Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression

Biol Psychiatry. 2009 Sep 1;66(5):451-9. doi: 10.1016/j.biopsych.2009.03.024. Epub 2009 May 17.


Background: Bipolar disorder is frequently misdiagnosed as major depressive disorder, delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation might therefore help discriminate bipolar from major depressive disorder.

Methods: Thirty-one depressed individuals-15 bipolar depressed (BD) and 16 major depressed (MDD), DSM-IV diagnostic criteria, ages 18-55 years, matched for age, age of illness onset, illness duration, and depression severity-and 16 age- and gender-matched healthy control subjects performed two event-related paradigms: labeling the emotional intensity of happy and sad faces, respectively. We employed dynamic causal modeling to examine significant among-group alterations in effective connectivity (EC) between right- and left-sided neural regions supporting emotion regulation: amygdala and orbitomedial prefrontal cortex (OMPFC).

Results: During classification of happy faces, we found profound and asymmetrical differences in EC between the OMPFC and amygdala. Left-sided differences involved top-down connections and discriminated between depressed and control subjects. Furthermore, greater medication load was associated with an amelioration of this abnormal top-down EC. Conversely, on the right side the abnormality was in bottom-up EC that was specific to bipolar disorder. These effects replicated when we considered only female subjects.

Conclusions: Abnormal, left-sided, top-down OMPFC-amygdala and right-sided, bottom-up, amygdala-OMPFC EC during happy labeling distinguish BD and MDD, suggesting different pathophysiological mechanisms associated with the two types of depression.

Publication types

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

MeSH terms

  • Adult
  • Amygdala / physiopathology*
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / physiopathology*
  • Case-Control Studies
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / physiopathology*
  • Diagnosis, Differential
  • Emotions / physiology
  • Facial Expression
  • Female
  • Humans
  • Male
  • Models, Neurological
  • Neural Pathways / physiopathology
  • Prefrontal Cortex / physiopathology*