| 1 | Genomics 2002 May 79: 635-56 |
|---|---|
| PMID | 11991713 |
| Title | An evaluation of the assembly of an approximately 15-Mb region on human chromosome 13q32-q33 linked to bipolar disorder and schizophrenia. |
| Abstract | The human 13q32-q33 region has been linked to both bipolar disorder and schizophrenia. Before completion of the draft sequences, we developed an approximately 15-Mb comprehensive map for the region extending from D13S1300 to ATA35H12. This map was assembled using publicly available mapping data and sequence-tagged site (STS)-based PCR confirmation. We then compared this map with the NCBI, Celera Genomics, and UCSC Golden Path data in February, June, and September 2001. All data sets showed gaps, misassignment of STSs, and errors in orientation and marker order. Surprisingly, the completed sequences of many bacterial artificial chromosomes (BACs) had been truncated. Of 21 gaps that were detected, 4 were present in both the NCBI and Celera databases. All gaps could be filled using 1-2 BAC clones. A total of 39 loci mapped to additional sites within the human genome, providing evidence of segmental duplications. Additionally, 61 unique cDNA clones were sequenced to increase available transcribed sequence, and 11,353 reference single-nucleotide polymorphisms (SNPs) with an average density of 1 SNP/3720 bases were identified. Overall, integration of the data from multiple sources is still needed for complete assembly of the 13q32-q33 region. (c) |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 2 | Genomics 2002 Apr 79: 560-72 |
| PMID | 11944989 |
| Title | An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders. |
| Abstract | Human chromosome Xp11.3-Xp11.23 encompasses the map location for a growing number of diseases with a genetic basis or genetic component. These include several eye disorders, syndromic and nonsyndromic forms of X-linked mental retardation (XLMR), X-linked neuromuscular diseases and susceptibility loci for schizophrenia, type 1 diabetes, and Graves' disease. We have constructed an approximately 2.7-Mb high-resolution physical map extending from DXS8026 to ELK1, corresponding to a genetic distance of approximately 5.5 cM. A combination of chromosome walking and sequence-tagged site (STS)-content mapping resulted in an integrated framework and transcript map, precisely positioning 10 polymorphic microsatellites (one of which is novel), 16 ESTS, and 12 known genes (RP2, PCTK1, UHX1, UBE1, RBM10, ZNF157, SYN1, ARAF1, TIMP1, PFC, ELK1, UXT). The composite map is currently anchored with 89 STSs to give an average resolution of approximately 1 STS every 30 kb. By a combination of EST database searches and in silico detection of UniGene clusters within genomic sequence generated from this template map, we have mapped several novel genes within this interval: a Na+/H+ exchanger (SLC9A7), at least two zincfinger transcription factors (KIAA0215 and Hs.68318), carbohydrate sulfotransferase-7 (CHST7), regucalcin (RGN), inactivation-escape-1 (INE1), the human ortholog of mouse neuronal protein 15.6, and four putative novel genes. Further genomic analysis enabled annotation of the sequence interval with 20 predicted pseudogenes and 21 UniGene clusters of unknown function. The combined PAC/BAC transcript map and YAC scaffold presented here clarifies previously conflicting data for markers and genes within the Xp11.3-Xp11.23 interval and provides a powerful integrated resource for functional characterization of this clonally unstable, yet gene-rich and clinically significant region of proximal Xp. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 3 | Psychiatry Res 2008 Apr 158: 287-96 |
| PMID | 18262285 |
| Title | Gaze-triggered orienting is reduced in chronic schizophrenia. |
| Abstract | Patients with schizophrenia have been reported to demonstrate subtle impairment in gaze processing, which in some cases indicates hypersensitivity to gaze, while in others, hyposensitivity. The neural correlate of gaze processing is situated in the superior temporal sulcus (STS), a major portion of which is constituted by the superior temporal gyrus (STG), and may be the underlying dysfunctional neural basis to the abnormal gaze sensitivity in schizophrenia. To identify the characteristics of gaze behavior in patients with chronic schizophrenia, in whom the STG has been reported to be smaller in volume, we tested 22 patients (mean duration of illness 29 years) in a spatial cueing paradigm using two central pictorial gaze cues, both of which effectively triggered attentional orienting in 22 age-matched normal controls. Arrow cues were also employed to determine whether any compromise in schizophrenia, if present, was gaze-specific. Results demonstrated that schizophrenic subjects benefit significantly less from congruent cues than normal subjects, which was evident for gaze cues but not for arrow cues. This finding is suggestive of a relatively gaze-specific hyposensitivity in patients with chronic schizophrenia, a finding that is in line with their clinical symptomatology and that may be associated with a hypoactive STS. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 4 | Psychiatry Res 2008 Apr 158: 287-96 |
| PMID | 18262285 |
| Title | Gaze-triggered orienting is reduced in chronic schizophrenia. |
| Abstract | Patients with schizophrenia have been reported to demonstrate subtle impairment in gaze processing, which in some cases indicates hypersensitivity to gaze, while in others, hyposensitivity. The neural correlate of gaze processing is situated in the superior temporal sulcus (STS), a major portion of which is constituted by the superior temporal gyrus (STG), and may be the underlying dysfunctional neural basis to the abnormal gaze sensitivity in schizophrenia. To identify the characteristics of gaze behavior in patients with chronic schizophrenia, in whom the STG has been reported to be smaller in volume, we tested 22 patients (mean duration of illness 29 years) in a spatial cueing paradigm using two central pictorial gaze cues, both of which effectively triggered attentional orienting in 22 age-matched normal controls. Arrow cues were also employed to determine whether any compromise in schizophrenia, if present, was gaze-specific. Results demonstrated that schizophrenic subjects benefit significantly less from congruent cues than normal subjects, which was evident for gaze cues but not for arrow cues. This finding is suggestive of a relatively gaze-specific hyposensitivity in patients with chronic schizophrenia, a finding that is in line with their clinical symptomatology and that may be associated with a hypoactive STS. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 5 | Schizophr. Res. 2008 Feb 99: 164-75 |
