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

Hypothesis

Hypothesis

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:
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.