident in FEBP. Similar to chronic patients, cognitive functions in FEBP lie intermediate between FES and healthy controls. Neurodevelopmental factors are likely to play a significant role not only in schizophrenia but also in BP.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
115Front Behav Neurosci 2015 -1 9: 322
PMID26733828
TitleComparison of Visuospatial and Verbal Abilities in First Psychotic Episode of Schizophrenia Spectrum Disorder: Impact on Global Functioning and Quality of Life.
AbstractDeficit in visuospatial functions can influence both simple and complex daily life activities. Despite the fact that visuospatial deficit was reported in schizophrenia, research on visuospatial functions as an independent entity is limited. Our study aims to elucidate the impact of visuospatial deficit in comparison with verbal deficit on global functioning and quality of life in the first psychotic episode of schizophrenia spectrum disorder (FES). The significance of clinical symptoms and antipsychotic medication was also studied.
Thirty-six FES patients and a matched group of healthy controls (HC group) were assessed with a neuropsychological battery focused on visuospatial (VIS) and verbal (VERB) functions. Using multiple regression analysis, we evaluated the cumulative effect of VERB and VIS functions, psychiatric symptoms (PANSS) and antipsychotic medication on global functioning (GAF) and quality of life (WHOQOL-BREF) in the FES group.
The FES group demonstrated significant impairment both in VIS and VERB cognitive abilities compared to the HC group. Antipsychotic medication did not significantly affect either VIS or VERB functioning. PANSS was not related to cognitive functioning, apart from the Trail Making Test B. In the FES group, the GAF score was significantly affected by the severity of positive symptoms and VERB functioning, explaining together 60% of GAF variability. The severity of negative and positive symptoms affected only the Physical health domain of WHOQOL-BREF. The degree of VERB deficit was associated with both Physical and Psychological health. Although we did not find any relation between VIS functioning, GAF, and WHOQOL-BREF, a paradoxical finding emerged in the Environment quality domain, where a worse quality of the environment was associated with better VIS functioning.
Our results suggest that the deficit in VIS functions is an integral part of cognitive deficit in schizophrenia spectrum disorders, rather than a side effect of symptomatology or antipsychotic medication. Moreover, VERB functioning was a better predictor of GAF and WHOQOL-BREF than VIS functioning. Given the findings of negative or missing effect of VIS deficit on WHOQOL-BREF and GAF, the accuracy of these measures in evaluating the impact of global cognitive deficit on everyday life in schizophrenia could be questioned.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
116Sci Rep 2015 -1 5: 18069
PMID26656662
TitleDuration of Untreated Psychosis and Brain Function during Verbal Fluency Testing in First-Episode Schizophrenia: A Near-Infrared Spectroscopy Study.
AbstractA longer duration of untreated psychosis (DUP) has been associated with poor clinical outcomes in patients with schizophrenia (SZ); however, it remains unclear whether this is due to neurotoxic effects of psychosis. The purpose of this study was to use near-infrared spectroscopy (NIRS) to investigate the influence of DUP on brain function using two verbal fluency tests (VFTs) in patients with first-episode SZ (FES). A total of 28 FES patients and 29 healthy controls (HC) underwent NIRS during VFTs. Group comparisons of cortical activity were made using two-tailed t-tests and the false discovery rate method. We then examined the associations between DUP and hemodynamic changes in each channel to identify any effects of DUP on brain cortical activity. During the letter VFT, the HC group exhibited significantly greater cortical activations over bilateral frontotemporal regions compared to FES patients. However, this distinction was not observed while performing a category version of the VFT. In addition, no associations between DUP and brain cortical activity were observed in the FES group during either VFT. In conclusion, we did not find an association between DUP and frontotemporal cortical activities. This might be because neurodevelopmental disturbances result in neurocognitive deficits long before psychotic symptoms onset.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
117Psychiatry Res 2015 Jan 225: 129-32
PMID25467699
TitleSeverity of core symptoms in first episode schizophrenia and long-term remission.
AbstractA definable concept of symptomatic remission in schizophrenia has been proposed by the Remission in schizophrenia Working Group (RSWG). Nevertheless no studies to date assessed eventual differences in core symptoms at onset between remitters and non-remitters. The present study evaluated whether the severity of core symptoms differed among 48 patients with first episode schizophrenia (FES), and whether it predicted long-term (16-years) remission. Particularly, the present study aimed to verify if RSWG remission criteria might identify a sub-group of patients with mild core symptoms at their first episode. In the present study the severity of core symptoms was significantly lower in remitted than in non-remitted patients; interestingly, five out of the eight core symptoms already satisfied the severity criteria for remission in most remitted patients. Among the core symptoms only the severity of social withdrawal predicted the long-term outcome, while age at onset, duration of untreated psychosis and employment status did not exert any effect. Concluding, patients with FES presenting, mild core symptoms, particularly low negative symptoms, were more likely to reach long-term remission. Therefore, RSWG remission criteria seem to identify a subgroup of FES patients with mild severe core symptoms so with a higher probability to reach remission.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
118Schizophr Bull 2015 Nov 41: 1237-47
PMID26409223
TitleRelationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders.
AbstractFirst-episode schizophrenia (FES) spectrum disorders are associated with pronounced cognitive dysfunction across all domains. However, less is known about the course of cognitive functioning, following the first presentation of psychosis, and the relationship of cognition to clinical course during initial treatment. The present longitudinal study examined the magnitude of neurocognitive impairment, using the MATRICS Consensus Cognitive Battery, in patients experiencing their first episode of psychosis at baseline and after 12 weeks of randomized antipsychotic treatment with either aripiprazole or risperidone. At baseline, FES patients evidenced marked impairments in cognitive functioning. Notably, performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial. Performance on indices of general cognitive function, working memory, and verbal learning improved over time, but these improvements were mediated by improvements in both positive and negative symptoms. We did not detect any differential effects of antipsychotic medication assignment (aripiprazole vs risperidone) on cognitive functioning. Our results suggest that a brief paper-and-pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication. However, improvements in cognitive functioning over time were related to clinical symptom improvement, reflecting "pseudospecificity."
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
119Shanghai Arch Psychiatry 2015 Jun 27: 175-82
PMID26300600
TitleComparisons of family environment between homeless and non-homeless individuals with schizophrenia in Xiangtan, Hunan.
AbstractHomelessness is an increasingly important problem for individuals with serious mental illness in China.
Identify the characteristics of families that are associated with homelessness among individuals with schizophrenia.
