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Neural Correlates of Three Promising Endophenotypes of Depression: Evidence from the EMBARC Study.

  • Webb CA Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, USA.
  • Dillon DG Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, USA.
  • Pechtel P Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, USA.
  • Goer FK Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, USA.
  • Murray L Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, USA.
  • Huys QJ Centre for Addiction Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Switzerland.
  • Fava M Clinical Research Program, Massachusetts General Hospital, Boston, MA, USA.
  • McGrath PJ Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
  • Weissman M Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
  • Parsey R Department of Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, NY, USA.
  • Kurian BT Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Adams P Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
  • Weyandt S Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Trombello JM Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Grannemann B Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Cooper CM Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Deldin P Department of Psychiatry, University of Michigan Health System, Ann Arbor, MI, USA.
  • Tenke C Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
  • Trivedi M Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Bruder G Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
  • Pizzagalli DA Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, USA.
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  • 2015-06-13
Published in:
  • Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - 2016
Adolescent
Adult
Aged
Anxiety Disorders
Brain
Depressive Disorder, Major
Electroencephalography
Endophenotypes
Humans
Middle Aged
Motor Activity
Neuropsychological Tests
Neuroticism
Psychiatric Status Rating Scales
Reaction Time
Rest
Reward
Tomography
Young Adult
English Major depressive disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes. Guided by the NIMH Research Domain Criteria initiative, we used source localization of scalp-recorded EEG resting data to examine the neural correlates of three emerging endophenotypes of depression: neuroticism, blunted reward learning, and cognitive control deficits. Data were drawn from the ongoing multi-site EMBARC study. We estimated intracranial current density for standard EEG frequency bands in 82 unmedicated adults with MDD, using Low-Resolution Brain Electromagnetic Tomography. Region-of-interest and whole-brain analyses tested associations between resting state EEG current density and endophenotypes of interest. Neuroticism was associated with increased resting gamma (36.5-44 Hz) current density in the ventral (subgenual) anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC). In contrast, reduced cognitive control correlated with decreased gamma activity in the left dorsolateral prefrontal cortex (dlPFC), decreased theta (6.5-8 Hz) and alpha2 (10.5-12 Hz) activity in the dorsal ACC, and increased alpha2 activity in the right dlPFC. Finally, blunted reward learning correlated with lower OFC and left dlPFC gamma activity. Computational modeling of trial-by-trial reinforcement learning further indicated that lower OFC gamma activity was linked to reduced reward sensitivity. Three putative endophenotypes of depression were found to have partially dissociable resting intracranial EEG correlates, reflecting different underlying neural dysfunctions. Overall, these findings highlight the need to parse the heterogeneity of MDD by focusing on promising endophenotypes linked to specific pathophysiological abnormalities.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/147315
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