title: Illness progression, recent stress, and morphometry of hippocampal subfields and medial prefrontal cortex in major depression.
abstract: BACKGROUND
  Longitudinal studies of illness progression in patients with major depressive disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in patients with MDD--especially in medial prefrontal cortex (mPFC) and the hippocampus--but few studies have investigated whether these changes are exacerbated by prior episodes.
  
  
  METHODS
  In a sample of 103 medication-free patients with depression and control subjects with no history of depression, structural magnetic resonance imaging was performed to examine relationships between number of prior episodes, current stress, hippocampal subfield volume and cortical thickness. Volumetric analyses of the hippocampus were performed using a recently validated subfield segmentation approach, and cortical thickness estimates were obtained using vertex-based methods. Participants were grouped on the basis of the number of prior depressive episodes and current depressive diagnosis.
  
  
  RESULTS
  Number of prior episodes was associated with both lower reported stress levels and reduced volume in the dentate gyrus. Cortical thinning of the left mPFC was associated with a greater number of prior depressive episodes but not current depressive diagnosis.
  
  
  CONCLUSIONS
  Collectively, these findings are consistent with preclinical models suggesting that the dentate gyrus and mPFC are especially vulnerable to stress exposure and provide evidence for morphometric changes that are consistent with stress-sensitization models of recurrence in MDD.
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital/Harvard Medical School, Belmont, Massachusetts.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Treadway
authors.affiliation: Department of Psychology, Stanford University, Palo Alto, California.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Waskom
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital/Harvard Medical School, Belmont, Massachusetts.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Dillon
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Department of Psychology, Yale University, New Haven, Connecticut.
authors.forename: Avram J
authors.initials: AJ
authors.lastname: Holmes
authors.affiliation: Kimel Family Imaging-Genetics Laboratory, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Min Tae M
authors.initials: MTM
authors.lastname: Park
authors.affiliation: Kimel Family Imaging-Genetics Laboratory, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry and Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut.
authors.forename: Sunny J
authors.initials: SJ
authors.lastname: Dutra
authors.affiliation: Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Frida E
authors.initials: FE
authors.lastname: Polli
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Dan V
authors.initials: DV
authors.lastname: Iosifescu
authors.affiliation: Depression Clinical and Research Program, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: John D E
authors.initials: JDE
authors.lastname: Gabrieli
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital/Harvard Medical School, Belmont, Massachusetts. Electronic address: dap@mclean.harvard.edu.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Pizzagalli
mesh_terms: D000328:Adult; D000679:Amygdala / Q000473:pathology; D003865:Major Depressive Disorder / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D017397:Prefrontal Cortex / Q000473:pathology*; D012008:Recurrence; D013315:Stress, Psychological / Q000473:pathology* / Q000503:physiopathology
keywords: Dentate gyrus; Hippocampus; MAGeT brain; MRI; Major depression; mPFC
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