| 1 | Arch. Gen. Psychiatry 2000 Aug 57: 769-75 |
|---|---|
| PMID | 10920465 |
| Title | Temporolimbic volume reductions in schizophrenia. |
| Abstract | Neuroanatomic studies of schizophrenia have reported temporolimbic abnormalities. Most magnetic resonance imaging studies have evaluated small samples of primarily men with chronic schizophrenia. Our goal was to evaluate sex differences in segmented temporal lobe subregions with reliable parcellation methods, relating volume with clinical and neurocognitive parameters. Magnetic resonance imaging was performed in 100 patients with schizophrenia (58 men, 42 women; 39 neuroleptic naive, 61 previously treated) and 110 healthy controls (51 men, 59 women). Gray and white matter volumes of temporolimbic (hippocampus and amygdala) and neocortical regions (superior temporal gyrus and temporal POLE) were examined. Symptoms, functioning, and neurocognition were assessed concurrently. Hippocampal gray matter volume was reduced in men (7%) and women (8.5%) with schizophrenia. In the amygdala, however, decreased volume was evident for men (8%) whereas women (10.5%) had increased volume. Magnetic resonance imaging of the temporal POLE showed decreased gray matter in men (10%) and women (8.5%). For the superior temporal gyrus, the decrease exceeded that of whole-brain only in men (11.5%). Volumes were largely uncorrelated with clinical measures, but higher hippocampal volumes were associated with better memory performance for all groups. Cortical volumes were associated with better memory performance in healthy women. schizophrenia is associated with reduced gray matter volume in temporolimbic structures. In men, reduction was manifested in all regions, whereas women showed decreased hippocampal volumes but increased amygdala volumes. The abnormalities are evident in patients with first-episode schizophrenia and correlate more strongly with cognitive performance than with symptom severity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 2 | Neuroimage 2000 Apr 11: 271-88 |
| PMID | 10725184 |
| Title | An MRI-based parcellation method for the temporal lobe. |
| Abstract | The temporal lobe has long been a focus of attention with regard to the underlying pathology of several major psychiatric illnesses. Previous postmortem and imaging studies describing regional volume reductions or perfusion defects in temporal subregions have shown inconsistent findings, which are in part due to differences in the definition of the subregions and the methodology of measurement. The development of precise reproducible parcellation systems on magnetic resonance images may help improve uniformity of results in volumetric MR studies and unravel the complex activation patterns seen in functional neuroimaging studies. The present study describes detailed guidelines for the parcellation of the temporal neocortex. It parcels the entire temporal neocortex into 16 subregions: temporal POLE, heschl's gyrus, planum temporale, planum polare, superior temporal gyrus (rostral and caudal), middle temporal gyrus (rostral, intermediate, and caudal), inferior temporal gyrus (rostral, intermediate, and caudal), occipitotemporal gyrus (rostral and caudal), and parahippocampal gyrus (rostral and caudal). Based upon topographic landmarks of individual sulci, every subregion was consecutively traced on a set of serial coronal slices. In spite of the huge variability of sulcal topography, the sulcal landmarks could be identified reliably due to the simultaneous display of three orthogonal (transaxial, coronal, and sagittal) planes, triangulated gray matter isosurface, and a 3-D-rendered image. The reliability study showed that the temporal neocortex could be parceled successfully and reliably; intraclass correlation coefficient for each subregion ranged from 0.62 to 0.99. Ultimately, this method will permit us to detect subtle morphometric impairments or to find abnormal patterns of functional activation in the temporal subregions that might reflect underlying neuropathological processes in psychiatric illnesses such as schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 3 | Epileptic Disord 2002 Sep 4 Suppl 1: S17-22 |
| PMID | 12424086 |
| Title | Investigating temporal pole function by functional imaging. |
| Abstract | Although the role of the temporal lobe especially its mesial part is becoming clearer, that of the temporal POLE remains more mysterious. Temporal POLE function can be investigated in various ways: by comparing anatomical and clinical data; through experiments in animals; and by using functional imaging techniques. Anatomo-clinical studies have suggested that the temporal POLE is important in autobiographical memory; and studies in monkeys (conditioning and lesional experiments) have revealed a role for the temporal POLE in a variety of functions, including taste and olfaction, face recognition, visual discrimination of two-dimensional pictures, and the mnemonic functions of matching and learning. Functional imaging techniques, whether based on positron emission tomography (PET) or magnetic resonance imaging (MRI), make it possible to observe the functioning of the temporal POLE in vivo in both healthy control subjects and patients. Initially, this type of approach was simply used to confirm observations made in animals. More recently it has shed light on other functions, especially with respect to processes associated with linguistic integration, which underlie the ability to make lexical and semantic links between different words and make it possible to understand a story in a general way without prior specific knowledge. Studies of epileptic, demented and schizophrenic patients have revealed that abnormal patterns of temporal POLE function are typical in all these conditions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 4 | J Am Psychoanal Assoc 2002 -1 50: 457-82 |
| PMID | 12206540 |
| Title | Quantitative research on the primary process: method and findings. |
| Abstract | Freud always defined the primary process metapsychologically, but he described the ways it shows up in dreams, parapraxes, jokes, and symptoms with enough observational detail to make it possible to create an objective, reliable scoring system to measure its manifestations in Rorschach responses, dreams, TAT stories, free associations, and other verbal texts. That system can identify signs of the thinker's efforts, adaptive or maladaptive, to control or defend against the emergence of primary process. A prerequisite and a consequence of the research that used this system was clarification and elaboration of the psychoanalytic theory of thinking. Results of empirical tests of several propositions derived from psychoanalytic theory are summarized. Predictions concerning the method's most useful index, of adaptive vs. maladaptive regression, have been repeatedly verified: People who score high on this index (who are able to produce well-controlled "primary products" in their Rorschach responses), as compared to those who score at the maladaptive POLE (producing primary-process-filled responses with poor reality testing, anxiety, and pathological defensive efforts), are better able to tolerate sensory deprivation, are more able to enter special states of consciousness comfortably (drug-induced, hypnotic, etc.), and have higher achievements in artistic creativity, while schizophrenics tend to score at the extreme of maladaptive regression. Capacity for adaptive regression also predicts success in psychotherapy, and rises with the degree of improvement after both psychotherapy and drug treatment. Some predictive failures have been theoretically interesting: Kris's hypothesis about creativity and the controlled use of primary process holds for males but usually not for females. This body of work is presented as a refutation of charges, brought by such critics as Crews, that psychoanalysis cannot become a science. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 5 | Arch. Gen. Psychiatry 2003 Dec 60: 1193-200 |
| PMID | 14662551 |
| Title | Decrements in volume of anterior ventromedial temporal lobe and olfactory dysfunction in schizophrenia. |
| Abstract | Patients with schizophrenia exhibit olfactory deficits, but it is unclear whether these represent a specific abnormality. The link between olfactory impairments and regional brain abnormalities has yet to be established. To determine whether patients with schizophrenia exhibit volumetric deficits in the anterior ventromedial temporal lobe, the target for neuronal inputs from the olfactory bulb, and whether these are related to olfactory performance deficits. A cohort study of patients and healthy control subjects who underwent both 1-mm spoiled-gradient echo magnetic resonance imaging and behavioral tests of olfaction and memory. schizophrenia Research Center at the University of Pennsylvania, Philadelphia. Fifty-two patients with a DSM-IV diagnosis of schizophrenia and 38 healthy control subjects. Individuals were excluded for history of head trauma, significant substance abuse, and medical conditions affecting brain function or olfactory capacity. Gray matter volumes of the left and right temporal POLEs and the perirhinal and entorhinal cortexes; olfactory threshold detection sensitivity and identification test scores; composite indexes of verbal and spatial memory ability. Patients had reduced volumes, relative to cranial size, in left (P =.003) and right (P =.01) perirhinal and left (P =.002) and right (P =.002) entorhinal cortexes, but not in the temporal POLE. Perirhinal, but not entorhinal, cortical volume decrement was associated with decreased olfactory threshold sensitivity. Neither region was associated with impaired memory performance. Patients with schizophrenia have reduced cortical volumes in brain regions that receive afferents directly from the olfactory bulb. Behavioral olfactory deficits are related to structural brain abnormalities in these regions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 6 | Arch. Gen. Psychiatry 2003 Nov 60: 1069-77 |
| PMID | 14609882 |
| Title | Differences and similarities in insular and temporal pole MRI gray matter volume abnormalities in first-episode schizophrenia and affective psychosis. |
| Abstract | Whether psychoses associated with schizophrenia and affective disorder represent manifestations of different disorders or the same disorder is an important but unresolved question in psychiatry. Results of previous volumetric magnetic resonance imaging investigations indicate that gray matter volume reductions in neocortical regions may be specific to schizophrenia. To simultaneously evaluate multiple olfactocentric paralimbic regions, which play crucial roles in human emotion and motivation, in first-episode patients with schizophrenia and affective psychosis. A cross-sectional study using high-spatial resolution magnetic resonance imaging in patients with schizophrenia and affective psychosis at their first hospitalization. Inpatient units at a private psychiatric hospital. Fifty-three first-episode patients, 27 with schizophrenia and 26 with affective (mainly manic) psychosis, and 29 control subjects. Using high-spatial resolution magnetic resonance imaging, the gray matter volumes of 2 olfactocentric paralimbic regions of interest, the insular cortex and the temporal POLE, were evaluated. A bilateral volume reduction in insular cortex gray matter was specific to first-episode patients with schizophrenia. In contrast, both first-episode psychosis groups showed a volume reduction in left temporal POLE gray matter and an absence of normal left-greater-than-right asymmetry. Region of interest correlations showed that only patients with schizophrenia lacked a positive correlation between left temporal POLE and left anterior amygdala-hippocampal complex gray matter volumes, whereas both psychosis groups were similar in lacking normal positive correlations between left temporal POLE and left anterior superior temporal gyrus gray matter volumes. These partially different and partially similar patterns of structural abnormalities in olfactocentric paralimbic regions and their associated abnormalities in other temporolimbic regions may be important factors in the differential and common manifestations of the 2 psychoses. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 7 | J. Neurochem. 2003 Aug 86: 736-48 |
| PMID | 12859686 |
| Title | Repeated variable prenatal stress alters pre- and postsynaptic gene expression in the rat frontal pole. |
| Abstract | Exposure of pregnant women to stress during a critical period of fetal brain development is an environmental risk factor for developing schizophrenia in the adult offspring. We have applied a repeated variable stress paradigm to pregnant Sprague-Dawley rats during the last week of gestation coinciding with the second trimester in human brain development. Here we report our findings from a microarray analysis of the frontal POLE of the prenatally stressed adult offspring and non-stressed adult controls complemented with measurement of plasma corticosterone levels following exposure to an acute stress. The direction of change of selected genes was confirmed by real time quantitative fluorescence PCR and in situ hybridization. The analysis revealed significant changes in genes associated with the NMDA receptor/postsynaptic density complex and the vesicle exocytosis machinery including NMDA receptor NR1 and NR2A subunits, densin-180, brain enriched guanylate kinase-associated protein, synaptosome-associated protein of 25 kDa, synaphin/complexin and vesicle-associated membrane protein 2/synaptobrevin 2. Interestingly, some of the changes in this animal preparation are analogous to changes observed in schizophrenic and bipolar patients. Our results suggest that application of a repeated variable prenatal stress paradigm during a critical period of fetal brain development reprograms the response of the hypothalamo-pituitary-adrenal axis to acute stress and results in gene expression changes that may have enduring effects on synaptic function in the offspring during adulthood. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 8 | J. Neurochem. 2003 Aug 86: 736-48 |
| PMID | 12859686 |
| Title | Repeated variable prenatal stress alters pre- and postsynaptic gene expression in the rat frontal pole. |
| Abstract | Exposure of pregnant women to stress during a critical period of fetal brain development is an environmental risk factor for developing schizophrenia in the adult offspring. We have applied a repeated variable stress paradigm to pregnant Sprague-Dawley rats during the last week of gestation coinciding with the second trimester in human brain development. Here we report our findings from a microarray analysis of the frontal POLE of the prenatally stressed adult offspring and non-stressed adult controls complemented with measurement of plasma corticosterone levels following exposure to an acute stress. The direction of change of selected genes was confirmed by real time quantitative fluorescence PCR and in situ hybridization. The analysis revealed significant changes in genes associated with the NMDA receptor/postsynaptic density complex and the vesicle exocytosis machinery including NMDA receptor NR1 and NR2A subunits, densin-180, brain enriched guanylate kinase-associated protein, synaptosome-associated protein of 25 kDa, synaphin/complexin and vesicle-associated membrane protein 2/synaptobrevin 2. Interestingly, some of the changes in this animal preparation are analogous to changes observed in schizophrenic and bipolar patients. Our results suggest that application of a repeated variable prenatal stress paradigm during a critical period of fetal brain development reprograms the response of the hypothalamo-pituitary-adrenal axis to acute stress and results in gene expression changes that may have enduring effects on synaptic function in the offspring during adulthood. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 9 | Psychiatry Res 2004 Dec 132: 107-15 |
| PMID | 15598545 |
| Title | Temporal pole morphology and psychopathology in males with schizophrenia. |
| Abstract | A dysfunction of the paralimbic system has been implicated in the pathophysiology of schizophrenia. The temporal POLE (TP) is a relevant component of the paralimbic circuit. Functional and structural imaging studies have shown circumscribed abnormalities in the TP. Subjects were 30 controls and 30 schizophrenia patients. Cortical surface size and gray matter volume of the TP were accurately measured to explore the morphology of the TP cortex and the relationship of TP measures to clinical variables in patients with schizophrenia. Correlations between structural measures and clinical dimensions, duration of illness, and cumulative neuroleptic exposure were determined. Neither macroscopic abnormalities in the TP nor differences in the pattern of asymmetry were demonstrated. The TP volume was correlated negatively to the psychotic and disorganized dimension scores. No other significant correlations were found. No morphological abnormalities in the TP were found in patients with schizophrenia. Interestingly, a reduction in the TP volume, a higher-order multimodal association cortex, was associated with the severity of disorganized and psychotic symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 10 | Can J Psychiatry 2005 Dec 50: 909-17 |
| PMID | 16494260 |
| Title | Neural correlates of sad feelings in schizophrenia with and without blunted affect. |
| Abstract | There have been reports that patients with schizophrenia have decreased activity in the prefrontal cortex during emotion processing. However, findings have been confounded by sample nonspecificity and explicit cognitive task interference with emotion processing. We aimed to further investigate this by examining the ventrolateral prefrontal cortex (VLPFC) activation in response to the passive viewing of sad film excerpts. We presented film excerpts depicting sad and neutral social situations to 25 schizophrenia patients (14 with blunted affect [BA+] and 11 without blunted affect [BA-]) in an implicit perception task to evoke prefronto-limbic activity illustrated by blood oxygenation level-dependent functional magnetic resonance imaging. A random-effects analysis (2-sample t test) using statistical parametric mapping indicated that BA+ patients differed from BA- patients at a 0.05 level (P corrected for multiple comparisons). Consistent with our a priori hypothesis, BA- patients (relative to BA+ patients) showed significant activation in the right VLPFC. An exploratory analysis revealed the following loci of activation: caudate nucleus, VLPFC, middle prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, and anterior temporal POLE in the BA- group; and hippocampus, cerebellum, anterior temporal POLE, and midbrain in the BA+ group. We observed not only hypofrontality in the BA+ group but also dysfunctional circuitry distributed throughout the brain. The temporal and midbrain activation seen in the BA+ group may indicate that these brain regions were working harder to compensate for inactivation in other regions. These distributed dysfunctional circuits may form the neural basis of blunted affect through impairment of emotion processing in the brain that prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as blunted affect. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 11 | Am J Psychiatry 2005 Oct 162: 1840-8 |
| PMID | 16199830 |
| Title | Levels-of-processing effect on frontotemporal function in schizophrenia during word encoding and recognition. |
| Abstract | Patients with schizophrenia improve episodic memory accuracy when given organizational strategies through levels-of-processing paradigms. This study tested if improvement is accompanied by normalized frontotemporal function. Event-related blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) was used to measure activation during shallow (perceptual) and deep (semantic) word encoding and recognition in 14 patients with schizophrenia and 14 healthy comparison subjects. Despite slower and less accurate overall word classification, the patients showed normal levels-of-processing effects, with faster and more accurate recognition of deeply processed words. These effects were accompanied by left ventrolateral prefrontal activation during encoding in both groups, although the thalamus, hippocampus, and lingual gyrus were overactivated in the patients. During word recognition, the patients showed overactivation in the left frontal POLE and had a less robust right prefrontal response. Evidence of normal levels-of-processing effects and left prefrontal activation suggests that patients with schizophrenia can form and maintain semantic representations when they are provided with organizational cues and can improve their word encoding and retrieval. Areas of overactivation suggest residual inefficiencies. Nevertheless, the effect of teaching organizational strategies on episodic memory and brain function is a worthwhile topic for future interventional studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 12 | Psychiatry Res 2005 Oct 140: 1-15 |
| PMID | 16143498 |
| Title | Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study. |
| Abstract | The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal POLE, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal POLE, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 13 | Eur Arch Psychiatry Clin Neurosci 2005 Aug 255: 236-44 |
| PMID | 16133741 |
| Title | Frontal lobe alterations in schizophrenia: neuroimaging and neuropsychological findings. |
| Abstract | Functional neuroimaging and neuropsychological performance indicate a prefrontal dysfunction in schizophrenia patients. Frontal morphological brain abnormalities are also evident in these patients, but the relationship between neuropsychology and neuroimaging findings remains unclear. In this study, thirty patients with schizophrenia and 30 control participants were assessed using a neuropsychological test battery sensitive to fronto-striatal system dysfunction. Computed tomography (CT) scans were used to calculate the distance from the corpus callosum to the frontal POLE corrected for brain size (anterioposterior length) in the group of patients and in a group of control participants with negative radiological findings. schizophrenia patients performed significantly worse than controls in all frontal lobe tests. Corrected length from the corpus callosum to the frontal POLE was reduced in patients with schizophrenia. This easy-to-perform measurement has not been used in previous studies, and indicates that schizophrenia patients have structural frontal abnormalities. However, correlations between structural and functional measures fail to show a clear relationship between the prefrontal performance and the main CT measures. As a rule, the trend observed in the correlation matrix pointed towards a relationship between CT parameters and a dysfunction on neuropsychological tests sensitive to frontal lobe damage. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 14 | J Clin Psychopharmacol 2005 Aug 25: 367-71 |
| PMID | 16012281 |
| Title | Differential hemodynamic brain activity in schizophrenia patients with blunted affect during quetiapine treatment. |
| Abstract | Blood-oxygenation-level-dependent (BOLD) brain changes underlying response to quetiapine were examined using passive viewing of emotionally negative stimuli. Twelve DSM-IV schizophrenia patients with blunted affect (BA+) were scanned before and after 22 weeks of quetiapine treatment. Whole-brain, voxel-based methods were used to assess the differential hemodynamic response to quetiapine. In addition, a post hoc comparison to an independent group of 11 schizophrenia patients without blunted affect (BA-) was performed to compare them with BA+ (postquetiapine) in response to emotion processing. A 22-week treatment with quetiapine resulted in significant clinical improvement in the 12 study completers (mean +/- SD posttreatment PANSS blunted affect score of 5.50 +/- 0.76 at baseline to 2.08 +/- 1.00 at end point; t = 7.78, df = 11, P < 0.0001). Treatment response was associated with significant BOLD changes: increases in prefrontal cortex activation particularly in the right dorsolateral prefrontal cortex (DLPFC, BA 46) and the right anterior cingulate cortex (ACC, BA 32); and in the left putamen, right anterior temporal POLE (ATP), and right amygdala. Conversely, before treatment with quetiapine, the same subjects activated the midbrain bilaterally and the right pons. The post hoc conjunctional analyses demonstrated that BA- subjects activated the left ACC, left insula, left ATP (BA 21), left ATP (BA 38), left amygdala, and right medial prefrontal cortex. Quetiapine seems to affect clinical recovery by modulating the functioning of specific brain regions. Unique BOLD changes in the putamen and DLPFC with quetiapine, in the BA+ postquetiapine, may reflect modality-specific effects. Controlled studies are needed to further assess these preliminary findings. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 15 | Schizophr. Res. 2005 Jul 76: 207-29 |
| PMID | 15949654 |
| Title | Cortical intercorrelations of temporal area volumes in schizophrenia. |
| Abstract | Abnormal temporal connections with other cortical areas may underlie some of the most prominent cognitive deficits described in schizophrenia. In order to evaluate the relationship between temporal and other cortical regions in schizophrenia, we examined the intercorrelations of volumetric measures of gray and white matter for each Brodmann's area of the temporal lobe with volumes in the rest of the cortex in patients with schizophrenia and normal comparison subjects. MR images were acquired in normal subjects (n=46) and patients with schizophrenia (n=106), divided into good-outcome (n=52) and poor-outcome (Kraepelinian; n=54) subtypes; and correlational patterns between the volumes of individual Brodmann's areas were compared and examined in relation to outcome. Positive frontotemporal intercorrelations were significantly stronger while negative frontotemporal intercorrelations were weaker in schizophrenia patients as compared to normal subjects. Correlations between the right temporal POLE and other temporal regions were significantly weaker in schizophrenia patients than in controls. When compared to normal controls and good-outcome patients, schizophrenia patients with poor outcomes showed a selective pattern of stronger gray matter correlations between the medial temporal vs. primary visual and between primary auditory vs. dorsolateral prefrontal cortices, all in the left hemisphere. Strengthening of positive associations among the temporal and extratemporal (mainly frontal and occipital) regions as well as weakening of regional intercorrelations within the temporal lobe in patients appear to constitute the major differences of correlational patterns in schizophrenia patients and normal subjects. Present findings may be implicated in object recognition deficits seen in patients with schizophrenia, as well as in purportedly deficient spatial and semantic processing of both auditory and visual information that may be associated with poor outcome. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 16 | Hum Brain Mapp 2005 May 25: 60-9 |
| PMID | 15846819 |
| Title | Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. |
| Abstract | Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper- and hypoactivation in schizophrenia. We utilize a quantitative meta-analysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal POLE regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper- and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 17 | Biol. Psychiatry 2005 Jan 57: 49-55 |
| PMID | 15607300 |
| Title | Neonatal lesions of the ventral hippocampal formation alter GABA-A receptor subunit mRNA expression in adult rat frontal pole. |
| Abstract | Gamma-aminobutyric acid (GABA)-ergic function is altered in schizophrenia. Of particular interest is the altered central nervous system expression of GABA-A receptor subunits, as changes in subunit expression account for recognized differences in mammalian brain function making them inviting targets for novel psychotropic agents. Excitotoxic neonatal lesions of the ventral hippocampal formation (NVHL) in rats reproduce numerous aspects of schizophrenia, including decreased mRNA expression of the GABA synthesizing enzyme glutamic acid decarboxylase-67, though their impact on subunit expression is unknown. We utilized quantitative reverse transcription polymerase chain reaction to investigate mRNA expression of the alpha1, alpha5, and gamma2s GABA-A receptor subunits in the frontal POLE of water-deprived adult NVHL and SHAM-lesioned animals. Messenger RNA expression for all three GABA-A subunits (alpha1-NVHL: 18.5 +/- 1.6 pg/mug total pooled RNA, SHAM: 11.3 +/- .4; alpha5-NVHL: 5.1 +/- .6; SHAM: 3.5 +/- .7; and gamma2s-NVHL: 10.8 +/- 1.7; SHAM: 7.2 +/- 1.5) was higher in NVHL, though only levels of alpha1 differed significantly after correction for multiple comparisons. Levels of a control mRNA, neuronal specific enolase, were similar in the two groups. These data indicate that NVHL reproduce changes in cortical GABA-A receptor subunit expression seen in schizophrenia, suggesting this animal model may facilitate efforts to clarify the physiologic significance of altered GABA function and to develop novel targets for therapeutic interventions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 18 | Arch. Gen. Psychiatry 2006 Aug 63: 844-54 |
| PMID | 16894060 |
| Title | Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia. |
| Abstract | There is evidence of linkage to a schizophrenia susceptibility locus on chromosome 8p21-22 found by several family linkage studies. To fine map and identify a susceptibility gene for schizophrenia on chromosome 8p22 and to investigate the effect of this genetic susceptibility on an endophenotype of abnormal brain structure using magnetic resonance imaging. Fine mapping and identification of a chromosome 8p22 susceptibility gene was carried out by finding linkage disequilibrium between genetic markers and schizophrenia in multiply affected families, a case-control sample, and a trio sample. Variation in brain morphology associated with pericentriolar material 1 (PCM1) alleles was examined using voxel-based morphometry and statistical parametric mapping with magnetic resonance imaging. Setting and Patients A family sample of 13 large families multiply affected with schizophrenia, 2 schizophrenia case-control samples from the United Kingdom and Scotland, and a sample of schizophrenic trios from the United States containing parents and 1 affected child with schizophrenia. Tests of transmission disequilibrium between PCM1 locus polymorphisms and schizophrenia using a family sample and tests of allelic association in case-control and trio samples. Voxel-based morphometry using statistical parametric mapping. The family and trio samples both showed significant transmission disequilibrium between marker D85261 in the PCM1 gene locus and schizophrenia. The case-control sample from the United Kingdom also found significant allelic association between PCM1 gene markers and schizophrenia. Voxel-based morphometry of cases who had inherited a PCM1 genetic susceptibility showed a significant relative reduction in the volume of orbitofrontal cortex gray matter in comparison with patients with non-PCM1-associated schizophrenia, who, by contrast, showed gray matter volume reduction in the temporal POLE, hippocampus, and inferior temporal cortex. The PCM1 gene is implicated in susceptibility to schizophrenia and is associated with orbitofrontal gray matter volumetric deficits. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 19 | Arch. Gen. Psychiatry 2006 Aug 63: 844-54 |
| PMID | 16894060 |
| Title | Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia. |
| Abstract | There is evidence of linkage to a schizophrenia susceptibility locus on chromosome 8p21-22 found by several family linkage studies. To fine map and identify a susceptibility gene for schizophrenia on chromosome 8p22 and to investigate the effect of this genetic susceptibility on an endophenotype of abnormal brain structure using magnetic resonance imaging. Fine mapping and identification of a chromosome 8p22 susceptibility gene was carried out by finding linkage disequilibrium between genetic markers and schizophrenia in multiply affected families, a case-control sample, and a trio sample. Variation in brain morphology associated with pericentriolar material 1 (PCM1) alleles was examined using voxel-based morphometry and statistical parametric mapping with magnetic resonance imaging. Setting and Patients A family sample of 13 large families multiply affected with schizophrenia, 2 schizophrenia case-control samples from the United Kingdom and Scotland, and a sample of schizophrenic trios from the United States containing parents and 1 affected child with schizophrenia. Tests of transmission disequilibrium between PCM1 locus polymorphisms and schizophrenia using a family sample and tests of allelic association in case-control and trio samples. Voxel-based morphometry using statistical parametric mapping. The family and trio samples both showed significant transmission disequilibrium between marker D85261 in the PCM1 gene locus and schizophrenia. The case-control sample from the United Kingdom also found significant allelic association between PCM1 gene markers and schizophrenia. Voxel-based morphometry of cases who had inherited a PCM1 genetic susceptibility showed a significant relative reduction in the volume of orbitofrontal cortex gray matter in comparison with patients with non-PCM1-associated schizophrenia, who, by contrast, showed gray matter volume reduction in the temporal POLE, hippocampus, and inferior temporal cortex. The PCM1 gene is implicated in susceptibility to schizophrenia and is associated with orbitofrontal gray matter volumetric deficits. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 20 | Psychiatry Res 2006 Dec 148: 151-63 |
| PMID | 17088050 |
| Title | Inter-rater reliability of manual segmentation of the superior, inferior and middle frontal gyri. |
| Abstract | Precise rules for locating the anatomical boundaries of the dorsolateral prefrontal cortex (DLPFC) or its subdivisions, i.e., superior, inferior and middle frontal gyri (SFG, IFG and MFG) on magnetic resonance images (MRI), have not been defined. The present study describes the inter-rater reliability of manual segmentation of the SFG, IFG and MFG using guidelines based on sulcal-gyral anatomical boundaries as well as the cytoarchitectonic features of the sub-regions of the prefrontal cortex (PFC). Variations in the application of these guidelines in different subjects to account for normal sulcal variability were developed using the atlas of Ono et al. (Ono, M., Kubik, S., Abernathey, C.D., 1990. Atlas of the Cerebral Sulci. Georg Thieme Verlag, New York). Based on previous cytoarchitectonic studies, the coronal plane of the anterior termination of olfactory sulcus (ATOS) was used as a landmark for delimiting the boundary between the frontal POLE (FP) and the frontal gyri. The left hemisphere gray-matter volumes of the SFG, IFG and MFG were determined using a set of 10 MRIs (5 normal and 5 schizophrenia subjects) by two trained raters independently. The intra-class correlation coefficients (ICC) for the SFG, IFG and MFG volumes by the two raters were 0.97, 0.94 and 0.93, respectively. Thus, we describe a reliable method of parcellating the SFG, IFG and MFG, which constitute the DLPFC, a brain region involved in a variety of neuropsychiatric conditions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 21 | Schizophr. Res. 2006 Apr 83: 131-43 |
| PMID | 16503399 |
| Title | Morphologic alterations of the parcellated superior temporal gyrus in schizophrenia spectrum. |
| Abstract | Morphologic abnormalities of the superior temporal gyrus (STG) as well as its sub-regions such as Heschl's gyrus (HG) or planum temporale (PT) have been reported in schizophrenia patients, but have not been extensively studied in schizotypal subjects. In the present study, magnetic resonance images were acquired from 65 schizophrenia patients, 39 schizotypal disorder patients, and 72 healthy controls. Volumetric analyses were performed using consecutive 1-mm coronal slices on the temporal POLE (TP) and superior temporal sub-regions [planum polare (PP), HG, PT, rostral STG, and caudal STG]. The HG was significantly smaller in schizophrenia patients compared with controls but not in schizotypal patients, while volume reductions of the left PT and bilateral caudal STG were common to both disorders. The TP gray matter was larger in female schizotypal patients compared with female schizophrenia patients. There were no significant group differences in the PP and rostral STG volume. In the subgroup of early phase schizophrenia patients (illness duration <1.0 year), smaller volumes for the left PP and rostral STG were correlated with hallucinations and delusions. Our findings suggest that morphologic changes in the posterior regions of the STG are common to the schizophrenia spectrum, whereas less involvement of the HG, and possibly the PP and rostral STG might be related to the sparing of schizotypal patients from developing overt psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 22 | Schizophr. Res. 2006 Apr 83: 131-43 |
| PMID | 16503399 |
| Title | Morphologic alterations of the parcellated superior temporal gyrus in schizophrenia spectrum. |
| Abstract | Morphologic abnormalities of the superior temporal gyrus (STG) as well as its sub-regions such as Heschl's gyrus (HG) or planum temporale (PT) have been reported in schizophrenia patients, but have not been extensively studied in schizotypal subjects. In the present study, magnetic resonance images were acquired from 65 schizophrenia patients, 39 schizotypal disorder patients, and 72 healthy controls. Volumetric analyses were performed using consecutive 1-mm coronal slices on the temporal POLE (TP) and superior temporal sub-regions [planum polare (PP), HG, PT, rostral STG, and caudal STG]. The HG was significantly smaller in schizophrenia patients compared with controls but not in schizotypal patients, while volume reductions of the left PT and bilateral caudal STG were common to both disorders. The TP gray matter was larger in female schizotypal patients compared with female schizophrenia patients. There were no significant group differences in the PP and rostral STG volume. In the subgroup of early phase schizophrenia patients (illness duration <1.0 year), smaller volumes for the left PP and rostral STG were correlated with hallucinations and delusions. Our findings suggest that morphologic changes in the posterior regions of the STG are common to the schizophrenia spectrum, whereas less involvement of the HG, and possibly the PP and rostral STG might be related to the sparing of schizotypal patients from developing overt psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 23 | Neuroimage 2006 Jan 29: 90-8 |
| PMID | 16122944 |
| Title | Neuronal correlates of theory of mind and empathy: a functional magnetic resonance imaging study in a nonverbal task. |
| Abstract | Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal POLE in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from Sarfati et al. (1997) [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. schizophrenia Research 25, 199-209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal POLEs. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 24 | Encephale 2007 Dec 33: 924-32 |
| PMID | 18789784 |
| Title | [The onset of psychiatric disorders and Wilson's disease]. |
| Abstract | Wilson's disease is an infrequent, autosomic recessive pathology, resulting from a loss of function of an adenosine triphosphatase (ATP7B or WDNP), secondarily to a change (more than 60 are described currently), insertion or deletion of the ATP7B gene located on the chromosome 13q14.3-q21.1, which involves a reduction or an absence of the transport of copper in the bile and its accumulation in the body, notably the brain. Wilson's disease is transmitted by an autosomic recessive gene located on the long arm of chromosome 13. The prevalence of the heterozygote is evaluated at 1/90 and the homozygote at 1/30,000. Consanguinity, frequent in the socially geographically isolated populations, increases the prevalence of the disease. The toxic quantities of copper, which accumulate in the liver since early childhood and perhaps before, remain concentrated in the body for years. Hence, cytological and histological modifications can be detected in the biopsies, before the appearance of clinical or biological symptoms of hepatic damage. The accumulation of copper in the liver is due to a defect in the biliary excretion of metal and is accompanied invariably by a deficit in ceruloplasmin; protein synthesized from a transferred ATP7B gene, which causes retention of the copper ions in the liver. The detectable cellular anomalies are of two types: hepatic lesions resulting in acute hepatic insufficiency, acute hepatitis and finally advanced cirrhosis and lesions of the central nervous system responsible for the neurological and psychiatric disorders. In approximately 40-50% of the patients, the first manifestation of Wilson's disease affects the central nervous system. Although copper diffuses in the liver towards the blood and then towards other tissues, it has disastrous consequences only in the brain. It can therefore cause either a progressive neurological disease, or psychiatric disorders. Wilson's disease begins in the form of a hepatic, neurological, or psychiatric disease in at least 90% of the patients. In some rare cases, the first manifestations of the disease can be psychiatric which, according to the literature, accounts for only 10% of the cases. The disease can be revealed by isolated behavioral problems, an irrational syndrome, a schizophrenic syndrome, or a manic-depressive syndrome. Damage to the central nervous system can be more severe, thus, several differential diagnoses have been discussed: a psychotic disorder of late appearance; a depressive state; a mental confusion disorder. The clinical syndrome is complex. Indeed, it is the polymorphism, which dominates in the description of the psychiatric demonstrations of the disease. This can lead to prejudicial diagnostic wandering, particularly since heavy sedative treatment may be required to suppress behavioral problems. Clinically, Wilson's disease generally appears between the age of 10 and 20. It rarely remains masked until after the age of 40. The first manifestations are hepatic (40% of the cases), neurological (35%) or psychiatric (10%). The inaugural disorder can finally take on a haematological, renal, or mixed form in approximately 15% of the cases. We have detailed the principal clinical elements. In approximately 40-50% of the patients, the first manifestation of the disease affects the central nervous system, where it can cause either a progressive neurological disease, or psychiatric disorders. The ophthalmologic disorder is dominated by Kayser-Fleischer's ring, representing a green or bronze colored ring on the periphery of the cornea. It occupies the higher POLE of the cornea, then the lower POLE, and extends to the whole circumference. It is generally only visible under examination with a slit lamp. It disappears on average within 3-5 years following copper chelating therapy. Kayser-Fleischer's ring has been described other than in Wilson's disease, in exceptional cases of prolonged cholestasis. On haematological level, the hyperhaemolysis is due to the toxicity of the ionic copper, released massively in the plasma by hepatocellular necrosis. The other manifestations can be found in the following organs: renal, osteoarticular, cardiac, endocrine, cutaneous, and in the teguments. Until 1952, the diagnosis was evoked only on clinical symptomatology. It can henceforth be marked unambiguous, even in the absence of any symptom, by the description of a ceruloplasmin plasma concentration of less than 200 ml/l, and of a Kayser-Fleischer's ring. Hepatic copper on sample is constantly increased during the disease (from 3 to 25 micromol/g of dry weight). On the other hand, the absence of a reduction in the plasma ceruloplasmin does not make it possible to exclude the diagnosis. Conversely, a reduction in ceruloplasmin can exist other than in Wilson's disease (nephritic syndrome, malabsorption syndrome, or severe hepatic insufficiency). Kayser-Fleischer's ring is quasiconstant among patients with neuropsychiatric demonstrations (thus, its absence represents a very strong argument against the diagnosis). It can on the other hand be lacking during hepatic forms, and in this case, its absence is not an argument against the diagnosis. Magnetic resonance imaging can reveal abnormal signals of the grey cores. A genetic study is conducted by liaison analysis in the event of a family history of the disease. When it is not treated, Wilson's disease induces lesions of the tissues, the outcome of which is always fatal. Treatment relies on the regulation of copper chelation, which improves the prognosis, and zinc, which captures the copper in a nontoxic form. The severe psychiatric disorders observed during Wilson's disease may require tranquilizers, but care should be taken because of potential neurological or hepatic side effects. Lithium seems an interesting treatment and remains theoretically indicated, taking into account the scarcity of the extrapyramidal symptoms and the hepatic dysfunction among patients at the stage of cirrhosis, since it is not metabolized in the liver. Although rare, it is important to approach Wilson's disease in psychiatry because the psychiatric manifestations can precede the somatic disorders and help to pose the diagnosis. We stress the importance of the early diagnosis of the pathology, the outcome of which is fatal in the absence of specific treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 25 | Psychopharmacol Bull 2007 -1 40: 7-14 |
| PMID | 18007564 |
| Title | Defining the clinical course of bipolar disorder: response, remission, relapse, recurrence, and roughening. |
| Abstract | This manuscript presents working definitions for key clinical course indicators for bipolar disorder, including response, remission, relapse, recurrence, and roughening. A work group of experts in bipolar disorder reviewed prior efforts to define clinical course indicators for unipolar depression and for schizophrenia. Using these efforts as templates, the work group developed consensus operational definitions. The rationale for each of the definitions was a point of time when a treatment decision needed to be made. The group defined response as a 50% reduction in a score from a standard rating scale of symptomatology from an appropriate baseline, regardless of index episode type (manic, depressed, or mixed). In addition, the other POLE cannot be significantly worsened during response. Remission was defined as absence or minimal symptoms of both mania and depression for at least 1 week. Sustained remission requires at least eight consecutive weeks of remission, and perhaps as many as 12 weeks. A relapse/recurrence was defined as a return to the full syndrome criteria of an episode of mania, mixed episode, or depression following a remission of any duration. Roughening was defined as a return of symptoms at a subsyndromal level, perhaps representing a prodrome of an impending episode. The work group recommends that all reports of clinical trials in bipolar disorder include results using these definitions. This will introduce standards for such reports. Hopefully, the definitions will be revised and improved over time. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 26 | Neuroimage 2007 Aug 37: 449-62 |
| PMID | 17587598 |
| Title | A comprehensive assessment of gray and white matter volumes and their relationship to outcome and severity in schizophrenia. |
| Abstract | Preliminary data suggest an association of posterior cortical gray matter reduction with poor outcome in schizophrenia. We made a systematic MRI assessment of regional gray and white matter volumes, parcellated into 40 Brodmann's areas, in 104 patients with schizophrenia (51 with good outcomes, 53 with poor outcomes) and 41 normal comparison subjects, and investigated correlations of regional morphometry with outcome and severity of the illness. schizophrenia patients displayed differential reductions in frontal and to a lesser degree temporal gray matter volumes in both hemispheres, most pronounced in the frontal POLE and lateral temporal cortex. White matter volumes in schizophrenia patients were bilaterally increased, primarily in the frontal, parietal, and isolated temporal regions, with volume reductions confined to anterior cingulate gyrus. In patients with schizophrenia as a group, higher illness severity was associated with reduced temporal gray matter volumes and expanded frontal white matter volumes in both hemispheres. In comparison to good-outcome group, patients with poor outcomes had lower temporal, occipital, and to a lesser degree parietal gray matter volumes in both hemispheres and temporal, parietal, occipital, and posterior cingulate white matter volumes in the right hemisphere. While gray matter deficits in the granular cortex were observed in all schizophrenia patients, agranular cortical deficits in the left hemisphere were peculiar to patients with poor outcomes. These results provide support for frontotemporal gray matter reduction and frontoparietal white matter expansion in schizophrenia. Poor outcome is associated with more posterior distribution (posteriorization) of both gray and white matter changes, and with preferential impairment in the unimodal visual and paralimbic cortical regions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 27 | Eur. Psychiatry 2007 Sep 22: 387-94 |
| PMID | 17416488 |
| Title | Insular cortex and neuropsychiatric disorders: a review of recent literature. |
| Abstract | The insular cortex is located in the centre of the cerebral hemisphere, having connections with the primary and secondary somatosensory areas, anterior cingulate cortex, amygdaloid body, prefrontal cortex, superior temporal gyrus, temporal POLE, orbitofrontal cortex, frontal and parietal opercula, primary and association auditory cortices, visual association cortex, olfactory bulb, hippocampus, entorhinal cortex, and motor cortex. Accordingly, dense connections exist among insular cortex neurons. The insular cortex is involved in the processing of visceral sensory, visceral motor, vestibular, attention, pain, emotion, verbal, motor information, inputs related to music and eating, in addition to gustatory, olfactory, visual, auditory, and tactile data. In this article, the literature on the relationship between the insular cortex and neuropsychiatric disorders was summarized following a computer search of the Pub-Med database. Recent neuroimaging data, including voxel based morphometry, PET and fMRI, revealed that the insular cortex was involved in various neuropsychiatric diseases such as mood disorders, panic disorders, PTSD, obsessive-compulsive disorders, eating disorders, and schizophrenia. Investigations of functions and connections of the insular cortex suggest that sensory information including gustatory, olfactory, visual, auditory, and tactile inputs converge on the insular cortex, and that these multimodal sensory information may be integrated there. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 28 | Hum Brain Mapp 2007 Jul 28: 625-35 |
| PMID | 17080442 |
| Title | Methylphenidate-induced activation of the anterior cingulate but not the striatum: a [15O]H2O PET study in healthy volunteers. |
| Abstract | The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders, such as schizophrenia, depression, and addiction. (Dys)function of the dopaminergic system may be studied by combining [15O]H2O PET with a dopaminergic drug challenge. In this pilot study we investigated the suitability of the dopamine reuptake blocker methylphenidate (MP) as a dopaminergic probe. Measurements of regional cerebral blood flow (rCBF) were made at 10 and 30 min after placebo and MP (0.25 mg/kg) injection to seven healthy volunteers. During scanning the behavioral condition of the subjects was standardized using a continuous performance task. Growth hormone levels were assessed and subjective ratings were obtained. MP significantly elevated growth hormone levels. After receiving MP, the subjective experience varied from neutral to highly pleasurable. Ten minutes after MP administration, significant relative increases in rCBF were found in the rostral anterior cingulate (AC), temporal POLEs, and the supplementary motor area. Significant reductions were seen in the superior temporal gyri, right medial frontal gyrus, and right inferior parietal cortex. At 30 min after MP administration, increases were seen in the AC, temporal POLE, and right cerebellum. No changes were observed in the striatum. The activation in the right rostral AC was significantly higher in the subjects with the highest euphoria scores compared to the subjects with minimal MP-induced changes in euphoria. We suggest that the combined MP challenge with functional imaging, as described in our study, may be a useful tool to study the functional integrity of the dopaminergic system in psychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 29 | Schizophr. Res. 2008 Jan 98: 278-86 |
