Dataset Information

DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia.

ABSTRACT:

Background

DISC1 is considered a susceptibility gene for schizophrenia and schizoaffective disorder, but little is known regarding the potential mechanisms through which it may confer increased risk. Given that DISC1 plays a role in cerebral cortex development, polymorphisms in this gene may have relevance for neurobiological models of schizophrenia that have implicated cortical deficits in its pathophysiology.

Methods

We investigated whether the DISC1 leu607phe polymorphism was associated with prefrontal gray matter volumes using magnetic resonance imaging in a cohort of patients with schizophrenia (N=19) and healthy volunteers (N=25) and positive and negative symptoms in 200 patients with schizophrenia.

Results

Among patients and healthy volunteers, phe carriers (N=11) had significantly less gray matter in the superior frontal gyrus and anterior cingulate gyrus compared to leu/leu homozygotes (N=33). Further, among patients left superior frontal gyrus gray matter volume was significantly negatively correlated with severity of hallucinations. In addition, patients who were phe carriers (N=144) had significantly greater severity of positive symptoms (hallucinations) compared to patients who were leu/leu homozygotes (N=56).

Discussion

These findings implicate DISC1 in variation of prefrontal cortical volume and positive symptoms, thus providing a potential mechanism through which DISC1 may confer increased risk for schizophrenia or schizoaffective disorder.

SUBMITTER: Szeszko PR

PROVIDER: S-EPMC2623247 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Publications

DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia.

Szeszko Philip R PR Hodgkinson Colin A CA Robinson Delbert G DG Derosse Pamela P Bilder Robert M RM Lencz Todd T Burdick Katherine E KE Napolitano Barbara B Betensky Julia D JD Kane John M JM Goldman David D Malhotra Anil K AK

Biological psychology 20071101 1

<h4>Background</h4>DISC1 is considered a susceptibility gene for schizophrenia and schizoaffective disorder, but little is known regarding the potential mechanisms through which it may confer increased risk. Given that DISC1 plays a role in cerebral cortex development, polymorphisms in this gene may have relevance for neurobiological models of schizophrenia that have implicated cortical deficits in its pathophysiology.<h4>Methods</h4>We investigated whether the DISC1 leu607phe polymorphism was a ...[more]

PMID: 18078707

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Project description:Widespread cortical gray matter alternations in people with schizophrenia are correlated with both psychotic symptoms and cognitive/behavioral abnormalities, including the impairments of exploratory eye movement (EEM). Particularly, the loss of gray matter density is specifically related to deficits of the responsive search score (RSS) of EEM in schizophrenia. It is unknown, however, whether the schizophrenia-related RSS deficits are associated with certain psychotic symptoms, such as hallucinations.In 33 participants with schizophrenia, the measurement of EEM, assessment of the hallucination severity using Positive and Negative Syndrome Scale (PANSS) and a voxel-based morphometric analysis of cortical gray matter volume (GMV) were conducted to investigate the relationships between the RSS of EEM, symptom severity, and GMV. In 29 matched healthy controls, the measurement of EEM and a voxel-based morphometric analysis of cortical GMV were also conducted to investigate the relationship between the RSS of EEM and GMV.In participants with schizophrenia, the hallucination severity was significantly negatively correlated with both the RSS and the GMV of a large number of brain regions in the frontal, temporal, parietal, orbitofrontal, calcarine, cingulate, and insular cortices, and rolandic operculum, hippocampus, parahippocampal gyrus, and thalamus. Also in participants with schizophrenia, the RSS was significantly positively correlated with the GMV in the left supplementary motor area (SMA), left superior frontal cortex (SFG), bilateral precentral gyri, bilateral postcentral gyri, and bilateral middle frontal cortices. More importantly, the GMV of the SMA, SFG, and precentral gyrus in the left hemisphere was not only significantly negatively correlated with the hallucination severity but also significantly positively correlated with the RSS. No significant correlation could be revealed between the RSS and the GMV of any brain regions in healthy controls.There was a significantly negative association between the hallucination severity and the RSS of EEM, suggesting that the RSS may be a potential biomarker for predicting the hallucination severity of schizophrenia. Also, the GMV of the left SMA, SFG, and precentral gyrus may be the common substrates underlying both hallucination induction and the RSS in people with schizophrenia.

Dataset Information

DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia.

Background

Methods

Results

Discussion

Publications

DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia.

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