Lefifi Lintlheng Tse sa Lebelloang Khatello ea Kelello (2015), George F. Koob, Ph.D.

Lefifi le ka Har'a Phapang e Tšoanang ea Khatello ea Kelello

Laboraro, la April 01, 2015

by: George F. Koob, Ph.D.

Tlhokomeliso ea Moqapi: Lintho tse ngata li etsa hore re arabele maemong ka tsela e fapaneng: lilemo, bong, thuto, likamano, maemo a bophelo, tikoloho, semelo sa setso, boiphihlelo ba bophelo. Empa joalo ka ha mongoli oa rona a hlalosa, metheo ea likokoana-hloko, joalo ka liphatsa tsa lefutso le methapo ea kutlo e ama likelello tsa rona, e fana ka leseli mabapi le bokhoba ba ho lemalla, khatello ea maikutlo ea morao-rao le khatello e meng eo a reng ke karolo ea bophelo ba sejoale-joale.

Sebaka sa khatello ea kelello se hohle. Ke karolo ea bophelo ba sejoale-joale. Empa khatello ea maikutlo ke eng? Boko bo sebetsana joang le maikutlo e le "khatello ea maikutlo"? Ke lik'hemik'hale li feng ka kelellong ea rona tse arabelang karabelo ea khatello ea maikutlo, 'me, ka ho fetisisa, na re ka e laola? Ho feta moo, ke eng e fanang ka phapang pakeng tsa karabelo ea khatello ea maikutlo e sieang ba bang ba rona ba le tlokotsing ea khatello ea maikutlo le ba bang ba tiileng? Khatello ea maikutlo e qala neng le ho hlahisa psychopathology? Mme ke hobaneng ke e nka e le "lehlakore le lefifi" la meputso tseleng.

Mehopolo ea ka ke hore liphapang tse fapaneng le batho ba bang ba ho imeloa kelellong le ho itsamaisa ke tsona lisosa tsa bohlokoa tsa nts'etsopele ea khatello ea maikutlo ea posttraumatic khatello ea maikutlo (PTSD) le bokhoba bona, 'me phapang ena e tsoa molomong oa methapo ea maikutlo. Ke tla u nka ka mokhoa ona o hlalosang seo ke se bolelang. 

Sepheo sa Khatello ke Eng?

Matšoenyeho a ka hlalosoa e le "sephetho se sa lebelloang (se tloaelehileng) sa tlhoko efe kapa efe 'meleng"1 kapa, ho ea ka pono ea kelello, "eng kapa eng e bakang phetoho ea ts'ebetso ea" homeostatic "ea kelello."2 Ho latela nalane, karabelo ea 'mele e amanang haholo le boemo ba khatello ea maikutlo ke boemo bo phahameng ba lik'hemik'hale tse bitsoang li-glucocorticoids tse thusang ho laola ho ruruha. Li-glucocorticoids li nkiloe ho adrenal cortex, tšoelesa e kaholimo ho liphio, 'me ho ne ho nahanoa hore bophahamo ba glucocorticoid bo laoloa ke hypothalamus ea kelello, sebaka se amanang le maikutlo. Ho boloka homeostasis ea kelello, ka hona, ho kenyelletsa likarabo har'a methapo ea kutlo, endocrine le boits'ireletso ba mmele. Nexus ena e bitsoa hypothalamic-pituitary-adrenal axis (HPA).

Boiteko ba ho fumana lits'ebetso tse kenyelletsang ho senya homeostasis ea kelello bo qalile ha ke ne ke le rasaense oa basebetsi setsing sa Arthur Vining Davis bakeng sa Behaeveal Neurobiology ho Salk Institute e California. Basebetsi-'moho le 'na Wylie Vale, Catherine Rivier, Jean Rivier, le Joachim Spiess ba bonts'itse pele hore peptide e bitsoang corticotropin-releasing factor (CRF) e qala karabelo ea khatello ea maikutlo ea HPA axis's neuroendocrine. Patlisiso e bonts'itse hore CRF e tsoa karolong ea hypothalamus e bitsoang "ketventricular nucleus", e leng molaoli oa mantlha oa li-axoth tsa hypothalamic-pituitary-adrenal. Ha hypothalamus e lokolla CRF, e tsamaea methapong ea mali ho ea sebakeng sa pituitary, e mokatong oa bokong. CRF e hokahanya li-receptor tse karolong e ka ntle ea tšoelesa ena hore li lokolle li-hormone tsa adrenocorticotropic (ACTH) molatsoaneng oa mali.3

ACTH le eona e fetela ka lehlakoreng la gland ea adrenal gland ho ea lokolla li-glucocorticoids. Glucocorticoids eona e hokahanya tsoekere ho eketsa matla a sebelisoang ke boko, 'me li-glucocorticoids le tsona li fokotsa ts'ebetso ea boits'ireletso ka ho thibela liprotheine tse "proinfigueatory" tseo ka tloaelo li hlahisang ho ruruha. Ka bobeli likarabo tsena li thusa ho kopanya mmele ho arabela ho khatello ea maikutlo e matla. Ka sebele, likarabo tse matla le tse sa foleng tsa glucocorticoid li ama ka tsela e fapaneng ts'ebetso ea boko, ka li-glucocortoids tse matla le tse matla tse fanang ka tšireletso. 4

Lintoa kapa Lifofane?

