Ukuqulunqa ama-Compulsive and Impulsive Behaviors, ukusuka kwiZimodeli zezilwanyana ukuya kwi-Endophenotypes: UkuHlola okuHlanganisiweyo (2010)

Iimpendulo: Yenza umahluko ocacileyo phakathi kokuziphatha okunyanzelekileyo njenge-OCD, kunye nokuziphatha okunganyanzelekanga okunjalo ukuba likhoboka lokungcakaza. Abantu abaphembelela ekuziphatheni okubi ngokwesini bahlala besithi abo baneziyobisi ezingamanyala banokuziphatha okunyanzelekileyo, kunokuba babe likhoboka. Oku kuyaphikisa ibango lesimanga.

Neuropsychopharmacology. I-2010 ngoFebruwari; 35(3): 591-604.

Ipapashwe kwi-intanethi ye-2009 ngo-Novemba 25. ikhonkco: 10.1038 / npp.2009.185

PMCID: PMC3055606

UNahomi nguFineberg,^1,^2,^3,^* UMarc N Potenza,⁴ USamuel R Chamberlain,^1,³ UHeather A Berlin,⁵ Lara Menzies,³ UAntoine Bechara,⁶ UBarbara J Sahakian,³ UTrevor W Robbins,⁷ U-Edward T Bullmore,^3,⁸ kwaye Eric Hollander⁹

Ulwazi loMbhali ► Amanqaku wenqaku ► Ulwazi lobunikazi kunye neLayisenisi ►

Eli nqaku liye khankanywe ngu amanye amanqaku kwi-PMC.

Abstract

Ukungaphumeleli kulawulo lwe-cortical ye-cyland-striatal neural circuits inokuthi iqhubele phambili ngokunyanzela kunye nezenzo ezinyanzelekileyo. Kolu phononongo lwengxelo, sivavanya ezi ndlela zokuziphatha ngokwembono yenkqubo ye-neural kwaye siqwalasele indlela ezi ndlela zokuziphatha kunye ne-neural process ezinegalelo ngayo kukuphazamiseka kwengqondo njengokujonga okungafunekiyo (i-OCD), ukuphazamiseka okunyanzelekileyo kubuntu, kunye nokuphazamiseka kokulawula okunje trichotillomania kunye ne-pathological ukugembula. Sibonisa iziphumo ezivela kuluhlu olubanzi lwedatha, equka ukuguqulelwa kunye nophando lwe-endophenotypes yovavanyo kunye nonyango lwezonyango, kugxilwe kwicala elingqinelanayo, ekwahlukanisiweyo, i-cortico-striatal neural projektions, ukusuka kwi-orbitof Pambal cortex (OFC) ukuya kwidiary striatum (i-caudate nucleus), ecetywayo ukuqhuba imisebenzi enyanzelekileyo, nokusuka kwi-cortate engaphandle / kwi-cortex ye-anterior ukuya kwi-ventral striatum (i-nucleus accumbens igobolondo), icetywayo ukuqhuba imisebenzi engxamisekileyo, kunye nokusebenzisana phakathi kwabo. W

Siphakamisa ukuba ukunyanzelwa nokunyanzeliswa nganye ibonakala ngathi inezinto ezininzi. Ukuziphatha okunganyanzelekanga okanye okunyanzelekileyo kuyacazululwa ngokugqagqana nangamaqelana e-neural ahlukileyo. TI-richotillomania inokuma ngandlel 'ithile njengoluphazamiso lolawulo lweemoto, ngelixa ukungcakaza kubandakanya ukungahambi ngendlela emiselweyo. I-OCD ibonakalisa ukunyanzeliswa kweemoto kunye nokunyanzelwa, mhlawumbi okunokuthanani nokuphazamiseka kwe-OFC-caudate ejikelezayo, kunye nolunye umphambili, i-cingulate kunye nokunxibelelana kweparietali. I-Serotonin kunye ne-dopamine zinxibelelana kuyo yonke imijikelezo ukulungisa imiba yokuphendula kunye nokunyanzela ukuphendula kwaye iinkqubo ezingekaziwa zobuchopho ezisekho zinokuba nayo imisebenzi ebalulekileyo. Ukusetyenziswa ekujoliswe kuko kwemisebenzi ye-neurocognitive, i-receptor -pecial neurochemical probes, kunye neesistim zobuchopho ze-neuroimaging technology zinokubakho kuphando lwexesha elizayo kulo mhlaba.

Internet: ukunyanzelwa, ukunyanzelwa, i-endophenotypes, i-serotonin, i-dopamine

INTSHAYELELO

Ngelixa izinto ezenziwa ngokunyanzelwa okanye ngokunyanzelwa zinokuba negalelo ngokukodwa kubuchule bokunyamezela kunye nonyamezelo kwaye ngokubanzi kulungelelwaniso lokuziphatha kwabantu, umgaqo ophazamisekileyo wokuziphatha okunganyanzelekanga okanye okunyanzelekileyo kunokunxulunyaniswa neziphumo ezibi kwaye ube nomsebenzi kuphuhliso lokuphazamiseka kwengqondo. Ukunyanzeliswa kunokuchazwa 'njengendawo ekubhekiswa kuyo ngokukhawuleza, ekuphenduleni okungalindelekanga kwisikhuthazo sangaphakathi okanye sangaphandle ngokubhekisele kwiziphumo ezibi zokuphendula komntu ongxamisekileyo okanye kwabanye' (I-Chamberlain kunye neSahakian, 2007; Umkhuhlane, i-2007b). Ngokwahlukileyo, ukunyanzelwa kukubonakalisa umkhwa wokwenza ngendlela engathandabuzekiyo ngendlela eqhelekileyo okanye ethandabuzekayo ukunqanda iziphumo ezibi ezibonakalayo, ezikhokelela kukhubazeko olusebenzayo (Ngubani, 1992; IHollander kunye noCohen, 1996; Chamberlain okqhubekayo, 2006b). Ezi zinto zimbini zinokujongwa njengezichasayo ngokwasemzimbeni, okanye kungenjalo, ngokufanayo, kwinto nganye ethi ukungasebenzi kakuhle kwembambanool (UStein kunye noHollander, 1995). Isizathu ngasinye sinokubandakanya ukutshintsha kuluhlu olubanzi lweenkqubo ze-neural, kubandakanya ingqalelo, ukuqonda, nokulungelelanisa iimpendulo zemoto okanye zokuqonda.

Iimodeli ze-Neuroanatomical zibonakalisa ubukho beesekethe ezi-cortico-striatal ezahlukileyo kodwa zonxibelelwano '' kunye 'nokuxhokonxwa', ngokwahlukileyo kwimodareyitha yi-neurotransmitters (Robbins, 2007; Brewer kunye nePotenza, i-2008). Kwisekethe enyanzelekileyo, icandelo le-striatal (i-caudate nucleus) inokuqhuba isimilo esinyanzelekileyo kunye necandelo langaphambili (i-orbitof mbeleal cortex, OFC) inokubonelela ngolawulo lwe-inhibitory phezu kwabo. Ngokufanayo, kwisekethe enganyanzelekanga, icandelo le-striatal (icandelo le-ventral striatum / i-nucleus accumbens shell) linokuqhuba isimilo esingxamisekileyo kunye necandelo langaphambili (i-anterior cingulate / i-ventromedial preortal cortex, VMPFC) inokunika ulawulo lwe-inhibitory.

Ke ngoko, kule modeli, kukho iisetyhula ezimbini ezinqabileyo zangaphakathi (eyodwa enyanzeliswayo kunye nenye enyanzeliswayo) eziqhuba ezi ndlela ziziphatha ngayo, kunye nezijikelezi zangaphambili ezihambelanayo ezinqanda ezi ndlela zokuziphatha. Umsebenzi woxinzelelo lwengqondo ngaphakathi kwezahlulo zesisu okanye ubuchwephesha (kucingela ukuba ne-hypoactivity) kwizinto eziphambili zangaphambili kungakhokelela kukonyuka kokuzenzekelayo kokuziphatha okungafunekiyo okanye okunyanzelekileyo, kuxhomekeke kwicandelo elicinezelweyo. Olunye uxhaphazo olunokwenzeka ngaphakathi kwimijikelezo ye-cortico-striatal (umz. Enxulumene nokunciphisa ukusebenza kwe-striatal ukuya kwimivuzo) inokuba negalelo ekubonakaleni ngokungahambi okanye ekuziphatheni okunyanzelekileyo ngexesha lokuzibandakanya kwihambo ezinxulumene nomvuzo. Ezi pilisi zinokuphononongwa kusetyenziswa imisebenzi yokusebenza kwengqondo ecofwa kule misebenzi ethile kunye / okanye ngezifundo ezisebenzayo zokulinganisa umsebenzi ngaphakathi kwezi nkqubo ze-neural. Ubuninzi phakathi kwezi nkqubo zisebenzayo, ukuze oko kuqalisa njengengxaki kwisekethe enganyanzelekanga kunokuphela njengengxaki kwisekethe enyanzelekileyo kwaye ngokuchaseneyo, kunganegalelo kwimodeli enganyanzelekanga-enyanzelekileyo yokuphambuka ecetyiweyo IHollander kunye neWong (1995) (Brewer kunye nePotenza, i-2008).

Kukho ukuphazamiseka kwengqondo okuthile apho iindlela zokuziphatha ezinganyanzelekanga kunye nezinyanzelekileyo zibonakala, ubuncinci kwizizathu ze-phenotypic, ukuba zezona zinto ziphambili nezona zonakalisayo. Ezi ngxaki zihlala zikhona, ezihlelwe ngokuhlelwa kwiindidi ze-DSM-IV-TR (APA), zibandakanya ukungaboni kakuhle-okunyanzelekileyo (OCD), ukuphazamiseka komzimba, isifo seTourette, trichotillomania, ukungahambi kakuhle kwengqondo (ADHD), ukungcakaza kwezifo, kunye neziyobisi (SAs). Umdla, i-autism ibonakaliswa kukuziphatha okunyanzelekileyo (njengenye yeendawo ezintathu eziphambili zeempawu) kunye nokuziphatha okungxamisekileyo (njengenye yeendawo ezinxulumene neempawu).

Ngokwesiko, ukuphazamiseka okunyanzelekileyo nokungxamisekileyo kujongiwe kwiziphelo ezihambelana nomlinganiso omnye; eyangaphambili eqhutywa ngumnqweno wokuphepha ukwenzakala kwaye eyokugqibela kukuziphatha okufuna umvuzo. Nangona kunjalo, ubungqina obuguqulweyo obuvela kwizifundo zoguqulo lubonisa ukuba utyekelo ekwabelwana ngalo malunga nokuziphatha kwe-disinhibition, ekucingelwa ukuba kubangelwa kukusilela kulawulo oluphezulu lwe-cortical ye-fronto-striatal circuits, okanye kungenjalo ukusuka ekusebenzeni kakhulu ngaphakathi kwisekethe ye-striatal, inokubangela ngokubonakalayo ukuphazamiseka okungxamisekileyo kunye nokunyanzeliswa . Ke ngoko, endaweni yokuchasana ne-polar, ukunyanzelwa kunye nokunyanzeliswa kunokubonisa izinto eziphambili ze-orthogonal ezinokuthi nganye inegalelo kumanqanaba ahlukeneyo kwezi ngxaki.

Uninzi lwezi ziphazamiso zidla ngokwenzeka kunye, nokuba kukokwangumntu omnye okanye ukuqubisana kwiintsapho, kuthetha ukuba kunokwenzeka iindlela zakwabelana (zengqondo)Hollander okqhubekayo, 2007b). Ngapha koko, bukhona ubungqina bokunqamka kwimpendulo-yokuphendula kunyango oluthile. Ngokuqhelekileyo i-OCD iphendula kwi-serotonin reuptake inhibitors (ii-SRIs; i-clomipramine kunye ne-SRIs ezikhethiweyo, ii-SSRIs) kunye nee-SSRIs ezidityaniswe neearhente ze-antipsychotic (Fineberg okqhubekayo, 2005). I-Antipsychotic imele unyango lonyango lokuqala lwe-Tourette's syndrome, kwaye ke, kuyathakazelisa ukuba ukudityaniswa kwazo nee-SSRI kubonisa ukusebenza okukhulu kwi-OCD enxulumene ne-tic (Bloch okqhubekayo, 2006). Ukunyanzelwa okunxulunyaniswa nokuphazamiseka kwe-autistic nako kusenokuphendula kwi-SSRI yedosi esezantsi kunye nakwi-antipsychotic (Kolevzon okqhubekayo, 2006). I-Trichotillomania inokuthi iphendule kwii-SRIs nakwii-antipsychotic, nangona kunjalo, kufuneka isiqinisekiso kwizifundo ezilawulwayo (Chamberlain okqhubekayo, 2007d). I-ADHD, kwelinye icala, iphendula kwii-inaditors ze-noradrenergic reuptake inhibitors kunye ne-dopaminergic agents (umz. Amphetamine), ukugembula kwe-pathological, kunye nokuphazamiseka kweziyobisi kunokukwabelana ngempendulo yonyango kubachasene ne-opiate antagonists (Brewer okqhubekayo, 2008).

Ukuchaphazeleka kwesizathu kunye nefuthe, kusetyenziswa idatha yeklinikhi yodwa, inokubhideka ngenxa yobuninzi beempawu ezinxulumene noko ezenzeka ngaphakathi kokuphazamiseka kwengqondo. Ewe, eli qela lokuphazamiseka liphawulwa ngokungafaniyo kwe-phenotypic heterogeneity kunye nokugqagqana. Umzekelo, ezinye iimeko ze-autism azibonisi zimpawu ze-ADHD okanye indlela yokuziphatha enyanzelekileyo, ezinye zibonisa i-ADHD, ezinye i-OCD, kwaye ezinye zibonisa iindlela zokuziphatha eziphindaphindayo ezingafaniyo ne-OCD. Uphando olwenziweyo luphanda ngokwembono yeendlela ezisisiseko, kwaye ngenxa yoko lunakho ukukhomba igalelo le-neural lokuqhuba imiba ethile yokuphazamiseka kwengqondo. Ii-Endophenotypes zinokulinganiswa, iimpawu ezinokuzuzwa, ezibekwe kwindawo ephakathi phakathi kwe-phenotype yeklinikhi kunye nesifo esinokubakho kwisifo. Ezi 'phenotypes ziphakathi' zithathwa njengezihambelana ngokuthe ngqo nomngcipheko wemfuza wokuphazamiseka kwengqondo kunesifo se-polygenic kunendlela yokuziphatha echazwe ekliniki (IGottesman kunye noGould, 2003; IChamberlain kunye neMenzies, 2009). Iimodeli zesifo i-Endophenotypic zesifo zinokuba luncedo ekucaciseni ukuqonda kwethu isiseko sofuzo sokuphazamiseka kwengqondo okuntsonkothileyo kwaye ke ngokwazisa ngokwahlulwa kolusu. Okwangoku, ukuphazamiseka okunyanzelekileyo nokunyanzelekileyo kudweliswa ngaphakathi kweendidi zeDSM-IV. Njengoko umbutho wezonyango lwezengqondo eMelika uthatha ingqalelo yokuhlelwa ngokutsha kwe-OCD, ukuphazamiseka koxinzelelo kunye nokuphazamiseka kolawulo lwempembelelo (ii-ICD) kuhlaziyo lweDSM-V oluzayo (Fineberg okqhubekayo, 2007a), lixesha elifanelekileyo lokujonga kwakhona iindlela zokwenza ezi ngxaki.

