Ho nahana ka litlhōlisano tse qobelloang le tse ferekanyang maikutlo, ho tloha ho liphoofolo tsa mefuta ea liphoofolo ho ea ho Endophenotypes: Tlhahlobo e Khutšoanyane (2010)

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

E phatlalalitsoe marang-rang Nov 25, 2009. Doi:  10.1038 / npp.2009.185

PMCID: PMC3055606

Sehlooho sena se bile teng e boletsoeng ke lihlooho tse ling ho PMC.

inahaneloang

Ho sitoa ha taolo ea "cortical control" ea li-circuits tsa fronto-striatal ho ka tsamaisa liketso tse potlakileng le tse qobelloang. Thutong ena e phetoang, re hlahloba boits'oaro bona ho tloha ka pono ea mekhoa ea neural mme re sheba hore na mekhoa ena le mekhoa ea neural e kenya letsoho joang ho mafu a kelello joalo ka ho senyeha hoa kelello (OCD), bofokoli bo amang botho le bofokoli ba taolo joalo ka. trichotillomania le ho becha ka methapo ea kutlo. Re hlahisa liphumano tse tsoang lipakeng tsa tlhaiso-leseling e akaretsang, e nang le lipatlisiso tsa phetolelo le phethoho ea batho ba liteko tsa bongaka, ho tsepamisa maikutlo lipapatsong tse tšoanang, tse arohaneng, cortico-striatal neural, ho tloha orbitof Pambal cortex (OFC) ho medial striatum (caudate nucleus), e khothalletsoang ho khanna tšebetso e qobelloang, le ho tloha anterior cingrate / ventromedial preortal cortex ho ea ventral striatum (nucleus accumbens shell), e khothalletsoang ho khanna ts'ebetso e sa tsitsang, le tšebelisano lipakeng tsa tsona. Re fana ka maikutlo a hore ho susumetsa le ho qobelloa ho bonahala e le mefuta e mengata. Boitšoaro bo susumetsang kapa bo qobelloang bo kopantsoe ke ho fetellana le likarolo tse ikhethileng tsa neural. Trichotillomania e kanna ea arohana le taolo ea taolo ea litšusumetso tsa makoloi, athe papali ea chelete ea ho becha e kenyeletsa moputso o sa tloaelehang oa meputso e e khethollang haufi le ts'ebeliso ea lithethefatsi. OCD e bonts'a ho ts'oaroa le ho qobelloa ha makoloi, mohlomong ho kenelletsoeng ka tšitiso ea potoloho ea OFC-caudate, hammoho le likhokahano tse ling tsa pele, cingulate le parietal. Serotonin le dopamine lia sebelisana ho potoloha lisekhete tsena ho feto-fetola maemo a ho arabela ka tsela e sa potlakileng le e qobelloang le ha lits'ebetso tse sa tsejoeng tsa boko li kanna tsa ba le mesebetsi ea bohlokoa. Ts'ebeliso e etselitsoeng ea mesebetsi ea methapo-kutlo, li-receptor tse ikhethang tsa li-neurochemical, le mekhoa ea boko ea ts'ebetso ea bokhoni ba bokhoni ba ho etsa lipatlisiso nakong e tlang lefapheng lena.

Keywords: e qobelloang, e qobelloang, e leng endophenotypes, serotonin, dopamine

SELELEKELA

Ha liketso tse nang le tšusumetso e matla kapa tse qobelloang li ka tlatsetsa molemong oa boiqapelo le mamello mme ka kakaretso e le ho feto-fetoha ha boitšoaro ba motho, taolo e sa sebetseng ea boits'oaro bo hlephileng kapa bo qobelloang e ka amahanngoa le litlamorao tse mpe mme ea ba le tšebetso kholisong ea lefu la kelello. Ho se tsotelle ho ka hlalosoa e le 'mokhoa oa ho itšoara ka potlako, o sa reroang liketsong tsa kahare kapa tsa kantle ka ho fokotseha ha litlamorao tsa litlamorao tsena ho motho ea susumetsoang kapa ho ba bang' (Chamberlain le Sahakian, 2007; Potenza, 2007b). Ho fapana le hoo, ho qobelloa ho emela tloaelo ea ho etsa lintho tse sa khahliseng ka mokhoa o tloahelehileng kapa o ts'oaroang ho thibela litlamorao tse sa lebelloang, tse lebisang ho oeng mosebetsing (WHO, 1992; Hollander le Cohen, 1996; Chamberlain et al a, 2006b). Matšoao ana a mabeli a ka nkoa e le a hanyetsanang ka mokhoa o fapaneng, kapa ka mokhoa o ts'oanang, ka mokhoa o ts'oanang, ka hore e 'ngoe le e' ngoe e fana ka maikutlo a ho hloka taolo ea taolo ea tšusumetso (Stein le Hollander, 1995). E 'ngoe le e' ngoe e ka kenyelletsa phetoho lipakeng tsa lits'ebetso tse fapaneng tsa neural, ho kenyelletsa tlhokomelo, kutlo, le ho hokahanya likarabo tsa makoloi kapa tsa kelello.

Mefuta ea Neuroanatomical e hlahisa boteng ba lipotoloho tsa "compulsive" le "impulsive" tsa "cortico-striatal" tse arotsoeng ka mokhoa o fapaneng ke li-neurotransmitters (Robbins, 2007; Brewer le Potenza, 2008). Potolohong e qobelloang, karolo ea "striatal elementus" (caudate nucleus) e ka tsamaisa boits'oaro bo potlakileng le karolo ea pele (orbitofrontal cortex, OFC) e ka fana ka taolo ea inhibitory holim'a bona. Ka mokhoa o ts'oanang, potolohong e sa tsitsang, karolo ea "striatal element" (ventral striatum / nucleus accumbens shell) e ka tsamaisa boits'oaro bo sa tsotelleng le karolo ea pele (anterior cingulate / ventromedial prefrontal cortex, VMPFC) e ka fana ka taolo ea thibelo. Kahoo, mohlaleng ona, ho na le bonyane lipotoloho tse peli tse tsamaeang ka bonoko (e le 'ngoe e qobelloang le e' ngoe e susumetsang) e tsamaisang boitšoaro bona, le lipotoloho tse peli tse tsamaellanang tsa pele tse khutlisang boitšoaro bona. Hyperacaction kahare ho likarolo tsa "striatal" kapa lintho tse sa sebetseng hantle (mohlomong hypoactivity) likarolong tse pele li ka baka tšekamelo e atileng ea ho etsa boits'oaro bo potlakileng kapa bo hatelletsang, ho latela karolo e tlase e hlorisoang. Litšitiso tse ling tse ka bang teng mekokotlong ea cortico-striatal (mohlala, e amanang le ts'ebetso e fokolitsoeng ea ts'ebetso ea litheko) le tsona li ka kenya letsoho boits'oarong bo bonahala bo sa susumetse kapa bo qobellehang nakong ea ho etsa boits'oaro bo amanang le moputso. Li-pathologies tsena li ka hlahlojoa ho sebelisoa mesebetsi ea ts'ebeliso ea kelello e kenang mesebetsing ena le / kapa ka lithuto tse inahaneloang tse lekanyang tšebetso ho litsamaiso tsena tsa neural. Phapang pakeng tsa lits'ebetso tsena tse sebetsang, e le hore se qalang e le bothata potolohong e sa qoseng se ka qetella e le bothata seterekeng se qobelloang mme ka lehlakoreng le leng, se ka kenya letsoho moetlong o sa qobelloang-o qobelloang oa tlhahiso-leseling o khothalletsoang ke Hollander and Wong (1995) (Brewer le Potenza, 2008).

Ho na le mathata a itseng a kelello ao ho ona boits'oaro bo potlakileng le bo qobelloang bo bonahalang, bonyane ka mabaka a phenotypic, e le eona ntho ea mantlha le e kotsi haholo. Ts'oaetso ena e atisang ho ba bonolo, eo hajoale e arotsoeng ka mekhahlelo e mengata ea tlhahlobo ea DSM-IV-TR (APA), e kenyelletsa boloetse ba "obsessive-compulsive" (OCD), lefu la 'mele dysmorphic, lefu la Tourette, trichotillomania, lefu la tlhokomelo ea khatello ea kelello (ADHD), papali ea chelete ea papali ea chelete, le ho lemalla lithethefatsi (SAs). Hoa thahasellisa hore autism e khetholloa ka boitšoaro bo qobelloang (e le e 'ngoe ea libaka tse tharo tsa matšoao a mantlha) hammoho le boits'oaro ba ho se tsotelle (e le se seng sa libaka tse amanang le matšoao).

Ka tloaelo, mathata a qobelloang le a susumetsang maikutlo a bonoe ka lehlakoreng le leng; ea pele e khannoa ke takatso ea ho qoba kotsi 'me ea morao ke boits'oaro ba ho batla moputso. Leha ho le joalo, bopaki bo fetohang bo tsoang liphuputsong tsa phetolelo bo fana ka maikutlo a hore tloaelo e arolelanoang ea boits'oaro ba boits'oaro, mohlomong e bakoang ke ho hloleha ha taolo ea 'top-down' ea taolo ea lipotoloho tsa fronto-striatal, kapa ho fapana le ho sebetsa haholo ka har'a lipotoloho tsa striatal, e kanna ea ts'ehetsa mathata a ho hlohlelletsa le a qobelloang . Kahoo, ho fapana le ho fapana le polar, ho qobelloa le ho se tsotelle ho ka supa lintlha tsa bohlokoa tsa orthogonal tseo e 'ngoe le e' ngoe e tlatsetsang maemong a fapaneng mathateng ana.