Ha re thulana le khatello ea maikutlo, ke eng e rerang hore na rea ​​loana kapa rea ​​baleha? Mekhoa ea "nalane ea" amygdala e atolositsoeng ea motho e sebetsa ka mokhoa o tšosang, ts'oso, le matšoenyeho (a bakang karabo kapa karabelo ea sefofane ho liphoofolo)5,6 'me e phallisa maemo a sithabetsang a maikutlo. Sebakeng se ka tlase sa bokong se bitsoang "basal forebrain", amygdala e atolositsoeng e entsoe ka likarolo tse 'maloa, ho kenyelletsa le amygdala le nucleus accumbens. 7 Sistimi ena e amohela lipontšo ho tsoa likarolong tsa boko tse kenyelletsang maikutlo, ho kenyelletsa hypothalamus mme, ho bohlokoa ka ho fetisisa bakeng sa tlhatlhobo ena, cortex ea pele. Li-neurons tsa amygdala tse atolositsoeng li romela li-axons kapa lihokela haholo ho hypothalamus le likarolo tse ling tsa midbrain tse amehang ho hlahiseng likarabo tsa maikutlo.7,8

Ho psychopathology, taolo ea amygdala e atolositsoeng e 'nile ea nkuoa e le ea bohlokoa mathateng a amanang le khatello ea maikutlo le maemo a mabe a maikutlo. Mathata ana a kenyelletsa PTSD, ho tšoenyeha ka kakaretso, phobias, mathata a amanang le boteng le bokhoba.9,10 Mohlala, liphoofolo tse pepesitsoeng khatello ea maikutlo li tla bonts'a karabelo e ntlafalitsoeng ea tšireletso molemong oa tšusumetso e nang le tšabo, karabelo e ntlafalitsoeng ea tšusumetso e qalang, le ho qoba libaka tse bulehileng, tseo kaofela e leng likarabelo tse tloaelehileng mohopolong o khathollang 'me li arotsoe ka karolo ke amygdala e atolositsoeng.

Barekisi ba Neurochemical

Hobaneng ha likarabelo tsa motho ka mong tsa khatello ea maikutlo li fapana? Ho na le lits'ebetso tse peli tsa bohlokoa tsa "neurochemical" tse thusang ho araba potso ena. Ea pele ke CRF, tsamaiso ea methapo e boletsoeng ka holimo. Ho ile ha fumaneha hore CRF le eona ke karolo e kholo ea amygdala e atolositsoeng mme e sebetsa ho etsa liphetoho tsa boitšoaro.

Ha karabelo ea glucocorticoid e hlasimolla 'mele bakeng sa likarabo tsa' mele ho ba khatello, CRF e tsosa karabelo ea boitšoaro ba 'mele ho khatello ea maikutlo ka mekhahlelo ea boko ka ntle ho hypothalamus. E 'ngoe ea linako tsa ka tsa pele tsa eureka e ne e le ha laboratori ea ka e thusa ho bontša hore CRF ha e arabe feela likarabo tsa' mele le lihormone ho li-stressors empa le likarabo tsa boitšoaro.

Thutong ea rona ea pele, ke ile ka kenya peptide ea CRF e sa tsoa sibolloa bokong ka likhoto mme ka bona boits'oaro bo ikhethang haholo. Likhoto li ile tsa hloella hohle masakeng a liteko tsa terata, ho kenyeletsoa le mabota. Ke ile ka bitsa Wylie Vale ho tla shebella liphoofolo hobane li ne li bonahala li le monate. Kamora moo re bonts'itse hore ho kenya CRF bokong ba likhoto ho hlahisitse hyperarousal tikolohong e tloaelehileng empa ho bile le karabelo e ts'oanang le leqhoa tikolohong e nang le khatello.11 Mosebetsi o latelang o bonts'itse hore amygdala e atolositsoeng e arabela likarabo tse joalo ho CRF le tšabo le matšoenyeho ka kakaretso. Ha basebelisi ba ne ba sebelisoa ho thibela li-receptor tsa CRF hore li se ke tsa tlama CRF, litla-morao tse khahlanong le khatello ea maikutlo li ile tsa etsahala, ho tiisa hore tokollo ea CRF e hlahisitsoeng ka tlhaho e bohareng ba karabelo ea boitšoaro ho bahatelli.12 Ka mokhoa o tsotehang, khatellong ea nako e telele, li-glucocorticoids li hlohlelletsa tlhahiso ea CRF ho amygdala ha e ntse e e thibela ho hypothalamus, e fana ka maikutlo a mokhoa oa ho itšireletsa 'meleng ho pepesehang peponeng ea glucocorticoids ka ho koala axis ea HPA empa o tsamaisa tsamaiso ea khatello ea extrahypothalamic CRF.

