Prefrontal Cortex Function in Nonpsychotic Siblings of Individuals with Schizophrenia

Background: Cognitive dysfunction is a hallmark feature of schizophrenia. In recent years, it has been proposed that impairments in attention, working memory and executive function may all reflect an underlying deficit in context processing. In individuals with schizophrenia, deficits in context processing have been associated with functional impairments of the dorsolateral prefrontal cortex (DLPFC). Methods: We used a variation of the continuous performance task, the AX-CPT, to test the hypothesis that genetic high-risk individuals (full siblings of individuals with schizophrenia) have deficits in context processing and abnormal activation of the DLPFC as compared to community controls. Results: Siblings of individuals with schizophrenia made significantly more B-X errors on the AX-CPT, indicative of a deficit in context processing. They also showed task-related hyper-activation in a number of brain regions, including the DLPFC. Conclusions: Inefficient hyper-activation of the DLPFC may underlie deficits in context processing and contribute to the genetic vulnerability for developing schizophrenia.