Boholo ba mathata ana a hlaha hammoho, ebang ke a motho a le mong kapa likhohlano ka har'a malapa, a fanang ka maikutlo a hore ho na le mekhoa ea ho arolelana lintho tse ling (Hollander et al a, 2007b). Ho feta moo, ho na le bopaki ba ho ata ha karabelo ea kalafo ho pholletsa le mathata a itseng. Ka tloaelo OCD e araba li-serotonin reuptake inhibitors (SRIs; clomipramine le SRIs tse khethiloeng, SSRIs) le li-SSRIs tse kopaneng le li-antipsychotic agents (Fineberg et al a, 2005). Li-antipsychotic li emela kalafo ea mohala oa pele bakeng sa lefu la Tourette's, ka hona, hoa thabisa hore kopanyo ea bona le li-SSRI e bonts'a katleho e kholo ho OCD e amanang le tic.Bloch et al a, 2006). Matšoenyeho a amanang le mathata a lefu la autistic le 'ona a ka araba karabo ea SSRI ea boemo bo tlase le li-antipsychotic (Kolevzon et al a, 2006). Trichotillomania e kanna ea arabela ho li-SRI le li-antipsychotic, leha ho le joalo netefatso lithutong tse laoloang e hlokahala (Chamberlain et al a, 2007d). ADHD, ka lehlakoreng le leng, e arabela li-inaditors tsa noradrenergic reuptake inhibitors hammoho le li-dopaminergic agents (mohlala, amphetamine), ts'ebetso ea papali ea tšebeliso ea mali le mathata a tlhekefetso ea lithethefatsi le tsona li ka arolelana karabelo ea kalafo ho bahanyetsi ba opiate (Brewer et al a, 2008).

Kabo ea sesosa le phello, ho sebelisa lintlha tsa bongaka feela, e ka ferekanngoa ke bongata ba libaka tse amanang le matšoao tse hlahang ka har'a mathata a kelello. Ho joalo, sehlopha sena sa mathata se khetholloa ke phenotypic heterogeneity le ho kopana ho hoholo. Mohlala, linyeoe tse ling tse nang le autism ha li bontše matšoao a ADHD kapa boits'oaro bo qobelloang, tse ling li bonts'a ADHD, tse ling OCD, empa tse ling li bonts'a boits'oaro ba makoloi a pheta-phetoang a sa ts'oaneng le OCD. Patlisiso ea phetolelo e etsa lipatlisiso ho latela mokhoa oa metheo, mme ka hona e ka khona ho supa menehelo ea methapo e tsamaisang likarolo tse itseng tsa lefu la kelello. Li-endophenotypes li ka lekanngoa, litšoaneleho tse fumanehang, tse ipolelang hore li maemong a mahareng lipakeng tsa phenotype ea kliniki le genotype ea ts'oaetso ea mafu. Li-phenotypes tse joalo tsa "lipakeng" li nahanoa hore li amana ka kotloloho le kotsi ea lefutso bakeng sa mathata a kelello a polygen ho feta boits'oaro bo bontšitsoeng ke lingaka (Gottesman le Gould, 2003; Chamberlain le Menzies, 2009). Mehlala ea lefu lena la Endophenotypic e ka re thusa ho hlakisa kutloisiso ea rona ea motheo ea liphatsa tsa lefutso tse rarahaneng, mme ka hona, ho tsebisa tlhahlobo ea lefutso. Hajoale, mathata a susumetsang le a qobelloang a khethollotsoe ka mekhahlelo e arohaneng ea DSM-IV. Ha Mokhatlo oa Amerika oa Psychiatric o nka ho hlophisoa botjha ha OCD, mathata a ho tšoenyeha le mathata a taolo ea tšusumetso (ICDs) bakeng sa ntlafatso e tlang ea DSM-V (Fineberg et al a, 2007a), ke ka nako e loketseng ho lekola mekhoa e ts'ebetso ea mathata ana.

Thutong ena e phetoang, re nka mekhoa ea neural le neuropsychological e amanang le liketso tse susumetsang le tse qobelloang le tlatsetso ea bona mehlaleng ea bofokoli bo susumetsang. Re bokella liphumano tse nepahetseng mabapi le tlhaiso-leseling e pharaletseng ea data e tlatselletsang, e nang le lithuto tse fetisitsoeng tse sa fetoleloang, patlisiso ea motho ea morao-rao, le liteko tsa kalafo ea bongaka, ho kenyelletsa mosebetsi o tsoelang pele ho tsoa lihlopheng tsa rona tsa United Kingdom le United States. Bohlahlobi ba rona bo shebane le ho hlahloba ho lekana, ho arohantsoeng ka mokhoa o hlakileng, oa cortico-striatal neural projeke ho tsoa ho OFC ho ea medial striatum (caudate nucleus), e khothalletsoang ho khanna ts'ebetso e qobelloang, le ho tloha anterior cingulate / VMPFC ho ea ventral striatum (khubung ea bokaholimo ba nucleus) ho khanna tšebetso e sa qoseng, le lipuo tse mahareng tsa bona (Robbins, 2007; Brewer le Potenza, 2008) (Setšoantšo sa 1).

Setšoantšo sa 1  

Ho qobelloa le ho se kenelle: lits'ebetso tsa neural tse kenyang li kenya letsoho ho mafu a kelello. Leha mathata a hohelang le a qobelloang a ka nkoa e le bohanyetsi ba polar, ho hloleha taolong ea cortical ea li-circuits tsa fronto-striatal neural ho ka tsamaisa bobeli ...

Re sebelisa lintlha tsena, re leka ho araba lipotso tsa bohlokoa ho kenyelletsa: (i) ho qobelloa le ho se kenelle ho tlatsetsa hakae likhathatsong tsena, (ii) li itšetleha hakae ho li-circinal tsa neural, kapa (ii) li-genaminergic tse arolelanang? methapo, (iv) na likarolo tsa boitšoaro tse sa tsotelleng kapa tse qobelloang li na le boleng bofe kapa bofe ba tsoelo-pele bo amanang le kalafo ea bongaka, 'me (v) na ho na le sebopeho se kopanyang se amohelang data ee ka botlalo? Re boetse re lebisa tlhokomelo holima menyetla ea lipatlisiso tsa nako e tlang tseo re lumelang hore li ka nts'etsa pele tšimo ka botlalo.

LITLHODU TSA BOPHELO TSE BONAHALANG LE BOPHELO

Liteko tsa morero tse amanang le methapo ea kutlo li na le monyetla oa ho hlakisa mekhoa eo li-pharmacological agents li fanang ka litlamorao tsa eona tsa kliniki le ho bolela esale pele sephetho sa tleliniki (Chamberlain et al a, 2007e; Brewer le Potenza, 2008). Re sebelisa mesebetsi e amanang le methapo e meng e amanang le "neurocognitive", ho susumetsoa le ho qobelloa ho ka aroloa ka likarolo tse ikhethileng le tse ka hlalosoang ka mokhoa o nepahetseng bathong ba batho le liphoofolo tse lekang, ka likarolo tse ikhethileng tse kenyeletsang likarolo tse ka se kopaneng tsa potoloho ea methapo ea methapo (Winstanley et al a, 2006).

Boitsebiso bo bontša hore ho hloka matla ho ka tsoa mekhoeng e le 'ngoe kapa tse ling tse arohaneng tsa methapo ea kutlo. Tsena li kenyelletsa tloaelo ea tšebeliso ea motlakase oa pre-potent motor, e lekantsoeng ke mosebetsi oa ho emisa ka lets'oao la ho emisa (SSRT) (Aron le Poldrack, 2005), e kopantsoeng le batho ka ho kenella cortex e nepahetseng e ka tlase-pele (RIF) le likhokahano tsa eona tsa subcortical (Rubia et al a, 2003) mme e fetotsoe literekeng le bathong ba motho ka norepinephrine (Chamberlain et al a, 2006c, 2007a; Cottrell et al a, 2008), empa eseng serotonin (Clark et al a, 2005; Chamberlain et al a, 2006d). Karolo e 'ngoe e kenyelletsa bothata ba ho lieha ho khotsofatsa le ho khetha meputso e menyenyane kapele le ha e na le litlamorao tse mpe tsa nako e telele, e lekantsoeng ke ho nka liqeto kapa mesebetsi ea papali ea chelete e kang Cambridge Gossip Task (CANTAB), e kopantsoeng le ho potoloha le ho potoloha ka kotloloho ka tšohanyetso ea potoloho ea serotonergic (Rogers et al a, 1999b), le potoloho ea subcortical tlasa taolo e kopaneng ea dopaminergic le serotonergic (Winstanley et al a, 2006). Karolo ea boraro e na le sampole ea tlhaiso-leseling e lekaneng pele u etsa khetho, e lekantsoeng ka mehlala ea mehlala ea tlhahisoleseling joalo ka Reflection Task (Clark et al a, 2006) mme mohlomong 5-Choice seri Reaction Time Task (5-CSRTT) (Robbins, 2002) (Lethathamo 1).

Lethathamo 1  

Ho Iphetetsa Ho Ikamahanya le ho Qobella ho ea ka Sebaka sa Neurocognitive: Mesebetsi le li-Neural / Neurochemical Correlates

Mohlomong ho qobelloa ho utloisisoa hamolemo. Ho sitoa ho (i) ho ithuta ka mokhoa o feto-fetohang (ke hore, bokhoni ba ho feto-fetola boitšoaro kamora ho fana ka maikutlo a fosahetseng, a lekantsoeng ke mesebetsi e meng e fetoloang ea ho ithuta) le (ii) ho feto-fetoha ha maikutlo ka mokhoa o fetelletseng, e mong le e mong a ka kenya letsoho ho hlahiseng polelo ea hae (Matsatsi et al a, 1996; Clarke et al a, 2005). Lits'oaetso tsena ka bobeli ke karolo ea bosholu ba kelello, empa e 'ngoe le e' ngoe e bonahala e ts'ehelitsoe ke potoloho e fapaneng ea neural.

Ho ithuta ka morao-rao ho sithabetsoa ke marapo ho OFC (empa eseng dorsolateral preortal cortex, DLPFC) mefuta eohle (Matsatsi et al a, 1996; Berlin et al a, 2004; Hornak et al a, 2004; Boulougouris et al a, 2007). Bophelong ba batho, OFC e sebetsa ka mokhoa o ikhethileng nakong ea thuto e feto-fetohang (Hampshire le Owen, 2006). Ho fapana le hoo, marang-rang a morao-rao a PFC a sitisa ho feto-fetoha ha maemo ho li-primates (Matsatsi et al a, 1996), 'me bathong ts'ebetso ea motho e tsamaisana le ts'ebetso e khethiloeng ea bilatal ventrolateral prefrontal cortex (VLPFC) (Hampshire le Owen, 2006) (Lethathamo 1).

Hona joale ho na le bopaki bo bongata bo hokahanyang thuto le phetoho ea 5-HT, ho kenyeletsoa le litonong (Masaki et al a, 2006; Boulougouris et al a, 2008; Lapiz-Bluhm et al a, 2009),Clarke et al a, 2004, 2005; Walker et al a, 2009), le batho (Park et al a, 1994; Rogers et al a, 1999a; Evers et al a, 2005) e thehiloe ho litlolo tsa meriana, methapo ea kutlo le lijo, le bopaki ba liphatsa tsa lefutso ho litšoene tsa rhesus (Izquierdo et al a, 2007). Ka kakaretso, ho fokotsa serotonin ea boko, haholo-holo libakeng tse ikhethang tse kang OFC (mohlala Clarke et al a, 2004), e sitisa ho ithuta ho pheta-pheta. Tsamaiso ea tsamaiso ea mohanyetsi oa li-receptor tsa 5-HT-2A e boetse e bontšitsoe ho sitisa ho ithuta ho feteletseng ha sebaka (Boulougouris et al a, 2008). Xagio ea 5-HT6 receptor antagonist e boetse e bontšitsoe ho ntlafatsa ho ithuta ka morao-rao le ho feto-fetoha ha maikutlo lithupeng (Hatcher et al a, 2005). Leha ho le joalo, ho bile le liphoso tse itseng tsa ho fumana litlamorao ho ho feto-fetoha ha thuto, hangata kamora ho putlama ha tryptophan, bathong ba batho (Talbot et al a, 2006) le likhoto (van der Plasse le Feenstra, 2008), le khaello ea transotter ea serotonin ho litoeba le eona ha e bonahale e ama phetoho e bonolo ea sepakapaka (Homberg et al a, 2007).

5-HT2 RECEPTOR SUBTYPES E KA BA LITLHAKISO TSA BOPHELO

Phapang e mengata ea li-receptor tsa 5-HT e se e sibolotsoe eo ligands tse ikhethang li ntseng li le tlasa nts'etsopele. Bopaki ba pele ho lithuto tsa liphoofolo le tsa batho bo bontša ts'ebetso bakeng sa li-receptors tsa 5-HT2 ka boitšoaro bo hatelletseng. Li-receptors tsa Transgenic tse haelloang ke 5-HT2C receptors li etsa mekhoa e qobelloang ea boits'oaro e hlahisang mohlala o hlakileng oa OCD (Chou-Green et al a, 2003). Leha ho le joalo, ho na le ts'isinyeho e hlakileng ea datha e fumanoeng tokisong ena ea liphatsa tsa lefutso le datha tse ling, mohlomong ka lebaka la lits'ebetso tse qobelloang tse qapiloeng ka har'a tokisetso ea transgenic, hobane data ea morao-rao ea pharmacological e bonts'a ho se ts'oane ho fumanang hore 5-HT2C activation activation e tsamaisana le ho qobelloa ho eketsehileng. Ka hona, ho mofuta oa moputso oa litekanyetso tsa T-maze o atlehileng oa OCD, Tsaltas et al a (2005) e fumane hore tsamaiso ea m-chlorophenylpiperazine (mCPP), agonist e kopaneng ea serotonin e nang le litlamorao tsa 5-HT2C e eketsehile ho phehella kapa ho qobelloa ho araba, athe ho iketsa eka o na le SSRI (fluoxetine), empa eseng benzodiazepine kapa desipramine, ho felisitse litlamorao tsa mCPP. Phephetso le 5-HT1B receptor agonist naratriptan e ne e se na phello ea ho qobelloa kahare ho mohlala ona, e fana ka tlhahiso ea ts'ebetso e itseng bakeng sa 5-HT2C receptor, e kanna ea laoloa ke kalafo e sa foleng ea SSRI. Ho bakuli ba OCD, phephetso e matla ea lithethefatsi le mCPP e hlahisang letšoao la OCD le feteletseng (Hollander et al a, 1991b). Matla ana a boetse a tumisoa ka ho qhekella ka fluoxetine (Hollander et al a, 1991a) le clomipramine (Zohar et al a, 1988). Ho feta moo, tumellanong le liphetho tsena. Boulougouris et al a (2008) o fumane hore 5-HT2C antagonist e ntlafalitse thuto e ntlafalitsoeng. Ka lehlakoreng le leng, ts'ebetso ea li-receptor tsa 5-HT2A ea pele e rerile ho tšehetsa ts'usumetso e matla ea li-SSRIs (Westenberg et al a, 2007). Li-antipsychotic tsa moloko oa bobeli li ka mpefatsa boitšoaro bo khothalletsang ho bakuli ba nang le lefu la kelello, 'me ho reriloe hore sena se etsahala ka ho qhekella ho matla ha 5-HT2A (Poyurovsky et al a, 2008), leha dopamine (DA) antagonism e emela mochine o mong o ka khonehang. Ho feta moo, li-antipsychotic tsa moloko oa bobeli le oa pele li bonts'a katleho ea bongaka ha li kopantsoe le li-SSRIs ho OCD (Fineberg le Gale, 2005), mohlomong ka ho eketsa tšebetso ea DA kahare ho cortex e ka pele (Likhathatso et al a, 2004).

HO FIHLELA PHARMACOLOGICAL HO BONAHALA LE BOPHELO; RELEBOHILE MAHALA

Mefuteng ea liphoofolo, ho khethollleha ho makatsang lipakeng tsa litlamorao tsa 5-HT2A le 5-HT2C lihanyetsi tsa receptor ka mehato ea ho susumetsoa le ho qobelloa ho hlokometsoe. Ho 5-CSRTT, tsamaiso ea methapo ea mohopolo oa 5-HT2C receptor antagonist (SB24284) e mpefalitse ts'usumetso e ntlafalitsoeng ka tloaelo e bonoang kamora ho putlama ha 5-HT ea lefats'e e hlahisitsoeng ke intracerebroventricular tsamaiso ea 5,7-dihydroxytrypt; ntlafatso e ts'oanang e amanang le SB24284 ho impulsivity e ile ea bonoa ho litoeba tse tsamaeang le sham (Winstanley et al a, 2004). Ka lehlakoreng le leng, tsamaiso ea methapo ea selekane ea 5-HT2A e khethiloeng e ne e e-na le liketso tse fapaneng, e neng e khalemela ho kenella ka likhoto tse sebelisang sham tse sebetsanang le 100907-HT. Litšusumetso tsena tse fapaneng tsa 5-HT5A le 2-HT5C lihanyetsi li ile tsa qhekelloa ke ts'ebetso ea lithethefatsi ho li-bokellase tsa nucleus, empa eseng mPFC, liphoofolong tse sa tsitsang (Cottrell et al a, 2008). Leha ho le joalo, ka ho fapana ha 5-CSRTT, ho ile ha khonahala ho bona phokotso ea bohlokoa kamora ho ts'oaroa kamora ho kenella kahare-mPFC ho kenella ha 5-HT2A receptor antagonist. Liphumano tsa morao-rao li ne li lumellana le ho hlokomela hore, ho baahi ba likhoto tsa Lister tse kentsoeng, hangata e ne e le liphoofolo tse qholotsoang ka ho fetisisa tse neng li e-na le mohopolo o moholo oa 5-HT ho mPFC, e bonts'a hore phapang e ikhethang le ho khetholoha ha tikoloho ke lintlha tsa bohlokoa ho nahanisiseng likamano lipakeng tsa 5-HT le boitšoaro bo thibelang boitšoaro.

Litlamorao tsa manonyeletso a 5-HT bohareng ka ho qobelloa ho ema ka ho fapana le liketso tsa bona mabapi le ts'ebetso ea tlhokomelo. ka bobeli ho 5-CSRTT. Lipampiri tse 'maloa li hlokometse hore ha li na litlamorao kapa tšibollo ea' nete ea tlhokomelo e nepahetseng ha boitšoaro bo sa susumetseng bo ntlafatsoa (Harrison et al a, 1997) kapa kamora kalafo ka methapo ea kutlo kapa ea intra-PFC 5-HT2A receptor antagonists joalo ka ketanserin kapa M100907 (Passetti et al a, 2003; Winstanley et al a, 2003) hammoho le 5-HT1A receptor agonist 8-OHDPAT (Winstanley et al a, 2003). Liphumano tsena li lumellana le khopolo-taba ea hore taolo ea inhibitory holim'a boitšoaro bo sa tsitsang le ts'ebetso ea tlhokomelo e kenelletse feela maemong ana a liteko mme e fana ka maikutlo a hore ha ho na kamano e bonolo pakeng tsa bobeli ho li-syndromes tse kang ADHD.

Ntho e 'ngoe e rarahaneng ea ho rarahana e hlahisoa ha ho nahanoa ka tšusumetso ea lithethefatsi tsena tse tšoanang ka mehato ea ho qobelloa. Ho sebelisa tlhahlobo ea morao-rao ea morao-rao e amanang le marapo a OFC (Boulougouris et al a, 2007), ho fumanoe hore antagonism ea 5-HT2C (e hlahisoang ke tsamaiso ea methapo) e thusitsoe ho ithuta hape. M1000907 e bile le litlamorao tse fapaneng tsa ho e senya (Tsaltas et al a, 2005). Hlokomela hore mabapi le khalemelo, sena se fapane le se fumanoeng bakeng sa mehato ea ho susumetsoa habonolo. Lintlafatso tse tšoanang tsa thuto e feto-fetohang ka mor'a ho phekoloa ka mohanyetsi oa 5-HT2C le tsona li fumanoe kamora ho kenngoa ka har'a OFC (Boulougouris, Glennon, Robbins, sephetho se sa phatlalatsoang) (Lethathamo 2).

