title: Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression.
abstract: BACKGROUND
  Increased sensitivity to stress and dysfunctional reward processing are two primary characteristics of major depressive disorder (MDD) that may persist after remission. Preclinical work has established the pivotal role of the striatum in mediating both stress and reward responses. Human neuroimaging studies have corroborated these preclinical findings and highlighted striatal dysfunction in MDD in response to reward but have yet to investigate striatal function during stress, in particular in individuals with recurrent depression.
  
  
  METHODS
  A validated mild psychological stress task involving viewing of negative stimuli during functional magnetic resonance imaging was conducted in 33 remitted individuals with a history of recurrent major depressive disorder (rMDD) and 35 matched healthy control subjects. Cortisol and anxiety levels were assessed throughout scanning. Stress-related activation was investigated in three striatal regions: caudate, nucleus accumbens, and putamen. Psychophysiologic interaction analyses probed connectivity of regions with central structures of the neural stress circuitry, such as the amygdala and hippocampus.
  
  
  RESULTS
  The task increased cortisol and anxiety levels, although to a greater extent in rMDD individuals than healthy control subjects. In response to the negative stimuli, rMDD individuals, but not controls, also exhibited significantly potentiated caudate, nucleus accumbens, and putamen activations and increased caudate-amygdala and caudate-hippocampus connectivity.
  
  
  CONCLUSIONS
  The findings highlight striatal hypersensitivity in response to a mild psychological stress in rMDD, as manifested by hyperactivation and hyperconnectivity with the amygdala and hippocampus. Striatal hypersensitivity during stress might thus constitute a trait mark of depression, providing a potential neural substrate for the interaction between stress and reward dysfunction in MDD.
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts.
authors.forename: Roee
authors.initials: R
authors.lastname: Admon
authors.affiliation: Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts; Connors Center for Women's Health and Gender Biology, Division of Women's Health, Department of Medicine; Department of Psychiatry, Brigham & Women's Hospital, Boston, Massachusetts.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Holsen
authors.affiliation: Connors Center for Women's Health and Gender Biology, Division of Women's Health, Department of Medicine; Department of Psychiatry, Brigham & Women's Hospital, Boston, Massachusetts.
authors.forename: Harlyn
authors.initials: H
authors.lastname: Aizley
authors.affiliation: Connors Center for Women's Health and Gender Biology, Division of Women's Health, Department of Medicine.
authors.forename: Anne
authors.initials: A
authors.lastname: Remington
authors.affiliation: Athinoula A. Martinos Center, Massachusetts General Hospital and Massachusetts Institute of Technology, Charlestown, Massachusetts; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.affiliation: Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts; Connors Center for Women's Health and Gender Biology, Division of Women's Health, Department of Medicine; Department of Psychiatry, Brigham & Women's Hospital, Boston, Massachusetts; Athinoula A. Martinos Center, Massachusetts General Hospital and Massachusetts Institute of Technology, Charlestown, Massachusetts.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Goldstein
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts; McLean Imaging Center, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts. Electronic address: dap@mclean.harvard.edu.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Pizzagalli
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology; D001007:Anxiety / Q000097:blood / Q000503:physiopathology; D001931:Brain Mapping; D003342:Corpus Striatum / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D012008:Recurrence; D013315:Stress, Psychological / Q000097:blood / Q000150:complications / Q000503:physiopathology*
chemical_list: D006854:Hydrocortisone
keywords: Caudate; Depression; Psychophysiologic Interaction (PPI); Reward; Stress; fMRI