| PMID | 17964761 |
| Title | The perception of emotion-free faces in schizophrenia: a magneto-encephalography study. |
| Abstract | To analyze how patients suffering from schizophrenia perceive faces of unknown individuals that show no actual emotions in order to investigate the attribution of meanings to a relatively non-significant but complex sensory experience. Analysis of baseline and poststimulation magneto-encephalographic recordings. The stimuli consisted of four pictures with neutral emotional expression of male and female faces of Spanish individuals unknown to research subjects. Twelve right-handed patients suffering from schizophrenia (DSM IV-TR criteria), age 18-65, with active delusional activity (SAPS score in delusions above 39) and 15 right-handed sex- and age-matched control subjects. Compared to controls patients have a significant higher activity of both hemispheres (0-700 ms) being the activity in the right hemisphere (RH) higher than in the left hemisphere (LH). Patients also have a higher activity on the middle fusiform gyrus (BA 37) in the LH (200-300 ms), on the superior temporal areas (BA 22, 41 and 42) in both hemispheres (100-700 ms) and on the temporal POLE (BA 38) in the RH (300-400 ms) and a lower activity in the LH of the latter. The areas that are more activated in our study are those involved in the process of thinking, in attributing meanings to perceptions and in activities such as theory of mind, which are essential for social interaction. The anterior temporal areas less activated indicate a reduced semantic memory for faces that could explain the social withdrawal of schizophrenia. These alterations are suggestive of a dysfunction of left hemisphere neuronal networks. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 30 | Nucl Med Commun 2008 Oct 29: 894-900 |
| PMID | 18769307 |
| Title | Fluordeoxyglucose-PET study in first-episode schizophrenic patients during the hallucinatory state, after remission and during linguistic-auditory activation. |
| Abstract | We tested the hypothesis that endogenous auditory verbal hallucinations (AVH) involve activation of auditory/linguistic association cortices that are usually activated by externally presented speech. Nine neuroleptic-naive patients with first-episode schizophrenia (Diagnostic and Statistical Manual for Mental Disorders-IV criteria) with prominent AVH underwent three PET scans using F-fluordeoxyglucose (FDG): (i) shortly after presentation, while experiencing prominent and frequent AVH; (ii) after medication-induced remission (R), using a stable dose of risperidone; (iii) also in remission, during bilateral linguistic auditory activation (LAA) induced by spoken text mimicking the content of the hallucinations experienced while the first PET was performed, using headphones. PET scans were acquired using an Advanced-Nxi Scanner (GE Healthcare). Intrasubject realignment, spatial normalization and statistical analysis of PET images were carried out using statistical parametric mapping. Differences between AVH and R and between LAA and R were statistically evaluated using a voxel-wise paired t-test. A voxel level threshold of P<0.01 was used to determine which regions underwent the most significant changes in F-FDG uptake. During AVH, patients demonstrated a significant activation of the supplementary motor area, anterior cingulum, medial superior frontal area and cerebelum. Activation was also observed in the left superior frontal area, right superior temporal POLE and right orbitofrontal region. During LAA, greater FDG uptake was observed in the right and left superior and middle temporal cortices, left hippocampus and parahippocampal regions. Our findings show a different pattern of regional cerebral glucose metabolism between AVH and physiological auditory activation. This feature does not support the hypothesis that AVH in acute schizophrenic patients reflects an abnormal activation of auditory-linguistic pathways. However, it does suggest that cortical regions implicated in the generation of inner speech could be involved. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 31 | Nucl Med Commun 2008 Oct 29: 894-900 |
| PMID | 18769307 |
| Title | Fluordeoxyglucose-PET study in first-episode schizophrenic patients during the hallucinatory state, after remission and during linguistic-auditory activation. |
| Abstract | We tested the hypothesis that endogenous auditory verbal hallucinations (AVH) involve activation of auditory/linguistic association cortices that are usually activated by externally presented speech. Nine neuroleptic-naive patients with first-episode schizophrenia (Diagnostic and Statistical Manual for Mental Disorders-IV criteria) with prominent AVH underwent three PET scans using F-fluordeoxyglucose (FDG): (i) shortly after presentation, while experiencing prominent and frequent AVH; (ii) after medication-induced remission (R), using a stable dose of risperidone; (iii) also in remission, during bilateral linguistic auditory activation (LAA) induced by spoken text mimicking the content of the hallucinations experienced while the first PET was performed, using headphones. PET scans were acquired using an Advanced-Nxi Scanner (GE Healthcare). Intrasubject realignment, spatial normalization and statistical analysis of PET images were carried out using statistical parametric mapping. Differences between AVH and R and between LAA and R were statistically evaluated using a voxel-wise paired t-test. A voxel level threshold of P<0.01 was used to determine which regions underwent the most significant changes in F-FDG uptake. During AVH, patients demonstrated a significant activation of the supplementary motor area, anterior cingulum, medial superior frontal area and cerebelum. Activation was also observed in the left superior frontal area, right superior temporal POLE and right orbitofrontal region. During LAA, greater FDG uptake was observed in the right and left superior and middle temporal cortices, left hippocampus and parahippocampal regions. Our findings show a different pattern of regional cerebral glucose metabolism between AVH and physiological auditory activation. This feature does not support the hypothesis that AVH in acute schizophrenic patients reflects an abnormal activation of auditory-linguistic pathways. However, it does suggest that cortical regions implicated in the generation of inner speech could be involved. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 32 | Brain Res. 2009 Dec 1301: 126-34 |
| PMID | 19747901 |
| Title | Association between myelin basic protein expression and left entorhinal cortex pre-alpha cell layer disorganization in schizophrenia. |
| Abstract | There is evidence for migrational disturbances in the entorhinal cortex (ERC) in schizophrenia that supports a neurodevelopmental origin of the disorder. Since impaired myelin basic protein (MBP) gene expression during the migration phase could lead to abnormalities in final laminar position, we performed layer specific measurements of MBP expression in the ERC and hypothesised that migrational disturbances of pre-alpha-cell clusters relate to decreased MBP expression. Paraffin embedded sections of the left entorhinal cortex of 16 schizophrenia patients and 10 control subjects were stained for MBP using routine immunohistochemistry. On each section representative regions of interest were scanned to attain optimal quality images of the gray matter. Results were correlated to previous published disturbed dispersion of pre-alpha-cell clusters in adjacent brain sections. Mean MBP stain-intensity was significantly reduced in schizophrenia patients. Absolute MBP stain-intensity was significantly reduced in layers III and IV in patients. A significant correlation of MBP stain-intensity with the distance of the deep POLE of the pre-alpha-cell cluster from the gray-white matter junction was observed in the ERC of schizophrenia patients. The present data provide evidence for reduced MBP expression in the ERC in schizophrenia, which implies deficits in axonal myelination and disturbed connectivity. MBP gene is expressed in oligodendrocytes and neuronal populations during embryonic development, which are important in establishing the structure of the cerebral cortex. Correlation between reduced MBP as a sign of down-regulated MBP gene expression and disorganization of pre-alpha-cell clusters supports a neurodevelopmental origin of pathological processes in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 33 | Eur Neuropsychopharmacol 2009 Dec 19: 835-40 |
| PMID | 19717283 |
| Title | Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia. |
| Abstract | Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal POLE on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 34 | Acta Psychiatr Scand 2009 Mar 119: 199-208 |
| PMID | 19016669 |
| Title | Regional gray matter reduction and theory of mind deficit in the early phase of schizophrenia: a voxel-based morphometric study. |
| Abstract | We tested the association between theory of mind (ToM) performance and structural changes in the brains of patients in the early course of schizophrenia. Voxel-based morphometry (VBM) data of 18 patients with schizophrenia were compared with those of 21 controls. ToM skills were assessed by computerized faux pas (FP) tasks. Patients with schizophrenia performed significantly worse in FP tasks than healthy subjects. VBM revealed significantly reduced gray matter density in certain frontal, temporal and subcortical regions in patients with schizophrenia. Poor FP performance of schizophrenics correlated with gray matter reduction in the left orbitofrontal cortex and right temporal POLE. Our data indicate an association between poor ToM performance and regional gray matter reduction in the left orbitofrontal cortex and right temporal POLE shortly after the onset of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 35 | Behav. Brain Res. 2009 Jan 197: 1-8 |
| PMID | 18793680 |
| Title | Enhancement of latent inhibition in patients with chronic schizophrenia. |
| Abstract | Latent inhibition (LI) refers to the retarding effects of inconsequential stimulus preexposure on subsequent conditioning to that stimulus, and reflects the organism's capacity to ignore irrelevant stimuli. LI is disrupted in schizophrenia patients, due to faster learning of the association between the conditioned stimulus (CS) and an unconditioned stimulus (US). It was recently proposed that LI has an additional POLE of abnormality indicated by LI persistence. Two experiments were performed to test this hypothesis. Both experiments applied a new within-subject, visual recognition LI procedure in which the association between a cue (CS) and the target (US) is acquired. In Exp 1 the task was applied to healthy volunteers (n=21). In Exp 2 chronic schizophrenia patients (n=19) were compared to control subjects (n=20). In Exp 1 the subjects showed LI in the initial trials of cue-target pairings, and an attenuation of the phenomenon at later trials. In Exp 2 control subjects showed a pattern of response comparable to the subjects of Exp 1, while the patients showed LI only on the later trials of the task. This result suggests that patients with chronic schizophrenia showed LI persistence. The possible advantages of the new LI paradigm are discussed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 36 | Eur Neuropsychopharmacol 2009 Dec 19: 835-40 |
| PMID | 19717283 |
| Title | Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia. |
| Abstract | Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal POLE on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 37 | Acta Psychiatr Scand 2009 Mar 119: 199-208 |
| PMID | 19016669 |
| Title | Regional gray matter reduction and theory of mind deficit in the early phase of schizophrenia: a voxel-based morphometric study. |
| Abstract | We tested the association between theory of mind (ToM) performance and structural changes in the brains of patients in the early course of schizophrenia. Voxel-based morphometry (VBM) data of 18 patients with schizophrenia were compared with those of 21 controls. ToM skills were assessed by computerized faux pas (FP) tasks. Patients with schizophrenia performed significantly worse in FP tasks than healthy subjects. VBM revealed significantly reduced gray matter density in certain frontal, temporal and subcortical regions in patients with schizophrenia. Poor FP performance of schizophrenics correlated with gray matter reduction in the left orbitofrontal cortex and right temporal POLE. Our data indicate an association between poor ToM performance and regional gray matter reduction in the left orbitofrontal cortex and right temporal POLE shortly after the onset of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 38 | Schizophr. Res. 2009 Oct 114: 154-60 |
| PMID | 19632816 |
| Title | Functional and structural brain correlates of theory of mind and empathy deficits in schizophrenia. |
| Abstract | Patients affected by schizophrenia show deficits in social cognition, with abnormal performance on tasks targeting theory of mind (ToM) and empathy (Emp). Brain imaging studies suggested that ToM and Emp depend on the activation of brain networks mainly localized at the superior temporal lobe and temporo-parietal junction. Participants included 24 schizophrenia patients and 20 control subjects. We used brain blood oxygen level dependent fMRI to study the neural responses to tasks targeting ToM and Emp. We then studied voxel-based morphometry of grey matter in areas where diagnosis influenced functional activation to both tasks. Outcomes were analyzed in the context of the general linear model, with global grey matter volume as nuisance covariate for structural MRI. Patients showed worse performance on both tasks. We found significant effects of diagnosis on neural responses to the tasks in a wide cluster in right posterior superior temporal lobe (encompassing BA 22-42), in smaller clusters in left temporo-parietal junction and temporal POLE (BA 38 and 39), and in a white matter region adjacent to medial prefrontal cortex (BA 10). A pattern of double dissociation of the effects of diagnosis and task on neural responses emerged. Among these areas, grey matter volume was found to be reduced in right superior temporal lobe regions of patients. Functional and structural abnormalities were observed in areas affected by the schizophrenic process early in the illness course, and known to be crucial for social cognition, suggesting a biological basis for social cognition deficits in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 39 | Psychiatry Res 2009 Sep 173: 163-9 |
| PMID | 19616415 |
| Title | Gray matter abnormalities in subjects at ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls. |
| Abstract | Neuroimaging studies have revealed gray matter abnormalities in schizophrenia in various regions of the brain. It is, however, still unclear whether such abnormalities are already present in individuals at ultra-high risk (UHR) for transition into psychosis. We investigated this issue using voxel-based morphometry of structural magnetic resonance images (MRI) and compared UHR patients with first-episode patients with schizophrenia and healthy controls. Gray matter volume maps from high-resolution MR T1-weighted whole brain images were analyzed in a cross-sectional study in 30 UHR patients, 23 first-episode schizophrenic patients and 29 controls. UHR patients showed significantly lower gray matter volume in the cingulate gyrus bilaterally, in the right inferior frontal and right superior temporal gyrus, as well as in the left and right hippocampus in comparison to healthy subjects. First-episode patients with schizophrenia showed smaller gray matter volume in the cingulate cortex bilaterally, in the left orbitofrontal gyrus, in the right inferior frontal and superior temporal gyrus, in the right temporal POLE, in the left and right hippocampus, in the left parahippocampus, left amygdala, and in the left fusiform gyrus compared to the UHR patients. This study provides further evidence that gray matter brain volume, especially in the anterior cingulate cortex, is already reduced in the prodromal state of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 40 | Am J Psychiatry 2009 Aug 166: 863-74 |
| PMID | 19411370 |
| Title | Prefrontal activation deficits during episodic memory in schizophrenia. |
| Abstract | Episodic memory impairments represent a core deficit in schizophrenia that severely limits patients' functional outcome. This quantitative meta-analysis of functional imaging studies of episodic encoding and retrieval tests the prediction that these deficits are most consistently associated with dysfunction in the prefrontal cortex. Activation likelihood estimation (ALE) was used to perform a quantitative meta-analysis of functional imaging studies that contrasted patients with schizophrenia and healthy volunteers during episodic encoding and retrieval. From a pool of 36 potential studies, 18 whole-brain studies in standard space that included a healthy comparison sample and low-level baseline contrast were selected. As predicted, patients showed less prefrontal activation than comparison subjects in the frontal POLE, dorsolateral and ventrolateral prefrontal cortex during encoding, and the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during retrieval. The ventrolateral prefrontal cortex encoding deficits were not present in studies that provided patients with encoding strategies, but dorsolateral prefrontal cortex deficits remained and were not secondary to group performance differences. The only medial temporal lobe finding was relatively greater patient versus comparison subject activation in the parahippocampal gyrus during encoding and retrieval. The finding of prominent prefrontal dysfunction suggests that cognitive control deficits strongly contribute to episodic memory impairment in schizophrenia. Memory rehabilitation approaches developed for patients with frontal lobe lesions and pharmacotherapy approaches designed to improve prefrontal cortex function may therefore hold special promise for remediating memory deficits in patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 41 | Schizophr. Res. 2009 Apr 109: 148-58 |
| PMID | 19185466 |
| Title | Differential relationship of frontal pole and whole brain volumetric measures with age in neuroleptic-naïve schizophrenia and healthy subjects. |
| Abstract | Brodmann's area (BA) 10, which occupies the frontal POLE (FP) of the human brain, has been proven to play a central role in the executive control of cognitive operations. Previous in vivo morphometric studies of the FP have been limited by the lack of an accepted boundary of its posterior limit. We studied the FP gray matter volume in 23 healthy subjects who were age-, sex-, and education-matched to 23 neuroleptic-naïve recent-onset schizophrenia subjects in the age span 20-40 years, using a cytoarchitectonically and functionally valid landmark-based definition of its posterior boundary that we proposed recently (John, J.P., Yashavantha, B.S., Gado, M., Veena, R., Jain, S., Ravishankar, S., Csernansky, J.G., 2007. A proposal for MRI-based parcellation of the frontal POLE. Brain Struct. Funct. 212, 245-253. 2007). Additionally, we examined the relationship between FP volume and age in both healthy and schizophrenia subjects to examine evidence for a possible differential relationship between these variables across the samples. A major finding of the study was the absence of a group-level difference in frontal POLE gray volumes between the healthy and schizophrenia participants. However, a more complex finding emerged in relation to age effects. The healthy participants showed an inverse relationship of FP gray volume with age, even after taking total brain volume differences into account. But this age effect was completely absent in the schizophrenia group. Moreover, all the volumetric measures in schizophrenia subjects showed substantially higher range, variance, skewness and kurtosis when compared to those of healthy subjects. These findings have implications in understanding the possible role of FP in the pathophysiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 42 | Schizophr. Res. 2009 Oct 114: 154-60 |
| PMID | 19632816 |
| Title | Functional and structural brain correlates of theory of mind and empathy deficits in schizophrenia. |
| Abstract | Patients affected by schizophrenia show deficits in social cognition, with abnormal performance on tasks targeting theory of mind (ToM) and empathy (Emp). Brain imaging studies suggested that ToM and Emp depend on the activation of brain networks mainly localized at the superior temporal lobe and temporo-parietal junction. Participants included 24 schizophrenia patients and 20 control subjects. We used brain blood oxygen level dependent fMRI to study the neural responses to tasks targeting ToM and Emp. We then studied voxel-based morphometry of grey matter in areas where diagnosis influenced functional activation to both tasks. Outcomes were analyzed in the context of the general linear model, with global grey matter volume as nuisance covariate for structural MRI. Patients showed worse performance on both tasks. We found significant effects of diagnosis on neural responses to the tasks in a wide cluster in right posterior superior temporal lobe (encompassing BA 22-42), in smaller clusters in left temporo-parietal junction and temporal POLE (BA 38 and 39), and in a white matter region adjacent to medial prefrontal cortex (BA 10). A pattern of double dissociation of the effects of diagnosis and task on neural responses emerged. Among these areas, grey matter volume was found to be reduced in right superior temporal lobe regions of patients. Functional and structural abnormalities were observed in areas affected by the schizophrenic process early in the illness course, and known to be crucial for social cognition, suggesting a biological basis for social cognition deficits in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 43 | Psychiatry Res 2009 Sep 173: 163-9 |
| PMID | 19616415 |
| Title | Gray matter abnormalities in subjects at ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls. |
| Abstract | Neuroimaging studies have revealed gray matter abnormalities in schizophrenia in various regions of the brain. It is, however, still unclear whether such abnormalities are already present in individuals at ultra-high risk (UHR) for transition into psychosis. We investigated this issue using voxel-based morphometry of structural magnetic resonance images (MRI) and compared UHR patients with first-episode patients with schizophrenia and healthy controls. Gray matter volume maps from high-resolution MR T1-weighted whole brain images were analyzed in a cross-sectional study in 30 UHR patients, 23 first-episode schizophrenic patients and 29 controls. UHR patients showed significantly lower gray matter volume in the cingulate gyrus bilaterally, in the right inferior frontal and right superior temporal gyrus, as well as in the left and right hippocampus in comparison to healthy subjects. First-episode patients with schizophrenia showed smaller gray matter volume in the cingulate cortex bilaterally, in the left orbitofrontal gyrus, in the right inferior frontal and superior temporal gyrus, in the right temporal POLE, in the left and right hippocampus, in the left parahippocampus, left amygdala, and in the left fusiform gyrus compared to the UHR patients. This study provides further evidence that gray matter brain volume, especially in the anterior cingulate cortex, is already reduced in the prodromal state of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 44 | Int. J. Neuropsychopharmacol. 2009 Mar 12: 227-41 |
| PMID | 18687163 |
| Title | Towards an animal model of an antipsychotic drug-resistant cognitive impairment in schizophrenia: scopolamine induces abnormally persistent latent inhibition, which can be reversed by cognitive enhancers but not by antipsychotic drugs. |
| Abstract | schizophrenia symptoms segregate into positive, negative and cognitive, which exhibit differential sensitivity to drugs. Recent efforts to identify treatments targeting cognitive impairments in schizophrenia have directed attention to the cholinergic system for its well documented role in cognition. Relatedly, muscarinic antagonists (e.g. scopolamine) produce an 'antimuscarinic syndrome', characterized by psychosis and cognitive impairments. Latent inhibition (LI) is the poorer conditioning to a stimulus resulting from its non-reinforced pre-exposure. LI indexes the ability to ignore irrelevant stimuli and aberrations of this capacity produced by pro-psychotic agents (e.g. amphetamine, MK-801) are used extensively to model attentional impairments in schizophrenia. We recently showed that LI was disrupted by scopolamine at low doses, and this was reversed by typical and atypical antipsychotic drugs (APDs) and the acetylcholinesterase inhibitor physostigmine. Here, at a higher dose (1.5 mg/kg), scopolamine produced an opposite POLE of attentional impairment, namely, attentional perseveration, whereby scopolamine-treated rats persisted in expressing LI under strong conditioning that prevented LI expression in controls. Scopolamine-induced persistent LI was reversed by cholinergic and glycinergic cognitive enhancers (physostigmine and glycine) but was resistant to both typical and atypical APDs (haloperidol and clozapine). The latter sets scopolamine-induced persistent LI apart from scopolamine- and amphetamine-induced disrupted LI, which are reversed by both typical and atypical APDs, as well as from other cases of abnormally persistent LI including MK-801-induced persistent LI, which is reversed by atypical APDs. Thus, scopolamine-induced persistent LI may provide a pharmacological LI model for screening cognitive enhancers that are efficient for the treatment of APD-resistant cognitive impairments in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 45 | Schizophr. Res. 2010 Feb 116: 252-8 |
| PMID | 20051318 |
| Title | Differential processing of metacognitive evaluation and the neural circuitry of the self and others in schizophrenia: a pilot study. |