Kolu phononongo lwengxelo, sijonga iindlela ze-neural kunye ne-neuropsychological ehambelana nezenzo zokunyanzelisa kunye nokunyanzelisa kunye negalelo labo kwimizekelo yokuphazamiseka okunganyanzelekanga kunye nokunyanzeliswa. Siqokelela iziphumo ezifunyenweyo kuluhlu olubanzi lweenkcukacha ezihlanganisiweyo, ezibandakanya kupapasho olusandula ukushicilelwa kunye nophando olungekashicilelwa, uphando lomntu, kunye nolingo kunyango, kubandakanya umsebenzi oqhubekayo ovela kwiiyunithi zethu e-United Kingdom naseMelika. Uhlalutyo lwethu lugxile ekufuneni ukulingana, ukusebenza okwahlulahlulwayo, ukuqikelelwa kwe-cortico-striatal neural eqikelelweyo evela kwi-OFC ukuya kwi-medial striatum (i-caudate nucleus), ecetywayo ukuqhuba umsebenzi wokunyanzeliswa, kunye nokusuka kwi-anterior cingulate / VMPFC ukuya kwi-ventral striatum (i-nucleus accumbens igobolondo), kucetywayo Ukuqhuba ngokuqhubekeka, kunye nentetho-enqamlezayo phakathi kwabo (Robbins, 2007; Brewer kunye nePotenza, i-2008) (Umzobo 1).

Ukunyanzeliswa kunye nokuxhonywa: Iinkqubo ze-neural zonyulo ezifaka isandla kwiingxaki zengqondo. Nangona ukuphazamiseka okunyanzelekileyo nokunyanzelekileyo kunokujongwa njengokuchasene nepolar, ukusilela kolawulo lwe-cortical striatal neural ejikelezayo kungalandela bobabini ...

Sisebenzisa le datha, sizama ukujongana nemibuzo ephambili kubandakanya: (i) kungakanani ukunyanzeliswa nokunyanzelwa kufaka igalelo kwezi ngxaki, (ii) baxhomekeke kangakanani kubume bezinto ezihlangeneyo okanye ezihluke ngokupheleleyo kwi-neural, (iii) zithini ezo meko zingumnqakathi Iindlela, (iv) Ngaba izinto zendlela ezinganyanzelekanga okanye ezinyanzelekileyo zokuziphatha zinalo naliphi na inani lenkqubela-phambili ezinxulumene nonyango lwezonyango, kwaye (v) kukho imodeli yokudibanisa-umda eyamkela ngokupheleleyo le datha? Sikwatsalela ingqalelo kwithemba lophando lwexesha elizayo esikholelwa ukuba lungaqhubekisela phambili intsimi.

IIModeli ZOKUGQIBELA ZOKUGCINWA NOKUPHAKATHI

Uvavanyo lwenjongo ye-neurocognitive lubambe amandla okucacisa iindlela iiarhente zekhemesti ezikhupha iziphumo zazo eziyinzuzo zekliniki kunye nokuqikelela iziphumo zeklinikhi (Chamberlain okqhubekayo, 2007e; Brewer kunye nePotenza, i-2008). Sebenzisa imisebenzi ebuthathaka kunye ne-domain ehambelana ngqo ne-neurocognitive, ukuthathwa ngokunyanzeliswa kunye nokunyanzelwa kungafakwa kumacandelo ahlukeneyo kunye nokucaciswa kwe-neurobiologic ekhethekileyo emntwini kunye nezilwanyana ezinokuvavanywa, kunye nezinto ezithile ezibandakanya ukungahambelani kwezinto ze-fronto-striatal circry (Winstanley okqhubekayo, 2006).

Idatha ibonisa ukuba ukunyanzeliswa kunokuvela kwinkqubo enye okanye ezingafaniyo ze-neurocognitive. Oku kubandakanya utyekelo lokwenza izinto ngaphambi kokunamandla e-motor disinhibition, elilinganiswa lixesha lokumisa ixesha lokuphendula (i-SSRT) umsebenzi (I-Aron kunye nePoldrack, 2005), ilamli phakathi kwabantu ngokuvula ukusebenza kwe-cortex ye-inferior ephantsi (RIF) kunye nokudityaniswa kwe-subcortical (Rubia okqhubekayo, 2003) kwaye iguqulwe kwiigundane kunye nabantu nge-norepinephrine (Chamberlain okqhubekayo, 2006c, 2007a; Cottrell okqhubekayo, 2008), kodwa hayi i-serotonin (Clark okqhubekayo, 2005; Chamberlain okqhubekayo, 2006d). Enye inkalo ibandakanya ubunzima bokulibazisa ukuzonwabisa kunye nokukhetha imivuzo emincinci ngokukhawuleza ngaphandle kwemiphumo emibi yexesha elide, ukulinganiswa ngokwenza izigqibo okanye imisebenzi yokungcakaza efana neCambridge Ginji Task (CANTAB), enqamlezwe ngokujikeleza kwendlela kunye nokujikeleza okunxulumene ne-cortical phantsi kotshintsho olunokwenzeka lwe-serotonergic (Rogers okqhubekayo, 1999b), kunye nokujikeleza kwe-subcortical under dopaminergic edibeneyo kunye nolawulo lwe-serotonergic (Winstanley okqhubekayo, 2006). Icandelo lesithathu liqukethe iisampulu zolwazi ezingonelanga ngaphambi kokwenza ukhetho, olulinganiswa ngemisebenzi yesampulu yolwazi efana ne-Reflection Task (Clark okqhubekayo, 2006) kwaye kunokwenzeka i5-Choice seri Reaction Time Task (5-CSRTT) (Robbins, 2002) (1 Table).

Ukwahlula amandla okunyanzeliswa kunye nokunyanzeliswa ngokweSizinda se-Neurocognitive: Imisebenzi kunye ne-Neural / Neurochemical Correlates

Ukunyanzelwa, mhlawumbi, akuqondwa kakuhle. Ukungaphumeleli (i) kokufunda ngokubuyela umva (okt amandla okutshintsha indlela yokuziphatha emva kwengxelo engentle, ukulinganiswa kwemisebenzi yokufunda egudileyo) kunye (ii) nokutshintsha kokujonga okuguqukayo, umntu ngamnye unokuba negalelo ekuvezeni kwakhe (Iintsuku okqhubekayo, 1996; Clarke okqhubekayo, 2005). Zombini iintsilelo zibonisa amanyathelo okuqonda okungaguquki, kodwa nganye ibonakala ixhaswe kukujikeleza okungafaniyo kwe-neural.

Ukubuyela umva kufundwe kukhubazeka zizilonda kwi-OFC (kodwa ingeyiyo eyokuqala ngaphambili, ye-DLPFC) kwiintlobo zonke (Iintsuku okqhubekayo, 1996; Berlin okqhubekayo, 2004; I-Hornak okqhubekayo, 2004; Boulougouris okqhubekayo, 2007). Ebantwini, i-OFC isebenze ngokukhetha xa kufundelwa umva (IHampshire kunye no-Owen, 2006). Ngokwahlukileyo, izilonda kwi-CCC yecala ephazamisayo iseti yokutshintsha kwe-primates (Iintsuku okqhubekayo, 1996), nakubantu ukusebenza komsebenzi kudityaniswa nokukhetha ukusebenza kwecortexal cortex yangaphambili yamazwe amabini ((VLPFC) (IHampshire kunye no-Owen, 2006) (1 Table).

Kukho ubungqina obuqhakamshelayo obudibanisa ukubuyela umva kufundiso kunye neendlela ze5-HT, kubandakanywa neentonga (Masaki okqhubekayo, 2006; Boulougouris okqhubekayo, 2008; I-Lapiz-Bluhm okqhubekayo, 2009), iziqu-ezingezizo ezomntuClarke okqhubekayo, 2004, 2005; Walker okqhubekayo, 2009), kunye nabantu (ipaka okqhubekayo, 1994; Rogers okqhubekayo, 1999a; Evers okqhubekayo, 2005) ngokusekwe kumachiza esayeza, nasekhempilini nakwindlela yokutya, kunye nobungqina bokuzala kwemfuza kwiinkawu ze-rhesus (Izquierdo okqhubekayo, 2007). Ngokubanzi, ukunciphisa i-serotonin yobuchopho, ngakumbi kwimimandla ethile efana ne-OFC (umz Clarke okqhubekayo, 2004), ukuphazamisa ukufunda okuphindaphindiweyo. Inkqubo yolawulo ye-5-HT-2A ye-antepton antagonist ikwabonakalisile ukuphazamisa ukubuyela umva komhlaba (Boulougouris okqhubekayo, 2008). Umchasi we-receptor we-5-HT6 ukwabonisile ukuphucula ukubuyela umva kokufunda kunye nokutshintshwa kwengqondo kwiigundane (Umdlali okqhubekayo, 2005). Nangona kunjalo, kuye kwakho ukusilela ukufumana iziphumo zokufunda ukubuyela umva, rhoqo emva kokudodobala kwe-tryptophan, ebantwiniTalbot okqhubekayo, 2006) kunye neegundane (van der Plasse kunye ne-Feenstra, 2008), kunye nokusilela kokuhambisa i-serotonin kumagundane kubonakala ngathi akuchaphazeli ukubuyela umva kwesithuba (IHomberg okqhubekayo, 2007).

I-5-HT2 RECEPTOR SUBTYPES IYAVELA NGOKUGQIBELA

Ukuphindaphindwa kwee-receptors ze-5-HT sele zichongelwe iigrands ezithile eziphantsi kophuhliso. Ubungqina bokuqala kwizilwanyana kunye nezifundo zabantu zicebisa umsebenzi we-5-HT2 receptors kwihambo ezinyanzelekileyo. Iimpuku zeTransgenic ezingekhoyo i-5-HT2C receptors ziphuhlisa iindlela zokuziphatha ezinyanzelekileyo ezenza imodeli ebonakalayo ye-OCD (I-Chou eluhlaza okqhubekayo, 2003). Nangona kunjalo, kukho ukungahambelani okubonakalayo kwedatha efunyenwe kolu lungiselelo lwemfuzo nenye idatha, mhlawumbi ngenxa yokungaxelwanga kweenkqubo zokunyanzeliswa kolungiselelo lwe-transgenic, njengoko idatha yamachiza yakutshanje ichaza ukufumanisa okuchaseneyo ukuba i-5-HT2C i-activation activept inxulunyaniswa nokunyanzelwa okunyanzelekileyo. Ke ngoko, kwimodeli ye-T-maze enye yemodeli yokutshintsha ye-OCD, I-Tsaltas okqhubekayo (2005) ifumene ukuba ulawulo lwe-m-chlorophenylpiperazine (mCPP), i-agonist exubeneyo ye-serotonin eneziphumo ezinamandla ze-5-HT2C agonist. yanda ukunyanzeliswa okanye ukunyanzelwa kokuphendula, ngelixa ukuxoka okungapheliyo nge-SSRI (fluoxetine), kodwa ingeyiyo i-benzodiazepine okanye i-desipramine, iyitshitshisile imiphumo ye-mCPP. Umceli mngeni nge-5-HT1B i-receptor agonist naratriptan yayingenampembelelo yokunyanzeliswa ngaphakathi kwale modeli, iphakamisa umsebenzi othile kwi-5-HT2C receptor, enokuthi ilawulwe phantsi yonyango olungapheliyo lwe-SSRI. Kwizigulana ze-OCD, ucelomngeni olukhulu lwe-pharmacological kunye ne-mCPP exacerbated OCD daliliHollander okqhubekayo, 1991b). Esi siphumo sakwamkelwa ngokuba lilize nge-fluoxetine (Hollander okqhubekayo, 1991a) kunye ne-Clomipramine (Zohar okqhubekayo, 1988). Ngapha koko, iyahambelana nezi ziphumo, Boulougouris okqhubekayo (2008) ifumanise ukuba i-5-HT2C i-receptor antagonist iphuculwe ukubuyela umva kokufunda. Kwelinye icala, ukwenziwa kwe-receptors ye-5-HT2A yangaphambili icetywayo ukuba iphakamise iziphumo ezichasayo ze-SSRIs (I-Westenberg okqhubekayo, 2007). Isibini sesibini se-antipsychotic sinokunyanzelisa isimilo esisinyanzelo kwizigulana ezine-schizophrenia, kwaye kuye kwacetywa ukuba oku kwenzeka ngenxa ye-5-HT2A ye-antagonismIPoyurovsky okqhubekayo, 2008), nangona i-dopamine (DA) i-receptor antagonism imele enye indlela enokwenzeka. Ngaphaya koko, ii-antipsychotic zesibini nezesibini zokuqala zibonisa ukusebenza kakuhle kweklinikhi xa kudityaniswa nee-SSRIs kwi-OCD (IFineberg kunye neGale, 2005), mhlawumbi ngokwandisa umsebenzi we-DA ngaphakathi kwe-cortex yangaphambili (Iitayile okqhubekayo, 2004).

UKUHLAZIYWA KOMGANGATHO WOKUZIPHATHA NOKUGQIBELA IIMPAWU ZOKUFUNDA

Kwimodeli yezilwanyana, ukwahlula okunomdla phakathi kweempembelelo ze-5-HT2A kunye ne-5-HT2C receptor ezichasayo malunga neendlela zokunyanzeliswa kunye nokunyanzelwa sele kuqaphelekile. Kwi-5-CSRTT, ulawulo lwenkqubo ye-5-HT2C ye-receptor antagonist (SB24284) ikhuphule ngakumbi ukubethelelwa okuxhaphakileyo okujongwa emva kokuphelelwa ngamandla kwe-5-HT ye-intracerebroventricular ye-5,7-dihydroxytrypt; ukuphuculwa okufanayo okunxulumene ne-SB24284 ekunyanzeliseni kwabonwa kwiirandi ezisebenza sham (Winstanley okqhubekayo, 2004). Ngokwahlukileyo, ulawulo lwenkqubo ye-5-HT2A ekhethiweyo ye-receptor antagonist (i-M100907) yayinezenzo ezichaseneyo, yokulungisa ukunyanzeliswa kokubini kwi-sham-esebenzayo kunye ne-5-HT -ededed rats. Ezi mpembelelo zingafaniyo ze-5-HT2A kunye ne-5-HT2C receptor antagonists zaye zenziwa izilungiso ngokuchaphazela amachiza kwii-nucleus accumbens, kodwa hayi i-mPFC, kwizilwanyana eziqinisekileyo.Cottrell okqhubekayo, 2008). Nangona kunjalo, kwiiyantlukwano ze-5-CSRTT, kwakunokwenzeka ukuba kufunyanwe unciphiso olubalulekileyo ekunyanzeliseni emva kokungena kwe-intra-mPFC ye-5-HT2A receptor antagonist. Iziphumo ezigqityiweyo zahambelana nokubona ukuba, kubemi be-Lister efakwe kwiigundane, yayiyezona zilwanyana zixhasayo ezazijolise kakhulu kwi-5-HT kwi-mPFC, ebonisa ukuba umohluko ngamnye kunye nokuthe ngqo komda kubalulekile ekuqwalaselweni kokuqonda ubudlelwane phakathi kwe5-HT kunye ne-disinhibition yokuziphatha.

Iziphumo zokungqengqiswa kwe-5-HT kumbindi wesinyanzelo kuma-impulsivity ume ngokungahambisani nezenzo zawo kwimisebenzi yokujonga ngomntu ngamnye kwi-5-CSRTT. Amaphepha aliqela aqaphele nokuba akukho ziphumo okanye zokwenyusa ukuchaneka kokunakwa xa kuqhutywa isimilo esinganyanzelekanga (Harrison okqhubekayo, 1997) okanye emva konyango kusetyenziswa inkqubo ye-receptor okanye ye-intra-PFC 5-HT2A ye-receptor echasene ne-ketanserin okanye i-M100907 (IPassetti okqhubekayo, 2003; Winstanley okqhubekayo, 2003) kunye ne-5-HT1A receptor agonist 8-OHDPAT (Winstanley okqhubekayo, 2003). Ezi zinto zifunyanisiweyo ziyahambelana ne-hypothesis ethi ulawulo lwe-inhibitory kwi-behaulsive yokuziphatha kunye nomsebenzi wengqwalaselo idityaniswa kuphela kule meko yovavanyo kwaye iphakamisa ukuba akunakubakho ulwalamano olulula phakathi kwezi zimbini kwii-syndromes ezifana ne-ADHD.

Into eyongezelelweyo yokuntsonkotha yaziswa xa ujonga iimpembelelo zala machiza afanayo kwiinyathelo zokunyanzelwa. Sebenzisa uvavanyo olulula lokubuyela umva kwesithuba esinovakalelo kwizilonda ze-OFC (Boulougouris okqhubekayo, 2007), kwafumaniseka ukuba i-5-HT2C receptor antagonism (eveliswe ngolawulo lwenkqubo) ziququzelelwe ukufunda umva. I-M1000907 yayinefuthe elibi lokuyonakalisa (I-Tsaltas okqhubekayo, 2005). Qaphela ukuba ngokubhekisele kulungiso, oku kuchasene noko kwafunyanwa ngamanyathelo okunyanzelwa. Uphuculo olufanayo lokufunda ukubuyela umva emva konyango kunye ne-5-HT2C antagonist baye bafunyanwa emva kokufakwa kwi-OFC (iBoulougouris, Glennon, Robbins, iziphumo ezingapapashwanga) (2 Table).

Iziphumo ezahlukileyo ze5-HT2C kunye ne-5-HT2A Receptor antagonists kwiRat Models of Impulsivity and Compulsivity

Ngaphandle kokucaciswa ngokuchanekileyo kwendlela yokusebenza, ezi datha zekhemistri ziyahlula-hlula ezi ndlela zokunyanzelwa nokunyanzelwa, kucetyiswa ukuba abanakukwazi hinge kwinkqubo eqhelekileyo yokuziphatha. Ukuzahlula akunakuchazwa ngokulula ngokubhekisele kwiiyantlukwano kwiintlobo, iziyobisi, okanye idosi yomamkeli osetyenzisiweyo osetyenzisiweyo okanye uhlobo lwenkxaso esetyenzisiweyo; Bamele baxhomekeke emsebenzini-njengoko le misebenzi yomibini ifuna ukuphendula kungasebenzi kakuhle. Ke ngoko, sigqiba kwelokuba kukho enye into yeenkqubo eziqhutywa ngumsebenzi, ezahlula phakathi. Ezi ziphumo zithetha ukuba ukunyanzeliswa nokunyanzelwa kusebenze ngendlela eyahlukileyo kwaye kubopheleleke ndawonye, ukuboleka ngenkxaso kwimodeli enganyanzelekanga-enyanzelekileyo yokwahlukahlukana (IHollander kunye neWong, 1995). Bacebisa ukuba ukunyanzeliswa kunye nokunyanzelwa kungasuswa ngokukhetha i-5-HT2 receptor ligands kunye nokucebisa kwizicelo zeklinikhi ezintsha zeearhente ezinjalo. Nangona kunjalo, kuya kubaluleka ukusombulula ukuba le datha ihambelana njani nokufumana okungaguqukiyo kwe-5-HT depletion kwi-OFC impairs visualnto ephindwayo yokufunda kwiinkawu ze marmoset (Clarke okqhubekayo, 2004, 2005; Yucel okqhubekayo, 2007). Ukongeza, kuya kubonakala ngathi ezi mpembelelo zibonakalayo zichasene neendlela eziphakathi: kwimeko yokuqhutywa, ngokusebenzisa iingqikelelo ezivela kwi-infralimbic VMPFC (indawo ye-25), indawo egcinwe ngokutyebileyo yi-5-HT2A receptors ummiselo, ukuya kwigobolondo yenyukliya (I-Vertes, 2004) kwaye, kwimeko yokunyanzelwa, kunxibelelwano phakathi kwe-OFC kunye ne-caudate nucleus (okanye i-dorsomedial striatum kumqolo) (Umfundi okqhubekayo, 2008).

UKUJONGA UKUFUNDA NOKUFUNDA NGOKUGQIBELA KUSETYENZISELWA IMISEBENZI YASEKHAYA

Ukuphazamiseka okunganyanzelekanga nokunyanzelekileyo kudla kubandakanya ukubekelwa ecaleni kokunciphisa okanye ukuthintela iingcinga eziphindaphindiweyo okanye isimilo. Ke, iingxaki zokucinezela okanye ukuthintela ukusebenza okungafanelekanga kunokubeka zombini iisampula zongxamiseko kunye nezinyanzelekileyo (Chamberlain okqhubekayo, 2005; Stein okqhubekayo, 2006). I-ADHD kukuphazamiseka kwasekuqaleni kubonakaliswa kukukhulelwa okungekho mgangathweni, iintshukumo ezinganyanzelekanga kunye nothintelo olungqingqwa kwi-inhibition yeemoto njengoko kulinganiswa kwimisebenzi efana ne-SSRT (Aron okqhubekayo, 2003; I-Lijffijt okqhubekayo, 2005). Ulawulo lwee-arhente zokuphucula ukuqonda njenge-atomoxetine kunye ne-methylphenidate ziphucula iimpawu kwaye zilungisa ukusilela kwe-SSRT kubantu abadala abane-ADHD, ngokuthatha amanyathelo ngokunyuka kwe-neuradrenergic (okanye i-dopaminergic) ye-neurotransuction (Chamberlain okqhubekayo, 2007a).

Izifundo kwizigulana ze-OCD zityhile ukukhubazeka kwe-SSRT kunye nokungasebenzi kakuhle kwimisebenzi yokutshintsha ye-ED (Chamberlain okqhubekayo, 2006a, 2007c; Iitshomi okqhubekayo, 2007a), kuthetha ukuba zombini izinyanzeliso zesinyanzeliso kunye nokunyanzelisa ukungahambi kakuhle. Izalamane zokuqala ezingafumaneki kwinqanaba lokuqala le-OCD zibelana ngezehlo ezifanayo kwi-SSRT nakwimisebenzi yokutshintsha kwe-ED (Chamberlain okqhubekayo, 2007c) kwaye ngenxa yoko kubonakala ngathi kubonakalisa amanqanaba afanayo okunyanzeliswa kweemoto kunye nokuguquguquka kwengqondo, ngaphandle kokungabikho kweempawu ze-OCD. Ngokwahlukileyo kwi-OCD, ukusetyenziswa kwebhetri yovavanyo oluhambelana ne-neurocognitive kubantu abane-trichotillomania kubonise ukungahambelani ngakumbi nokukhetha ukungalunganga kwi-motor inhibition, ngokuhambelana nohlelo lwe-DSM-IV njenge-ICD (Chamberlain okqhubekayo, 2006b, 2007b). I-MRI enengqondo yonke kwi-trichotillomania engacaciswanga ichonge ukwanda koxinano lwezinto ezingwevu kwindawo esekhohlo nakwimimandla emininzi yecortical (Chamberlain okqhubekayo, 2008b). Ukunyusa umba ompunga kwimimandla yamanxweme kuye kwanikelwa ingxelo kwizifundo zeTourette syndrome (I-Bohlhalter okqhubekayo, 2006; Igarraux okqhubekayo, 2006) kunye ne-OCD (Iitshomi okqhubekayo, 2008a). Kwelinye icala, abaguli abane-Tourette's syndrome bafunyenwe babelana ngokungazinzi kwengqondo kwaye banokukhubazeka ngakumbi kunezigulana ze-OCD kwimisebenzi yokwenza izigqibo, kodwa bengakhubazekanga kangako kumsebenzi wokuthintela iimoto (Watkins okqhubekayo, 2005), nangona olunye uphando oluphanda ulutsha ngeTourette alufumananga bungqina bokungafundi umvuzo wokufunda xa kuthelekiswa nolawulo lomsebenzi wokungcakaza (Crawford okqhubekayo, 2005). Li okqhubekayo (2006) isilele ukubonisa intsilelo yokusebenza xa kuthelekiswa nolawulo kwi-SSRT kubantwana abangama-30 abane-Tourette's syndrome.

Ubuninzi bokuphendula okunyanzelekileyo nokunganyanzelekanga ngaphakathi kwe-OCD kuphakamisa umbuzo ukuba ngaba ukuzingisa kuqhuba kuqhutywa unyanzeliso, kwaye ke nokuba kunokwenzeka ukubonakalisa ukunyanzeliswa kwengqondo ngaphandle Ukuqhutywa yimoto. Ukuba kunjalo, zeziphi iingxaki ezinokubonisa ukunyanzelwa 'okunyulu'? Abantu abane-obsessive-enyanzelekileyo kubuntu bokuphazamiseka kwi-OCD babonakalise ukwanda kokuphazamiseka ngokuthe ngqo kwidomeyini yokutshintsha kwe-ED. Oku kufumanisa kuyahambelana nenkcazo yeklinikhi yokuphazamiseka okungafunekiyo, ebonakaliswa kukungazinzi kokuziphatha kunye nokuziphatha, kodwa akubandakanyi iindlela eziphindaphindayo zokuziphatha (okt ukutyeba okanye ukunyanzelwa). Yiyo loo nto, ukuphazamiseka okungafunekiyo kubuntu obunokubangela ukuphazamiseka okunyanzelekileyo (Fineberg okqhubekayo, 2007b). Izifundo ezingqinayo usebenzisa abantu abane-OCPD engeyo-comorbid ziya kwamkelwa.

INDLELA YOKUGQIBELA YOKUGQIBELA, OCD, NANGAPHAMBILI

Ngelixa imisebenzi ye-neurocognitive isenokusetyenziselwa ukucacisa iindawo ezithile ezichazayo ze-neuropsychological, i-neuroimaging ehambelana nayo ingasetyenziselwa ukubonakalisa ii-anatomical substrates kunye neesetyhula ze-neural eziphantsi komngcipheko wemfuza wokungabikho kwesifo. Ngokudibanisa iiparameter ze-MNocococitive kunye nolwakhiwo, kusetyenziswa uhlalutyo lobuchwephesha bobuchopho (ubuchule bezikwere ezimbalwa, UMcIntosh kunye noLobaugh, 2004) novavanyo lokuvunywa kwenoveli, Iitshomi okqhubekayo (2007a) kuchonge iimpembelelo zosapho kwindlela yokusebenza kumsebenzi wokuthintela i-motor (i-SSRT) enxulunyaniswa nokwahluka kwiindawo ezininzi ezinamanzi. Zombini izigulana ze-OCD kunye nezalamane zabo zokuqala ukuboniswa kolawulo lwe-inhibitory motor engalunganga, eyalathiswa ixesha elide le-SSRT kunye nokuhamba kwexesha elide kunxulunyaniswa nomthamo omncinci we-grey kwi-OFC kunye ne-RIF cortex (iindawo ezinxulunyaniswe ne-OCD kunye ne-SSRT activation, ngokulandelanayo) kunye nokunyusa ivolumu yemicimbi yeengwevu iindawo ze-striatum, i-cingulate, kunye ne-parietal cortex. Ezi ziphumo ziphikisana ngolungelelwaniso lokuqala lwe-MRI endophenotype-yokulamla usapho, kwaye mhlawumbi imfuzo, umngcipheko wokunxulumana nokunxulumene ne-OCD. Izifundo zexa elizayo zinokuvavanya inzuzo yokufumana iziphumo zofuzo ezithile kwiiyantlukwano eziphakathi, njengenye indlela yoyilo lobumbano, ukufumana izinto ezinokubakho.

Iziphumo ezifunyenweyo kunye ne-SSRT, isifo esingangqinelani nesifo sokuxhuzula kwi-motor, kuphakamisa ukuba kungenzeka ukuba i-endophenotype ingavunyelwa i-OCD, kodwa ukongeza inxulumene nolunye uphazamiseko ngaphakathi, kwaye mhlawumbi ngaphandle, ukunganyanzeleki-okunyanzelekileyo ukuphazamiseka isikram. Umzekelo, abantu abane-ADHD kunye nezalamane zabo babonakala ngathi bathintelekile kwimisebenzi yokuthintela iimoto (I-Crosbie kunye neSchachar, 2001), kodwa okwangoku akukacaci nokuba ingaba ulungelelwaniso lobuchwephesha bokupheliswa kwabantu abasemngciphekweni wosapho kwi-ADHD ziyafana okanye ziyahluka kubantu abasemngciphekweni wosapho kwi-OCD.

Uqhakamshelwano lwangaphakathi lwesifundo phakathi kokuncipha kwento egreyini esecaleni kwemimandla yangaphambili yecortex kunye nokunyuka kwemilinganiselo kwiziseko zestriatum zineemodeli ze-OCD ezibonakalayo ezivela kwizifundo zophando lokuqala (Baxter okqhubekayo, 1987) kunye nophando lwe-MRI olwakhiweyo nolusebenzayo (lokujonga kwakhona, Iitshomi okqhubekayo, 2008a). Iziphumo zophando lokuqala olwenziwa emva kokusebenzisa ubuchule bokucinga ngaphakathi kumalungu osapho lwe-OCD (Iitshomi okqhubekayo, 2008b) ubungqina obuchongiweyo bokungahambi kakuhle kwezinto ezimhlophe kwiindawo ezihambelana nobuchopho kubandakanya indawo yangaphambili yezendali (ecaleni kwe-cortex cortex, i-ACC) kunye neendawo ezichanekileyo zeparietal (ecaleni kwe-cortex ye-parietal), ehambelana nesiphumo sophononongo lwangaphambili olubandakanya izigulana ze-OCD (Szeszko okqhubekayo, 2005). Nangona kunjalo, ngokwandisa olu phononongo ukuba lubandakanye amalungu osapho e-OCD angakhuselekanga, sicebise ngezi zinto zifunyanisiweyo njengezinto ezinokwenzeka emhlophe endophenotypes ye-OCD (Iitshomi okqhubekayo, 2008b).

