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Author Notes:

Diego A. Pizzagalli, Ph.D., Center for Depression, Anxiety and Stress Research, McLean Hospital, 115 Mill Street, Belmont, MA 02478, mtreadway@mclean.harvard.edu or dap@mclean.harvard.edu, Phone 617-855-4230, Fax: 617-855-4231.

The authors are grateful to Elena L. Goetz, Jeffrey Birk, Sunny J. Dutra and Nancy Brooks Hall for their skilled assistance with this study.

Drs. Treadway, Dillon, Holmes, Chakravarty, Polli, and Gabrieli, Mr. Waskom, Mr. Park and Ms. Dutra report no biomedical financial interests to disclose.

Complete list of disclosures available in full text.


Research Funding:

This study was supported by the W. Garfield Weston Foundation to MMC; and the National Institute of Mental Health (NIMH) grant R01 MH068376 awarded to DAP; as well as National Center for Complementary & Alternative Medicine (NCCAM) grant R21 AT002974 awarded to DAP; and NCCAM R01 AT001638 awarded to MF.

AJH and DGD were supported by grants K01 MH099232 and K99 MH094438, respectively.


  • Dentate gyrus
  • Hippocampus
  • MAGeT brain
  • MRI
  • Major depression
  • mPFC
  • Adult
  • Amygdala
  • Depressive Disorder, Major
  • Disease Progression
  • Female
  • Hippocampus
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Organ Size
  • Prefrontal Cortex
  • Recurrence
  • Stress, Psychological

Illness progression, recent stress, and morphometry of hippocampal subfields and medial prefrontal cortex in major depression

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Journal Title:

Biological Psychiatry


Volume 77, Number 3


, Pages 285-294

Type of Work:

Article | Post-print: After Peer Review


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.

Copyright information:

© 2015 Society of Biological Psychiatry.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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