Kuvandudza Neurocircuitry yekukurudzirwa Muhuduku: Nguva Yakaoma yekudhakwa Kunetseka (2003)

Am J Psychiatry. 2003 June; 160(6): 1041-1052.
 
PMCID: PMC2919168
R. Andrew Chambers, MD, Jane R. Taylor, Ph.D., uye Marc N. Potenza, MD, Ph.D.

ngovepo

vavariro

Epidemiological zvidzidzo zvinoratidza kuti kuyedza nemishonga inopinda muropa uye kutanga kwekupindwa muropa kwakanyanya kunoiswa pakukura uye mudiki. Vanyori vacho vanotsanangura dudziro yekutanga uye yekiriniki inotsigira kuyaruka kuyera senge nguva yakakosha yekuzvidzivirira zvakanyanya pakuedza zvinhu uye kuwanikwa kwekunetseka kwekushandiswa kwezvinodhaka.

nzira

Vanyori vakaongorora zvinyorwa zvichangoburwa nezve zvemukati zvemagetsi zvinosimbisa kukurudzira, kushingairira, uye kupindwa muropa, nechinangwa chekuongorora kunoongorora vechidiki vekuyaruka.

Results

Adolescent neurodevelopment inoitika munzvimbo dzehuropi dzakabatana nekukurudzira, kushamisira, uye kupindwa muropa. Adolescent impulsivity uye / kana nehutsva kutsvaga seyakachinjika maitiro maitiro anogona kutsanangurwa muchikamu nekuchinja kwematanho mu frontal cortical uye subcortical monoaminergic system. Aya maitiro ekusimudzira anogona kubatsira kusimudzira madhiraivha ekudzidza kuti aenderane neyevakuru mabasa asi zvinogona zvakare kupa kusagadzikana kukuru kumabasa akapindwa muropa nezvinodhaka.

mhedziso

Kuongorora kwekuvandudza shanduko muurocircuitry inobatanidzwa mukudzora kwekukanganisa kune zvakakomba mhedzisiro yekunzwisisa maitiro evechiri kuyaruka, kupindwa muropa nenjodzi, nekudzivirira kwekudzvinyirira mukuyaruka uye kukura.

Zvirwere zvekushandiswa kwezvinodhaka zvinotungamira chikonzero chekurwara kusasimba, kufa, uye kushandiswa kwehutano muUnited States (1. Kuwanika kwenzvimbo yezvinhu uye maitiro emagariro zvinopesvedzera kuwanda kweiyo chaiyo yekushandiswa kwezvinodhaka zvinokanganisa (2. Kutarisa kukuru kwakakura kunoratidza kuti inguva dzekuvandudzwa kwekuyaruka uye yekutanga kuva vakuru ndiyo yekutanga mamiriro ekushandiswa kwezvinodhaka uye kusagadziriswa kwekushandiswa kwezvinodhaka, zvichishanda mumamiriro ezvinhu etsika uye zvinhu. Kutanga, vachiri kuyaruka uye vechidiki vakuru vanowanzoratidza yakakwira miedzo yekushandiswa kwekushandisa uye zvinoshandiswa mukushandiswa kwezvinodhaka kupfuura vakuru, sezvakaratidzwa nezvidzidzo zvehuwandu hwevanhu vanotanga makumi maviri emakore apfuura uye nekushandiswa kwedzimwe nzira dzekuongorora (3-5. Chechipiri, zvipingaidzo zvinopinda muropa zvinoonekwa muvakuru zvinowanzoitika mukukura kana kukura kwevechidiki (6, 7. Semuenzaniso, vazhinji vakuru vekusvuta veU.S. vanotanga kuputa usati zera 18 (8), uye kutanga kwekuputa kwemazuva ese hakuna kujairika mushure memazera 25 (9. Pamusoro pe40% yevakuru vakadhakwa vanoona zviratidzo zvine chekuita nedoro pakati pemazera 15 uye 19, uye 80% yemhosva dzose dzechidhakwa dzinotanga vasati vasvika zera 30 (10. Wepakati akataura zera rekutanga kwekushandiswa zvisiri pamutemo kwekushandiswa kwezvinodhaka muvakuru vane dambudziko rekushandiswa kwezvinodhaka ndeye 16 makore, ne50% yematare anotangira pakati pemazera 15 uye 18 uye isingawanzo kuvambwa mushure mezera 20 (3. Yetatu, kutanga kwekushandiswa kwezvinoshandiswa kunofanotaura kupenga kwakanyanya uye kushupika, kusanganisira kushandiswa kwe- uye zvinokanganiswa nekushandiswa kwezvinoshandiswa zvinoenderana ne — zvinhu zvakawandisa (6, 11, 12. Kunyangwe ongororo yezvirwere inowanzoratidza kuwanda kwekunetseka kwekushandiswa kwezvinoshandiswa mune zvechirume kupfuura muzvidzidzo zvevakadzi pazera rese, aya maitiro ezvezera anoonekwa mune zvese zvevakadzi nevarume, zvichiratidza kuvapo kwezvikonzero zvevakadzi - mukuzvitangisa kwe kutanga kwezvinhu zvinoshandiswa mukushandiswa kwezvinoshandiswa. (4, 13).

Makiyi maviri akasiyana mune genesis yekupinda muropa kusagadzikana ndeye 1) dhigari / huwandu hwechinwiwa chinodhaka uye 2) iyo yekuzvidzivirira njodzi yekupindwa muropa yakapihwa huwandu hwakatemwa hwekudhakwa (14, 15. Kunzwisisa kana chimwe kana zviviri zvezvinhu izvi zvakakura mukuyaruka zvakakosha mukutsanangura kutanga kwekutanga kwekushomeka kwekushandiswa kwezvinodhaka. Kunyangwe tsika, vezera, uye kufurira kwemhuri kuchikonzera kuwanikwa kwezvinodhaka uye kuedza kwezvinodhaka (16), huwandu hwakawanda hweuchapupu hunoratidza kuti magariro uye hutano hwevachiri vega havaratidze zvakakwana nezvekudhakwa kwakawanda kwezvinodhaka. Kunyangwe kushambadzira uye kuwanikwa kwemishonga yapamutemo (doro uye chikakananda) zviri zvese pakati pemazera mumagariro eAmerican uye zvakatemerwa zviri pamutemo chete kune vakuru, kutanga kwekushomeka kwezvinodhaka zvekushandisa zvinodhaka nemishonga iyi kunoiswa mukukura uye mudiki. mune yekuwedzera nzira nezera rekuwedzera. MuEurope, uko tsika dzevechidiki uye tsika dzemagariro nezvezvinhu zvinosiyana kubva kune izvo zvinowanikwa muUnited States, zvinoitika uye kusagadzikana kunosangana nechirwere chekushandiswa kwezvinodhaka zvinowanzoitika muvachiri kuyaruka uye vakuru vechidiki (17, 18).

