title: Functional connectivity of negative emotional processing in adolescent depression.
abstract: BACKGROUND
  The subgenual anterior cingulate cortex (sgACC) and its connected circuitry have been heavily implicated in emotional functioning in adolescent-onset major depressive disorder (MDD). While several recent studies have examined sgACC functional connectivity (FC) in depressed youth at rest, no studies to date have investigated sgACC FC in adolescent depression during negative emotional processing.
  
  
  METHODS
  Nineteen medication-naïve adolescents with MDD and 19 matched healthy controls (HCL) performed an implicit fear facial affect recognition task during functional magnetic resonance imaging (fMRI). We defined seeds in bilateral sgACC and assessed FC using the psychophysiological interaction method. We also applied cognitive behavioral modeling to estimate group differences in perceptual sensitivity in this task. Finally, we correlated connectivity strength with clinical data and perceptual sensitivity.
  
  
  RESULTS
  Depressed adolescents showed increased sgACC-amygdala FC and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus FC compared to HCL (p<0.05, corrected). Among the MDD, sgACC-precuneus FC negatively correlated with depression severity (p<0.05, corrected). Lastly, MDD adolescents exhibited poorer perceptual sensitivity in the task than HCL, and individual differences in perceptual sensitivity significantly correlated with sgACC FC and depression scores (p<0.05, corrected).
  
  
  CONCLUSIONS
  Subjects were clinically homogenous, possibly limiting generalizability of the findings.
  
  
  CONCLUSIONS
  Adolescent depression is associated with biased processing of negative stimuli that may be driven by sgACC dysregulation and may possibly lead to an imbalance among intrinsic functional brain networks. This work also establishes the use of combining neuroimaging and cognitive behavioral modeling methods to investigate cognitive and neural differences between psychiatric and healthy populations.
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Tiffany C
authors.initials: TC
authors.lastname: Ho
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Pete
authors.initials: P
authors.lastname: Cassey
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Brown
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Napoleon
authors.initials: N
authors.lastname: Hoang
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Melanie
authors.initials: M
authors.lastname: Chan
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Colm G
authors.initials: CG
authors.lastname: Connolly
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Eva
authors.initials: E
authors.lastname: Henje-Blom
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Larissa G
authors.initials: LG
authors.lastname: Duncan
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Chesney
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Paulus
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Max
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Ronak
authors.initials: R
authors.lastname: Patel
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States.
authors.forename: Alan N
authors.initials: AN
authors.lastname: Simmons
authors.affiliation: University of California, San Francisco, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, 94143, United States. Electronic address: tony.yang@ucsf.edu.
authors.forename: Tony T
authors.initials: TT
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D001921:Brain / Q000503:physiopathology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012720:Severity of Illness Index
keywords: Adolescent depression; Functional connectivity; Functional magnetic resonance imaging; Linear ballistic accumulator model; Psychophysiological interaction; Subgenual anterior cingulate cortex