Participants were 1856 homeless individuals with schizophrenia (defined as those who had no place of residence or involved caregivers for 7 consecutive days) and 1728 non-homeless individuals with schizophrenia from Xiangtan, Hunan. The self-completion Family Environment Scale-Chinese Version (FES-CV) was administered to these participants after their acute psychotic symptoms resolved.
Compared to individuals in the non-homeless group, those in the homeless group were older and more likely to be non-locals (i.e., from outside of Xiangtan), be residents of rural (versus urban) communities, have temporary (versus permanent) jobs, be married, and have a low level of education. After controlling for demographic differences using multivariate logistic regression models, homelessness was independently associated higher scores in the FES-CV intellectual-cultural orientation, organization, achievement orientation, and control subscales and with lower scores in the FES-CV cohesion, moralreligious emphasis, independence, and active-recreational orientation subscales.
After controlling for sociodemographic factors, certain aspects of the family environment areassociated with being homeless among patients with schizophrenia in China. Further work is needed to identify interventions that can reduce the risk of homelessness in high-risk individuals.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
120Early Interv Psychiatry 2015 Aug -1: -1
PMID26279283
TitleDifferences in omega-3 and omega-6 polyunsaturated fatty acid consumption in people at ultra-high risk of psychosis, first-episode schizophrenia, and in healthy controls.
AbstractSupplementation with omega-3 PUFA showed efficacy in reducing the risk of transition into psychosis in UHR individuals. It is uncertain whether dietary patterns can be partly responsible for n-3 deficiencies observed in susceptible participants before the diagnosis of schizophrenia. The study was designed to assess differences in omega-3 and omega-6 PUFA consumption in healthy controls (HC), UHR participants and FES patients as well as to verify the hypothesis that dietary changes in PUFA consumption are present before active psychosis develops, that is, in UHR individuals.
Dietary habits during the previous year were assessed in 34 patients at UHR of psychosis, 33 patients diagnosed with FES and 33 HC participants using a validated Food-Frequency Questionnaire and the Polish Food Composition Tables.
Significant differences in omega-3 and omega-6 PUFA intake were observed between study groups. UHR and FES groups reported significantly higher consumption of omega-6 PUFA in comparison with HC. FES patients also reported a higher consumption of alpha-linolenic acid (omega-3) in comparison with HC. No significant differences were seen in consumption of long-chain marine PUFA.
Differences in omega-6 and omega-3 PUFA consumption exist before development of psychotic symptoms, fulfilling the criteria of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
121Schizophr. Res. 2015 Oct 168: 381-7
PMID26278336
TitleMetabolic syndrome and aerobic fitness in patients with first-episode schizophrenia, including a 1-year follow-up.
AbstractTo compare the prevalence of metabolic syndrome (MetS) and metabolic abnormalities in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls; to investigate changes in MetS during 1year of treatment; and to investigate predictors of MetS.
Patients with FES (N=99) and healthy controls (N=50) were included in the study. MetS was defined according to IDF based on waist circumference (WC), blood pressure (BP), triglycerides (TG), high-density lipoprotein (HDL), and fasting-glucose. Data on physical activity, aerobic fitness, smoking, and dietary habits, sleeping disturbances, psychopathology and psychotropic medication were also obtained. Patients were assessed at baseline and at 1year follow-up.
Compared with healthy controls patients with FES had a higher baseline prevalence of MetS (p=.07), and metabolic abnormalities: WC (p<.01), TG (p<.01), HDL (p=.017), and fasting glucose (p=.04). Patients with FES had significantly increased prevalence of MetS (p=.03), WC (p=.04), and TG (p=.01) during the study period. Antipsychotics and low physical activity were significantly correlated with the increase in metabolic abnormalities. In multivariate analyses low aerobic fitness was the most consistent and significant predictor of metabolic abnormalities and MetS.
MetS and metabolic abnormalities are highly prevalent in patients with FES, and both increase significantly during 1year of treatment. Apart from confirming the metabolic adverse effects of antipsychotics, our study highlights that low aerobic fitness is a significant risk factor for MetS. Promoting a healthier liFEStyle should be part of psychiatric treatment and rehabilitation.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
122Psychiatry Res 2015 Sep 229: 252-6
PMID26210651
TitleClinical variables associated with suicide attempts in schizophrenia before and after the first episode.
AbstractThe aim of this study was to investigate variables associated with suicide attempts in schizophrenia before and after the first episode. We evaluated history of past sucide attempts, clinical symptoms, level of functioning and cognitive performances of 172 patients with first-episode schizophrenia at first admission. Information was collected regarding clinical symptom severity, treatment compliance, and suicide attempts during the follow-up. We found that 16.5% of the patients attempted suicide before admission, and 6.2% of them attempted suicide during the follow-up. The patients who had attempted suicide before admission were mostly women, and more likely to be hospitalized in first year of follow up. BPRS-depression subscale score at admission and alcohol/substance use appeared as independent variables that found associated with suicide attempts prior to admission in logistic regression analysis. The patients who attempted suicide during the follow-up had significantly higher BPRS-depression subcale scores at sixth months of follow-up. Treatment compliance during the first 6 months and duration of remission was lower in this group. Our findings suggest that longer duration of first hospital treatment, the presence of depressive symptoms, and nonadherence to treatment in early phases of follow up after FES are predictors of suicide attempts. On the other hand, keeping remission during the follow-up protects against suicide attempts.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
123Zhonghua Yi Xue Za Zhi 2015 Mar 95: 823-6
PMID26080913
Title[Prepulse inhibition of startle reflex in schizophrenics and healthy adults].
AbstractTo evaluate the characteristics of sensory gating inhibition and variation of schizophrenia with both prepulse inhibition (PPI) and P50.
The PPI of startle reflex and P50 were tested by an event-related potential (ERP) recorder in 82 first episode schizophrenics (FES) recruited from September 2007 to February 2014 at Shanghai Mental Health Hospital and 78 healthy controls (NC) from hospital staffs and local residents for the same period. All patients fulfilled the evaluation of PPI with strong stimulus alone and strong + weak stimulus paradigm, P50 with conditioning (S1)-testing (S2) paradigm. The psychotic symptoms were assessed with Positive and Negative Syndrome Scale (PANSS).
(1) Compared with control group, schizophrenia group had increased P(L) (NC: (89 ± 14) ms, FES: (97 ± 17) ms, P < 0.05) and PPL, decreased amplitude (NC: (92 ± 21) ms, (24 ± 14) µV, FSZ: (96 ± 20) ms, (41 ± 29) µV, P < 0.05, 0.01), lower PPI inhibition ratio (NC: (67 ± 32)%, FSZ: (41 ± 37)%, P < 0.05). (2) Compared with NC group, there were increased S2 amplitude [NC: (3 ± 2) µV vs FES: (5 ± 3) µV, P < 0.05] and ratio of S2/S1 amplitude [(43 ± 22) % vs (82 ± 41)%, P < 0.05] in schizophrenia group. And P50 inhibition decreased significantly.
schizophrenics have both PPI and P50 impairments. And a combination of PPI inhibition ratio and S2/S1 (P50) may be a better electrocerebrophysiological index for schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
124Neuro Endocrinol. Lett. 2015 -1 36: 153-60
PMID26071585
TitleExecutive functioning improves after remission of psychosis and may not deteriorate at short follow-up in early-onset schizophrenia.
AbstractCognitive functions are important determinants of outcome in schizophrenia. Psychiatric hospitalization and intensive treatment in the early-onset psychosis may reduce the severity of psychotic symptoms and improve cognitive functions. It is not clear if after discharge improvement or further deterioration of cognition is observed. The aim of the current study is the evaluation of executive functioning in early onset schizophrenia (EOS) across stages of illness.
Two groups of EOS patients: hospitalized subjects with first episode (FES, n=16) at the introduction of pharmacotherapy (T1) and after mean 7 weeks (T2) and stable outpatients group (SO, n=24) were assessed with the Wisconsin Card Sorting Test (WCST) the Positive and Negative Syndrome Scale. Matched healthy (n=32) controls were assessed with WCST.
All patients performed significantly worse in WCST than healthy controls. Subjects in acute psychotic episode (FES T1) presented more pronounced executive impairment and psychopathological symptoms than after the resolution of psychotic symptoms (FES T2). No differences in executive function between FES T2 and SO group were observed. In all assessments perseverative errors correlated with negative symptoms.
Cognitive impairment is present at the onset of EOS and persists in attenuated but stable form after the resolution of psychotic symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
125Curr Behav Neurosci Rep 2015 Mar 2015: 1-10
PMID25883891
TitleNeuroimaging Biomarkers for Psychosis.
AbstractBiomarkers provide clinicians with a predictable model for the diagnosis, treatment and follow-up of medical ailments. Psychiatry has lagged behind other areas of medicine in the identification of biomarkers for clinical diagnosis and treatment. In this review, we investigated the current state of neuroimaging as it pertains to biomarkers for psychosis.
We reviewed systematic reviews and meta-analyses of the structural (sMRI), functional (fMRI), diffusion-tensor (DTI), Positron emission tomography (PET) and spectroscopy (MRS) studies of subjects at-risk or those with an established schizophrenic illness. Only articles reporting effect-sizes and confidence intervals were included in an assessment of robustness.
Out of the identified meta-analyses and systematic reviews, 21 studies met the inclusion criteria for assessment. There were 13 sMRI, 4 PET, 3 MRS, and 1 DTI studies. The search terms included in the current review encompassed familial high risk (FHR), clinical high risk (CHR), First episode (FES), Chronic (CSZ), schizophrenia spectrum disorders (SSD), and healthy controls (HC).
Currently, few neuroimaging biomarkers can be considered ready for diagnostic use in patients with psychosis. At least in part, this may be related to the challenges inherent in the current symptom-based approach to classifying these disorders. While available studies suggest a possible value of imaging biomarkers for monitoring disease progression, more systematic research is needed. To date, the best value of imaging data in psychoses has been to shed light on questions of disease pathophysiology, especially through the characterization of endophenotypes.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
126Schizophr. Res. 2015 Jun 165: 60-5
PMID25864951
TitleImpaired facial emotion recognition in individuals at ultra-high risk for psychosis and with first-episode schizophrenia, and their associations with neurocognitive deficits and self-reported schizotypy.
AbstractThis study aims to quantify facial emotion recognition abnormalities and their relation to neurocognitive dysfunction and schizotypy in individuals at ultra-high risk (UHR) for psychosis and patients with first-episode schizophrenia (FES).
Forty individuals at UHR for psychosis, 24 patients with FES and 46 normal controls performed a facial emotion recognition task that presented facial photographs encompassing all basic emotions. The perceptual aberration scale and revised social anhedonia scale were employed for self-reported assessment of schizotypy. An intellectual functioning (IQ) test and a broad battery of neurocognitive tests were conducted. Emotional task performance indexed by accuracy rate of specific emotion was compared among three groups. The correlation of accuracy rate with neurocognitive tests and schizotypy scales were analyzed within each clinical group.
A recognition deficit of facial emotions was present in both clinical groups, even after adjusting for IQ and gender as covariates. This emotional deficit showed few significant relationships with broad range of individual neurocognitive measures. Meanwhile, this deficit demonstrated significant relationships with schizotypy, especially perceptual aberration in each clinical group.
Facial emotion recognition deficit may not only be present in FES patients, but may already have evolved prior to the onset of overt psychotic symptoms. This emotion recognition deficit may be linked to a perceptual aberration and largely independent of broad range of neurocognitive dysfunction.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
127Nord J Psychiatry 2015 May 69: 254-61
PMID25731069
TitleEffect of time and duration of untreated psychosis on cognitive and social functioning in Chinese patients with first-episode schizophrenia: A 1-year study.
AbstractDuration of untreated psychosis (DUP) is believed to exert a deleterious effect on cognitive and social function. However, to date, results remain inconclusive.
To investigate the effect of time and DUP on cognitive and social functioning in first-episode schizophrenia (FES) subjects in Shanghai, China.
FES patients were subjected to a comprehensive neuropsychological battery, the Personal and Social Performance scale (PSP) and the Positive and Negative Symptoms Scale (PANSS) at baseline, 6 month and 1 year. DUP was defined as the time from onset of first psychotic symptoms to first contact made with psychiatric services.
Though the rate of non-completers in our observational study was relatively high (40%), we did not find any significant differences between the completers and non-completers (P-values > 0.05). Significant impairments in verbal learning and memory and executive function were noted over the course of 1 year. Meanwhile, social function improved significantly over the course of 1 year. Although, DUP did not share any significant relationship with cognitive or social function the effect estimate (range: - 0.03 to 0.02) of an increase of 1 month in DUP was clinically non-negligible in this study.
In Chinese FES patients, the longitudinal course of cognitive function tends to worsen in verbal learning and memory, executive function and motor speed, while that of social function tends to improve. DUP was not found to be associated with cognitive or social deterioration in Chinese FES.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
128Compr Psychiatry 2015 Apr 58: 146-51
PMID25595518
TitleAssessment of cigarette smoking status with respect to symptomatic manifestation in first-episode schizophrenia patients.
