title: Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Jorge Renner Cardoso de
authors.initials: JR
authors.lastname: Almeida
authors.forename: Amelia
authors.initials: A
authors.lastname: Versace
authors.forename: Andrea
authors.initials: A
authors.lastname: Mechelli
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hassel
authors.forename: Karina
authors.initials: K
authors.lastname: Quevedo
authors.forename: David Jerome
authors.initials: DJ
authors.lastname: Kupfer
authors.forename: Mary Louise
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000503:physiopathology*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000503:physiopathology*; D003937:Diagnosis, Differential; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D005260:Female; D006801:Humans; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology*