Amygdala excitability to subliminally presented emotional faces distinguishes unipolar and bipolar depression: an fMRI and pattern classification study

Hum Brain Mapp. 2014 Jul;35(7):2995-3007. doi: 10.1002/hbm.22380. Epub 2013 Sep 13.

Abstract

Background: Bipolar disorder and Major depressive disorder are difficult to differentiate during depressive episodes, motivating research for differentiating neurobiological markers. Dysfunctional amygdala responsiveness during emotion processing has been implicated in both disorders, but the important rapid and automatic stages of emotion processing in the amygdala have so far never been investigated in bipolar patients.

Methods: fMRI data of 22 bipolar depressed patients (BD), 22 matched unipolar depressed patients (MDD), and 22 healthy controls (HC) were obtained during processing of subliminal sad, happy and neutral faces. Amygdala responsiveness was investigated using standard univariate analyses as well as pattern-recognition techniques to differentiate the two clinical groups. Furthermore, medication effects on amygdala responsiveness were explored.

Results: All subjects were unaware of the emotional faces. Univariate analysis revealed a significant group × emotion interaction within the left amygdala. Amygdala responsiveness to sad>neutral faces was increased in MDD relative to BD. In contrast, responsiveness to happy>neutral faces showed the opposite pattern, with higher amygdala activity in BD than in MDD. Most of the activation patterns in both clinical groups differed significantly from activation patterns of HC--and therefore represent abnormalities. Furthermore, pattern classification on amygdala activation to sad>happy faces yielded almost 80% accuracy differentiating MDD and BD patients. Medication had no significant effect on these findings.

Conclusions: Distinct amygdala excitability during automatic stages of the processing of emotional faces may reflect differential pathophysiological processes in BD versus MDD depression, potentially representing diagnosis-specific neural markers mostly unaffected by current psychotropic medication.

Keywords: amygdala; bipolar disorder; depression; fMRI; pattern classification; subliminal emotion processing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amygdala / blood supply*
  • Amygdala / drug effects
  • Amygdala / physiopathology
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder / classification
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / drug therapy
  • Brain Mapping*
  • Depressive Disorder, Major / classification
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / drug therapy
  • Emotions / drug effects
  • Emotions / physiology*
  • Face
  • Facial Expression*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Oxygen / blood
  • Pattern Recognition, Visual / drug effects
  • Pattern Recognition, Visual / physiology
  • Photic Stimulation
  • Reaction Time / drug effects
  • Signal Detection, Psychological

Substances

  • Antidepressive Agents
  • Oxygen