title: Emotion-Dependent Functional Connectivity of the Default Mode Network in Adolescent Depression.
abstract: BACKGROUND
  Functional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD.
  
  
  METHODS
  We collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13-17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level-dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset.
  
  
  RESULTS
  Relative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC-subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset.
  
  
  CONCLUSIONS
  Adolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks.
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California, San Francisco, San Francisco, California. Electronic address: tiffany.ho@ucsf.edu.
authors.forename: Tiffany C
authors.initials: TC
authors.lastname: Ho
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California, San Francisco, San Francisco, California.
authors.forename: Colm G
authors.initials: CG
authors.lastname: Connolly
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California, San Francisco, San Francisco, California; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Henje Blom
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California, San Francisco, San Francisco, California.
authors.forename: Kaja Z
authors.initials: KZ
authors.lastname: LeWinn
authors.affiliation: Department of Psychiatry Veterans Affairs San Francisco Health Care System, San Francisco; Department of Psychiatry Veterans Affairs San Diego Health Care System, San Diego; Department of Psychiatry, University of California, San Diego, La Jolla, California.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Strigo
authors.affiliation: Department of Psychiatry Veterans Affairs San Diego Health Care System, San Diego.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Paulus
authors.affiliation: Department of Psychiatry, University of Colorado, Denver, Denver, Colorado.
authors.forename: Guido
authors.initials: G
authors.lastname: Frank
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Max
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, Washington.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.
authors.forename: Melanie
authors.initials: M
authors.lastname: Chan
authors.affiliation: Department of Psychiatry Veterans Affairs San Diego Health Care System, San Diego; Department of Psychiatry, University of California, San Diego, La Jolla, California.
authors.forename: Susan F
authors.initials: SF
authors.lastname: Tapert
authors.affiliation: Department of Psychiatry Veterans Affairs San Diego Health Care System, San Diego; Department of Psychiatry, University of California, San Diego, La Jolla, California; Veterans Affairs Center of Excellence for Stress and Mental Health, San Diego, California.
authors.forename: Alan N
authors.initials: AN
authors.lastname: Simmons
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California, San Francisco, San Francisco, California.
authors.forename: Tony T
authors.initials: TT
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D001921:Brain / Q000254:growth & development / Q000503:physiopathology*; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology*; D000066499:Facial Recognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000254:growth & development / Q000503:physiopathology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D011571:Psychoacoustics; D000297:Psychology, Adolescent; D012146:Rest; D012720:Severity of Illness Index
chemical_list: D010100:Oxygen
keywords: Adolescence; Default mode network; Functional connectivity; Functional magnetic resonance imaging; Major depressive disorder; Psychophysiologic interaction