| PMID | 18053686 |
| Title | Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders. |
| Abstract | schizophrenia and autism both feature significant impairments in social cognition and social functioning, but the specificity and mechanisms of these deficits remain unknown. Recent research suggeSTS that social cognitive deficits in both disorders may arise from dysfunctions in the neural systems that underlie social cognition. We explored the neural activation of discrete brain regions implicated in social cognitive and face processing in schizophrenia subgroups and autism spectrum disorders during complex social judgments of faces. Twelve individuals with autism spectrum disorders (ASD), 12 paranoid individuals with schizophrenia (P-SCZ), 12 non-paranoid individuals with schizophrenia (NP-SCZ), and 12 non-clinical healthy controls participated in this cross sectional study. Neural activation, as indexed by blood oxygenation level dependent (BOLD) contrast, was measured in a priori regions of interest while individuals rated faces for trustworthiness. All groups showed significant activation of a social cognitive network including the amygdala, fusiform face area (FFA), superior temporal sulcus (STS), and ventrolateral prefrontal cortex (VLPFC) while completing a task of complex social cognition (i.e. trustworthiness judgments). ASD and P-SCZ individuals showed significantly reduced neural activation in the right amygdala, FFA, and left VLPFC as compared to controls and in the left VLPFC as compared to NP-SCZ individuals during this task. These findings lend support to models hypothesizing well-defined neural substrates of social cognition and suggest a specific neural mechanism that may underlie social cognitive impairments in both autism and paranoid schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 6 | Psychiatry Res 2009 Feb 171: 82-93 |
| PMID | 19185468 |
| Title | Reduced language lateralization in first-episode schizophrenia: an fMRI index of functional asymmetry. |
| Abstract | Patients with schizophrenia exhibit a decrease or loss of normal anatomical brain asymmetry that also extends to functional levels. We applied functional magnetic resonance imaging (fMRI) to investigate language lateralization in patients with schizophrenia during their first episode of illness, thus excluding effects of chronic illness and treatment. Brain regions activated during language tasks of verb generation and passive music listening were explored in 12 first-episode patients with schizophrenia and 17 healthy controls. Regions of interest corresponded to Broca's area in the inferior frontal gyrus (IFG) and Wernicke's area in the superior temporal sulcus (STS). Patients with schizophrenia had significantly smaller lateralization indices in language-related regions than controls. A similar effect was observed in their IFG and STS regions. There was no difference between the groups in the auditory cortex for the music task. Patients with schizophrenia demonstrated greater activation than the controls in temporal regions: the difference was larger in patients with more severe positive symptom subscores. In conclusion, patients with schizophrenia demonstrated loss of normal functional brain asymmetry, as reflected in diminished lateralization of language-related activation in frontal and temporal regions. This phenomenon was already present during their first episode of psychosis, possibly reflecting developmental brain abnormalities of the illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 7 | Schizophr. Res. 2010 Aug 121: 75-89 |
| PMID | 20362418 |
| Title | Factors in sensory processing of prosody in schizotypal personality disorder: an fMRI experiment. |
| Abstract | Persons diagnosed with schizophrenia demonstrate deficits in prosody recognition. To examine prosody along the schizophrenia spectrum, antipsychotic-naïve schizotypal personality disorder (SPD) subjects and healthy control subjects were compared. It was hypothesized that SPD subjects would perform more poorly; with cognitive and demographic factors contributing to the poor performance. The superior temporal gyrus (STG) was selected as the region-of-interest (ROI) given its known abnormalities in SPD and its important role in the processing of prosody. SPD and healthy comparison (HC) subjects were matched on age, IQ, and parental social-economic status (PSES). Cognitive measures included the Speech Sound Perception Test (SSPT) to examine phonological processing (SPD=68, HC=74) and the Verbal Fluency task to examine executive functioning (SPD=129, HC=138). The main experiment was a novel fMRI task of prosody identification using semantically neutral sentences spoken with emotional prosody (SPD=16, HC=13). Finally, volumetric measurement of the superior temporal sulcus (STS), a key region for processing prosody, and partially overlapping with the STG, was performed (SPD=30, HC=30). Phonological processing and executive functioning were both impaired in SPD subjects compared with HC subjects. Contrary to the prediction, SPD subjects, as a group, were similar to HC subjects in terms of correctly indentifying the emotion conveyed and reaction time. Within the SPD group, prosody identification accuracy was influenced by executive functioning, IQ and perhaps PSES, relationships not found with HC subjects. Phonological perception aided prosody identification in both diagnostic groups. As expected, both groups activated the STG while performing the prosody identification task. However, SPD subjects may have been less "efficient" in their recruitment of STG neurons. Finally, SPD subjects demonstrated a trend toward smaller STS volumes on the left, particularly the lower bank. These data suggest that subtle differences between SPD and controls in phonological processing, executive functioning, IQ, and possibly PSES, contributed to difficulty in processing prosody for some SPD subjects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 8 | Schizophr. Res. 2010 Aug 121: 75-89 |