Sistimi e 'ngoe ea bohlokoa ea neurotransmitter e amehang karohanong ea motho ka mong ea ho arabela ka khatello ea maikutlo e bitsoa dynorphin-kappa opioid system (e fumanehang ho amygdala e atolositsoeng). Sisteme ena e na le tšusumetso e matla liphumatsong tse mpe tsa maikutlo ka ho hlahisa litlamorao tse kang tsa dysphoric joalo ka liphoofolo le bathong.13 Dysphoria ke boemo bo seng botle ba maikutlo. Li-dynorphin li ajoa haholo tsamaisong ea methapo ea kutlo.14 Ba na le karolo ea ho laola mesebetsi e mengata, e kenyeletsang neuroendocrine le ts'ebetso ea makoloi, bohloko, mocheso, ts'ebetso ea pelo, ho phefumoloha, boits'oaro ba ho fepa, le ho arabela ka khatello ea maikutlo.15

Ntle le lits'ebetso tsena tse peli tsa methapo ea kutlo, joale rea tseba hore lits'ebetso tse ling tsa methapo li sebelisana le amygdala e atolositsoeng ho arabela likarabo tsa boits'oaro ho khatello ea maikutlo. Li kenyelletsa norepinephrine, vasopressin, hypocretin (orexin), Dutu la P, le li-cytokine tsa proinfigue. Ka lehlakoreng le leng, lits'ebetso tse ling tsa methapo ea kutlo li sebetsa ka ho fapana le tsamaiso ea khatello ea kelello. Har'a tsona ke neuropeptide Y, nociceptin, le endocannabinoids. Ho kopantsoe ha lits'ebetso tsena tsa lik'hemik'hale ho etsa hore molumo oa maikutlo a feto-fetole maikutlo, haholo-holo maemo a seng monate a maikutlo, ka mofuta oa amygdala o atolositsoeng.16

Psychopathology le Stress Systems

Lisebelisoa tsa khatello ea maikutlo li kenella joang ho PTSD? PTSD e tšoauoa ka karabelo e feteletseng ea hyperarousal le hyperstress. Litsi tsena li kenya letsoho haholo ho li-Symbols tsa PTSD tsa sehlopha sa boiphihlelo, ho qoba, le ho tsosa. Mohlomong e bolotsana le ho feta, liperesente tsa 40 tsa batho ba nang le PTSD ba qetella ba na le mathata a tšebeliso ea lithethefatsi le joala. Boitsebiso bo fana ka maikutlo a hore ho ata ha bothata ba tšebeliso ea joala ho batho ba nang le PTSD e kanna ea ba lipalo tsa 30.17 Moetso o moholo oa li-neurocircuitry tsa PTSD li bile teng ka tšohanyetso mesebetsing ea liphoofolo tsa pele ho liserekisi tse tšabang,18 e ileng ea fana ka maikutlo a hore lits'ebetso tsa khatello ea kelello li sebetsa haholo ho amygdala e atolositsoeng.

Bakuli ba PTSD ba bonts'a sensitivity e phahameng haholo ea glucocorticoid receptor. Hypersensitivity ena e baka ho hatella ho feteletseng ha axis ea HPA ka karabelo e mpe ea corticosteroid.19 Patlisiso e fumane hore karolo ea sesole e ntlafalitseng matšoao a PTSD kamora ho fallisoa e ne e le ba nang le maemo a phahameng haholo a tlhahiso ea "glucocorticoid receptor" pele ho ts'ebeliso.20 Phuputso e 'ngoe ea bohlokoa ea pele ho nako e bontšitse hore ts'ebetso e matla ea ho amohela lets'oao la CRF mefuteng ea liphoofolo e ka baka khatello ea maikutlo e ts'oanang le khatello ea maikutlo e tsamaellanang le khatello e matla ea maikutlo le ts'abo e bonoang ho bakuli ba PTSD.21 Patlisiso e boetse e bontšitse hore bakuli ba nang le PTSD e matla ba bonts'a ts'ebetso ea ts'ebetso ea phepo e kholo ea CRF, e lekantsoeng ke keketseho ea CRF maling a bona a "cerebrospinal fluid".22

Le ha data ho PTSD le dynorphin-kappa e na le moeli, lintlha tsa bohlokoa li fana ka maikutlo a hore li-receptor tsa kappa-opioid receptors li bapala karolo ea bohlokoa ho arabiseng likarabo tse kang khatello ea maikutlo le ho kenyeletsa litlamorao tse tlisoang ke khatello ea maikutlo.13 Phuputso e thabisang ea morao tjena ea ho nahana ka tracer ea kappa-opioid e bontšitse ho fokotseha ho tlama ha kappa-opioid bokong ho bakuli ba PTSD. Seo ba se fumaneng se fana ka maikutlo a ho eketseha ha dynorphin ho bakuli ba fumanoang ba na le kalafo ea PTSD.23

Ho tsoa ponong ea neurocircuitry, lithuto tse inahaneloang tse sebetsang tsa bakuli ba nang le PTSD li bonts'a hore amygdala e na le khatello e matla ha sebaka sa "ventroedial prefrontal cortex" (PFC) le sebaka se ka tlase sa "gyrus" se bonts'a ts'ebetso e fokotsehileng.24 Liphumano tsena li fana ka maikutlo a hore PFC ea boemo bo phahameng ha e sa hlola e thibela amygdala. Ho felloa ke matla ha tšibollo hona ho etsa hore batho ba tšohe haholo, ho lebisa tlhokomelo e kholo tšosong, ho liehise kapa ho fokotsehe hoa mehopolo e bohloko, le khatello ea maikutlo.25

Khopolo-taba e 'ngoe e khahlehang bakeng sa liphetoho tse sebetsang tsa tšebetso ea methapo ea kutlo tse etsahalang PTSD e fana ka maikutlo a phetoho ea boemo ba kelello ho tsoa ho khatello ea maikutlo (eo ho eona PFC e thibelang amygdala) ho khatello e kholo (eo ho eona PFC e kenang kantle ho naha mme amygdala e busa; bona setšoantšo 1).26 Tlas'a paradigm ena (rubric e bolela "maemo a ts'ebetso bakeng sa sechaba se hlalositsoeng"), taolo e lekanyelitsoeng ke bokhabane ba cortex e fana ka tiisetso, le taolo e lekanyelitsoeng ke amygdala e fana ka ts'oaetso.26 Ho hopola ka ho eketsehileng litlamorao tsa taolo ea pele, lithuto tse peli tse amanang li bonts'a ts'ebetso ea ts'ebetso ea PFC e lumellana le ho fela ha tšabo, athe ts'ebetso ea amygdala ke dorsal anterior cingrate cortex (ACC) e lumellana le ho sitoa ho felisa tšabo.27,28
Setšoantšo sa 1. Li-neurocircuitry tse tloaelehileng tsa ho lemalla le khatello ea khatello ea kelello ea posttraumatic (PTSD) ka sepheo sa taolo ea prefrontal cortex (PFC) holim'a amygdala e atolositsoeng. Mokhatlo oa lithuso oa PFC o sitisa mosebetsi ho amygdala e atolositsoeng, moo li-neurotransmitter tsa khatello ea maikutlo li arabelang likarabo tsa boits'oaro ho khatello ea maikutlo le maemo a mabe a maikutlo. Li-neurotransmitters tsa bohlokoa li kenyelletsa corticotropin-releasing factor (CRF) le dynorphin empa le li-modulators tse ling tsa khatello le li-antistress. Hlokomela ho phahama ho hoholo hoa matšoao a PTSD le boemo bo amang mofetoheli.

'Lefifi le ka Hare'

Khafetsa ke bolella batho hore ke qetile lilemo tse leshome le metso e mehlano tsa mosebetsi oa ka oa ho ithuta hobaneng re ikutloa re le monate le lilemong tse leshome le metso e mehlano tsa morao tjena ke ithuta lebaka leo re utloang bohloko. Leha ho le joalo, linaha tsena tse peli tsa maikutlo li hokahane haufi-ufi, e tsosetsang monyetla o shebahalang eka o hanana le oa hore ts'ebetso e feteletseng ea sistimi ea moputso e ka lebisa ho maemo a kang khatello ea maikutlo hore, ka sebopeho sa bona se matla, ba tšoana le PTSD. Joale ho tla joang hore ke be ka lehlakoreng le “lefifi”? Ho qala ka ho ithuta ka "lehlakoreng le bobebe" kapa hore na lithethefatsi li hlahisa melemo ea tsona joang.

Sehlopha sa ka sa lipatlisiso le ba bang ba ne ba nahana hore bokhoba bo kenyelletsa mekhahlelo e meraro e kenyelletsang likokoana-hloko tse arohaneng empa li tlolaka le litsamaiso tsa neurotransmitter tse loketseng: ho itlopa joala / tahi, ho hula / ho ameha hampe, le ho tsepamisa mohopolo / tebello kapa "ho lakatsa".29,30 Mohato oa ho itlopa joala kapa ho tahoa ho kenyelletsa ho nolofalloa ha ho hlohlelletsa (ho hokahanya hoa tšusumetso e neng e sa nke lehlakore tikolohong ho fumana meputso ho fana ka thepa eo e khothalletsang), e kopantsoeng haholo le methapo ea methapo ka hara basal ganglia. Ho shebiloe haholo ts'ebetsong ea "moputso" oa li-neurotransmitters dopamine le li-peptide tsa opioid tse tlamang ho li-mu-opioid receptors bokong. Mosebetsi oa pele lebaleng la bokhoba ba lithethefatsi o bonts'itse hore li-nucleus bokella e ne e le karolo ea bohlokoa ea ts'ebetso ena ea methapo e kopanyang thepa e ruisang ea lithethefatsi tse hlekefelitsoeng.

