Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: state versus trait vulnerability markers of depression in bipolar disorder.
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.
Versace
Amelia
A
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Thompson
Wesley K
WK
Zhou
Donli
D
Almeida
Jorge R C
JR
Hassel
Stefanie
S
Klein
Crystal R
CR
Kupfer
David J
DJ
Phillips
Mary L
ML
D000328:Adult; D000339:Affect; D000679:Amygdala / Q000503:physiopathology*; D016880:Anisotropy; D001714:Bipolar Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology*; D003937:Diagnosis, Differential; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005145:Face; D005149:Facial Expression; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011795:Surveys and Questionnaires