| PMID | 20362418 |
| Title | Factors in sensory processing of prosody in schizotypal personality disorder: an fMRI experiment. |
| Abstract | Persons diagnosed with schizophrenia demonstrate deficits in prosody recognition. To examine prosody along the schizophrenia spectrum, antipsychotic-naïve schizotypal personality disorder (SPD) subjects and healthy control subjects were compared. It was hypothesized that SPD subjects would perform more poorly; with cognitive and demographic factors contributing to the poor performance. The superior temporal gyrus (STG) was selected as the region-of-interest (ROI) given its known abnormalities in SPD and its important role in the processing of prosody. SPD and healthy comparison (HC) subjects were matched on age, IQ, and parental social-economic status (PSES). Cognitive measures included the Speech Sound Perception Test (SSPT) to examine phonological processing (SPD=68, HC=74) and the Verbal Fluency task to examine executive functioning (SPD=129, HC=138). The main experiment was a novel fMRI task of prosody identification using semantically neutral sentences spoken with emotional prosody (SPD=16, HC=13). Finally, volumetric measurement of the superior temporal sulcus (STS), a key region for processing prosody, and partially overlapping with the STG, was performed (SPD=30, HC=30). Phonological processing and executive functioning were both impaired in SPD subjects compared with HC subjects. Contrary to the prediction, SPD subjects, as a group, were similar to HC subjects in terms of correctly indentifying the emotion conveyed and reaction time. Within the SPD group, prosody identification accuracy was influenced by executive functioning, IQ and perhaps PSES, relationships not found with HC subjects. Phonological perception aided prosody identification in both diagnostic groups. As expected, both groups activated the STG while performing the prosody identification task. However, SPD subjects may have been less "efficient" in their recruitment of STG neurons. Finally, SPD subjects demonstrated a trend toward smaller STS volumes on the left, particularly the lower bank. These data suggest that subtle differences between SPD and controls in phonological processing, executive functioning, IQ, and possibly PSES, contributed to difficulty in processing prosody for some SPD subjects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 9 | Psychol Med 2010 Oct 40: 1607-17 |
| PMID | 20056024 |
| Title | Neuronal correlates of affective theory of mind in schizophrenia out-patients: evidence for a baseline deficit. |
| Abstract | schizophrenia out-patients have deficits in affective theory of mind (ToM) but also on more basal levels of social cognition, such as the processing of neutral and emotional expressions. These deficits are associated with changes in brain activation in the amygdala and the superior temporal sulcus (STS). However, until now there have been no studies that examined these different levels of social cognition and their neurobiological underpinnings in patients within one design. Sixteen medicated schizophrenia out-patients and 16 matched healthy controls were studied with functional magnetic resonance imaging (fMRI) during a social cognition task that allows the investigation of affective ToM (aToM), emotion recognition and the processing of neutral facial expressions. Patients showed a deficit in emotion recognition and a more prominent deficit in aToM. The performance in aToM and in emotion recognition was correlated in the control group but not in the schizophrenia group. Region-of-interest analysis of functional brain imaging data revealed no difference between groups during aToM, but a hyperactivation in the schizophrenia group in the left amygdala and right STS during emotion recognition and the processing of neutral facial expressions. The results indicate that schizophrenia out-patients have deficits at several levels of social cognition and provide the first evidence that deficits on higher-order social cognitive processes in schizophrenia may be traced back to an aberrant processing of faces per se. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 10 | 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 |
| 11 | Soc Neurosci 2011 -1 6: 548-58 |
| PMID | 21943127 |
| Title | Social impairment in schizophrenia revealed by Autism-Spectrum Quotient correlated with gray matter reduction. |
| Abstract | One of the difficulties facing schizophrenia patients is a failure to construct appropriate relationships with others in social situations. This impairment of social cognition is also found in autism-spectrum disorder (ASD). Considering such commonality between the two disorders, in this study we adopted the Autism-Spectrum Quotient (AQ) score to assess autistic traits, and explored the association between such traits and gray matter (GM) alterations of the brain in schizophrenia. Twenty schizophrenia patients and 25 healthy controls underwent structural magnetic resonance imaging (MRI), and AQ was assessed, comprising five subscales measuring different facets of autistic traits. Voxel-based morphometry (VBM) was applied to investigate the correlation between these AQ scores and regional GM alterations. schizophrenia patients showed significantly higher scores in total AQ, and in four of the five subscales, compared to healthy controls. The total AQ score in schizophrenia showed significant negative correlation with GM volume reduction in the cortical area surrounding the left superior temporal sulcus (STS), which is considered to be important in social perception. Our findings suggest a possible neuroanatomical basis of autistic tendencies in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 12 | Neuroimage 2011 Oct 58: 716-23 |
| PMID | 21723397 |
| Title | A robust cerebral asymmetry in the infant brain: the rightward superior temporal sulcus. |
