Editing Hypothalamic–pituitary–adrenal axis (section)

==Stress==
[[File:ХПА-оска на стрес во мозокот.jpg|thumb|175px|right| Schematic overview of the hypothalamic-pituitary-adrenal (HPA) axis. Stress activates the HPA-axis and thereby enhances the secretion of glucocorticoids from the adrenals.]]

Activation of the HPA axis causes release of glucocorticoids, which target numerous organ systems to activate energy reserves in response to stress demands.<ref name="herman">{{cite journal |vauthors=Herman JP, McKlveen JM, Ghosal S, Kopp B, Wulsin A, Makinson R, Scheimann J, Myers B |title=Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response |journal=Comprehensive Physiology |volume=6 |issue=2 |pages=603–21 |date=March 2016 |pmid=27065163 |doi=10.1002/cphy.c150015|pmc=4867107 |isbn=978-0-470-65071-4 }}</ref> The HPA stress response is controlled mostly by neural mechanisms, which cause release of corticotrophin releasing hormone (CRH). Neural mechanisms determining responses to chronic stress are different from those that control acute reactions. Individual responses to acute or chronic stress are determined by multiple factors, including age, gender, genetics, environmental factors, and early life experiences.<ref name=herman/>

===Stress and development===
{{medical references|section|date=March 2025}}
====Prenatal stress====

There is evidence that [[prenatal stress]] can influence HPA regulation. In humans, prolonged [[Prenatal stress|maternal stress]] during [[gestation]] is associated with mild [[Cognitive impairment|impairment of intellectual activity]] and [[language development]] in their children, and with behavior disorders such as [[ADHD|attention deficits]], [[schizophrenia]], [[anxiety]] and [[mood disorders|depression]]; self-reported maternal stress is associated with a higher irritability, emotional and attentional problems.<ref>{{cite journal |author=Weinstock M |title=The long-term behavioural consequences of prenatal stress |journal=Neuroscience and Biobehavioral Reviews |volume=32 |issue=6 |pages=1073–86 |date=August 2008 |pmid=18423592 |doi=10.1016/j.neubiorev.2008.03.002 |s2cid=3717977 |url=http://www.hkmacme.org/course/2008BW07-01-00/SP0708.pdf |access-date=2014-05-04 |archive-date=2023-08-10 |archive-url=https://web.archive.org/web/20230810072550/http://www.hkmacme.org/course/2008BW07-01-00/SP0708.pdf |url-status=live }}</ref>

There is evidence that prenatal stress can affect HPA regulation in humans. Children who were stressed prenatally may show altered [[cortisol]] rhythms. Prenatal stress has also been implicated in a tendency toward depression and short attention span in childhood.<ref>{{cite journal |vauthors=Buitelaar JK, Huizink AC, Mulder EJ, de Medina PG, Visser GH |title=Prenatal stress and cognitive development and temperament in infants |journal=Neurobiology of Aging |volume=24 |pages=S53–60; discussion S67–8 |year=2003 |issue=Suppl 1 |pmid=12829109 |doi=10.1016/S0197-4580(03)00050-2|s2cid=3008063 }}</ref>{{better source|date=March 2025}}

====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"/>