Reduced amygdala-prefrontal connectivity is associated with symptom severity in major depression

Introduction: The amygdala plays a pivotal role in a cortico-limbic network involved in emotion processing. Amygdala-prefrontal connectivity has been implicated in the regulation of affective states. Since depressed patients were reported to show impaired emotion regulation, we hypothesized that reduced amygdala-prefrontal connectivity might be a neural correlate of major depression. Method: Functional connectivity of bilateral amygdala was investigated during an overt facial emotion processing task in a sample of 36 acutely depressed inpatients and 32 healthy controls by means of fMRI. Participants viewed blocks of angry, sad, happy, and neutral facial expressions. Individual amygdala signal time series were extracted and correlated with whole brain activity (seed regression method). Results: Depressed patients demonstrated reduced amygdala connectivity in the supragenual anterior cingulate cortex and lateral prefrontal areas. Furthermore, reduced connectivity in these areas was associated with a longer and severer course of disease (e.g., more episodes and longer hospitalization time). Discussion: The present data suggest that the interplay of the amygdala and prefrontal areas is impaired in acutely depressed patients. Reduced connectivity was found particularly in areas implicated in the regulation of affective states (supragenual ACC and lateral PFC). A reduced ability for emotion regulation could be a determinant for a less benign course of disease.