Genetic uye neurobiological zvinhu zviri mukati mevanhu zvinofungidzirwa kudzikisira mukana wekuratidzwa kwezvinodhaka unodiwa kuti "uchipinze switch" kubva pakuedza kuenda pakapindwa muropa nekushandisa zvinodhaka (15. Kukura kwekirinari humbowo kunoratidza kuti kuyaruka kunomiririra nguva yekuwedzeredzwa kwechiitiko kuzvipfeko zvekupindwa muropa nezvinhu zvisiri pamutemo uye zvisiri pamutemo. Semuenzaniso, vayaruki vanoratidza kuwedzera mberi kwekushandisa zvisiri pamutemo kwekushandiswa kwezvinodhaka kupfuura vanhu vakuru (4, 19. Pasinei nekuputa fodya mashoma kupfuura vakuru, vachiri kuyaruka vanoratidza huwandu hwakanyanya hwekuvimba pamazinga akafanana ekushandisa (20), uye kunyangwe mitengo yezvinwiwa zvinodhaka yakafanana mukuyaruka uye mukukura, huwandu hwekushungurudzwa / kuderera kwakasiyana mune zera.5. Ichi chinyorwa chinoongorora hwakakosha uye hwechipatara humbowo hwevachiri kuyaruka neurodevelopment senguva yakakosha yekupindwa muropa. Behaviors inoita kunge ichiratidzwa nekusanzwisisika uye kuita zvisarudzo zvisinga tsanangurike zvinotsanangurwa se hunhu hwekuyaruka hunowirirana nekusimudzira kwekufambiswa kwekutenderera kwakabatanidzwa muhutachiona hwekupindwa muropa. Zviitiko zvebudiriro zvinogonesa kufambisa zvinosimudzira kudzidza nezve zviitiko zvevakuru panguva imwechete zvinowedzera kusakwana panjodzi dzekuvandudza mhedzisiro yemishonga inopindwa muropa, zvichitungamira mukushomeka kwekushandiswa kwezvinodhaka.

Enda ku:

Impulsivity uye Kuronga Kuita

Kuwanda kwekunetseka kwekushandiswa kwezvinodhaka kunokwidziridzwa muvakuru vane schizophrenia, hukuru hwekunetseka, kusagadzikana uye kusagadzikana kwehunhu hunhu, uye chirwere chekubhejera.2, 3, 10, 21, 22. Vechidiki vane antecedent kana yakanyatsotsanangurwa shanduro dzekushushikana uku zvakare vanogona kuve nedambudziko rekushandisa zvinodhaka (23-25. Masangano ezvirwere zvepfungwa idzi uye kuyaruka nehuremu hwekushomeka kwezvekushandisa zvinoratidza kuti zvinowanzoitika muhuropi zvinogona kukanganisa dambudziko rekushomeka kwezvinodhaka mune idzi mamiriro akasiyana. Aya maratidziro anogona kuratidzika seyakawanda kliniki motif kana maitiro ane maitiro anopfuudza kuyaruka, psychiatric, kana zvinodhaka zvinoshandiswa mapoka. Kukanganisika kwekumanikidza kudzora kunomiririra imwe yakadai motif (23, 26, 27. Sezvimwe nezvimwe zvinotsanangurwa zvinoumbira kurapwa kwepfungwa, chirevo chaicho chekusanzwisisika uye hukama hwayo kuzvimiro zvenguva pfupi kana kwekutsvagira kutsvaga zvinokanganisika. Kusiyana-siyana kwekumanikidzwa kwakatsanangurwa, zvichienderana nekiriniki chiyero uye nekushanda kwenzvimbo dzeuropi chaiongororwa (28. Pano tinogadzira kusakendenga sehunhu-hwakanangidzirwa hwehunhu hunoratidzwa nekutadza kusagadzikana mukuwana mibairo, senge zvinodhaka zvinopinda muropa, bonde, chikafu, simba remagariro (nenzira yechisimba), mari, kana zvimwe zviwanikwa (27, 28. Neiyi tsananguro, maitiro ekumanikidza anowanzo kukonzera kukuvadza kana kusabvisa migumisiro; hunhu hunoratidzwa nekuwedzera kutsva kutsvaga kana kuita zvisarudzo zvisarudzo zvakanaka kunganzi kurasisa (29).

Zvirwere zvepfungwa zvinowanzozivikanwa pamwe nekuvhiringidza kwekukurudzira kwemubairo uye kushandiswa kwezvinodhaka kusagadzikana comorbidity inosanganiswa nekusagadzikana (3, 27, 28, 30. Zvishandiso kuyera kuita sarudzo zvinoratidza kusanzwisisika senge sarudzo yekuda kukuru-njodzi / shoma-mubatsiri sarudzo kana shoma shoma mubayiro pamusoro wakanyanya kunonoka mubayiro (wepadiki kuderedzwa) (31, 32. Mhinduro dzekumanikidza dzakaonekwa dzakabatana nekukanganisa-kudzora kusagadzikana, kusagadziriswa kwekushandiswa kwezvinodhaka, uye kurapwa kwepfungwa nepfungwa yekukanganisa-uye / kana chinwiwa chinoshandiswa kusagadzikana comorbidity (26, 33. Kunyangwe zviridzwa zvakafanana hazvisati zvave kushandiswa muvachiri kuyaruka, kukurumidza uye / kana kungwara kutsvagirwa kazhinji kunoonekwa kuwedzera muhuduku uye kuderera nezera (34, 35).

Kunzwisisa hukama pakati pekumanikidzira uye kusagadzikana kwekushandiswa kwezvinoshandiswa kunogona kuratidza kukosha kwekuzwisisa pathogenesis yekushomeka kwekushandiswa kwezvinodhaka uye kukura kwavo kwakanyanya mune chaiwo mamiriro ekiriniki, kusanganisira kuyaruka. Conceptualizations yekiriniki syndromes yekushandiswa kwekushandiswa kwezvinodhaka uye kusagadzikana kwekumanikidza kudzora kana kusarudza sarudzo maficha anoratidza mafomu akafanana ekukurudzira psychopathology. Ivo vanhu vane hurombo husina kusimba kudzora vanoratidza vane hukama hunhu hwekuita hunhu hunoratidzwa neyakareba mhedzisiro yakaipa mhedzisiro. Saizvozvowo, zvinhu zvinopinda muropa zvakabatana pamwe chete nekushanduka kwemakemikari uye kuchinja kwemaitiro muuropi hwekurapa kwepasi, zvichitungamira mukuwedzera kushandiswa kwezvinodhaka pakurasikirwa kwemagariro uye ebasa pabasa (15. Analogous yekiriniki conceptualizations yekushungurudzika uye kupindwa muropa maererano nesystem yekuita basa repertoires inogona kuratidza yakajairika neurobiological maitiro emisangano inosanganisira kukurudzira neurocircuitry.

Enda ku:

Neurocircuitry yeMotivational Substrates

Kunzwisisa anatomy uye basa rekusimudzira uropi masisitimu kunogona kupa ruzivo rwakakosha nezvehukama pakati pekusanzwisisika, njodzi yekushomeka kwezvinodhaka zvekushandisa, uye kuyaruka. Kukurudzira kunogona kushandurwa senge chiitiko chehuropi chinogadzirisa "kupinza" ruzivo nezve mamiriro emukati memunhu uye yekunze nzvimbo uye kunotarisisa hunhu "kubuda" (36. Panzvimbo pekushanda seyakareruka Refresh system inogadzira maitiro akaoma kupindura kushushikana kusimudzira, kukurudzira kunosanganisira kumusoro-kurongedza kugadzirwa kwakagadzirirwa kuronga hunhu kukwidziridza kupukunyuka (37. Chinangwa chinotungamirirwa nechinangwa chinosanganisira kubatanidza ruzivo nezve dzakawanda shanduko dzemukati (semuenzaniso, nzara, chishuwo chebonde, kana kurwadziwa) nemamiriro ekunze (zvinosanganisira zviwanikwa kana mikana yekubereka, kuvapo kwengozi) mukugadzira mhinduro ine hunhu (31. Kuenzanisa nekunetseka uku, zvirongwa zvekupona zvakati wandei zvinogona kuve nekukosha asi zvakaringana zvinowanikwa munzvimbo uye nguva, uye panogona kunge paine huwandu hukuru hweanogona kubudirira maitiro ekugona kuwana imwe kana yakawanda yeizvi zvinangwa. Motivational neurocircuitry inofanira kubatanidza matekiniki anokwanisa kumiririra mamwe anofambisa anodhiraivha uye nekufanogadza uye kusarudza madhiraivha akakurudzira ekutevedzera (36, 38).

Dudziro neuroscience yave kutanga kuburitsa nerobiological proof inotsigira izvi zvekufungidzira. Kukosha kwekukurudzira kune kushanduka kwemasimba kusimba kungafanozivisa kuti kwakakura zvikamu zveuropi zvinobatanidzwa, zvichitevera hutongi hwehumambo hwehumambo hwehupfumi uye inoshanda yakachengetedzwa pamarudzi ese marudzi. Zvidzidzo zvemhuka nevanhu zvakaratidza kuvepo kweiyo yekutanga kukurudzira kutenderera kunobatanidza neyekutanga cortex uye ventral striatum, ine mukana wakananga kupinda uye kufurira kune mota "kubuda" zvimiro (37. Iyi anterior system inotsigirwa neinonyanya kuparadzirwa uye yepashure yakaiswa sekesitiri kukurudzira kutenderera iyo inopa huwandu modalities of sensory "yekuisa" ruzivo kuburikidza nenzira yakananga axonal kufungidzira kushandurwa kuve kwekutanga kukurudzira maseketeMufananidzo 1) (39-41. Semuenzaniso, iyo hippocampus uye amygdala inopa mamiriro ekurangarira uye ruzivo rwakakodzera rwunoita kune kukurudzira kukurudzira (31, 39, 42, 43), nepo hypothalamic uye septal nuclei ichipa ruzivo rwakakodzera kune hwepakutanga kana hunhu hunokurudzirwa hunhu hunhu, sekusimbisa muviri, kurwisa, uye mhinduro dzekubereka (44).

FIGURE 1  

Huru Kukurudzira Brain Circuitry Kuiswa mune Impulsivity, Kuita Chisarudzo Kuita, uye Kupindwa Muropa Nezvinodhaka.a

Zvichangobva kuwanikwa zvinoratidza hunhu hwekukurudzira hwekuita kunge huine huwandu hwevanhu vemutsinga vanokwanisa kugadzira mapundu ekupfura ayo anogona kusimbisa akawanda maficha ekukurudzira kana mamwe madhiraira anokurudzira (45. Izvi zvinomiririra zvinoitika pakati pemitsipa inonzi neuronal ensembles yakabatana neparutivi zvimisheni zve serial axonal zvinofungidzirwa kubva kumberi yepamberi cortex kuenda kune ventral striatum (iyo nucleus inoungana kune iyo ventral globus pallidus) kune thalamus uye kumashure kwecortex (46, 47) (Mufananidzo 1 uye Mufananidzo 2. Cortical-striatal-thalamic-cortical loops inotsanangurwa seyakafanana nekuti subquions chaiyo yeiyo yepamberi cortex (semuenzaniso, anterior cingate, ventromedial, uye dorsolateral kumatunhu) chirongwa kune chakati compartments mukati me striatum, iyo inochengetedza imwe nhanho yekuparadzanisa muzvirongwa iyo thalamus uye kudzokera ku cortex (48. Zvese zviviri anatomical uye neurophysiological humbowo hunoratidza kuti kupfura maitiro eanoronal ensembles mukati anoshanda chaiwo ma compartments eiyo striatum ari muchikamu akapindirana nehurongwa hwekupfura mune yakatarwa preortal cortex subregions (42, 49. Nekudaro, maitiro ekupfura mune ese ari maviri nucleus anounganidza uye prefrontal cortex inokonzerwa nekupinza glutamatergic mukati meiyo hippocampus uye amygdala, zvichidaro kuti kusabatwa kwezvinhu izvi muzvikamu zve distal kunogona kuburitsa zvese chirwere chepfungwa uye kusimudzira kukanganisika (50. Nekuda kwekuti striatal popople ine simba yakananga pazvivakwa zve motor uye mota cortices uye brainstem mota nzvimbo, basa ravo rinonyanya kutarisana inokurudzira yenzvimbo uye maitiro ezvekuburitsa (39, 44. Kuunganidzwa kwakakomba kwe γ-aminobutyric acid (GABA) -ergic inhibitory neurons mune striatum kutaurirana nenzira yekudzokorora kubatana inhibition iyo inotsanangudza nezvehupamhi hwepamusoro hwepamhepo neural network yekuvhara huwandu hwakakura hweimwe nzira yekupfura inogona kushanda seanobhowa kuvaka zvidhinha. yeakawanda, yakanyatsokwiridzwa yakakurudzira inofambisa (39, 47, 51-67).

FIGURE 2  

Cortical-Striatal-Thalamic-Cortical Loops Pakati YePakati Yekusimudzira Denderedzwa Inosanganisirwa Mukuratidzwa Kwekurudziro Kufambisa uye Neurocomputational Zviitiko zveMota Yekuita Kuronga uye Kuzvibataa

Uchapupu hunowedzera hunoratidza kuti neurocircuitry encoding repertoires yemamwe mafambiro anofambiswa anoitiswa nezviitiko zveuropi zvinoisa pamberi uye sarudza zvinokurudzirwa zvinofambiswa zvekuita. Makuru-neural substrates ave achibatanidzwa nekusimudzira (kuwedzera mukana wekunyorwa) kana kudzivirira zvinofambisa zvinofambiswa. Kuvhiringidzika kwekukurudzira kudzokorora, kusanganisira mhando dzekumanikidza uye kupindwa muropa, saka zvinogona kuratidza kusagadzikana kurongeka kana kushanda zvisina kujairika kwekusimudzira kana inhibitory neural system yakakosha kune yekutanga kukurudzira kutenderera.41, 52. Zvinoenderana nepfungwa iyi, zvidzidzo zvehupfumi zvinoratidzira zviwanikwa zvepasipasi-zvekunamatira matunhu uye chepamberi cortex mune zvemukati nekuziva mashandiro ezvekuita sarudzo uye nekuita kwecompacological kwema zvinodhaka akapindwa muropa (53. Kuenderera mberi nekuongorora iyi hypothesis, data inomiririra yekusimudzira uye inhibitory yekukurudzira substrates icharondedzerwa, ichiteverwa nekuongororwa kwekuchinja mukati menzira idzi panguva yekuyaruka.

