Frontotemporal White Matter in Adolescents with, and at-Risk for, Bipolar Disorder

Frontotemporal neural systems are highly implicated in the emotional dysregulation characteristic of bipolar disorder (BD). Convergent genetic, postmortem, behavioral and neuroimaging evidence suggests abnormalities in the development of frontotemporal white matter (WM) in the pathophysiology of BD. This review discusses evidence for the involvement of abnormal WM development in BD during adolescence, with a focus on frontotemporal WM. Findings from diffusion tensor imaging (DTI) studies in adults and adolescents are reviewed to explore possible progressive WM abnormalities in the disorder. Intra- and interhemispheric frontotemporal abnormalities were reported in adults with BD. Although evidence in children and adolescents with BD to date has been limited, similar intrahemispheric and interhemispheric findings have also been reported. The findings in youths suggest that these abnormalities may represent a trait marker present early in the course of BD. Functional connectivity studies, demonstrating a relationship between WM abnormalities and frontotemporal dysfunction in BD, and DTI studies of vulnerability in first-degree relatives of individuals with BD, are discussed. Together, findings suggest the involvement of abnormal frontotemporal WM development in the pathophysiology of BD and that these abnormalities may be early trait markers of vulnerability; however, more studies are critically needed.