| Abstract | In order to understand how genetic mutations might have favored language development in our species, we need a better description of the human brain at the beginning of life. As the linguistic network mainly involves the left perisylvian regions in adults, we used anatomical MRI to study the structural asymmetries of these regions in 14 preverbal infants. Our results show four significant asymmetries. First and foremost, they stress an important but little-known asymmetry: the larger depth of the right superior temporal sulcus (STS) at the base of Heschl's gyrus. Then, we characterized the early forward and upward shift of the posterior end of the right Sylvian fissure, the elongation of the left planum temporale as well as the thickening of the left Heschl's gyrus. The rightward bias of the STS is robust and large, and is not correlated with the leftward asymmetries of the planum and Heschl's gyrus, suggesting that different morphogenetic factors drive these asymmetries. As this sulcus is engaged in multiple high-level functions (e.g. language and theory of mind), and has been spotted as abnormal in several developmental disorders (e.g. schizophrenia, autism), this early rightward asymmetry should be further explored as a target for a genetic evolutionary pressure. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 13 | PLoS ONE 2011 -1 6: e25322 |
| PMID | 21998649 |
| Title | Autism spectrum disorders and schizophrenia: meta-analysis of the neural correlates of social cognition. |
| Abstract | Impaired social cognition is a cardinal feature of Autism Spectrum Disorders (ASD) and schizophrenia (SZ). However, the functional neuroanatomy of social cognition in either disorder remains unclear due to variability in primary literature. Additionally, it is not known whether deficits in ASD and SZ arise from similar or disease-specific disruption of the social cognition network. To identify regions most robustly implicated in social cognition processing in SZ and ASD. Systematic review of English language articles using MEDLINE (1995-2010) and reference liSTS. Studies were required to use fMRI to compare ASD or SZ subjects to a matched healthy control group, provide coordinates in standard stereotactic space, and employ standardized facial emotion recognition (FER) or theory of mind (TOM) paradigms. Activation foci from studies meeting inclusion criteria (n = 33) were subjected to a quantitative voxel-based meta-analysis using activation likelihood estimation, and encompassed 146 subjects with ASD, 336 SZ patients and 492 healthy controls. Both SZ and ASD showed medial prefrontal hypoactivation, which was more pronounced in ASD, while ventrolateral prefrontal dysfunction was associated mostly with SZ. Amygdala hypoactivation was observed in SZ patients during FER and in ASD during more complex ToM tasks. Both disorders were associated with hypoactivation within the Superior Temporal Sulcus (STS) during ToM tasks, but activation in these regions was increased in ASD during affect processing. Disease-specific differences were noted in somatosensory engagement, which was increased in SZ and decreased in ASD. Reduced thalamic activation was uniquely seen in SZ. Reduced frontolimbic and STS engagement emerged as a shared feature of social cognition deficits in SZ and ASD. However, there were disease- and stimulus-specific differences. These findings may aid future studies on SZ and ASD and facilitate the formulation of new hypotheses regarding their pathophysiology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 14 | Seishin Shinkeigaku Zasshi 2012 -1 114: 915-20 |
| PMID | 23012853 |
| Title | [Pathology of social brain and social cognitive impairments in schizophrenia]. |
| Abstract | schizophrenia patients often have a difficulty in constructing appropriate relationships with others in social situations. This impairment of social cognition is also found in autism-spectrum disorder (ASD). To elucidate the neural basis of such commonality between these two disorders, we explored the association between Autism-Spectrum Quotient (AQ) and gray matter (GM) alterations measured by MRI in schizophrenia subjects. schizophrenia patients showed significantly higher scores in total AQ compared with control subjects. In addition, the total AQ score in schizophrenia subjects showed significant negative correlation with GM volume in the cortical area surrounding the left superior temporal sulcus (STS). As STS is the area which has been reported to be pathological in ASD, our findings suggest a partial neuroanatomical commonality between ASD and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 15 | Psychiatry Res 2012 May 202: 155-60 |
| PMID | 22698762 |
| Title | Functional involvement of superior temporal sulcus in quality of life of patients with schizophrenia. |
| Abstract | The aim of this study was to investigate the neural substrate underlying quality of life (QoL) in patients with schizophrenia. Thirty-one right-handed patients were included. Patients were grouped according to 'high' and 'low' QoL levels. Whole-brain single photon emission computed tomography (SPECT) with (99m)Tc-labeled ethylcysteinate dimer ((99m)Tc-ECD), for the measurement of voxel-based regional cerebral blood flow (rCBF), was used to compare these two groups with Statistical Parametric Mapping. Correlations of rCBF with QoL scores were secondarily explored. Nineteen of the 31 patients had a high QoL level. There was no significant difference in demographic and clinical characteristics between patients with high and low QoL levels. In comparison to patients with low QoL, those with high QoL exhibited significant bilateral temporal hypoperfusions, primarily in the superior temporal sulcus (STS). In the total group of patients, perfusion in the left STS was negatively correlated with psychological well-being, self-esteem, and sentimental life, as well as with the global index of the questionnaire. This study shows that perfusion of the STS, a brain area thought to contribute to self/other awareness and metacognition, is involved in the functional substrate underlying QoL. Our findings contribute to clarifying the scientific foundation required for a better clinical use of QoL questionnaires by suggesting that the recognition of illness-related impairment is associated with alteration of QoL. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 16 | Schizophr. Res. 2013 Oct 150: 197-204 |
