Jussi Jokinen, Adrian E. Boström, Manuela Chatzittofis, ʻO Diana M. Ciuculete, Katarina Görts Öberg, ʻO John N. Flanagan, ʻO Stefan Arver, Helgi B. Schiöth
DOI: http://dx.doi.org/10.1016/j.psyneuen.2017.03.007
o ka Naauao
- •ʻO nā maʻi me ka maʻi kūkino i hōʻemi i nā anuu o ka methylation ma kahi wahi o ka gene CRH.
- •ʻO nā maʻi me ka maʻiʻehaʻeha ua kiʻekiʻe aʻe (TNF) -a mau kiʻekiʻe i ka hoʻohālikeʻana i nā limahana olakino.
Hōʻuluʻulu Manaʻo
Hypersexual kāna hana (HD) hoakakaia like 'ole-paraphilic moe makemake kāna hana me eiiiiiaiou o ka compulsivity, impulsivity a me ka hana' ino, a me ka manao like me kaʻike, i loko o ka DSM 5, puu kekahi overlapping hiʻona me ka waiwai a pau i kāna hana a me na neurotransmitter nenoai a me dysregulated hypothalamic-pituitary -ahana axis (HPA). Ma kēia hoʻokolohua, me nā poʻe maʻi 67 HD a me ka 39 kāne kāne limahana ola olakino, ua makemake mākou eʻike i nā pūnaewele HPA i hui pūʻia me nā pūnaewele CpG, kahi e pili ana i nā hoʻololi o ka epigenetic profile me ka moekolohe.
Ua anaʻia keʻano o ka methylation hulu genome i ke koko holoʻokoʻa e hoʻohana ana i ka Illinina Infinium Methylation EPIC BeadChip, e ana ana i keʻano methylation o nā pūnaewele 850 K CpG. Ma mua o ka hoʻoukaʻana, ua hana muaʻia ka'ōnaehana methylation DNA āpau e like me nā kūlana maʻamau a hoʻololiʻia no ka nui o ka hili o ke koko. Mākou komo CpG kahua ke aupuni 'loko o 2000 BP o ka transcriptional hoʻomaka' ana kahua o nā kēia mau HPA-(axis) hui nā'ōewe: Corticotropin ka hoʻokuʻu 'hōmona (CRH), corticotropin ka hoʻokuʻu' hōmona ka paa kumuʻiʻo (CRHBP), corticotropin ka hoʻokuʻu 'hōmona mea loaʻa 1 (CRHR1), corticotropin ka hoʻokuʻu' hōmona 2 pūnana (CRHR2), FKBP5 a me ka diacorticoid receptor (NR3C1). Ua hana mākou i nā hiʻohiʻona hoʻohālike maʻamau o nā methylation M-mau waiwai i kahiʻano kālai'āina o ka moekolohe, hoʻololi no ka pilikia, deachamethasone ke kū'ēʻole i ke kūlana, Childhood Trauma Questionnaire ka helu piha a me nā plasma o ka TNF-alpha a me IL-6.
No 76 i hoʻokolohua i nā pūnaewele CpG pākahi, ʻehā mau mea nui nominally (p <0.05), e pili pū ana me nā genes CRH, CRHR2 a me NR3C1. Cg23409074 – Aia 48 bp i uka o ka ka pūnaewele pūnaewele o ka gene CRH - ua kaumaha hypomethylated nui ma nā mea maʻamau ma hope o nā hoʻoponopono no nā ho'āʻo nui e hoʻohana ana i ke kaʻina FDR. Ua hoʻopili maikaʻiʻia nā methylation o cg23409074 me ka hōʻikeʻana o ka genH CRH ma kahi hui kūʻokoʻa o 11 mau kāne kāne ola ola. ʻO ka methylation ma kahi pae CRH i heluʻia, cg23409074, ua hoʻokaʻina nuiʻia ma waena o nā koko a me nāʻano loloʻehā.
