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


OBJECTIVE
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.


CONCLUSIONS
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.
Yehuda
Rachel
R
Department of Psychiatry, James J. Peters Veterans Affairs Medical Center, 526 OOMH, 130 W. Kingsbridge Rd, Bronx, NY, USA. rachel.yehuda@va.gov
Flory
Janine D
JD
Pratchett
Laura C
LC
Buxbaum
Joseph
J
Ising
Marcus
M
Holsboer
Florian
F
D000328:Adult; D000818:Animals; D002648:Child; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008960:Models, Psychological; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology* / Q000235:genetics / Q000523:psychology; D013315:Stress, Psychological / Q000150:complications*
D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone