title: Altered insular activation and increased insular functional connectivity during sad and happy face processing in adolescent major depressive disorder.
abstract: BACKGROUND
  Major depressive disorder (MDD) is a leading cause of disability worldwide and occurs commonly first during adolescence. The insular cortex (IC) plays an important role in integrating emotion processing with interoception and has been implicated recently in the pathophysiology of adult and adolescent MDD. However, no studies have yet specifically examined the IC in adolescent MDD during processing of faces in the sad-happy continuum. Thus, the aim of the present study is to investigate the IC during sad and happy face processing in adolescents with MDD compared to healthy controls (HCL).
  
  
  METHODS
  Thirty-one adolescents (22 female) with MDD and 36 (23 female) HCL underwent a well-validated emotional processing fMRI paradigm that included sad and happy face stimuli.
  
  
  RESULTS
  The MDD group showed significantly less differential activation of the anterior/middle insular cortex (AMIC) in response to sad versus happy faces compared to the HCL group. AMIC also showed greater functional connectivity with right fusiform gyrus, left middle frontal gyrus, and right amygdala/parahippocampal gyrus in the MDD compared to HCL group. Moreover, differential activation to sad and happy faces in AMIC correlated negatively with depression severity within the MDD group.
  
  
  CONCLUSIONS
  Small age-range and cross-sectional nature precluded assessment of development of the AMIC in adolescent depression.
  
  
  CONCLUSIONS
  Given the role of the IC in integrating bodily stimuli with conscious cognitive and emotional processes, our findings of aberrant AMIC function in adolescent MDD provide a neuroscientific rationale for targeting the AMIC in the development of new treatment modalities.
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California San Francisco, San Francisco, CA, USA; Department of Clinical Neuroscience, Karolinska Institutet, 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, 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, University of California San Francisco, San Francisco, CA, USA.
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, CA, USA.
authors.forename: Kaja Z
authors.initials: KZ
authors.lastname: LeWinn
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Nisreen
authors.initials: N
authors.lastname: Mobayed
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California San Francisco, San Francisco, CA, USA; Institute for Interdisciplinary Studies, Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Psychiatry, University of California, San Diego, CA, USA; Laureate Institute for Brain Research, Tulsa, OK, USA.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Paulus
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California San Francisco, San Francisco, CA, USA; Department of Bioengineering at the University of Washington, Seattle, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, University of California, San Diego, CA, USA; The Veterans Affairs Health Care System of San Diego, 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, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Tony T
authors.initials: TT
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology; D002540:Cerebral Cortex / Q000503:physiopathology*; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D004644:Emotions; D005149:Facial Expression; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D006240:Happiness; D006801:Humans; D008032:Limbic System / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D012720:Severity of Illness Index
keywords: Adolescent major depressive disorder; Anterior insular cortex; Functional connectivity; Functional magnetic resonance imaging
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