The inferior frontal gyrus and familial risk for bipolar disorder

Bipolar disorder (BD) is a familial disorder with high heritability. Genetic factors have been linked to the pathogenesis of BD. Relatives of probands with BD who are at familial risk can exhibit brain abnormalities prior to illness onset. Given its involvement in prefrontal cognitive control and in frontolimbic circuitry that regulates emotional reactivity, the inferior frontal gyrus (IFG) has been a focus of research in studies of BD-related pathology and BD-risk mechanism. In this review, we discuss multimodal neuroimaging findings of the IFG based on studies comparing at-risk relatives and low-risk controls. Review of these studies in at-risk cases suggests the presence of both risk and resilience markers related to the IFG. At-risk individuals exhibited larger gray matter volume and increased functional activities in IFG compared with low-risk controls, which might result from an adaptive brain compensation to support emotion regulation as an aspect of psychological resilience. Functional connectivity between IFG and downstream limbic or striatal areas was typically decreased in at-risk individuals relative to controls, which could contribute to risk-related problems of cognitive and emotional control. Large-scale and longitudinal investigations on at-risk individuals will further elucidate the role of IFG and other brain regions in relation to familial risk for BD, and together guide identification of at-risk individuals for primary prevention.