Bipolar I disorder and major depressive disorder show similar brain activation during depression

Depression is a dysfunctional affective state characterized by persistent negative mood as well as significant neurovegetative and cognitive symptoms (1). Despite different treatments and courses of illness, depressive symptoms are similar in major depressive (MDD) and bipolar disorder type I (BP-I) and these two disorders cannot be distinguished without knowledge of the patient's prior mood episodes (i.e., a history of mania) (2). These common depressive symptoms in both BP-I and MDD suggest significant overlap in brain pathways underlying the neurovegetative, mood, and cognitive symptoms of both disorders (2). Consequently, it is possible that shared neurofunctional abnormalities may underlie the pathophysiology of depressive symptoms in both disorders, and that similar activation of brain structures would be observed in individuals with MDD or BP-I during functional magnetic resonance imaging (fMRI). Yet these two mood disorders have different prognoses, treatments and courses of illness, and there is evidence that they exhibit different alterations within brain circuits that modulate mood (2-4). Differences in brain activation between individuals with BPI and MDD observed during a depressive episode may therefore represent abnormalities unique to each condition. Increased understanding of these pathways would help to clarify the neurophysiology of depression and to advance understanding of the etiology and treatment of depressive disorders. This is the first study to use fMRI to evaluate attentional and emotional processing together in depressed participants with MDD or BP-I. While the specific neuropathophysiology of BP-I is unknown, neuroimaging studies suggest impairments in cortico-limbic regions responsible for regulating emotion (2-8). Specifically, altered brain activation has been shown in the amygdala, anterior cingulate gyrus (ACC), ventrolateral prefrontal cortex (VLPFC), insula, and medial prefrontal cortex when compared to healthy comparison participants (HC) (2-8). In MDD, the extant neuroimaging data suggests involvement of a different set of brain regions than in BP-I (9-15). Prior imaging studies of patients with MDD have emphasized the roles of abnormalities within hippocampus and dorsolateral prefrontal cortex (DLPFC) (9-15). Moreover, Ketter et al. (16) suggested that hypofunction in DLPFC may lead to over-activation of hippocampus during depression. In addition, functional neuroimaging studies examining the treatment of depression have also found changes in DLFPC and hippocampus and their interaction (9, 13, 17). Structural imaging studies consistently find a decrease in the volume of the hippocampus, and a recent meta-analysis by Videbech and Ravnkilde (10) confirmed these results, but also found no changes in hippocampus in BP-I. In contrast to finding increased striatal volumes in patients with BP-I, several studies found decreased volumes of striatum in subjects with MDD (18-22). Pillay et al. (23) reported volume reductions in striatum in unipolar patients that correlated with illness severity (Hamilton Depression Inventory score). With these considerations in mind, the current study was designed to examine differences in brain activation during depression between individuals with MDD and BP-I during a dual emotional and cognitive task (24). The task was designed to discriminate between ventral emotional and dorsal cognitive brain networks and requires effective regulation of emotion to complete successfully. When HC subjects performed this task in an MRI scanner, Yamasaki et al. (24) found that dorsal prefrontal regions were activated in response to the attentional component of the task while ventral prefrontal regions were activated in response to the emotional component of the task, consistent with models proposed by Mayberg and colleagues (9, 13-15). Given previous findings in MDD and BP-I, we predicted that the BP-I group would show altered activation in the ACC, VLPFC, insula, and medial prefrontal cortex compared to the MDD group. In contrast, we predicted the MDD group would show altered activation in the hippocampus and DLPFC.