| PMID | 23932663 |
| Title | Deconstructing sub-clinical psychosis into latent-state and trait variables over a 30-year time span. |
| Abstract | Our aim was to deconstruct the variance underlying the expression of sub-clinical psychosis symptoms into portions associated with latent time-dependent states and time-invariant traits. We analyzed data of 335 subjects from the general population of Zurich, Switzerland, who had been repeatedly measured between 1979 (age 20/21) and 2008 (age 49/50). We applied two measures of sub-clinical psychosis derived from the SCL-90-R, namely schizotypal signs (STS) and schizophrenia nuclear symptoms (SNS). Variance was decomposed with latent state-trait analysis and associations with covariates were examined with generalized linear models. At ages 19/20 and 49/50, the latent states underlying STS accounted for 48% and 51% of variance, whereas for SNS those estimates were 62% and 50%. Between those age classes, however, expression of sub-clinical psychosis was strongly associated with stable traits (75% and 89% of total variance in STS and SNS, respectively, at age 27/28). Latent states underlying variance in STS and SNS were particularly related to partnership problems over almost the entire observation period. STS was additionally related to employment problems, whereas drug-use was a strong predictor of states underlying both syndromes at age 19/20. The latent trait underlying expression of STS and SNS was particularly related to low sense of mastery and self-esteem and to high depressiveness. Although most psychosis symptoms are transient and episodic in nature, the variability in their expression is predominantly caused by stable traits. Those time-invariant and rather consistent effects are particularly influential around age 30, whereas the occasion-specific states appear to be particularly influential at ages 20 and 50. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 17 | Schizophr. Res. 2013 Oct 150: 197-204 |
| PMID | 23932663 |
| Title | Deconstructing sub-clinical psychosis into latent-state and trait variables over a 30-year time span. |
| Abstract | Our aim was to deconstruct the variance underlying the expression of sub-clinical psychosis symptoms into portions associated with latent time-dependent states and time-invariant traits. We analyzed data of 335 subjects from the general population of Zurich, Switzerland, who had been repeatedly measured between 1979 (age 20/21) and 2008 (age 49/50). We applied two measures of sub-clinical psychosis derived from the SCL-90-R, namely schizotypal signs (STS) and schizophrenia nuclear symptoms (SNS). Variance was decomposed with latent state-trait analysis and associations with covariates were examined with generalized linear models. At ages 19/20 and 49/50, the latent states underlying STS accounted for 48% and 51% of variance, whereas for SNS those estimates were 62% and 50%. Between those age classes, however, expression of sub-clinical psychosis was strongly associated with stable traits (75% and 89% of total variance in STS and SNS, respectively, at age 27/28). Latent states underlying variance in STS and SNS were particularly related to partnership problems over almost the entire observation period. STS was additionally related to employment problems, whereas drug-use was a strong predictor of states underlying both syndromes at age 19/20. The latent trait underlying expression of STS and SNS was particularly related to low sense of mastery and self-esteem and to high depressiveness. Although most psychosis symptoms are transient and episodic in nature, the variability in their expression is predominantly caused by stable traits. Those time-invariant and rather consistent effects are particularly influential around age 30, whereas the occasion-specific states appear to be particularly influential at ages 20 and 50. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 18 | Schizophr. Res. 2013 Oct 150: 197-204 |
| PMID | 23932663 |
| Title | Deconstructing sub-clinical psychosis into latent-state and trait variables over a 30-year time span. |
| Abstract | Our aim was to deconstruct the variance underlying the expression of sub-clinical psychosis symptoms into portions associated with latent time-dependent states and time-invariant traits. We analyzed data of 335 subjects from the general population of Zurich, Switzerland, who had been repeatedly measured between 1979 (age 20/21) and 2008 (age 49/50). We applied two measures of sub-clinical psychosis derived from the SCL-90-R, namely schizotypal signs (STS) and schizophrenia nuclear symptoms (SNS). Variance was decomposed with latent state-trait analysis and associations with covariates were examined with generalized linear models. At ages 19/20 and 49/50, the latent states underlying STS accounted for 48% and 51% of variance, whereas for SNS those estimates were 62% and 50%. Between those age classes, however, expression of sub-clinical psychosis was strongly associated with stable traits (75% and 89% of total variance in STS and SNS, respectively, at age 27/28). Latent states underlying variance in STS and SNS were particularly related to partnership problems over almost the entire observation period. STS was additionally related to employment problems, whereas drug-use was a strong predictor of states underlying both syndromes at age 19/20. The latent trait underlying expression of STS and SNS was particularly related to low sense of mastery and self-esteem and to high depressiveness. Although most psychosis symptoms are transient and episodic in nature, the variability in their expression is predominantly caused by stable traits. Those time-invariant and rather consistent effects are particularly influential around age 30, whereas the occasion-specific states appear to be particularly influential at ages 20 and 50. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 19 | Front Psychol 2013 -1 4: 436 |
| PMID | 23882242 |
| Title | An asymmetry of translational biological motion perception in schizophrenia. |
