Toward a functional neuroanatomical signature of bipolar disorder: quantitative evidence from the neuroimaging literature.

The present meta-analysis quantitatively reviewed the functional neuroimaging literature on bipolar disorder (BPD) to better characterize its neuroanatomical signature with respect to the influence of mood state, test conditions, and clinical demographics on regional brain activation. Fifty-five functional neuroimaging studies published between 1987 and 2010 met criteria for inclusion, encompassing a total of 774 adult patients with BPD and 810 healthy adult controls. A meta-analysis was conducted comparing the activation states of multiple brain regions in BPD patients and control subjects. Despite heterogeneity across studies, our findings support the view that limbic hyperactivity and frontal hypoactivity are neurobiological correlates of BPD. Our findings also highlight the involvement of many brain regions and circuits, as well as the critical role of mood state and test conditions in the functional impairments of BPD. This review represents the first attempt to quantitatively articulate the magnitude of functional brain abnormality in BPD, and, in so doing, provides a synthesis of evidence in line with current network models of the disorder. Overall, this review offers support for, and seeks to help guide, the continued use of functional neuroimaging as an informative probe into the complex neurobiology of BPD.