Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: state versus trait vulnerability markers of depression in bipolar disorder

Biol Psychiatry. 2010 Mar 1;67(5):422-31. doi: 10.1016/j.biopsych.2009.11.025.


Background: Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD).

Methods: Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined.

Results: The BD versus HC showed significantly greater right amygdala-OFC FC (p < or = .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p = .01). There was a significant nonlinear relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001).

Conclusions: In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC-FA relationships in BD and HC require further study.

Publication types

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

MeSH terms

  • Adult
  • Affect*
  • Amygdala / physiopathology*
  • Anisotropy
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / physiopathology*
  • Bipolar Disorder / psychology*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / physiopathology*
  • Depressive Disorder, Major / psychology*
  • Diagnosis, Differential
  • Diagnostic and Statistical Manual of Mental Disorders
  • Face*
  • Facial Expression*
  • Female
  • Functional Laterality / physiology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Nerve Net / physiopathology*
  • Prefrontal Cortex / physiopathology*
  • Surveys and Questionnaires