Prefrontal Cortex Dysfunction as a Risk Factor for the Development of Schizophrenia

Deanna M. Barch

Washington University

Funded in September, 2000: $100000 for 4 years
LAY SUMMARY . ABSTRACT . BIOGRAPHY . HYPOTHESIS . FINDINGS . SELECTED PUBLICATIONS .

ABSTRACT

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Prefrontal Cortex Dysfunction as a Risk Factor for the Development of Schizophrenia

Individuals with a disorder called schizotypal personality disorder (SPD) share a genetic link with schizophrenia, and SPD is considered part of the spectrum of schizophrenia-related illnesses. Individuals with schizophrenia show consistent problems in the ability to represent and maintain goal or context information that normally helps to guide behavior. In addition, individuals with schizophrenia show problems in activating brain regions such as the dorsolateral prefrontal cortex (DLPFC) when trying to maintain such context information. However, it is not yet clear whether these problems are present prior to the onset of schizophrenia and whether they contribute to the development of schizohprenia.

The purpose of this project is to expand upon prior research by examining brain activity during cognitive processing, using carefully controlled tasks designed to measure context processing and novel functional magnetic resonance imaging (fMRI) methods to study individuals at risk for the development of schizophrenia. We will study 40 individuals with Schizotypal Personality Disorder, a a group of individuals known to be at heightened risk for the development of schizophrenia, as well as 40 control subjects. We will have all participants perform a task specifically designed to assess context processing (an AX version of the Continuous Performance task), as well as tasks used in prior high risk  research (CPT-IP and degraded CPT). In addition, we will ask everyone to participate in an fMRI session, allowing us to determine the integrity of PFC function while these individuals perform cognitive tasks.

Results from this initial cross-sectional study will provide a starting point for follow-up longitudinal studies to further establish the causal and developmental relationships among PFC dysfunction, cognitive deficits and symptoms in schizophrenia, and their ability to predict risk for this debilitating disease.

INVESTIGATOR BIOGRAPHIES

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Deanna M. Barch

Assistant Professor of Psychology and Psychiatry
Washington University

HYPOTHESIS

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Hypothesis:
Prefrontal cortex (PFC) dysfunction, particularly in dorsolateral regions of PFC, and specific cognitive deficits that are present prior to the onset of schizophrenia predict risk for later development of schizophrenia and are potential targets for interventions aimed at preventing the onset of this disabling illness.

Goals:
1. To determine whether a more theoretically-driven assessment of cognitive function can improve sensitivity and specificity in predicting risk for schizophrenia over cognitive tasks used in prior high-risk studies.

2. To determine whether assessing functional brain activity can increase sensitivity and/or specificity in identifying individuals at risk for developing schizophrenia over the use of purely behavioral measures.

Methods:
We are assessing individuals with a task designed specifically to evaluate the representation and maintenance of context information (an AX version of the Continuous Performance Test; AX-CPT), as well as cognitive tasks used in prior behavioral high risk research (i.e., the degraded CPT and the CPT Identical Pairs). In addition, we are using functional magnetic resonance imaging (fMRI) to examine cortical activity during performance of our version of the AX-CPT, as well as during performance of several additional tasks tapping cognitive functions also thought to be critically dependent on PFC function (i.e., episodic memory encoding and retrieval, selective attention).

 

FINDINGS

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Our goal was to begin to address these questions by examining whether individuals with SPD show similar problems in using context information and in activating DLPFC. Our results confirmed that individuals with SPD showed problems in context processing similar to those found in individuals with schizophrenia, and that such problems were associated with problems in the function of DLPFC in SPD. In addition, we found that the severity of cognitive deficits in individuals with SPD were related to the severity of the negative (social anxiety and withdrawal) and disorganization symptoms (disorganized speech, odd behavior) of this illness, but were not related to the positive symptoms (odd thoughts, perceptual abnormalities). These results are consistent with the hypothesis that problems in context processing and DPFC function are related to vulnerability for the development of schizophrenia spectrum disorders.

 

SELECTED PUBLICATIONS

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Barch D. M., Mitropoulou V., Harvey P., New A. S., Silverman J. M., and Siever L. J. Context processing deficits in schizotypal personality disorder. J Abnorm Psychol. 2004 Nov;113(4):556-68.

Barch D. M.  What can research on schizophrenia tell us about the cognitive neuroscience of working memory? Neuroscience. 2006 Apr 28;139(1):73-84.