title: Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression.
abstract: The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents.
  
  
  
  We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24).
  
  
  
  Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later.
  
  
  
  Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized.
  
  
  
  Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time.
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA. Electronic address: colm.connolly@ucsf.edu.
authors.forename: Colm G
authors.initials: CG
authors.lastname: Connolly
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA; Department of Psychology, Stanford University, Stanford, CA, USA.
authors.forename: Tiffany C
authors.initials: TC
authors.lastname: Ho
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eva Henje
authors.initials: EH
authors.lastname: Blom
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA.
authors.forename: Kaja Z
authors.initials: KZ
authors.lastname: LeWinn
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA; Department of Psychology, Stanford University, Stanford, CA, USA; Neurosciences Program, Stanford University, Stanford, CA, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Sacchet
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, 1700 4th St., San Francisco, CA, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Tymofiyeva
authors.affiliation: Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, USA; Veterans Affairs San Diego Health Care System, La Jolla, CA, USA.
authors.forename: Alan N
authors.initials: AN
authors.lastname: Simmons
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA.
authors.forename: Tony T
authors.initials: TT
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D003863:Depression / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D018450:Disease Progression; D004644:Emotions; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012146:Rest; D000068356:Self-Control; D012720:Severity of Illness Index
keywords: Adolescent major depression; Amygdala; Dorsolateral prefrontal cortex; Resting-state; Ventromedial prefrontal cortex