Kukurudzira Kusimudzira Substrates

Dopamine kuburitswa mukati me striatum chiitiko chikuru chetsitsi chakasimudzirwa mukushandurwa kwema encodised anofambisa kuita chiito, achishanda sechiratidzo chekuti "enda" (54. Dopamine kuburitswa mukati meiyo ventral striatum (nucleus accumbens) uye dorsal striatum (caudate putamen) inotsamwiswa nezviratidzo zvekunakidzwa kubva ku cortex uye dzimwe nzvimbo dzinomutsa dopamine neuron chiitiko mune ventral tegmental nzvimbo uye substantia nigra, zvichiteedzana (55, 56) (Mufananidzo 1. Nekudaro, izvo zvemukati nepadorsal zvikamu zvinosanganisirwa nemazinga akasiyana ekugadzirwa kwepanyama. Dopamine kubudiswa mune dorsal striatum, inokanganisika mune pathogenesis yechirwere cheParkinson, inonyanya kufambidzana nekutanga uye kuyerera kweye concrete mota chiitiko uye hunhu hunhu.57. Mukupesana, kubudiswa kwe dopamine muiyo nucleus accumbens kwakabatana nekukurudzira kukurudzira, subjential mubairo, premotor cognition (pfungwa), uye kudzidza kwemaitiro matsva (43, 46, 58. Iyo chaiyo nzira iyo dopamine kubudiswa inobatanidzwa mukushandurwa kwepfungwa muchiito hazvizivikanwe. Rimwe basa rinoratidza kuti dopamine discharge inokanganisa zvakananga maitiro ekuputika kweiyo neuronal ensembles muiyo nucleus inounganidza uye inokanganisa kupindura kwavo kune glutamatergic pembevo kubva ku cortex, amygdala, uye hippocampus (51, 59) (Mufananidzo 2B. Tsvagurudzo iyi inoratidza kuti ruzivo rwekunzwa, rwakakodzera, uye rwemamiriro ezvinhu ekurangarira, anotungamira kuchizvarwa chekufananidzirwa kwemadhiraivhi anokurudzirwa, inobatwa nekuburitswa kwe dopamine mu striatum, zvekuti nzvimbo dzinodzika dzemvura dzinogona kugashira uye kuita chimwe chiitiko cheruzivo rwekukurudzira (51, 59, 60. Saizvozvo, neurotootic maronda epamberi cortex, amygdala, kana hippocampus inoshandura maitiro repertoires anotsamwiswa neachemicological kukurudzira kwe dopamine kubudiswa muiyo nucleus accumbens (61-63).

Yakasiyana-siyana yekukurudzira kukurudzira yakaratidzwa kuwedzera dopamine muiyo nucleus accumbens. Izvi zvinosanganisira macopacological zviitiko zvinodhaka zvinopinda muropa (zvinosanganisira nicotine, doro, cocaine, amphetamine, opiates, cannabis), mubayiro wechisikigo (chikafu, zvepabonde, kana zvimwe zviwanikwa), kukurudzira kunoenderana nemubayiro uye mamiriro (vhidhiyo-mutambo kutamba), uye zvinoshungurudza kana anodzora anokurudzira (43, 64-67. Kuziva kwezvakatipoteredza kwakakosha kuti utore zviwanikwa zvemubhadharo zviwanikwa, uye kutyaira nekutsvaga zvisingazivikanwe pachako chinhu chine simba kukurudzira43. Zvekudyidzana zvakasikwa zvinotsamwisa ventral-striatal dopamine kubudiswa (68) uye, semishonga inodhakisa, inogadzira maitiro e locomotor mune mhuka dzemabara (69. Novelty, inoonekwa nenzira yemamiriro ezvinhu asina kufanotaurwa kana kukurudzira kwenzvimbo, pamwe nemishonga inodhaka, inonyanya kukurudzira (70. Mibayiro inounzwa muzvipakati, zvisina tsarukano, kana mafashoni asingatarisirwi ane simba rakakura pamusoro pemiedzo inodzokororwa kuchengetedza dopamine cell kupfura uye mubairo-wakagadziriswa maitiro (71, 72. Kusiyana neizvi, akawanda anodzidziswa anokurudzirwa maitiro kana maitiro anoitwa pasi pezvematekiniki anotarisirwa anova mashoma pakuvimba neti nucleus accumbens dopamine kubudiswa. Nekudaro, zvakananga chemacological kukurudzira kwema dopamine masvikiro akapindirwa nemishonga inodhaka anoita kunge anotevedzera uye / kana kuita synergistically nemasikirwo ekuchidzira-encoding zvivakwa zvechisiko zvakapusa.

Chechipiri chakakosha basa re dopamine, pamwe chete ne glutamatergic affilint chiitiko muiyo nucleus inounganidza uye inopinda mukati meGABA-yakaipa basa reiyo nyukiriya inounganidza neurons, inosanganisira kutsanangurwa kwerinomiririra ramangwana uye kusarudzika zvido zvekufambiswa kwemadhiraivhi anokurudzira. Mukudzidza zvine chekuita nemubairo, hunhu hwemangwana hunoumbwa zvichienderana nezvakamboitika zvakapindirana nemubayiro nenzira dzekushandurwa kwemitsipa muuropi.73. Yakadzokororwa inodzvanywa-inodzvinyirirwa dopamine kubudiswa muiyo nyukiriya inovandudza shanduko mumasero mapuroteni akabatanidzwa mune intracellular receptor signaling nzira, gene expression, uye cellular architecture.15. Dopamine kuendesa mukati memagineti nucleus accumbens uye yepamberi cortex matunhu anomisikidza kune nucleus accumbens kwave kuchinjirwa mumatanho ekudzidza uye epurasitiki, kusanganisira shanduko mukuita kwenguva refu uye morphology yemitsipa inonzi neuronal dendritic (74-77. Aya ma neuroplastic maitiro anogona pasi pehunhu hwekunzwa, uko iyo yekukurudzira drive inosanganiswa nemubairo inowedzera kusimba sezvo iro mubairo mamiriro uchidzokororwa ruzivo (78, 79. Sensitization, sekuwedzera kwechinangwa chekutanga chakabatana nechero rudzidziso rwemubhadharo wehukama kune mamwe ma encoded drive anodhiraivha, inogadzira mubairo-wakananga wekuwana maitiro uyo unowedzera kuve unomanikidza.78. Nenzira iyi, dopamine masisitimu chiitiko chinogona kushanda kwenguva yakareba basa rekudzikisa kana kutarisisa repertoire yezvinokurudzira zvinofambisa zveiye.

Inhibitory Kukurudzira Substrates

Kuremara kwekushanda kana chimiro chemasisitimendi system kwakabatana nekuitwa kweanokurudzirwa madhiraivha anoonekwa seanodarika kana asina kukodzera. Chief pakati peava serotonin (5-HT) neurotransmitter system uye yepamberi cortex zvikamu zve kukurudzira wedunhu (Mufananidzo 1. Zviyero zvekudzora kweuropi 5-HT zviitiko zvinosanganiswa nehunhu hunokasira, kusanganisira chisimba chekunze nekuzvitungamira, kuzviuraya, kutanga moto, uye kubhejera kwepfungwa (80-82. Pharmacological kukuvara kwe5-HT masystem emhuka kunoguma nekupindura kusingafadzi mukudzidza-zvine chekudzidza uye kukurudzira kukurudzira (83. Sezvineiwo, pro-serotonergic vamiririri vanodzora hutsinye hwemagariro uye kushushikana mumhuka nevanhu (84, 85. Kunyangwe michina yezvawanikwa iyi isina kunyatsotsanangurwa, 5-HT inofungidzira kubva mudumbu raphae nuclei kune inokurudzira circry, kusanganisira iyo ventral tegmental nzvimbo, nucleus accumbens, prefrontal cortex, amygdala, uye hippocampus, inoratidzika inobatanidzwa (55, 86).

Prefrontal cortex basa rakabvumirana nekubatana kusingadzoreki. Yakanyorwa sepakutanga se1848, kukuvara kweiyo ventromedial prefrontal cortex inokonzeresa kukurudzira kunokonzerwa nekushamwaridzana kune kusagadzikana kwakabatana, kusarongeka kwekuita sarudzo uye kuronga kwemutungamiri, uye kusava nehanya nemagariro ehupenyu (87. Kusagadzikana kwekumanikidza kudzoreredza kwakazove kutaurwa mune dzakawanda neuropsychiatric mamiriro (semuenzaniso, antisocial hunhu kusagadzikana, affidence kusagadzikana, schizophrenia, kusashanda kwezvinhu zvinokuvadza, dementias, uye zvinoshungurudza uropi kukuvara) inoratidzirwa neisina kujairika matanho e prefrontal cortex basa (26, 30, 88-90).

Prefrontal cortex abnormalities inosanganisirwa nenjodzi yakakura yekukudziridzika kwekushandiswa kwekushandiswa kwezvinodhaka, pamwe inosanganisira shanduko mukupindura kunokurudzira kune zvinodhaka zvinodhaka. Zvidzidzo zvemakiriniki zvinoratidza kusonganirana kwekukuvara kwehuropi kurwara, kazhinji kuchisanganisira yekutanga cortex, nehuremu hwekushandiswa kwekushomeka kwenyaya nyonganiso uye kupa pfungwa yekuti kutanga kwechimwe chezvinhu izvi chete kunowedzera njodzi kune imwe yacho (91-93. Basa kana anatomical abnormalities yepamberi pekutanga cortex yeasingaverengeki etiology zvakare inozivikanwa muhuwandu mune zvinetso zvekushandiswa kwezvinodhaka (94-97. Izvo zvinoenderana nezvekuongororwa kwekiriniki, prewardal cortex lesions mumakonzo inogona kuwedzera kusimbisa kushanda kweecocaine panguva yekuzvitonga.98, 99).

Kuongorora kwe corticostriatal kudyidzana kunopa gadziriro yekumberi kwecortex dysfunction, kuburitsa zvese zviri kukurumidza uye ngozi huru yekushomeka kwezvinodhaka zvekushandisa. Kunakidza glutamatergic kufungidzira kubva kwepamberi pekutanga cortex kusvika kuiyo nucleus anounganidza uye ventral tegmental nharaunda inokurudzira dopamine kubudiswa, neuronal kupfura, uye neuroplastic maitiro muiyo nucleus accumbens (39, 100, 101. Aya mabatomiki uye anoshanda anobatana anoratidza kuti prefrontal cortex inobatanidzwa mumiririri, kuuraya, uye inhibition yeiyo inokurudzira dhiraivha nekufurira maitiro e neural ensemble kupfura mukati meiyo nucleus accumbens. Kubvumirana kweiyo yepamberi cortex kana magedhi ayo kune nucleus accumbens inogona 1) kushandura akasiyana-siyana mimiririri yeiyo inosimudzira yekutyaira musarudzo muiyo nucleus accumbens, 2) inoshandura maitiro ekupfuura nepakati peiyo nucleus inounganidza neuronal ensembles kune "enda" chiratidzo chakapihwa dopamine protx , zvichikonzera mukana wakakura wekunyorwa kwemamwe madhiraivha akadhirowewa, uye / kana 3) inokanganisa mashandiro emagetsi europlastic muiyo nucleus accumbens iyo ingangove ichideredza simba rekurudzira kwekutyaira kunoonekwa sekusina kufanira neyakaitika. Hosha yepamberi cortex basa, zvisinei neiyo chaiyo pathology, inogona kuwedzera mukana wekuita zvisina kukodzera dhiraivha kunoonekwa kiriniki sekumanikidza. Saizvozvo, prefrontal cortex dysfunction inogona kukonzera 1) yekusarudzira inosimbisa kupindura kune yakananga yakavharwa mibayiro yakapihwa neyeprodopamine mhedzisiro yezvinodhaka uye / kana 2) kufambira mberi kusinga tsanangurike kwekuneuroadaptive mhedzisiro yezvinodhaka zvinokonzeresa kukurudzira kwekunzwa (102, 103. Nekudaro, kukanganisika kwakaringana kweye inhibitory kukurudzira masisitimu mukugadzikwa kweiyo yakasimba kukurudzira kukurudzira masisitimu chiitiko kunogona kuwedzera kukurumidza kukurumidza uye njodzi yekunetseka kwekushandiswa kwezvinodhaka. Neurodevelopmental changes panguva yekuyaruka inotungamira kune aya mamiriro anogona kuunza yakawedzera kupindwa muropa.

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Kureba kweMotivational Neurocircuitry Munguva Yekuyaruka

Profound psychophysiological shanduko inoitika panguva yekuyaruka. Vechidiki vanowedzera kuwedzera-kunge vakuru uye sekudzora maitiro104, 105) uye nekuwedzerwa kukurudzirwa nevanhu vakuru kwezvakatipoteredza kukurudzira (106. Muhucheche, kukurudzira kutamba kunosimudzira kudzidza kusiri kwekutanga nezve zviitiko zvevakuru, maitiro anodzikisira kukuvadza migumisiro (43. Mukuyaruka, kurudziro yekutamba inofambira mberi mukutora chikamu mune zvinoitika zvevakuru zvevakuru, pasina mabhenefiti eruzivo rwekuziva ruzivo rwekutungamira kuita sarudzo (107. Kubva pamaonero evakuru, maitiro asina kujairika evachiri kuyaruka anogona kuita sekutadza uye kushushikana (34, 35).