Ukongeza kubuchwephesha bokuchaphazeleka kwengqondo kwizigulana ezine-OCD nezihlobo zazo, uphando sele luqalisile ukubonisa ubungqina bokusebenza komjikelo we-fronto-striatal circry besebenzisa ubuhlakani be-fMri elungiselelwe le njongo. Sebenzisa i-fMRI yengqondo eguquguqukayo eguquguqukayo, kwaboniswa ukuba abaguli abane-OCD kunye nezihlobo zabo ezingafumanekiyo baboniswe phantsi kogqithiso lwe-AUC yamuva ngexesha lokubuyiswa kweempendulo; bakwathanda ukwenza izinto ezingavakaliyo kwi-PFC ngexesha lokutshintsha kwe-ED kumanqanaba enkqubo (Chamberlain okqhubekayo, 2008a).

Ngokudibeneyo, ezi ziphumo zibonisa ukuba ubuchule be-neuroimaging bunokubonelela ngomthombo otyebileyo we-endophenotypes yomgqatswa we-OCD. Iziphumo ziyahambelana neethiyori ezibonisa ukungaphumeleli kwe-cortical cortical inhibition ye-striatally mediated behaviour. Bacebisa ukuba ukukhanya okungafunekiyo kwe-idiosyncratic kunye nezithethe ezinyanzelekileyo ezibonakalisa i-OCD zikhatshwa zizinto ngokubanzi zokuziphatha okungqongqo kunye nokungathintelwa ekwabelwana ngako phakathi kwamalungu osapho angachaphazelekiyo. Ke, ubunzima 'kuthintelo lokuqonda kunye nokuguquguquka' kunokuba negalelo elibonakalayo kuphuhliso lweempawu ze-OCD. Umsebenzi wexesha elizayo kufuneka ujonge ukuba ingaba le ndlela inokuphicothwa ngempumelelo kwezinye iingxaki kuphazamiseko olungxamisekileyo. Ukubaluleka kweklinikhi kwee-endophenotypes ezibekiweyo zifuna uphando olongezelelekileyo ukumisela ukuba (kwaye njani) izihlobo ezingachaphazelekiyo ezabelana ngezimpawu zokumakisha kunye ne-OCD probands zinokwahlulwa kulawulo olunxulumene ne-OCD. Ukuqonda okuphuculweyo kuyafuneka kwiindlela ezinokuthi zibangele imeko ye-OCD kubantu abasemngciphekweni wemfuza, kwaye nokuba ingaba unyango lunokunceda njani ukuguqula ukuqala kwesifo.

I-ICDS kunye neendlela zokwenza imbuyekezo

Ngokwahlukileyo kukuphazamiseka okunyanzelekileyo njenge-OCD, ezinye ii-ICD, ezinjengongcakazo lwengqondo, zibonakaliswa ngokukhetha ukwaneliseka kwethuba elifutshane ngaphandle kwemiphumo emibi yexesha elide. Berlin okqhubekayo (2008) Thelekisa umntu kunye nokungabinamali yokungcakaza kwi-betop ye-neuropsychological betri (Berlin okqhubekayo, 2008). Abantu abaphethe ukungcakaza kwe-pathological abaye bafumana amanqaku kakhulu okuzixela njenge-Barratt Impulsivity Scale babenemilinganiselo ye-subjective ekhawulezileyo yexesha (ixesha elandisiweyo) ngokuthelekiswa nolawulo kwaye babonisa ukusilela okulinganiswa nemibuzo yendlela yokuziphatha yangaphambili ethathelwe ingqalelo ukubonakalisa okungaphambili. -Ukungasebenzi kakuhle. Izihloko ezinxulumene nokungcakaza kwe-pathological zikwabonakalise ukwenza izigqibo okungathandekiyo kwi-Iowa Gamble Task (Bechara okqhubekayo, 1994) kunye nentsilelo yesicwangciso sokulawula (umz. kuCwangciso lweSithuba kunye nokuThunyelwa kwamacandelo eKambridge yeCANTAB), ibeka imijikelezo yangaphambili ebandakanya umda we-OFC / VMPFC. Ngokwahlukileyo kwi-OCD (Watkins okqhubekayo, 2005; Chamberlain okqhubekayo, 2006b), Ukuseta-ukutshintsha bekungaphazanyiswa kukungcakaza kwe-pathological. Nangona kunjalo, olunye uphononongo lubonisa ukuba abantu abanengxaki yokungcakaza ngokwendalo bafumana amanqaku athile kunyanzeliso okanye kuthintelo lokulimala, kwaye amanyathelo okunyanzelwa nokunyanzeliswa anokutshintsha ngokuhamba kwexesha (umzekelo, ngexesha lonyango (Umkhuhlane, i-2007a; Mhlophe okqhubekayo, 2009). Ezi ziphumo zibonisa ukuba ukunyanzeliswa kunye nokunyanzelwa akuphikiswa ngokuchaseneyo kwaye kwabelwane ngobunzima, ubudlelwane be-orthogonal, kunye nokuphazamiseka okuthe ngqo kubonakalisa ubungakanani besakhiwo esinye ngaphezulu kwesinye esinokutshintsha ngendlela eguquguqukayo yokwexeshana.

Hollander okqhubekayo (2007a) Ndithelekisa amaqela amathathu aneminyaka yobudala kunye nabantu abalingana ngokwesini, equka ukugembula kwengqondo (ikakhulu inyanzelo) kunye ne-OCD kunye ne-autism (inyanzelekileyo) ukuphazamiseka, kusetyenziswa ibhetri yezonyango, ingqondo kunye nemisebenzi yokucinga. Ngexesha lokuqhutywa kwemisebenzi yokuphendula (ukuya / ukungahambi) eyenza isebenze ngokujikeleza kwe-fronto-striatal, onke amaqela amathathu e-spectrum-disorder abonise ukusebenza okungemthetho kwe-fMRI kwiindawo ezikwi-dorsal (engqondweni) nakwimimandla engaphakathi (yeemvakalelo) ye-ACC xa kuthelekiswa nolawulo olusempilweni. . Akukho mahluko ubalulekileyo wokusebenza phakathi kwala maqela mane. Nangona kunjalo, phakathi kweqela uhlalutyo lubonakalisile ukunciphisa ukusebenza kwe-ACC kumacandelo amathathu ezigulana xa kuthelekiswa nolawulo olusempilweni. Ke ngoko, ngexesha lokuphendula kuthintelo, zombini ezi ngxaki ziphazamisayo nezingxamisekileyo zibonakaliswe kukupheliswa kwendlela yokusebenza kwe-ACC, enokuthi inegalelo ekusilelekeni kokuziphatha ngokufanelekileyo kwezithomalaliso kwezi ngxaki.

Xa iipateni zentsebenzo ze-ACC yangaphakathi zadityaniswa nemilinganiselo yokunyanzelwa okanye ukunyanzelwa, kwavela ukungangqinelani okwahlukileyo phakathi kweqela. Ngaphakathi kwiqela lokungcakaza le-pathological, ukwanda kwe-ACC / i-ventral striatum activation kulungelelaniswe kakuhle neendlela zekliniki zokuziphatha okunyanzelekileyo zokufuna umvuzo (njengoko kulinganiswe yi-TCI Impulsiveness kunye noThintelo lokulimala ngokupheleleyo, i-NEO-FFI Extraversion, iXesha elipheleleyo loQikelelo, kunye ne-Iowa Gask Task ). Ngaphaya koko, abagembuli ngenkuthazo eyandisiweyo kwi-ventral ACC (indawo ye-25) babonisa amanqaku asezantsi okunyanzeliswa kwimisebenzi yokutshintsha kokuseta kwengqondo (inqanaba le-ID / ED ligqityiwe). Ngokwahlukileyo, kwiqela le-autistic (enyanzelekileyo), yanda i-ACC / ye-ventral striatum yemisebenzi edityaniswa nobukhali bokwanda nyanzelwa imikhwa yokuphelisa uxinzelelo (ukuqinisa), kunye nokunyusa ukusebenza ngaphakathi kweendawo ezifanayo ze-ACC ye-ventral (indawo ye-25) edibene nokunyanzeliswa okwandisiweyo (i-ID / ED yokutshintsha iimpazamo zilungisiwe) kunye nokunciphisa ukunyanzeliswa komsebenzi weXesha lokuQalwa.

Oku 'kukwahlulahlula kabini' kucebisa ukuba kungcakazo lwe-pathological kunye ne-autism, ukungafani okukhoyo kwimpembelelo ye-neuromodulation kwi-ventral corticostriatal pathways ngexesha lokuthintela indlela yokuziphatha, ethi yona ekungcakazeni kwe-pathological kungakhokelela ekuqhubeni ukunganyanzeleki nakwi-autism ukuqhuba ukunyanzelwa. Ikwakhumbuza idatha kwiigundane ezichazwe kwenye indawo apha zibonisa iimpembelelo ezichaseneyo ze-5-HT2C kunye ne-5-HT2A receptor antagonists ekunyanzelweni kwi-5-CSRTT kunye nokunyanzelwa (indawo yokubuyela umva yokufunda)) (I-Tsaltas okqhubekayo, 2005; Boulougouris okqhubekayo, 2007) -Nokufunyanwa ngokuchaseneyo kukaCarl okqhubekayo-Ukufikiswa kwe-agonist ye-5-HT1A kwi-infralimbic kunciphise indlela yokuziphatha (kwi-5-CSRTT) ngaphandle kokuphembelela ukuphendula okunyanzelekileyo, nge-5-HT2A receptor antagonist has achasne (Chambers okqhubekayo, 2004). Ngokudibeneyo, ezi ziphumo zibonisa ukuba ukujikeleza okufanayo kwe-neural kunokuqhuba okanye kunganyanzelekanga kwindlela yokuziphatha kwabantu kunye nokuba i-5-HT subtypes kwi-VMPFC (5-HT2A) kunye ne-OFC (5-HT2C), kunye nokusilela kwe-ACC. ukungaphumeleli kokuthintela ukuphendula kwisimo sokuxhuzula (ukugembula kwengqondo) kunye nokuphazamiseka (OCD, autism).

UMBULELO, UQINISEKISO, NODA

Iindlela ze-DA kwinkqubo ye-mesolimbic inomsebenzi obalulekileyo kumvuzo nasekuqiniseni (Ubulumko, 2002). Kwiimeko zokuphazamiseka kolawulo lwempembelelo, ukunyanzelwa kokusebenza kwe-ACC ye-ventral ngexesha lokuphendula inhibition kunokuhambelana nokunyuka kokufuna umvuzo. Iziphumo zokuqala zibonisa ukuba abagembuli bomzimba abawuthathi lula umvuzo kwi-TCI umvuzo wokuxhomekeka kumvuzo kunolawulo olusempilweni kwaye bafune amanqanaba aphezulu okukhuthaza (ukufuna into entsha) (Berlin okqhubekayo, 2008). Nangona kunjalo, ezinye izifundo zezifundo ezinomngcakazo we-pathological ziye zafumanisa ukunciphisa ukusebenza kwe-ACC, ngakumbi kwicandelo layo le-ventral, ngexesha lokutya kunye novavanyo lokulawulwa kwengqondo (Potenza okqhubekayo, 2003a, 2003b). Ngokumalunga nokuphazamiseka okunyanzelekileyo, ukunxibelelana okuqinisekileyo phakathi kokunyanzeliswa kwe-ACC ye-ventral ngexesha lokuphendula imisebenzi kunye nokunyuka kokunyanzeliswa kumanqanaba e-ID / ED kunye neempazamo zizonke ezilungisiweyo zinokubonisa ukwanda komsebenzi we-dopaminergic ukusuka kwintsilelo yesihlobo, ngokuhambelana nemodeli ye-mesolimbic ye-OCD. (Joel, 2006).

Hypothetically, okwethutyana kunye nokuvuselela okuphindaphindiweyo kweendlela ze-mesolimbic ze-DA 'kunokuvuselela' inkqubo yomvuzo kwaye kukhokelele ekukhuleni ekufuneni umvuzo (URobinson noBerridge, i-1993), enokuthi, xa idibene nolawulo lwe-inhibitory ye-prepalal-preortal-cortex-mediated, inokuthi ihambise indlela yokuziphatha enxulumene ne-DA kwaye ibonakale ngathi iyashukuma. Ukukhutshwa okuphezulu kwe-DA kunye nokukhuthaza kunokuphelisa iivenkile ze-DA kwaye kukhokelele kwi-anhedonia kunye noxinzelelo (UKoob noLe Moal, i-1997). Ewe, kubaxhaphazi beziyobisi, ukunciphisa inkqubo yenkqubo ye-mesolimbic / mesocortical ye-DA, njengoko kulinganiswa ngorekhodo lwe-elektroniki kunye kwi vivo i-microdialysis, iyaqina emva kokunyuka kokutya iziyobisi. Oku kunokuvelisa umnqweno (wokunyanzelwa) wokufuna imbuyekezo eyomeleleyo 'yokuzalisa' ukusilela kwe-DA. Umboniso wokuncipha kwe-striatal D2-efana ne-receptors kubasebenzisi be-cocaine engapheliyo, ngokucinga kwe-PET (Volkow okqhubekayo, 1999), iphakamisa ukuhla komgaqo wokuphendula kukuphakanyiswa okuphezulu kwezikhundla ze-DA, ngokungqinelana nenkqubo yenkqubo yeDys ebhalisiweyo emva kokuvuselelwa okuphindiweyo kukhutshwe yi-DA. Ke ngoko, into eqala njengokonyusa ukukhutshwa kwe-DA ekhokelela ekonyuseni kwe-ACC ye-ventral kunye nokunyusa ukufuna umvuzo (Ubulumko, 2002) inokuphelisa njengesixhobo esinyanzelayo kumanqanaba anyukayo okukhuthaza umvuzo ukubuyisela ukusilela kwe-DA. Ukuqhuba okunyanzelekileyo kunokongezwa kukulawulwa okungafunekiyo kokuthathwa kwezigqibo kunye nokwenza izigqibo, okunxulunyaniswe ne-orbitofadalal, umphambili we-ventromedial, kunye ne-ACC (I-Adinoff, i-2004). Nangona kunjalo, indlela le hypothesis inxibelelana ngayo nee-ICD ezithile zifuna uphando oluthe ngqo.