AbstractIt has been repeatedly found that cigarette smoking may influence schizophrenia psychopathology. However, little is known about the relationship between nicotine consumption and symptomatic maniFEStation of first-episode schizophrenia (FES).
We recruited 109 minimally medicated FES patients. Cigarette smoking was assessed using the Fagerström test for nicotine dependence (FTND) and pack-year index. Psychopathology on the day of recruitment was examined using the Positive and Negative Syndrome Scale (PANSS).
Smokers had significantly lower severity of negative and depressive symptoms in comparison with non-smokers. Patients with severe nicotine dependence had significantly later age of psychosis onset in comparison with those with mild nicotine dependence and non-smokers. Significantly lower severity of negative and depressive symptoms was also observed in patients with severe nicotine dependence in comparison with non-smokers. The associations between the severity of nicotine dependence and scores of negative and depressive symptoms as well as age of psychosis onset remained significant after co-varying for gender, education, duration of untreated psychosis (DUP) and measures of antipsychotic treatment.
Our results indicate that cigarette smoking might be associated with less severe negative and depressive symptoms as well as delayed age of psychosis onset. However, longitudinal studies are required to indicate the direction of causality.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
129Eur Arch Psychiatry Clin Neurosci 2015 Oct -1: -1
PMID26499939
TitleDriving skills in unmedicated first- and recurrent-episode schizophrenic patients.
AbstractThe present study was designed to examine driving skills according to regulations of the German guidelines for road and traffic safety in unmedicated schizophrenic inpatients. A total of 13 first-episode (FES) and 13 recurrent-episode (RES) schizophrenic inpatients were included in the analysis and compared with a group of 20 healthy controls (HC). Data were collected with the computerised Wiener Testsystem measuring visual perception, reactivity and stress tolerance, concentration and vigilance. Analysis of data indicates that a great proportion (58 %) of schizophrenic patients were impaired in psychomotor functions related to driving skills. FES and RES significantly differed with respect to driving ability with a greater proportion in the FES (38 %) showing severe impairments when compared with RES (25 %). Differences with respect to HC performance were most pronounced in concentration and for the FES additionally in visual perception. Analysis of our data indicates that a great proportion of schizophrenic patients are impaired in psychomotor functions related to driving skills that cannot be attributed to adverse side effects of psychopharmacological treatment. Besides, we cannot confirm a chronical decline of psychomotor functions related to driving skills at least in the early course of schizophrenic illness.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
130Sci Rep 2015 -1 5: 14505
PMID26403064
TitleDecreased bilateral thalamic gray matter volume in first-episode schizophrenia with prominent hallucinatory symptoms: A volumetric MRI study.
AbstractStudies comparing gray matter (GM) volume of schizophrenic patients with or without auditory verbal hallucinations (AVHs) to that of normal controls remain controversial. This project aims to investigate changes of GM volumes of drug-naïve schizophrenic patients with and without AVHs. Eighteen first episode schizophrenic (FES) patients with AVHs, 18 FES patients without AVHs, and 18 healthy controls were scanned using structural MRI. Voxel-based morphometry (VBM) analysis was conducted to investigate changes of GM volume among the three groups. Patients with and without AVHs exhibited reduced GM volumes relative to normal controls in the left superior temporal gyrus, frontal regions, cerebellum and caudate. Further analysis of the GM of subcortical structures found that patients with AVHs had reduced thalamic volume than healthy controls. No significant difference was found between patients with and without AVHs. Significant correlation was found between the total scores of the Positive and Negative Syndrome Scale and bilateral thalamic volume. ROC analysis of thalamic volumes of the patients with AVHs and normal controls showed that the area under the curve was 0.698 (P = 0.043). The decreased thalamic volumes might serve as a biomarker for discriminating FES AVHs patients from normals.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
131Aust N Z J Psychiatry 2015 May 49: 462-70
PMID25425742
TitleNeurocognitive impairments in individuals at ultra-high risk for psychosis: Who will really convert?
AbstractImpairments in neurocognitive function are considered as core features of schizophrenia. Individuals at ultra-high risk (UHR) for psychosis, the 'putative' prodrome of schizophrenia, generally show levels of impairments intermediate between schizophrenia patients and healthy controls. We investigated the neurocognitive performance of individuals at UHR for psychosis, comparing them with patients with first-episode schizophrenia (FES) and healthy controls (HC), and explored the predictivity of baseline neurocognitive function in the UHR group for transition to overt psychosis.
Individuals at UHR for psychosis (n = 60), patients with FES (n = 39), and HC subjects (n = 94) participated in the present study. All participants performed a comprehensive neurocognitive battery, consisting of tests for five separate neurocognitive domains (executive function, attention/working memory, processing speed, verbal memory, and spatial memory). UHR subjects were assessed for transition every month during 24 months of follow-up.
Neurocognitive performance in the UHR group was largely at intermediate levels. Attention/working memory and verbal memory were significantly different from both the FES and HC groups. In the UHR group, processing speed was decreased to the level of the FES group, while executive function and spatial memory were relatively preserved. In the Cox regression model, spatial memory significantly predicted the transition to overt psychosis in the UHR group.
The present study showed that neurocognitive impairments were evident in UHR individuals prior to the onset of overt psychosis. Our findings generally support the neurodevelopmental model of schizophrenia and suggest that there could be different developmental trajectories between converters and non-converters.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
132Aust N Z J Psychiatry 2015 Mar 49: 246-54
PMID25318995
TitleRegional white matter abnormalities in drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings.
AbstractShared neuropathological features between schizophrenia patients and their siblings may represent intermediate phenotypes of schizophrenia and can be used to investigate genetic susceptibility to the illness. This study aimed to discover regional white matter abnormalities in first-episode schizophrenia (FES) patients and their unaffected siblings compared to healthy subjects in the Chinese Han population using optimized Voxel-Based Morphometry (VBM).
A total of 51 drug-naive, FES patients, 45 of their unaffected siblings and 59 healthy comparisons were studied with magnetic resonance imaging (MRI).
FES patients exhibited significant regional white matter deficits in the left inferior frontal gyrus and left joint of external capsule and internal capsule compared with healthy subjects (corrected FDR, p<0.005). The sibling group also showed significant white matter deficits in these two regions compared with the healthy comparison group (uncorrected, p<0.001). White matter deficits with a less stringent threshold for significance in the left cerebellum anterior lobe, left middle frontal gyrus, left hippocampus, right anterior cingulate and right internal capsule were observed in patients compared to their siblings.