Lethathamo 2  

Litlamorao tse fapaneng tsa 5-HT2C le 5-HT2A Receptor antagonists ka Mehlala ea Rat ea Impulsivity le Compulsivity

Ho sa tsotellehe ho hlaka ho hlakileng ha mochine, datha tsena ka boqhetseke li khetholla mekhoa ena ea ho qhekella le ho qobelloa, ho fana ka maikutlo a hore ba ke ke hatch ka ts'ebetso e tloaelehileng ea boits'oaro. Dissociation e ke ke ea hlalosoa habonolo mabapi le phapang ea mefuta, lithethefatsi, kapa lethathamo la mohanyetsi oa receptor le sebelisitsoeng kapa mokhoa oa tšusumetso o sebelisitsoeng; li tlameha ho its'oara mesebetsing-kaha mesebetsi ka bobeli e hloka thibelo ea karabo hore e sebetse hantle. Kahoo, re fihlela qeto ea hore ho na le karolo e 'ngoe ea lits'ebetso tse etsoang ke mosebetsi, e li khethollang. Liphetho tsena li boetse li bolela hore ho susumetsoa le ho qobelloa ho arohantsoe ka tsela e fapaneng le ho kopanngoe hammoho, ho tšehetsa tšehetso ho mohlala o sa qobelloang-o qobelloang oa tlhahlobo-leseling (Hollander le Wong, 1995). Ba boetse ba fana ka maikutlo a hore ho susumetsoa le ho qobelloa ho ka qhalakanngoa ka ho khetha li-ligands tsa 5-HT2 tsa li-receptor le tlhaiso lits'ebetsong tse ncha tsa kliniki bakeng sa basebeletsi ba joalo. Leha ho le joalo, ho tla ba bohlokoa ho rarolla hore na lintlha tsena li tsamaisana joang le ho fumana ho sa feleng hore ho fokotseha ha 5-HT ho OFC ho sitisa ho ithuta ho khutlisetsang maikutlo ho litšoene tsa marmoset (Clarke et al a, 2004, 2005; Yucel et al a, 2007). Ntle le moo, ho ka bonahala eka litla-morao tsena tse bonahalang li hanyetsoa li tsamaisoa ka litsela tse fapaneng tse fapaneng: maemong a ho ba le tšusumetso, ka likhakanyo ho tsoa infralimbic VMPFC (sebaka sa 25), sebaka se kenyellelitsoeng haholo ke 5-HT2A regulation, lebopong la khetla ea li-nucleus accumbens (Vertes, 2004) hape, maemong a qobelloang, likhokahanong lipakeng tsa OFC le nucleus ea caudate (kapa dorsomedial striatum ho rat) (Schilman et al a, 2008).

HO FUMANA LITLHAKISO TSE KHUTLISANG LE TLHALOSO E SEBELISANG MESEBETSI EA NEUROPSYCHOLOGICAL

Mathata a susumetsang le a qobelloang hangata a kenyelletsa bokhoni bo fokotsehang ba ho lieha kapa ho thibela menahano kapa boits'oaro bo phetetsang. Kahoo, mathata a hatellang kapa a thibelang boits'oaro bo sa lokang a ka ts'oara matšoao a potlakileng le a phehellang (Chamberlain et al a, 2005; Stein et al a, 2006). ADHD ke bokuli ba ho qalella ho qala ka tšohanyetso bo khetholloang ka liketso tse sa tsamaeang hantle, liketso tse sa potlakeloang le ho senyeha hoa litšitiso tsa koloi ka mokhoa o lekantsoeng mesebetsing e kang SSRT (Arone et al a, 2003; Lijffijt et al a, 2005). Tsamaiso ea li-ejenti tse ntlafatsang kelello tse kang atomoxetine le methylphenidate e ntlafatsa matšoao le ho hlakola bofokoli ba SSRT ho batho ba baholo ba nang le ADHD, ka ho etsa lintho ka tšohanyetso ka Noradrenergic (kapa mohlomong dopaminergic) neurotransmission (Chamberlain et al a, 2007a).

Boithuto ho bakuli ba OCD bo senotse ho senyeha ha SSRT le ts'ebetso e mpe mesebetsing ea ho feto-fetoha ha ED (Chamberlain et al a, 2006a, 2007c; Menzies et al a, 2007a), e bolelang liphallelo tse susumetsang le tse qobelloang bothateng bona. Beng ka li-degree tsa pele tsa OCD ba sa angoeng ba arolelana ho senyeha ho tšoanang ho SSRT le mesebetsi e fetohang ea ED (Chamberlain et al a, 2007c) mme ka hona ho bonahala eka e bonts'a maemo a tšoanang a ho khanna hoa koloi le ho ba le ts'oaetso ea kelello, leha ho se na matšoao a OCD. Ho fapana le OCD, ts'ebeliso ea betri e tšoanang ea tlhahlobo ea methapo ho batho ba nang le trichotillomania e bontsitse ho senyeha ho tsepamisitsoeng le ho khetholoha ho thibelo ea makoloi, e lumellanang le tokiso ea eona ea DSM-IV joalo ka ICD (Chamberlain et al a, 2006b, 2007b). MRI ea kelello eohle ho trichotillomania e sa hlophisehang e bonts'a ho eketseha ha letsoalo la batho ba putsoa libakeng tse bolokiloeng ka letsohong le letšehali le libakeng tse ngata tsa cortical (Chamberlain et al a, 2008b). Taba e ntseng e eketseha ea bohlooho libakeng tse nang le mathata e boetse e tlalehiloe lithutong tsa Tourette syndrome (Bohlhalter et al a, 2006; Garraux et al a, 2006) le OCD (Menzies et al a, 2008a). Ka lehlakoreng le leng, bakuli ba nang le lefu la Tourette ba fumanoe ba arolelana ts'oaetso ea kelello le ho holofala haholo ho feta bakuli ba OCD mesebetsing ea ho etsa liqeto, empa ba sa holofala haholo mosebetsing oa ho thibela likoloi (Watkins et al a, 2005), leha boithuto bo bong bo fuputsang bacha ba nang le Tourette ha boa ka ba fumana bopaki ba ho senyeha ha moputso oa ho ithuta ha ho bapisoa le taolo ea papali ea papali ea chelete (Crawford et al a, 2005). Li et al a (2006) e hlotsoe ho bonts'a likhaello tsa ts'ebetso ha e bapisoa le taolo ea SSRT ho bana ba 30 ba nang le lefu la Tourette.

Phallo e fetelletseng ea karabelo e qobelloang le e sa qobelloeng ka hare ho OCD e phahamisa potso ea hore na ho ts'oaroa hangata ho etsa hore motho a be le ts'usumetso kapa ka lebaka leo, hore na ho ka khonahala ho bonts'a qobello ea methapo. ntle khatello ea koloi. Haeba ho joalo, ke mathata afe a ka bonts'ang ho qobelloa ho 'hloekileng'? Batho ba nang le bothata ba botho bo qobelloang bo qobelloang bo nang le OCD ba bonts'itse ho holofala ho hoholo setsing sa phetoho ea ED. Tlhahiso ena e tsamaellana le tlhahiso ea kliniki ea bothata ba botho bo qobelloang, bo khetholloang ka ho se lumellane ho fetelletseng le boits'oaro, empa ha e kenyeletse boits'oaro bo pheta-phetoang (ke ho re, ho hlonama kapa ho qobelloa). Ka hona, bothata ba botho bo qobelloang bo qobelloang bo ka baka bothata ba prototypic-compulsive (Fineberg et al a, 2007b). Lithuto tse netefatsang tse sebelisang batho ba nang le nonCorbid OCPD li ka amoheloa.

NEUROCOGNITIVE ENDOPHENOTYPES, OCD, LE PELE

Le ha mesebetsi ea methapo ea kutlo e ka sebelisoa ho khetholla libaka tse ikhethang tsa methapo ea kutlo, li-neuroimaging tse tlatselletsang li ka sebelisoa ho bona likarolo tse ka tlase tsa anatomical le li-circuits tsa neural tse tlasa kotsi ea liphatsa tsa lefutso bakeng sa lefu le itseng. Ka ho kopanya methapo ea MRI ea methapo ea kutlo le sebopeho, ho sebelisa tlhahlobo ea bokhabane ea bokong bohle McIntosh le Lobaugh, 2004) le teko ea tumello ea nova, Menzies et al a (2007a) e bonts'a litlamorao tsa lelapa ts'ebetsong ea ts'ebetso ea motor-inhibition task (SSRT) e neng e amana le phapang libakeng tsa libaka tse ngata tsa anatomical. Ka bobeli bakuli ba OCD le beng ka bona ba maemo a pele a sa amoheleheng e bonts'ang taolo ea koloi e thibelang mathata, e bonts'itsoeng ke nako ea nako e telele ea SSRT le latency e telele e hokahantsoe le bophahamo ba modumo oa lintlha tsa bohlooho ho OFC le RIF cortex (libaka tseo ka nako e 'ngoe li amanang le ts'ebetso ea OCD le SSRT, ka ho latellana) le ho eketseha ha litaba tsa bohlooho-bohlooho ho libaka tsa striatum, cingulate, le parietal cortex. Liphetho tsena li pheha khang bakeng sa lelapa la pele la sebopeho sa MRI endophenotype-mediating, mme mohlomong le liphatsa tsa lefutso, le kotsi bakeng sa ho qobelloa ho amanang le OCD. Lithuto tsa nako e tlang li ka leka ka mokhoa o atlehileng bakeng sa litlamorao tse itseng tsa liphatsa tsa lefutso ka ho fapana hoa maemo a mahareng joalo ka mokhoa o fapaneng le meralo ea mokhatlo oa khale, bakeng sa ho sibolla likotsi tsa ho hlaseloa habonolo.