IZIXHOBO ZOKUGQIBELA ZOLWAZI LOLWAZI LOKUFUNDA, UMBULELO, kunye ne-DA

Iimodeli zokunyanzelwa kunye nokunyanzeliswa zibeka ulungelelwaniso phakathi kwe-5-HT (2A, 2C) umsebenzi we-receptor kwimimandla ye-VMPFC / ye-OFC elawula izinto zokuthintela ukuphendula, kunye nelizwi le-DA kwimigudu ye-ventral yokudibanisa i-ventral ye-ACC kunye ne-ventral striatum / nucleus isimilo. I-neurotransuction ye-DA, ngakumbi ukukhutshwa kwe-phasic, kwi-nucleus accumbens inxulunyaniswa nokufuna umvuzo kunye nokomeleza (Schultz, 2002). Isohlwayo esingalindelekanga (ilahleko yemali) icetyelwe ukuba ibangelwe kukuntywila kwimisebenzi ephambili yedopaminergic, ukubuyela umva ekufundeni, kunye nokuncitshiswa komvuzo (Frank okqhubekayo, 2007). Amachiza e-Pro-dopamanergic, kubandakanya i-levo-dopa kunye nepramipexole (i-D2-efana ne-DA receptor agonist), inxulunyaniswa nokutshintsha umva wokufunda kwisohlwayo esingalindelekanga nakwii-ICD kwizigulana ezinesifo sikaParkinson (Ukupholisa, 2006; Ukuphola okqhubekayo, 2006). IPrimipexole ikwanxulumene nokufunyanwa okungalunganga kokuziphatha okunxulumene nomvuzo kubathathi-nxaxheba abasempilweni, ngokuhambelana nedatha ebonisa ukuba ukusayinwa kwe-phasic ye-DA kubalulekile ekuqiniseni isenzo esikhokelela kumvuzo (IPizzagalli okqhubekayo, 2008). Nangona kunjalo, enye idatha ibonakalisa ukuba i-pramipexole, xa isenziwa kubantu abadala abaphilayo, ayiguquli ekuziphatheni, ekunyanzeliseni, okanye ekubumbeni kubandakanya ukubambezela ukunciphisa, ukuthatha ingozi, ukuthintela impendulo,I-Hamidovic okqhubekayo, 2008). Ngapha koko, i-olanzapine, ichiza elinepropathi yomchasi kwi-D2-efana ne-receptor yosapho ye-receptors ye-DA, ayibonisanga ukubaluleka kwe-placebo kwizilingo ezimbini ezilawulwayo ezibandakanya izifundo zokungcakaza kwe-pathological (Fong okqhubekayo, 2008; McElroy okqhubekayo, 2008), kwaye enye i-D2-efana ne-antagonist, i-haloperidol, ifunyenwe inyusa izizathu ezinxulumene nokungcakaza kunye nokuziphatha kubantu abanomngcipheko we-pathological (I-Zack kunye nePoulos, 2007). Izifundo zeRadioligand zibalulekile ukucacisa imisebenzi enokubakho ye-D3 kunye ne-D2 receptors kwi-pathophysiology yokugembula kwe-pathological, kwaye ezo zifundo ziyanyanzelwa zezi zi-receptors zabelana ngokuhambelana nee-radioligands.

Ukuthatha ezi zinto zifunyanisiweyo, uphando oluthe kratya luyafuneka ukuqonda ngcono ubudlelwane phakathi kokunyanzelwa, ukunyanzelwa, kunye nomsebenzi we-DA njengoko zihambelana nochaphazeleko oluthile lwengqondo njengokungcakaza kwe-pathological. Ukuphazamiseka okunyanzelekileyo okanye okunyanzelekileyo kunokufumana ukusuka ekusweleni kwe-mesolimbic DA. Nangona kunjalo, abalinganiswa be-D2-njengabachasi babonise inzuzo yonyango kwezinye (i-OCD), kodwa hayi okunye (ukungcola komoya) okuphazamiseka okubangelwa kukunganyanzelekanga kunye / okanye nokunyanzelwa kwezinto. Ukucinga zombini i-ventral kunye ne-dorsal striatal circry kwizifundo zabantu ngesifo esithile sokunyanzeliswa kunye nokunyanzelwa usebenzisa i-serotonergic ekhethekileyo kunye ne-dopaminergic ligands iya kuba linyathelo elilandelayo lokuqonda le mibandela. Kungangumdla okhethekileyo ukuphonononga iziphumo zabachasi be5-HT2A kunye nabachasi be2C kuthumelo lwe-DA kule sekethe. Olu phando lungabonelela ngolwazi olongezelelekileyo kwizinto ezinje ngokuncitshiswa kwendlela etyhutyha ngaphakathi kunye ne-VMPFC esebenzayo ebonakalayo kuzo zonke izifundo ezibandakanya ukuphazamiseka ekwabelaneni ngeempawu ezinyanzelekileyo kunye ezinyanzelekileyo, ezinjengokungcakaza kwe-pathological kunye nee-SA (Ngaphandle okqhubekayo, 2005; Umkhuhlane, i-2007a).

Inkcazo yethu yangaphambi kokunyanzelwa (ukuthanda ukwenza izinto eziphindwayo ngendlela eqhelekileyo / ethandabuzekwayo ukuzama ukunqanda iziphumo) kunye nenkcazo yangoku (ukupheliswa kwengxamiseko yokuphambuka efana nokurhoxa) zihambelana ngokwembono. Umzekelo, ukuphendula ngokuhlala kwimikhwa yamachiza kunokuthathwa njengesixhobo sokulindela ngokuzenzekelayo isifo sokurhoxisa kunye nokuthintela ngaphambi kokuba kwenzeke. Idatha inxibelelanisa ezi ndlela zokufunda (okanye zokunyanzeliswa) kumacandelo e-dorsal striatum (umzekelo we-caudate), njengoko kuhlolwe ngaphambili. Ubungqina bamva nje ngoku bunxibelelanisa i-dorsal striatum (icandelo layo elingasemva) kunye nokufunda okukuqhubela phambili ukufunda (Seymour okqhubekayo, 2007). Ke, ngokombono we-neural, ubungqina buxhasa ukungqamana phakathi kwezi ngcinga zimbini zokunyanzelwa.

Impembelelo kunye 'nokuziphatha'

Ukungcakaza okungapheliyo kunye nee-SA zabelana ngeempawu ezininzi. Iingxaki zihlala zenzeka rhoqo kwaye zibonisa izinto ezifanayo ngokunxulumene neeprofayili zempawu, umahluko ngokwesini, imbali yendalo, kunye nobungakanani bosapho (Isibonelelo kunye nePotenza, 2006). Ukungcakaza okungapheliyo kunye ne-SA zibonisa amanqanaba aphezulu okunyanzeliswa kwimisebenzi yokuncitshiswa komvuzo, ehambelana nemilinganiselo engeyiyo yokusebenza (Bechara, 2003kunye nesiphumo sonyango olungalunganga (I-Krishnan-Sarin okqhubekayo, 2007) kubantu abanee-SAs kwaye ke banokuba nexabiso lenkqubela-phambili yokungcakaza kwe-pathological kunye nezinye ii-ICD. Idatha ye-Neurocognitive kunye ne-fMRI iphakamisa ukungcakaza kwe-pathological kwaye ii-SAs zabelana ngokufanayo kwi-neurocircuitry, apho, xa kuthelekiswa nezifundo zokulawula, kuncitshiswa kokusebenza kwe-ventral striatum kunye ne-VMPFC kubonwe ekusebenzeni kwemivuzo kunye nezinye iiparadigms (Potenza okqhubekayo, 2003a, 2003b). Ukuqalwa okungalunganga kwe-fMRI ye-ventral striatum ngexesha lokulungiswa kwemivuzo kuchongiwe kwiintsapho zabantu abane-SA kwaye banokuthi babonise umlinganiswa osebenzayo we-endophenotype wokuphazamiseka okuluthayo, nangona le hypothesis ifuna uviwo ngqo kwizalamane ezingaphazanyiswayo ze-pathological ukugembula.

Ixesha elingaphezulu, ukuphendula okuqhubekayo kokungcakaza kwendalo kunye ne-SA kungaguqukela kwindlela yokuziphatha enyanzelekileyo, kwaye kuye kwaqinisekiswa ukuba ukufunyanwa ngokuqhubekekayo kokuqeshana kwamalungu afanayo kunye nokwandayo kuya kusenziwa esidlangalaleni, ii-cortico-striatal loops zenzeka ngendlela evuthayo.Brewer kunye nePotenza, i-2008) ukukhumbuza ukujikeleza ngokuthe chu kwe-striato-nigrostriatal kuchongwe kwisimo sentengo (ULynd-Balta kunye noHaber, 1994) kunye neentongaBelin okqhubekayo, 2008) imizekelo yeendlela zokuziphatha ezixhasayo kwimephu yeenkqubo zotshintsho ukusuka kwi-ventral ukuya kwi-drial striatum. Izifundo ezinokulindeleka, ezinokubakho emva kotshintsho ngaphakathi kwabantu ekuhambeni kwexesha ziya kuba ziyafundisa kwaye zibalulekile kwikliniki. Ukuthembisa uphando ekunyangeni abantu abangcakazayo nge-pathological kunye ne-opioid antagonists (Brewer okqhubekayo, 2008) ayisi kuphela ucalucalulo lwendlela yokungcakaza evela kwi-OCD, apho abachasi be-opioid abanjenge-naloxone baboniswe ukuba benze i-OCD ibe mandundu (Insel kunye nePickar, 1983), kodwa kwakhona yacebisa umsebenzi wonyango lwabachasene ne-opioid kwezinye ii-ICD (Grant okqhubekayo, 2007).

IINDAWO ZOKUJONGA ENTSHA

Ukuyiqonda ngokupheleleyo i-neurobiology yokunyanzeliswa kunye nokunyanzelwa kunye nokubanakho ekuphuhliseni unyango olutsha, sinokufuna ukuphonononga ngaphaya kweesekethe ze-neural ekuxoxwe ngazo kweli nqaku ukubandakanya ezinye izakhiwo ze-neural, ezinje nge-insula. Idatha iphakamisa ukuba i-insula ibalulekile ekuququzeleleni 'ukwazi' ukubongoza. Izilonda zentsimbi, umzekelo emva kokubetha, zinxulunyaniswa nokuyeka ukutshaya ngokukhawuleza (Naqvi okqhubekayo, 2007). Ukubonakaliswa kwimikhombandlela kwindalo esingqongileyo, okanye kwimimandla ye-homeostatic njengokurhoxa, uxinzelelo, okanye unxunguphalo, kunokubangela ukumelwa 'kokungena' kwindawo ekuguqulela kuyo 'ukubongoza'. I-insula i-anatomically kwaye isebenza ngokukuko kwezi nkqubo zikhankanyiweyo zikhankanyiwe kunyanzeliso, ukunyanzelwa kunye nolawulo lwe-inhibitory. Ngokuqinisekileyo, i-insula inxibelelana neendlela zokunyanzeliswa kunye nokunyanzeliswa ngokudlulisela imiqondiso (ukusuka kwindalo esingqongileyo okanye kwi-viscera) ukuya kwi-5-HT 2C vs I-5-HT 2A ii-receptors kwindawo yangaphambili. Yiyo loo nto, imiqondiso yokungena ngaphakathi phakathi kwento engenayo inokuthi, kwelinye icala, ivuselele imijikelezo ye-neural yokuqhuba ukunganyanzelekanga okanye ukunyanzelwa. Kwelinye icala, imisebenzi ye-insula 'inokuthimba' iindlela zolawulo lwe-inhibitory zecortex yangaphambili kunye nokuguqula ingqalelo, ukuqiqa, ukucwangcisa, kunye neenkqubo zokwenza izigqibo kude ekuboneni kwangaphambili imiphumo emibi yesenzo esinikiweyo, kwaye sengqondo Ukwenza izicwangciso zokukhangela kunye nokufumana amandla anomdla anje ngeziyobisi (Naqvi okqhubekayo, 2007).

ISIPHELO

Ukubuyela, ke, kwimibuzo yethu eshukumisayo: (i) kungakanani ukunyanzelwa kunye nokuxhonywa kufaka igalelo lini kwezi ngxaki, (ii) baxhomekeke kangakanani kubekanye ekusetyenzisaneni okwabelweyo okanye okwahlukileyo kwe-neural, (iii) zithini iindlela zokulamla ze-monoaminergic, ( iv) ingaba izinto zokuziphatha ezinyanzelekileyo okanye ezinyanzelekileyo zinalo naliphi na inani lenkqubela phambili enxulumene nonyango, kwaye (v) kukho imodeli yokudibanisa imilinganiselo ehambelana nedatha? Ngokobungqina obufumanekayo, ukunganyanzeleki, kunye nokunyanzelwa, nganye ibonakala ngathi yeyamazwe amaninzi kwaye iphantsi kwezinye iingxaki zokunyanzeliswa kunye nokunyanzelwa, nangona ukuphazamiseka kubonakalisa ukugqagqana, kodwa kunye neeprofayili ezihlukileyo. Ke ngoko, ukusilela okuphezulu ngaphakathi kwe-cortico-striatal neurocircuitry yokulawula imiba yolawulo lwe-inhibitory kuye kwaqwalaselwa kwizifundo zengqondo kunye nokucinga kwazo konke ukuphazamiseka okuphantsi koqwalaselo, nangona kulolunye uhlobo lokuphazamiseka idatha ihlala ingenakuthelekiswa nanto. I-Trichotillomania inokuthi ime ngokwahlukana kolawulo lwe-motor-impulse kunye nokungasebenzi kakuhle ngaphakathi kwe-RIF cortex kunye nokudibana kwayo kwe-cortico-subcortical, ngelixa ukungcakaza kwe-pathological kunxulunyaniswa nokunganyanzelekanga okunxulumana nokwenza izigqibo okungalunganga kunye nokujikeleza okungaqhelekanga kwe-cortico-striatal, ingakumbi ebandakanya i-VMPFC kunye ne-ventral striatum, eyichonga ngokusondeleyo nee-SA. Amanqanaba aphakamileyo okuhambelana nomvuzo wokunxulumana nemiphumo engalunganga yonyango lwe-SAs kwaye unokubaluleka kokuqhubeka kokungcakaza kwe-pathological kunye nezinye ii-ICD. Ukuziphatha okunyanzelekileyo okwenzeka nge-autism kunxulunyaniswa nezinto ezigwenxa ezifanayo kwimjikelezo lomvuzo we-ventral. Kwelinye icala, i-OCD, ibonakalisa ukunyanzeliswa kweemoto kunye nokunyanzelwa, okuthethwe ngokuthe ngqo kukuphazamiseka kwe-OFC-caudate circry, kunye neVLPFC, i-RIF cortex, cingulate, kunye nokunxibelelana kweparietal. Kwezi zinto ziphazamisayo, i-serotonin enxulumene, i-DA, kunye nezinto eziqikelelweyo ze-noradrenaline zinokuba nemisebenzi ebalulekileyo yokumodareyitha, kunye nezinye iinkqubo ezingekaphelelwa kwaphela. Ixesha elingaphezulu, ukunyanzeliswa kunokuvela kukunyanzeliswa kwaye ngokuchaseneyo.