He mea koʻikoʻi nui CRH o nā pane no ka neuroendocrine i loko o ka lolo, me kahi koʻikoʻi i nā kaʻina hana hoʻonāukiuki. Hōʻikeʻia nā hualoaʻa o ka epigenetic i nā kinona CRH e pili ana i ka maʻiʻehaʻeha i loko o nā kāne.
kūkākūkā
I loko o kēia haʻawina, uaʻike mākou he mea hōʻemi nā kāne kāne me ka maʻiʻeha i ka methylation ma kahi o ka methylation locus (cg23409074) kahi i kūkuluʻia ma 48 bp ma kahi kiʻekiʻe o ka pūnaewele hoʻomaka o ka CRH gene. Eia kekahi, ua hoʻohui maikaʻiʻia kēia wahi o ka methylation me ka hōʻike genhā CRH ma kahi hui kūʻokoʻa o nā kāne kāne ola olakino. I ko mākouʻike,ʻo kēia ka hōʻike mua o nā hanana epigenetic e pili ana i ka maʻiʻeha. Ua hoʻohana mākou i nā'āpana methylation genome-whānui a me nā pūnaewele 850K CpG, akā naʻe, ma muli o kā mākouʻike muaʻana i ka Dysregulation HPA i nā kāne me ka maʻiʻeha (Chatzittofis et al., 2016), ua noi mākou i kahi i kaupalenaʻia e pili ana i nā kinakahi o ka axis HPA.
ʻO CRH kahi mea hoʻohui nui o nā neuroendocrine stress pane i ka lolo, hoʻololi i ka lawena a me ka ʻōnaehana autonomic (Arborelius et al., 1999), a me nā neuroplasticity (Regev & Baram, 2014). Ke noʻonoʻo nei i ka maʻi hypersexual i ke ʻano o ka neurobiology hōʻalo, ua hoʻokūpaʻa maikaʻi ʻia he kuleana nui ko CRH i ke kaʻina hana hōʻalo (Zorrilla et al., 2014). I nā ʻōkuhi rodent, hoʻokau ka ʻōnaehana CRF i ka hana maʻa ma o nā hana ma ka amygdala i hoʻonui ʻia, e hana ana i nā ʻano like me ka hopohopo, nā uku o ka uku, ka hoʻoponopono ponoʻī ʻana i ka lāʻau a me ka ʻimi ʻana i ka lāʻau e ʻimi nei i ka hana (Zorrilla et al., 2014). Eia kekahi, ʻo ka hoʻoulu ʻana o nā neurons CRF i ka medial prefrontal cortex e hāʻawi i ka nalo ʻana o ka mana i ʻike ʻia ma nā mea HD. Ua hōʻike ʻia ka hoʻohana ʻana o ka lāʻau maʻamau i alakaʻi i kahi axis hyperpa HPA me ka hoʻonui ʻia o nā pae ACTH ʻoiai he kuleana nui ka CRH i ka hoʻoponopono ʻana i nā pane hopena maikaʻi ʻole i ke koʻikoʻi i ka haʻalele ʻana o ka lāʻau (Kakko et al., 2008; Koob et al., 2014). Pēlā nō, kahi axis HPA hyperactive me nā pae ACTH kiʻekiʻe a me nā loli epigenetic i ka gen CRH i nā kāne kāne me ka maʻi hypersexual hiki ke alakaʻi i kahi pōʻai o ka ʻiʻini a hoʻi hou, me kahi kūlana allostatic manaʻo maikaʻi ʻole, e mālama nei i ka hana hypersexual i kahi hana lapuwale e uku panai no ka mokuʻāina manaʻo dysphoric. E hana pinepine i nā moemoeā moekolohe, kaomi ʻana a i ʻole nā lawena i ka pane ʻana i nā kūlana dysphoric a me / a i ʻole i ka pane ʻana i nā hanana ola koʻikoʻi he mau ʻōuli nui ia i nā pae hoʻohālikelike diagnostics o ka maʻi hypersexual (Kafka, 2010). ʻO kā mākou ʻike o ka hypomethylation o kahi ʻāpana CRH e pili ana i ka hui methylation locus i pili me ka'ōlelo maʻamau ma kahi hui kūʻokoʻa, e hoʻohui i nā hōʻike mua o ka dysregulation axis o ka HPA i nā maʻi kāne me ka maʻiʻeha koko ma kahi pāʻani mole. Heroin pakiko-aaieieno? Hana i pili me ka palena pau CRH ka hōʻikeʻana'ōewe 'aoʻao o kekahi hooponopono ma ka methylation hoʻololi ai i loko o ka holoholona ÷ (McFalls listen'ōlelo., 2016) a me ka mea hoʻopaipai methylation i ua hoike e ka hopena ma luna o ka hōʻike kumu o CRH (Chen listen'ōlelo., 2012). Eia naʻe, ka nui o ka methylation ma kahi o ka CRH gene locus (cg23409074) he haʻahaʻa loa (mean meaning like 1.60%), a me keʻano pilikino o ke hoʻololi ponoʻia nā methylation maaleaʻole. Aia nō naʻe, heʻano ulu o ka puke palapala nā keneka pono'ī, e kuhikuhi ana i nā hua'ōlelo a me nā huapalapala nui o nā hua'ōlelo ka hoʻololiʻana o ka methylation (1-5%), ma kahi o ka nui o nā syndromes multifactorial e like me ka puʻuwai. schizophrenia (Leenen et al., 2016).
I loko o kēia haʻawina, ua lawe mākou i nā mea hōʻeha kūpono loa, e like me ke kaumaha, ka DST hanaʻole ka hoʻopauʻana, CTQ helu helu a me nā helu plasma o ka TNF-alpha, no kaʻikeʻana o nā hui ma waena o ka methylation o nā genes e pili ana i ke axis Horder a me ka maʻi kūkino . ʻO ka mea e mahalo ai,ʻo ka poʻe maʻi me ka maʻiʻehaʻeha uaʻoi aʻe ka kiʻekiʻe (TNF) -a mau mea i ka hoʻohālikelikeʻana i nā limahana olakino (Jokinen et al., 2016). No ka mea i ka pilina ma waena o nā glucocorticoids a me ka mumū a me nāʻokoʻa o ka hui ma TNF-alpha a me ka IL-6 kiʻekiʻe ma waena o nā maʻi a me nā mana olakino, ua hoʻohana mākou i nā hōʻailona inflammatory as covariates to e noʻonoʻo i ka hōhonu o ka neuroinflammation haʻahaʻa. ʻO keʻano o ka dysregulation he mea nui ia i ka pathophysiology e hilinaʻi ana i nā maʻi psychiatric me ke kaumaha nui, ka maʻi bipolar a me ka schizophrenia (Danzer et al., 2008). Low papa neuroinflammation ua pinepine ike i loko o nā mea maʻi me ka HPA (axis) dysregulation (Horowitz listen'ōlelo., 2013) a me ka hoʻoʻino kuhiakau Pono nń ke kūlana o psycho-neuroimmunological dysfunctions (Zunszain listen'ōlelo., 2013). Hiki i ka hoʻonui a me ka hōʻailona glucocorticoid ke hanaʻokoʻa ma nāʻano likeʻole a me nā kaʻina hana me ka hopena maʻamau i ka hopena o ka hopena o ka hopena; i kēia mau kāne'ōpiopio me HD he kiʻekiʻe ka helu kiʻekiʻe o ka TNFa i kūlikeʻia i nā kāne kōkua maikaʻi me ka nānāʻole i ka dysregulation axis (Jokinen et al., 2016). As i hōʻike muaʻia (Chatzittofis et al., 2016),ʻaʻohe hōʻailona antidepressant a iʻole ka kaumaha kaumaha. pili nui i ka hana hana HPA i loko o kēia heluna haumāna.
Eia hou i loko o kēia noi ʻana, ma muli o ka hōʻike ʻana o nā mea maʻi i nā pilikia o ke ola mua i hoʻohālikelike ʻia i nā kaohi olakino a me nā hopena kaulana o ka trauma kamaliʻi ma epigenome, ua hoʻohana mākou i ka pilikia o ke ola mua i nā hiʻohiʻona regression e noʻonoʻo i ka hopena hoʻohoka paha o ka wā kamaliʻi. trauma ma nā methylation lauana. ʻO ka disregulation HPA-axis e pili ana i ka pilikia o ke ola mua e hōʻike i ka nāwaliwali a me ka hana no ka uku o nā hopena o ka pilikia o ke kamaliʻi (Heim et al. 2008) a me ka pilikia o ke ola mua e pili ana i nā hoʻololi epigenetic o nā genes e pili ana i ka HPA-axis (Turecki & Meaney, 2016).
Ke conceptualization o ka hypersexual kāna hana i ua intensively hoopaapaa ana, a hiki nae i kaʻike, i me i loko o ka DSM-5, ke kahua o ke ao ua hōʻike he kiʻekiʻe degere o ka pono a me ka ho'ōia no ka mea i manaoia PalekanaEND_LINK ana hoʻohālike no hypersexual kāna hana (Reid listen'ōlelo. , 2012).