Kukurudzira Kusimudzira Substrates

Kufambira mberi kwekushandurwa kwekutanga kukurudzira kutenderera panguva yekuyaruka kunogona kukurudzira hunhu-kutsvaga hunhu uye nekuwedzera kukurudzira kukurudzira maitiro. Neuropsychiatric kusagadzikana inosanganisira epakati dopamine basa tevedza kukura maitiro inoenderana neiyi pfungwa. Tic kushushikana, kurapwa nekuvharidzira dopamine chiitiko, inonyanya kuitika mukuchechechecheche uye kutanga kwekuyaruka uye inowanzoita kuregererwa mukukura (108. Mukupesana, kuitika kwechirwere cheParkinson, chinosanganisira kushomeka dopamine basa, inowedzera nezera rechikuru (57. Kuti izvi zviongorori zvinoratidza zvadzose kukura kwebudiriro zvinotsigirwa nezvidzidzo zvemhuka zvinoratidza mutsauko peri-yekuyaruka maitiro inosanganisira dopamine system basa (109. Mapere-pwere ari kuyaruka anoratidza yakakwenenzvera maitiro ekuongorora mune inovhurika vheji uye kuita zvakanyanya mumutambo wekutamba kupfuura vadiki nevakuru makonzo (110. Peri-kuyaruka makonzo anoratidza motaic hyporesponsivity kune prodopaminergic vamiririri uye hypersensitivity kune dopamine blockade, zvichidudzira kuti dopamine yavo system inoshanda pane yekutanga padyo neinoshanda ceiling pamberi petekinoroji dambudziko (110. Makonzo epwere-dzechiri kuyaruka anoratidza yakakura saruro yekuda kwenzvimbo nharaunda kupfuura mbeva dzevakuru (111. Pamusoro pekurapwa kweAmphetamine, vanhu vakuru vanoratidza kuwedzera mune zvido zvekuda uye zviitiko zvevechidiki zvichiderera, vachidaro nharaunda yakajairwa yepakutanga neamfetamini kuendesa (111. Peri-achiri kuyaruka makonzo anoratidza akanyanya maitiro ekunzwa uye striatal dopamine kubudiswa mushure mekudzokororwa psychostimulant majekiseni pane vakuru makonzo (112, 113. Pamwe chete, izvi zvakawanikwa zvinoratidza kuti kuyedzwa kwevachiri kuyaruka uye kusagadzikana nemishonga inopinda muropa kunosanganisira kukura kwekusiyana mune dopamine system basa uye kunzwa.

Kusiyana kwemabatiro mune yekukurudzira dopamine masisitimu uye inhibitory 5-HT masystem anogona kubatsira mukuyaruka kuyaruka kutsvaga / impulsivity. CSF kuongororwa kwe dopamine uye 5-HT metabolites inoderera panguva yehucheche uye kuderera kusvika padanho revakuru nezera 16 (114. Nekudaro, chiyero chedopamine metabolite homovanillic acid kune 5-HT metabolite 5-hydroxyindole-acetic acid inowedzera, zvichidaro uwandu hwepamusoro hwe dopamine kune 5-HT Turnover (114. Mune mhungu, huwandu hwe dopamine-inobereka presynaptic magumo mu prefrontal cortex inowedzera kubva kune imwe-hafu yemazero emukuru kune 6 mwedzi yezera kusvika kune yakura mazinga nekunonoka kwekuyaruka (2 makore), apo iyo density ye dopamine axonal yekupinda inenge kanenge katatu. ye5-HT (115. Kusiyana neizvi, 5-HT nzvimbo dzekugadzira pane prefrontal cortex neurons inosvika mazinga evakuru nevhiki yechipiri mushure mekuzvarwa (115. Pamwe chete, izvi zvakawanikwa zvinoratidza kuti kuyaruka kunogona kuratidzwa nebasa rakakura mumabasa ekukurudzira dopamine pane mune inhibitory 5-HT system.

Shanduko yemahormone ekuchinja inokanganisa sekondari kukurudzira kutenderera inogona zvakare kubatsira kukurudzira kushanda kweadopamine masisitimu. DzeBonde steroid receptors mediating zvakakomba neuroplastic mhedzisiro inoratidzwa zvakanyanya mu hippocampus uye hypothalamus (116, 117. Neuroplastic kudzokorora panguva yekuyaruka inogona kushandura maimiriri ezvekukurudzira kukurudzira kukurudzira mune izvi zvimiro, zvichichinja chimiro chechimiro chekufambisa chinomiririrwa mukutanga kukurudzira kutenderera (118, 119. Semuenzaniso, kuwanda kwemahara emahara pabonde kunobatsira kukurudzira kwakanyanya pabonde, kunzwa kune zvishuwo zvepabonde uye zvemagariro, kukwikwidza pabonde, uye kuyaruka.43, 120, 121).

Hippocampal basa inogona kuve yakakosha kune zvepabonde-mahormoni-anoenderana neshanduko muhutsika-yakatarisana maitiro. Nenzira yekubatana kwakadzama necortex, iyo hippocampus inofananidza mamiriro ezvinhu epamba nekumwe ndangariro dzekusvika kuti vaone hunyanzvi hwenzvimbo (122. Ruzivo rwunogonesa runogona kuve rwakavharidzirwa mune zvinofambisa zvinofambiswa nenzira yehippampal kudzora kweaya amplitude kana kukanganiswa kweadopamin discharge mukati meiyo nucleus accumbens kana nekumanikidza kwakananga pane neuronal chiitiko cheiyo nucleus accumbens (51, 123, 124. Pfungwa iyi inowirirana neye anatomical uye yepamoyo data inoratidza kuti hippocampal kukuvadza anogadzirisa kuwanda dopamine kubudiswa muiyo nucleus accumbens uye maitiro ekupindura kune ino nharaunda mamiriro (69. Pamwe chete, idzi data dzinoratidza muchina unogadzirisa mamiriro emahormone mune mamwe matanho ehupenyu (hwehudiki, kuyaruka, kukura) anogona kushandura kukurudzira dopamine masystem ekutenda hunhu hunofambidzana zvakanyanya padanho rekukura.