Ke, umfanekiso ubonakala ukude kwi-diathesis elula yomgama kunye nokunyanzeliswa kokuhlala kwiipali ezichaseneyo, kwaye 'imodeli' inokuthi ibandakanye unxibelelwano oluntsonkothileyo lwezinto ezininzi ezinento yokwenza nokunxibelelana, ezichazwe ngokwahlukeneyo kwezi setyhula kunye nokuphazamiseka. Ukuphazamiseka okunganyanzelekanga kunye nokunyanzeliswa ngokungafaniyo ngokungafaniyo, nokwabelana ngemiba yokungxamiseka kunye nokunyanzelwa, kwaye kuya kusiba nzima ngakumbi kwaye ke kube nzima ngakumbi ukuphazamisa ixesha. Umzekelo, kukuphazamiseka okungxamisekileyo kunye nokulutha, ukunyamezelana nomvuzo kunokukhula kwaye isimilo sinokuqhubeka njengeyona ndlela yokunciphisa ukungonwabi (okt baya banyanzeleka). Ukuphazamiseka okunyanzelekileyo, kunokwenzeka ukuba ukusebenza kweendlela zokuziphatha eziphindaphindayo ngokwazo kuya komelela ngokuhamba kwexesha, ngaphandle kweziphumo ezibi zexesha elide (okt baqhutywa ngokungxamisekileyo). Ukwenza imephu kwezi ngxaki kusetyenziswa ibhetri ekuvunyelwene ngayo yabamakishi bokugqibela be-endophenotypic inokucacisa ngakumbi ubudlelwane babo, kwaye amashishini ophando abambisanayo azayo kuwo onke amaziko anobuchule obongezelelweyo kufuneka akhuthazwe. Iindlela zenoveli zinokufuneka ukuphanda ngokwaneleyo ngeendlela 'zonxantathu' ezinjengokunxibelelana okunzima. Kule meko, ubuchwephesha bokuchonga iinkqubo zokusebenza kwengqondo kwidatha ye-neuroimaging, enje ngendlela yezikwere ezincinci (ezivumela ukuphononongwa kokuziphatha kunye nokucinga okuguqukayo), kunokuba nakho ukubakho njengeenkqubo zekamva kule ndima. Sinokwenza inkqubela phambili ngakumbi ekusasazeni iindlela ze-receptor ezibandakanyekayo kulawulo lokunyanzelwa nokuziphatha okungafunekiyo ngokusetyenziswa kwamalungiselelo e-mouse kwimisebenzi efanayo eyenzelwe iigundane (umz. 5-CSRTT kunye nokubuyisela umva ukufunda) kunye nokuhlola uluhlu olupheleleyo lwe-5- Ii-receptors ze-HT zisebenzisa ii-ligands ezintsha ze-pharmacological.

Imibulelo

UGqr Fineberg ubonisane noLundbeck, uGlaxo-Smith Kline, uServer, noBristol Myers squibb; Ufumene inkxaso yophando kuLundbeck, Glaxo-SmithKline, Astra Zeneca, Wellcome; ifumene i-honaria kunye nenkxaso yokufunda ezintlanganisweni zesayensi ezivela eJanssen, Jazz, Lundbeck, Server, Astra Zeneca, Wyeth. UGqr Potenza ucebisa kwaye ucebise ngo-Boehringer Ingelheim; Uthethathethane kwaye unomdla kwimali eSomaxon; ifumene inkxaso yophando kumaZiko ezeMpilo kaZwelonke, ezoLawulo lweZilwanyana, iMohegan Sun Casino, iZiko leLizwe lokuNgcakaza ngoXanduva kunye neZiko loPhando malunga nokuPhazamiseka koNgcakazo, kunye neGlaxo-SmithKline, iilebhu zeLebhu, iOrtho-McNeil kunye neOy-Control / Biotie amayeza; uthathe inxaxheba kuphando, ukuthumela iposi, okanye ukubonisana ngomnxeba okunxulumene neziyobisi, ii-ICD okanye ezinye izihloko zempilo; Uthethathethane neeofisi zomthetho kunye neofisi yomkhuseli woluntu kwimicimbi enxulumene nee-ICD kunye neziyobisi; wenze uhlolo lwesibonelelo samaZiko ezeMpilo kaZwelonke kunye nezinye iiarhente; unike iintetho zemfundo kwimijikelo emikhulu, iminyhadala ye-CME, kunye nezinye iindawo zeklinikhi okanye zesayensi; inamacandelo eejenali ahlelwe ngabatyeleli; uvelise iincwadi okanye izahluko zeencwadi zabapapashi beetekisi zempilo yengqondo; kwaye ibonelela ngononophelo lweklinikhi kwiSebe laseConnecticut leMpilo yeNgqondo kunye neeNkonzo zoMlutha Ingxaki yeNkqubo yokuNgcakaza. UGqr Chamberlain uvavanya uCambridge Cognition, iShire, kunye neP1Vital. UGqr Menzies ufumene imbuyekezo yemali ebangelwe kukutshintshwa kwetekhnoloji engahambelani nomxholo weli nqaku phakathi kweCambridge Enterprise Limited, iYunivesithi yaseCambridge, iCambridge, i-UK, kunye neCypress Bioscience, Inc, San Diego. UGqr Bechara ufumana imali evela kwi-PAR, Inc. UGqr Sahakian ubambe izabelo eCeNeS; Ubonisane noCambridge Cognition, Novartis, Shire, GlaxoSmithKline, kunye noLilly; Uye wafumana i-honaria malunga nemijikelezo enkulu yesifo sengqondo kwizibhedlele iMassachusetts General (iikhredithi zeCME) kunye nokuthetha kwiNkomfa yaMazwe ngaMazwe yokuNgasebenzi kakuhle eSchizophrenia naseMood Disways (2007). UGqr Robbins uceba uCambridge Cognition, uE. I-Lilly, GlaxoSmithKline, kunye ne-Allon Therapeutics. UGqr Bullmore ungumqeshwa waseGlaxoSmithKline (50%) kunye neYunivesithi yaseCambridge (50%) kunye nomnini-zabelo eGlaxoSmithKline. UGqr Bullmore ufumene imbuyekezo yemali ebangelwe kukutshintshwa kwetekhnoloji engahambelani nomxholo weli nqaku phakathi kweCambridge Enterprise Limited, iYunivesithi yaseCambridge, iCambridge, i-UK, kunye neCypress Bioscience, Inc, San Diego. UGqr Hollander udibene noSomaxon, Neuropharm, Transcept, kunye neNastech. Ugqirha Hollander uye wadlana iindlebe nee-ofisi zomthetho kwaye wangqina ngecala lemveliso yeMveliso ye-Mirapex. Uye wafumana inkxaso yophando kwiZiko lezeMpilo leSizwe, kwiCandelo leMveliso yeNkedama kuLawulo lokuTya nokuTya iziyobisi, iNational Alliance for Research eSchizophrenia kunye neAfficial Diswords, Autism Speaks, iSiseko seLwandle, kunye neSolvay, Oy Contral, neSomaxon. Lo msebenzi uxhaswe ngenxalenye yesibonelelo seNkqubo yeWellcome Trust (076274 / Z / 04 / Z) kuGqr Robbins, uGqr Sahakian, BJ Everitt, kunye no-AC Roberts. IZiko lokuziphatha kunye neClinical Neuroscience Institute ixhaswa ngamabhaso adityanisiweyo avela kwi-Medical Research Council (MRC) kunye neWellcome Trust (G001354). Ixhaswe yi-National Alliance yoPhando kwi-Schizophrenia kunye noXinzelelo (i-RG37920 i-Award ePhanzileyo yoPhando kuDkt Bullmore), Ingxowa-mali yeHarnett kunye neJames Baird Fund (iYunivesithi yaseCambridge) kunye neYunivesithi yaseCambridge yeZonyango lweKlinikhi, (MB / PhD yabafundi kuDkt. I-Menzies), kunye neBhunga loPhando lwezoNyango (ukufundwa kwe-MB / PhD kugqirha). UGqr Bechara ufumana inkxaso-mali evela kumaZiko kaZwelonke wezeMpilo (i-NIDA R01 DA023051, DA11779, DA12487, kunye ne-DA1670), (NINDS P01 NS019632), kunye ne-National Science Foundation (NSF IIS 04-42586). s DA019039, DA020908, DA015757, DA020709; I-R37 DA15969; I-RL1 AA017539; I-P50s DA09241, AA12870, AA015632), i-VA (VISN1 MIRECC kunye ne-REAP), kunye noPhando lwezeMpilo lwaBasetyhini eYale. UGqr.Robbins ubonisana ne-pfizer, uGqr Menzies ufumene imbeko ngokubonisa kwinkomfa ye-8th yoNyaka yoPhando lwe-psychopathology kunye nomsebenzi kwi-UK Government Project Foreores on capital capital and wellbeing.

Imihlathi

UKUQALA

Ababhali bavakalisa ukuba akukho mpikiswano.