| Abstract | Impaired awareness of the self and others (i.e., metacognitive evaluations) are seen in schizophrenia. We compared patterns of activation in schizophrenia (SZ) and nonclinical subjects during a functional magnetic resonance imaging (fMRI) task of metacognitive evaluations that has been demonstrated to engage the neural circuitry of the self in healthy subjects. Eleven SZ subjects (7 males, mean age 26.6+/-8) and 10 healthy control subjects (4 males, mean age 29.6+/-8.4) were enrolled. Participants completed two runs of a metacognitive evaluation task (self vs. other vs. word meaning). fMRI data was obtained using a full body Bruker MedSped 4.0Tesla system. Group contrasts were performed using an uncorrected p<0.005 with a 50voxel extent threshold. We observed a significant hypoactivation in the left superior temporal sulcus (STS) during metacognitive evaluations of others (OE) vs. semantic positivity evaluations (SPE) and a trend toward significant hypoactivation in the OE vs. self evaluations (SE) in the SZ group. Significant hypoactivation was also seen in the right inferior temporal gyrus (ITG) in the OE vs. SE contrasts in the SZ group. A trendworthy hypoactivation was seen in the SZ group in the right middle frontal gyrus and POLE of the left STS during OE vs. SPE and SE contrasts respectively. These results extend previous findings of impaired metacognitive evaluative processes in schizophrenia to aberrations of the neural circuitry implicated in self/other awareness among SZ patients. Greater understanding of the neural basis of deficits of self/other awareness in early schizophrenia may contribute to improvements in the identification and treatment of individuals at risk for the illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 46 | Brain Struct Funct 2010 Jun 214: 495-517 |
| PMID | 20512377 |
| Title | The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. |
| Abstract | The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal POLE as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 47 | Psychiatry Res 2010 Dec 184: 189-91 |
| PMID | 21055908 |
| Title | Temporal pole morphology in first-episode schizophrenia patients: clinical correlations. |
| Abstract | Studies of the temporal POLE (TP) in schizophrenia patients are not consistent. The aim of this study was to investigate morphometric anomalies of the TP in first-episode schizophrenia patients. Patients did not significantly differ from controls in the TP morphometric variables evaluated. Clinical variables were not significantly related to the TP. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 48 | Psychiatry Res 2010 May 182: 183-6 |
| PMID | 20418073 |
| Title | Gray matter volume differences specific to formal thought disorder in schizophrenia. |
| Abstract | Formal thought disorder (FTD) is one of the main symptoms of schizophrenia. To date there are no whole brain volumetric studies investigating gray matter (GM) differences specifically associated with FTD. Here, we studied 20 right-handed schizophrenia patients that differed in the severity of formal thought disorder and 20 matched healthy controls, using voxel-based morphometry (VBM). The severity of FTD was measured with the Scale for the Assessment of Thought, Language, and Communication. The severity was negatively correlated with the GM volume of the left superior temporal sulcus, the left temporal POLE, the right middle orbital gyrus and the right cuneus/lingual gyrus. Structural abnormalities specific for FTD were found to be unrelated to GM differences associated with schizophrenia in general. The specific GM abnormalities within the left temporal lobe may help to explain language disturbances included in FTD. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 49 | Neurocase 2010 Jun 16: 267-72 |
| PMID | 20104391 |
| Title | A case of post-traumatic complex auditory hallucinosis treated with rTMS. |
| Abstract | Previous studies of auditory hallucinations in schizophrenia found that the hallucinations were reduced by the application of transcranial magnetic stimulation (rTMS). Here we describe a case of traumatic brain injury associated with continuous music hallucinations. An MRI scan showed a structural lesion of the right temporal POLE and a PET scan indicated a hyperactive area of the posterior right temporal lobe. We hypothesized that rTMS applied to the right temporal area would reduce this activity and the corresponding hallucinations. The patient's music hallucinations were significantly reduced by rTMS treatment. A PET scan following treatment also indicated that rTMS treatment reduced brain activity in the right temporal lobe. This case provides initial evidence that rTMS may be a successful treatment of syndromes associated with hyperactive brain areas. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 50 | Psychiatry Res 2010 Feb 181: 121-9 |
| PMID | 20080395 |
| Title | Multi-level comparison of empathy in schizophrenia: an fMRI study of a cartoon task. |
| Abstract | Empathy deficits might play a role in social dysfunction in schizophrenia. However, few studies have investigated the neuroanatomical underpinnings of the subcomponents of empathy in schizophrenia. This study investigated the hemodynamic responses to three subcomponents of empathy in patients with schizophrenia (N=15) and healthy volunteers (N=18), performing an empathy cartoon task during functional magnetic resonance imaging. The experiment used a block design with four conditions: cognitive, emotional, and inhibitory empathy, and physical causality control. Data were analyzed by comparing the blood-oxygen-level-dependent (BOLD) signal activation between the two groups. The cognitive empathy condition activated the right temporal POLE to a lesser extent in the patient group than in comparison subjects. In the emotional and inhibitory conditions, the patients showed greater activation in the left insula and in the right middle/inferior frontal cortex, respectively. These findings add to our understanding of the impaired empathy in patients with schizophrenia by identifying a multi-level cortical dysfunction that underlies a deficit in each subcomponent of empathy and highlighting the importance of the fronto-temporal cortical network in ability to empathize. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 51 | Mol. Psychiatry 2010 Jun 15: 615-28 |
| PMID | 19048012 |
| Title | A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia. |
| Abstract | Markers at the pericentriolar material 1 gene (PCM1) have shown genetic association with schizophrenia in both a University College London (UCL) and a USA-based case-control sample. In this paper we report a statistically significant replication of the PCM1 association in a large Scottish case-control sample from Aberdeen. Resequencing of the genomic DNA from research volunteers who had inherited haplotypes associated with schizophrenia showed a threonine to isoleucine missense mutation in exon 24 which was likely to change the structure and function of PCM1 (rs370429). This mutation was found only as a heterozygote in 98 schizophrenic research subjects and controls out of 2246 case and control research subjects. Among the 98 carriers of rs370429, 67 were affected with schizophrenia. The same alleles and haplotypes were associated with schizophrenia in both the London and Aberdeen samples. Another potential aetiological base pair change in PCM1 was rs445422, which altered a splice site signal. A further mutation, rs208747, was shown by electrophoretic mobility shift assays to create or destroy a promoter transcription factor site. Five further non-synonymous changes in exons were also found. Genotyping of the new variants discovered in the UCL case-control sample strengthened the evidence for allelic and haplotypic association (P=0.02-0.0002). Given the number and identity of the haplotypes associated with schizophrenia, further aetiological base pair changes must exist within and around the PCM1 gene. PCM1 protein has been shown to interact directly with the disrupted-in-schizophrenia 1 (DISC1) protein, Bardet-Biedl syndrome 4, and Huntingtin-associated protein 1, and is important in neuronal cell growth. In a separate study we found that clozapine but not haloperidol downregulated PCM1 expression in the mouse brain. We hypothesize that mutant PCM1 may be responsible for causing a subtype of schizophrenia through abnormal cell division and abnormal regeneration in dividing cells in the central nervous system. This is supported by our previous finding of orbitofrontal volumetric deficits in PCM1-associated schizophrenia patients as opposed to temporal POLE deficits in non-PCM1-associated schizophrenia patients. Caution needs to be exercised in interpreting the actual biological effects of the mutations we have found without further cell biology. However, the DNA changes we have found deserve widespread genotyping in multiple case-control populations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 52 | J. Neurosci. 2010 Nov 30: 15915-26 |
| PMID | 21106830 |
| Title | Aberrant frontal and temporal complex network structure in schizophrenia: a graph theoretical analysis. |
| Abstract | Brain regions are not independent. They are interconnected by white matter tracts, together forming one integrative complex network. The topology of this network is crucial for efficient information integration between brain regions. Here, we demonstrate that schizophrenia involves an aberrant topology of the structural infrastructure of the brain network. Using graph theoretical analysis, complex structural brain networks of 40 schizophrenia patients and 40 human healthy controls were examined. Diffusion tensor imaging was used to reconstruct the white matter connections of the brain network, with the strength of the connections defined as the level of myelination of the tracts as measured through means of magnetization transfer ratio magnetic resonance imaging. Patients displayed a preserved overall small-world network organization, but focusing on specific brain regions and their capacity to communicate with other regions of the brain revealed significantly longer node-specific path lengths (higher L) of frontal and temporal regions, especially of bilateral inferior/superior frontal cortex and temporal POLE regions. These findings suggest that schizophrenia impacts global network connectivity of frontal and temporal brain regions. Furthermore, frontal hubs of patients showed a significant reduction of betweenness centrality, suggesting a less central hub role of these regions in the overall network structure. Together, our findings suggest that schizophrenia patients have a less strongly globally integrated structural brain network with a reduced central role for key frontal hubs, resulting in a limited structural capacity to integrate information across brain regions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 53 | Encephale 2010 Sep 36: 277-84 |
| PMID | 20850598 |
| Title | [Neuro-anatomic activations of prepotent responses in schizophrenia in Hayling's task]. |
| Abstract | In schizophrenia, alteration in the prefrontal cortex can induce some deficiencies of the executive functions, and among them errors in inhibition of prepotent responses. This type of inhibitory processes was called "restraint function" by Hasher et al. It implies a conscious and voluntary inhibition which demands attentional resources. Among the tasks exploring this function, the Hayling completion sentence task (Burgess and Shallice) appears to be the most specific. Moreover, healthy subjects performing this task in functional magnetic resonance imaging (fMRI) show activation of the prefrontal cortex. In this study, we investigated inhibitory processes in schizophrenic patients using two versions of the Hayling completion sentence task, a behavioural version and an fMRI version in order to assess both performance levels and brain correlates of inhibitory processes. Forty-eight schizophrenic participants according to DSM-IV, (mean age: 32.8, S.D. 7.7), stabilized for at least one month, receiving antipsychotic medication and with IQ higher than 70 (mean: 96.86, S.D. 20.67) and education level (mean: 11.15, S.D. 3.26) participated in the behavioural study. They were matched on age (mean: 33.8, S.D. 7.6) and education level (mean: 12.28, S.D. 2.87) with thirty-two healthy controls. Nineteen of schizophrenic participants (mean age: 33, S.D. 6.9 and IQ: 99, S.D. 10.74) were assessed by an fMRI adaptation of the Hayling task, matched with 12 controls (mean: 33.9, S.D. 7.3). All the participants had to perform the Hayling task and a speed accuracy task. The Hayling task consists in sentences for which the last word is missing. In the initiation condition, the participants had to complete the sentence with the appropriate word, whereas in inhibition condition the participants had to complete the sentence with inappropriate and unrelated words. Compared to controls, schizophrenics showed an increased number of errors in the inhibition of prepotent responses associated with increased reaction times, even when considering information processing speed. fMRI results showed fairly similar frontal activations in both groups. Nevertheless, schizophrenic patients presented principally large activations in dorsolateral and ventrolateral frontal cortex, the superior frontal sulcus, the frontal POLE and the premotor cortex, and stronger activations (bilateral) in the posterior parietal cortex. Control subjects demonstrated a network of deactivated brain regions whereas the schizophrenics did not. Our results are in favour of poorer efficacy of restraint function, sometimes comprising impairment of inhibitory processes inducing errors in schizophrenics. This deficiency might be considered as insufficiency in attentional resources and/or in working memory. Hence patients cannot simultaneously restrain prepotent response and find appropriate controlled strategy for correct completion of the task. Moreover, bilateral patterns of parietal hyperactivation and absence of patterns of deactivation seem also in favour of an attentional hypothesis. The Hayling task might be interesting for assessment of inhibitory processes in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 54 | Schizophr. Res. 2010 Oct 123: 15-21 |
| PMID | 20705433 |
| Title | Regional prefrontal cortex gray matter volumes in youth at familial risk for schizophrenia from the Harvard Adolescent High Risk Study. |
| Abstract | Regional prefrontal cortex gray matter reductions have been identified in schizophrenia, likely reflecting a combination of genetic vulnerability and disease effects. Few morphometric studies to date have examined regional prefrontal abnormalities in non-psychotic biological relatives who have not passed through the age range of peak risk for onset of psychosis. We conducted a region-of-interest morphometric study of prefrontal subregions in adolescent and young adult relatives of schizophrenia patients. Twenty-seven familial high-risk (FHR) first-degree relatives of schizophrenia patients and forty-eight control subjects without a family history of psychosis (ages 13-28) underwent high-resolution magnetic resonance imaging at 1.5Tesla. The prefrontal cortex was parcellated into polar, dorsolateral, ventrolateral, ventromedial and orbital subregions. The Chapman scales measured subpsychotic symptoms. General linear models examined associations of prefrontal subregion volumes with familial risk and subpsychotic symptoms. FHR subjects had significantly reduced bilateral ventromedial prefrontal and frontal POLE gray matter volumes compared with controls. Ventromedial volume was significantly negatively correlated with magical ideation and anhedonia scores in FHR subjects. Selective, regional prefrontal gray matter reductions may differentially mark genetic vulnerability and early symptom processes among non-psychotic young adults at familial risk for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 55 | Brain 2010 Oct 133: 3113-22 |
| PMID | 20639549 |
| Title | Handedness, heritability, neurocognition and brain asymmetry in schizophrenia. |
| Abstract | Higher rates of non-right-handedness (i.e. left- and mixed-handedness) have been reported in schizophrenia and have been a centrepiece for theories of anomalous lateralization in this disorder. We investigated whether non-right-handedness is (i) more prevalent in patients as compared with unaffected siblings and healthy unrelated control participants; (ii) familial; (iii) associated with disproportionately poorer neurocognition; and (iv) associated with grey matter volume asymmetries. We examined 1445 participants (375 patients with schizophrenia, 502 unaffected siblings and 568 unrelated controls) using the Edinburgh Handedness Inventory, a battery of neuropsychological tasks and structural magnetic resonance imaging data. Patients displayed a leftward shift in Edinburgh Handedness Inventory laterality quotient scores as compared with both their unaffected siblings and unrelated controls, but this finding disappeared when sex was added to the model. Moreover, there was no evidence of increased familial risk for non-right-handedness. Non-right-handedness was not associated with disproportionate neurocognitive disadvantage or with grey matter volume asymmetries in the frontal POLE, lateral occipital POLE or temporal POLE. Non-right-handedness was associated with a significant reduction in left asymmetry in the superior temporal gyrus in both patients and controls. Our data neither provide strong support for 'atypical' handedness as a schizophrenia risk-associated heritable phenotype nor that it is associated with poorer neurocognition or anomalous cerebral asymmetries. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 56 | Neuroinformatics 2010 Dec 8: 213-29 |
| PMID | 20607449 |
| Title | Identification of imaging biomarkers in schizophrenia: a coefficient-constrained independent component analysis of the mind multi-site schizophrenia study. |
| Abstract | A number of recent studies have combined multiple experimental paradigms and modalities to find relevant biological markers for schizophrenia. In this study, we extracted fMRI features maps from the analysis of three experimental paradigms (auditory oddball, Sternberg item recognition, sensorimotor) for a large number (n=154) of patients with schizophrenia and matched healthy controls. We used the general linear model (GLM) and independent component analysis (ICA) to extract feature maps (i.e. ICA component maps and GLM contrast maps), which were then subjected to a coefficient-constrained independent component analysis (CCICA) to identify potential neurobiological markers. A total of 29 different feature maps were extracted for each subject. Our results show a number of optimal feature combinations that reflect a set of brain regions that significantly discriminate between patients and controls in the spatial heterogeneity and amplitude of their feature signals. Spatial heterogeneity was seen in regions such as the superior/middle temporal and frontal gyri, bilateral parietal lobules, and regions of the thalamus. Most strikingly, an ICA feature representing a bilateral frontal POLE network was consistently seen in the ten highest feature results when ranked on differences found in the amplitude of their feature signals. The implication of this frontal POLE network and the spatial variability which spans regions comprising of bilateral frontal/temporal lobes and parietal lobules suggests that they might play a significant role in the pathophysiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 57 | Eur Arch Psychiatry Clin Neurosci 2010 Sep 260: 455-64 |
| PMID | 20112027 |
| Title | Reduced prefrontal gyrification in obsessive-compulsive disorder. |
| Abstract | Structural magnetic resonance imaging (MRI) studies reveal evidence for brain abnormalities in obsessive-compulsive disorder (OCD), for instance, reduction of gray matter volume in the prefrontal cortex. Disturbances of gyrification in the prefrontal cortex have been described several times in schizophrenia pointing to a neurodevelopmental etiology, while gyrification has not been studied so far in OCD patients. In 26 OCD patients and 38 healthy control subjects MR-imaging was performed. Prefrontal cortical folding (gyrification) was measured bilaterally by an automated version of the automated-gyrification index (A-GI), a ratio reflecting the extent of folding, from the slice containing the inner genu of the corpus callosum up to the frontal POLE. Analysis of covariance (ANCOVA, independent factor diagnosis, covariates age, duration of education) demonstrated that compared with control subjects, patients with OCD displayed a significantly reduced A-GI in the left hemisphere (p = 0.021) and a trend for a decreased A-GI in the right hemisphere (p = 0.076). Significant correlations between prefrontal lobe volume and A-GI were only observed in controls, but not in OCD patients. In conclusion, prefrontal hypogyrification in OCD patients may be a structural correlate of the impairment in executive function of this patient group and may point to a neurodevelopmental origin of this disease. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 58 | Brain Topogr 2010 Mar 23: 82-104 |
| PMID | 19943100 |
| Title | Somatosensory system deficits in schizophrenia revealed by MEG during a median-nerve oddball task. |
| Abstract | Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal-parietal-temporal "attention network", containing dorsal- and ventral-lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal POLE, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal-parietal-temporal networks in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 59 | Mol. Psychiatry 2010 Jun 15: 615-28 |
| PMID | 19048012 |
| Title | A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia. |
| Abstract | Markers at the pericentriolar material 1 gene (PCM1) have shown genetic association with schizophrenia in both a University College London (UCL) and a USA-based case-control sample. In this paper we report a statistically significant replication of the PCM1 association in a large Scottish case-control sample from Aberdeen. Resequencing of the genomic DNA from research volunteers who had inherited haplotypes associated with schizophrenia showed a threonine to isoleucine missense mutation in exon 24 which was likely to change the structure and function of PCM1 (rs370429). This mutation was found only as a heterozygote in 98 schizophrenic research subjects and controls out of 2246 case and control research subjects. Among the 98 carriers of rs370429, 67 were affected with schizophrenia. The same alleles and haplotypes were associated with schizophrenia in both the London and Aberdeen samples. Another potential aetiological base pair change in PCM1 was rs445422, which altered a splice site signal. A further mutation, rs208747, was shown by electrophoretic mobility shift assays to create or destroy a promoter transcription factor site. Five further non-synonymous changes in exons were also found. Genotyping of the new variants discovered in the UCL case-control sample strengthened the evidence for allelic and haplotypic association (P=0.02-0.0002). Given the number and identity of the haplotypes associated with schizophrenia, further aetiological base pair changes must exist within and around the PCM1 gene. PCM1 protein has been shown to interact directly with the disrupted-in-schizophrenia 1 (DISC1) protein, Bardet-Biedl syndrome 4, and Huntingtin-associated protein 1, and is important in neuronal cell growth. In a separate study we found that clozapine but not haloperidol downregulated PCM1 expression in the mouse brain. We hypothesize that mutant PCM1 may be responsible for causing a subtype of schizophrenia through abnormal cell division and abnormal regeneration in dividing cells in the central nervous system. This is supported by our previous finding of orbitofrontal volumetric deficits in PCM1-associated schizophrenia patients as opposed to temporal POLE deficits in non-PCM1-associated schizophrenia patients. Caution needs to be exercised in interpreting the actual biological effects of the mutations we have found without further cell biology. However, the DNA changes we have found deserve widespread genotyping in multiple case-control populations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 60 | Encephale 2010 Sep 36: 277-84 |
| PMID | 20850598 |
| Title | [Neuro-anatomic activations of prepotent responses in schizophrenia in Hayling's task]. |
| Abstract | In schizophrenia, alteration in the prefrontal cortex can induce some deficiencies of the executive functions, and among them errors in inhibition of prepotent responses. This type of inhibitory processes was called "restraint function" by Hasher et al. It implies a conscious and voluntary inhibition which demands attentional resources. Among the tasks exploring this function, the Hayling completion sentence task (Burgess and Shallice) appears to be the most specific. Moreover, healthy subjects performing this task in functional magnetic resonance imaging (fMRI) show activation of the prefrontal cortex. In this study, we investigated inhibitory processes in schizophrenic patients using two versions of the Hayling completion sentence task, a behavioural version and an fMRI version in order to assess both performance levels and brain correlates of inhibitory processes. Forty-eight schizophrenic participants according to DSM-IV, (mean age: 32.8, S.D. 7.7), stabilized for at least one month, receiving antipsychotic medication and with IQ higher than 70 (mean: 96.86, S.D. 20.67) and education level (mean: 11.15, S.D. 3.26) participated in the behavioural study. They were matched on age (mean: 33.8, S.D. 7.6) and education level (mean: 12.28, S.D. 2.87) with thirty-two healthy controls. Nineteen of schizophrenic participants (mean age: 33, S.D. 6.9 and IQ: 99, S.D. 10.74) were assessed by an fMRI adaptation of the Hayling task, matched with 12 controls (mean: 33.9, S.D. 7.3). All the participants had to perform the Hayling task and a speed accuracy task. The Hayling task consists in sentences for which the last word is missing. In the initiation condition, the participants had to complete the sentence with the appropriate word, whereas in inhibition condition the participants had to complete the sentence with inappropriate and unrelated words. Compared to controls, schizophrenics showed an increased number of errors in the inhibition of prepotent responses associated with increased reaction times, even when considering information processing speed. fMRI results showed fairly similar frontal activations in both groups. Nevertheless, schizophrenic patients presented principally large activations in dorsolateral and ventrolateral frontal cortex, the superior frontal sulcus, the frontal POLE and the premotor cortex, and stronger activations (bilateral) in the posterior parietal cortex. Control subjects demonstrated a network of deactivated brain regions whereas the schizophrenics did not. Our results are in favour of poorer efficacy of restraint function, sometimes comprising impairment of inhibitory processes inducing errors in schizophrenics. This deficiency might be considered as insufficiency in attentional resources and/or in working memory. Hence patients cannot simultaneously restrain prepotent response and find appropriate controlled strategy for correct completion of the task. Moreover, bilateral patterns of parietal hyperactivation and absence of patterns of deactivation seem also in favour of an attentional hypothesis. The Hayling task might be interesting for assessment of inhibitory processes in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 61 | Encephale 2010 Sep 36: 277-84 |
