Editing Hypothalamic–pituitary–adrenal axis (section)

====Early life stress====
Exposure to mild or moderate [[stressor]]s early in life has been shown to enhance HPA regulation and promote a lifelong resilience to stress. In contrast, early-life exposure to extreme or prolonged [[Stress (biology)|stress]] can induce a hyper-reactive HPA axis and may contribute to lifelong vulnerability to stress.<ref name="Flinn MV, Nepomnaschy PA, Muehlenbein MP, Ponzi D 1611–29">{{cite journal |vauthors=Flinn MV, Nepomnaschy PA, Muehlenbein MP, Ponzi D |title=Evolutionary functions of early social modulation of hypothalamic–pituitary–adrenal axis development in humans |journal=Neurosci Biobehav Rev|volume=35|issue=7 |pages=1611–29 |date=June 2011|pmid=21251923 |doi=10.1016/j.neubiorev.2011.01.005|s2cid=16950714 }}</ref> 

Adult survivors of childhood abuse have exhibited increased [[ACTH]] concentrations in response to a [[psychosocial]] stress task compared to unaffected controls and subjects with [[Depression (mood)|depression]], but not childhood abuse.<ref name = "Heim et al. 2000">{{cite journal |author1=Heim C. |author2=Newport D. J. |author3=Heit S. |author4=Graham Y. P. |author5=Wilcox M. |author6=Bonsall R. |author7=Nemeroff C. B. | year = 2000 | title = Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood | journal = JAMA | volume = 284 | issue = 5| pages = 592–597 | doi=10.1001/jama.284.5.592 | pmid=10918705| doi-access=free }}</ref>

The HPA axis was present in the earliest vertebrate species, and has remained highly conserved by strong positive selection due to its critical adaptive roles.<ref>{{cite journal | author = Denver RJ | date = Apr 2009 | title = Structural and functional evolution of vertebrate neuroendocrine stress systems | url = https://deepblue.lib.umich.edu/bitstream/2027.42/74370/1/j.1749-6632.2009.04433.x.pdf | journal = Ann N Y Acad Sci | volume = 1163 | issue = 1 | pages = 1–16 | doi = 10.1111/j.1749-6632.2009.04433.x | pmid = 19456324 | hdl = 2027.42/74370 | bibcode = 2009NYASA1163....1D | s2cid = 18786346 | hdl-access = free | access-date = 2019-09-01 | archive-date = 2023-08-10 | archive-url = https://web.archive.org/web/20230810073053/https://deepblue.lib.umich.edu/bitstream/handle/2027.42/74370/j.1749-6632.2009.04433.x.pdf;jsessionid=63DD8A308C8F78D25A2FD5213858CF25?sequence=1 | url-status = live }}</ref> The programming of the HPA axis is strongly influenced by the perinatal and early juvenile environment, or "early-life environment".<ref name="Neurosci Biobehav Rev 2009">{{cite journal |vauthors=Oitzl MS, Champagne DL, van der Veen R, de Kloet ER | date = May 2010 | title = Brain development under stress: hypotheses of glucocorticoid actions revisited | journal = Neurosci Biobehav Rev | volume = 34 | issue = 6| pages = 853–66 | doi = 10.1016/j.neubiorev.2009.07.006 | pmid = 19631685 | s2cid = 25898149 }}</ref> Maternal stress and differential degrees of caregiving may constitute early life adversity, which has been shown to profoundly influence, if not permanently alter, the offspring's stress and emotional regulating systems.<ref name="Neurosci Biobehav Rev 2009"/>