Liphumano tse nang le SSRT, mosebetsi o sa hlokeheng oa ho qobelloa ke makoloi, li hlahisa monyetla oa hore mofuta o joalo oa endophenotype o ka se fuoe OCD feela, empa ka ho eketsehileng e amana le mathata a mang a teng, mme mohlomong le kantle, mathata a qobelloang-a qobelloang. sebopeho. Mohlala, batho ba nang le ADHD le beng ka bona ba bonahala ba haelloa ke mosebetsi oa ho thibela likoloi (Crosbie le Schachar, 2001), empa ha e e-so hlake hore na lintho tse amanang le mathata a ho senyeha bakeng sa ba nang le kotsi ea lelapa bakeng sa ADHD li ts'oana kapa li fapana le batho ba nang le kotsi ea lelapa bakeng sa OCD.

Khokahano e ka hare ho taba lipakeng tsa cortex e fokotsehileng kahare ho libaka tse ka pele tsa cortex le litekanyetso tse eketsehang lithutong tsa striatum tse nang le mehlala ea li-OCD tse nkiloeng lithutong tsa pele tsa monahano (Baxter et al a, 1987) le lithuto tsa MRI tsa sebopeho le tšebetso (bakeng sa tlhahlobo bona, Menzies et al a, 2008a). Liphumano tsa pele ho tlhahlobisiso e ileng ea latela ea ho sebelisa litšoantšo tsa boiphihlelo ka har'a litho tsa lelapa la OCD (Menzies et al a, 2008b) o bonts'itse bopaki ba tlhekefetso ea taba e tšoeu libakeng tsa boko tse tlatselletsang ho kenyelletsa letsoho la letsoho le nepahetseng (haufi le anterior cingrate cortex, ACC) le libaka tse nepahetseng tsa "parietal" tse haufi le libaka tsa parietal cortex) tse tsamaellanang le litholoana tsa phuputso e entsoeng pele e amang bakuli ba OCD.Szeszko et al a, 2005). Leha ho le joalo, ka ho atolosa thuto ena ho kenyelletsa litho tsa lelapa tsa OCD tse sa sebetseng, re hlahisitse lipatlisiso tsena ka hohle kamoo ho ka khonehang li-endophenotypes tse tšoeu tse tšoeu bakeng sa OCD (Menzies et al a, 2008b).

Ntle le tlhekefetso ea ts'ebetso ea boko ho bakuli ba OCD le baena, lipatlisiso li se li qalile ho netefatsa ts'ebetso ea ts'ebetso ea potoloho ea litereke li sebelisa mekhoa ea fMRI e hlophiselitsoeng morero ona. Re sebelisa mokhoa oa ho feto-fetoha ha maemo ka bokhutšoanyane oa fMRI, ho ile ha bonts'oa hore bakuli ba nang le OCD le beng ka bona ba maemong a pele ba sa sebetseng ba bonts'itse ts'ebetso ea boikemisetso ba bong ba morao ba OFC nakong ea phetoho ea likarabo; ba bile ba tloaetse ho se sebetse kamorao ho PFC nakong ea liphetoho tsa maemo a EDChamberlain et al a, 2008a).

Hammoho, liphuputso tsena li bonts'a hore mekhoa ea neuroimaging e ka fana ka mohloli o enneng oa li-endophenotypes tsa likhetho bakeng sa OCD. Liphetho li tsamaellana le likhopolo tse supang ho hloleha ha top-down cortical inhibition ea boits'oaro bo kopaneng. Ba fana ka tlhahiso ea hore maqhubu a bonoang ka mokhoa o fetelletseng le litloaelo tse qobelloang tse khethollang OCD li tsamaisana le boits'oaro bo akaretsang mabapi le boits'oaro bo thata le bo thibetsoeng bo arolelanoang hara litho tsa lelapa tse sa amehang. Kahoo, mathata a 'ts'oaetso ea ts'ebeliso ea kelello' me a fetoha habonolo 'a ka kenya letsoho kholisong ea matšoao a OCD. Mosebetsi oa nakong e tlang o lokela ho lekola hore na mokhoa ona o ka atleha ho akaretsa mathata a mang ka bongata bo qobelloang. Bohlokoa ba kliniki ea li-endophenotypes tsa putative li hloka lipatlisiso tse eketsehileng ho fumana hore na (le joang) beng ka bona ba sa amehang ba arolelanang matšoao le litlhahlobo tsa OCD ba ka fapana le taolo e sa amaneng le OCD. Kutloisiso e ntlafalitsoeng ea hlokahala bakeng sa mekhoa eo maemo a tikoloho a ka hlahisang OCD ho batho ba nang le ts'oaetso ea lefutso, le hore na kalafo e ka thusa ho fetola maloetse kapa joang.

ICDS LE METSI A PUSO

Ho fapana le mathata a qobelloang a kang OCD, li-ICD tse ling, joalo ka papali ea papali ea methapo, li tšoauoa ka ho khetha boithabiso ba nako e khuts'oanyane ntle le sephetho se sebe sa nako e telele. Berlin et al a (2008) bapisa batho ba bang le ba se nang ts'oaetso ea ho becha ho betri e khethiloeng ea neuropsychological (Berlin et al a, 2008). Batho ba nang le ts'ebeliso ea ts'ebeliso ea ts'ebeliso ea ts'ebeliso ea ts'ebeliso ea marang-rang ba tšoaileng haholoanyane litekanyetso tsa ho itlhahisa tse kang Barratt Impulsivity Scale ka kakaretso ba ne ba e-na le mohopolo oa nako e potlakileng ea nako (nako e nyane) ha ba bapisoa le taolo mme ba bonts'a bofokoli bo lekantsoeng ke potso ea boits'oaro bo shebileng ho bonts'a pele. -Koala ho sa sebetseng. Likarolo tse nang le papali ea chelete ea ho becha li boetse li bonts'itse liqeto tse fosahetseng ho Iowa Gamble Task (Bechara et al a, 1994) le bofokoli ba tokisetso ea phethahatso (mohlala ho Rala ea Spatial le Li-stockings tsa litereke tsa Cambridge tsa CANTAB), ho kenyeletsa lipotoloho tse etellang pele pele ho kenyelletsa sebaka sa OFC / VMPFC. Ho fapana le OCD (Watkins et al a, 2005; Chamberlain et al a, 2006b), ho feto-fetoha ho ne ho sa lekanyetsoa papaling ea papali ea chelete. Leha ho le joalo, liphuputso tse ling li bonts'a hore batho ba nang le ts'ebeliso ea ts'ebetso ea ho becha ea methapo ea methapo ba tšoaea haholo mehato e itseng ea ho qobelloa kapa ho qoba ho tsoa likotsi, le hore mehato ea ho susumetsoa le ho qobelloa e ka fetoha ha nako e ntse e feta (mohlala, nakong ea phekolo (Potenza, 2007a; E tšoeu et al a, 2009). Liphumano tsena li fana ka maikutlo a hore ho susumetsoa le ho qobelloa ha ho hanyetsanoe ka diametric mme ho arolelana kamano e rarahaneng kapa e ts'oanang, e nang le mathata a itseng a bonts'a mohopolo o mong oa o hahiloeng holim'a o mong o ka fetohang ka mokhoa o matla oa nakoana.

Hollander et al a (2007a) bapisa lihlopha tse tharo tsa batho ba lilemo li pakeng tsa bona le ba batona kapa ba batšehali, e leng papali ea chelete ea ho becha (hangata e qobelloang) le mathata a OCD le a autism (a qobelloang), a sebelisa betri ea tlhahlobo ea bongaka, ea kelello le e sebetsang. Nakong ea ts'ebetso ea mesebetsi e thibelang karabelo (e-ea / ha ho ea) e atisang ho kenya tšebetsong potoloho ea litereke, lihlopha tsohle tse tharo tse bonts'itseng li bonts'itse ts'ebetso e sa tloaelehang ea ts'ebetso ea FMRI libakeng tsa dorsal (cognitive) le ventral (maikutlo) tsa ACC ha li bapisoa le taolo e phetseng hantle. . Ho ne ho se na phapang e kholo ea tšebetso lipakeng tsa lihlopha tsena tse 'ne. Leha ho le joalo, lipatlisiso tsa sehlopha se pakeng tsa sehlopha li bontsitse ho fokotseha ha ts'ebetso ea dorsal ACC ka lihlopha tsohle tse tharo tsa bakuli tse amanang le taolo e phetseng hantle. Ka hona, nakong ea thibelo ea karabo, mathata ohle a qobelloang le a sa qobelloang a ile a tšoauoa ka ho fokotseha hoa ts'ebetso ea dorsal ACC, ho ka bakang ho hloleha ho thibela boits'oaro bo botle ba koloi ho pholletsa le mathata ana.