| PMID | 20850598 |
| Title | [Neuro-anatomic activations of prepotent responses in schizophrenia in Hayling's task]. |
| Abstract | In schizophrenia, alteration in the prefrontal cortex can induce some deficiencies of the executive functions, and among them errors in inhibition of prepotent responses. This type of inhibitory processes was called "restraint function" by Hasher et al. It implies a conscious and voluntary inhibition which demands attentional resources. Among the tasks exploring this function, the Hayling completion sentence task (Burgess and Shallice) appears to be the most specific. Moreover, healthy subjects performing this task in functional magnetic resonance imaging (fMRI) show activation of the prefrontal cortex. In this study, we investigated inhibitory processes in schizophrenic patients using two versions of the Hayling completion sentence task, a behavioural version and an fMRI version in order to assess both performance levels and brain correlates of inhibitory processes. Forty-eight schizophrenic participants according to DSM-IV, (mean age: 32.8, S.D. 7.7), stabilized for at least one month, receiving antipsychotic medication and with IQ higher than 70 (mean: 96.86, S.D. 20.67) and education level (mean: 11.15, S.D. 3.26) participated in the behavioural study. They were matched on age (mean: 33.8, S.D. 7.6) and education level (mean: 12.28, S.D. 2.87) with thirty-two healthy controls. Nineteen of schizophrenic participants (mean age: 33, S.D. 6.9 and IQ: 99, S.D. 10.74) were assessed by an fMRI adaptation of the Hayling task, matched with 12 controls (mean: 33.9, S.D. 7.3). All the participants had to perform the Hayling task and a speed accuracy task. The Hayling task consists in sentences for which the last word is missing. In the initiation condition, the participants had to complete the sentence with the appropriate word, whereas in inhibition condition the participants had to complete the sentence with inappropriate and unrelated words. Compared to controls, schizophrenics showed an increased number of errors in the inhibition of prepotent responses associated with increased reaction times, even when considering information processing speed. fMRI results showed fairly similar frontal activations in both groups. Nevertheless, schizophrenic patients presented principally large activations in dorsolateral and ventrolateral frontal cortex, the superior frontal sulcus, the frontal POLE and the premotor cortex, and stronger activations (bilateral) in the posterior parietal cortex. Control subjects demonstrated a network of deactivated brain regions whereas the schizophrenics did not. Our results are in favour of poorer efficacy of restraint function, sometimes comprising impairment of inhibitory processes inducing errors in schizophrenics. This deficiency might be considered as insufficiency in attentional resources and/or in working memory. Hence patients cannot simultaneously restrain prepotent response and find appropriate controlled strategy for correct completion of the task. Moreover, bilateral patterns of parietal hyperactivation and absence of patterns of deactivation seem also in favour of an attentional hypothesis. The Hayling task might be interesting for assessment of inhibitory processes in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 62 | J. Nerv. Ment. Dis. 2011 Jan 199: 25-9 |
| PMID | 21206243 |
| Title | A functional magnetic resonance imaging paradigm of expressed emotion in schizophrenia. |
| Abstract | Chronic exposure to adverse interpersonal environment in schizophrenia is associated with vulnerability to relapse. The construct of expressed emotion (EE) measures the quality of interpersonal environment, of which criticism is a main component. To use functional magnetic resonance imaging and to investigate the neural basis of vulnerability of schizophrenic patients to EE, the effects of critical comments on brain mechanisms in 11 patients with schizophrenia were examined, comparing evoked responses to familiar (key relative) and unfamiliar (matched stranger) critical and neutral commentary. High EE stimuli evoked enhanced activation of brain regions concerned with the processing of aversive social information. Activations in the right BA44, rostral anterior cingulate, middle superior frontal gyrus, bilateral middle frontal gyrus, left temporal POLE, left inferior frontal gyrus, and left insula were significantly modulated to familiar criticism. Such a pattern of neural response may represent a putative neural network responsible for mediating High EE in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 63 | J. Psychopharmacol. (Oxford) 2011 Jun 25: 722-33 |
| PMID | 20360158 |
| Title | Emotion processing in schizophrenia: fMRI study of patients treated with risperidone long-acting injections or conventional depot medication. |
| Abstract | We employed two event-related functional magnetic resonance imaging tasks using the pictures of mild and intense facial emotions of fear or happiness. The sample comprised 16 chronic schizophrenia patients treated with risperidone long-acting injections (RLAI), 16 patients treated with conventional antipsychotic depots (CONV) and 16 healthy controls (HC). The HC and RLAI groups demonstrated greater activation in the left amygdala in response to intensively fearful faces, and in right cerebellum to intensively happy faces compared with CONV patients. The CONV group demonstrated under-activation in the right temporal POLE in response to intensively happy faces (compared with HC) and over-activation in ventro-medial prefrontal cortex (VMPFC) in response to both intensively happy and fearful expressions, compared with HC and RLAI groups. Our results suggest that networks implicated in the allocation of attentional resources (VMPFC) and emotion processing (amygdala, cerebellum) are differentially affected in patients on CONV versus RLAI. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 64 | J. Nerv. Ment. Dis. 2011 Jan 199: 25-9 |
| PMID | 21206243 |
| Title | A functional magnetic resonance imaging paradigm of expressed emotion in schizophrenia. |
| Abstract | Chronic exposure to adverse interpersonal environment in schizophrenia is associated with vulnerability to relapse. The construct of expressed emotion (EE) measures the quality of interpersonal environment, of which criticism is a main component. To use functional magnetic resonance imaging and to investigate the neural basis of vulnerability of schizophrenic patients to EE, the effects of critical comments on brain mechanisms in 11 patients with schizophrenia were examined, comparing evoked responses to familiar (key relative) and unfamiliar (matched stranger) critical and neutral commentary. High EE stimuli evoked enhanced activation of brain regions concerned with the processing of aversive social information. Activations in the right BA44, rostral anterior cingulate, middle superior frontal gyrus, bilateral middle frontal gyrus, left temporal POLE, left inferior frontal gyrus, and left insula were significantly modulated to familiar criticism. Such a pattern of neural response may represent a putative neural network responsible for mediating High EE in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 65 | J Int Neuropsychol Soc 2011 Nov 17: 1080-93 |
| PMID | 22013998 |
| Title | Brain cortical thickness and surface area correlates of neurocognitive performance in patients with schizophrenia, bipolar disorder, and healthy adults. |
| Abstract | Relationships between cortical brain structure and neurocognitive functioning have been reported in schizophrenia, but findings are inconclusive, and only a few studies in bipolar disorder have addressed this issue. This is the first study to directly compare relationships between cortical thickness and surface area with neurocognitive functioning in patients with schizophrenia (n = 117) and bipolar disorder (n = 121) and healthy controls (n = 192). MRI scans were obtained, and regional cortical thickness and surface area measurements were analyzed for relationships with test scores from 6 neurocognitive domains. In the combined sample, cortical thickness in the right rostral anterior cingulate was inversely related to working memory, and cortical surface area in four frontal and temporal regions were positively related to neurocognitive functioning. A positive relationship between left transverse temporal thickness and processing speed was specific to schizophrenia. A negative relationship between right temporal POLE thickness and working memory was specific to bipolar disorder. In conclusion, significant cortical structure/function relationships were found in a large sample of healthy controls and patients with schizophrenia or bipolar disorder. The differences that were found between schizophrenia and bipolar may indicate differential relationship patterns in the two disorders, which may be of relevance for understanding the underlying pathophysiology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 66 | Arch. Gen. Psychiatry 2011 Sep 68: 871-80 |
| PMID | 21893656 |
| Title | Changes in cortical thickness during the course of illness in schizophrenia. |
| Abstract | Whether cortical thickness changes in schizophrenia over time are more pronounced relative to the changes that can be attributed to normal aging has not been studied. To compare patients with schizophrenia and healthy control participants on cortical thickness change. A 5-year longitudinal study comparing schizophrenic patients and healthy controls using 2 magnetic resonance images of the brain. Patients were recruited from the Department of Psychiatry at the University Medical Centre Utrecht and from other psychiatric hospitals in the Netherlands. Healthy controls were recruited via advertisement in newspapers and notice boards. Ninety-six schizophrenic patients and 113 healthy controls aged 16 to 56 years. Cortical thickness and change in cortical thickness on a vertex-by-vertex basis across the cortical mantle, measures of functional and symptomatic outcome, and cumulative intake of antipsychotics during the scan interval. At baseline, the schizophrenic patients had thinner left orbitofrontal and right parahippocampal and superior temporal cortices and a thicker superior parietal lobule and occipital POLE compared with the controls. Mean cortical thickness did not differ between the groups. Over time, excessive cortical thinning was found in widespread areas on the cortical mantle, most pronounced bilaterally in the temporal cortex and in the left frontal area. Poor outcome in patients was associated with more pronounced cortical thinning. Higher cumulative intake of typical antipsychotics during the scan interval was associated with more pronounced cortical thinning, whereas higher cumulative intake of atypical antipsychotic medication was associated with less pronounced cortical thinning. In schizophrenia, the cortex shows excessive thinning over time in widespread areas of the brain, most pronounced in the frontal and temporal areas, and progresses across the entire course of the illness. The excessive thinning of the cortex appears related to outcome and medication intake. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 67 | Acta Psychiatr Scand 2011 Jan 123: 43-54 |
| PMID | 20712827 |
| Title | Disrupted theory of mind network processing in response to idea of reference evocation in schizophrenia. |
| Abstract | This study examined the neural pathophysiology of the theory of mind network by eliciting self-referential processing during an idea of reference evocating situation in patients with schizophrenia. Functional MRI was conducted on 14 schizophrenic in-patients with the idea of reference and 15 healthy participants while viewing video vignettes of referential conversations, non-referential conversations or no conversations between two people, which were filmed at varying distances of 1, 5 or 10 m. The patient group did not show normal patterns of superior temporal sulcus activation to conversational context, and reciprocal deactivation and activation of the ventromedial and dorsomedial prefrontal cortex to referential conversational context. Instead, the patient group showed overall greater ventromedial prefrontal activities across different conversational contexts and inverse correlation between superior temporal sulcus activity and delusional severity. Differential activations of the temporal POLE and its posterior extension to varying distances were observed in the control group but not in the patient group. The present study demonstrates that theory of mind-related responses of the medial prefrontal-superior temporal network are attenuated during the self-referential processing in patients with schizophrenia and that these abnormalities may be related to the formation of their referential or persecutory delusion. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 68 | Neuroimage 2011 Jan 54 Suppl 1: S272-9 |
| PMID | 20441795 |
| Title | Gray matter loss in young relatives at risk for schizophrenia: relation with prodromal psychopathology. |
| Abstract | The maturation of neocortical regions mediating social cognition during adolescence and young adulthood in relatives of schizophrenia patients may be vulnerable to heritable alterations of neurodevelopment. Prodromal psychotic symptoms, commonly emerging during this period in relatives, have been hypothesized to result from alterations in brain regions mediating social cognition. We hypothesized these regions to show longitudinal alterations and these alterations to predict prodromal symptoms in adolescent and young adult relatives of schizophrenia patients. 27 Healthy controls and 23 relatives were assessed at baseline and one-year follow-up using scale of prodromal symptoms and gray matter volumes of hypothesized regions from T1-MRI images. Regional volumes showing deficits on ANCOVA and repeated-measures ANCOVAs (controlling intra cranial volume, age and gender) were correlated with prodromal symptoms. At baseline, bilateral amygdalae, bilateral pars triangulares, left lateral orbitofrontal, right frontal POLE, angular and supramarginal gyrii were smaller in relatives compared to controls. Relatives declined but controls increased or remained stable on bilateral lateral orbitofrontal, left rostral anterior cingulate, left medial prefrontal, right inferior frontal gyrus and left temporal POLE volumes at follow-up relative to baseline. Smaller volumes predicted greater severity of prodromal symptoms at both cross-sectional assessments. Longitudinally, smaller baseline volumes predicted greater prodromal symptoms at follow-up; greater longitudinal decreases in volumes predicted worsening (increase) of prodromal symptoms over time. These preliminary findings suggest that abnormal longitudinal gray matter loss may occur in regions mediating social cognition and may convey risk for prodromal symptoms during adolescence and early adulthood in individuals with a familial diathesis for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 69 | Arch. Gen. Psychiatry 2011 Sep 68: 871-80 |
| PMID | 21893656 |
| Title | Changes in cortical thickness during the course of illness in schizophrenia. |
| Abstract | Whether cortical thickness changes in schizophrenia over time are more pronounced relative to the changes that can be attributed to normal aging has not been studied. To compare patients with schizophrenia and healthy control participants on cortical thickness change. A 5-year longitudinal study comparing schizophrenic patients and healthy controls using 2 magnetic resonance images of the brain. Patients were recruited from the Department of Psychiatry at the University Medical Centre Utrecht and from other psychiatric hospitals in the Netherlands. Healthy controls were recruited via advertisement in newspapers and notice boards. Ninety-six schizophrenic patients and 113 healthy controls aged 16 to 56 years. Cortical thickness and change in cortical thickness on a vertex-by-vertex basis across the cortical mantle, measures of functional and symptomatic outcome, and cumulative intake of antipsychotics during the scan interval. At baseline, the schizophrenic patients had thinner left orbitofrontal and right parahippocampal and superior temporal cortices and a thicker superior parietal lobule and occipital POLE compared with the controls. Mean cortical thickness did not differ between the groups. Over time, excessive cortical thinning was found in widespread areas on the cortical mantle, most pronounced bilaterally in the temporal cortex and in the left frontal area. Poor outcome in patients was associated with more pronounced cortical thinning. Higher cumulative intake of typical antipsychotics during the scan interval was associated with more pronounced cortical thinning, whereas higher cumulative intake of atypical antipsychotic medication was associated with less pronounced cortical thinning. In schizophrenia, the cortex shows excessive thinning over time in widespread areas of the brain, most pronounced in the frontal and temporal areas, and progresses across the entire course of the illness. The excessive thinning of the cortex appears related to outcome and medication intake. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 70 | Acta Psychiatr Scand 2011 Jan 123: 43-54 |
| PMID | 20712827 |
| Title | Disrupted theory of mind network processing in response to idea of reference evocation in schizophrenia. |
| Abstract | This study examined the neural pathophysiology of the theory of mind network by eliciting self-referential processing during an idea of reference evocating situation in patients with schizophrenia. Functional MRI was conducted on 14 schizophrenic in-patients with the idea of reference and 15 healthy participants while viewing video vignettes of referential conversations, non-referential conversations or no conversations between two people, which were filmed at varying distances of 1, 5 or 10 m. The patient group did not show normal patterns of superior temporal sulcus activation to conversational context, and reciprocal deactivation and activation of the ventromedial and dorsomedial prefrontal cortex to referential conversational context. Instead, the patient group showed overall greater ventromedial prefrontal activities across different conversational contexts and inverse correlation between superior temporal sulcus activity and delusional severity. Differential activations of the temporal POLE and its posterior extension to varying distances were observed in the control group but not in the patient group. The present study demonstrates that theory of mind-related responses of the medial prefrontal-superior temporal network are attenuated during the self-referential processing in patients with schizophrenia and that these abnormalities may be related to the formation of their referential or persecutory delusion. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 71 | PLoS ONE 2012 -1 7: e38128 |
| PMID | 22675514 |
| Title | A new mouse model for mania shares genetic correlates with human bipolar disorder. |
| Abstract | Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary rodent models for the manic POLE of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain termed Madison (MSN) that naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a novel genome enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Using a functional network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Our findings suggest that MSN mice represent a polygenic model for the manic POLE of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 72 | Eur Neuropsychopharmacol 2012 May 22: 379-86 |
| PMID | 21982117 |
| Title | Alteration in RGS2 expression level is associated with changes in haloperidol induced extrapyramidal features in a mutant mouse model. |
| Abstract | Antipsychotic induced Parkinsonism (AIP) is a common adverse effect of antipsychotic drug treatment among schizophrenia patients. Two previous studies showed association of the rs4606 SNP in the 3' untranslated region of the regulator of G protein signaling 2 gene (RGS2) with susceptibility to AIP. Since rs4606 reportedly influences expression of RGS2, we applied a translational approach and studied the effect of chronic (24 days) exposure to haloperidol on AIP-like features in mice carrying a mutation that causes lower Rgs2 gene expression. Haloperidol and vehicle treated male mice heterozygous (HET) or homozygous (HOM) for the mutation, or wild type (WT), were evaluated for open field locomotion, catalepsy duration, POLE test performance and rota-rod latency to fall. We showed that in haloperidol treated mice lower Rgs2 expression is associated with better performance on the open field, catalepsy and rota-rod tests but not the POLE test. Results were most consistent for the 0.2 mg/kg/d haloperidol dose. These observations support the possible involvement of RGS2 in mechanisms underlying susceptibility to AIP. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 73 | Schizophr. Res. 2012 Nov 141: 197-203 |
| PMID | 22998933 |
| Title | Regional cortical thinning in subjects with high genetic loading for schizophrenia. |
| Abstract | Although recent studies have revealed regional cortical thinning in patients with schizophrenia, it is not clear whether cortical thinning reflects a genetic liability for schizophrenia. The present study investigated the change of cortical thickness in subjects at genetic high risk (GHR) for schizophrenia with a relatively high genetic loading compared with healthy controls (HC) and patients with schizophrenia. The effect of genetic loading on cortical thinning was also measured by comparing GHR subgroups according to the levels of genetic loading. Cortical thickness was measured by the Constrained Laplacian-based Automated Segmentation with Proximities algorithm using 1.5-T structural MRI scans. The cortical thickness of the subjects at GHR (n=31) was compared with that of HC (n=29) and patients with schizophrenia (n=31). We then compared the cortical thickness of the GHR subgroups according to the number of first-degree relatives with schizophrenia to measure the effect of genetic loading. Relative to HC, GHR subjects showed significant cortical thinning in the right anterior cingulate cortex (ACC), left paracingulate and posterior cingulate regions; bilateral frontal regions including frontal POLE and ventromedial prefrontal cortex; bilateral temporal regions including the left parahippocampal gyrus; and bilateral inferior parietal and occipital regions; however, patients with schizophrenia showed more widespread cortical thinning in the fronto-temporo-parietal region. GHR subjects who had two or more first-degree relatives with schizophrenia showed a greater reduction in cortical thickness in the right ACC and in the left paracingulate cortex than did those who had only one first-degree relative with schizophrenia. Our findings suggest that the level of genetic loading may have a dose-dependent effect on cortical thinning in the right ACC and in the left paracingulate cortex and that cortical thinning in GHR subjects may represent neurodevelopmental alterations that result from genetic liability for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 74 | Biol. Psychiatry 2012 Jan 71: 136-45 |
| PMID | 21993193 |
| Title | Meta-analysis of functional neuroimaging studies of emotion perception and experience in schizophrenia. |
| Abstract | Neuroimaging studies of emotion in schizophrenia have reported abnormalities in amygdala and other regions, although divergent results and heterogeneous paradigms complicate conclusions from single experiments. To identify more consistent patterns of dysfunction, a meta-analysis of functional imaging studies of emotion was undertaken. Searching Medline and PsycINFO databases through January 2011, 88 potential articles were identified, of which 26 met inclusion criteria, comprising 450 patients with schizophrenia and 422 healthy comparison subjects. Contrasts were selected to include emotion perception and emotion experience. Foci from individual studies were subjected to a voxelwise meta-analysis using multilevel kernel density analysis. For emotional experience, comparison subjects showed greater activation in the left occipital POLE. For emotional perception, schizophrenia subjects showed reduced activation in bilateral amygdala, visual processing areas, anterior cingulate cortex, dorsolateral frontal cortex, medial frontal cortex, and subcortical structures. schizophrenia subjects showed greater activation in the cuneus, parietal lobule, precentral gyrus, and superior temporal gyrus. Combining across studies and eliminating studies that did not balance on effort and stimulus complexity eliminated most differences in visual processing regions as well as most areas where schizophrenia subjects showed a greater signal. Reduced reactivity of the amygdala appeared primarily in implicit studies of emotion, whereas deficits in anterior cingulate cortex activity appeared throughout all contrasts. Processing emotional stimuli, schizophrenia patients show reduced activation in areas engaged by emotional stimuli, although in some conditions, schizophrenia patients exhibit increased activation in areas outside those traditionally associated with emotion, possibly representing compensatory processing. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 75 | Open Neuroimag J 2012 -1 6: 26-36 |
| PMID | 22870167 |
| Title | Changes in Event-Related Desynchronization and Synchronization during the Auditory Oddball Task in Schizophrenia Patients. |
