The maudsley bipolar disorder project: Insights into pathophysiology

Neuroanatomical changes in bipolar disorder are mostly regional and involve the prefrontal cortex (PFC), the anterior cingulate and the amygdala. Reductions in grey matter volume (or density) have been found in the dorsal PFC and they appear to be more pronounced on the left. 1–3 Similarly, reduction has been reported in the ventral PFC particularly in Brodmann areas 44 and 47. 1, 3 Volume (or density) decreases in the left cingulate gyrus have been reported in some 3, 4 but not all studies. 1, 5 In contrast, the volume of the amygdala has appeared to be enlarged bilaterally or only on the left in recent studies. 1, 5–7 Resting-state functional imaging studies, despite differences in methodological approaches, have found reduced activity in the dorsal PFC, mostly on the left 8 and increased activity in the amygdala in depressive states. 9 Manic states have been associated with decreased activity in the ventral PFC and increased activity in the anterior cingulate cortex (ACC). 10, 11 Trait-related decreases in brain activation have also been reported within the left ventral PFC (Brodmann areas 47 and 10). 12 However, the relative contributions of dorsal and ventral prefrontal functioning in bipolar disorder remain unclear.