{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T15:03:07Z","timestamp":1722697387983},"reference-count":64,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,10,13]],"date-time":"2012-10-13T00:00:00Z","timestamp":1350086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:p><jats:bold>Dysregulation of the hypothalamic\u2013pituitary\u2013adrenal (<jats:styled-content style=\"fixed-case\">HPA<\/jats:styled-content>) axis pathway is associated with several neuropsychiatric disorders, including post\u2010traumatic stress disorder (<jats:styled-content style=\"fixed-case\">PTSD<\/jats:styled-content>), major depressive disorder (<jats:styled-content style=\"fixed-case\">MDD<\/jats:styled-content>), schizophrenia and alcohol abuse. Studies have demonstrated an association between <jats:styled-content style=\"fixed-case\">HPA<\/jats:styled-content> axis dysfunction and gene variants within the cortisol, serotonin and opioid signaling pathways. We characterized polymorphisms in genes linked to these three neurotransmitter pathways and tested their potential interactions with <jats:styled-content style=\"fixed-case\">HPA<\/jats:styled-content> axis activity, as measured by dexamethasone (<jats:styled-content style=\"fixed-case\">DEX<\/jats:styled-content>) suppression response. We determined the percent <jats:styled-content style=\"fixed-case\">DEX<\/jats:styled-content> suppression of adrenocorticotropic hormone (<jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content>) and cortisol in 62 unrelated, male rhesus macaques. While <jats:styled-content style=\"fixed-case\">DEX<\/jats:styled-content> suppression of cortisol was robust amongst 87% of the subjects, <jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content> suppression levels were broadly distributed from \u221221% to 66%. Thirty\u2010seven monkeys from the high and low ends of the <jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content> suppression distribution (18 \u2018high\u2019 and 19 \u2018low\u2019 animals) were genotyped at selected polymorphisms in five unlinked genes (rh<jats:italic>CRH<\/jats:italic>, rh<jats:italic>TPH2<\/jats:italic>, rh<jats:italic>MAOA<\/jats:italic>, rh<jats:italic>SLC6A4<\/jats:italic> and rh<jats:italic>OPRM<\/jats:italic>). Associations were identified between three variants (rh<jats:italic>CRH<\/jats:italic>\u20102610C&gt;T, rh<jats:italic>TPH2<\/jats:italic> 2051A&gt;C and rh<jats:italic>5\u2010HTTLPR<\/jats:italic>) and level of DEX suppression of ACTH. In addition, a significant additive effect of the \u2018risk\u2019 genotypes from these three loci was detected, with an increasing number of \u2018risk\u2019 genotypes associated with a blunted ACTH response (<jats:italic>P<\/jats:italic>\u2009=\u20090.0009). These findings suggest that assessment of multiple risk alleles in serotonin and cortisol signaling pathway genes may better predict risk for HPA axis dysregulation and associated psychiatric disorders than the evaluation of single gene variants alone.<\/jats:bold><\/jats:p>","DOI":"10.1111\/j.1601-183x.2012.00856.x","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T18:03:16Z","timestamp":1348250596000},"page":"949-957","source":"Crossref","is-referenced-by-count":12,"title":["Genetic load is associated with hypothalamic\u2013pituitary\u2013adrenal axis dysregulation in\u00a0macaques"],"prefix":"10.1111","volume":"11","author":[{"given":"B.","family":"Ferguson","sequence":"first","affiliation":[{"name":"Division of Neurosciences, Oregon National Primate Research Center Oregon Health &amp; Sciences University  Beaverton OR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. E.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine  Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Luty","sequence":"additional","affiliation":[{"name":"Division of Neurosciences, Oregon National Primate Research Center Oregon Health &amp; Sciences University  Beaverton OR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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