| Abstract | We studied differences in the spatiotemporal dynamics of cortical oscillation across brain regions of patients with schizophrenia and normal subjects during the auditory oddball task using magnetoencephalography (MEG) and electroencephalography (EEG). Ten right-handed male schizophrenia patients were studied. We used a newly developed adaptive spatial filtering algorithm optimized for robust source time-frequency reconstruction of MEG and EEG data, and obtained consecutive images in functional maps of event-related desynchronization (ERD) and synchronization (ERS) in theta, lower alpha (8-10 Hz), upper alpha (10-13 Hz), and beta bands. Beta ERD power at 750-1000 ms in patients was significantly increased in large right upper temporal and parietal regions and small upper portions of bilateral dorsal frontal and dorsal-medial parietal regions. Theta ERS power in schizophrenic patients during the oddball task was significantly increased in the left temporal POLE at 250-500 ms, and was significantly increased in dorsal, medial frontal, and anterior portions of the anterior cingulate cortex in both hemispheres, and the left portion of lateral temporal regions at 500-750 ms, compared to the control group (family-wise error correction p<0.05). Lower alpha ERS power was significantly decreased in the right occipital region at 500-750 ms and in the right midline parietal and bilateral occipital regions at 750-1000 ms. Upper alpha ERS power was significantly decreased in right midline parietal and left occipital regions at 750-1000 ms. ERD/ERS changes were noted in the left temporal POLE and midline frontal and anterior cingulate cortex in theta ERS, occipital lobe in alpha ERS, and right temporal-frontal-parietal, midline frontal, and anterior cingulate cortex in beta ERD. These findings may reflect disturbances in interaction among active large neuronal groups and their communication with each other that may be related to abnormal cognitive and psychopathological function. Study of ERD and ERS by time-frequency analyses using MEG is useful to clarify data processing dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 76 | Schizophr. Res. 2012 Aug 139: 13-8 |
| PMID | 22633527 |
| Title | Altered default network resting state functional connectivity in patients with a first episode of psychosis. |
| Abstract | Default network (DN) abnormalities have been identified in patients with chronic schizophrenia using "resting state" functional magnetic resonance imaging (R-fMRI). Here, we examined the integrity of the DN in patients experiencing their first episode of psychosis (FEP) compared with sex- and age-matched healthy controls. We collected R-fMRI data from 19 FEP patients (mean age 24.9 ± 4.8 yrs, 14 males) and 19 healthy controls (26.1 ± 4.8 yrs, 14 males) at 3T. Following standard preprocessing, we examined the functional connectivity (FC) of two DN subsystems and the two DN hubs (P<0.0045, corrected). Patients with FEP exhibited abnormal FC that appeared largely restricted to the dorsomedial prefrontal cortex (dMPFC) DN subsystem. Relative to controls, FEP patients exhibited weaker positive FC between dMPFC and posterior cingulate cortex (PCC) and precuneus, extending laterally through the parietal lobe to the posterior angular gyrus. Patients with FEP exhibited weaker negative FC between the lateral temporal cortex and the intracalcarine cortex, bilaterally. The PCC and temporo-parietal junction also exhibited weaker negative FC with the right fusiform gyrus extending to the lingual gyrus and lateral occipital cortex, in FEP patients, compared to controls. By contrast, patients with FEP showed stronger negative FC between the temporal POLE and medial motor cortex, anterior precuneus and posterior mid-cingulate cortex. Abnormalities in the dMPFC DN subsystem in patients with a FEP suggest that FC patterns are altered even in the early stages of psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 77 | Psychol Med 2012 Sep 42: 1847-56 |
| PMID | 22357376 |
| Title | Brain volume reductions in medication-naive patients with schizophrenia in relation to intelligence quotient. |
| Abstract | Global brain abnormalities such as brain volume loss and grey- and white-matter deficits are consistently reported in first-episode schizophrenia patients and may already be detectable in the very early stages of the illness. Whether these changes are dependent on medication use or related to intelligence quotient (IQ) is still debated. Magnetic resonance imaging scans were obtained for 20 medication-naive patients with first-episode schizophrenia and 26 matched healthy subjects. Volume measures of total brain grey and white matter, third and lateral ventricles and cortical thickness/surface were obtained. Differences between the groups were investigated, taking into account the effect of intelligence. Medication-naive patients showed statistically significant reductions in whole-brain volume and cerebral grey- and white-matter volume together with lateral ventricle enlargement compared to healthy subjects. IQ was significantly lower in patients compared to controls and was positively associated with brain and white-matter volume in the whole group. No significant differences in cortical thickness were found between the groups but medication-naive patients had a significantly smaller surface in the left superior temporal POLE, Heschl's gyrus and insula compared to controls. Our findings suggest that brain volume loss is present at illness onset, and can be explained by the reduced surface of the temporal and insular cortex. These abnormalities are not related to medication, but IQ. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 78 | Psychiatry Res 2012 Jan 201: 25-33 |
| PMID | 22284150 |
| Title | Progressive membrane phospholipid changes in first episode schizophrenia with high field magnetic resonance spectroscopy. |
| Abstract | Patients with a first episode of schizophrenia generally have increased phospholipid membrane breakdown products within the brain, while findings in chronic patients have been inconsistent. In this study we examine progressive changes in phosphorus membrane metabolites in the same patient group through the early years of schizophrenia in brain regions associated with the disease. Sixteen never-treated and medicated first episode schizophrenic patients were assessed at 10 months and 52 months after diagnosis. Sixteen matched volunteers were assessed at baseline and after 35 months. Phospholipid membrane metabolism was assessed with phosphorous magnetic resonance spectroscopy in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex, parieto-occipital cortex, superior temporal gyrus and temporal POLE. At 10 months, glycerophosphocholine was increased in the anterior cingulate in patients as compared to controls. Glycerophosphocholine was decreased in the anterior cingulate and increased in the posterior cingulate and left superior temporal gyrus; glycerophosphoethanolamine was decreased in the left thalamus and increased in the left hippocampus within patients over time. At 52 months, compared to controls phosphocholine was increased in the left thalamus and glycerophosphoethanolamine was increased in the left hippocampus. These results imply a gradual inclusion of brain regions in schizophrenia where an initial increase, followed by a decrease in phospholipid membrane metabolites was observed. This pattern, observed in the early years of schizophrenia, is consistent with excitotoxic neural membrane breakdown in these regions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 79 | Schizophr Bull 2012 Sep 38: 1074-82 |
| PMID | 21527413 |
| Title | Auditory hallucinations elicit similar brain activation in psychotic and nonpsychotic individuals. |
| Abstract | While auditory verbal hallucinations (AVH) are most characteristic for schizophrenia, they also occur in nonpsychotic individuals in the absence of a psychiatric or neurological disorder and in the absence of substance abuse. At present, it is unclear if AVH in these nonpsychotic individuals constitute the same phenomenon as AVH in psychotic patients. Comparing brain activation during AVH between nonpsychotic and psychotic individuals could provide important clues regarding this question. 21 nonpsychotic subjects with AVH and 21 matched psychotic patients indicated the presence of AVH during 3T functional magnetic resonance imaging (fMRI) scanning. To identify common areas of activation during the experience of AVH in both groups, a conjunction analysis was performed. In addition, a 2-sample t-test was employed to discover possible differences in AVH-related activation between the groups. Several common areas of activation were observed for the psychotic and nonpsychotic subjects during the experience of AVH, consisting of the bilateral inferior frontal gyri, insula, superior temporal gyri, supramarginal gyri and postcentral gyri, left precentral gyrus, inferior parietal lobule, superior temporal POLE, and right cerebellum. No significant differences in AVH-related brain activation were present between the groups. The presence of multiple common areas of AVH-related activation in psychotic and nonpsychotic individuals, in the absence of significant differences, implicates the involvement of the same cortical network in the experience of AVH in both groups. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 80 | Open Neuroimag J 2012 -1 6: 26-36 |
| PMID | 22870167 |
| Title | Changes in Event-Related Desynchronization and Synchronization during the Auditory Oddball Task in Schizophrenia Patients. |
| Abstract | We studied differences in the spatiotemporal dynamics of cortical oscillation across brain regions of patients with schizophrenia and normal subjects during the auditory oddball task using magnetoencephalography (MEG) and electroencephalography (EEG). Ten right-handed male schizophrenia patients were studied. We used a newly developed adaptive spatial filtering algorithm optimized for robust source time-frequency reconstruction of MEG and EEG data, and obtained consecutive images in functional maps of event-related desynchronization (ERD) and synchronization (ERS) in theta, lower alpha (8-10 Hz), upper alpha (10-13 Hz), and beta bands. Beta ERD power at 750-1000 ms in patients was significantly increased in large right upper temporal and parietal regions and small upper portions of bilateral dorsal frontal and dorsal-medial parietal regions. Theta ERS power in schizophrenic patients during the oddball task was significantly increased in the left temporal POLE at 250-500 ms, and was significantly increased in dorsal, medial frontal, and anterior portions of the anterior cingulate cortex in both hemispheres, and the left portion of lateral temporal regions at 500-750 ms, compared to the control group (family-wise error correction p<0.05). Lower alpha ERS power was significantly decreased in the right occipital region at 500-750 ms and in the right midline parietal and bilateral occipital regions at 750-1000 ms. Upper alpha ERS power was significantly decreased in right midline parietal and left occipital regions at 750-1000 ms. ERD/ERS changes were noted in the left temporal POLE and midline frontal and anterior cingulate cortex in theta ERS, occipital lobe in alpha ERS, and right temporal-frontal-parietal, midline frontal, and anterior cingulate cortex in beta ERD. These findings may reflect disturbances in interaction among active large neuronal groups and their communication with each other that may be related to abnormal cognitive and psychopathological function. Study of ERD and ERS by time-frequency analyses using MEG is useful to clarify data processing dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 81 | Psychiatry Res 2012 Jan 201: 25-33 |
| PMID | 22284150 |
| Title | Progressive membrane phospholipid changes in first episode schizophrenia with high field magnetic resonance spectroscopy. |
| Abstract | Patients with a first episode of schizophrenia generally have increased phospholipid membrane breakdown products within the brain, while findings in chronic patients have been inconsistent. In this study we examine progressive changes in phosphorus membrane metabolites in the same patient group through the early years of schizophrenia in brain regions associated with the disease. Sixteen never-treated and medicated first episode schizophrenic patients were assessed at 10 months and 52 months after diagnosis. Sixteen matched volunteers were assessed at baseline and after 35 months. Phospholipid membrane metabolism was assessed with phosphorous magnetic resonance spectroscopy in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex, parieto-occipital cortex, superior temporal gyrus and temporal POLE. At 10 months, glycerophosphocholine was increased in the anterior cingulate in patients as compared to controls. Glycerophosphocholine was decreased in the anterior cingulate and increased in the posterior cingulate and left superior temporal gyrus; glycerophosphoethanolamine was decreased in the left thalamus and increased in the left hippocampus within patients over time. At 52 months, compared to controls phosphocholine was increased in the left thalamus and glycerophosphoethanolamine was increased in the left hippocampus. These results imply a gradual inclusion of brain regions in schizophrenia where an initial increase, followed by a decrease in phospholipid membrane metabolites was observed. This pattern, observed in the early years of schizophrenia, is consistent with excitotoxic neural membrane breakdown in these regions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 82 | Neuroimage 2013 Dec 83: 751-60 |
| PMID | 23876243 |
| Title | Sex differences in the development of brain mechanisms for processing biological motion. |
| Abstract | Disorders related to social functioning including autism and schizophrenia differ drastically in incidence and severity between males and females. Little is known about the neural systems underlying these sex-linked differences in risk and resiliency. Using functional magnetic resonance imaging and a task involving the visual perception of point-light displays of coherent and scrambled biological motion, we discovered sex differences in the development of neural systems for basic social perception. In adults, we identified enhanced activity during coherent biological motion perception in females relative to males in a network of brain regions previously implicated in social perception including amygdala, medial temporal gyrus, and temporal POLE. These sex differences were less pronounced in our sample of school-age youth. We hypothesize that the robust neural circuitry supporting social perception in females, which diverges from males beginning in childhood, may underlie sex differences in disorders related to social processing. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 83 | Psychiatry Res 2013 Sep 209: 155-9 |
| PMID | 23261182 |
| Title | Ictal EEG fractal dimension in ECT predicts outcome at 2 weeks in schizophrenia. |
| Abstract | Studies of electroconvulsive therapy (ECT) have found an association between ictal electroencephalographic (EEG) measures and clinical outcome in depression. Such studies are lacking in schizophrenia. Consenting schizophrenia patients receiving ECT were assessed using the Brief Psychiatric Rating Scale (BPRS) before and 2 weeks after the start of ECT. The patients' seizure was monitored using EEG. In 26 patients, completely artifact-free EEG derived from the left frontal-POLE (FP1) channel and electrocardiography (ECG) were available. The fractal dimension (FD) was computed to assess 4-s EEG epochs, and the maximal value from the earliest ECT session (2nd, 3rd or 4th) was used for analysis. There was a significant inverse correlation between the maximum FD and the total score following 6th ECT. An inverse Inverse correlation was also observed between the maximum FD and the total number of ECTs administered as well as the maximum heart rate (HR) and BPRS scores following 6th ECT. In patients with schizophrenia greater intensity of seizures (higher FD) during initial sessions of ECT is associated with better response at the end of 2 weeks. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 84 | Schizophr. Res. 2013 Jul 147: 339-47 |
| PMID | 23706416 |
| Title | Schizophrenia and the brain's control network: aberrant within- and between-network connectivity of the frontoparietal network in schizophrenia. |
| Abstract | The deficit of executive control is a core feature of schizophrenia, and as such, it provides hints for the neural signature of this devastating mental illness. The frontoparietal network (FPN) is a newly defined network important for various tasks requiring executive control. This study aims to investigate both the within- and between-network connectivity of the FPN in schizophrenia using functional connectivity MRI (fcMRI). Thirty-six subjects with schizophrenia and thirty-six healthy controls were enrolled. Each subject received resting fMRI scanning, clinical evaluations and cognitive examinations. Twenty-two regions of interest (ROIs) in the key hubs of the FPN were defined according to the functional connectivity map of the left and right dorsolateral prefrontal cortex (dlPFC) and included the bilateral frontal POLE, inferior parietal lobe (IPL), insula, dorsomedial prefrontal cortex (dmPFC), middle cingulate cortex (mCC), precuneus, caudate, thalamus and cerebellum. Between-group comparisons were conducted using both multiple ROI-based and brain-wise analyses. The ROI-based analysis revealed that the schizophrenic participants were associated with a prominent cortico-subcortical disconnection within the FPN. Further brain-wise analyses demonstrated that the schizophrenia patients showed increased functional connectivity between several ROIs in the FPN and regions belonging to the primary sensory processing or default mode networks. These results indicated that schizophrenia is associated with both within- and between-network dysconnectivity of the FPN. Together with our previous findings of the cortico-striatal disconnection of the cingulo-opercular network, we suggest that the brain's control networks may play an important role in the neural mechanisms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 85 | Open Neuroimag J 2013 -1 7: 15-26 |
| PMID | 23750187 |
| Title | Dysfunctional cortical connectivity during the auditory oddball task in patients with schizophrenia. |
| Abstract | We studied the imaginary coherence (IC) of gamma frequency oscillations between brain regions of male schizophrenia patients during an auditory oddball task using magnetoencephalography (MEG) and electroencephalography (EEG). Subjects were 10 right-handed male schizophrenia patients, evaluated by the positive and negative symptom scale (PANSS), and 10 healthy controls. Functional connectivity during the auditory oddball task was reconstructed in low (30-50 Hz) and high (50-100 Hz) gamma bands, and represented by imaginary coherence (IC) based on significant oscillatory power changes. We calculated correlations between PANSS scores and IC. In the high gamma band, IC between left occipital and right prefrontal lobe areas during the time window 750-1000 ms from stimulus onset showed negative correlations with total negative scores, total positive scores, the sum of positive and negative scores in PANSS, conceptual disorganization, and social avoidance scores. In the low gamma band, IC between the same areas from 250-500 ms also showed a negative correlation with the conceptual disorganization score. In the same time window, IC between left occipital and right frontoparietal lobe areas in the low gamma band showed a positive correlation with hallucinatory behavior; IC between right temporal POLE and left prefrontal lobe areas showed a positive correlation with delusion scores, although these ICs were decreased relative to controls. Functional disconnection of high and low gamma bands in auditory oddball task may play an important role in the auditory processing in schizophrenia patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 86 | Behav. Brain Res. 2013 Apr 243: 146-52 |
| PMID | 23318463 |
| Title | Association of MTHFR C677T polymorphism with schizophrenia and its effect on episodic memory and gray matter density in patients. |
| Abstract | Growing evidence suggests that the methylenetetrahydrofolate reductase (MTHFR) may play a role in the pathogenesis of schizophrenia. Recent studies suggested that the MTHFR 677T, as a risk allele, has an impact on brain activation and memory function in schizophrenia patients. To confirm further the association between this functional polymorphism and schizophrenia, we detected genotypes of MTHFR C677T polymorphism in 1002 schizophrenic patients and 1036 controls of Chinese Han population, by using direct DNA sequencing method. To explore further effects of MTHFR C677T polymorphism on memory and brain function in schizophrenia, 33 schizophrenia patients and 29 healthy participants were selected from above samples to be assessed with MRI scanning and episodic memory (EM) examination. The case-control association study results showed that the MTHFR C677T was associated with schizophrenia (?(2)=14.11, P=1.74 × 10(-4), OR=0.79; 95% CI=0.70-0.89). We also found that the MTHFR 677T allele had a load-dependent effect on EM in schizophrenic patients, but not in healthy control participants. Further analysis on gray matter density (GMD) revealed significant diagnostic effects in bilateral frontal cortices, bilateral insula, left medial temporal cortex and bilateral occipital cortices, effects of MTHFR genotype in the right insula, right inferior frontal gyrus, right rolandic opercula, right parahippocampal gyrus and right medial temporal POLE, and effects of genotype-diagnosis interaction in the right temporal gyrus. Our findings suggested that the MTHFR 677T allele might have effect on risk of schizophrenia, memory impairment and GMD changes in patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 87 | PLoS ONE 2013 -1 8: e75115 |
| PMID | 24124469 |
| Title | Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study. |
| Abstract | It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18-65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal POLE and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18-65 year age range. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 88 | Brain Imaging Behav 2013 Sep 7: 335-52 |
| PMID | 23686576 |
| Title | Human middle longitudinal fascicle: segregation and behavioral-clinical implications of two distinct fiber connections linking temporal pole and superior temporal gyrus with the angular gyrus or superior parietal lobule using multi-tensor tractography. |
| Abstract | The middle longitudinal fascicle (MdLF) is a major fiber connection running principally between the superior temporal gyrus and the parietal lobe, neocortical regions of great biological and clinical interest. Although one of the most prominent cerebral association fiber tracts, it has only recently been discovered in humans. In this high angular resolution diffusion imaging (HARDI) MRI study, we delineated the two major fiber connections of the human MdLF, by examining morphology, topography, cortical connections, biophysical measures, volume and length in seventy-four brains. These two fiber connections course together through the dorsal temporal POLE and the superior temporal gyrus maintaining a characteristic topographic relationship in the mediolateral and ventrodorsal dimensions. As these pathways course towards the parietal lobe, they split to form separate fiber pathways, one following a ventrolateral trajectory and connecting with the angular gyrus and the other following a dorsomedial route and connecting with the superior parietal lobule. Based on the functions of their cortical affiliations, we suggest that the superior temporal-angular connection of the MdLF, i.e., STG(MdLF)AG plays a role in language and attention, whereas the superior temporal-superior parietal connection of the MdLF, i.e., STG(MdLF)SPL is involved in visuospatial and integrative audiovisual functions. Furthermore, the MdLF may have clinical implications in neurodegenerative disorders such as primary progressive aphasia, frontotemporal dementia, posterior cortical atrophy, corticobulbar degeneration and Alzheimer's disease as well as attention-deficit/hyperactivity disorder and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 89 | Schizophr. Res. 2013 Feb 143: 253-9 |
| PMID | 23290607 |
| Title | Abnormalities of middle longitudinal fascicle and disorganization in patients with schizophrenia. |
| Abstract | The middle longitudinal fascicle (MdLF) is a long association fiber connecting the superior temporal gyrus (STG) and temporal POLE with the angular gyrus through the white matter of the STG, structures which are known to play a crucial role in the pathology of schizophrenia. Functions of MdLF are thought to be related to language and thought processing in the left hemisphere, and with attention in the right hemisphere. While deficits of these functions are core clinical features of schizophrenia, no study has investigated the structural abnormalities of MdLF in schizophrenia. 3T diffusion tensor data was acquired from twenty-six patients with schizophrenia and twenty-five healthy control subjects. Streamline tractography technique was used to extract MdLF. Fractional anisotropy (FA) was compared between the two groups. In addition, relationships were investigated between FA in the left MdLF and the Disorganized Thoughts Factor derived from the Positive and Negative Symptom Scale five factor model, and between FA in the right MdLF and the Poor Attention. Relative to control subjects, the patients with chronic schizophrenia showed significant mean FA reductions in the bilateral MdLF. The FA of the left MdLF demonstrated a significant negative association with the Disorganized Thoughts Factor, and the FA of the right MdLF showed a significant negative relationship with the Poor Attention. This study provides new evidence for structural deficits in the bilateral MdLF in patients with chronic schizophrenia. It further demonstrates the contribution of these abnormalities to the core clinical features - especially to disorganization and attention deficit. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 90 | Schizophr. Res. 2013 Jul 147: 339-47 |
| PMID | 23706416 |
| Title | Schizophrenia and the brain's control network: aberrant within- and between-network connectivity of the frontoparietal network in schizophrenia. |
