Amygdala Activation and Connectivity to Emotional Processing Distinguishes Asymptomatic Patients With Bipolar Disorders and Unipolar Depression

Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Apr;4(4):361-370. doi: 10.1016/j.bpsc.2018.08.012. Epub 2018 Aug 31.


Background: Mechanistically based neural markers, such as amygdala reactivity, offer one approach to addressing the challenges of differentiating bipolar and unipolar depressive disorders independently from mood state and acute symptoms. Although emotion-elicited amygdala reactivity has been found to distinguish patients with bipolar depression from patients with unipolar depression, it remains unknown whether this distinction is traitlike and present in the absence of an acutely depressed mood. We addressed this gap by investigating patients with bipolar disorder (BP) and unipolar major depressive disorder (MDD) in remission.

Methods: Supraliminal and subliminal processing of faces exhibiting threat, sad, happy, and neutral emotions during functional magnetic resonance imaging was completed by 73 participants (23 BP patients and 25 MDD patients matched for age and gender, number of depressive episodes and severity; 25 age- and gender-matched healthy control subjects). We compared groups for activation and connectivity for the amygdala.

Results: BP patients had lower left amygdala activation than MDD patients during supraliminal and subliminal threat, sad, and neutral emotion processing and for subliminal happy faces. BP patients also exhibited lower amygdala connectivity to the insula and hippocampus for threat and to medial orbitofrontal cortex for happy supraliminal and subliminal processing. BP patients also demonstrated greater amygdala-insula connectivity for sad supraliminal and subliminal face processing. Both patient groups were distinct from control subjects across several measures for activation and connectivity.

Conclusions: Independent of valence or level of emotional awareness, amygdala activation and connectivity during facial emotion processing can distinguish BP patients and MDD patients. These findings provide evidence that this neural substrate could be a potential trait marker to differentiate these two disorders largely independent of illness state.

Keywords: Amygdala; Bipolar disorders; Depression; Emotion processing; Remission; fMRI connectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amygdala / diagnostic imaging
  • Amygdala / physiopathology*
  • Bipolar Disorder / diagnostic imaging
  • Bipolar Disorder / physiopathology*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology*
  • Connectome*
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / physiopathology*
  • Emotions / physiology*
  • Facial Expression
  • Facial Recognition / physiology*
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Remission Induction
  • Social Perception
  • Subliminal Stimulation
  • Young Adult