Ha mekhoa ea ts'ebetso ea motho ka mong ea ts'ebetso ea ventral ACC e ne e lumellana le mehato ea ho susumetsoa kapa ho qobelloa, ho se tšoane ho ikhethang pakeng tsa sehlopha sa lihlopha ho hlahile. Kahare ho sehlopha sa papali ea chelete ea ho becha, ts'ebetso e matla ea ACC / ventral striatum e kopantsoe hantle le mehato ea bongaka ea boits'oaro bo batlang bo potlakileng ba ho batla moputso (joalo ka ha bo lekantsoe ke TCI Impulsiveness le Kakaretso ea Kotsi ea Kotsi, NEO-FFI Extraversion, Kakaretso ea Nako, le Iowa Task ). Ntle le moo, barekisi ba marang-rang ba nang le ts'ebetso e eketsehileng ea ts'ebetso ea maemo a marang-rang a ACC (sebaka sa 25) ba bonts'a lintlha tse tlase tsa ts'ebetso ea ho feto-fetoha ha maemo (ID / ED mekhahlelo e felisitsoe). Ka lehlakoreng le leng, sehlopheng sa autistic (se qobelloang), ts'ebetso e eketsehang ea ACC / ventral striatum e amanang le ho teba ha matla ho qobella tloaelo ea ho imolla khatello (ho tiisa), le ts'ebetso e eketsang kahare ho libaka tse tšoanang tsa ventral ACC (sebaka sa 25) e hokahaneng le ts'usumetso e eketsehang (ID / ED shift Jumla ea liphoso tse fetotsoeng) mme e fokotse ho ts'oaroa ha mosebetsi oa Tekanyo ea Nako.

'Ho ikarola habeli' hona ho fana ka maikutlo a hore ho becheng hoa mafu le autism, liphapang tse atileng tsa ts'oaetso ea neuromodulation litseleng tsa ventral corticostriatal nakong ea boits'oaro ba boits'oaro, eo ho becheng ho hoholo ho ka 'nang ha etsa hore motho a be le khatello ea kelello le ha autism e qobella ho qobelloa. E boetse e re hopotsa tlhaiso-leseling e tsoang ho likhoto tse hlalositsoeng kae kae mona tse bonts'ang litlamorao tsa bahanyetsi ba 5-HT2C le 5-HT2A mabapi le ho se ts'oenyehe ho 5-CSRTT le ho qobelloa ho ithuta (sebaka sa ho ithuta se feto-fetohang) (Tsaltas et al a, 2005; Boulougouris et al a, 2007) - le lintlha tse fumanoeng tse sa lumellaneng tsa Carli et al a-E leng litekanyetso tsa agonist tsa 5-HT1A sebakeng sa infralimbic li fokotsitse boits'oaro (5-CSRTT) ntle le ho susumetsa karabelo e potlakileng, ka 5-HT2A receptor antagonist e na le litlamorao tse fapaneng (Likamore et al a, 2004). Ka kopanelo, liphumano tsena li bonts'a hore li-circular tse tšoanang tsa neural li ka tsamaisa likarolo tse potlakileng kapa tse qobelloang tsa boitšoaro ba motho le hore li-subtypes tsa 5-HT tsa VMPFC (5-HT2A) le OFC (5-HT2C), le liphoso tsa dorsal ACC, li ka ba le ts'ebetso ho ho se atlehe ha karabelo ea karabo matsatsing a bohlasoa a tšusumetso ea (ho tsuba) le mathata a phephetsang (OCD, autism).

TLHOKOMELISO, TLHAKISETSO, LE DA

Litsela tsa DA tsamaisong ea mesolimbic li na le mosebetsi oa bohlokoa moputsong le matlafatsong (Bohlale, 2002). Mathateng a taolo ea tšusumetso, ts'ebetso e eketsang ea ts'ebetso ea ACC nakong ea thibelo ea karabelo e ka amana le boitšoaro bo eketsehileng ba ho batla moputso. Liphetho tsa pele li fana ka maikutlo a hore batho ba betšang ba sa tsubeng ha ba na taba le moputso ho tlhaiso-leseling ea moputso oa TCI ho feta lits'ebetso tse phetseng hantle mme ba batla maemo a holimo a ho susumetsa (ho batla bocha) (Berlin et al a, 2008). Leha ho le joalo, lithuto tse ling tsa lithuto tse nang le ho becha ha methapo ea methapo li fumane ho fokola ha ts'ebetso ea ACC, haholo-holo karolong ea eona ea moea, nakong ea litlhahlobo tsa boipheliso le liteko tsa taolo ea kelello (Potenza et al a, 2003a, 2003b). Mabapi le litsietsi tse qobelloang, khokahano e nepahetseng lipakeng tsa ts'ebetso e matla ea ACC ea ts'ebetso nakong ea ts'ebetso ea karabelo nakong ea mesebetsi le karabelo e eketsehang mehatong ea ID / ED le liphoso tse felletseng li ka bonts'a tšebetso e eketsehang ea dopaminergic ho tsoa bofokoling ba setho, tumellanong le mofuta oa mesolimbic oa DA oa OCD (Joel, 2006).

Ho tsosa khopolo-taba, ho pheta-pheta le ho pheta-pheta litsela tsa mesolimbic tsa DA ho ka 'matlafatsa' tsamaiso ea moputso mme ho lebise ho nyoloheng ha ho batloa meputso (Robinson le Berridge, 1993), eo, haeba e kopantsoe le taolo e nyane ea prepaleal-cortex-Mediated inhibitory, e ka tsamaisa boits'oaro bo amanang le DA mme bo bonahala bo susumetsa. Ho lokolloa le ho susumetsoa haholo ha DA ho ka nyahlatsa mabenkele a DA mme ha lebisa ho anhedonia le khatello ea maikutlo (Koob le Le Moal, 1997). Ho joalo, ho basebelisi ba lithethefatsi, ts'ebetso e fokotsehile ea mesolimbic / mesocortical DA, joalo ka ha ho lekantsoe ke lirekoto tsa motlakase le Ka vivo microdialysis, e matlafala kamora ho nyoloha ha tšebeliso ea lithethefatsi. Sena se ka baka tšusumetso (qobello) ea ho batla meputso e matla ho 'tlatsa' khaello ea DA. Pontšo ea ho fokotseha ha li-receptor tse kang tsa D2 ho basebelisi ba sa foleng ba cocaine, ka ho nka litšoantšo tsa PET (Volkow et al a, 1999), e fana ka maikutlo a ho theoha ha karabelo ho likhatiso tse phahameng tsa DA tsa li-postynaptic, tse lumellanang le khopolo-taba ea tsamaiso ea DA e sa sebetseng kamora ho hlohlelletsa khaolo ea DA. Kahoo, se qalang e le ho lokolloa ha DA ho lebisang tšebetsong ea mesebetsi ea ACC e kenang le ho batla moputso o eketsehileng (Bohlale, 2002) e ka fela joalo ka mokhoa o qobellang ho lebisa maemong a eketsehang a ho hlohlelletsa moputso ho khutlisa khaello ea DA. Ts'ebetso ena e qobelloang e ka eketsoa ke taolo e sa lekanyetsoang ea ho etsa liqeto le ho etsa liqeto, e hokahane le orbitofrontal, ventromedial prefrontal, le ACC (Adinoff, 2004). Leha ho le joalo, hore na mohopolo ona o amana joang le li-ICD tse itseng o hloka tlhahlobo e tobileng.

MEKHOA E FUMANANG LITLHAKISO TSA TLHAKISO TSA TLHAKISO, MOTSOALLE LE DA

Mehlala ea ho qobella le ho qobella ho beha botsitso pakeng tsa ts'ebetso ea 5-HT (2A, 2C) libakeng tsa VMPFC / OFC tse laolang likarolo tsa thibelo ea karabelo, le molumo oa DA ho loops tse kenang tse kopanyang ventral ACC le ventral striatum / nucleus boits'oaro. DA neurotransmission, haholo-holo ho lokolloa ha phasic, bokong ba nyutlelie e amahanngoa le ho batla moputso le ho matlafatsoa (Schultz, 2002). Ho fuoe kotlo e sa lebelloang (tahlehelo ea chelete) ho fella ka ho kenella mosebetsing oa bohareng ba dopaminergic, ho khutlela morao thutong, le ho fokotseha ha ho batla moputso (Frank et al a, 2007). Lithethefatsi tsa Pro-dopamanergic, ho kenyeletsoa levo-dopa le pramipexole (D2-like DA receptor agonist), li amahanngoa le ho fetola thuto e khutlisetsang morao kotlong e sa lebelloang le li-ICD ho bakuli ba nang le lefu la Parkinson (Cools, 2006; Ho fola et al a, 2006). Pramipexole e boetse e amahantsoe le phihlello e mpe ea boits'oaro bo amanang le moputso ho barupeluoa ba phetseng hantle, e lumellanang le tlhaiso ea tlhahiso ea hore phasic DA ho saena ho bohlokoa ho tiisa liketso tse lebisang moputsong (Pizzagalli et al a, 2008). Leha ho le joalo, datha e ngoe e bonts'a hore pramipexole, ha e fuoa batho ba baholo ba phetseng hantle, ha e fetole boitšoaro bo sa lebelloang, ho qobelloa, kapa litlatsetso tse amanang le eona ho kenyelletsa ho fokotsa, ho nka kotsi, ho thibela karabo, kapa ho tsitsipanya (Hamidovic et al a, 2008). Ntle le moo, olanzapine, sethethefatsi se nang le thepa ea antagonist ho lelapa la receptor la D2, ha sea ka sa bonts'a bophahamo ba placebo litekong tse peli tse laoloang tse kenyelletsang lithuto tse nang le papali ea thuto ea kelello (Fong et al a, 2008; McElroy et al a, 2008), le mohanyetsi e mong ea tšoanang le D2, haloperidol, o fumanoe a eketsa sepheo le boits'oaro bo amanang le papali ea chelete ho batho ba nang le papali ea chelete ea methapo ea kutlo (Zack le Poulos, 2007). Lithuto tsa Radioligand li bohlokoa ho hlakisa mesebetsi e ka bang teng bakeng sa li-receptor tsa D3 le D2 ho pathophysiology ea ho becha ha methapo, mme lithuto tse joalo li thatafatsoa ke li-receptors tsena tse arolelanang li-affinities tsa li-radioligands tse teng.

Ho nka liphumano tsena ho etsa lipatlisiso, ho hlokahala lipatlisiso tse ling ho utloisisa kamano pakeng tsa ho ts'oaroa, ho qobelloa, le ts'ebetso ea DA ha li ntse li amana le mathata a itseng a kelello a kang ho ts'oaroa hoa marang-rang. Mathata a qobelloang kapa a qobelloang a ka hlaha ka lebaka la khaello ea mesolimbic ea DA. Leha ho le joalo, bahanyetsi ba kang D2-ba bontšitse phaello ea kalafo ho a mang (OCD), empa eseng mathata a mang (a ts'ebeliso ea ho becha ka methapo ea methapo) a tšoailoeng ke likarolo tse sa qobelloang le / kapa tse qobelloang. Ho batla li-circry le dorsal striatal circry lithutong tsa batho tse nang le mathata a itseng a sa qalang le a qobelloang a sebelisang li-ligoton tse khethehileng tsa "recotorergic" le "dopaminergic ligands" e tla ba mohato o latelang oa ho utloisisa maemo ana. E kanna ea ba ho khahla haholo ho hlahloba litlamorao tsa bahanyetsi ba 5-HT2A le 2C mabapi le phetiso ea DA potolohong ena. Patlisiso tsena li ka fana ka leseli le tlatselletsang mabapi le likarolo tse kang ho fokotsoa ha boemo ba moea oa boiphihlelo le ts'ebetso ea VMPFC e bonoang lithutong tsohle tse kenyelletsang mathata a arolelanang likarolo tse susumetsang le tse qobelloang, joalo ka ho becha ha li-pathological le li-SA (Reuter et al a, 2005; Potenza, 2007a).

Tlhaloso ea rona ea pejana ea ho qobelloa (tloaelo ea ho etsa lintho tse pheta-phetoang ka mokhoa o tloahelehileng / o ts'oanang oa ho leka ho thibela litla-morao) le tlhaloso ea hona joale (phokotso ea tšohanyetso e joalo ka boitsibollo) e amana. Mohlala, ho arabela ka tloaelo litloaelong tsa lithethefatsi ho ka nkuoa e le mokhoa oa ho lebella ka bohona mofuta o ka 'nang oa fokotsa ho se sebetse le ho o qoba pele o ka etsahala. Data e hokahanya mekhoa ena e tloaetseng ho ithuta (kapa ho qobelloa) le likarolo tsa dorsal striatum (mohlala oa caudate), joalo ka ha ho hlahlojoa pejana. Bopaki ba morao-rao hona joale bo hokahanya dorsal striatum (karolo ea eona e ka morao) le thuto e khothalletsang ho ithuta (Seymour et al a, 2007). Kahoo, ho latela pono ea neural, bopaki bo tšehetsa phapano lipakeng tsa maikutlo ana a mabeli a ho qobelloa.

KHOTHATSO LE LITLHAKISO TSA 'METSOALLE'

Papali ea chelete ea thuto ea tlhaho le liSA li arolelana likarolo tse ngata. Khafetsa likoluoa ​​li etsahala khafetsa 'me li bonts'a ho ts'oana le matšoao a phapang, phapang ea bong, nalane ea tlholeho le boleng ba lelapa (Grant le Potenza, 2006). Papali ea papali ea thuto ea tlhaho le SA li bonts'a maemo a phahameng a ho hlonepha mesebetsi e fokotsang meputso, e lumellanang le mehato e fosahetseng ea ho sebetsa (Bechara, 2003) le sephetho se sebe sa kalafo (Krishnan-Sarin et al a, 2007) bakeng sa batho ba nang le li-SA, ka hona ba ka ba le boleng ba tsoelo-pele bakeng sa papali ea chelete ea ho becha le li-ICD tse ling. Lintlha tsa Neurocognitive le fMRI li fana ka maikutlo a ho becha ha methapo le li-SA li arolelana li-neurocircuitry tse tšoanang, tseo, ha li bapisoa le lithuto tsa taolo, ts'ebetso e fokolitsoeng ea ts'ebetso ea "ventral striatum" le VMPFC e hlokometsoe ts'ebetsong ea moputso le liphapang tse ling (Potenza et al a, 2003a, 2003b). FMRI e sa sebetseng ea ts'ebetso ea "ventral striatum" nakong ea ts'ebetso ea moputso e fumanoe malapeng a batho ba nang le SA mme e ka emela tlhahlobo e sebetsang ea endophenotype bakeng sa mathata a lemallo, leha ho le joalo khopolo ena e hloka tlhatlhobo e tobileng ho beng ka bona ba sa tsubeng.

Kamora nako, karabelo e sa fetoheng e tloaetsoeng papaling ea papali ea chelete le SA e ka fetoha sebopeho se phehellehang sa boits'oaro, 'me ho nahanoa hore ts'ebetso e tsoelang pele ea ho hira batho ba tšoanang le ba dorsal, cortico-striatal loops e etsahala ka tsela e qalang.Brewer le Potenza, 2008) o re hopotsa ka ho potoloha ka mokhoa o hlakileng oa "striato-nigrostriatal".Lynd-Balta le Haber, 1994) le litoeba (Belin et al a, 2008) mefuta ea boits'oaro bo susumetsang ba 'mapa oa liphetoho ho tloha ho li-ventral ho ea ho dorsal striatum. Boithuto ba nako e tlang, ba ho nka nako e telele kamora liphetoho tsena e ka ba boithuto bo botle le tlhahlobo ea bophelo. Ho holisa patlisiso ho tsoa ho phekola batho ba bang ka ho becha ha methapo ea methapo le bahanyetsi ba opioid (Brewer et al a, 2008) eseng feela khethollo ea 'mele ea ho becha ho tsoa ho OCD, moo bahanyetsi ba opioid ba joalo ka naloxone ba bontšitsoeng ho etsa OCD hampe (Insel le Pickar, 1983), empa hape o fana ka tlhahiso ea ts'ebetso ea kalafo bakeng sa bahanyetsi ba opioid ho li-ICD tse ling tse amanang (Grant et al a, 2007).

LITLHAKISO TSE NTLE TSE KHOLO

Ho utloisisa ka botlalo neurobiology ea ho se ts'oenyehe le ho qobelloa le ho ba le monyetla oa ho theha mekhoa e mecha ea kalafo, ho ka hlokahala hore re batlisise ka nqane ho li-circuits tsa neural tse boletsoeng sengolong sena ho kenyelletsa likarolo tse ling tsa methapo ea kutlo, joalo ka insula. Lintlha li fana ka maikutlo a hore insula e bohlokoa ho hokahanya litlhahiso tsa 'ho tseba'. Likokoana-hloko tsa insula, ka mohlala ka mor'a ho otloa ke lefu, li 'nile tsa amahanngoa le ho khaotsa ho tsuba ka potlako (Naqvi et al a, 2007). Ho hlahisa maikutlo tikolohong, kapa maemong a homeostatic joalo ka ho ikhula, khatello ea maikutlo, kapa matšoenyeho, ho ka tsosa lipontšo tsa 'ho kenella' ka har'a insula e fetolelang ho ba 'litakatso' tse lemohuoang hantle. Insula e hokahane ka tsela ea anatomically le e sebetsang ho litsamaiso tse boletsoeng ka holimo tse amanang le ho se ts'oenyehe, ho qobelloa le taolo ea thibelo. Ka mokhoa o hlakileng, insula e sebelisana le mekhoa ea ho qobelloa le ho qobelloa ho fetisa matšoao (ho tloha tikolohong kapa viscera) ho 5-HT 2C vs Li-receptor tsa 5-HT 2A ka har'a cortex ea pele. Kahoo, lipontšo tse kenelletseng tse kenelletsoeng ka har'a insula, ka lehlakoreng le leng, li ka matlafatsa lipotoloho tsa neural tse khannang ho se tsotelle kapa ho qobelloa. Ka lehlakoreng le leng, tšebetso ea li-insula e kanna ea 'koetela' mekhoa ea taolo ea thibelo ea "preortal cortex" le ho senya tlhokomelo, ho beha mabaka, ho rala le ho etsa liqeto hang ho bona esale pele litlamorao tse mpe tsa ketso e itseng, mme ho ea ka ho theha merero ea ho batla le ho fumana lintho tse u khothatsang tse kang lithethefatsi (Naqvi et al a, 2007).

QETELLO

Joale, ha re khutlela lipotsong tsa rona tse susumetsang: (i) ho qobelloa le ho susumetsoa ho kenya letsoho hakae mathateng ana, (ii) li itšetleha ho isa kae ho latela li-circular tsa neural tse arolelanoang, kapa (iii) mekhoa ea bongaminergic e arolelanang, ( iv) na likarolo tsa boitšoaro tse qobelloang kapa tse qobelloang li na le boleng bofe kapa bofe bo amanang le kalafo, 'me (v) ho na le sebopeho se kopaneng se lumellanang le datha? Ho latela bopaki bo teng, ho susumetsoa, ​​le ho qobelloa, e 'ngoe le e' ngoe e bonahala e le multidimensional ebile e ts'ehetsa bonyane mathata a mang a susumetsang le a qobelloang, leha mathata a bontša ho fetela, empa hape le lintlha tse ikhethileng. Kahoo, liphoso tse ntseng li tsoela pele kahare ho cortico-striatal neurocircuitry e laolang likarolo tsa taolo ea thibelo e hlokometsoe lithutong tsohle tsa kelello le tsa ho nahana ka mathata ohle a hlahlojoang, leha ho le joalo, bakeng sa mathata a mang, data e lula e sa fella. Trichotillomania e kanna ea ba karohano ea taolo le tšusumetso ea makoloi kahare ho RIF cortex le likhokahano tsa eona tsa cortico-subcortical, athe ts'ebetso ea papali ea chelete ea methapo e tsamaisana le ho nkeha maikutlo ho amanang le ho etsa liqeto tse sa sebetseng le potoloho e mpe ea "cortico-striatal". le ventral striatum, e e khethollang haufi-ufi le li-SA. Maemo a phahameng a amanang le moputso o amanang le moputso ka phello e mpe ea kalafo bakeng sa li-SA ebile e kanna ea ba le bohlokoa ba tsoelo-pele bakeng sa papali ea chelete ea ho becha le li-ICD tse ling. Boitšoaro bo qobellehang bo etsahalang ka autism bo amahanngoa le litlolo tse tšoanang ho potoloho ea moputso oa ventral. OCD, ka lehlakoreng le leng, e bonts'a ho ts'oaroa ha motor le ho qobelloa, ka mokhoa o kopanetsoeng ka tšohanyetso ea potoloho ea OFC-caudate circry, hammoho le VLPFC, cortex ea RIF, cingulate le khokahano ea parietal. Bakeng sa mathata ana, li-serotonin tse amanang, DA le lipalo tsa noradrenaline li kanna tsa ba le mesebetsi ea bohlokoa ea ho feto-fetoha, hammoho le lits'ebetso tse ling tse seng li sa sebetse hantle. Ha nako e ntse e tsamaea, ho nkeha maikutlo ho ka fetoha ho fetoha mafolofolo le ka mokhoa o fapaneng.

