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Functional connectivity of negative emotional processing in adolescent depression.

  • Author(s): Ho, Tiffany C;
  • Yang, Guang;
  • Wu, Jing;
  • Cassey, Pete;
  • Brown, Scott D;
  • Hoang, Napoleon;
  • Chan, Melanie;
  • Connolly, Colm G;
  • Henje-Blom, Eva;
  • Duncan, Larissa G;
  • Chesney, Margaret A;
  • Paulus, Martin P;
  • Max, Jeffrey E;
  • Patel, Ronak;
  • Simmons, Alan N;
  • Yang, Tony T
  • et al.


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.


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.


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).


Subjects were clinically homogenous, possibly limiting generalizability of the findings.


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.

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