| Abstract | Biological motion perception is served by a network of regions in the occipital, posterior temporal, and parietal lobe, overlapping areas of reduced cortical volume in schizophrenia. The atrophy in these regions is assumed to account for deficits in biological motion perception described in schizophrenia but it is unknown whether the asymmetry of atrophy found in previous studies has a perceptual correlate. Here we look for possible differences in sensitivity to leftward and rightward translation of point-light biological motion in data collected for a previous study and explore its underlying neurobiology using functional imaging. n = 64 patients with schizophrenia and n = 64 controls performed a task requiring the detection of leftward or rightward biological motion using a standard psychophysical staircase procedure. six control subjects took part in the functional imaging experiment. We found a deficit of leftward but not rightward biological motion (leftward biological motion % accuracy patients = 57.9% ± 14.3; controls = 63.6% ± 11.3 p = 0.01; rightward biological motion patients = 62.7% ± 12.4; controls = 64.1% ± 11.7; p > 0.05). The deficit reflected differences in distribution of leftward and rightward accuracy bias in the two populations. Directional bias correlated with functional outcome as measured by the Role Functioning Scale in the patient group when co-varying for negative symptoms (r = -0.272, p = 0.016). Cortical regions with preferential activation for leftward or rightward translation were identified in both hemispheres suggesting the psychophysical findings could not be accounted for by selective atrophy or functional change in one hemisphere alone. The findings point to translational direction as a novel functional probe to help understand the underlying neural mechanisms of wider cognitive dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 20 | Nat Commun 2014 -1 5: 4858 |
| PMID | 25224588 |
| Title | A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness. |
| Abstract | Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability to catalyse the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homologue of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 21 | Neuropsychiatr Dis Treat 2014 -1 10: 2221-30 |
| PMID | 25484590 |
| Title | Absent activation in medial prefrontal cortex and temporoparietal junction but not superior temporal sulcus during the perception of biological motion in schizophrenia: a functional MRI study. |
| Abstract | Patients with schizophrenia show disturbances in both visual perception and social cognition. Perception of biological motion (BM) is a higher-level visual process, and is known to be associated with social cognition. BM induces activation in the "social brain network", including the superior temporal sulcus (STS). Although deficits in the detection of BM and atypical activation in the STS have been reported in patients with schizophrenia, it remains unclear whether other nodes of the "social brain network" are also atypical in patients with schizophrenia. We aimed to explore whether brain regions other than STS were involved during BM perception in patients with schizophrenia, using functional magnetic resonance imaging (fMRI). Seventeen patients with schizophrenia, and 17 age- and sex- matched healthy controls, underwent fMRI scanning during a one-back visual task, containing three experimental conditions: (1) BM, (2) scrambled motion (SM), and (3) static condition. We used one-sample t-teSTS to examine neural responses selective to BM versus SM within each group, and two-sample t-teSTS to directly compare neural patterns to BM versus SM in schizophrenics versus controls. We found significant activation in the STS region when BM was contrasted with SM in both groups, with no significant difference between groups. On the contrary, significant activation in the medial prefrontal cortex (MPFC) and bilateral temporoparietal junction (TPJ) was found only in the control group. When we directly compared the two groups, the healthy controls showed significant greater activation in left MPFC and TPJ to BM versus SM than patients with schizophrenia. Our findings suggest that patients with schizophrenia show normal activation to biologically and socially relevant motion stimuli in the STS, but atypical activation in other regions of the social brain network, specifically MPFC and TPJ. Moreover, these results were not due to atypical processing of motion, suggesting that patients with schizophrenia lack in the recruitment of neural circuits needed for the visual perception of social cognition. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 22 | Neuropsychiatr Dis Treat 2014 -1 10: 2221-30 |
| PMID | 25484590 |
| Title | Absent activation in medial prefrontal cortex and temporoparietal junction but not superior temporal sulcus during the perception of biological motion in schizophrenia: a functional MRI study. |
| Abstract | Patients with schizophrenia show disturbances in both visual perception and social cognition. Perception of biological motion (BM) is a higher-level visual process, and is known to be associated with social cognition. BM induces activation in the "social brain network", including the superior temporal sulcus (STS). Although deficits in the detection of BM and atypical activation in the STS have been reported in patients with schizophrenia, it remains unclear whether other nodes of the "social brain network" are also atypical in patients with schizophrenia. We aimed to explore whether brain regions other than STS were involved during BM perception in patients with schizophrenia, using functional magnetic resonance imaging (fMRI). Seventeen patients with schizophrenia, and 17 age- and sex- matched healthy controls, underwent fMRI scanning during a one-back visual task, containing three experimental conditions: (1) BM, (2) scrambled motion (SM), and (3) static condition. We used one-sample t-teSTS to examine neural responses selective to BM versus SM within each group, and two-sample t-teSTS to directly compare neural patterns to BM versus SM in schizophrenics versus controls. We found significant activation in the STS region when BM was contrasted with SM in both groups, with no significant difference between groups. On the contrary, significant activation in the medial prefrontal cortex (MPFC) and bilateral temporoparietal junction (TPJ) was found only in the control group. When we directly compared the two groups, the healthy controls showed significant greater activation in left MPFC and TPJ to BM versus SM than patients with schizophrenia. Our findings suggest that patients with schizophrenia show normal activation to biologically and socially relevant motion stimuli in the STS, but atypical activation in other regions of the social brain network, specifically MPFC and TPJ. Moreover, these results were not due to atypical processing of motion, suggesting that patients with schizophrenia lack in the recruitment of neural circuits needed for the visual perception of social cognition. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 23 | Schizophr Bull 2014 Jul 40: 936-44 |