Nna le Franco Vaccarino re bonts'itse hore re ka thibela tsamaiso ea heroin ha re kenya methapo ea methylnaloxonium, e thibelang li-opioid receptors, ho li-nucleus tsa liphoofolo.31 Kamora nako, liphuputso tse 'maloa tsa ho nahana ka batho tsa khale li bontšitse hore litekanyetso tse tahang tsa joala li fella ka tokollo ea li-peptide tsa dopamine le li-opioid ka har'a li-nucleus accumbens.32,33 Joale rea tseba hore ts'ebetso ea "activus" ea li-nucleus e lebisa ho hoketsoeng ha liserekisi tsa basal ganglia tse kenyang ho theha le ho matlafatsa mekhoa. Ts'ebetso ena e anngoe maikutlo ho bonts'a qaleho ea ho araba ka mokhoa o qobelloang joalo ka lithethefatsi-ka mantsoe a mang, bokhoba.

Teko e ileng ea fapana hantle le eo ke neng ke e boletse esale pele ke lona lebaka la bobeli leo ke ileng ka lula ka lehlakoreng lena la lithethefatsi. Tamara Wall, Floyd Bloom, le nna re ile ra qala ho supa hore na ke likarolo life tsa boko tse arohanang ho tlosoa hoa 'mele ho opiates. Re ile ra qala ka ho koetlisa likhoto tse itšetlehileng ka opiate ho sebeletsa lijo. Ebe re sitisa mokhoa oa bona oa ho batla lijo ka ho li enta ka naloxone. Ena lithethefatsi a khaotsa ho ikhula, a hlahisa malaise- le dysphoric-state; ka lebaka leo, likhoto li ile tsa emisa ho tobetsa lever. Ho fihlela joale, re atlehile ho hatisa lipatlisiso tsa pele.34 Ka mor'a moo re ile ra qala ho kenya methylnaloxonium, sethethefatsi se thibelang li-opioid receptors libakeng tsa boko tse neng li ameha nakong e fetileng ka lebaka la ho ikhula ho li-opiate. Re entile setlhare sena hobane e ne e le analog ea naloxone e neng e ka hasana hanyane bokong mme ea fokotsa ho tlosoa ha "lehae" joalo ka ha e lekantsoe ke phokotso ea lever e hatellang lijo.

Re ile ra nahana hore libaka tse tebileng ka ho fetisisa tsa boko ho hlahisa ho fokotseha ha khatello ea lever e tla ba griaqueductal grey le medial thalamus hobane ba ne ba bonts'itsoe ho khaola ho tlosoa hoa 'mele ho opiates. Leha ho le joalo, ente ea "periaqueductal grey" le "medial thalamus" e ne e sa sebetse ho fokotsa khatello ea lever bakeng sa lijo. Ho e-na le hoo, ente ea li-nucleus tsa li-nucleus e ipakile e sebetsa — e sebetsa hoo re ileng ra tlameha ho tlohella lethal dose. Le ha re ne re sebelisa tekanyetso e tlase haholo, re bone ha re fokotsa ho phehella lijo.35 Ke ile ka qala ho tseba hore na sebaka se le seng sa boko se ikarabelletseng ho ho etsa hore u ikutloe hantle, le sona se ile sa u utloisa bohloko ha u ne u ba motšehetsi. Epiphany ena e ile ea etsa hore ke qete nako eohle ea bophelo ba ka ke leka ho utloisisa hantle hore na likarabelo tse fapaneng joalo li etsahala joang nakong ea ho ikhula, tseo ho thoeng ke lira tsa bohanyetsi.

Boitlhotlhollo bona bo ile ba etsa hore ke be le mohopolo o mocha ka ho fetesisa oa mokhahlelo oa ho tlohela / ho se sebe. Ke ile ka fihlela qeto ea hore sethaleng sena ha ho tšoaetsoe feela ho itlhatsoa ka lithethefatsi ka ho khetheha ka “ho itlhahisa” 'meleng empa hape le ho iketla ho tloaelehileng ka sepheo sa "ho susumetsa", ho tsejoang ke dysphoria, malaise, ho se ts'oanehe, likhathatso tsa boroko le ho sithabela ha bohloko. (Matšoao ana a batla a tšoana le matšoao a hyperarousal / khatello ea maikutlo a bonoang ho PTSD; bona setšoantšo 1).  

Tsamaiso e 'meli e ile ea sebelisoa kamora nako hore e thehe motheo oa neurobiological bakeng sa sethala se amehang sa ho tlohela / se sebe. E 'ngoe ke tahlehelo ea ts'ebetso lits'ebetsong tsa meputso karolong ea methapo ea methapo e bokellaneng ea amygdala e atolositsoeng. Tahlehelo ea tsamaiso ena ea moputso e kopanngoa le tahlehelo ea ts'ebetso ho li-dopamine system. Ts'ebetso e 'ngoe ke ho haptjoa ha lits'ebetso tsa khatello ea kelello likarolong tse ling tsa amygdala tse atolositsoeng (haholo-holo, karolo e bohareng ea amygdala), ho kenyelletsa ho hira methapo ea methapo ea methapo CRF le dynorphin.36,37 Motsoako oa ho fokotseha hoa ts'ebetso ea neurotransmitter ea moputso le ho hira ha methapo ea khatello ea kelello e fana ka tšusumetso e matla ea ho khutlisetsa ts'ebeliso ea lithethefatsi le ho batleng lithethefatsi.

Tlhatlhobo e 'ngoe e ile ea tla ha laboratori ea ka e qala ho bona karolo e makatsang ea CRF ho batla joala bo qobelloang, ka ho khahlisoa ha likarabo tse kang ho tšoenyeha ha CRF receptor antagonist kapa receptor blocker e sebelisoa ho thibela likarabo tse kang tsa ho tlohela joala.38 Kamora moo, re bonts'itse hore ho itlopa joala bo matla ho kenya ts'ebetsong litsamaiso tsa CRF karolong e bohareng ea amygdala.39 Ho feta moo, liphoofolong re fumane hore liente tse ikhethileng tsa li-CRF receptor antagonists karolong e bohareng ea li-amygdala kapa li-systemic injections tsa molek'hule tse nyane tsa CRF li fokolitse letsoalo la liphoofolo tse joalo ka boits'oaro le ho itaola ka mokhoa o feteletseng oa lintho tse lemalloang nakong ea ho khaotsa ho matla. .12,40 Mohlomong e qobella ka tsela e lekanang, Leandro Vendruscolo le 'na re sa tsoa supa hore mohanyetsi oa "glucocortoid receptor" a ka thibela ho nooa ho fetelletseng nakong ea ho itlopa joala bo matla, a hokela maikutlo a CRF tsamaisong ea amygdala le ts'ebetso e sa feleng ea karabelo ea HPA ea glucocorticoid. 41

Empa ts'ebetso e feteletseng ea sistimi ea moputso e hokahana joang le ts'ebetso ea lits'ebetso tsa khatello ea kelello? Mosebetsi oa semina o entsoeng ke Bill Carlezon le Eric Nestler o bonts'itse hore ts'ebetso ea li-d opamine receptors tse ngata ka bongata khetla ea li-nucleus li phahamisa moferefere oa liketsahalo tse qetellang li lebisang ho diphetoho ho tekanyo ea ho qala ha sengoloa sa DNA le liphetoho lipuisanong tsa mofuta oa gene. Qetellong, phetoho e hlokomelehang haholo ke ts'ebetso ea litsamaiso tsa dynorphin. Ts'ebetso ena ea dynorphin e ntan'o fepa ka morao ho fokotsa ho lokolloa ha dopamine.37 Bopaki ba morao-rao bo tsoang laboratoring ea ka le ea Brendan Walker bo fana ka maikutlo a hore sisteme ea dynorphin-kappa opioid e boetse e sebetsana le likarabo tse tlamang joalo ka lithethefatsi (ho methamphetamine, heroin, nikotine le joala); Karabelo ena e bonoa mehlaleng ea litekanyo nakong ea phetoho ea ho lemalla. Mona, molek'hule e monyane ea kappa-opioid receptor o ikhethile ka mokhoa o ikhethileng o thibetse nts'etsopele ea liphoofolo le ho itaola.42-45 Kaha ho ts'ebetso ea li-receptor tsa kappa ho hlahisa litholoana tse tebileng tsa dysphoric, polasetiki ena ka har'a amygdala e atolositsoeng e kanna ea kenya letsoho ho dysphoric syndrome e amanang le ho tlosoa hoa lithethefatsi eo ho nahanoang hore e khanna likarabo tse qobelloang tse kopantsoeng le ts'usumetso e mpe.46

Ntho e 'ngoe e ileng ea makatsa ke hore o ile a hlokomela hore mohopolo oa pele kapa ho “lakatsa,” mohato oa bokhoba ba joala o kopanya ho tlosoa hoa taolo ea maemong a phahameng ka lipotoloho tsa pele tsa cortex. Taba ea bohlokoa ke hore lipotoloho tsena e ka ba sebaka sa mantlha bakeng sa karohano le boits'oaro ba motho ka mong. Bafuputsi ba bangata ba qopile mekhoa e 'meli e hanyetsanang eo hangata e leng “E-ea” le "Stop", moo Sisteme ea Go e nkang likarabo tse tloaelehileng le tsa maikutlo mme tsamaiso ea Stop e fana ka likarabo tse tloaelehileng le tsa maikutlo. Potoloho ea "Go system" e na le "cortex" ea anterior cingex le dorsolateral PFC, 'me e kenya ts'ebetso ea tikoloho ka sehlopha sa basal ganglia. Potoloho ea Stop Stop e na le polypedial PFC le ventral anterior cingrate cortex mme e thibela sebopeho sa tloaelo ea basal ganglia, hammoho le sistimi e atolositsoeng ea khatello ea amygdala. Batho ba nang le lithethefatsi kapa lithethefatsi tsa joala ba na le tšitiso ea ho etsa liqeto, ho sitisoa hoa ts'ebeliso ea tlhaiso-leseling ea sebaka, mathata a sitisang boitšoaro, le ntlafatso ea ts'ebetso ea khatello ea maikutlo, tseo kaofela li ka tsamaisang takatso. Habohlokoa le ho feta, Sisteme ena ea Stop e laola “lehlakore le lefifi” la ho lemalla le khatello ea kelello e bonoang ho PTSD.

Ho tseba sena ho ile ha tlisoa lapeng ha 'na le mphato oa ka Olivier George le' na re bonts'a hore, le litekong tse neng li etsa joala bo lekanang le ho itlopa joala, ho ne ho na le khokahano ea taolo ea "cortex" ea pele ho li-amygdala empa eseng li-nucleus.47 Liphetho tsena li bonts'a hore pele ho ts'ebeliso e ngata ea joala, ho qhekella ho etsahala tseleng e pakeng tsa PFC le khubu ea mantlha ea amygdala, 'me ho khaola hona e ka ba senotlolo taolong e mpe ea taolo holim'a boitšoaro ba maikutlo.

Bopaki ba Mechanism ea genetic / Epigenetic

Ke belaela hore neurocircuitry e shebane le cortex e ka pele le amygdala nts'etsopele ea PTSD le ho lemalla ho bonts'a liphofu tsa liphapang tse ka bang tlokotsing le ho tiisetsa. Lithuto tsa ho nahana ka batho li thehile hore ts'ebetso e fokotsang ts'ebetso ea "ventromedial PFC" le "anterior cingrate cortex" le tšebetso e eketsehang ea amygdala ke liphetho tse tšepahalang ho PTSD.26. Ka mokhoa o ts'oanang, ts'ebeliso ea lithethefatsi le eona e amahantsoe le ts'ebeliso e akaretsang ea PFC ea ventromedial.48 Joale monehelo oa "ventralmedial PFC" le "anterior cingrate cortex" ke khatello ea maikutlo le maikutlo a mabe a amanang le ho lakatsa, haholoholo ha re fuoa seo re seng re se tseba ho PTSD? Ha ho shebelloa pherekano e phahameng ea tlhekefetso ea lithethefatsi le PTSD le karolo ea bohlokoa ea PFC ho laola lits'ebetso tsa khatello, taolo ea litheko tse ikhethileng tsa PFC e kanna ea ba le seabo mananeong ana ka bobeli.  

Ho fana ka bopaki ho batho ho supa phapang e kholo e le 'ngoe karabelong ea maikutlo a atileng a maikutlo, haholo-holo tse nkoang e le khatello ea maikutlo, le ho ba kotsing ea PTSD le bokhoba. Patlisiso e bonts'itse hore khubu ea mantlha ea amygdala (dorsal amygdala ho batho) e nka karolo ts'ebetsong e tsebahalang ea lifahleho tse tšosang ho baithaopi ba phetseng hantle mme, ho bohlokoa le ho feta, hore liphapang tsa ho tšoenyeha ha motho ka mong li boletse karabelo ea konopo ea bohlokoa bohareng. khubu ea amygdala, basyati ea basolateral, ho ea sa tsebeng letho ho sefahleho se tšosang.49 Ntle le moo, phuputso e ikhethang e neng e sebelisa positron emission tomography e bontšitse hore amygdala e kenngoa ho batho ba lemaletseng koae ka nako ea litakatso tsa lithethefatsi empa eseng nakong ea ho pepesetsoa litloaelo tse sa amaneng le lithethefatsi.50

Ka mokhoa o ts'oanang, liphetoho tsa tšebetso ea "cortex" ea pele li ka hlahisa liphapang tsa batho ba tlokotsing le ho imeloa. Phuputsong e 'ngoe e lebelletsoeng e ileng ea etsoa kamora ts'isinyeho ea lefats'e ea 9.0 Tohoku e Japane ka 2011, barupeluoa ba neng ba e-na le bophahamo bo phahameng ba lintlha tsa bohlooho ka har'a "cortex" e nepahetseng ea "cortex" ba ne ba se na monyetla oa ho ba le matšoao a kang PTSD.51 Tekanyo ea ntlafatso ea matšoao kamora kalafo ea boits'oaro ea kelello e ne e tsamaellana hantle le ho eketseha ha ts'ebetso ea cortex ea anterior.52 Ho fapana le hoo, liphuputso tse ling li bonts'itse hore batho ba nang le PTSD le mafahla a bona a kotsing e kholo ba bonts'a tšebetso e kholo ea ho phomola ha metabolism ka har'a dorsal anterior cingrate cortex ha e bapisoa le batho ba hlahetsoeng ke koluoa ​​ntle le PTSD, ba fana ka maikutlo a hore ts'ebetso ea dorsal anterior cingate cortex e ka ba kotsi. Ntho ea ho nts'etsapele PTSD.53