Our findings extend those from previous VBM analyses showing that FES patients and their unaffected siblings may share white matter deficits in the left inferior frontal gyrus and the left joint of external capsule and internal capsule. These regional white matter deficits may be related to genetic factors related to schizophrenia susceptibility.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
133Eur. Psychiatry 2015 Jan 30: 14-9
PMID25174272
TitleNegative symptom subgroups have different effects on the clinical course of schizophrenia after the first episode: a 24-month follow up study.
AbstractThe aim of this study was to assess the factor structure of negative symptoms in first-episode schizophrenia (FES), and to examine the relationship of these factors with clinical course and functioning of patients during the two-year follow up.
We assessed 174 drug-naïve patients with FES using Brief Psychiatric Rating Scale-Expanded (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Global Assessment of Functioning (GAF) and a cognitive battery at admission. The scales were repeated monthly during follow up. We recorded the patients' functioning levels, remission, and work status after 12 and 24 months.
A two-factor structure was found at the baseline, whereas one factor was found after 12 and 24 months. Expressive deficit (ED) factor consisted of alogia and blunted affect, and motivation-pleasure deficit (MPD) factor consisted of avolition and anhedonia. ED factor was related to earlier onset and remission, and it was negatively correlated with duration of education and cognitive test scores. MPD factor was related to duration of untreated psychosis, family history of schizophrenia, and work status, and it appeared as the only independent variable that contributed to the baseline GAF score in linear regression analysis.
Our findings suggest that the factors have different aetiologies and impacts on the clinical course of schizophrenia and functioning after FES.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
134Psychopharmacology (Berl.) 2015 Jan 232: 369-77
PMID25080851
TitleBrain differences in first-episode schizophrenia treated with quetiapine: a deformation-based morphometric study.
AbstractWith the development of various imaging techniques, the deformation-based morphometry (DBM) method provides an objective automatic examination of the whole brain.
This study aims to assess the abnormalities in the brains of first-episode schizophrenia (FES) patients treated with quetiapine using another advanced nonrigid registration method, hierarchical attribute matching mechanism for elastic registration, through the application of DBM in the entire brain.
Thirty FES patients and 30 normal controls were grouped by age and handedness and subjected to magnetic resonance imaging examination. The patients had relatively short durations of untreated psychosis (DUP; 6.4?±?5.2 months), and only a single antipsychotic drug, quetiapine (dosage, 200?±?75 mg), was used for treatment. Statistically significant changes in regional volume were analyzed via DBM. In addition, a voxel-wise analysis of correlations between the duration of treatment or dosage and volume was also performed.
Compared with control subjects, FES patients showed contracted regions located in Brodmann area (BA) 42 and BA 19. By contrast, expanded regions were observed in BA 38, BA 21, BA 6 and 8, and left cerebellum. A negative correlation was observed between dosage and volume in the hippocampus, while a positive correlation was found in the caudate. Meanwhile, a negative correlation was observed between duration of treatment and volume in BA 38.
Both regional volume reductions and increases were detected in the brains of FES patients treated with quetiapine compared with healthy control subjects. Such differences may be partially relevant to dosage and treatment duration in clinic.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
135Zhonghua Yi Xue Za Zhi 2015 Mar 95: 823-6
PMID26080913
Title[Prepulse inhibition of startle reflex in schizophrenics and healthy adults].
AbstractTo evaluate the characteristics of sensory gating inhibition and variation of schizophrenia with both prepulse inhibition (PPI) and P50.
The PPI of startle reflex and P50 were tested by an event-related potential (ERP) recorder in 82 first episode schizophrenics (FES) recruited from September 2007 to February 2014 at Shanghai Mental Health Hospital and 78 healthy controls (NC) from hospital staffs and local residents for the same period. All patients fulfilled the evaluation of PPI with strong stimulus alone and strong + weak stimulus paradigm, P50 with conditioning (S1)-testing (S2) paradigm. The psychotic symptoms were assessed with Positive and Negative Syndrome Scale (PANSS).
(1) Compared with control group, schizophrenia group had increased P(L) (NC: (89 ± 14) ms, FES: (97 ± 17) ms, P < 0.05) and PPL, decreased amplitude (NC: (92 ± 21) ms, (24 ± 14) µV, FSZ: (96 ± 20) ms, (41 ± 29) µV, P < 0.05, 0.01), lower PPI inhibition ratio (NC: (67 ± 32)%, FSZ: (41 ± 37)%, P < 0.05). (2) Compared with NC group, there were increased S2 amplitude [NC: (3 ± 2) µV vs FES: (5 ± 3) µV, P < 0.05] and ratio of S2/S1 amplitude [(43 ± 22) % vs (82 ± 41)%, P < 0.05] in schizophrenia group. And P50 inhibition decreased significantly.
schizophrenics have both PPI and P50 impairments. And a combination of PPI inhibition ratio and S2/S1 (P50) may be a better electrocerebrophysiological index for schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
136Curr Behav Neurosci Rep 2015 Mar 2015: 1-10
PMID25883891
TitleNeuroimaging Biomarkers for Psychosis.
AbstractBiomarkers provide clinicians with a predictable model for the diagnosis, treatment and follow-up of medical ailments. Psychiatry has lagged behind other areas of medicine in the identification of biomarkers for clinical diagnosis and treatment. In this review, we investigated the current state of neuroimaging as it pertains to biomarkers for psychosis.
We reviewed systematic reviews and meta-analyses of the structural (sMRI), functional (fMRI), diffusion-tensor (DTI), Positron emission tomography (PET) and spectroscopy (MRS) studies of subjects at-risk or those with an established schizophrenic illness. Only articles reporting effect-sizes and confidence intervals were included in an assessment of robustness.
Out of the identified meta-analyses and systematic reviews, 21 studies met the inclusion criteria for assessment. There were 13 sMRI, 4 PET, 3 MRS, and 1 DTI studies. The search terms included in the current review encompassed familial high risk (FHR), clinical high risk (CHR), First episode (FES), Chronic (CSZ), schizophrenia spectrum disorders (SSD), and healthy controls (HC).
Currently, few neuroimaging biomarkers can be considered ready for diagnostic use in patients with psychosis. At least in part, this may be related to the challenges inherent in the current symptom-based approach to classifying these disorders. While available studies suggest a possible value of imaging biomarkers for monitoring disease progression, more systematic research is needed. To date, the best value of imaging data in psychoses has been to shed light on questions of disease pathophysiology, especially through the characterization of endophenotypes.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
137Schizophr. Res. 2015 Jun 165: 60-5
PMID25864951
TitleImpaired facial emotion recognition in individuals at ultra-high risk for psychosis and with first-episode schizophrenia, and their associations with neurocognitive deficits and self-reported schizotypy.
AbstractThis study aims to quantify facial emotion recognition abnormalities and their relation to neurocognitive dysfunction and schizotypy in individuals at ultra-high risk (UHR) for psychosis and patients with first-episode schizophrenia (FES).
Forty individuals at UHR for psychosis, 24 patients with FES and 46 normal controls performed a facial emotion recognition task that presented facial photographs encompassing all basic emotions. The perceptual aberration scale and revised social anhedonia scale were employed for self-reported assessment of schizotypy. An intellectual functioning (IQ) test and a broad battery of neurocognitive tests were conducted. Emotional task performance indexed by accuracy rate of specific emotion was compared among three groups. The correlation of accuracy rate with neurocognitive tests and schizotypy scales were analyzed within each clinical group.
A recognition deficit of facial emotions was present in both clinical groups, even after adjusting for IQ and gender as covariates. This emotional deficit showed few significant relationships with broad range of individual neurocognitive measures. Meanwhile, this deficit demonstrated significant relationships with schizotypy, especially perceptual aberration in each clinical group.
Facial emotion recognition deficit may not only be present in FES patients, but may already have evolved prior to the onset of overt psychotic symptoms. This emotion recognition deficit may be linked to a perceptual aberration and largely independent of broad range of neurocognitive dysfunction.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
138Psychiatry Res 2016 Apr 238: 60-7
PMID27086212
TitleMetabolic dysregulation in first-episode schizophrenia patients with respect to genetic variation in one-carbon metabolism.
AbstractThe aim of this study was to investigate the prevalence of metabolic disturbances in patients with first-episode schizophrenia (FES) and test the hypothesis that genetic variation in one-carbon metabolism may account for metabolic dysregulation in early psychosis. We measured fasting glucose, lipid profile parameters, homocysteine, folate and vitamin B12 in 135 patients with FES and 146 healthy controls (HCs). Polymorphisms in the following genes were determined: MTHFR (C677T and A1298C), MTHFD1 (G1958A), MTRR (A66G) and BHMT (G742A). Serum levels of folate and high-density lipoproteins (HDL) were significantly lower in patients with FES compared to HCs. In turn, serum levels of homocysteine and triglycerides were significantly higher in patients with FES than in HCs. Prevalence of hyperhomocysteinemia, low folate and HDL levels together with dyslipidemia was significantly higher in patients with FES compared to HCs. Higher homocysteine levels, lower vitamin B12 levels and the presence of metabolic syndrome were associated with higher severity of negative symptoms. None of studied polymorphisms was associated with schizophrenia risk. Several associations between studied polymorphisms and cardio-metabolic parameters were found. None of them remained significant after Bonferroni correction. Our results indicate that metabolic dysregulation in patients with FES is not associated with genetic variation in one-carbon metabolism.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
139Psychiatry Res 2016 Apr 241: 201-206
PMID27183105
TitleSystemic oxidative DNA and RNA damage are not increased during early phases of psychosis: A case control study.
AbstractIt has been suggested that patients with schizophrenia develop higher levels of oxidative stress, which may contribute to deteriorating mental illness. In order to examine oxidative stress in the early stages of severe mental illness, we examined the levels of systemic Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine, perceived stress and recent life events in patients at ultra high-risk (UHR) of developing psychosis, in antipsychotic naïve patients with first-episode schizophrenia (FES), and in healthy controls. We included 41 UHR patients, 35 FES patients, and 29 healthy controls. There was no difference in the level of DNA/RNA oxidative damage between UHR patients and FES patients compared with healthy controls. We found no association between levels of DNA/RNA oxidative damage and perceived stress/life events. Based on the results, we suggest that DNA and RNA oxidative markers are not increased during the early stages of illness, but further longitudinal studies in first-episode psychosis should be carried out to examine whether DNA and RNA oxidative damage are potential markers of severe illness.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
140Nord J Psychiatry 2016 May -1: 1-7
PMID27147081
TitlePhysical activity and anomalous bodily experiences in patients with first-episode schizophrenia.
AbstractLow physical activity is strongly correlated with metabolic syndrome (MetS) and poor physical health. Although the prevalence of MetS is high in patients with first-episode schizophrenia (FES), little is still known about the level of and possible barriers for physical activity in FES.
The purpose of the study was to compare physical activity in patients with FES with healthy controls; to investigate changes in physical activity over 1 year of follow-up; and to explore the correlations of physical activity and anomalous bodily experiences reported by patients with FES.
Both physical activity and aerobic fitness were measured. Anomalous bodily experiences were measured by selected items from the Examination of Anomalous Self-Experience and The Body Awareness Scale. Psychopathological data comprising negative and positive symptoms and data on psychotropic medication were obtained from medical records of all patients.
Physical activity and aerobic fitness was significantly lower in patients with FES compared with healthy controls (p?Physical activity and aerobic fitness is low in patients with FES. Both anomalous bodily experiences and negative symptoms are significantly correlated with low physical activity.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
141Psychiatry Res 2016 Jan 247: 42-8
PMID26651180
TitleWhite matter microstructure in ultra-high risk and first episode schizophrenia: A prospective study.
AbstractThere is increasing evidence of white matter (WM) pathology in schizophrenia, but its role at the very early stage of the disorder remains unclear. In an exploration of WM microstructure in ultra-high risk (UHR) subjects and first episode schizophrenia (FES), 34 FES, 27 UHR and 26 healthy control (HC) subjects underwent a magnetic resonance imaging (MRI) tract based spatial statistics (TBSS) investigation. Whole brain fractional anisotropy (FA), mean diffusivity (MD), radial (RD) and axial diffusivity (AD) values were extracted. UHR subjects who later developed psychosis showed lower FA compared with HC in the corpus callosum (CC), the left superior and inferior longitudinal fasciculus, the left inferior fronto-occipital fasciculs (IFO), and the forceps; RD was significantly higher in the CC, the forceps, the anterior thalamic radiation bilaterally, and the cingulum bundle. FES, compared to HC, showed a significant FA reduction of the CC, the superior and inferior longitudinal fasciculi bilaterally, the IFO bilaterally, the corona radiate bilaterally, and the forceps; while RD was found to be significantly increased in the left superior longitudinal fasciculus. UHR who later developed psychosis had WM abnormalities affecting brain pathways that are crucial for intra- and inter-hemispheric connections.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
142Schizophr. Res. 2016 Apr -1: -1
PMID27146474
TitleImpact of duration of untreated psychosis and premorbid intelligence on cognitive functioning in patients with first-episode schizophrenia.
AbstractThe neurotoxic hypothesis suggests that psychosis is toxic to the brain leading to clinical consequences. In this study, we hypothesized that a longer duration of untreated psychosis (DUP) in first episode schizophrenia (FES) patients is associated with poorer cognitive functioning, and that higher premorbid intelligence buffers against DUP-related cognitive impairment.
Eighty-one FES patients completed a neuropsychological battery, the Brief Assessment of Cognition in schizophrenia (BACS). Composite scores of the BACS, which were normalized to a matched healthy control of seventy-three subjects, were used as an index of general cognition. A median split using the Wide Range Achievement Test-Reading Test scores was used to divide the patients into low versus high premorbid IQ groups. Hierarchical linear regression was performed to examine predictors of general cognition, including DUP.
Longer DUP was found to be a significant predictor of poorer general cognition. In addition, DUP predicted general cognition in the low premorbid IQ group but not in the high premorbid IQ group.
Our findings demonstrate that longer DUP in FES patients is associated with worse cognitive scores, and that this association is more pronounced in a subgroup of patients who have lower premorbid intelligence. Our results suggest the importance of earlier identification and management of patients with low premorbid IQ, given that their cognition may be more vulnerable to the toxicity of psychosis.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
143J Affect Disord 2016 Aug 200: 1-5
PMID27107261
TitleThree-year clinical and functional outcome comparison between first-episode mania with psychotic features and first-episode schizophrenia.
AbstractThe early course of first-episode mania with psychotic features (FEMP) is under-studied. Accumulating evidence suggests that FEMP is associated with substantial functional impairment. Very few studies were conducted to directly compare clinical and functional outcomes between FEMP and first-episode schizophrenia (FES).
Four-hundred-twenty patients aged 15-25 years who presented with FEMP or FES to a territory-wide early intervention service in Hong Kong from July 2001 to August 2003 and completed 3-year follow-up were studied. Baseline and follow-up variables were collected via systematic medial file review. Functional remission was operationalized as attaining sustained employment, and Social and Occupational Functioning Assessment Scale (SOFAS) score >60 in the last 12 months of follow-up.
At baseline, FEMP patients were younger, more likely to be hospitalized, had shorter duration of untreated psychosis, more severe positive symptoms and lower SOFAS score than FES patients. By the end of 3-year follow-up, FEMP patients had significantly milder positive symptom severity, higher SOFAS score, and higher rates of sustained employment (45.7%) and functional remission (36.9%) than FES patients. Regression analyses showed that diagnostic group membership of FEMP (vs. FES) independently predicted better clinical and functional outcomes.
Our results indicate that FEMP patients had better clinical and functional outcomes than FES patients in the initial 3 years of treatment. Yet, only approximately 37% of FEMP patients attained functional remission at 3 years. This underscores the need to develop specialized early intervention for FEMP populations to promote functional recovery in the early stage of illness.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
144J Abnorm Psychol 2016 May 125: 543-9
PMID27030995
TitleVisual integration dysfunction in schizophrenia arises by the first psychotic episode and worsens with illness duration.
AbstractVisual integration dysfunction characterizes schizophrenia, but prior studies have not yet established whether the problem arises by the first psychotic episode or worsens with illness duration. To investigate the issue, we compared chronic schizophrenia patients (SZs), first episode psychosis patients (FES), and well-matched healthy controls on a brief but sensitive psychophysical task in which subjects attempted to locate an integrated shape embedded in noise. Task difficulty depended on the number of noise elements co-presented with the shape. For half of the experiment, the entire display was scaled down in size to produce a high spatial frequency (HSF) condition, which has been shown to worsen patient integration deficits. Catch trials-in which the circular target appeared without noise-were also added so as to confirm that subjects were paying adequate attention. We found that controls integrated contours under noisier conditions than FES, who, in turn, integrated better than SZs. These differences, which were at times large in magnitude (d = 1.7), clearly emerged only for HSF displays. Catch trial accuracy was above 95% for each group and could not explain the foregoing differences. Prolonged illness duration predicted poorer HSF integration across patients, but age had little effect on controls, indicating that the former factor was driving the effect in patients. Taken together, a brief psychophysical task efficiently demonstrates large visual integration impairments in schizophrenia. The deficit arises by the first psychotic episode, worsens with illness duration, and may serve as a biomarker of illness progression. (PsycINFO Database Record
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
145Compr Psychiatry 2016 Apr 66: 17-22
PMID26995231
TitleChildhood traumatic events and types of auditory verbal hallucinations in first-episode schizophrenia patients.
AbstractEvidence is accumulating that childhood trauma might be associated with higher severity of positive symptoms in patients with psychosis and higher incidence of psychotic experiences in non-clinical populations. However, it remains unknown whether the history of childhood trauma might be associated with particular types of auditory verbal hallucinations (AVH).
We assessed childhood trauma using the Early Trauma Inventory Self-Report - Short Form (ETISR-SF) in 94 first-episode schizophrenia (FES) patients. Lifetime psychopathology was evaluated using the Operational Criteria for Psychotic Illness (OPCRIT) checklist, while symptoms on the day of assessment were examined using the Positive and Negative Syndrome Scale (PANSS). Based on ETISR-SF, patients were divided into those with and without the history of childhood trauma: FES(+) and FES(-) patients.
FES(+) patients had significantly higher total number of AVH types and Schneiderian first-rank AVH as well as significantly higher PANSS P3 item score (hallucinatory behavior) in comparison with FES(-) patients. They experienced significantly more frequently third person AVH and abusive/accusatory/persecutory voices. These differences remained significant after controlling for education, PANSS depression factor score and chlorpromazine equivalent. Linear regression analysis revealed that the total number of AVH types was predicted by sexual abuse score after controlling for above mentioned confounders. This effect was significant only in females.
Our results indicate that the history of childhood trauma, especially sexual abuse, is associated with higher number AVH in females but not in males. Third person AVH and abusive/accusatory/persecutory voices, representing Schneiderian first-rank symptoms, might be particularly related to childhood traumatic events.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
146Schizophr. Res. 2016 Apr 172: 9-15
PMID26873807
TitleAssociation between impaired brain activity and volume at the sub-region of Broca's area in ultra-high risk and first-episode schizophrenia: A multi-modal neuroimaging study.
