Differential abnormalities of functional connectivity of the amygdala and hippocampus in unipolar and bipolar affective disorders.

Objective: The amygdala and hippocampus - two structures intimately associated with mood and cognition - have been reported to exhibit altered neural activity or volume in affective disorders. We hypothesized the amygdala and hippocampus would show altered and differential patterns of connectivity in patients with bipolar (BPs) and unipolar (UPs) disorder compared to healthy volunteers.

Method: Thirty BPs, 34 UPs, and 66 healthy volunteers were imaged using F-18-fluorodeoxyglucose and positron emission tomography while performing an auditory continuous performance task (CPT). Normalized mean activity of the amygdala and hippocampus was correlated with the rest of the brain.

Results: In BPs, the amygdalae displayed exaggerated positive metabolic correlations with prefrontal and ventral striatal areas, while the hippocampus showed a paucity of normal inter-relations compared to controls. In contrast, in UPs the amygdala was significantly negatively correlated with prefrontal and anterior cingulate cortex, while the hippocampus was significantly more positively correlated to these same prefrontal areas.

Conclusions: During a simple cognitive task, the functional connectivity of the amygdala and hippocampus, regions usually associated with emotion and memory regulation, was substantially different in affective illness compared to healthy controls whether or not there were baseline abnormalities in these areas. These striking differences in functional connectivity of amygdala and hippocampus should be further explored in ill and well states and using more specific emotion and cognitive evocative tasks.