Empa ke liphetoho life tsa limolek'hule tse tsamaisang liphetoho tsee? Liphuputso tsa lefutso li bontšitse hore 30 ho ea 72 lekholong ea ho ba kotsing ea PTSD le liperesente tsa 55 tsa ho ba kotsing ea bokhoba ba tahi li ka bakoa ke ho ba le heritability. Boholo bo ka pheha khang ea hore litšusumetso tsa liphatsa tsa lefutso ka bobeli li tsoa liphatseng tsa lefutso tse ngata, 'me mokhoa oa "gene" oa motsoako ha o so khetholle mefuta e meholo ea liphatsa tsa lefutso e fetisang boteng ba PTSD. Leha ho le joalo, litlhahlobong tse peli tsa borutehi, bonyane mefuta e leshome le metso e supileng ea mefuta e amanang le PTSD le ba bang ba bangata ba tahi.26 Mefuta e mengata e fapa-fapaneng e fumanoeng mathateng ana ka bobeli e kenyelletsa gamma-aminobutyric acid, dopamine, norepinephrine, serotonin, CRF, neuropeptide Y, le mabaka a neurotrophic, ao kaofela a amanang le khopolo-taba ea hona joale. 

Ho latela pono ea epigenetic, mefuta e meng e ka hlahisoa feela tlasa maemo a sithabetsang kapa khatello ea maikutlo, mme mathata ana a tikoloho a ka fetola polelo ea liphatsa tsa lefutso ka DNA methylation kapa acetylation. Ka bobeli PTSD le bokhoba ba tahi bo bonts'a liphetoho tsa epigenetic tse fanang ka maikutlo a eketsehang a liphatsa tsa lefutso tse amanang le tsamaiso ea khatello ea maikutlo.54,55 Bakeng sa PTSD, mofuta o le mong o kentsoeng phetolelong ea epigenetic ke SLC6A4, e laolang synaptic serotonin reuptake mme e bonahala e na le karolo ea mantlha ea ho sireletsa batho ba nang le liketsahalo tse bohloko ho tsoa ho PTSD ka ts'ebetso ea methylation e phahameng.56 Bakeng sa joala, histone deacetylase (HDAC) e bile le tšusumetso ho modumo oa epigenetic. Mofuta ona o kentse letsoho taolong e its'epahalleng ea tšebetso e tsoang ho bokong bo tsoang ho neurotrophic factor (BDNF) ho li-neuron. Ho khetha likhoto tse nang le tahi tse nang le likarabo tse ngata tse kang tsa ho tšoenyeha ho feta tekano ho ile ha bonts'a boemo bo holimo HDAC Ketsahalo e khubung ea khubu ea amygdala. Knockdown ea mofuta o itseng oa HDAC o bitsoang HDAC2 karolong e bohareng ea amygdala e ile ea eketsa ts'ebetso ea BDNF mme ea fokotsa boitšoaro bo kang ho tšoenyeha le tšebeliso e mpe ea joala ka boithaopo moleng o khethiloeng oa likhoto tse fuoeng khetho e phahameng ea joala.57

Ka hona, khopolo-taba ea ka ka kakaretso ke hore liphapang tse fapaneng le batho ba leng maemong a tlokotsi le ho tiiseha, tseo e leng liqeto tsa mantlha tsa nts'etsopele ea PTSD le bokhoba ba litumellano tse tsoang manonyeletsong a "lehlakore le lefifi" la maikutlo. hyperacaction ea amygdala e atolositsoeng (dynorphin le CRF e tsamaisoang ke tšebeliso e mpe ea lithethefatsi) le mosebetsi o fokotsoang oa marapo oa PFC (o tsamaisoa ke tšebeliso e mpe ea lithethefatsi le khatello ea kelello). Khatelo-pele e ncha kutloisisong ea rona ea methapo ea kutlo ka lehlakoreng le lefifi le ho khetholloa hoa lintlha tsa epigenetic tse lekantseng ts'ebetso ea li-circuits tsena e tla ba senotlolo sa moriana o nepahetseng bakeng sa tlhahlobo le kalafo ea litšitiso tsena.

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- Sheba tse ling ho: http://www.dana.org/Cerebrum/2015/The_Darkness_Within__Individual_Differences_in_Stress/#sthash.YOJ3H1R0.dpuf