Mekhoa ea Neurobiological ea Bothata ba ho Tšoenyeha ka Sechaba (2001)

Mohlala oa khatello ea khatello ea maikutlo

Joalo ka motho, boholo-holo bo itšetlehile haholo ka likamano tsa sechaba, mme litloaelo tsa boitsoaro tse thehiloeng mahlaleng li ka tsamaisoa habonolo. Ketsiso (2) ba entse lithuto tse futsanehileng tsa batho ba sa amaneng le batho ka ho ikokobelletsa maemo a phahameng sechabeng le taolong ea litšoene tse tšehali tse bitsoang cynomolgus. Phuputso e mabapi le boitšoaro e bontšitse hore batho ba tlaasana ba qeta nako e ngata ba le bang, ka tšabo ba lekola tikoloho ea bona ea boithabiso ho feta babusi. Liphuputso tsa baeloji tsa ba kaholimo-limo tsena li senotse bopaki ba ts'ebetso ea li-hyperactive hypothalamic-pituitary-adrenal (HPA), ts'ebetso ea serotonergic e senyehileng le ts'ebetso ea methapo ea methapo ea dopaminergic. Phuputsong e nang le phephetso le ACTH, li-cortisol tsa maemo a tlase tsa sechaba, tse bonts'ang ts'ebetso ea axero ea HPA. Ha bafuputsi ba etsa tlhahlobo ea phephetso ea fenfluramine (e bakang ho lokolloa ha serotonin), li-cynomolgus macaques tse entsoeng ka laboratoring li bonts'itse karabelo ea "prolactin" e senotsoeng, e fanang ka maikutlo a fokotsa mosebetsi o bohareng ba serotonergic. Litšoene tsena li ile tsa qheleloa ka thoko ho sechaba 'me tsa qeta nako e nyane li ikopanye le' mele ho feta tse bonts'itseng karabelo e kholo ea prolactin (3). Ha bafuputsi ba etsa tlhahlobo ea haloperidol ea liteko le mohanyetsi oa dopamine ea ntlafatsang secretion ea prolactin ka litsela tsa dopamine tsa tubero-infundibular dopamine, likarabo tse fokotsitsoeng li ile tsa bonoa libakeng tse ka tlase. (2). Sephetho sena se khothalelitse ho fokola hoa kutloisiso ea li-postynaptic dopamine receptors tseleng ena libakeng tse ka tlasa lefatše. E lumellana le datha ea neuroendocrine, thuto ea positron emission tomography (PET) (4) ba ka tlase ho moo ba bonts'a dopamine D e fokotsehileng₂ receptor binding, e fanang ka maikutlo a sa tloaelehang a dopaminergic neurotransication, ho fumana hore ho etsahalla sephetho sa thuto e le 'ngoe ea photon emission computerized tomography (SPECT) (5) bathong ba nang le mathata a ho tšoenyeha ka sechaba.

Boithuto ba litšoene tse tlase sechabeng bo senotse litlolo tse ling tsa neuroendocrine tse etsisang lintho tse fumanoeng lithutong tse ling tsa batho tse tšoenyehileng le tse tepelletseng maikutlo. Hypercortisolemia, hammoho le ho hanyetsa thibelo ea maikutlo ka dexamethasone, ho tlalehiloe ke Sapolsky et al. (6) ka litšoene. Ntho e 'ngoe e khahlisang ke hore litšoene tse tona tse tlaasana li na le inshorense e tlase joalo ka "insulin" ho feta batseteli (7). Ho fumana sena ho ka 'na ha hlalosa kamano e hlokometsoeng lipakeng tsa bokhuts'oanyane bo bokhutšoanyane le bokuli ba matšoenyeho sechabeng bo fumanoeng thutong e le' ngoe (8).

Ho na le meeli e 'maloa ea bohlokoa ea mohlala ona kaha e sebetsa ho bakuli ba nang le khatello ea maikutlo ea sechaba. Taba ea pele, ha ho na bopaki ba pherekano ea axel ea HPA ea ho tšoenyeha ka maemo a sechaba joalokaha e lekantsoe ke tekanyo ea dexamethasone nonsuppression (9). Ntlha ea bobeli, karabelo ea prolactin ho fenfluramine e fapana ka mehlala e ka tlase ho bapisa bakuli ba nang le khatello ea maikutlo ea sechaba. (10). Moeli o mong oa bohlokoa oa mofuta ona oa liphoofolo le oa liphoofolo tse ling ke hore batho ba nang le lefu la ho tšoenyeha sechabeng ba tloaetse ho "ts'oara ka thata" ho qoba, ho ikokobelletsa le ho tšoenyeha maemong a sechaba, athe litloholo tseo e seng batho, ka lebaka la taolo ea tikoloho ka ho busa le ho ikokobelletsa. polasetiki e itseng ho arabela khatello ea tikoloho. Mohlala, litšoene tse hlaheletseng tsa vervet li na le maemo a phahameng a serotonin ho feta ba tlase, empa li-serotonin tsa tsona li theoha haholo ha li tlosoa sehlopheng (11). Kahoo, ho bonahala eka mokhoa o ka sehloohong oa ho fumana maikutlo maemong a sithabetsang a tlisoang ke khatello ea maikutlo ea maemo a bophelo ke ho se sebetse hantle ho tlisoang ke dopaminergic dysfunction. Hore na ho se sebetse hona ke tšusumetso ea khatello ea maikutlo sechabeng kapa karolo ea boiketlo ba sechaba ka seng ha e hlake.

Mohlala o Fetohileng-oa tlhokahalo ea Mohlala

Moetso o mong oa tšebeliso ke mokhoa o batang oa litlhoko tse fapaneng tsa batho bao e seng batho. Rosenblum le Paully (12) o ntlafalitse mokhoa ona oa ho ba lihlong sechabeng le ho se ts'oenyehe ka ho pepesetsa bo-'mè maemong a sa lebelloang a ho batla ho ts'oaroa le ho kenya mekhoa e sa tsitsang ea khokahano ho masea a bona. Liphoofolo tse holileng tse holisitsoeng tlasa maemo a batang a ho fapanyetsana lintho ka bongata, ha li bapisoa le litaba tse bapisoang esale pele, li bontšitse keketseho e tsitsitseng ea maemo a bophelo — mohlala, ho ipeha tlaase sechabeng, ho qoba ho tobana le bohanyetsi le ho fokotsa mefuta e tloahelehileng ea ho tsikinyeha ha motho a bapisoa le ho holisoa esale pele. lipapiso (13). Ho latela pono ea likokoana-hloko, lithuto tse ntlafalitsoeng tlasa mohlala o batsi oa tlhaselo e bonts'ang ho eketseha hoa maemo a CSF corticotropin-releasing factor (CRF) (14), dopamine metabolite Homovanillic acid (HVA), le serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). Ke feela lithutong tse holisitsoeng tlasa mofuta o batloang oa tlhaselo eo maemo a CRF a lumellanang hantle le maemo a HVA le 5-HIAA, a fanang ka tumellano ea ho sebetsa pakeng tsa boemo ba CRF le litsamaiso tsa dopaminergic le serotonergic hantle. (15). Ntle le moo, ka har'a sehlopha se batloang ka bongata se batloang, keketseho ea bongata maemong a CRF e ne e hokahantsoe le phokotso e amanang le karabelo ea hormone ea kholo (GH) ho α₂ adrenergic agonist clonidine (16), hammoho le likarabo tse feteletseng tsa ho tšoenyeha ka yohimbine, α₂ mohanyetsi (17).

Neurochemically, se neng se bonahala e le sa bohlokoa haholo bakeng sa khatello ea ho tšoenyeha ka sechaba ke ho fumana li-metabolites tse fetotsoeng tsa dopaminergic ho CSF ​​maemong a morao-rao a holisitsoeng tlas'a maemo a batlang a batang a ho ts'oana, a tšoanang le litlolo tse ngata tsa dopaminergic tse hlokometsoeng ho bakuli ba nang le khatello ea maikutlo ea sechaba. Ka boomo, li-primates li holisitsoe tlasa maemo a batang a ho fepa a tšoanang le seo Kagan et al. (18) e hlalositsoe sehlopheng sa bana ba banyane ba bonts'itseng litšobotsi tsa "thibelo ea boits'oaro ho ba sa tloaelehang." Bana bana ba bontšitse ho feteletsa ha sekhahla sa pelo ho potlakisa khatello ea maikutlo, maemo a phahameng a hoseng a "salivary" a cortisol, le maemo a boits'oaro a boitšoaro a amanang le ts'ebetso e phahameng ea norepinephrine. Kahoo, mofuta o batloang oa ho batla lijo o bohlokoa molemong oa tlhahiso ea ona ea hore khatello ea tikoloho ea mantlha, haholoholo e nang le tšusumetso, e kanna ea fetola boits'oaro le neurobiology ho ea boemong bo ts'oenyehileng sechabeng. Tleliniking, leha ho le joalo, liphetho tsa neuroendocrine tsa karohano lipakeng tsa maemo a eketsehang a CRF le ho fokotsa maemo a cortisol li ts'oana haholo le boemo ba bakuli ba nang le lefu la khatello ea maikutlo (PTSD) (19, 20).