| PMID | 23956120 |
| Title | Superior temporal sulcus disconnectivity during processing of metaphoric gestures in schizophrenia. |
| Abstract | The left superior temporal sulcus (STS) plays an important role in integrating audiovisual information and is functionally connected to disparate regions of the brain. For the integration of gesture information in an abstract sentence context (metaphoric gestures), intact connectivity between the left STS and the inferior frontal gyrus (IFG) should be important. Patients with schizophrenia have problems with the processing of metaphors (concretism) and show aberrant structural connectivity of long fiber bundles. Thus, we tested the hypothesis that patients with schizophrenia differ in the functional connectivity of the left STS to the IFG for the processing of metaphoric gestures. During functional magnetic resonance imaging data acquisition, 16 patients with schizophrenia (P) and a healthy control group (C) were shown videos of an actor performing gestures in a concrete (iconic, IC) and abstract (metaphoric, MP) sentence context. A psychophysiological interaction analysis based on the seed region from a previous analysis in the left STS was performed. In both groups we found common positive connectivity for IC and MP of the STS seed region to the left middle temporal gyrus (MTG) and left ventral IFG. The interaction of group (C>P) and gesture condition (MP>IC) revealed effects in the connectivity to the bilateral IFG and the left MTG with patients exhibiting lower connectivity for the MP condition. In schizophrenia the left STS is misconnected to the IFG, particularly during the processing of MP gestures. Dysfunctional integration of gestures in an abstract sentence context might be the basis of certain interpersonal communication problems in the patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 24 | Transl Psychiatry 2015 -1 5: e626 |
| PMID | 26305477 |
| Title | Apoptotic markers in cultured fibroblasts correlate with brain metabolites and regional brain volume in antipsychotic-naive first-episode schizophrenia and healthy controls. |
| Abstract | Cultured fibroblaSTS from first-episode schizophrenia patients (FES) have shown increased susceptibility to apoptosis, which may be related to glutamate dysfunction and progressive neuroanatomical changes. Here we determine whether apoptotic markers obtained from cultured fibroblaSTS in FES and controls correlate with changes in brain glutamate and N-acetylaspartate (NAA) and regional brain volumes. Eleven antipsychotic-naive FES and seven age- and gender-matched controls underwent 3-Tesla magnetic resonance imaging scanning. Glutamate plus glutamine (Glx) and NAA levels were measured in the anterior cingulate (AC) and the left thalamus (LT). Hallmarks of apoptotic susceptibility (caspase-3-baseline activity, phosphatidylserine externalization and chromatin condensation) were measured in fibroblast cultures obtained from skin biopsies after inducing apoptosis with staurosporine (STS) at doses of 0.25 and 0.5 ?M. Apoptotic biomarkers were correlated to brain metabolites and regional brain volume. FES and controls showed a negative correlation in the AC between Glx levels and percentages of cells with condensed chromatin (CC) after both apoptosis inductions (STS 0.5 ?M: r = -0.90; P = 0.001; STS 0.25 ?M: r = -0.73; P = 0.003), and between NAA and cells with CC (STS 0.5 ?M induction r = -0.76; P = 0.002; STS 0.25 ?M r = -0.62; P = 0.01). In addition, we found a negative correlation between percentages of cells with CC and regional brain volume in the right supratemporal cortex and post-central region (STS 0.25 and 0.5 ?M; P < 0.05 family-wise error corrected (FWEc)). We reveal for the first time that peripheral markers of apoptotic susceptibility may correlate with brain metabolites, Glx and NAA, and regional brain volume in FES and controls, which is consistent with the neuroprogressive theories around the onset of the schizophrenia illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 25 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2015 Apr 58: 81-8 |
| PMID | 25545410 |
| Title | Involvement of the dorsolateral prefrontal cortex and superior temporal sulcus in impaired social perception in schizophrenia. |
| Abstract | schizophrenia is a mental disorder characterized by impairments in diverse thinking and emotional responses, which are related to social perception dysfunction. This fMRI study was designed to investigate a neurobiological basis of social perception deficits of patients with schizophrenia in various social situations of daily life and their relationship with clinical symptoms and social dysfunction. Seventeen patients and 19 controls underwent functional magnetic resonance imaging, during which participants performed a virtual social perception task, containing an avatar's speech with positive, negative or neutral emotion in a virtual reality space. Participants were asked to determine whether or not the avatar's speech was appropriate to each situation. The significant group×appropriateness interaction was seen in the left dorsolateral prefrontal cortex (DLPFC), resulting from lower activity in patients in the inappropriate condition, and left DLPFC activity was negatively correlated with the severity of negative symptoms and positively correlated with the level of social functioning. The significant appropriateness×emotion interaction observed in the left superior temporal sulcus (STS) was present in controls, but absent in patients, resulting from the existence and absence of a difference between the inappropriate positive and negative conditions, respectively. These findings indicate that dysfunction of the DLPFC-STS network may underlie patients' abnormal social perception in various social situations of daily life. Abnormal functioning of this network may contribute to increases of negative symptoms and decreases of social functioning. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 26 | Neuroimage 2016 Jan 125: 724-30 |