ʻO nā ikaika o ka hoʻonaʻauaoʻana he mau maʻi hoʻomanawanui likeʻole me nā diagnostical diagnostic o ka maʻi ka wahine, ke kākoʻo o ka makahiki o nā limahana olakino, me kaʻole o nā maʻi o nā maʻi āpau a me ka moʻolelo o kaʻohana no nā maʻi maʻi nui a me nā mea koʻikoʻi koʻikoʻi. Eia kekahi, hiki keʻikeʻia ka ikaika o ka noʻonoʻoʻana o nā mea hōʻoia pilikia e like me ka hoʻopiliʻana o ka'ōpiopio, ke kaumaha, nā hōʻailona neuroinflammatory a me nā hualoaʻa dexamethasone.
Nā hopena: hōʻike pūʻokoʻa o ke ola mua o ka nohona a me keʻano o ka hoʻolālā'eneke o ka aʻoʻana,ʻaʻole eʻae i nā manaʻo e pili ana i ka hopena. Eia kekahi, no ka meaʻo kēia ka hoʻomaka muaʻana o ka nānāʻana i nā'ōpikōpika i nā kāne me ka maʻiʻeha koko, he mea nui ka hoʻopiliʻana i kā mākou mauʻike ma kahi hui kūʻokoʻa o nā kumu o HD. Eia kekahi,ʻoiai ka cg23409074 i hōʻikeʻia e hoʻopiliʻia me ka hōʻikeʻana o ka genH CRH i nā mana olakino,ʻaʻole i hōʻikeʻia i ka hopena o kēia hiki ke hoʻololi i ka hoʻololiʻana i nā hanana HD a ʻo ka ana o CRF he mea waiwai ia no ka noiʻana. Pono e hoʻonui hou i nā noi e nānā i ka hōʻailonaʻano likeʻole o CRH ma nā kāne me HD. An ʻO ka nīnau nui keʻano o ka methylation holoʻokoʻa holoʻokoʻa a pau e hōʻike i nā hopena ma ka lolo. Me ka mea hana pono e hoʻohālikelike i ka methylation ma waena o ke koko a me ka lolo,ʻo ka methylation i ka ʻO ka pae CRH i heluʻia, cg23409074, ua pilikino loaʻia ma waena o ke koko aʻehā mau mea likeʻole ka lolo lolo, me ka hulina ikaika loa no ka huihuʻi mua, kahi mea hoʻonohonoho nui o ka pane pilikia. Hāʻawi kēia i kekahi kākoʻo e hiki keʻikeʻia ke kūlana methylation ma ke koko holoʻokoʻa e hoʻololi i nā loli i hanaʻia ma kekahi mau lolo. Eia kekahi, ua hanaʻia kaʻimi i ka methylation a me ka'ōlelo ma kahi'āpana liʻiliʻi o nā limahana olakino a he mea nui i nā hiʻohiʻona koʻikoʻi, akā,ʻaʻole ma nā hua'ōlelo Pearson. Hiki ke ho'ākākaʻia kēia hopena i loko o ia mauʻano loiloiʻoihana ikaika e hoʻohanaʻia i keʻano o kahiʻano liʻiliʻi liʻiliʻi, no kaʻikeʻana i kēlā me kēia mea'ē aʻe a iʻole heteroscedasticity ma kaʻikepili i hiki i nā hualoaʻaʻikeʻole (Joubert et al., 2012). Eia kekahi, ma ka hanaʻana i nā hoʻoponopono hoʻoponopono i nā mea pākahi a pau, hiki ke hōʻemi i ka hiki ke hōhonuʻia no ka kū'ē'ē likeʻole,ʻO kekahi mau kumu hana hōʻano hikiʻole ke hoʻololi i nā loli o nāʻano methylation, e like me nā hiʻohiʻona meaʻai aiʻole nā moku kūikawā (Rask-Andersen et al., 2016) aʻaʻole ke hoʻolālāʻana i nā hālau plasma dexamethasone ma ka DST (Menke et al., 2016).
I ka hopena o ka loaʻaʻana o ka epigenetic moku'āina i ka CRH gene, e pili ana i nā puke e pili ana i ka neurobiology o ke olakino, i nā kāne me ka maʻiʻeha koko, hiki ke kōkua i ka hoʻokiʻekiʻeʻana i nāʻano hana olapili o ka maʻi koko.
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