Kahoo, setšoantšo se bonahala se le hole le moelelo o bonolo o nang le tatellano le ho qobelloa ho lula lipalo tse fapaneng, mme 'mohlala' mohlomong o kenyelletsa tšebelisano e thata ea li-diatheses tse ngata tse amanang le orthogonally, tse hlalositsoeng ka mokhoa o fapaneng ho potoloha le lipotoloho tsena. Mathata a ho qhekella le a qobelloang a fapane ka ho totobetseng, a arolelana likarolo tsa ho se ts'oenyehe le ho qobelloa, mme a ba thata le ho feta mme ka hona ho ba thata ho a sitisa ha nako e ntse e tsamaea. Mohlala, bakeng sa mathata a ho qhekella le a lemalloang, mamello ea moputso e ka ba teng mme boits'oaro bo ka phehella e le mokhoa oa ho fokotsa mathata (ke hore, ba ba qobelloang haholo). Bakeng sa mathata a qobelloang, ho ka etsahala hore ts'ebetso ea boits'oaro bo pheta-phetang ka boeona e tla matlafala ha nako e ntse e tsamaea, leha ho bile le litlamorao tse mpe tsa nako e telele (ke hore, ba khannoa ka mokhoa o potlakileng). Ho etsa 'mapa oa mathata ana ho sebelisoa betri eo ho lumellanoeng ka eona ea likhetho tsa endophenotypic ho ka hlakisa kamano ea bona,' me likhoebo tse kopanetsoeng tsa lipatlisiso tsa nakong e tlang litsing tse nang le boiphihlelo bo tlatselletsang li lokela ho khothaletsoa. Mekhoa ea libuka e ka hlokahala ho fuputsa ka mokhoa o lekaneng ka mekhoa ea ho 'khabisa' joalo ka litšebelisano tse rarahaneng. Ntlheng ena, mekhoa ea ho khetholla litsamaiso tse sebetsang tsa boko ho data ea neuroimaging, joalo ka mokhoa oa likarolo tse nyane (tse lumellang hape ho lekola mekhoa e mengata ea boits'oaro le litšoantšo), e kanna ea ba le bokhoni ba ho ba mekhoa ea bokamoso lebaleng lena. Re ka boela ra etsa tsoelo-pele e eketsehileng ho aroleng mekhoa ea ho amohela lintho tse amanang le ho laola boitšoaro bo qobelloang le bo susumetsoang ka ho sebelisa litokisetso tsa panya ea transgenic mesebetsing e tšoanang e etselitsoeng likhoto (mohlala, 5-CSRTT le phetoho ea ho ithuta) le tlhahlobo ea mefuta eohle ea 5- Li-receptors tsa HT li sebelisa li-ligand tse ncha tsa litlhare.

lumela hore baa fokola

Ngaka Fineberg o buisane le Lundbeck, Glaxo-Smith Kline, Servier, le Bristol Myers squibb; o fumane tšehetso ea lipatlisiso ho Lundbeck, Glaxo-SmithKline, Astra Zeneca, Wellcome; e amohetse honaria le tšehetso ea ho fana ka lipuo libokeng tsa mahlale ho tsoa Janssen, Jazz, Lundbeck, Servier, Astra Zeneca, Wyeth. Ngaka Potenza o botsa le ho eletsa Boehringer Ingelheim; o rerile ebile o na le lithahasello tsa lichelete ho Somaxon; e fumane ts'ehetso ea lipatlisiso ho tsoa ho Mekhatlo ea Naha ea Bophelo bo Botle, Tsamaiso ea Veteran, Mohegan Sun Casino, Setsi sa Naha sa Papali e Ikarabellang le Setsi sa Patlisiso mabapi le Mathata a Ho becha, le Glaxo-SmithKline, Forest Laboratories, Ortho-McNeil le Oy-Control / Biotie meriana; o nkile karolo lipatlisisong, posong, kapa lipuisanong tsa mohala tse amanang le bokhoba ba lithethefatsi, li-ICD kapa litaba tse ling tsa bophelo bo botle; e rerile liofisi tsa molao le ofisi ea mosireletsi oa sechaba litabeng tse amanang le li-ICD le bokhoba ba lithethefatsi; e phethile litlhahlobo tsa lithuso bakeng sa Mekhatlo ea Naha ea Bophelo le mekhatlo e meng; o fane ka lipuo tsa thuto lipapaling tse kholo, liketsahalo tsa CME, le libaka tse ling tsa bongaka kapa tsa mahlale; e na le likarolo tsa likoranta tse hlophisitsoeng ke baeti; e hlahisitse libuka kapa likhaolo tsa libuka bakeng sa baphatlalatsi ba litemana tsa bophelo bo botle ba kelello; hape e fana ka tlhokomelo ea bongaka Lefapheng la Connecticut la Bophelo bo Botle ba kelello le Lits'ebeletso tsa Lithethefatsi Lits'ebeletso Lenaneo la Litšebeletso tsa Ho becha. Ngaka Chamberlain o rapella Cambridge Cognition, Shire, le P1Vital. Ngaka Menzies o amohetse matšeliso a lichelete ka lebaka la phetisetso ea theknoloji e sa amaneng le taba ea taba ena lipakeng tsa Cambridge Enterprise Limited, Univesithi ea Cambridge, Cambridge, UK, le Cypress Bioscience, Inc, San Diego. Ngaka Bechara e fumana chelete ea borena ho tsoa ho PAR, Inc. Ngaka Sahakian o na le likarolo ho CeNeS; e buile le Cambridge Cognition, Novartis, Shire, GlaxoSmithKline, le Lilly; hape e amohetse honaria bakeng sa ho potoloha ka matla ho tsa mafu a kelello Sepetleleng sa Massachusetts General (CME) le bakeng sa ho bua Sebokeng sa Machaba sa Tsebo ea ho Tsebahala ho Schizophrenia le Mood Dis shida (2007). Ngaka Robbins o kopa thapelo ea Cambridge Cognition, E. Lilly, GlaxoSmithKline, le Allon Therapeutics. Ngaka Bullmore ke mohiruoa oa GlaxoSmithKline (50%) le Univesithi ea Cambridge (50%) le ramabelo ho GlaxoSmithKline. Ngaka Bullmore o amohetse matšeliso a lichelete ka lebaka la phetisetso ea theknoloji e sa amaneng le taba ea taba ena lipakeng tsa Cambridge Enterprise Limited, Univesithi ea Cambridge, Cambridge, UK, le Cypress Bioscience, Inc, San Diego. Ngaka Hollander o buisane le Somaxon, Neuropharm, Transcept, le Nastech. Ngaka Hollander o buisane le liofisi tsa molao le ho paka nyeoeng ea Mirapex Product Liability. O amohetse tšehetso ea lipatlisiso ho tsoa ho National Institutes of Health, Orphan Products Division of the Food and Drug Administration, National Alliance for Research in Schizophrenia and Affective Dis shida, Autism Speaks, Seaver Foundation, le Solvay, Oy Contral, le Somaxon. Mosebetsi ona o ile oa tšehetsoa ke karolo ea Wellcome Trust Program Grant (076274 / Z / 04 / Z) ho Dr Robbins, Dr Sahakian, BJ Everitt, le AC Roberts. Institute of Behavioral and Clinical Neuroscience Institute e tšehetsoa ke moputso o kopaneng o tsoang ho Medical Research Council (MRC) le Wellcome Trust (G001354). E tšehelitsoe ke National Alliance bakeng sa Patlisiso mabapi le Schizophrenia le Ho Tepella Maikutlo (RG37920 Dispecitised Inarcherator Award to Dr Bullmore), Harnett Fund le James Baird Fund (University of Cambridge) le Yunivesithi ea Cambridge School of Clinical Medicine, (MB / PhD) ho Dr Menzies), le Lekhotla la Boithuto ba Bongaka (MB / PhD liithuti ho Dr Chamberlain). Dr Bechara o fumana tšehetso ea lithuso ho tsoa ho National Institutes on Health (NIDA R01 DA023051, DA11779, DA12487, le DA1670), (NINDS P01 NS019632), le National Science Foundation (NSF IIS 04-42586). s DA019039, DA020908, DA015757, DA020709; R37 DA15969; RL1 AA017539; P50s DA09241, AA12870, AA015632), VA (VISN1 MIRECC le REAP), le Lipatlisiso tsa Bophelo ba Basali Yale. Ngaka Robbins o buisana le pfizer, Dr Menzies o amohetse honaria bakeng sa ho hlahisa kopanong ea selemo le selemo ea bo8 mabapi le Patlisiso ea psychopathology le bakeng sa mosebetsi ho Morero oa Ponelopele ea Mmuso oa UK mabapi le matla a kelello le bophelo bo botle.

Mongolo o botlaaseng ba leqephe

QETHA

Bangoli ba phatlalatsa hore ha ho na likhohlano tsa thahasello.

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