Dissociable patterns of abnormal frontal cortical activation during anticipation of an uncertain reward or loss in bipolar versus major depression

Objectives: Recent research has found abnormalities in reward-related neural activation in bipolar disorder (BD), during both manic and euthymic phases. However, reward-related neural activation in currently depressed individuals with BD and that in currently depressed individuals with major depressive disorder (MDD) have yet to be directly compared. Here, we studied these groups, examining the neural activation elicited during a guessing task in fronto-striatal regions identified by previous studies. Methods: We evaluated neural activation during a reward task using fMRI in two groups of depressed individuals, one with bipolar I disorder (BD-I) (n = 23) and one with MDD (n = 40), with similar levels of illness severity, and a group of healthy individuals (n = 37). Results: Reward expectancy-related activation in the anterior cingulate cortex was observed in the healthy individuals, but was significantly reduced in depressed patients (BD-I and MDD together). Anticipation-related activation was increased in the left ventrolateral prefrontal cortex in the BD-I depressed group compared with the other two groups. There were no significant differences in prediction error-related activation in the ventral striatum across the three groups. Conclusions: The findings extend previous research which has identified dysfunction within the ventrolateral prefrontal cortex in BD, and show that abnormally elevated activity in this region during anticipation of either reward or loss may distinguish depressed individuals with BD-I from those with MDD. Altered activation of the anterior cingulate cortex during reward expectancy characterizes both types of depression. These findings have important implications for identifying both common and distinct properties of the neural circuitry underlying BD-I and MDD.