Genetics of cognitive control: Implications for Nimh's research domain criteria initiative

Cognitive control refers to a set of mental processes that modulate other cognitive and emotional systems in service of goal-directed adaptive behavior. There is growing support for the notion that cognitive control abnormalities are a central component of many of the neuropsychological deficits observed in individuals with mental illnesses, particularly those with psychotic disorders. NIMH's research domain criteria (RDoC) initiative, which is designed to develop biologically informed constructs to better understand psychopathology, designated cognitive control a construct within the cognitive systems domain. Identification of genes that influence cognitive control or its supportive brain systems will improve our understating of the RDoC construct and provide candidate genes for psychotic disorders. We examine evidence for cognitive control deficits in psychosis, determine if these measures could be useful endophenotypes, and explore work linking genetic variation to cognitive control performance. While there is a wealth of evidence to support the notion the cognitive control is a valid endophenotype for psychosis, its genetic underpinning remains ill characterized. However, existing work provides a promising foundation on which future endeavors might build. Confirming existing individual gene associations will go some way to expanding our understanding of the genetics of cognitive control, and by extension, psychotic disorders. Yet, to truly understand the molecular underpinnings of such complex traits, it may be necessary to evaluate genes in tandem, focusing not on single genes but rather on empirically derived gene sets or on functionally defined networks of genes.