title: Amygdala hyperactivation during face emotion processing in unaffected youth at risk for bipolar disorder.
abstract: OBJECTIVE
  Youth at familial risk for bipolar disorder (BD) show deficits in face emotion processing, but the neural correlates of these deficits have not been examined. This preliminary study tests the hypothesis that, relative to healthy comparison (HC) subjects, both BD subjects and youth at risk for BD (i.e., those with a first-degree BD relative) will demonstrate amygdala hyperactivation when viewing fearful and happy faces. The at-risk youth were unaffected, in that they had no history of mood disorder.
  
  
  METHODS
  Amygdala activity was examined in 101 unrelated participants, 8 to 18 years old. Age, gender, and IQ-matched groups included BD (N = 32), unaffected at-risk (N = 13), and HC (N = 56). During functional magnetic resonance imaging, participants attended to emotional and nonemotional aspects of fearful and happy faces.
  
  
  RESULTS
  While rating their fear of fearful faces, both BD and unaffected at-risk subjects exhibited amygdala hyperactivity versus HC. There were no between-group differences in amygdala activity in response to happy faces. Post-hoc comparisons revealed that, in at-risk youth, familial risk status (offspring versus sibling), presence of Axis I diagnosis (n = 1 attention-deficit/hyperactivity disorder [ADHD], n = 1 social phobia), and history of medication exposure (n = 1) did not influence imaging findings.
  
  
  CONCLUSIONS
  We found amygdala hyperactivation in both unaffected at-risk and BD youth while rating their fear of fearful faces. These pilot data suggest that both face emotion labeling deficits and amygdala hyperactivity during face processing should receive further study as potential BD endophenotypes. Longitudinal studies should test whether amygdala hyperactivity to fearful faces predicts conversion to BD in at-risk youth.
authors.affiliation: Section on Bipolar Spectrum Disorders, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health (NIH), US Department of Health and Human Services, Bethesda, Maryland, USA. aolsavsky@mednet.ucla.edu
authors.forename: Aviva K
authors.initials: AK
authors.lastname: Olsavsky
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brotman
authors.forename: Julia G
authors.initials: JG
authors.lastname: Rutenberg
authors.forename: Eli J
authors.initials: EJ
authors.lastname: Muhrer
authors.forename: Christen M
authors.initials: CM
authors.lastname: Deveney
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fromm
authors.forename: Kenneth
authors.initials: K
authors.lastname: Towbin
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.forename: Ellen
authors.initials: E
authors.lastname: Leibenluft
mesh_terms: D000293:Adolescent; D000342:Affective Symptoms / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D000679:Amygdala / Q000503:physiopathology*; D001714:Bipolar Disorder / Q000235:genetics*; D002648:Child; D058068:Endophenotypes; D005149:Facial Expression; D005190:Family; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009483:Neuropsychological Tests; D010775:Photic Stimulation / Q000379:methods; D012307:Risk Factors