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Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD

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Abstract

Rationale

Early Life Stress (ELS) increases risk for both adult traumatization and posttraumatic stress disorder (PTSD). Adult PTSD may also reflect a continuation of a response to an earlier exposure to adversity. Given similarities between neuroendocrine aspects of PTSD and ELS, such as in reduced cortisol signaling and glucocorticoid receptor (GR) responsiveness, some aspects of the biology of PTSD may reflect biological correlates of risk.

Objectives

This paper will examine how empirical findings regarding the biological basis of ELS can inform our understanding of the neuroendocrinology of PTSD. This paper will also propose a hypothetical model to guide future research that integrates genetic, epigenetic, neuroendocrine, and psychological observations to understand the contribution of ELS neurobiology to PTSD.

Results

Recent genetic findings demonstrate heritable aspects of at least some of these cortisol-related disturbances. Furthermore, ELS may produce at least some of the PTSD-associated changes in glucocorticoid responsiveness through epigenetic mechanisms such as developmental programming. These, then, may contribute to enduring changes in stress responsiveness as well as enhanced risk for adult exposure and PTSD.

Conclusion

Molecular mechanisms associated with gene x environment interactions or GR programming are essential in explaining current observations in the neuroendocrinology of PTSD that have been difficult to understand through the lens of contemporary stress theory.

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Acknowledgements of funding and grants

This work was supported by the following funding: NIMH MH088101, DOD PT073577 and 10164894, and VA Merit Review to RY. We thank Dr. Linda M. Bierer for her careful reading of this manuscript and thoughtful suggestions.

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Authors and Affiliations

  1. Department of Psychiatry, James J. Peters Veterans Affairs Medical Center, 526 OOMH, 130 W. Kingsbridge Rd, Bronx, NY, USA

    Rachel Yehuda, Janine D. Flory & Laura C. Pratchett

  2. Department of Psychiatry and Neurobiology Mount Sinai School of Medicine, New York, NY, USA

    Rachel Yehuda & Joseph Buxbaum

  3. Department of Psychology, Queens College and the Graduate Center, City University of New York, New York, NY, USA

    Janine D. Flory

  4. Max Planck Institute of Psychiatry, Munich, Germany

    Marcus Ising & Florian Holsboer

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  1. Rachel Yehuda
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  2. Janine D. Flory
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  3. Laura C. Pratchett
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  4. Joseph Buxbaum
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  5. Marcus Ising
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  6. Florian Holsboer
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Correspondence to Rachel Yehuda.

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Yehuda, R., Flory, J.D., Pratchett, L.C. et al. Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD. Psychopharmacology 212, 405–417 (2010). https://doi.org/10.1007/s00213-010-1969-6

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  • DOI: https://doi.org/10.1007/s00213-010-1969-6

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