Inhibitory Kukurudzira Substrates

Shanduko mukusimudzira kukurudzira substrates kunoitika pamwe chete nezviitiko zvebudiriro mu prefrontal cortex. Mukuyaruka, iyo pre-prepostal cortex haisati yawedzera mabasa akasiyana siyana ekuziva ayo anogona kusanganisira simba rayo rekutadzisa zvido. Nhanho dzekutanga kwecortex basa, kusanganisira kushanda mundangariro, kugadzirisa dambudziko rakaoma, kufunga zvisinganzwisisike, uye kwakagadzika kufunga kwakanaka, kunatsiridza zvakanyanya panguva yekuyaruka (104, 105, 125. Kunyangwe kugona kudzora psychomotor mhinduro kuchivandudza kuburikidza neudiki, kukwirira nekukurumidza kusvika kwekuyaruka (126), matanho akananga ekuti achiri kuyaruka abatanidzwe (semuenzaniso, kuita sarudzo) anoramba asina kubatidzwa.

Shanduko muuropi anatomy uye inoshanda zvinoenderana kwenguva kune shanduko yekubata kwekuziva. Munguva yose yekuyaruka, shanduko muEEG matanho ezvekuita cortical chiitiko uye mhinduro kune yekunzwa kwepfungwa dzinoonekwa (104, 127. Kubva pamazera 6 kusvika 12, chiyero che lateral ventricle kune huwandu hwehuropi chinoramba chichienderera; iyo ipapo inowedzera zvishoma nezvishoma kubva pazera 12 kusvika 18 (128. Kubva pamazera 4 kusvika 17, kune inowedzera kuenderera mberi kweiyo chena nyaya density mu frontal cortex, pamwe nekuda kwekuwedzera myelination ye neurons uye axonal diameter uye inobatsira mukuwedzera kwakanyanya kwekuita kunogona kuitika kupararira (129. Shanduko muuropi metabolism inoratidza yakachinja neuroplasticity uye kugadzirisa kweruzivo kunoonekwawo. Pasi rese, uropi hunowedzera mashandisirwo esimba, kuenzanisa huwandu hwevakuru nezera 2, hunowedzera huwandu hwakapetwa kaviri kupfuura huwandu hwevakuru nezera 9, uye kuderera kusvika kumazinga evakuru nekupera kwekuyaruka (130, 131. Kufananidzwa nematunhu akadzika, nzvimbo dzecortical dzinoenda dzakafanana asi dzakanyanya kududzirwa kutendeuka kwemetabolic uye nekuratidza shanduko idzi gare gare, nenzvimbo dzepamberi dzecortical shanduko yekupedzisira (131).

Kukura kwekukura kwekuchinja mune yekutanga cortex inofananidzwa nekushandurwa kwema neuroplastic, sekuratidzwa nedensities of dendritic process, synapses, uye myelination, mitengo yeanestonal membrane synthesis, uye kubuda kwevakuru vanoziva maitiro (129, 132-134. Kuderera mune metabolic chiitiko pamberi uye mamwe cortical kumatunhu anogona kuratidza kutapurirana kutapudza, uko kudzoreredzwa kunoitwa mune inopedza simba neuroni yekubatanidza iyo isinganyatso kuendesa ruzivo zvine chekuita nekuunganidza ruzivo. Mune yepamberi yeportal yemunhu, iyo synaptic density munzvimbo huru dzekugamuchira axonal inowedzera kune 17 × 108 pa mm3 pakati pemazera e1 ne5 uye kuderera kusvika kumazinga evakuru ve11 × 108 pa mm3 nekukurumidza kuyaruka (135. Synaptic kudzvanya mune mhere-pwere dzekuyaruka inoitika muzvikamu zvecortical microarchitecture inoratidza yemimwe mhedzisiro pakugadzirisa ruzivo (134. Kuderedzwa kwepamberi preortal cortex synapses kwakakura kune iwo ema axon anobva munzvimbo dzenzvimbo dzecortical kwete kubva kure kusangano cortices uye anokurudzirwa kuratidza kuwedzera kwakasimba pachivimbiso chemukati epamberi cortex masekete pane akanyanya kufambiswa multimodal ruzivo (125. Ichi chiitiko chinogona kubvumira kumusoro-pasi kugadziriswa, uko kwakakura, kwakawanda kudhirowa repertoire yezvakaitika zvekare yakachengetwa muzvivakwa zviri kure kune hukuru hwekumanikidza (134. Peri-kuyaruka kuyananiswa kutapudza kudonhedza zviri zviviri zvinonakidza uye zvipingaidzo zvinopinza (136. Izvi zvinopesana nekuderedzwa zvinogona kuwedzera kudzikama kwekupfura maitiro e cortical neurons (137) uye nekuvandudza mukana we ensembles of prefrontal cortex neurons pamoto mune yakasimbiswa, concerted fashoni (134, 138), ichifambisa pfupi-yenguva yekuchengetedza yehuwandu hunowedzera ruzivo. Zvinoenderana nepfungwa iyi, kushanda kwakanaka kwekuyeuka kushanda mumakwere ekuyaruka kunoenderana chaizvo nehuwandu hwepamberi cortex neurons inoratidza chiitiko chakasimba panguva yekunonoka kwebasa (139).

Neural network simulation inoratidza kuti kuwedzera kwe cortical kubatana muhucheche kunoteverwa nekuderera kusvika kune vakuru mazera pamusoro pehudiki kunoratidza optimization yekugona kugona, inoenderana nekuderera kwezinga rekushanduka kweiyo neuroplastic (125, 140. Maitiro aya anotsvaga tradoff pakati pekugona kudzidza ruzivo rutsva kupesana neizvozvo kushandisa uye kuwedzera pane ruzivo rwekare rwaidzidziswa (140. Sezvo kuunganidza ruzivo kuchichengeterwa kwakabatana mukati memukati maNeural network, zviyero zvekufunda, kana masimba echiropoto kana sekumiririrwa nenhamba yekubatana kweiyo synaptic, inofanira kuderera, zvichikonzera hurongwa hunoshanda kudzivirira kurasikirwa kweruzivo rwekare rwaidzidziswa (140. Synaptic pruning uye dzimwe nzira dzekuvandudza mu prefrontal cortex, inowirirana neyekukurudzira kukurukuri kune zvezvinoitika zvevakuru zviitiko, zvinogona kushanda pamwe chete kuti zvigone kutorwa kwekuyaruka kwekuziva kwekuwedzera uye kwekunzwisisa kwezvakatipoteredza. Kugadziriswa kwekombiki yepamberi yekutanga saka kunoitwa nekukurudzira kunotora mukana mune zvinoitika zvekare zvevakuru zviitiko, pakupedzisira zvichizotungamira kuchirongwa-chakasimbiswa chinotungamira kuitiswa kwe “kwakakodzera” sarudzo yekuita.

