title: Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties.
abstract: BACKGROUND
  Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored.
  
  
  METHODS
  In this study 26 unmedicated adults with MDD and 29 matched healthy controls (HCs) completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psychophysiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e. monetary gains and penalties).
  
  
  RESULTS
  Relative to HCs, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC subregion in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with greater improvement in symptoms 12 weeks later.
  
  
  CONCLUSIONS
  These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action-outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD.
authors: Center for Depression, Anxiety and Stress Research,McLean Hospital/Harvard Medical School Belmont,MA,USA.
authors: R
authors: R
authors: Admon
authors: McLean Imaging Center,McLean Hospital/Harvard Medical School Belmont,MA,USA.
authors: L D
authors: LD
authors: Nickerson
authors: Center for Depression, Anxiety and Stress Research,McLean Hospital/Harvard Medical School Belmont,MA,USA.
authors: D G
authors: DG
authors: Dillon
authors: Department of Psychology,Harvard University,Cambridge, MA,USA.
authors: A J
authors: AJ
authors: Holmes
authors: Department of Psychology,Washington University in St Louis,St Louis, MO,USA.
authors: R
authors: R
authors: Bogdan
authors: Center for Depression, Anxiety and Stress Research,McLean Hospital/Harvard Medical School Belmont,MA,USA.
authors: P
authors: P
authors: Kumar
authors: Department of Psychiatry,Massachusetts General Hospital/Harvard Medical School Boston,MA,USA.
authors: D D
authors: DD
authors: Dougherty
authors: Mood and Anxiety Disorders Program,Mount Sinai School of Medicine,New York, NY,USA.
authors: D V
authors: DV
authors: Iosifescu
authors: Department of Psychiatry,Massachusetts General Hospital/Harvard Medical School Boston,MA,USA.
authors: D
authors: D
authors: Mischoulon
authors: Department of Psychiatry,Massachusetts General Hospital/Harvard Medical School Boston,MA,USA.
authors: M
authors: M
authors: Fava
authors: Center for Depression, Anxiety and Stress Research,McLean Hospital/Harvard Medical School Belmont,MA,USA.
authors: D A
authors: DA
authors: Pizzagalli
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D016022:Case-Control Studies; D015283:Citalopram / Q000627:therapeutic use; D003342:Corpus Striatum / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009042:Motivation; D011569:Psychiatric Status Rating Scales; D011678:Punishment; D012044:Regression Analysis; D012436:S-Adenosylmethionine / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D012436:S-Adenosylmethionine