| Abstract | The deficit of executive control is a core feature of schizophrenia, and as such, it provides hints for the neural signature of this devastating mental illness. The frontoparietal network (FPN) is a newly defined network important for various tasks requiring executive control. This study aims to investigate both the within- and between-network connectivity of the FPN in schizophrenia using functional connectivity MRI (fcMRI). Thirty-six subjects with schizophrenia and thirty-six healthy controls were enrolled. Each subject received resting fMRI scanning, clinical evaluations and cognitive examinations. Twenty-two regions of interest (ROIs) in the key hubs of the FPN were defined according to the functional connectivity map of the left and right dorsolateral prefrontal cortex (dlPFC) and included the bilateral frontal POLE, inferior parietal lobe (IPL), insula, dorsomedial prefrontal cortex (dmPFC), middle cingulate cortex (mCC), precuneus, caudate, thalamus and cerebellum. Between-group comparisons were conducted using both multiple ROI-based and brain-wise analyses. The ROI-based analysis revealed that the schizophrenic participants were associated with a prominent cortico-subcortical disconnection within the FPN. Further brain-wise analyses demonstrated that the schizophrenia patients showed increased functional connectivity between several ROIs in the FPN and regions belonging to the primary sensory processing or default mode networks. These results indicated that schizophrenia is associated with both within- and between-network dysconnectivity of the FPN. Together with our previous findings of the cortico-striatal disconnection of the cingulo-opercular network, we suggest that the brain's control networks may play an important role in the neural mechanisms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 91 | Behav. Brain Res. 2013 Apr 243: 146-52 |
| PMID | 23318463 |
| Title | Association of MTHFR C677T polymorphism with schizophrenia and its effect on episodic memory and gray matter density in patients. |
| Abstract | Growing evidence suggests that the methylenetetrahydrofolate reductase (MTHFR) may play a role in the pathogenesis of schizophrenia. Recent studies suggested that the MTHFR 677T, as a risk allele, has an impact on brain activation and memory function in schizophrenia patients. To confirm further the association between this functional polymorphism and schizophrenia, we detected genotypes of MTHFR C677T polymorphism in 1002 schizophrenic patients and 1036 controls of Chinese Han population, by using direct DNA sequencing method. To explore further effects of MTHFR C677T polymorphism on memory and brain function in schizophrenia, 33 schizophrenia patients and 29 healthy participants were selected from above samples to be assessed with MRI scanning and episodic memory (EM) examination. The case-control association study results showed that the MTHFR C677T was associated with schizophrenia (?(2)=14.11, P=1.74 × 10(-4), OR=0.79; 95% CI=0.70-0.89). We also found that the MTHFR 677T allele had a load-dependent effect on EM in schizophrenic patients, but not in healthy control participants. Further analysis on gray matter density (GMD) revealed significant diagnostic effects in bilateral frontal cortices, bilateral insula, left medial temporal cortex and bilateral occipital cortices, effects of MTHFR genotype in the right insula, right inferior frontal gyrus, right rolandic opercula, right parahippocampal gyrus and right medial temporal POLE, and effects of genotype-diagnosis interaction in the right temporal gyrus. Our findings suggested that the MTHFR 677T allele might have effect on risk of schizophrenia, memory impairment and GMD changes in patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 92 | Schizophr. Res. 2014 Dec 160: 57-66 |
| PMID | 25458859 |
| Title | Both volumetry and functional connectivity of Heschl's gyrus are associated with auditory P300 in first episode schizophrenia. |
| Abstract | Reduced 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 Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 93 | Neuropsychobiology 2014 -1 70: 142-51 |
| PMID | 25358262 |
| Title | Different and shared brain volume abnormalities in late- and early-onset schizophrenia. |
| Abstract | The differences in clinical characteristics between late- (LOS) and early-onset schizophrenia (EOS) are well documented. However, very little is known about the neural mechanisms underlying these differences. Here, we compared morphometric abnormalities between patients with EOS and those with LOS. A total of 22 patients with LOS, 24 patients with EOS and 41 healthy control subjects were included in this magnetic resonance imaging study. Brain images were analyzed using DARTEL preprocessing for voxel-based morphometry in SPM8. We tested a main effect of diagnosis in the whole-brain analysis and compared the results among the three groups. We also carried out correlation analyses between regional volumes and clinical variables. Patients with LOS showed larger gray matter (GM) volume of the left precuneus compared with healthy subjects and patients with EOS. Patients with LOS and EOS showed decreased GM volumes in the right insula, left superior temporal gyrus and left orbitofrontal gyrus compared with healthy subjects. A longer duration of illness was associated with reduced GM volume in the temporal POLE in patients with EOS. Our findings may help improve our understanding of schizophrenia pathophysiology and shed light on the different and shared neurobiological underpinnings of LOS and EOS. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 94 | Neuroimage Clin 2014 -1 6: 463-74 |
| PMID | 25389520 |
| Title | Altered functional connectivity links in neuroleptic-naïve and neuroleptic-treated patients with schizophrenia, and their relation to symptoms including volition. |
| Abstract | In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS) patients, and 60 healthy controls (HC). Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS), that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal POLE. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits) than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 95 | Psychiatry Res 2014 Dec 224: 211-7 |
| PMID | 25453165 |
| Title | Subsequent memory effects in schizophrenia. |
| Abstract | Differential neural activation at encoding can predict which stimuli will be subsequently remembered or forgotten, and memory deficits are pronounced in schizophrenia. We used event-related functional magnetic resonance imaging (fMRI) to investigate subsequent memory (SM) effects for visual fractals in patients with schizophrenia (n=26) and healthy controls (n=28). Participants incidentally encoded the fractals during an oddball task and 10 min later they made old/new recognition memory judgments on 30 target fractals and 30 foil fractals. We found evidence for subsequent memory (SM, subsequently remembered>subsequently forgotten) effects on regional brain activation in both groups but with distinct patterns. Region of interest (ROI) analyses in controls demonstrated SM activation in both medial temporal lobe (MTL) and fusiform cortex (FF), whereas patients showed SM effects only in the FF. There were no significant between group differences in MTL activation; however, patients demonstrated greater FF activation than controls. Notably, greater FF activation during successful encoding was associated with more severe negative symptoms. Exploratory whole brain analyses in patients demonstrated SM activation in the occipital POLE, lateral occipital cortex, left inferior temporal gyrus, and fusiform cortex; whereas in controls there was no significant activation that survived correction for multiple comparisons. Our findings suggest that patients, particularly those with prominent negative symptoms, may activate FF as a compensatory strategy to promote successful encoding, with relatively less reliance on MTL recruitment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 96 | Am J Psychiatry 2014 Sep 171: 939-48 |
| PMID | 25073506 |
| Title | Cortical thinning, functional connectivity, and mood-related impulsivity in schizophrenia: relationship to aggressive attitudes and behavior. |
| Abstract | Aggression in schizophrenia is a major societal issue, leading to physical harm, stigmatization, patient distress, and higher health care costs. Impulsivity is associated with aggression in schizophrenia, but it is multidetermined. The subconstruct of urgency is likely to play an important role in this aggression, with positive urgency referring to rash action in the context of positive emotion, and negative urgency referring to rash action in the context of negative emotion. The authors examined urgency and its neural correlates in 33 patients with schizophrenia or schizoaffective disorder and 31 healthy comparison subjects. Urgency was measured using the Urgency, Premeditation, Perseverance, and Sensation-Seeking scale. Aggressive attitudes were measured using the Buss-Perry Aggression Questionnaire. Positive urgency, negative urgency, and aggressive attitudes were significantly and selectively elevated in schizophrenia patients (Cohen's d values, 1.21-1.50). Positive and negative urgency significantly correlated with the Aggression Questionnaire total score (r>0.48 in all cases) and each uniquely accounted for a significant portion of the variance in aggression over and above the effect of group. Urgency scores correlated with reduced cortical thickness in ventral prefrontal regions including the right frontal POLE, the medial and lateral orbitofrontal gyrus and inferior frontal gyri, and the rostral anterior cingulate cortex. In patients, reduced resting-state functional connectivity in some of these regions was associated with higher urgency. These findings highlight the key role of urgency in aggressive attitudes in people with schizophrenia and suggest neural substrates of these behaviors. The results also suggest behavioral and neural targets for interventions to remediate urgency and aggression. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 97 | Br J Psychiatry 2014 Feb 204: 115-21 |
| PMID | 24311551 |
| Title | Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain structure and attributional style. |
| Abstract | A single nucleotide polymorphism (rs7914558) within the cyclin M2 (CNNM2) gene was recently identified as a common risk variant for schizophrenia. The mechanism by which CNNM2 confers risk is unknown. To determine the impact of the rs7914558 risk 'G' allele [corrected] on measures of neurocognition, social cognition and brain structure. Patients with schizophrenia (n = 400) and healthy controls (n = 160) completed measures of neuropsychological function and social cognition. Structural magnetic resonance imaging data were also acquired from an overlapping sample of Irish healthy controls (n = 159) and an independent sample of Italian patients (n = 82) and healthy controls (n = 39). No effects of genotype on neuropsychological test performance were observed. However, a dosage effect of the risk allele was found for an index of social cognition (i.e. attributional style), such that risk status was associated with reduced self-serving bias across groups (GG>AG>AA, P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions putatively supporting social cognition, risk carriers had relatively increased grey matter volume in the right temporal POLE and right anterior cingulate cortex (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical associations between CNNM2 and grey matter volume in anterior cingulate cortex were also observed in the Italian schizophrenia and healthy controls samples. Although the biological role of CNNM2 in schizophrenia remains unknown, these data suggest that this CNNM2 risk variant rs7914558 may have an impact on neural systems relevant to social cognition. How such effects may mediate the relationship between genotype and disease risk remains to be established. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 98 | Schizophr. Res. 2014 Jan 152: 184-90 |
| PMID | 24280350 |
| Title | Prefrontal cortex volume deficit in schizophrenia: a new look using 3T MRI with manual parcellation. |
| Abstract | In this study we use high resolution Magnetic Resonance imaging (MRI) and apply rigorous manual tracing criteria in order to assess volumetrically the prefrontal cortex (PFC) in schizophrenia. Previous MRI studies suggested PFC is included in neural systems necessary for emotional processing and cognition, and regional PFC abnormalities might, thus, lead to specific negative symptoms, as well as a frequent association of poorer performance in category switching. The aim of this study was to use 3T imaging and reliable manual parcellation to determine if, as hypothesized, this higher precision would reveal additional MRI abnormalities in PFC in schizophrenia, and an association between PFC abnormalities and specific negative symptoms, as well as in category switching. Using 3-T MRI, 27 schizophrenia patients and 27 healthy controls were examined. PFC was manually parcellated into frontal POLE, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Left SFG (p=0.004), bilateral MFG (left: p=0.007; right: p=0.007), and bilateral IFG (left: p<0.001; right: p=0.002) showed volume reduction. There were symptom associations between smaller left MFG volumes and more affective flattening (R=-0.465, p=0.015), and smaller left IFG volumes and poorer performance on the alternating semantic category test (R=0.440, p=0.025). In summary, 3-T imaging revealed widespread gyral volume deficits in PFC gyri, and specific associations with selective negative symptoms, such as affective flattening, and with deficits in cognitive switching. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 99 | Magn Reson Imaging 2014 Jan 32: 1-8 |
| PMID | 24161847 |
| Title | A combined DTI and structural MRI study in medicated-naïve chronic schizophrenia. |
| Abstract | Disconnection in white matter (WM) pathway and alterations in gray matter (GM) structure have been hypothesized as pathogenesis in schizophrenia. However, the relationship between the abnormal WM integrity and the alteration of GM in anatomically connected areas remains uncertain. Moreover, the potential influence of antipsychotic medication on WM anisotropy and cortical morphology was not excluded in previous studies. In this study, a total number of 34 subjects were enrolled, including 17 medicated-naïve chronic schizophrenia patients and 17 healthy controls. Tract-based spatial statistics (TBSS) were applied to investigate the level of WM integrity. The FreeSurfer surface-based analysis was used to determine GM volume, cortical thickness and the surface area of GM regions which corresponded to abnormal WM fiber tracts. We observed that patients possessed lower fractional anisotropy (FA) values in the left inferior fronto-occipital fasciculus (IFOF) and left inferior longitudinal fasciculus (ILF), along with smaller GM volume and cortical thinning in temporal lobe than the healthy controls, which reflected the underlying WM and GM disruption that contributed to the disease. In the patient population, the lower connectivity of ILF and IFOF was positively associated with cortical thickness in left lateral orbitofrontal cortex, superior temporal gyrus and lingual gyrus in males, and positively correlated with GM volume in left lateral orbitofrontal cortex in females. On the other hand, it was negatively correlated with cortical area of middle temporal gyrus in males and temporal POLE in females respectively, but not when genders were combined. These findings suggested that abnormal WM integrity and anatomical correspondence of GM alterations in schizophrenia were interdependent on gender-separated analysis in patients with schizophrenia. Moreover, combining TBSS and FreeSurfer might be a useful method to provide significant insight into interacting processes related to WM fiber tracts and GM changes in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 100 | Soc Cogn Affect Neurosci 2014 Sep 9: 1261-7 |
| PMID | 23912681 |
| Title | Default mode network connectivity and reciprocal social behavior in 22q11.2 deletion syndrome. |
| Abstract | 22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and other default mode network (DMN) nodes, including the precuneus, precentral gyrus and left frontal POLE. 22q11DS patients did not show age-associated FC changes observed in typically developing controls. Increased connectivity between PCC, medial prefrontal regions and the anterior cingulate cortex, was associated with lower SRS scores (i.e. improved social competence) in 22q11DS. DMN integrity may play a key role in social information processing. We observed disrupted DMN connectivity in 22q11DS, paralleling reports from idiopathic autism and schizophrenia. Increased strength of long-range DMN connectivity was associated with improved social functioning in 22q11DS. These findings support a 'developmental-disconnection' hypothesis of symptom development in this disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 101 | Clin EEG Neurosci 2014 Apr 45: 122-5 |
| PMID | 23760035 |
| Title | Maximum fractal dimension of cerebral seizure remains constant through the course of electroconvulsive therapy. |
| Abstract | Electroconvulsive therapy (ECT), in which electrical current is used to induce seizures, is an effective treatment in psychiatry. Different methods of analyzing the electroencephalogram (EEG) changes during ECT have been studied for predicting clinical outcome. Analysis of the fractal dimension (FD) is one such method. Mid-seizure and post-seizure FD has been shown to correlate with antidepressant effect. In this study, we examined whether the highest fractal dimension achieved during each ECT session changed over the course of 6 ECTs. The sample for this study came from a randomized controlled trial, comparing the efficacy of bifrontal and bitemporal electrode placements in schizophrenia. EEG was recorded using bilateral frontal POLE leads during all ECT sessions. In 40 of the 114 randomized patients, we could obtain artifact-free EEGs for the first 6 ECT sessions. FD was calculated using standardized algorithms. For each session, the average of 5 highest FDs was calculated. The change in this value over a course of 6 ECTs was analyzed using repeated-measures analysis of variance. The average highest FD remained virtually unchanged across the 6 ECT sessions. Means (standard deviations) average maximum FDs over the 6 sessions were 1.57 (0.075), 1.57 (0.064), 1.56 (0.064), 1.57 (0.062), 1.55 (0.07), and 1.56 (0.067); occasion effect, F = 0.5, P = .75. Group effect (F = 0.01, P = .92) and group × occasion interaction effect (F = 1.88, P = .1) were not significant, suggesting no influence of electrode placement on maximum FD. Seizure duration, however, showed significant decline over the course of ECT. Maximum FD of ECT-induced EEG seizure remains fairly constant over frontal POLEs across the first 6 ECT sessions, which is true irrespective of ECT electrode placements. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 102 | Neuropsychologia 2014 Aug 61: 280-90 |
| PMID | 25010933 |
| Title | Greater positive schizotypy relates to reduced N100 activity during rejection scenes. |
| Abstract | Social anxiety due to rejection sensitivity (RS) exacerbates psychosis-like experiences in the general population. While reduced dorsal anterior cingulate cortex (dACC) activity during social rejection in high schizotypy has suggested self-distancing from rejection, earlier stages of mental processing such as feature encoding could also contribute to psychosis-like experiences. This study aimed to determine the stage of mental processing of social rejection that relates to positive schizotypy. Forty-one healthy participants were assessed for schizotypy and RS. Event-related potential amplitudes (ERPs) were measured at frontal, temporal and parieto-occipital sites and their cortical sources (dACC, temporal POLE and lingual gyrus) at early (N100) and late (P300 and late slow wave, LSW) timeframes during rejection, acceptance and neutral scenes. ERPs were compared between social interaction types. Correlations were performed between positive schizotypy (defined as the presence of perceptual aberrations, hallucinatory experiences and magical thinking), RS and ERPs during rejection. Amplitude was greater during rejection than acceptance or neutral conditions at the dACC-P300, parieto-occipital-P300, dACC-LSW and frontal-LSW. RS correlated positively with positive schizotypy. Reduced dACC N100 activity during rejection correlated with greater positive schizotypy and RS. Reduced dACC N100 activity and greater RS independently predicted positive schizotypy. An N100 deficit that indicates reduced feature encoding of rejection scenes increases with greater positive schizotypy and RS. Higher RS shows that a greater tendency to misattribute ambiguous social situations as rejecting also increases with positive schizotypy. These two processes, namely primary bottom-up sensory processing and secondary misattribution of rejection, combine to increase psychosis-like experiences. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 103 | Behav. Brain Res. 2015 Oct 293: 74-80 |
| PMID | 26192913 |
| Title | Standardized extract of Ficus platyphylla reverses apomorphine-induced changes in prepulse inhibition and locomotor activity in rats. |
| Abstract | Preparations of Ficus platyphylla are used in Nigeria's folk medicine to manage a plethora of diseases including, insomnia, psychoses, depression, epilepsy, pain and inflammation. In this study, we examined the effects of the standardized methanol extract of F. platyphylla stem bark (FP) on apomorphine-induced changes in prepulse inhibition and locomotor activity in rats, as well as on the retrieval of a conditioned reaction in one-way active avoidance in mice. FP did not affect basal prepulse inhibition, but significantly reduced locomotor activity. The apomorphine-induced prepulse inhibition deficit and hyperactivity were significantly reversed by co-administration of clozapine or FP. Furthermore, FP inhibited the retrieval of a conditioned avoidance reaction. Our results revealed that FP contains psychoactive ingredients with neuroleptic-like properties, thus supporting the isolation and development of the biologically active components of this medicinal plant as antipsychotic agents. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 104 | Hum Brain Mapp 2015 Jan 36: 378-90 |
| PMID | 25220293 |
| Title | A genome-wide supported psychiatric risk variant in NCAN influences brain function and cognitive performance in healthy subjects. |
| Abstract | The A allele of the single nucleotide polymorphism (SNP) rs1064395 in the NCAN gene has recently been identified as a susceptibility factor for bipolar disorder and schizophrenia. NCAN encodes neurocan, a brain-specific chondroitin sulfate proteoglycan that is thought to influence neuronal adhesion and migration. Several lines of research suggest an impact of NCAN on neurocognitive functioning. In the present study, we investigated the effects of rs1064395 genotype on neural processing and cognitive performance in healthy subjects. Brain activity was measured with functional magnetic resonance imaging (fMRI) during an overt semantic verbal fluency task in 110 healthy subjects who were genotyped for the NCAN SNP rs1064395. Participants additionally underwent comprehensive neuropsychological testing. Whole brain analyses revealed that NCAN risk status, defined as AA or AG genotype, was associated with a lack of task-related deactivation in a large left lateral temporal cluster extending from the middle temporal gyrus to the temporal POLE. Regarding neuropsychological measures, risk allele carriers demonstrated poorer immediate and delayed verbal memory performance when compared to subjects with GG genotype. Better verbal memory performance was significantly associated with greater deactivation of the left temporal cluster during the fMRI task in subjects with GG genotype. The current data demonstrate that common genetic variation in NCAN influences both neural processing and cognitive performance in healthy subjects. Our study provides new evidence for a specific genetic influence on human brain function. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 105 | Sci Rep 2015 -1 5: 17650 |
| PMID | 26632639 |
| Title | Neural substrate of quality of life in patients with schizophrenia: a magnetisation transfer imaging study. |
| Abstract | The aim of this study was to investigate the neural substrate underlying quality of life (QoL) and to demonstrate the microstructural abnormalities associated with impaired QoL in a large sample of patients with schizophrenia, using magnetisation transfer imaging. A total of 81 right-handed men with a diagnosis of schizophrenia and 25 age- and sex-similar healthy controls were included and underwent a 3T MRI with magnetization transfer ratio (MTR) to detect microstructural abnormalities. Compared with healthy controls, patients with schizophrenia had grey matter (GM) decreased MTR values in the temporal lobe (BA21, BA37 and BA38), the bilateral insula, the occipital lobe (BA17, BA18 and BA19) and the cerebellum. Patients with impaired QoL had lower GM MTR values relative to patients with preserved QoL in the bilateral temporal POLE (BA38), the bilateral insula, the secondary visual cortex (BA18), the vermis and the cerebellum. Significant correlations between MTR values and QoL scores (p < 0.005) were observed in the GM of patients in the right temporal POLE (BA38), the bilateral insula, the vermis and the right cerebellum. Our study shows that QoL impairment in patients with schizophrenia is related to the microstructural changes in an extensive network, suggesting that QoL is a bio-psychosocial marker. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 106 | J. Neurosci. 2015 Aug 35: 11266-80 |
| PMID | 26269635 |
| Title | Zic2 Controls the Migration of Specific Neuronal Populations in the Developing Forebrain. |