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mhedziso

Adolescent neurodevelopment inosanganisira shanduko muhurongwa hwehuropi uye inoshanda nehukuru hwakanyanya hwekukurudzira kukurudzira kukurudzira substrates mukugadzwa kweyemukati inhibitory substrates. Kukurudzira kukuru kwekufambisa kwezvinoitika zviitiko, pamwe chete neyakaremara yekudzivirira system, inogona kufungidzira kuita kwezvekuita zviito zvisina hunhu uye maitiro ane njodzi, kusanganisira kuyedza uye kushandisa zvisizvo zvinodhaka zvinodhaka. Saizvozvo, chirwere chepfungwa chinowanzoitika comorbid nekushomeka kwekushandiswa kwezvinodhaka kazhinji chinosanganisira kusimbisa dyscontrol putatively inoratidza kusakwana kusakwana inhibitory uye / kana hyperactive kukurudzira maitiro eanokurudzira neurocircuitry. Mukuyaruka zvakajairika kuyaruka, kukurudzira kwemukati memutsindo kunopinda muchikamu chakafanana nemamiriro ezvinhu aya. Direct pharmacological-inosimudzira mhedzisiro yezvinodhaka zvinodhaka pane dopamine masystem anogona kukurumidza panguva idzi dzekuvandudza, kuwedzera shambadziro kana kusingaperi kwekushanduka kweiyo neural kupindwa muropa.

Chinhu chikuru chinoreva modhi iyi ndechekuti kusagadziriswa kwekushandiswa kwezvinhu zvinoumba mitsipa. Saka nekudaro, kutsvaga nekurapa kwakanangana nevachiri kuyaruka uye vakuru vechidiki zvinogona kubatsira mazera ese ezvikanganiso zvekushandiswa kwezvinodhaka. Uyezve hunhu hwezvimwe zvikamu zveyakakurudzira neurocircuitry iri kuitika kuyaruka neurodevelopment (inosanganisira subcortical dopamine uye prefrontal cortex uye zvimwe zvakabatana zvidimbu) zvinogona kuburitsa nzira dzakasarudzika dzakanangana nehukama kana chirwere chepfungwa-chirwere chinopesana mukusagadzikana kwekusagadzikana kwekushandiswa kwezvinodhaka. Mhedzisiro yemiitiro muvana uye yevachiri psychopharmacology pakuvandudzwa kweiyo activational neurocircuitry uye njodzi yekushomeka kwezvinodhaka zvinosemesa. Idzo data diki iripo, neruzivo ruzhinji rwunobva pamishumo yekushandiswa kwe psychostimulants yekutarisira kushomeka hyperactivity kusagadzikana. Zviwanikwa zvinoratidzira zvinodzivirira pamatambudziko ekushandiswa kwezvinodhaka mune mamwe mapoka ekuongorora kana magroups uye zvingangodaro zvisipo kana zvinokuvadza mune vamwe (141-144).

Kuwedzera kuongorora kunodiwa kuti uedze nzira dzakatsanangurwa uye zvinorehwa nemhando iyi. Hufakazi hwehukama pakati pekufungidzira uye njodzi yekushomeka kwekushandiswa kwezvinodhaka pamakiriniki, kusanganisira kuyaruka uye / kana chirwere chepfungwa, chakasimba asi chakanyanya kuwirirana. Yakabatanidzwa kutsvagiridzwa nemhando dzakasiyana nzira dzinodiwa kuti uongorore zvakananga hwakanangidzirwa causal hukama. Mhuka mhuka dzekumanikidza uye kupindwa muropa nemaitiro mukuzvibata-mbichana dzinofanirwa kuongororwa mukati mezvidzidzo nezvose zviri zviviri nzira-yekureba uye nzira refu. Genetic, molekhi, neurochemical, uye neurophysiological nzira dzinofanirwa kuisirwa kune aya manyoro kuti awone zvinowanzoitika uye zvakasiyana zvezvinhu zvinokurudzira kufambiswa kwemukati kwekutenderera kune zvese kukurudzirwa uye kupindwa muropa. Neurocomputational simulations yeiyo yekutanga activational circry, inosanganisira yakawanda mitsara yedheti data, inogona kudikanwa kuti iongorore zviitiko pane neural system level isina kudzidziswa zviri nyore mukusafungisisa kwehupenyu hwekuzvarwa.

Tichifunga nezve huripo hwepfungwa dzehuropi maitiro ayo anowanzoburitsa kukurumidza uye njodzi yekushomeka kwekushandiswa kwezvinodhaka muzvirwere zvepfungwa zvinowanzowanzoonekwa muhudiki, zvinoramba zvichitsanangurwa kusvika papi mukana wekusvika panguva yekuyaruka kwekushomeka kwezvinodhaka 1) inoratidza kuratidzwa kwekutanga kwemunhu mukuru psychiatric syndromes iyo inopa yakakura njodzi yekushandiswa kwezvinodhaka kusagadzikana uye / kana 2) inomiririra njodzi yakakura kune vese vechidiki vari kuyaruka. Zvimwe zvese sarudzo dzinoitika, dzichigadzira kushomeka kukuru kwekushomeka kwekushomeka kwezvinodhaka mune vese vachiri kuyaruka asi kusvika padanho rakakura mune yepfungwa dzakakanganiswa nevechidiki. Dudziro yakadaro yaizoenderana nekuvapo kwehumwe humwe humwe humusikirwo hwenzvimbo uye nharaunda yekuchengetedza uye zvinhu zvinodzivirira zvichishanda pamwe nekushanduka kwenzvimbo kusimudzira shanduko yebasa rehuropi kuti iwane imwe nhanho yekunetseka kupindwa muropa. Mukuongorora mipiro yakaringana yeiyi mikana, mhuka yekuenzanisira yekushomeka kwezvinodhaka zvekushandisa muzvidzidzo panguva dzakasiyana dzekusimudzira, nedzimwe nzira dzekutarisira zvinodhaka peri-pwere, zvichave zvakakosha, kusanganisira kushandiswa kwemukati-zvidzidzo zvemhuka zvechirwere chepfungwa uye chinhu. shandisa matambudziko. Longitudinal kliniki zvidzidzo, kunyanya izvo zvinoshandisa chinangwa matanho ekushungurudza uye kuita sarudzo uye nekushandisa genetic uye inoshanda neuroimaging matekinoroji, zvichave zvakakosha mukunzwisisa kupindwa muropa kwemahure emapoka ezera mune hutano uye chirwere chepfungwa chinorwara31. Kuzivikanwa kwevachiri kuyaruka vechidiki vane hurema hwekushomeka kwekushandiswa kwezvinodhaka, kuvandudzwa kwemaitiro-ekudzivirira maitiro, pamwe nekuvandudzwa kwekurapa nemishonga yepfungwa ndezve nzvimbo dzakakosha kutevedzera kuitira kudzikisa kukanganisika kukuru kwekunetseka kwezvinodhaka zvinoshandiswa munharaunda.

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Kutenda

Inotsigirwa neVeterans Administration Special Neuroscience Research Fsoci Grant uye rubatsiro kubva kuNational Alliance yeIkutsvagisa nezve Schizophrenia uye Kushungurudzika (Mudiki Muongorori Award), National Institute on Drug Abuse (DA-11717, DA-00167), iyo American Psychiatric Association (DA -00366), uye iyo National Center Yekuremekedza Mutambo.

Vanyori vanotenda George Heninger nekutaura pamanyoro.

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