AbstractRecent studies have suggested that functional abnormalities in Broca's area, which is important in language production (speech and thoughts before speech), play an important role in the pathophysiology of schizophrenia. While multi-modal approaches have proved useful in revealing the specific pathophysiology of psychosis, the association of functional abnormalities with gray matter volume (GMV) here in subjects with an ultra-high risk (UHR) of schizophrenia, those with first-episode schizophrenia (FES), and healthy controls has yet to be clarified. Therefore, the relationship between cortical activity measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, and GMV in the Broca's area assessed using a manual tracing in magnetic resonance imaging (MRI), which considers individual structural variation, was examined for 57 subjects (23 UHR/18 FES/16 controls). The UHR and FES group showed significantly reduced brain activity compared to control group in the left pars triangularis (PT) (P=.036, .003, respectively). Furthermore in the FES group, the reduced brain activity significantly positively correlated with the volume in the left PT (B=0.29, P=.027), while significant negative association was evident for all subjects (B=-0.18, P=.010). This correlation remained significant after adjusting for antipsychotics dosage, and voxel-wise analysis could not detect any significant correlation between impaired cortical activity and volume. The significant relationship between neural activity and GMV in the left PT may reflect a specific pathophysiology related to the onset of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
147Schizophr. Res. 2016 Mar 171: 16-26
PMID26817402
TitleDiscriminating autism spectrum disorders from schizophrenia by investigation of mental state attribution on an on-line mentalizing task: A review and meta-analysis.
AbstractIn recent years, theories of how humans form a "theory of mind" of others ("mentalizing") have increasingly been called upon to explain impairments in social interaction in mental disorders, such as autism spectrum disorders (ASD) and schizophrenia. However, it remains unclear whether tasks that assess impairments in mentalizing can also contribute to determining differential deficits across disorders, which may be important for early identification and treatment. Paradigms that challenge mentalizing abilities in an on-line, real-life fashion have been considered helpful in detecting disease-specific deficits. In this review, we are therefore summarizing results of studies that assess the attribution of mental states using an animated triangles task. Behavioral as well as brain imaging studies in ASD and schizophrenia have been taken into account. While for neuroimaging methods, data are sparse and investigation methods inconsistent, we performed a meta-analysis of behavioral data to directly investigate performance deficits across disorders. Here, more impaired abilities in the appropriate description of interactions were found in ASD patients than in patients with schizophrenia. Moreover, an analysis of first-episode (FES) versus longer lasting (LLS) schizophrenia showed that usage of mental state terms was reduced in the LLS group. In our review and meta-analysis, we identified performance differences between ASD and schizophrenia that seem helpful in targeting differential deficits, taking into account different stages of schizophrenia. However, to tackle the deficits in more detail, studies are needed that directly compare patients with ASD and schizophrenia using behavioral or neuroimaging methods with more standardized task versions.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
148JAMA Psychiatry 2016 Mar 73: 211-20
PMID26764163
TitlePrognosis of Brief Psychotic Episodes: A Meta-analysis.
AbstractThe prognostic significance of competing constructs and operationalizations for brief psychotic episodes (acute and transient psychotic disorder [ATPD], brief psychotic disorder [BPD], brief intermittent psychotic symptoms [BIPS], and brief limited intermittent psychotic symptoms [BLIPS]) is unknown.
To provide a meta-analytical prognosis of the risk of psychotic recurrence in patients with remitted first-episode ATPD, BPD, BIPS, and BLIPS and in a benchmark group of patients with remitted first-episode schizophrenia (FES). We hypothesized a differential risk: FES?>?ATPD?>?BPD?>?BIPS?>?BLIPS.
The Web of Knowledge and Scopus databases were searched up to May 18, 2015; the articles identified were reviewed as well as citations of previous publications and results of a manual search of the reference lists of retrieved articles.
We included original articles that reported the risk of psychotic recurrence at follow-up for patients in remission from first-episode ATPD, BPD, BLIPS, BIPS, and FES.
Independent extraction by multiple observers. Random-effects meta-analysis was performed, and moderators were tested with meta-regression analyses, Bonferroni corrected. Heterogeneity was assessed with the I2 index. Sensitivity analyses tested the robustness of the results. Publication bias was assessed with funnel plots and the Egger test.
Proportion of patients with baseline ATPD, BPD, BLIPS, and BIPS who had any psychotic recurrence at 6, 12, 24, and 36 or more months of follow-up.
Eighty-two independent studies comprising up to 11?133 patients were included. There was no prognostic difference in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS at any follow-up (P?>?.03). In the long-term analysis, risk of psychotic recurrence (reported as mean [95% CI]) was significantly higher in the FES group (0.78 [0.58-0.93] at 24 months and 0.84 [0.70-0.94] at ?36 months; P?There are no prognostic differences in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS constructs of brief psychotic episodes. Conversely, there is consistent meta-analytical evidence for better long-term prognosis of brief psychotic episodes compared with remitted first-episode schizophrenia. These findings should influence the diagnostic practice and clinical services in the management of early psychosis.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy
149Cereb. Cortex 2016 Mar 26: 1027-35
PMID25452567
TitleDifferential Alterations of Auditory Gamma Oscillatory Responses Between Pre-Onset High-Risk Individuals and First-Episode Schizophrenia.
AbstractAlterations in gamma-band auditory steady-state response (ASSR) are the most robust finding of abnormal neural oscillations in patients with first-episode (FES) and chronic schizophrenia. Gamma-band ASSRs may indicate GABAergic interneuron dysfunction. Nevertheless, it is unknown whether abnormal gamma-band ASSRs are present before the onset of psychosis. Subjects were 15 ultra-high-risk (UHR) individuals, 13 FES patients, and 21 healthy control (HC) subjects. We performed electroencephalogram recordings and measured ASSRs in each group as they were presented with click trains at 20, 30, and 40 Hz. We then conducted time-frequency analyses and calculated intertrial phase coherence and event-related spectral perturbation. The time course of gamma-band ASSRs showed significantly different features among groups. Compared with the HC group, the UHR group was characterized by intact early-latency (0-100 ms) and reduced late-latency (300-500 ms) ASSRs. In contrast, both early- and late-latency ASSRs were significantly reduced in the FES group. Gamma-band ASSRs were correlated with clinical symptoms and attentional functioning in FES (|rs| > 0.70). These results suggest differential alterations of gamma-band ASSRs between UHR and FES groups. The late-latency ASSR alteration may represent a biomarker for early detection of psychosis, while the early-latency ASSR abnormality may develop through the onset of psychosis.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics, schizotypy