| Abstract | Human mutations in ZIC2 have been identified in patients with holoprosencephaly and schizophrenia. Similarly, Zic2 mutant mice exhibit holoprosencephaly in homozygosis and behavioral and morphological schizophrenic phenotypes associated with forebrain defects in heterozygosis. Despite the devastating effects of mutations in Zic2, the cellular and molecular mechanisms that provoke Zic2-deficiency phenotypes are yet unclear. Here, we report a novel role for this transcription factor in the migration of three different types of forebrain neurons: the Cajal-Retzius cells that populate the surface of the telencephalic vesicles, an amygdaloid group of cells originated in the caudal POLE of the telencephalic pallium, and a cell population that travels from the prethalamic neuroepithelium to the ventral lateral geniculate nucleus. Our results also suggest that the receptor EphB1, previously identified as a Zic2 target, may mediate, at least partially, Zic2-dependent migratory events. According to these results, we propose that deficiencies in cell motility and guidance contribute to most of the forebrain pathologies associated with Zic2 mutations. Although the phenotype of Zic2 mutant individuals was reported more than 10 years ago, until now, the main function of this transcription factor during early development has not been precisely defined. Here, we reveal a previously unknown role for Zic2 in the migration of forebrain neurons such as Cajal-Retzius cells, interneurons moving to the ventral lateral geniculate nucleus, and neocortical cells going to the amygdala. We believe that the role of this transcription factor in certain populations of migratory cells contributes to defects in cortical layering and hypocellularity in the ventral LGN and amygdala and will contribute to our understanding of the devastating phenotypes associated with Zic2 mutations in both humans and mice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 107 | Schizophr. Res. 2015 Jun 165: 90-3 |
| PMID | 25892719 |
| Title | Reduced default mode network connectivity in schizophrenia patients. |
| Abstract | In the present study, we explored possible alterations in the default mode network (DMN) and its functional connectivity in 41 schizophrenia patients and 42 age-matched healthy controls. schizophrenia patients displayed reduced activation in the ventromedial prefrontal cortex, left superior temporal gyrus including auditory cortex and temporal POLE. Psychophysiological interaction analysis revealed reduced connectivity between left superior temporal gyrus including auditory cortex and the left temporal POLE in schizophrenia patients compared to healthy subjects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 108 | Sci Rep 2015 -1 5: 11258 |
| PMID | 26058049 |
| Title | Selective Functional Disconnection of the Dorsal Subregion of the Temporal Pole in Schizophrenia. |
| Abstract | Although extensive resting-state functional connectivity (rsFC) changes have been reported in schizophrenia, rsFC changes in the temporal POLE (TP) remain unknown. The TP contains several subregions with different connection patterns; however, it is not known whether TP subregions are differentially affected in schizophrenia. Sixty-six schizophrenia patients and 76 healthy comparison subjects underwent resting-state fMRI using a sensitivity-encoded spiral-in (SENSE-SPIRAL) imaging sequence to reduce susceptibility-induced signal loss and distortion. The TP was subdivided into the dorsal (TPd) and ventral (TPv) subregions. Mean fMRI time series were extracted for each TP subregion and entered into a seed-based rsFC analysis. Direct between-group comparisons revealed reduced rsFC between the right TPd and brain regions involved in language processing and multisensory integration in schizophrenia, including the left superior temporal gyrus, left mid-cingulate cortex, and right insular cortex. The rsFC changes of the right TPd in schizophrenia were independent of the grey matter reduction of this subregion. Moreover, these rsFC changes were unrelated to illness severity, duration of illness and antipsychotic medication dosage. No significant group differences were observed in the rsFC of the left TPd and bilateral TPv subregions. These findings suggest a selective (the right TPd) functional disconnection of TP subregions in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 109 | J Psychiatr Res 2015 Jun 65: 80-6 |
| PMID | 25937503 |
| Title | Reduced paralimbic system gray matter volume in schizophrenia: Correlations with clinical variables, symptomatology and cognitive function. |
| Abstract | Psychopathy is associated with dysfunction in regions that compose the paralimbic system, such as the orbitofrontal cortex (OFC), insular cortex (IC), temporal POLE (TP), parahippocampal gyrus (PHG) and cingulate cortex (CC). However, findings of structural alterations in these regions are inconsistent in schizophrenia, and correlations between paralimbic system measures and symptomatology and cognitive function have not been investigated. 93 patients with schizophrenia and 99 healthy controls received structural magnetic resonance imaging and clinical and cognitive assessment. We compared gray matter volume (GMV) between the two groups using voxel-based morphometry, and evaluated correlations between abnormal GMVs and clinical variables, symptomatology and cognitive function. The assessment of cognition included measures of processing speed, verbal fluency and memory. Patients with schizophrenia demonstrated significant GMV decreases in the paralimbic system, including bilateral OFC, IC and TP (p < 0.05, FWE corrected). GMV decreases were also observed in bilateral superior temporal gyri (STG). The GMVs in bilateral OFC, left IC, left TP and bilateral STG were positively correlated with processing speed, and the GMVs in bilateral OFC were positively correlated with memory function in all participants. In our patient group, the GMV deficits were also associated with earlier age of onset, longer duration of illness, greater number of hospitalizations and more severe positive symptoms. GMVs in the paralimbic system were significantly reduced in schizophrenia, and these abnormalities were correlated with clinical variables, symptomatology and cognitive function. These results suggest the paralimbic system plays an important role in the pathophysiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 110 | Neurosci Bull 2015 Jun 31: 275-87 |
| PMID | 25813916 |
| Title | Compromised small-world efficiency of structural brain networks in schizophrenic patients and their unaffected parents. |
| Abstract | Several lines of evidence suggest that efficient information integration between brain regions is disrupted in schizophrenia. Abnormalities in white matter tracts that interconnect brain regions may be directly relevant to this pathophysiological process. As a complex mental disorder with high heritability, mapping abnormalities in patients and their first-degree relatives may help to disentangle the risk factors for schizophrenia. We established a weighted network model of white matter connections using diffusion tensor imaging in 25 nuclear families with schizophrenic probands (19 patients and 41 unaffected parents) and two unrelated groups of normal controls (24 controls matched with patients and 26 controls matched with relatives). The patient group showed lower global efficiency and local efficiency. The decreased regional efficiency was localized in hubs such as the bilateral frontal cortices, bilateral anterior cingulate cortices, and left precuneus. The global efficiency was negatively correlated with cognition scores derived from a 5-factor model of schizophrenic psychopathology. We also found that unaffected parents displayed decreased regional efficiency in the right temporal cortices, left supplementary motor area, left superior temporal POLE, and left thalamus. The global efficiency tended to be lower in unaffected parents. Our data suggest that (1) the global efficiency loss in neuroanatomical networks may be associated with the cognitive disturbances in schizophrenia; and (2) genetic vulnerability to schizophrenia may influence the anatomical organization of an individual's brain networks. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 111 | Doc Ophthalmol 2015 Aug 131: 35-41 |
| PMID | 25791769 |
| Title | Aripiprazole-induced chorioretinopathy: multimodal imaging and electrophysiological features. |
| Abstract | To report the first documented case of aripiprazole-induced chorioretinopathy. A 47-year-old schizophrenic patient with loss of vision due to an atypical retinopathy was investigated. She had been treated with aripiprazole for 8 years. Multimodal imaging showed in the right eye a large area of retinal atrophy predominating in the outer retina, including the posterior POLE up to the upper temporal periphery, and in the left eye a serous retinal detachment. The electroretinogram exhibited decreased and delayed responses of both the rod and cone systems; the electrooculogram showed no light peak. Aripiprazole, an atypical antipsychotic, was introduced more recently than the antipsychotics commonly incriminated in chorioretinopathies, such as thioridazine. Optical coherence tomography was not used to document former cases of antipsychotic-related chorioretinopathies. Although pathophysiological mechanisms are poorly understood, imaging of the present case points toward an involvement of the retinal pigmentary epithelium. Clinicians should be aware of the potential chorioretinal toxicity of new atypical antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 112 | PLoS ONE 2015 -1 10: e0119176 |
| PMID | 25748858 |
| Title | The selective impairment of resting-state functional connectivity of the lateral subregion of the frontal pole in schizophrenia. |
| Abstract | Although extensive resting-state functional connectivity (rsFC) changes have been reported in schizophrenia, rsFC changes of the frontal POLE (FP) remain unclear. The FP contains several subregions with different connection patterns; however, it is unknown whether the FP subregions are differentially affected in schizophrenia. To explore this possibility, we compared rsFC differences of the FP subregions between schizophrenia patients and healthy controls. One hundred healthy controls and 91 patients with schizophrenia underwent resting-state functional MRI with a sensitivity-encoded spiral-in (SENSE-SPIRAL) imaging sequence to reduced susceptibility-induced signal loss and distortion. The FP was subdivided into the orbital (FPo), medial (FPm), and lateral (FPl) subregions. Mean fMRI time series were extracted for each FP subregion and entered into a seed-based rsFC analysis. The FP subregions exhibited differential rsFC patterns in both healthy controls and schizophrenia patients. Direct comparison between groups revealed reduced rsFCs between the bilateral FPl and several cognitive-related regions, including the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex/precuneus, temporal cortex and inferior parietal lobule in schizophrenia. Although the FPl exhibited obvious atrophy, rsFC changes were unrelated to volumetric atrophy in the FPl, to duration of illness, and to antipsychotic medication dosage. No significant differences were observed in the rsFCs of other FP subregions. These findings suggest a selective (the lateral subregion) functional disconnection of the FP subregions in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 113 | Schizophr Bull 2015 Jan 41: 223-32 |
| PMID | 24619536 |
| Title | Visual hallucinations are associated with hyperconnectivity between the amygdala and visual cortex in people with a diagnosis of schizophrenia. |
| Abstract | While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH. We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory). Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal POLE and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting. VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 114 | J. Neurosci. 2015 Aug 35: 11266-80 |
| PMID | 26269635 |
| Title | Zic2 Controls the Migration of Specific Neuronal Populations in the Developing Forebrain. |
| Abstract | Human mutations in ZIC2 have been identified in patients with holoprosencephaly and schizophrenia. Similarly, Zic2 mutant mice exhibit holoprosencephaly in homozygosis and behavioral and morphological schizophrenic phenotypes associated with forebrain defects in heterozygosis. Despite the devastating effects of mutations in Zic2, the cellular and molecular mechanisms that provoke Zic2-deficiency phenotypes are yet unclear. Here, we report a novel role for this transcription factor in the migration of three different types of forebrain neurons: the Cajal-Retzius cells that populate the surface of the telencephalic vesicles, an amygdaloid group of cells originated in the caudal POLE of the telencephalic pallium, and a cell population that travels from the prethalamic neuroepithelium to the ventral lateral geniculate nucleus. Our results also suggest that the receptor EphB1, previously identified as a Zic2 target, may mediate, at least partially, Zic2-dependent migratory events. According to these results, we propose that deficiencies in cell motility and guidance contribute to most of the forebrain pathologies associated with Zic2 mutations. Although the phenotype of Zic2 mutant individuals was reported more than 10 years ago, until now, the main function of this transcription factor during early development has not been precisely defined. Here, we reveal a previously unknown role for Zic2 in the migration of forebrain neurons such as Cajal-Retzius cells, interneurons moving to the ventral lateral geniculate nucleus, and neocortical cells going to the amygdala. We believe that the role of this transcription factor in certain populations of migratory cells contributes to defects in cortical layering and hypocellularity in the ventral LGN and amygdala and will contribute to our understanding of the devastating phenotypes associated with Zic2 mutations in both humans and mice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 115 | Neurosci Bull 2015 Jun 31: 275-87 |
| PMID | 25813916 |
| Title | Compromised small-world efficiency of structural brain networks in schizophrenic patients and their unaffected parents. |
| Abstract | Several lines of evidence suggest that efficient information integration between brain regions is disrupted in schizophrenia. Abnormalities in white matter tracts that interconnect brain regions may be directly relevant to this pathophysiological process. As a complex mental disorder with high heritability, mapping abnormalities in patients and their first-degree relatives may help to disentangle the risk factors for schizophrenia. We established a weighted network model of white matter connections using diffusion tensor imaging in 25 nuclear families with schizophrenic probands (19 patients and 41 unaffected parents) and two unrelated groups of normal controls (24 controls matched with patients and 26 controls matched with relatives). The patient group showed lower global efficiency and local efficiency. The decreased regional efficiency was localized in hubs such as the bilateral frontal cortices, bilateral anterior cingulate cortices, and left precuneus. The global efficiency was negatively correlated with cognition scores derived from a 5-factor model of schizophrenic psychopathology. We also found that unaffected parents displayed decreased regional efficiency in the right temporal cortices, left supplementary motor area, left superior temporal POLE, and left thalamus. The global efficiency tended to be lower in unaffected parents. Our data suggest that (1) the global efficiency loss in neuroanatomical networks may be associated with the cognitive disturbances in schizophrenia; and (2) genetic vulnerability to schizophrenia may influence the anatomical organization of an individual's brain networks. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 116 | Aust N Z J Psychiatry 2016 Mar 50: 275-83 |
| PMID | 26013316 |
| Title | Changes in cortical N-methyl-d-aspartate receptors and post-synaptic density protein 95 in schizophrenia, mood disorders and suicide. |
| Abstract | In humans, depending on dose, blocking the N-methyl-d-aspartate receptor (NMDAR) with ketamine can cause psychomimetic or antidepressant effects. The overall outcome for drugs such as ketamine depends on dose and the number of its available binding sites in the central nervous system, and to understand something of the latter variable we measure NMDAR in the frontal POLE, dorsolateral prefrontal, anterior cingulate and parietal cortices from people with schizophrenia, bipolar disorder, major depressive disorders and age/sex matched controls. We measured levels of NMDARs (using [(3)H]MK-801 binding) and NMDAR sub-unit mRNAs (GRINs: using in situ hybridisation) as well as post-synaptic density protein 95 (anterior cingulate cortex only; not major depressive disorders: an NMDAR post-synaptic associated protein) in bipolar disorder, schizophrenia and controls. Compared to controls, levels of NMDAR were lower in the outer laminae of the dorsolateral prefrontal cortex (-17%, p?=?0.01) in people with schizophrenia. In bipolar disorder, levels of NMDAR binding (laminae IV-VI; -19%, p?POLE (+22%, p?These data suggest that differences in cortical NMDAR expression and post-synaptic density protein 95 are present in psychiatric disorders and suicide completion and may contribute to different responses to ketamine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 117 | Schizophr Bull 2016 Apr -1: -1 |
| PMID | 27060129 |
| Title | Reduced Frontoparietal Activity in Schizophrenia Is Linked to a Specific Deficit in Goal Maintenance: A Multisite Functional Imaging Study. |
| Abstract | Patients with schizophrenia (SZ) previously demonstrated specific deficits in an executive function known as goal maintenance, associated with reduced middle frontal gyrus (MFG) activity. This study aimed to validate a new tool-the Dot Pattern Expectancy (DPX) task-developed to facilitate multisite imaging studies of goal maintenance deficits in SZ or other disorders. Additionally, it sought to arrive at recommendations for scan length for future studies using the DPX. Forty-seven SZ and 56 healthy controls (HC) performed the DPX in 3-Tesla functional magnetic resonance imaging (fMRI) scanners at 5 sites. Group differences in DPX-related activity were examined with whole brain voxelwise analyses. SZs showed the hypothesized specific performance deficits with as little as 1 block of data. Reduced activity in SZ compared with HC was observed in bilateral frontal POLE/MFG, as well as left posterior parietal lobe. Efficiency analyses found significant group differences in activity using 18 minutes of scan data but not 12 minutes. Several behavioral and imaging findings from the goal maintenance literature were robustly replicated despite the use of different scanners at different sites. We did not replicate a previous correlation with disorganization symptoms among patients. Results were consistent with an executive/attention network dysfunction in the higher levels of a cascading executive system responsible for goal maintenance. Finally, efficiency analyses found that 18 minutes of scanning during the DPX task is sufficient to detect group differences with a similar sample size. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 118 | Schizophr Bull 2016 May 42: 790-801 |
| PMID | 26675295 |
| Title | Initial and Progressive Gray Matter Abnormalities in Insular Gyrus and Temporal Pole in First-Episode Schizophrenia Contrasted With First-Episode Affective Psychosis. |
| Abstract | Although the insula and temporal POLE (TP) of paralimbic regions are important in both affective and cognitive processing, it is not well known whether gray matter volume (GMV) abnormalities in these regions show post-onset progression and differentially affect first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients. To determine whether there are initial and progressive GMV deficits in insula and TP in FESZ and FEAFF (mainly manic) patients, their relative specificity to FESZ or FEAFF, and relationship to symptoms, we conducted a naturalistic study at first hospitalization for psychosis and follow-up ~1.5 years later. Initial 1.5T magnetic resonance imaging (MRI) scans and follow-up scans were on the same scanner. Twenty-two FESZ, 23 FEAFF, and 23 healthy control (HC) subjects were group matched for age, gender, parental socioeconomic status, and handedness. At first hospitalization, FESZ showed significantly smaller bilateral insular GMV compared with FEAFF, and smaller left TP GMV compared with FEAFF and HC. Moreover, on 1.5 years follow-up, FESZ showed progressive GMV decreases in bilateral insula compared with FEAFF and HC, and in TP GMV compared with HC. In contrast, FEAFF showed no progression. Progression of FESZ GMV in both insula and TP was inversely associated with changes in the overall Brief Psychiatric Rating Scale symptom score, indicating less improvement or worsening of symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 119 | Schizophr. Res. 2016 Jan 170: 123-9 |
| PMID | 26621001 |
| Title | Alterations of lateral temporal cortical gray matter and facial memory as vulnerability indicators for schizophrenia: An MRI study in youth at familial high-risk for schizophrenia. |
| Abstract | Structural alterations of the lateral temporal cortex (LTC) in association with memory impairments have been reported in schizophrenia. This study investigated whether alterations of LTC structure were linked with impaired facial and/or verbal memory in young first-degree relatives of people with schizophrenia and, thus, may be indicators of vulnerability to the illness. Subjects included 27 non-psychotic, first-degree relatives of schizophrenia patients, and 48 healthy controls, between the ages of 13 and 28. Participants underwent high-resolution magnetic resonance imaging (MRI) at 1.5Tesla. The LTC was parcellated into superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and temporal POLE. Total cerebral and LTC volumes were measured using semi-automated morphometry. The Wechsler Memory Scale - Third Edition and the Children's Memory Scale - Third Edition assessed facial and verbal memory. General linear models tested for associations among LTC subregion volumes, familial risk and memory. Compared with controls, relatives had significantly smaller bilateral middle temporal gyri. Moreover, right middle temporal gyral volume showed a significant positive association with delayed facial memory in relatives. These results support the hypothesis that smaller middle temporal gyri are related to the genetic liability to schizophrenia and may be linked with reduced facial memory in persons at genetic risk for the illness. The findings add to the growing evidence that children at risk for schizophrenia on the basis of positive family history have cortical and subcortical structural brain abnormalities well before psychotic illness occurs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 120 | Hum Brain Mapp 2016 Feb 37: 491-500 |
| PMID | 26510167 |
| Title | Associations between polygenic risk for schizophrenia and brain function during probabilistic learning in healthy individuals. |
| Abstract | A substantial proportion of schizophrenia liability can be explained by additive genetic factors. Risk profile scores (RPS) directly index risk using a summated total of common risk variants weighted by their effect. Previous studies suggest that schizophrenia RPS predict alterations to neural networks that support working memory and verbal fluency. In this study, we apply schizophrenia RPS to fMRI data to elucidate the effects of polygenic risk on functional brain networks during a probabilistic-learning neuroimaging paradigm. The neural networks recruited during this paradigm have previously been shown to be altered to unmedicated schizophrenia patients and relatives of schizophrenia patients, which may reflect genetic susceptibility. We created schizophrenia RPS using summary data from the Psychiatric Genetic Consortium (schizophrenia Working Group) for 83 healthy individuals and explore associations between schizophrenia RPS and blood oxygen level dependency (BOLD) during periods of choice behavior (switch-stay) and reflection upon choice outcome (reward-punishment). We show that schizophrenia RPS is associated with alterations in the frontal POLE (PWHOLE-BRAIN-CORRECTED = 0.048) and the ventral striatum (PROI-CORRECTED = 0.036), during choice behavior, but not choice outcome. We suggest that the common risk variants that increase susceptibility to schizophrenia can be associated with alterations in the neural circuitry that support the processing of changing reward contingencies. Hum Brain Mapp 37:491-500, 2016. © 2015 Wiley Periodicals, Inc. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 121 | Mol. Psychiatry 2016 May 21: 686-92 |
| PMID | 26169975 |
| Title | Association of serum VEGF levels with prefrontal cortex volume in schizophrenia. |
| Abstract | A large body of evidence indicates alterations in brain regional cellular energy metabolism and blood flow in schizophrenia. Among the different molecules regulating blood flow, vascular endothelial growth factor (VEGF) is generally accepted as the major factor involved in the process of angiogenesis. In the present study, we examined whether peripheral VEGF levels correlate with changes in the prefrontal cortex (PFC) volume in patients with schizophrenia and in healthy controls. Whole-blood samples were obtained from 96 people with schizophrenia or schizoaffective disorder and 83 healthy controls. Serum VEGF protein levels were analyzed by enzyme-linked immunosorbent assay, whereas quantitative PCR was performed to measure interleukin-6 (IL-6, a pro-inflammatory marker implicated in schizophrenia) mRNA levels in the blood samples. Structural magnetic resonance imaging scans were obtained using a 3T Achieva scanner on a subset of 59 people with schizophrenia or schizoaffective disorder and 65 healthy controls, and prefrontal volumes were obtained using FreeSurfer software. As compared with healthy controls, individuals with schizophrenia had a significant increase in log-transformed mean serum VEGF levels (t(177)=2.9, P=0.005). A significant inverse correlation (r=-0.40, P=0.002) between serum VEGF and total frontal POLE volume was found in patients with schizophrenia/schizoaffective disorder. Moreover, we observed a significant positive association (r=0.24, P=0.03) between serum VEGF and IL-6 mRNA levels in patients with schizophrenia. These findings suggest an association between serum VEGF and inflammation, and that serum VEGF levels are related to structural abnormalities in the PFC of people with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 122 | Brain Struct Funct 2016 Jan 221: 447-61 |
| PMID | 25362539 |
| Title | Cortical thickness and surface area in neonates at high risk for schizophrenia. |
| Abstract | schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal POLE, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal POLE, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly smaller cortical surface area in the right pars triangularis (before FDR correction), compared with control neonates. This preliminary study provides the first evidence that early development of cortical thickness and surface area might be abnormal in the neonates at genetic risk for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |