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Research Article

Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum

Martin H. Teicher, Carl M. Anderson, and Ann Polcari
PNAS first published February 13, 2012; https://doi.org/10.1073/pnas.1115396109
Martin H. Teicher
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  • For correspondence: martin_teicher@hms.harvard.edu
Carl M. Anderson
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Ann Polcari
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  1. Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved December 28, 2011 (received for review September 19, 2011)

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Abstract

Childhood maltreatment or abuse is a major risk factor for mood, anxiety, substance abuse, psychotic, and personality disorders, and it is associated with reduced adult hippocampal volume, particularly on the left side. Translational studies show that the key consequences of stress exposure on the hippocampus are suppression of neurogenesis in the dentate gyrus (DG) and dendritic remodeling in the cornu ammonis (CA), particularly the CA3 subfield. The hypothesis that maltreatment is associated with volume reductions in 3-T MRI subfields containing the DG and CA3 was assessed and made practical by newly released automatic segmentation routines for FreeSurfer. The sample consisted of 193 unmedicated right-handed subjects (38% male, 21.9 ± 2.1 y of age) selected from the community. Maltreatment was quantified using the Adverse Childhood Experience study and Childhood Trauma Questionnaire scores. The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG subfields, and were not mediated by histories of major depression or posttraumatic stress disorder. Comparing subjects with high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed an average volume reduction of 6.3% and 6.1% in the left CA2-CA3 and CA4-DG, respectively. Volume reductions in the CA1 and fimbria were 44% and 60% smaller than in the CA2-CA3. Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively. These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.

  • child abuse
  • physical abuse
  • sexual abuse
  • allostatic load

Footnotes

  • ↵1M.H.T. and C.M.A. contributed equally to this work.

  • ↵2To whom correspondence should be addressed. E-mail: martin_teicher{at}hms.harvard.edu.
  • Author contributions: M.H.T. and A.P. designed research; M.H.T., C.M.A., and A.P. performed research; C.M.A. contributed new reagents/analytic tools; M.H.T. and C.M.A. analyzed data; and M.H.T., C.M.A., and A.P. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1115396109/-/DCSupplemental.

Freely available online through the PNAS open access option.

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Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum
Martin H. Teicher, Carl M. Anderson, Ann Polcari
Proceedings of the National Academy of Sciences Feb 2012, 201115396; DOI: 10.1073/pnas.1115396109

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Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum
Martin H. Teicher, Carl M. Anderson, Ann Polcari
Proceedings of the National Academy of Sciences Feb 2012, 201115396; DOI: 10.1073/pnas.1115396109
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