Mehlala ea Phatlalatso ea Liphoofolo

Ho tloha khale, bofokoli bo amanang le boits'oaro bo hokahantsoe le kamano ea batho ba hokahaneng bo amana haufi haholo le 'nete. Ebile, phapang e atileng haholo ea tleliniki lipakeng tsa bakuli ba nang le bothata ba ho tšoenyeha sechabeng le ba nang le lefu la autism le schizoid botho bo maemong a takatso ea kamano le kamano le ba bang. Hobane bakuli ba nang le bothata ba ho tšoenyeha ka maemo a bophelo ba sechaba (le "axis II" e amanang le tšireletso ea botho bo sa sebetseng) li nkuoe hangata e le batho ba lakatsang ho hokahanngoa le ho ikamahanya le batho ba bang empa ba tšaba litlamorao tse mpe tsa litšebelisano tse joalo, empa batho ba autistic le schizoid ka kakaretso ba sa lakatsa lits'ebetso tsena le ho hloka boits'oaro bo kopanetsoeng, meetso e hokahaneng ha e so nkuoe e le ea bohlokoa ho utloisiseng mathata a ho tšoenyeha ka sechaba. Leha ho le joalo, likhokahano tse hlahang tsa liphatsa tsa lefutso pakeng tsa autism le bokuli ba matšoenyeho sechabeng li fana ka maikutlo a ho lekola botjha ba kamano ea methapo. Mohlala, Smalk et al. (21) o fumane hore beng ka motho oa pele oa "autistic probands" ba na le keketseho ea bokuli ba matšoenyeho sechabeng bo amanang le lithuto. Phuputso ea morao tjena (22) e bonts'a hore batsoali ba Autistic probands ba ne ba na le litekanyetso tse phahameng haholo tsa phobia ea sechaba ho feta batsoali ba Down's syndrome probands, leha ho ne ho se na bopaki ba mokhatlo pakeng tsa batho ba nang le mathata a ho tšoenyeha ka sechaba le litaba tsa autism tse akaretsang (ho hlalositsoe e le likarolo tse bobebe tsa autism, ho kenyeletsa khaello ea boiketlo ba sechaba le puisano le boits'oaro bo pheta-phetoang). Lithuto tsena li supa biology e arolelanoang ea ho ikamahanya, e etsang hore neurobiology ea khokahano ea liphoofolo e tšoanelehe haholo bothateng ba matšoenyeho a sechaba ho feta kamoo ho neng ho amoheloa pele.

Lits'ebetso tse ngata tsa methapo ea kutlo li phenya lipatlisiso tsa bongaka lithutong tse nang le autism le litekanyetso tsa maemo a morao-rao a khokahanyo le kamano. Raleigh le basebetsi mmoho (23) e bonts'itse hore ntlafatso ea ts'ebetso ea serotonergic e lebisitse ho ntlafatso ea kamano ea sechaba ho li-primates, athe maemo a tlase a serotonin a khothalelitse ho qoba. Mosebetsing o arohaneng empa o amanang, li-primate tsa mahala tse nang le maemo a tlase a CSF 5-HIAA li bonts'itse bokhoni bo tlase sechabeng mme ba na le monyetla oa ho falla ba sa le banyenyane ho tsoa lihlopheng tsa bona tsa sechaba ho feta primates e nang le maemo a phahameng a CSF 5-HIAA (24).

Sistimi ea opioid ea boko e ne e le ts'ebetso ea pele ea methapo ea kutlo ho kenya letsoho joalo ka taolo ea boits'oaro bo ikopantseng lithutong tsa khale le mefuta e meng. Phuputsong e 'ngoe ea li-primates tse seng tsa botho (25), MacNque ea bana ba 10 ba lulang sehlopheng se tsitsitseng sa bo-'mè le bo-'mè ba bona le lithuto tse ling tsa bo-mphato ba sehlopha li ile tsa tsamaisoa le ezinexone, mohanyetsi oa opiate. Li-primates tse amohelang naloxone li ile tsa kopa likeletso tse ngata tsa boikoetliso 'me tsa fumana boikoetliso bo eketsehileng' me tsa eketsa kamano ea tsona le bo-mme ba tsona. Kalin et al. (26) o ithutile ho kopana hape ha masea a se nang botho ka mor'a ho arohana le bo-mme ba bona mme a bontša hore masea le bo-'mè ba fuoeng morphine ba bontšitse phokotso e kholo litekanyetsong tsa boitšoaro, athe ba ba fuoeng naltrexone ba ile ba eketsa ho tsitsipana ha bona. Kamora moo, ho bile le bopaki ba likhohlano tse rarahaneng pakeng tsa ts'ebetso ea opioid ea endoid le lits'ebetso tse ling tse amanang le li-neurotransmitter, kaha ho ile ha boleloa hore ts'ebetso ea opiate e eketsehile ka liente tsa oxytocin ka hara rat (27). Ka karolelano, ho na le bopaki bo bong ba hore ba hlekefetsang opioid ba na le litheko tse phahameng tsa boiketlo ba sechaba le matšoenyeho (28).

Nexohormone oxetocin e thehiloe hantle qalong empa e se ts'ebetso ea boits'ebetso ba bo-mme le ho tlamahana. (29), hammoho le litšebelisanong tsa sechaba le lithutong tse seng tsa batho (30). Lintlha tsa morao-rao tse tsoang Insel le Winslow (29) e bonts'itse hore toeba e entsoeng ka liphatsa tsa lefutso e haelloang ke oxytocin e ntšitse mohala o fokolang oa ho itšehla thajana mme e fokolitse likamano tsa sechaba. Ba ile ba nahana hore likaroloana tsa maiketsetso tsa "neural" ke litsela tse kopanyang ho tsebahala sechabeng (lintho tse khahlisang, tse mameloang le tse bonoang) litseleng tsa methapo ea kutlo bakeng sa matlafatso, joalo ka likhakanyo tsa [dopaminergic] mesolimbic ho tloha sebakeng sa karoloana ea sekhahla ho ea bokong bo bokellanang le prefrontal cortex ”(leq. 888). Hoa tsebahala hore dopaminergic neurotransuction e amehile ho likhakanyo tsa tsela ea moputso oa boko. Boloetse ba khatello ea maikutlo sechabeng, joalo ka Stein (31) e khothalelitsoe, ka hona e ka ba bokuli "bo khetholloang ke ho se sebetse hantle ka har'a sistimi e lekanyang (likotsi) le melemo le boiketlo ba boiketlo ba sechaba" (leq. 1280) ka ho hira litsela tsa moputso oa boko. Ka tlhaho, boholo ba litsela tsena tse arohaneng li ikamahanya le kantle ho naha, e leng sebaka se sa tsoa susumetsoa ke litšoantšo tse sebetsang tsa matla a khoheli (fMRI) ntlheng ea tlamo ea motho ea masea le masea: karabelo ea lillo tsa masea (32). Ka kakaretso, meetso ea khokahano ea liphoofolo ha e qobelle feela oxytocin, empa mefuta e fapaneng ea serotonergic, opioid le dopaminergic pathways.

Le ha li sa fella ho hlalosa litlolo tse fapaneng tsa kelello tse hlokometsoeng ho bakuli ba nang le bothata ba ho tšoenyeha ka maemo a bophelo, meetso ea ho ikamahanya le maemo e fana ka mohaho o ka sebelisoang bakeng sa ho utloisisa kamano e kopaneng ea batho e bonoang lithutong tse nang le khatello ea maikutlo ea sechaba le ho fana ka tataiso bakeng sa lipatlisiso tsa nako e tlang tsa bongaka ba bongaka ba bongaka. ho hloka kelello. Ka bomalimabe, palo ea datha tse phetoang ho "neurobiology" ea primate e kenyellelitsoeng e atile haholo, haholoholo ho ts'ebelisong. Kahoo, ts'ebeliso e tobileng ea mefuta ena ea liphoofolo ho tsietsing ea matšoenyeho a sechaba e hlile e lekanyelitsoe ka nako ena. (Bona t1 ka kakaretso ea mehlala ea mathata a bophelo ba matšoenyeho sechabeng.)

Neuroplasticity, Neurogeneis, le Dominance ea Sechaba

Ho phatloha hoa lipatlisiso ho li-neurodevelopment ho fane ka monyetla oa ho nka mofuta o ikhethang oa phoofolo oa ho tšoenyeha, joalo ka motho ea amehileng ka khatello ea khatello kapa khatello ea maikutlo, le ho etsa lipatlisiso ka methapo ea kutlo ea methapo ea kutlo ka mokhoa oa vivo neuroimaging kapa sampole ea postmortem. E 'ngoe ea lipatlisiso tsa bohlokoa ka ho fetisisa tsa neurobiology ea motho lilemong tse leshome tse fetileng ke bopaki bo bokellanang ba polasetiki e ikhethang ea kelello le nts'etsopele ea neurogeneis libakeng tse fapaneng tsa boko, joalo ka cortex, hippocampus, cerebellum, le bulb ea olgicory. (33). Gould et al. (34) bonts'a li-neuroplasticity tse fetotsoeng meriring ea sefate kamanong e tšoarellang e tlatselletsang ho tsoa paradigm ea maemo a phahameng sechabeng (35). Ka ho khetheha, sehlopha sa hae se bontšitse ho fokotseha ho potlakileng ha palo ea lisele tse ncha tse hlahisitsoeng ka har'a meno a bonojoana ba menoana e tlasana ea sefate ha a bapisoa le ba sa tsebeng boiphihlelo bo sithabetsang. (34). Sena se sibolotsoe haufinyane tjena se tšoeroe haholo ke litšoene tsa 'mampuli ka ho sebelisa paradigm ea moahi, e leng mohlala oa khatello ea kelello le kelello joalo ka mohlala o ikhethileng o tlase ho lihlahla tsa sefate. (36). Ka nako ena, ha re tsebe mofuta oa liphetoho tsa neuroplastic bokong ba masea a batho ba nang le matšoao a matšoao a matšoenyeho sechabeng; ka hona, mehopolo ea phetolelo ea khatello ea maikutlo e fokotsehileng tlhahiso ea lisele tsa granule mefuteng ea liphoofolo ha e tsejoe. Leha ho le joalo, phuputso ea morao-rao e bontšitse hore li-neurons tsa granule li na le monyetla oa ho etsa mesebetsi ea ho ithuta e itšetlehileng ka hippocampal (37) mme ka lebaka leo ho fokotseha palong ea li-neuron tsa granule ho ka etsahala hore li fetole sebopeho sa hippocampal ea batho ba baholo (37). Liphihlelo tse sithabetsang, tse eketsang litekanyetso tsa li-glucocorticoids tse potolohang le tse khothalletsang ho lokolloa ha hippocampal glutamate (38), ka hona e ka thibela granule cell neurogeneis. Mathateng a batho ba baholo ba bophelo, re nahana hore phetisetso e feteletseng ea glutamatergic libakeng tsa hippocampal le cortical e ka ba karolo ea mantlha ea ho se sebetse hantle ha kalafo, 'me kalafo e atlehileng e ka thusa ho thibela thibelo ea neurogenesis ha e ntse e ntlafatsa glutamatergic neurotransmission.

Le ha lithuto tse ngata tsa liphoofolo li tsepamisitse maikutlo hodima sebopeho sa hippoampal, ho na le bopaki ba hore khatello ea maikutlo le eona e ama li-cortical neurons (39). Liphetoho tsa Neuroplastic li boetse li itšetlehile ka maemo a li-neurotrophins, joalo ka ntlha ea kholo ea methapo, e tsejoang hore e fetoloa ka mokhoa o fapaneng le boiphihlelo (40). Ebile, lithethefatsi tse joalo ka selotonin reuptake inhibitors (SSRIs), e sebetsang ho phekola matšoenyeho a sechaba, li tsejoa ho eketsa polelo ea motsoako o tsoang bokong oa neurotrophic ho hippocampus (41, 42).

Course le Neural Circuitry of Precursors

Ka lebaka la kholo e makatsang ea nts'etsopele ea likarolo tsa bohlokoa tsa neural, ho na le tjantjello e kholo ea ho nchafatsa tšabo le matšoenyeho a potolohileng methati eohle ea ntlafatso. (43, 44). Nako e telele, mosebetsi oa morao-rao o netefalitse hore palo e kholo ea bana ba khethiloeng e le "ba thibetsoeng" ba tla holisa matšoenyeho a akaretsang sechabeng ka ho ba batho ba baholo (45, 46). Kagan (47) o hlokometse hore masea a likhoeli tsa 4 a neng a e-na le sebaka se tlase sa ho sithabela le ho ts'oaroa ka koloi ka mokhoa o sa tloaelehang a ne a ka tšoha mme a kokobetsoa bongoaneng. Ka mokhoa o ts'oanang, bana ba tsejoang e le ba sa thibeloang boitshwaro likhoeling tsa 21 ba ileng ba lula ba thibetse ketelong tse latelang tsa lilemo tsa 4, 5.5, le 7.5 lilemo, ba bonts'a litekanyetso tse phahameng tsa mathata a ho tšoenyeha ho feta bana ba neng ba sa thibeloa ka boits'oaro. (48), le ha liphumano li ne li sa qalella bakeng sa matšoenyeho a sechaba. Leha ho le joalo, tlhahlobo ea morao-rao e lebelletsoeng ke Pine et al. (43) o khothalelitse kamano e ikhethang lipakeng tsa bongoana le phobia ea batho ba baholo, e fumanehang e lumellanang le ea lithuto tsa lelapa har'a batho ba baholo (49).

Ts'oaetso ea melaetsa ea methapo ea kutlo ho batho ba baholo ba nang le khatello ea maikutlo bathong e thusa ho netefatsa lipontso tsa bongaka le tsa lefutso tse hokahanyang bana ba nang le ts'oaetso le bakuli ba baholo (50). Liphetoho tse hlokomelehang ka ho fetisisa tsa likokoana-hloko tsa bongaka e bile lithuto tsa morao-rao tsa bongo tse entsoeng ho bana ba mahlahahlaha le ba sitisang bana. (51, 52) le liphoofolong (53). Davidson (52, 54) bontšitsoe ho masea le ho batho ba baholo hore maikutlo a amanang le ho ikhula, joalo ka matšoenyeho, a ne a amahanngoa le ts'ebetso ea sebaka se ka pele sa letsoho le letšehali, athe ts'ebetso ea ts'ebetso ea "cortex" ea pele e ne e amana le maikutlo a amanang. Bakuli ba baholo ba nang le bothata ba ho tšoenyeha ka maemo a sechaba ba bontšitse keketseho e kholo ea ts'ebetso libakeng tse nepahetseng tsa nakoana tsa pele le tsa morao-rao tsa pele tsa letlalo ha ba lebelletse ho etsa puo e amanang le lithuto tse bapisoang. (52, 55). Mosebetsing o amanang le bokhachane, lirekoto tsa EEG litsing tse tšabehang tsa rhesus li bonts'itse ts'ebetso ea boemo bo holimo ba lobe, boemo bo phahameng ba cortisol le lintlha tsa CSF CRF, le likarabo tse matla tsa ts'ireletso. (53, 56). Leha lipatlisiso tsena li le monate, li kanna tsa ba mafu a sa hlonepheng, ho Rauch et al. (57) e bonts'itse ts'ebetso e atileng ka kotloloho e ka tlase e ka pele ea bokapele, hara libaka tse ling, ho fihlela lits'oants'o tse tharo tsa ho tšoenyeha (diagnostive-activive disorder [OCD], PTSD, le phobia e bonolo) ho paradigm ea PET ea lipontšo. Ka hona, leha kamano ea mafu a pakeng tsa boits'oaro bo botle le ho ts'oenyeha ha batho ba baholo e bonahala e netefalitsoe ke liphetoho tse tloaelehileng tikolohong ea ts'ebetso ea boko, litloaelano tsa likokoana-hloko e kanna ea ba moferefere.

