Neuroimaging Intermediate Phenotypes of Executive Control Dysfunction in Schizophrenia

Genetic risk for schizophrenia is associated with impairments in the initiation and performance of executive control of cognition and action. The nature of these impairments and of the neural dysfunction that underlies them has been extensively investigated using experimental psychology and neuroimaging methods. In this article, we review schizophrenia-associated functional connectivity and activation abnormalities found in subjects performing experimental tasks that engage different aspects of executive function, such as working memory, cognitive control, and response inhibition. We focus on heritable traits associated with schizophrenia risk (intermediate phenotypes or endophenotypes) that have been revealed using imaging genetics approaches. These data suggest that genetic risk for schizophrenia is associated with dysfunction in systems supporting the initiation and application of executive control in neural circuits involving the anterior cingulate and dorsolateral prefrontal cortex. This article discusses current findings and limitations and their potential relevance to symptoms and disease pathogenesis.