Ucaphulo

Iinkqubo ze-Adinoff B. Neurobiologic kwimbuyekezo yeziyobisi kunye neziyobisi. Harv Rev Psychiatry. 2004;12: 305-320. [Inkcazelo yamahhala ye-PMC] [PubMed]
I-Aron AR, uDowson JH, iSahakian BJ, iRobbins TW. I-Methylphenidate iphucula i-inhibition yokuphendula kubantu abadala abanesidala sokujonga / ukuphazamiseka kwengqondo. Biol Psychiatry. 2003;54: 1465-1468. [PubMed]
I-Aron AR, iPoldrack RA. I-neuroscience yengqondo yempendulo kuthintelo: ukubaluleka kokusebenza kophando lwemfuzo kunyango-nakuthungelwano / kukungasebenzi kakuhle. Biol Psychiatry. 2005;57: 1285-1292. [PubMed]
Baxter LR, Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE. Amanqanaba okusuka kweswekile ye-glucose kwingxaki yokujonga ngokunyanzelekileyo. Thelekisa amaxabiso kuxinzelelo lwe-unipolar nakulawulo oluqhelekileyo. Arch Gen Psychiatry. 1987;44: 211-218. [PubMed]
Bechara A. Ishishini elinobungozi: iimvakalelo, izigqibo kunye nokulutha. J Gambl Stud. 2003;19: 23-51. [PubMed]
Bechara A, Damasio AR, Damasio H, Anderson SW. Ukungakhathaleli kwiziphumo ezizayo kulandela ukulimala kwembonakalo yabantu. Ingqiqo. 1994;50: 7-15. [PubMed]
Belin D, Mar AC, Dalley JW, Robbins TW, Everitt BJ. Ukunyanzelwa okuphezulu kuxela kutshintsho ekuthatheni i-cocaine. Sayensi. 2008;320: 1352-1355. [Inkcazelo yamahhala ye-PMC] [PubMed]
IBerlin HA, iHamilton H, iHollander E. I-Neurocognition kunye neThemesti yoThungelwano lwePathological. Umbutho wezengqondo zaseMelika, ingqungquthela: IWashington DC; 2008.
I-Berlin HA, i-Rolls ET, i-Kischka U. Ukunyanzeliswa, ukuqonda kwexesha, imvakalelo kunye nokuqiniswa kokuqina kwizigulana ezinezilonda ze-cortex ye-orbitofrontal. Ubunjani. 2004;127 (Pt 5: 1108-1126. [PubMed]
Blanco C, Potenza MN, Kim SW, Ibanez A, Zaninelli R, Saiz-Ruiz J, et al. Uphononongo lokuqhuba ngokungxamisekileyo kunye nokunyanzeliswa ekungcakazeni kwe-pathological. Psychiatry Res. 2009;167: 161-168. [Inkcazelo yamahhala ye-PMC] [PubMed]
I-Bloch MH, i-Landeros-Weisenberger A, iKelmendi B, i-Coric V, i-Bracken MB, uLeckman JF. Uhlalutyo olucwangcisiweyo: Ukunyanzeliswa kwe-antipsychotic ngonyango olunokuphazamisa ukunganyanzeleki. Mol Psychiatry. 2006;11: 622-632. [PubMed]
Bohlhalter S, Goldfine A, Matteson S, Garraux G, Hanakawa T, Kansaku K, et al. Ukudityaniswa kwe-Neural kwesizukulwana se-tic kwisifo seTourette syndrome: isifundo esimalunga nomsitho esinxulumene nomsebenzi. Ubunjani. 2006;129 (Pt 8: 2029-2037. [PubMed]
Boulougouris V, Dalley JW, Robbins TW. Iziphumo ze-orbitof Pambal, infralimbic kunye ne-prelimbic cortical lesion on backal spatial learning back in the rat. Behav Brain Res. 2007;179: 219-228. [PubMed]
Boulougouris V, Glennon JC, Robbins TW. Iziphumo ezingahambelaniyo ekukhetheni i-5-HT2A kunye ne-5-HT2C receptor antagonists on serial spatial real learning in rats. Neuropsychopharmacology. 2008;33: 2007-2019. [PubMed]
Brewer JA, Grant JE, Potenza MN. Unyango lokungcakaza kwe-pathological. Unyango lwe-Disord Disord. 2008;7: 1-14.
Brewer JA, Potenza MN. I-neurobiology kunye ne-genetics yokupheliswa kokulawulwa kwempembelelo: ubudlelwane neziyobisi. Biochem Pharmacol. 2008;75: 63-75. [Inkcazelo yamahhala ye-PMC] [PubMed]
IChamberlain SR, iBlackwell AD, iFineberg NA, iRobbins TW, iSahakian BJ. I-neuropsychology ye-obsessive ngokunyanzelekisa ukuphazamiseka: ukubaluleka kokungaphumeleli ekuthinteleni ukuqonda kunye nokuziphatha njengeempawu zokumakishwa komntu wokugqibela. Neurosci Biobehav Rev. 2005;29: 399-419. [PubMed]
IChamberlain SR, iBlackwell AD, iFineberg NA, iRobbins TW, iSahakian BJ. Ukuphunyezwa kwesicwangciso kubuchwephesha bokujonga ngokunyanzela kunye ne-trichotillomania. Psychol Med. 2006a;36: 91-97. [Inkcazelo yamahhala ye-PMC] [PubMed]
IChamberlain SR, Del Campo N, Dowson J, Muller U, Clark L, Robbins TW, et al. I-Atomoxetine iphuculwe impendulo yokuphendula kubantu abadala abanesifo sokungakhathali / isifo sokungasebenzi kakuhle. Biol Psychiatry. 2007a;62: 977-984. [PubMed]
IChamberlain SR, iFineberg NA, iBlackwell AD, iClark L, iRobbins TW, iSahakian BJ. Ukuthelekisa kwe-neuropsychological yesifo sokungaboni kakuhle-kunye nokunyanzelwa kwe-trichotillomania. Neuropsychologia. 2007b;45: 654-662. [PubMed]
IChamberlain SR, iFineberg NA, iBlackwell AD, iRobbins TW, iSahakian BJ. Inhibition yeemoto kunye nokuguquguquka kwengqondo kubuchwephesha bokujonga ngokunyanzelekileyo kunye ne-trichotillomania. IJ Psychiatry. 2006b;163: 1282-1284. [PubMed]
IChamberlain SR, iFineberg NA, iMenzies LA, iBlackwell AD, iBullmore ET, iRobbins TW, et al. Ukungaguquki kwengqondo eguqukayo kunye nesithintelo se-motor kwizalamane zokuqala ezingafikelelekiyo zabaguli abanesifo esibonakalayo. IJ Psychiatry. I-2007c;164: 335-338. [Inkcazelo yamahhala ye-PMC] [PubMed]
IChamberlain SR, i-Menzies L. I-Endophenotypes ye-obsessive-wanyanzeleko ukuphazamiseka: rationale, ubungqina kunye nexesha elizayo. Iingcali zeRev Neurother. 2009;9: 1133-1146. [PubMed]
I-Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, et al. Ukungasebenzi kwe-Orbitofrontal kwizigulana ezinokuphazamiseka okunyanzelekileyo kunye nezihlobo zazo ezingathintekiyo. Sayensi. 2008a;321: 421-422. [PubMed]
IChamberlain SR, iMenzies L, iSahakian BJ, iFineberg NA. Ukuphakamisa isigqubuthelo kwi-trichotillomania. IJ Psychiatry. I-2007d;164: 568-574. [PubMed]
IChamberlain SR, iMenzies LA, Fineberg NA, Del Campo N, Suckling J, Craig K, et al. Imicimbi yokuphazamiseka grey kwi-trichotillomania: isifundo sokucingela imbonakalo ye-morphometric. Br J Psychiatry. 2008b;193: 216-221. [Inkcazelo yamahhala ye-PMC] [PubMed]
IChamberlain SR, iMuller U, iBlackwell AD, iClark L, iRobbins TW, iSahakian BJ. I-Neocochemical modulection of inhibition inhibition kunye nokufunda kwe-probabilistic ebantwini. Sayensi. I-2006c;311: 861-863. [Inkcazelo yamahhala ye-PMC] [PubMed]
UChamberlain SR, uMuller U, uDeakin JB, uCorlett PR, uDowson J, Cardinal R, et al. Ukunqongophala kweziphumo ezibi zokungabi nasimilo kwisifo sokuqaqanjelwa kwamavolontiya angamadoda aphilayo. J Psychopharmacol. I-2006d;21: 210-215. [PubMed]
IChamberlain SR, iRobbins TW, iSahakian BJ. I-neurobiology ye-ingqalelo-deficit / ukuphazamiseka kwengqondo Biol Psychiatry. 2007e;61: 1317-1319. [PubMed]
IChamberlain SR, iSahakian BJ. I-neuropsychiatry yokunyanzeliswa. I-Curr Opin Psychiatry. 2007;20: 255-261. [PubMed]
Amagumbi eMMS, Atack JR, Carling RW, Collinson N, Cook SM, Dawson GR, et al. I-bioavava yomlomo esebenzayo, ekhethiweyo esebenza ngokungafaniyo kwi-agonist kwindawo ye-benzodiazepine ye-GABAA alpha5 receptors enokwazisa iipropathi. J med Chem. 2004;47: 5829-5832. [PubMed]
I-Chou-Green JM, iHolscher TD, iDallman MF, Akana SF. Ukuziphatha okunyanzeliswayo kwi-5-HT2C receptor knockout mouse. Physiol Behav. 2003;78: 641-649. [PubMed]
UClark L, iRobbins TW, i-Ersche KD, iSahakian BJ. Ukucingiswa kokugxothwa kwabasebenzisi bezinto zangoku kunye zangaphambili. Biol Psychiatry. 2006;60: 515-522. [PubMed]
Clark L, Roiser JP, Cools R, Rubinsztein DC, Sahakian BJ, Robbins TW. Isithintelo sokuphendula umqondiso wokumisa asihlelwanga ngokudodobala kwe-tryptophan okanye i-serotonin transporter polymorphism kumavolontiya aphilayo: iimpembelelo kwithiyori ye5-HT yokuxhonywa. Psychopharmacology (Berl) 2005;182: 570-578. [PubMed]
UClkeke HF, uDalley JW, Crofts HS, Robbins TW, Roberts AC. Ukuguquguquka kwengqondo emva kokudodobala kwangaphambi kokudodobala kweeserotonin. Sayensi. 2004;304: 878-880. [PubMed]
Clarke HF, Walker SC, Crofts HS, Dalley JW, Robbins TW, Roberts AC. Ukudodobaliswa kwangaphambili kwe-serotonin kuchaphazela ukubuyela umva kodwa kungasuki kugqithiso. J Neurosci. 2005;25: 532-538. [PubMed]
Clarke HF, Walker SC, Dalley JW, Robbins TW, Roberts AC. Ukuguquguquka kwengqondo emva kokudodobala kwangaphambili kwe-serotonin kukuziphatha kunye nokuchazwa kwe-neurochemically. Cereb Cortex. 2007;17: 18-27. [PubMed]
I-Cools R.Dopaminergic modulation yengqondo yokusebenza-iimpembelelo zonyango lwe-L-DOPA kwisifo sikaParkinson. Neurosci Biobehav Rev. 2006;30: 1-23. [PubMed]
Ukupholisa R, Altamirano L, D'Esposito M.Ukuguqula ukufunda kwisifo sikaParkinson kuxhomekeke kwimeko yamayeza nakwiziphumo zobundlobongela. Neuropsychologia. 2006;44: 1663-1673. [PubMed]
UCottrell S, Tilden D, Robinson P, Bae J, Arellano J, Edgell E, et al. Uvavanyo oluhleliweyo lweemodeli ngokuthelekisa i-atomoxetine kunye nonyango olunokuvuselela kunyango lwabantwana abanesiphene sokukhathalela / isifo sokungasebenzi kakuhle eUnited Kingdom. Ixabiso lezeMpilo. 2008;11: 376-388. [PubMed]
UCrawford S, uChannon S, uRobertson MM. Isifo sikaTourette: ukusebenza kwiimvavanyo zokuthintela isimilo, inkumbulo yokusebenza kunye nokungcakaza. J Umntwana Psychol Psychiatry. 2005;46: 1327-1336. [PubMed]
I-Crosbie J, Schachar R. Inhibition eyonwele njengophawu lwe-ADHD yosapho. IJ Psychiatry. 2001;158: 1884-1890. [PubMed]
Denys D, Zohar J, Westenberg HG. Indima ye-dopamine kukungaboni kakuhle-ngokunyanzelekileyo: ubungqina bokuqala kunye nonyango. J Clin Psychiatry. 2004;65 (I-Suppl 14: 11-17. [PubMed]
I-Dias R, iRobbins TW, iRobert AC. Ukwahlulahlula kwi-cortex yangaphambili yenguqu ebandakanyekayo kunye neqwalaselo. Uhlobo. 1996;380: 69-72. [PubMed]
I-Evers ye-EA, i-Cools R, uClark L, i-van der Veen FM, uJolles J, uSahakian BJ, et al. Ukuguqulwa kweSerotonergic ye-cortex yangaphambili kwangaphambili ngexesha lokuphendula okungalunganga kwimfundo yokubuyela umva kwe-probabilistic. Neuropsychopharmacology. 2005;30: 1138-1147. [PubMed]
IFineberg NA, Gale TM. Ubungqina obusekwe kwi-pharmacotherapy yesifo sokungaboni kakuhle. Int J Neuropsychopharmacol. 2005;8: 107-129. [PubMed]
IFineberg NA, Saxena S, Zohar J, Craig KJ. 2007a. Ukuphazamiseka okungapheliyo: iingxaki zemida Umvavanyi we-CNS 12I-359-364.364367-375. [PubMed]
IFineberg NA, iSharma P, iSivakumaran T, iSahakian B, iChamberlain SR. Ngaba ukungaphazamiseki okunyanzelekileyo kobuntu kungaphakathi komfanekiso obonakalayo. CNS Spectr. 2007b;12: 467-482. [PubMed]
I-Fineberg NA, Sivakumaran T, Roberts A, Gale T. Yongeza i-quetiapine kwi-SRI kwisifo esinganyangekiyo esinganyangekiyo kunyango: isifundo sonyango esilawulwa ngokungalawulwa. Intlu Clin Psychopharmacol. 2005;20: 223-226. [PubMed]
I-Fong T, i-Kalechstein A, i-Bernhard B, i-Rosenthal R, i-Rugle L. Isilingo esise-olanzapine esiphindwe kabini, esilawulwa i-olanzapine kunyango lwabadlali abangcakazayo be-poker ye-video. Pharmacol Biochem Behav. 2008;89: 298-303. [PubMed]
UFrank MJ, Moustafa AA, Haughey HM, uCurran T, uHutchison KE. Ukusasazwa kofuzo kathathu kutyhila iindima ezininzi zedopamine kwimfundo yokuqinisa. Proc Natl Acad Sci USA. 2007;104: 16311-16316. [Inkcazelo yamahhala ye-PMC] [PubMed]
UGarraux G, uGoldfine A, uBohlhalter S, uLerner A, uHanakawa T, uHallett M. Ukonyusa into engwevu kumbindi wesisu kwi-Tourette's syndrome. Ann Neurol. 2006;59: 381-385. [PubMed]
Gottesman II, Gould TD. Umqondo we-endophenotype kunonyango lwengqondo: i-etymology kunye neenjongo zesicwangciso. IJ Psychiatry. 2003;160: 636-645. [PubMed]
Isibonelelo JE, Odlaug BL, Potenza MN. Ngaba ulikhoboka lokudonsa iinwele? Emnye imodeli ye-trichotillomania ingasiphucula njani isiphumo sonyango. Harv Rev Psychiatry. 2007;15: 80-85. [PubMed]
Isibonelelo JE, Potenza MN. Iinkalo ezinyanzelekileyo zokuphazamiseka okungalawulekiyo. I-Psychiatr Clinic North Am. 2006;29: 539-551. [Inkcazelo yamahhala ye-PMC] [PubMed]
I-Hamidovic A, i-Kang UJ, de Wit H. Iziphumo eziphantsi ukuya kumgangatho ophakamileyo wethamo le-pramipexole kwi-impulsivity kunye nokuqonda kumavolontiya asempilweni. J Clin Psychopharmacol. 2008;28: 45-51. [PubMed]
IHampshire A, Owen AM. Ulawulo lwezinto ezinomdla ezihambelana nomnyhadala onxulumene nomsitho. Cereb Cortex. 2006;16: 1679-1689. [PubMed]
IHarrison AA, i-everitt BJ, iRobbins TW. Ukudodobala kwe-5-HT yeCentral kuphucula ukuphendula okunyanzelekileyo ngaphandle kokuchaphazela ukuchaneka kokusebenza ngocoselelo: ukusebenzisana neendlela zedopaminergic. Psychopharmacology (Berl) 1997;133: 329-342. [PubMed]
I-Hatcher PD, uBrown VJ, Tait DS, Bate S, Overend P, Hagan JJ, et al. I-5-HT6 i-receptor antagonists iphucula ukusebenza kwintsebenzo yokuguqula umsebenzi kwiigundane. Psychopharmacology (Berl) 2005;181: 253-259. [PubMed]
Hollander E, Berlin HA, Bartz J, Anagnostou E, Pallanti S, uSimeon D, et al. 2007a. Isibonisi esinganyanzelekanga: inyanzeliso engacacanga, imbonakalo esebenzayo kunye neziphumo zonyango ziyazisa uhlobo lwe phenotype Inkcazo ye-ACNPIiNzululwazi zeZilumko ze-ACNP 2007 Intlanganiso yoNyaka, i-p50.
Hollander E, Cohen LJ. Ukunyanzeliswa kunye nokunyanzeliswa. I-American Psychiatric Press Inc, eWashington DC; 1996.
Hollander E, DeCaria C, Gully R, Nitescu A, Suckow RF, Gorman JM, et al. Iziphumo zokunyanga okungapheliyo kwe-fluoxetine kwindlela yokuziphatha kunye ne-neuroendocrine kwiimpendulo ze-meta-chlorophenylpiperazine kwisifo esinganyanzelekanga. Psychiatry Res. 1991a;36: 1-17. [PubMed]
