Elevated amygdala activity to sad facial expressions: a state marker of bipolar but not unipolar depression

Abstract

Background: Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression.

Methods: Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series.

Results: The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity.

Conclusions: Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression.

Figure 1

(A) Anatomical location of left amygdala activity where the main effect of group was statistically different during the sad experiment. Foci of significance were overlaid on sagittal, coronal, and axial brain slices spatially normalized into the Montreal Neurologic Institute coordinates system (x = −18, y = − 3, z = −18; cluster size = 11 voxels; F = 4.96; p = .003, corrected for multiple comparisons). (B) Mean left amygdala activity to faces in the sad experiment in each group; *trend toward significance; **significant comparison after controlling for multiple comparisons. (C) Activity in the left amygdala in response to intense and mild sad and neutral faces in each group. BOLD, blood oxygen level dependent; BDd, bipolar disorder patients in depressed episode; BDr, bipolar disorder patients in remission; MDD, major depression disorder patients in depressed episode; HC, healthy control