Litefiso tse tlase tsa liphatsa tsa lefutso bakeng sa pherekano ea ho tšoenyeha ka sechaba mafahla a monozygotic (62) ba khothalelitse hore liphatsa tsa lefutso li bapala karolo e lekanyelitsoeng kholisong ea eona. Joalokaha re khothalelitse ka lebaka la ho tšoha (1), se shebahalang eka se fuoe lefa ke monyetla oa ho tšoenyeha ka maemo a bophelo, eseng pherekano ka boeona. Le ha ho se lithuto tse amanang le liphatsa tsa lefutso tse sebelisang tlhahlobo ea genomic kapa lipatlisiso lipakeng tsa mofuta oa khetho e entsoe bakeng sa pherekano ea matšoenyeho a sechaba ho fihlela joale, lithuto tse joalo li ntse li tsoela pele ka lebaka la ho tšoha ha letsoalo (63) le OCD (64). Ka mokhoa o ts'oanang, liphuputso tsa liphatsa tsa lefutso tsa liphatsa tsa lefutso tsa mofuta oa li-neurotransmitter tse kentsoeng matšoenyehong a sechaba, haholo-holo serotonin transporter le dopamine receptor le li-subtypes tsa bona tse fapaneng, li lumelletse likamano lipakeng tsa mefuta e ikhethang le mekhoa ea boits'oaro, joalo ka ho qoba ho senya le ho batla bocha (65, 66)- Lintho tse amanang le tloaelo ea ho tšoenyeha ka boemo ba sechaba. Ka hona, lipatlisiso tsa lefutso le tsa malapa tse ho batho ba nang le mathata a ho tšoenyeha ka bophelo ba setšo li ntse li le lilemong tsa bona empa li tšehetsa lintlha tsa bongaka tse telele tse fanang ka maikutlo a kamano pakeng tsa bongoana le batho ba baholo ba lefu lena.

Litekanyetso tsa Pharmacological

Boithuto ba phephetso bo bonts'itse ho senyeha ho monoamine (dopamine, norepinephrine) le indoleamine (serotonin) neurotransmission. Ho lithuto tsa serotonergic, Tancer et al. (10) e tlaleha karabelo ea cortisol e sa tsitsitseng ea fenfluramine ho bakuli ba nang le matšoenyeho a sechaba ho bapisa lithuto, ba fumane se tšoanang le se bonoang lithutong tse nang le ho tšoha. Hollander et al. (67) a tlaleha likarabo tse eketsehang tsa ho tšoenyeha mabapi le phuputso ea serotonergic m-CPP, empa ha ho na liphetoho tsa bohlokoa tsa neuroendocrine. Ha a ithuta mosebetsi oa dopamine, sehlopha sa Tancer (10) ha a ka a fumana letho le sa tloaelehang la tšebetso ea dopaminergic ha a sebelisa l-dopa e le probe ea meriana (Bona F1 bakeng sa kakaretso ea litlolo tsa dopaminergic tse hlokometsoeng khaellong ea matšoenyeho a sechaba [68-72]). Mathata a mang a sebelisoang hangata lithutong tsa ho tšoha ha letsoalo, joalo ka CO₂, lactate, pentagastrin, le epinephrine, ka kakaretso li hlahisitse karabelo e mahareng, pakeng tsa bakuli ba nang le ts'abo ea ho tšaba le lithuto tse bapisoang, ho bakuli ba nang le bothata ba ho tšoenyeha sechabeng. (73, 74). Tlaleho ea morao-rao ke Pine et al. (75) e senotse ho hloka setsoalle pakeng tsa CO₂ sensitivity and phumia ea lesea sechabeng, e lumellanang le lithuto tse sa fumaneng kamano pakeng tsa phobia ea kahisano ea bongoaneng le pherekano ea batho ba baholo (76). Re phethela ho tsoa lithutong tsena tse fokolang hore ho na le lefu le akaretsang le fapaneng la khatello ea maikutlo le khatello ea maikutlo bathong.  

Norepinephrine ho Social Phobia

Kaha autonomic hyperarousal (e bonts'itsoeng ka ho sesa, ho tachycardia, le ho thothomela) ke lets'oao le tloaelehileng la bakuli ba nang le letsoalo la ho tšoha le ho ts'oenyeha ha sechaba maemong a ts'ebetso, ho utloisisa ts'ebetso ea tsamaiso ea methapo ea kutlo ho bakuli bana ho ka hlakisa ho se sebetse hantle ha potoloho ea ts'ebetso ea matšoenyeho a sechaba. Stein et al. (77) o entse tlhahlobo ea phephetso ea orthostatic ho bakuli ba nang le bothata ba ho tšoenyeha ka sechaba, ho tšoha ka letsoalo, le lithuto tsa bophelo bo botle mme a fumana hore sehlopha sa pele se ne se e-na le maemo a phahameng a plasma ea norepinephrine pele le kamora phephetso. Phumano ena e ne e sa phetoe thutong e ileng ea latela ea ho bapisa lithuto le phobia ea maemo a bophelo, 'me ha e le hantle ho bile le tlhahiso ea ts'ebetso ea ho se lekane ea batho ba sa tsotelleng (e se nang kutloelo-bohloko) sehlopheng se nang le mathata a ho tšoenyeha a sechaba ka kakaretso mabapi le lithuto tse bapisoang. (78).

Lintlha tse lekantsoeng li khothalelitse hore α₂ adrenergic antagonist yohimbine e eketsa matšoenyeho a sechaba ho bakuli ba nang le khatello ea maikutlo ea sechaba mme e amana le ho eketseha ha plasma 3-methoxy-4-hydroxyphenylglycol (79). Ka lehlakoreng le leng, Papp et al. (80) e kentse epinephrine e kenang ho bakuli ba nang le mathata a ho tšoenyeha sechabeng mme a hlokomela hore ke a le mong ho bakuli ba 11 ea nang le matšoenyeho a bonoang, a fanang ka maikutlo a hore keketseho ea maemo a epinephrine a le mong ha a na ho lekana ho baka matšoenyeho sechabeng. Haholo, Tancer et al. (81) o ile a bona karabelo e fokotsehileng ea GH ho intravenous, empa eseng ka molomo, clonidine, α₂ adrenergic agonist. Karabelo ea GH e sa sebetseng ho clonidine e boetse e bonoa lithutong tse nang le ho tšoha, ho sithabela ho hoholo ha khatello ea maikutlo, le ho tšoenyeha ka kakaretso mme ho nahanoa hore e ka supa mesebetsi e fokotsehileng ea postynaptic adrenergic-2 e sebetsang ka lebaka la ho eketseha ha mosebetsi oa norepinephrine. Ntle le moo, Coplan et al. (16) hypothesised hore karabelo e hlakileng ea GH ho clonidine kapa li-secagogues tse ling tsa GH e ka bonts'a ts'ebetso e kholo ea hare ea ts'ebetso ea neuropeptide CRF e tšosang. Ka kakaretso, le ha ho na le datha tse lekantsoeng mabapi le karolo ea ho se sebetse ha tsamaiso ea methapo ea kutlo maemong a ho tšoenyeha ka boemo ba bophelo, khatello ea maikutlo e hlokometsoeng ke lingaka ho bakuli ba bang e supa ho se sebetse hantle ha tsamaiso ea methapo ea kutlo.

Ho na le lipotso tse ngata tse sa arajoang mabapi le neurobiology ea bokuli ba matšoenyeho sechabeng. Ha re fuoa polelo ea rona ea hore khatello ea kelello ea ho tšoenyeha ka sechaba e lokela ho hlalosoa e le lefu le sa foleng la neurodevelopmental le qalang bongoaneng, litaba tse 'maloa li hloka ho botsoa ho eketsehileng. Taba ea mantlha, ha re na tsebo ea lithuto tse hlahlobang tšebeliso ea kalafo ea kalafo le kalafo ea bokuli ba matšoenyeho sechabeng le mathata a eona a comorbid le li-futuremor tsa bana. Boloetse ba ho tšoenyeha ka boemo ba bophelo ba bongoaneng hangata bo tsamaisana le ho tšoenyeha ka ho felletseng ka khatello ea kelello kapa bokuli bo arohaneng (91), 'me mefuta ena ea bokuli bo hlasimollang e na le kamano e kholo le lefu la ho tšoha (92). Lipapiso tsa kalafo ea li-neurobiological le neuroimaging tsa kalafo tse sebetsanang ka katleho le bakuli ba kenang pele ho nako 'me ba phekola ka katleho bakuli ba laoloang feela ha ba se ba le baholo li tla ba monate, joalo ka ha ho hlahlojoa karabelo ea kalafo ho pholletsa le lihlopha tse nyane tsa comorbid. Lithuto tse latelang tsa thibelo e ka ba tlatsetso ea tlhaho ea lithuto tse telele tsa bana ba sitisitsoeng.

Taba ea bobeli, kutlwisiso e ntlafalitsoeng ea "neurobiology" ea tsoelo-pele ea likarolo tsa bokong ho bohlokoa molemong oa matšoenyeho a sechaba, joalo ka amygdala le striatum, le tšebelisano ea bona le cortex, litsamaiso tse nyolohang tsaaminaminergic, le hippocampus, ka ho hlakileng lia hlokahala. E amanang le morero ona oa lipatlisiso tsa liphatsa tsa lefutso, re lokela ho leka ho shebana le mefuta ea tlokotsi bakeng la phenotype e pharalletseng ea sechaba. Re na le kutloisiso e fokolang ea tšebelisano lipakeng tsa ho ba kotsing ea liphatsa tsa lefutso le ho pepesetsoa khatello ea maikutlo bathong ba tšoenyehileng sechabeng. Litaba tse matlafatsang tse tlatselletsang tlas'a maemo a batang a kopantsoeng ka mokhoa o batsi li abeloa bana ka boomo kapa bo-mme ba nang le boiphihlelo bo ka thusa ho araba potso ea hore na ho pepesetsoa khatello ea maikutlo ho na le tšusumetso e mpe ho batho ba kotsing ea lefutso.

Taba ea boraro, ho nahana ka MRS ho ka sebelisoa ho ithuta lits'ebetso tsa methapo ea kutlo tse sa fumaneng tlhokomelo e kholo matšoenyehong a sechaba, joalo ka sistimi ea glutamatergic. Mefuta ea kalafo ea litoeba e pheha khang ea hore li-cortical efferents tsa pele ho moo, ekaba ka kotloloho kapa ka thalamic nuclei efferents, li sebelisa sistimi ea glutamatergic e le mohloli o ka sehloohong oa tšusumetso ea methapo ea kutlo ea "ts'abo" ea methapo ea kutlo, e tsoang khubung ea mantlha ea amygdala le khubu ea bethe ea ea stria terminalis (93, 94). Maemo a sithabetsang ao motho ea nang le bothata ba ho tšoenyeha ka maemo a bophelo a ka bang le ona a ka susumetsa ho tsoa ha glutamate ka hippocampal (38) le likarolo tse ling tsa boko. Ka leseli lena, li-agents tse amohelang glutamatergic neurotransication li lokela ho fokotsa maemo a ho tšoenyeha, hammoho le liphetoho tse kopaneng tsa biochemical tse amanang le khatello ea maikutlo. Liteko tsa bongaka tsa bahanyetsi ba glutamatergic li kanna tsa lumelloa, hobane li-SSRI li atlehile ka mokhoa o fokolang ho phekola lefu lena. MRS e boetse e lumella bafuputsi ho lekola litšebelisano tsa neurotransmitter ho vivo, joalo ka tšebelisano pakeng tsa serotonin le glutamate, ka boqhetseke bo sa tsoa sibolloa ke Rosenberg et al. (95) ho OCD ea bana.

Qetellong, moeli oa bohlokoa oa kutloisiso ea rona ea neurobiology ea matšoenyeho a sechaba ke bothata ba ho khetholla se fumanoeng e le karabelo ea matšoenyeho kapa khatello ea maikutlo le lintlha tsa nnete tsa kotsi bakeng sa nts'etsopele ea matšoenyeho. Ho bohlokoa hore kliniki ea neuroendocrinology ea matšoenyeho a sechaba e bonts'a boemo bo lefelletsoeng ka botlalo ho ba motho e moholo, ka hore ha ho na pherekano (ke hore, HPA axis) pathology e hlahang. Ka leseli lena ho tla ba ho khahlisang ho ithuta bakuli ba nang le ts'oaetso ea khatello ea maikutlo ea morao-rao khahlanong le bakuli ba nang le nako e telele haholo ho bona hore na ke liphetho life tsa neuroendocrine tse phehellang le tse fetohang nakong ea bokuli. Phapang e 'ngoe ea bohlokoa e ne e tla ba ho ithuta bakuli ba nang le khatello ea maikutlo ea ho ba le matšoenyeho sechabeng le bakuli ba tšoareloang. Kutloisiso e ntlafalitsoeng haholoanyane ea ketsahalo ena e tlatselletsang e ka fana ka leseli la bohlokoa eseng feela bothateng ba matšoenyeho sechabeng empa hape le mathateng a mang a kelello le mathata a sa tloaelehang a neuroendocrine.

E amohetse Julayi 13, 2000; ntlafatso e amohetse Jan. 10, 2001; e amohetsoe Jan. 18, 2001. Ho tsoa New York State Psychiatric Institute, Mafapha a Psychiatry le Clinical Psychobiology, K'holejeng ea Lingaka le Boholo Ikopanye le likopo tsa phetisetso ho Dr. Mathew, Lefapha la Psychiatry, K'holejeng ea Lingaka le Boholo, Yunivesithi ea Columbia, 1051 Riverside Dr., Box 84, New York, NY 10032; [imeile e sirelelitsoe] (imeile). E filoe chelete ke karolo ea NiH ho fa MH-00416 le Setsi sa Neural Systems of Tšabo le Matšoenyeho a ho Ts'oenyeha MH-58911 le MH-00416 (ho Dr. Gorman), Moputso oa nts'etsopele ea Bo-ramahlale bakeng sa Tleliniki e fa MH-01039 (ho Dr. Coplan) , le Lenaneo la Naha la Patlisiso mabapi le Schizophrenia le Depression Young Inarcherator Award le Tjhelete ya Thuso ya Tshehetso ya Patlisiso ya Psychiatric Institute (ho Dr. Mathew). Bangoli ba leboha Marc Laruelle, MD, ka liphallelo tsa hae.