Objectives. Patients affected by bipolar disorder (BP) and major depressive disorder (UP) share the susceptibility to experience depression and differ in their susceptibility to mania, but clinical studies suggest that the biological substrates of the two disorders could influence the apparently similar depressive phases. The few brain imaging studies available described different brain metabolic and neural correlates of UP and BP. Methods. We studied the BOLD neural response to a moral valence decision task targeting the depressive biases in information processing in 36 subjects (14 BP, 11 UP, and 11 controls). Results. Main differences between UP and controls and between UP and BP were detected in left ventrolateral prefrontal cortex (PFC, BA 47). Neural responses of BP patients differed from those of control subjects in multiple brain areas, including anterior cingulate cortex (ACC) and medial PFC, bilateral dorsolateral PFC, temporal cortex and insula, and parietal and occipital cortex. Conclusions. Our results are in agreement with hypotheses of dysfunctions in corticolimbic circuitries regulating affects and emotions in mood disorders and suggest that specific abnormalities, particularly in ventrolateral PFC, are not the same in UP and BP depression. 1. Objective Though grouped in the “mood disorders” section of DSM, primary depressive disorder (unipolar depression, UP) and bipolar disorder (BP) show clearly distinctive features, most strikingly because patients share the possibility of experiencing major depression but differ in the susceptibility for mania. Several findings suggest a biological basis for this difference. Genetic studies confirmed overlapping in the heritability of the two disorders but showed also that approximately 71% of the genetic influence on liability to mania is distinct from the genetic liability to depression [1]. The occurrence of mania seems to be related to alterations in dopaminergic function [2, 3], with CSF homovanillic levels raising before the switch into manic phase [4] and urinary dopamine levels predicting manic mood [5], and it is then hypothesized that the biological mechanisms leading to these changes should be specific of BP. Treatment options for UP and BP patients are different [6]. A lack of pharmaceutical trials comparing UP and BP prevents definite conclusions, but current opinions suggest different strategies for the treatment of BP and UP depression [7–9], and the clinical evidence is that BP patients experience depressive episodes that are more numerous and less responsive to antidepressant drug
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