Hollander E, DeCaria C, Nitescu A, Cooper T, Stover B, Gully R, et al. Umsebenzi weNoradrenergic kukuphazamiseka okungapheliyo: iimpendulo zokuziphatha kunye neuroendocrine kwi-clonidine kunye nokuthelekisa kulawulo olusempilweni. Psychiatry Res. 1991b;37: 161-177. [PubMed]
I-Hollander E, Kim S, Khanna S, Pallanti S. Ukungaphazamisi okunyanzelekileyo kunye nokuphazamiseka okubukhali okungapheliyo: imiba yokuxilonga kunye nobungakanani. CNS Spectr. 2007b;12 (I-2 Suppl 3: 5-13. [PubMed]
Hollander E, Wong CM. 1995. Ukuphazamiseka okungafunekiyo okubangelwa bubuso J Clin Psychiatry 56(I-Suppl 43-6.6discussion 53-5. [PubMed]
Homberg JR, Pattij T, Janssen MC, Ronken E, De Boer SF, Schoffelmeer AN, et al. Ukusilela kokuhambisa i-Serotonin kumagundane kuphucula ulawulo lwe-inhibitory kodwa kungabi nokuguquguquka kokuziphatha. Eur J Neurosci. 2007;26: 2066-2073. [PubMed]
UHornak J, u-O'Doherty J, uBramham J, uRolls ET, uMorris RG, uBullock PR, et al. Ukubuyela umva okunxulumene nomvuzo emva kokufundwa kotyando kwi-orbito-frontal okanye dorsolateral preortal cortex ebantwini. J Cogn Neurosci. 2004;16: 463-478. [PubMed]
I-Insel TR, uPickar D. Ulawulo lweNaloxone kwisifo esinganyanzelekanga: ingxelo yamatyala amabini. IJ Psychiatry. 1983;140: 1219-1220. [PubMed]
Izquierdo A, Newman TK, Higley JD, Murray EA. Ukuguqulwa kwemfuza ngokuguquguquka kwengqondo kunye nokuziphatha ngokwasentlalweni kwiinkawu ze-rhesus. Proc Natl Acad Sci USA. 2007;104: 14128-14133. [Inkcazelo yamahhala ye-PMC] [PubMed]
UJoel D. Iimodeli zezilwanyana zangoku zokungaboni ngasonye: uphononongo olunzulu. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30: 374-388. [PubMed]
I-Kolevzon A, iMathewson KA, iHollander E. Ukukhetha i-serotonin ukuphinda inhibitors kwi-autism: ukuphononongwa kokusebenza kunye nokunyamezeleka. J Clin Psychiatry. 2006;67: 407-414. [PubMed]
I-Koob GF, i-Le Moal M. Ukuxhatshazwa kweziyobisi: dysregulation ye-hedonic homeostatic. Sayensi. 1997;278: 52-58. [PubMed]
UKrishnan-Sarin S, uReynolds B, uDuhig AM, uSmith A, uLiss T, uMcFetridge A, et al. Ukuziphatha okunyanzelekileyo kuqikelela isiphumo sonyango kwinkqubo yokuyeka ukutshaya kwabatshaya abakwishumi elivisayo. Ukusetyenziswa kotywala kotywala. 2007;88: 79-82. [Inkcazelo yamahhala ye-PMC] [PubMed]
Lapiz-Bluhm MD, Soto-Pina AE, Hensler JG, Morilak DA. Uxinzelelo olungapheliyo lokubanda okungapheliyo kunye nokudodobala kwe-serotonin kukhuthaza ukusilela ekufundeni okuphindaphindayo kuvavanyo lokutshintsha olushukumisayo kwiigundane. Psychopharmacology (Berl) 2009;202: 329-341. [Inkcazelo yamahhala ye-PMC] [PubMed]
U-Li CS, u-Chang HL, u-Hsu YP, u-Wang HS, u-Ko NC. Ukuthintela ukuphendula kweemoto kubantwana abanesifo sikaTourette. J Neuropsychiatry Clin Neurosci. 2006;18: 417-419. [PubMed]
I-Lijffijt M, i-Kenemans JL, i-Verbaten MN, i-van Engeland H. Uphononongo lwe-meta-analytic lokumisa intsebenzo kwi-ingqalelo-deficit / hyperactivity ukuphazamiseka: ulawulo olunqabileyo lwe-inhibitory. J Abnorm Psychol. 2005;114: 216-222. [PubMed]
U-Lynd-Balta E, uHaber SN. Umbutho wolungiselelo lwebelekisi yasesibelekweni kwi-ventral striatum kwisiphelo. Neuroscience. 1994;59: 609-623. [PubMed]
UMasaki D, uYokoyama C, Kinoshita S, Tsuchida H, Nakatomi Y, Yoshimoto K, et al. Ubudlelwane phakathi kwe-neuron kunye ne-cortical 5-HT neurotransmission kunye nokufumana kunye nokubuyela umva ekufundeni komsebenzi wokuhamba / ukungahambi-hamba kumagundane. Psychopharmacology (Berl) 2006;189: 249-258. [PubMed]
McElroy SL, Nelson EB, Welge JA, Kaehler L, Keck PE., Jr Olanzapine kunyango lokungcakaza: J Clin Psychiatry. 2008;69: 433-440. [PubMed]
McIntosh AR, Lobaugh NJ. Uhlaziyo oluncinci lwesikwere sedatha ye-neuroimaging: usetyenziso kunye nokuqhubela phambili. Neuroimage. 2004;23 (I-Suppl 1: S250-S263. [PubMed]
Menzies L, Achard S, Chamberlain SR, Fineberg N, Chen CH, del Campo N, et al. I-endophenotypes ye-Neococitiveitive yesifo sokujonga ngokunyanzelekileyo. Ubunjani. 2007a;130 (Pt 12: 3223-3236. [PubMed]
I-Menzies L, i-Chamberlain SR, i-Laird AR, i-Thelen SM, iSahakian BJ, iBullmore ET. Ukudibanisa ubungqina obuvela kwi-neuroimaging kunye nezifundo ze-neuropsychological zesifo sokubona ukunyanzeliswa: Imodeli ye-orbitofronto-striatal iphinde yaqwalaselwa. Neurosci Biobehav Rev. 2008a;32: 525-549. [Inkcazelo yamahhala ye-PMC] [PubMed]
UMenzies L, u-Williams GB, eChamberlain SR, u-Ooi C, uFineberg N, uSuckling J, et al. Imicimbi emhlophe engalunganga kwizigulana ezinokuphazamiseka okungabonakaliyo kunye nezihlobo zazo zokuqala. IJ Psychiatry. 2008b;165: 1308-1315. [PubMed]
Naqvi NH, Rudrauf D, Damasio H, Bechara A. Umonakalo kwindawo yokuphazamiseka uphazamisa umlutha wokutshaya. Sayensi. 2007;315: 531-534. [PubMed]
Ipaki SB, Coull JT, McShane RH, Ncinci AH, Sahakian BJ, Robbins TW, et al. Ukuzama ukuncipha kwi-Tryptophan kubasebenzi bokuzithandela abaqhelekileyo kuvelisa ukungahambi kakuhle ekufundeni nakwimemori. Neuropharmacology. 1994;33: 575-588. [PubMed]
IPassetti F, iDalley JW, iRobbins TW. Ukususwa kabini kwendlela ye-serotonergic kunye neendlela zokwenza dopaminergic ekusebenzeni ngocoselelo kusetyenziswa umsebenzi onokukhetha isihlanu ngexesha lokuphendula. Psychopharmacology (Berl) 2003;165: 136-145. [PubMed]
Pizzagalli DA, Evins AE, Schetter EC, uFrank MJ, Pajtas PE, Santesso DL, et al. Idosi enye ye-dopamine agonist iphazamisa ukuqiniswa kokufunda ebantwini: ubungqina bokuziphatha okuvela kumlinganiso osekwe elabhoratri wokuphendula komvuzo. Psychopharmacology (Berl) 2008;196: 221-232. [Inkcazelo yamahhala ye-PMC] [PubMed]
Potenza MN. Ukunyanzeliswa kunye nokunyanzeliswa ekungcwabeni kwe-pathological kunye nokuphazamiseka okungabonakaliyo. I-Bra Bras Psiquiatr. 2007a;29: 105-106. [PubMed]
Potenza MN. Ukwenza okanye ukungakwenzi? Ubunzima bokulutha, ukushukumisela, ukuzeyisa, kunye nokungxamiseka. IJ Psychiatry. 2007b;164: 4-6. [PubMed]
Potenza MN, Leung HC, Blumberg HP, Peterson BS, Fulbright RK, Lacadie CM, et al. Isifundo se-FMri Stroop sokwenza umsebenzi we-ventromedial wangaphambili we-cortical kubagembuli be-pathological. IJ Psychiatry. 2003a;160: 1990-1994. [PubMed]
Potenza MN, Steinberg MA, Skudlarski P, Fulbright RK, Lacadie CM, uWilber MK, et al. Ukungcakaza kukhuthaza ukugembula kwendawo: uvavanyo lokucinga ngemagneti. Arch Gen Psychiatry. 2003b;60: 828-836. [PubMed]
I-Poyurovsky M, uFaragian S, uShabeta A, uKosov A. Thelekisa iimpawu zeklinikhi, ukuqina kwonyango kunye ne-pharmacotherapy kwizigulana zekrizophrenia yezigulana ezingena kwaye zingaphazamiseki. Psychiatry Res. 2008;159: 133-139. [PubMed]
Reuter J, Raedler T, Rose M, Isandla I, Glascher J, Buchel C. Ingxaki yokungcakaza inxulumene nokuncitshiswa kwenkqubo yomvuzo we-mesolimbic. Nat Neurosci. 2005;8: 147-148. [PubMed]
Robbins TW. Umsebenzi we-5-wokukhetha ngokulandelelana wexesha lokuphendula: yokuziphatha kweekhemikhnoloji kunye ne-neurochemistry esebenzayo. Psychopharmacology (Berl) 2002;163: 362-380. [PubMed]
Robbins TW. Ukutshintshela kunye nokuma: i-subonto-ye-fronto-striatal, imodemophylical modochemical kunye neziphumo zeklinikhi. I-Philos Trans Trans R Soc Lond B Biol Sci. 2007;362: 917-932. [Inkcazelo yamahhala ye-PMC] [PubMed]
URobinson TE, iBerridge KC. Isiseko se-neural sokukhanga izidakamizwa: intsholongwane yokukhuthaza ukunyanzela. Ubungqina Bombongo Ubungqina Bobuxoki. 1993;18: 247-291. [PubMed]
Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, et al. I-Tryptophan depletion impairs yokuvuselela-umvuzo wokufunda ngelixa i-methylphenidate iphazamisa ukulawula kwengqwalaselo kubantu abadala abancinci abanempilo: iimpembelelo zesiseko se-monoaminergic yokuziphatha engxamisekileyo. Psychopharmacology (Berl) 1999a;146: 482-491. [PubMed]
Rogers RD, Everitt BJ, Baldacchino A, Blackshaw AJ, Swainson R, Wynne K, et al. Ukusilela okungahambelaniyo kwisigqibo sokuthathwa kwezigqibo zabaxhaphazi abaphethe i-amphetamine, abaxhaphazi be-opiate, abaguli abanomonakalo ogqalileyo kwi-cortex yangaphambili, kunye ne-tryptophan-iphelise amavolontiya aqhelekileyo: ubungqina beendlela ze-monoaminergic. Neuropsychopharmacology. 1999b;20: 322-339. [PubMed]
URubia K, Smith AB, Brammer MJ, Taylor E. ekunene ongaphambi kwangaphambi kwecortex cortex uxolelanise ukuziphendulela ngelixa i-mesial pre kwangaphambilial cortex inoxanduva lokuchaphazeleka kwimpazamo. Neuroimage. 2003;20: 351-358. [PubMed]
Schilman EA, Uylings HB, Galis-de Graaf Y, Joel Joel, Groenewegen HJ. Icortex ye-orbital kwiirati ngokweeprojekthi zeendawo ezithile kumbindi we-caudate-putamen tata. Neurosci Lett. 2008;432: 40-45. [PubMed]
I-Schultz W. Ukufumana ngokusesikweni nge-dopamine kunye nomvuzo. Neuron. 2002;36: 241-263. [PubMed]
I-Seymour B, iDaw N, i-Dayan P, i-Singer T, i-Dolan R. Ukufakelwa okungafaniyo kokulahleka kunye nokufumana kwi-striatum yabantu. J Neurosci. 2007;27: 4826-4831. [Inkcazelo yamahhala ye-PMC] [PubMed]
UStein DJ, uChamberlain SR, uFineberg N. Imodeli yeABC yokuphazamiseka kwemikhwa: ukutsalwa kweenwele, ukukhetha isikhumba, kunye nezinye iimeko zestereotypic. CNS Spectr. 2006;11: 824-827. [PubMed]
I-Stein DJ, iHollander E. Ukuphazamiseka okunyamekileyo okunyanzelekileyo. J Clin Psychiatry. 1995;56: 265-266. [PubMed]
Szeszko PR, Ardekani BA, Ashtari M, Malhotra AK, Robinson DG, jpg iRM, et al. Izinto ezingalunganga kwimicimbi emhlophe ekuphazamisekeni okungafunekiyo: uphononongo lokucinga lokuphambuka. Arch Gen Psychiatry. 2005;62: 782-790. [PubMed]
Talbot PS, Watson DR, Barrett SL, Cooper SJ. Ukukhawuleza kwe-tryptophan depletion kuphucula ukuthathwa kwezigqibo kubantu abaphilayo ngaphandle kokuchaphazela ukubuyela umva kokufunda okanye ukuseta ukutshintsha. Neuropsychopharmacology. 2006;31: 1519-1525. [PubMed]
I-Tsaltas E, Kontis D, Chrysikakou S, Giannou H, Biba A, Pallidi S, et al. Ukunyanzeliswa kwakhona kotshintsho lwemozulu njengemodeli yezilwanyana yokuchaphazeleka okungafunekiyo (OCD): uphando lwe-5-HT2C kunye ne-5-HT1D receptor inxaxheba kwi-OCD pathophysiology. Biol Psychiatry. 2005;57: 1176-1185. [PubMed]
van der Plasse G, Feenstra MG. Ukubuyela umva kwesifundo kunye nokuphelelwa ngamandla kwe-tryptophan depletion. Behav Brain Res. 2008;186: 23-31. [PubMed]
Iirisk RP. Ukuqikelelwa okwahlukileyo kwe-infralimbic kunye ne-prelimbic cortex kumgangatho. Synapse. 2004;51: 32-58. [PubMed]
Volkow ND, Fowler JS, Wang GJ. Izifundo zokulinganisa kwindima ye-dopamine ekuqiniseni i-cocaine kunye nokulutha ebantwini. J Psychopharmacol. 1999;13: 337-345. [PubMed]
I-Walker SC, iRobbins TW, iRobert AC. Igalelo lokwahlula i-dopamine kunye ne-serotonin kwi-orbitofrontal cortex yomsebenzi kwi-marmoset. Cereb Cortex. 2009;19: 889-898. [Inkcazelo yamahhala ye-PMC] [PubMed]
Watkins LH, Sahakian BJ, Robertson MM, Veale DM, Rogers RD, Pickard KM, okqhubekayo. Umsebenzi wokulawula kwisifo sikaTourette kunye nokuphazamiseka okungafunekiyo. Psychol Med. 2005;35: 571-582. [PubMed]
I-Westenberg HG, i-Fineberg NA, i-Denys D. I-Neurobiology yesifo esinganyanzelekanga: serotonin nangaphaya. CNS Spectr. 2007;12 (I-2 Suppl 3: 14-27. [PubMed]
IWinstanley CA, Chudasama Y, Dalley JW, Theobald DE, Glennon JC, Robbins TW. I-Intra-pre-prealal 8-OH-DPAT kunye ne-M100907 iphucula ukubonwa okubonakalayo kunye nokunciphisa ukunyanzeliswa kwimisebenzi ye-serial ye-serial reaction time kumagundane. Psychopharmacology (Berl) 2003;167: 304-314. [PubMed]
IWinstanley CA, i-Eagle DM, iRobbins TW. Iimodeli zokuziphatha zokungxamiseki ngokunxibelelene ne-ADHD: uguqulelo phakathi kwezifundo zeklinikhi kunye naphambi kokuba kufundwe. Clinic Psychol Rev. 2006;26: 379-395. [Inkcazelo yamahhala ye-PMC] [PubMed]
IWinstanley CA, iTheobald DE, i-Dalley JW, iGlennon JC, iRobbins TW. I-5-HT2A kunye ne-5-HT2C ye-receptor antagonists ineziphumo ezichasayo kumlinganiso wokungahambelani: ukusebenzisana nokupheliswa kwe5-HT yehlabathi. Psychopharmacology (Berl) 2004;176: 376-385. [PubMed]
Ulumkile RA. Ukujikeleza komvuzo wobongo: ukukhanya okuvela kwizikhuthazi ezingafakwanga. Neuron. 2002;36: 229-240. [PubMed]
Umbutho WezeMpilo Wehlabathi Ulwahlulo lwehlabathi lweZifo, i10th edition (ICD-10) Umbutho wezeMpilo weHlabathi, eGeneva; 1992.
U-Yucel M, uHarrison BJ, u-Wood SJ, u-Fornito A, u-Wellard RM, u-Pujol J, et al. Ukuguqulwa kokusebenza kunye ne-biochemical ye-cialex yangaphambili ye-medial kwiphazamiso-ngokunyanzelekileyo. Arch Gen Psychiatry. 2007;64: 946-955. [PubMed]
UZack M, Poulos CX. Umchasi we-D2 uphucula iziphumo ezinomvuzo kunye nezokuncoma kwesiqephu sokungcakaza kubagembuli be-pathological. Neuropsychopharmacology. 2007;32: 1678-1686. [PubMed]
UZohar J, Insel TR, Zohar-Kadouch RC, Hill JL, Murphy DL. Ukuphendula kweSerotonergic kukungaboni kakuhle. Iziphumo zonyango olungapheliyo lwe-clomipramine. Arch Gen Psychiatry. 1988;45: 167-172. [PubMed]