| PMID | 26546865 |
| Title | GABA concentration in superior temporal sulcus predicts gamma power and perception in the sound-induced flash illusion. |
| Abstract | In everyday life we are confronted with inputs of multisensory stimuli that need to be integrated across our senses. Individuals vary considerably in how they integrate multisensory information, yet the neurochemical foundations underlying this variability are not well understood. Neural oscillations, especially in the gamma band (>30Hz) play an important role in multisensory processing. Furthermore, gamma-aminobutyric acid (GABA) neurotransmission contributes to the generation of gamma band oscillations (GBO), which can be sustained by activation of metabotropic glutamate receptors. Hence, differences in the GABA and glutamate systems might contribute to individual differences in multisensory processing. In this combined magnetic resonance spectroscopy and electroencephalography study, we examined the relationships between GABA and glutamate concentrations in the superior temporal sulcus (STS), source localized GBO, and illusion rate in the sound-induced flash illusion (SIFI). In 39 human volunteers we found robust relationships between GABA concentration, GBO power, and the SIFI perception rate (r-values=0.44 to 0.53). The correlation between GBO power and SIFI perception rate was about twofold higher when the modulating influence of the GABA level was included in the analysis as compared to when it was excluded. No significant effects were obtained for glutamate concentration. Our study suggeSTS that the GABA level shapes individual differences in audiovisual perception through its modulating influence on GBO. GABA neurotransmission could be a promising target for treatment interventions of multisensory processing deficits in clinical populations, such as schizophrenia or autism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 27 | Schizophr Bull 2016 May 42: 666-74 |
| PMID | 26453911 |
| Title | The Core Brain Region for Face Processing in Schizophrenia Lacks Face Selectivity. |
| Abstract | Face perception impairment in schizophrenia has long been recognized. However, brain mechanisms underlying this socially important perceptual deficit are not well understood. Previous magnetic resonance imaging (MRI) studies have shown that patients have altered structure in brain regions responsible for processing face information, but functional properties of these brain regions are not clearly determined. A key functional property of the face-processing system-face selectivity-has yet to be evaluated in schizophrenia. We used functional MRI (fMRI) to examine face selectivity of 3 core face-processing regions-fusiform face area (FFA), occipital face area (OFA), and superior temporal sulcus (STS)-in schizophrenia patients (n = 24) and healthy controls (n = 23). To disassociate face-specific processing from general perceptual processing, we compared cortical activations during performance of perceptually equated face and tree detection tasks. Activation levels of the 3 putative face-processing regions during face detection did not differ between patients and controls, being similar for FFA and OFA and absent for STS. However, face selectivity, indexed by the difference in cortical activation between face and tree detection, was significantly reduced in patients for FFA, especially for low-contrast stimuli. FFA activation and perceptual performance during face detection were associated in patients. These results show a lack of face-specific processing in the schizophrenic brain region presumably subserving face perception. This finding suggeSTS boosting visual salience of face images as a potential therapeutic venue for improving face perception in this psychiatric disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 28 | Schizophr Bull 2016 May 42: 666-74 |
| PMID | 26453911 |
| Title | The Core Brain Region for Face Processing in Schizophrenia Lacks Face Selectivity. |
| Abstract | Face perception impairment in schizophrenia has long been recognized. However, brain mechanisms underlying this socially important perceptual deficit are not well understood. Previous magnetic resonance imaging (MRI) studies have shown that patients have altered structure in brain regions responsible for processing face information, but functional properties of these brain regions are not clearly determined. A key functional property of the face-processing system-face selectivity-has yet to be evaluated in schizophrenia. We used functional MRI (fMRI) to examine face selectivity of 3 core face-processing regions-fusiform face area (FFA), occipital face area (OFA), and superior temporal sulcus (STS)-in schizophrenia patients (n = 24) and healthy controls (n = 23). To disassociate face-specific processing from general perceptual processing, we compared cortical activations during performance of perceptually equated face and tree detection tasks. Activation levels of the 3 putative face-processing regions during face detection did not differ between patients and controls, being similar for FFA and OFA and absent for STS. However, face selectivity, indexed by the difference in cortical activation between face and tree detection, was significantly reduced in patients for FFA, especially for low-contrast stimuli. FFA activation and perceptual performance during face detection were associated in patients. These results show a lack of face-specific processing in the schizophrenic brain region presumably subserving face perception. This finding suggeSTS boosting visual salience of face images as a potential therapeutic venue for improving face perception in this psychiatric disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |