Striatal Dopamine D2 / 3 Receptor Ho fumaneha ha Phekolo ea ho Tepella Maikutlong (2015)

PloS One. 2014; 9 (11): e113612.

E hatisitsoe Inthaneteng 2014 Nov 20. doi:  10.1371 / journal.pone.0113612

PMCID: PMC4239080

Huaibin Cai, Mohlophisi

Sengoliloeng sena se lokisitsoe. Bona PLoS One. 2015 Phato 13; 10 (8): e0135764.

Eya ho:

inahaneloang

Boithuto bo 'maloa bo bontšitse ntlafatso ea matšoao a nyahamisang ho tepelletseng ho sa feleng ha khatello ea maikutlo (TRD) kamora ho fana ka dopamine agonists e fanang ka maikutlo a sa tloaelehang a dopaminergic neurotransmission ho TRD. Leha ho le joalo, karolo ea dopaminergic signaling ka tekanyo ea driamine dopamine D2/3 li-receptor (D2 / 3R) ha li so ka li batlisisoa lithutong tsa TRD. Re sebelisitse [123I] IBZM single photon emission computed tomography (SPECT) ho fuputsa striatal D2 / 3R tlamo ho TRD. Re kenyelelitse bakuli ba matla ba TRD ba 6, bakuli ba 11 ba matla ba TRD ho li-antipsychotic (sehlopha sa TRD AP) le 15 e tsamaisanang le taolo e phetseng hantle. Liphetho ha li bontše phapang e kholo (p = 0.75) ho fumaneha ha D2 / 3R ha lesea le fumanoa lipakeng tsa bakuli ba TRD le taolo e phetseng hantle. Sehlopheng sa TRD AP sehlopha sa D2 / 3R se fokotsehile haholo (se bonts'a ho lula ha D2 / 3Rs ka li-antipsychotic) mabapi le bakuli ba TRD le taolo e phetseng hantle (p <0.001) empa ho ne ho se na phapang lipakeng tsa matšoao a kliniki lipakeng tsa bakuli ba TRD AP le TRD. Phuputso ena ea mantlha ka hona ha e fane ka bopaki ba phapang e kholo ea ho fumaneha ha D2 / 3 ho bakuli ba boima ba TRD mme e fana ka maikutlo a hore sehlotshwana sena sa TRD ha se khetholloe ka phetiso ea dopaminergic e fetotsoeng. Li-antipsychotic tsa Atypical ho bonahala eka ha li na molemo oa tleliniki ho bakuli ba matla ba TRD ba lulang ba tepelletse maikutlo, leha ba lula ka thata ho D2 / 3R.

Selelekela

Hoo e ka bang karolo ea boraro ea bakuli ba nang le bothata bo boholo ba khatello ea maikutlo (MDD) ha ba arabe liteko tse peli kapa ho feta tse nang le lihlopha tse fapaneng tsa li-antidepressants mme ba nkuoa e le kalafo e hanyetsanang [1], [2]. Ho tepella maikutlo ho hanyetsanang le kalafo (TRD) ho tsamaisana le ramatiki e mpe le ho feta ka litšenyehelo tse phahameng tsa bongaka [3]. Hajoale ha ho tsejoe letho ka pathophysiology ea TRD, leha ho le joalo lithuto tse 'maloa lithutong tsa TRD li bonts'itse ntlafatso ea matšoao a sithabetsang kamora kalafo le dopamine agonists [4]-[6]. Liphumano tsena li fana ka maikutlo a hore ts'ebetso ea dopaminergic neurotransmission e ea sebetsa ho pathophysiology ea TRD [7].

Ntle le moo, neuropransication ea derraminergic e boetse e amahanngoa le moputso o sa sebetseng / tsamaiso ea ts'usumetso le anhedonia; ho se khonehe ka ho felletseng kapa ho sa feleng. Anhedonia ke e 'ngoe ea matšoao a mabeli a bohlokoa a hlokahalang bakeng sa tlhahlobo ea MDD [8]. Ho TRD, anhedonia hangata e matla ebile e nka nako e telele ebile e amana le khaello ea meputso / lits'ebetso tse bokong. Meputso le tšusumetso li tsamaisoa ke sisteme ea mesolimbic, e leng e 'ngoe ea lipampitšana tse kholo tsa dopaminergic tsa boko [7]. Morero ona oa mesolimbic o hlaha ho tsoa sebakeng sa ventral tegmental (VTA) le liprojeke ho ea ho ventral striatum (ho kenyelletsa le li-nucleus accumbens), hippocampus le amygdala.

Boithuto bo fokolang ba morao-rao bo hlokometseng sisteme ea dopaminergic ho MDD ka positron emission tomography (PET) kapa e le 'ngoe ea Photon emission computer tomography (SPECT),' me ba tlalehetse liphetho tse sa lumellaneng. [9], [10]. Boithuto bo etsang lipatlisiso tsa dopamine D2/3 ho fumaneha ha li-receptor (D2 / 3R) ho tlalehiloe ka keketseho e fumanehang ea ho fumaneha ha D2 / 3R ho bakuli ba MDD ha ho bapisoa le taolo [11], [12], hammoho le ho eketseha ha driatal D2 / 3R ka har'a sehlopha sa bakuli ba MDD ba nang le khatello ea maikutlo ea morao-rao [13], [14]. Keketseho e fumanehang ea D2 / 3R e ka bonts'a phallo ea D2/3 li-receptor, keketseho e atamelaneng ea li-receptor bakeng sa radioligand kapa mokokotlo o fokotsoeng oa synaptic dopamine [7]. Ka hona, bopaki ba mosebetsi o fetotsoeng oa dopaminergic ho MDD ke toka, hape, joalo ka ha lithuto tse ling li bonts'itse phapang lipakeng tsa MDD le taolo e phetseng hantle. [15], [16]. Tlhaloso bakeng sa liphumano tsena tse sa lumellaneng e kanna ea ba hore liphuputso tsena li kenyelletsa bakuli ba MDD ba nang le litšobotsi tse ngata tsa kliniki tse ka fokolisang lihlopha tse fapaneng tsa kliniki. Ho khahlisang, ho fanoe ka maikutlo a hore TRD e tšoauoa ka ho hloka taolo ho hoholo ha maikutlo a laoloang ke marang-rang a amanang le khatello ea maikutlo e sa phekoleng [17], [18], e fanang ka maikutlo a hore bakuli ba TRD ba pheletsong e mpe ka ho fetesisa ea pono e tsoelang pele ea khatello ea maikutlo. Ntle le moo, ha bakuli ba TRD hangata ba anhedonic le psychomotoricard ba khutlisoa haholo, 'me hangata nako ha e arabe lithethefatsi tsa serotonergic kapa noradrenergic, tlhekefetso ho bakuli ba TRD e kanna ea amana le ho saena hoa dopaminergic. Ho fihla joale, ho kopanya striatal D2 / 3R ha ho so ka ho batlisisoa ho bakuli ba TRD.

Ka hona, sepheo sa thuto ea morao-rao e ne e le ho etsa lipatlisiso tsa kalafo ea striatal D2 / 3R ho bakuli ba boima ba TRD ho hlahloba maikutlo a hore na bakuli ba TRD ba tšoauoa ka ho fokotseha phetiso ea dopaminergic, e bonts'itsoeng ke ho eketseha ha D2 / 3R. Re sebelitse ka mehato ea vivo ea st2atal D3 / 6 e tlamang ho bakuli ba 15 ba TRD ha ba bapisoa le taolo e 2 e phetseng hantle. Re boetse ra etsa lipatlisiso ka litlamorao tsa li-antipsychotic ho fumaneha ha driatal D3 / 11R ho bakuli ba XNUMX ba TRD le hore na lithethefatsi tsena li ne li amana le ntlafatso ea matšoao.

mekhoa

Lihlooho

Re kenyelelitse bakuli ba 6 ba TRD, bakuli ba 11 ba TRD ho li-antipsychotic (sehlopha sa TRD AP) le lithuto tse 15 tsa taolo e phetseng hantle tse tsamaeang le lilemo le bong. Bakuli ba TRD ba ile ba hiroa Lefapheng la Psychiatry la Setsi sa Bongaka sa Thutong (AMC) se Amsterdam le sepetlele sa St. Elisabeth se Tilburg. Boithuto bona bo amohetsoe ke Komiti ea Boitšoaro ea Bongaka ea Bongaka ea AMC ea Univesithi ea Amsterdam (METC AMC), le Komiti ea Boitšoaro ea Bongaka ea Sepetlele sa St. Elizabeth (METC St. Elisabeth). Lithuto tsohle li fane ka tumello e ngotsoeng e ngotsoeng. Mekhoa ea ho kenyelletsa lithuto tsa TRD le TRD AP e ne e le: (i) lilemo tse pakeng tsa 18 le 65; (ii) kakaretso ea Hamilton Depression Rating Scale (HAM-D) ≥18; (iii) tlhahlobo ea mantlha ea MDD ho ea ka Diagnostic and Statistical Manual of Mental Dis shida (DSM-IV) mme e hlahlojoe ke The Structured Clinical Interview for DSM-IV (SCID) [19]. Ho hapa bakuli ba TRD ba matla ka ho fetesisa, re kenyelelitse feela bakuli ba nang le nako ea ho kula lilemo tse> 2, ba sa kang ba arabela (i) bonyane kalafo tse peli tse lekaneng tsa li-anti-depressing tse peli tsa sejoale-joale (serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors. , kapa noradrenergic le serotonergic antidepressants), le (ii) tricyclic antidepressant, le (iii) monoamine oxidase (MAO) inhibitor e ke keng ea qojoa, le (iv) bonyane likopano tse 6 tsa kalafo ea motlakase ea motlakase (ECT). Mekhoa ea ho khetholla e ne e le: (i) Lefu la Parkinson, 'dementia' kapa lefu la sethoathoa; (ii) lefu la ho ferekana kelellong; (iii) schizophrenia kapa nalane ea psychosis e sa amaneng le MDD; (iv) tšebeliso e mpe ea tahi kapa lithethefatsi likhoeling tse 6 tse fetileng; le (v) ho hloka taolo ea botho. Litaolo tse phetseng hantle li ile tsa hlahlojoa ke lipuisano tse hlophisitsoeng tsa bongaka bakeng sa mathata a DSM-IV molemong oa ho netefatsa ho ba sieo ha mafu a kelello kapa methapo. [19]. Ha ho le ea mong oa karolo ea phetseng hantle ea tlalehileng nalane ea lelapa ea bokuli ba kelello. Re sebelisitse HAM-D [20] le Montgomery Asberg Depression Rating Scale (MADRS) [21] ho hlakola khatello ea maikutlo. Mokhoa oa Maudsley Staging (MSM) o ne o sebelisoa ho hlakola boemo ba ho hanyetsa kalafo [22],[23]. Mohato oa MSM o kenyeletsa likarolo tse fapaneng tsa kliniki; Nako ea ketsahalo e sithabetsang ea hona joale, matšoao a boima, le boemo ba tšebetso ha bo lekantsoe ke lintlha tsa Global Test of Functioning (GAF). Bakeng sa lenane le felletseng la mefuta ena ea bongaka re bua ka Fekadu et al [22].

Protocol e le 'ngoe ea Photon Emission Computed Tomography

Ho hlahlojoa ha SPECT ho entsoe ka ho sebelisa sekepe se inthaneteng se sebetsanang le sekepe se nang le lisebelisoa tse 12 (Neurofocus, Inc., Medfield, MA, USA). Lintho li hlophisitsoe ka tekanyo ea bokhoni ba striatal D2 / 3R e tlamang (BP)ND) U sebelisa mohanyetsi ea khethiloeng oa D2 / 3R [123I] iodobenzamide ([123I] IBZM). Re sebelisitse mokhoa oa bolus / infusion kamehla, o 'nileng oa hlalosoa ka mokhoa o qaqileng pele [24], [25]. Lintlha tsa SPECT li fumanoe metsotso e 60, ho qala metsotso e 120 kamora ho kenngoa ha radioligand. Ka letsatsi la ho hlahloba lithuto ho ne ho sa lumelloa ho sebelisa joala, kofi le koae kaha sena se kopantsoe le ho fetoloa ha dopamine e fetotsoeng. [26], [27].

Ho aha bocha litšoantšo le ho e sekaseka

Lintlha tsa SPECT li ne li hahiloe bocha ka mokhoa oa 3-D le khalemelo ea litšoantšo tsohle e entsoe joalo ka ha ho hlalositsoe pejana [28]. Bakeng sa quanifying, ho ile ha etsoa tlhahlobo ea tikoloho ea thahasello (ROI). Li-ROI tse tsitsitseng li ne li behiloe sebakeng sa striatum 'me, ka mokhoa oa ho bua, occipital cortex [25]. Ho bolela litlamo tsa striatal le ho bolela hore li tlangoa ka matla a moea li ne li khelosoa ka ho le letona le ka ho le letšehali tsa ROI. Ebe, BPND e ne e baloa e le karolelano ea tse ikhethileng ho tse tlamang tse sa ikhethileng ((kakaretso ea ts'ebetso ea striatum - ts'ebetso ho occipital cortex) / ts'ebetso ho cortex ea occipital). Lisebelisoa tsohle li ile tsa hlahlojoa ke mofuputsi a le mong (CP) ea neng a sa bone lintlha tsa bongaka. Ho lekanya tumellano ea li-inter-rater, bangoli ba babeli (CP le BdK) ba ile ba hlahloba BP ka boikemeloND lithutong tse leshome. Intraclass correlation coeffnty (ICC) e ne e le 0.94 bakeng sa leqele- le 0.95 bakeng sa striatum e nepahetseng e bonts'ang tumellano e ntle pakeng tsa li-raters ka bobeli.

Tlhahlobo ea statistical

Phapang ea lilemo, lintlha tsa HAM-D le MADRS li ile tsa hlahlojoa ka tlhahlobo e le 'ngoe ea phapang (ANOVA), le liphapang tsa bong tse sebelisang tlhahlobo ea chi-mraba. Ho bapisa ho fumaneha ha striatal D2 / 3R pakeng tsa TRD, TRD AP le lithuto tse phetseng hantle li ile tsa etsoa le ANOVA hape. U sebelisa tlhahlobo ea Bohlokoa ea Phapang (LSD) ANOVA ea post-hoc, ho se fumanehe lipakeng tsa D2 / 3R ho fumanoe lipakeng tsa bakuli ba TRD le taolo e phetseng hantle, lipakeng tsa bakuli ba TRD AP le taolo e phetseng hantle le lipakeng tsa bakuli ba TRD AP le ba TRD. Kaha ho fumaneha ha D2 / 3R ho susumetsoa ke lilemo [29] le bong [30], ka kenyelletso re kenyelletsa lintho tse fapaneng joalo ka li-covariate sehlopheng se hlahlobang ho sebelisa tlhahlobo e le 'ngoe ea covariance (ANCOVA). Bophahamo ba menyetla e 'meli ea taolo ea 0.05 bo ile ba khethoa e le bohlokoa ba bohlokoa.

Results

Litšobotsi tsa mamello

TRD, TRD AP le lithuto tsa taolo li ne li bapisoa le lilemo le bong.Lethathamo 1). Lipalo tsa HAM-D le MADRS li ne li sa fapana lipakeng tsa bakuli ba TRD le TRD AP tse bonts'ang phapang ea ho teba ha khatello ea maikutlo pakeng tsa lihlopha tsena ka bobeli. Lipalo tsa li-MSM tsa bakuli ba TRD e ne e le 11.8 (± 1.0) le bakeng sa bakuli ba TRD AP 11.8 (± 0.5) e bontšang boemo bo phahameng ba khanyetso ea kalafo lihlopheng ka bobeli. Phuputso e akaretsang ea tšebeliso ea meriana ea mokuli e mong le e mong oa TRD le TRD ho tlalehiloe ho Lethathamo 2.

Lethathamo 1 

Mehato ea demographic le ea bongaka ea TRD, TRD AP le lithuto tsa taolo e phetseng hantle.
Lethathamo 2 

Lithethefatsi tsa Psychopharmacological tse sebelisoang ho bakuli ba TRD le TRD AP.

TLHOKOMELISOA

Ho ne ho se na phapang e kholo ea ho fumaneha ha striatal D2 / 3R pakeng tsa bakuli ba TRD le taolo e phetseng hantle (p = 0.75) e fanang ka maikutlo a hore dopaminergic neurotransication ha e ea fetoloa haholo ho bakuli ba TRD (Lethathamo 1, Setšoantšo sa 1 'me Le2) .2). Boholo ba litlamorao bo ne bo le 0.21. Ntle le moo, ho fumaneha ha D2 / 3R ho bolelang ha sehlopha sa TRD AP ho ne ho le tlase haholo ha ho bapisoa le TRD (p = 0.001) le sehlopha sa taolo e phetseng hantle (p <0.001). Kaha li-antipsychotic tse sebelisoang ke bakuli ba TRD AP kaofela e ne e le bahanyetsi ba li-receptor tsa dopamine, sena se bontša ho lula ho matla ha D2 / 3Rs tsa masea a bolaeang (Lethathamo 1, Setšoantšo sa 2; ho lula ha 50% ± 20%). Khalemelo bakeng sa lilemo le bong ha ea ka ea ama litholoana tsena haholo.

Setšoantšo sa 1 

Litšoantšo tse pharalletseng tsa ho fumaneha ha D2 / 3R
Setšoantšo sa 2 

Phihlelo ea Striatal D2 / 3R bakeng sa TRD, TRD AP le li-control tsa bophelo bo botle.

Puisano

Boithuto bona ba pele ke, ka tsebo ea rona eohle, ke oa pele oa ho etsa lipatlisiso ka ho fumaneha ha STriatal D2 / 3R ho TRD. Re kentse sehlopha se ikhethileng sa bakuli ba boima ba TRD ba neng ba tšoaneleha bakeng sa ho susumetsoa ke boko bo tebileng, ka nako e telele ea ho kula e hlalositsoeng e le karabelo ho bonyane liphekolo tse 'ne tse lekaneng tsa li-antidepressants tse fapaneng le bonyane makhetlo a 2 a likarolo tse peli tsa mokete oa lefatše. Ha re a bonts'a phapang e kholo ho fumaneheng ha striatal D2 / 3R ho bakuli ba TRD mabapi le taolo e phetseng hantle e fanang ka maikutlo a hore dopaminergic neurotransuction ha e fetoloe haholo ho TRD. Ntle le moo, lithuto tsa TRD AP li bonts'itse phokotso ea ho fumaneha hoa litheko tsa D2 / 3R ka botlalo ho li-TRD le li-taolo tse phetseng hantle, tse bonts'ang karolo e kholo ea li-D2 / 3R (tse hakanyetsoang ho ba 50%) ke li-antipsychotic tsena tsa atypical. Ho khahlisang, ho sa tsotelehe liphapang tsena tse kholo tsa matšoao a sithabetsang a receptor ho lula ha batho ha a ka a ntlafatsoa ho lithuto tsa TRD AP.

Pejana ho ne ho fanoa ka tlhahiso ea hore haholo-holo TRD e amana le ho hlobaela ha dopaminergic [7]. Kaha TRD e tšoauoa ka ho hloka taolo ho hoholo ha meea e laoloang ke marang-rang [17], [18], re ne re lebelletse hore ba bonts'e bothata bo matla ba dopaminergic mme ka hona ho fumaneha ha D2 / 3R ha ho bapisoa le taolo. Leha ho le joalo, ha re bone phapang ea bohlokoa ea ho fumaneha ha D2 / 3R ho bakuli ba TRD ha ho bapisoa le taolo. Re fana ka litlhaloso tse 'maloa mabapi le ho fumana sena. Taba ea pele, lithuto tse ling li tlaleha liphapang tsa ho fumaneha ha D2 / 3R ho bakuli ba ferekaneng kelellong [13], [14]. Mohlaleng oa rona re sebelisitse ntho ea 8 (bophara ba 0 ho isa ho 4) ea lintlha tsa HAM-D ho lekanya puseletso ea psychomotor e bonts'itseng bakuli bana ba TRD ba le mahlomoleng a lekanang feela le ho khutla ha psychomotor. Ka bomalimabe, lithuto tsa rona ha li na liteko tse tebileng ho lekanya ho khutla hoa koloi joalo ka mosebetsi oa ho kokota menoana [14]. Ka hona ha re khone ho khetholla khetho eo bakuli ba rona ba neng ba khutlisetsoe ho eona kelellong le ho feta lithutong tse fetileng [13], [14]. Taba ea bobeli, mohlaleng oa hona joale oa bakuli ba TRD ba kenyellelitsoe feela kamora karabelo ho ba-MAO-inhibitors. Ha MaO-inhibitors e eketsa ho tsepamisa mohopolo oa dopamine, ho ka tšeptjoa hore ka ho khetheha sehlotšoaneng sa bakuli ba nang le karabelo e ntle ho MAO-inhibitors boemo ba hypodopaminergic bo ka ba teng. Sena se ka hlalosa hore na hobaneng ha sampole ea batho ba sa arabeng li-MAO-inhibitors ho se liphapang tsa ho fumaneha ha driatal D2 / 3R. Le ha ho le joalo, khopolo-taba ena ha e so ka e phenyekolloa. Taba ea boraro, mohlala o teng hona joale o kanna oa fokola haholo ho bona phapang lipakeng tsa striatal D2 / 3R fumaneha lipakeng tsa TRD le lithuto tsa taolo. Taba ea bohlokoa, leha ho le joalo, boholo ba phello e ne e le nyane (d = 0.21). Sena se bolela hore bonyane bakuli ba 343 ba lokela ho kenyelletsoa ho bontša phapang ea bohlokoa ea sehlopha (ho matla a lipalo a 0.8). Ka hona menyetla ea hore lithuto tse kholo tsa nako e tlang li tla fumaneha ho eketseha ha D2 / 3R ho sehlopha sena sa bakuli ba TRD ho bonahala e le tlase. Ntle le moo, liphumano tsa rona tsa morao-rao li lumellana le lithuto tse 'maloa tsa MDD tse bileng li sa tlaleheng liphapang tsa ho fumaneha ha D2 / 3R mabapi le taolo e ntle [15], [16]. Leha ho le joalo lithuto tsena li ne li kenyelletsa lihlopha tse fapaneng tsa kliniki le bakuli ba amehang haholo kalafo le nako e khuts'oane ea bokuli ka hona e sitisang lipapiso tse tobileng.

Joalo ka ha ho lebelletsoe, lithuto tsa TRD AP li bonts'itse ho fokotseha ho fumaneha hoa litheko tsa D2 / 3R ka mokhoa o amanang le lithuto tsa TRD (e bonts'ang ho lula ha D2 / 3R ke li-antipsychotic). Baahi ba hona joale ba D2 / 3R (ba ka bang 50%) sehlopheng sa TRD AP ba bapisoa le ba antipsychotic ea atypical ho bakuli ba schizophrenia [31], [32]. Kaha ha rea ​​ka ra bontša phapang e kholo liponong tse sithabetsang lipakeng tsa lihlopha tsena maemong a lekaneng a ho lula, sena se fana ka maikutlo a hore phekolo ea monotherapy kapa ho khothaletsoa ka li-antipsychotic tsa atypical ha e fane ka melemo ea tliliniki sehlopheng sena se ikhethang sa TRD, ho fana ka maikutlo a hore li-antipsychotic tsena li ka fuoa ho bakuli bana. Habohlokoa, lithethefatsi tsohle tsa antipsychotic tse sebelisoang ke bakuli ba TRD AP li na le kananelo ea 5-HT2A ho amoheloa hoa motho ho bontšitsoeng ho ntlafatsa matšoao a sithabetsang [33]. 5-HT2A ho lula ha bakuli ba amohelang bakuli ka hona ho ke ke ha hlalosa ho fokola ha ntlafatso ea bongaka sehlopheng sena. Tlhaloso bakeng sa karabo e ka ba hore li-antipsychotic tsena tsa atypical kaofela ke lihanyetsi tsa dopamine receptor. Ho khahlisang, liphuputso tse 'maloa li bontšitse hore li-agopist tsa dopamine adjunctive dopamine tse kang pramipexole li sebetsa hantle ho bakuli ba TRD [6], [34], [35] e fanang ka maikutlo a hore kalafo ea dopamine agonist augmentation e kanna ea sebetsa le ho bakuli ba matla ba TRD ba teng. Re nahana hore ho hlohlelletsa ka kotloloho li-receptor tsa dopamine D2 / 3 ho ka ba molemo ho eketsa lits'ebetso bokong [36].

Leha a sebelisa khafetsa lithethefatsi tsa antipsychotic khafetsa maikutlong a kelello [37], [38], aucationation ea litekanyetso tse tlase tsa bakuli ba (li-non-psychotic) bakuli ba TRD e netefalitsoe hore e ea sebetsa [39], [40]. Leha ho le joalo, lithutong tsena tsa tlatsetso TRD e ne e hlalosoa haholo e le karabelo ho liteko tse peli feela tsa litlhare tsa khatello ea maikutlo. Bakuli ba hona joale ba TRD ho fapana le bona ha baa ka ba araba lihlopha tse eketsehileng tsa li-antidepressants tse kang li-antidepressants tsa li-tridclic le li-inhibitors tsa MAO tse ka 'nang tsa hlalosa ho se arabe ka li-antipsychotic tsa atypical, tse ka' nang tsa se be le molemo oa kliniki ho bakuli ba boima ba TRD. Leha ho le joalo, teko e laoloang ka mokhoa o ikhethileng e tla hlokahala ka mokhoa o hlakileng ho fihlela qeto ea hore na antipychotic augmentation e matla ea TRD e bohlokoa.

Re amohela meeli e 'maloa ea thuto ea joale. Taba ea pele, lithuto tse 'maloa li bontšitse hore striatum ha e na li-receptor tsa D2 / 3 feela empa e na le li-receptor tsa Dopamine D1 tse sebetsang ka litsela tse fapaneng tsa bohlokoa. [41]. Recopor ea dopamine D1 ke karolo ea subfamily e tšoanang le D1 eo hape e nang le dopamine D5 receptor [41]. Li-receptor tsa Striatal D1 ke karolo ea tsela e etsoang ka kotloloho ea nigrostriatal, athe li-receptor tsa D2 li atile haholo tseleng e sa tsejoeng. [42]. Leha ho na le liphapang tsena tse sebetsang, phuputso ea liphoofolo e bonts'itse hore ts'ebetso e ts'oanang ea li-receptor tsa D1 le D2 khetla ea li-nucleus li hlahisa tšebelisano-mmoho ho taolo ea sepheo, ke ho re dopamine Medielo process moputso. [43]. Ho tloha ha khatello ea maikutlo e amahantsoe le moputso o sa sebetseng / tsamaiso e susumetsang [44], [45], liphumano tsena li fana ka maikutlo a hore polelo e fetotsoeng ea li-receptor tsa D1 e ka lebisa ho ferekanyang tsamaisong ea khothatso ho bakuli ba MDD. Leha ho le joalo, ho ea kamoo re tsebang hore ha ho na thuto ea motho ea entseng lipatlisiso tsa ho fumaneha ha D1 ho MDD kapa ho TRD. The Positron Emission Tomography (PET) radioligand [11C] SCH23390 e tlama ho dopamine D1-receptors [46], le ho isa tekanyong e nyane ho li-receptor tsa D5. Kaha polelo ea li-receptor tsa D5 ho striatum e tlase, [11C] SCH23390 tlama e tla bonts'a ho fumaneha ha D1 receptor. [11C] SCH23390, empa le ligands tse ling tse kang [11C] NNC 756 [47] kapa [11C] SKF 82957 [48] ka hona e ka sebelisoa ho etsa lipatlisiso tsa ho fumaneha ha dopamine D1 receptor ho bakuli ba MDD le ba TRD.

Taba ea bobeli, bakuli ba bararo ho ba tšeletseng ba TRD ba sebelisitse meriana ea psychotropic e neng e ka susumetsa ho fumaneha ha Dri / DR. E mong oa bakuli bana o sebelisitse MAO-inhibitor e eketsang mahloriso a dopamine ea synaptic [49]. Ka hona, ts'ebeliso ea lithethefatsi ena e kanna ea fokotsa ho fumaneha ha Dri / 2R ho mokuli enoa ka tlholisano e eketsehileng le radioligand. Leha ho le joalo, ho khetholloa ha mokuli enoa ha hoa ka ha fetola liphetho. Ebile, keketseho e kholo ea likhakanyo tsa dopamine ea hlokahala ho fokotsa [123I] IBZM e tlamang ho vivo. Mokuli e mong oa TRD o sebelisitse mirtazapine e leng Noradrenergic le serotonergic antidepressant (NaSSA). Le ha mirtazapine e sena kamano ea li-dopamine receptors empa e etsa hore dopamine e lokolloe ka kotloloho ea pele le ea methapo.1A receptor le blockade ea li-receptors tsa í2-adrenergic [50], [51]. Leha ho le joalo, ha ho na bopaki ba hore mirtazapine e eketsa tlhahiso ea drietal dopamine e bontshang hore striatal D2 / 3R binding ha e fetoloe ke ts'ebeliso ea mirtazapine. Ea boraro, ka [123I] IBZM re khona ho lekanya li-striatal D2 / 3Rs ka vivo. Leha ho le joalo, ka lebaka leo re ke ke ra qhelela ka thoko liphapang tsa li-D2 / 3R tse eketsehileng tsa TRD, tse ke keng tsa hlakoloa. Kamora nako, ha rea ​​khetha bakuli ba TRD-ba thehiloeng ho matšoao a ts'ebetso joaloka psychomotor retardation le / kapa anhedonia e ka emelang sehlotshwana se nang le phumaneho ea D2 / 3R.

Qetellong, thuto ea hona joale ha ea ka ea fumana phapang ea ho fumaneha ha li-receptor D2 / 3R receptor kalafong e matla ea bakuli ba MDD e amanang le taolo e phetseng hantle. Sena se hanana le monahano oa hore TRD e tšoauoa ka phetiso ea dopaminergic e fetotsoeng. Ho feta moo, liphetho li bontšitse hore kalafo e eketsehileng ka li-antipsychotic e fokotsehile ho fumaneha ha li-receptor D2 / 3R (ka lebaka la ho lula ha D2 / 3R ke li-antipsychotic) ho TRD. Taba ea bohlokoa ke hore matšoao a sithabetsang ha a ka a fokotsoa ho bakuli ba TRD AP, sena se fana ka maikutlo a hore ho bakuli ba filoeng meriana e fapaneng ea li-antidepressant mme ba lula ba sithabetse maikutlo, li-antipsychotic tsa atypical ha li na molemo oa bongaka.

lumela hore baa fokola

Re leboha ka kananelo Elsmarieke van de Giessen le Evelien Zoons bakeng sa ho fana ka taolo e phetseng hantle, le bakuli ka bobeli le taolo e phetseng hantle ea ho nka karolo ho hlahlobeng ha SPECT. E fanoe ka li-taolo tse phetseng hantle: EvdG, EZ.

Tlhaloso ea lithuso

Dr. HG Ruhé o tšehelitsoe ke NWO / ZonMW VENI-Grant # 016.126.059. Bafani ba lichelete ba ne ba sena karolo morerong oa ho ithuta, ho bokella data le ho hlahlobisisa, qeto ea ho phatlalatsa, kapa ho hlophisa sengoloa.

References

1. Greden JF (2001) Moroalo oa maloetse bakeng sa khatello ea maikutlo e hananang le kalafo. J Clin Psychiatry 62 Suppl 1626–31. [E fetotsoe]
2. Rush AJ, Trivesi MH, Wisnviewski SR, Nierenberg AA, Stewart JW, et al. (2006) Liphetho tse sebetsang le tse telele tsa maikutlo ho batho ba sa ts'oaneng le bona ba hlokang mehato e le 'ngoe kapa tse' maloa tsa kalafo: Tlaleho ea STAR * D. Am J Psychiatry 163: 1905–1917. [E fetotsoe]
3. Ustun TB, Kessler RC (2002) Moroalo oa lefatše lohle oa mathata a sithabetsang: bothata ba nako. Br J Psychiatry 181: 181-183. [E fetotsoe]
4. Cusin C, Iovieno N, Iosifescu DV, Nierenberg AA, Fava M, et al. (2013) Teko e sa laoleheng, e sa boneng mahlo a mabeli, e laoloang ke placebo ea pramipexole augmentation ho ts'oaetso e kholo e sa hlokofatseng ea kalafo. J Clin Psychiatry 74: e636-e641. [E fetotsoe]
5. Inoue T, Kitaichi Y, Masui T, Nakagawa S, Boku S, et al. (2010) Pramipexole ea mophato oa 2 o hananang le khatello ea maikutlo e kholo: thuto e bulehileng. Prog Neuropsychopharmacol Biol Psychiatry 34: 1446–1449. [E fetotsoe]
6. Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, et al. (2002) Pramipexole ho khatello ea maikutlo e sa thibeleng kalafo: thuto ea tlhaho ea libeke tse 16. Bothata ba Bipolar 4: 307-314. [E fetotsoe]
7. Dunlop BW, Nemeroff CB (2007) Karolo ea dopamine ho pathophysiology ea khatello ea maikutlo. Arch Gen Psychiatry 64: 327–337. [E fetotsoe]
8. Mokhatlo oa American Psychiatric Association (1994) Buka ea Boholo ba Tlhahlobo le Tlhahlobo ea Mathata a Kelello, 4th ed: American Psychiatric Press.
9. Dunlop BW, Nemeroff CB (2007) Karolo ea dopamine ho pathophysiology ea khatello ea maikutlo. Arch Gen Psychiatry 64: 327–337. [E fetotsoe]
10. Ruhe HG, Visser KD, Frokjaer VG, Haarman CM, Klein C, et al. (2014) Ho nahana ka molek'hule ka mathata a sithabetsang PET le TLHOKOMELA ho Psychiatry, den Boer, JA; ed: Springer Verlag, maq. 93-172.
11. D'haenen HA, Bossuyt A (1994) Dopamine D2 receptors ho tepelletse maikutlong e lekantsoe le single photon emission computed tomography. Biol Psychiatry 35: 128-132. [E fetotsoe]
12. Shah PJ, Ogilvie AD, Goodwin GM, Ebmeier KP (1997) Ditliliniki tsa bongaka le tsa psychometric tsa dopamine D2 e ​​tlamang tlasa khatello ea maikutlo. Psychol Med 27: 1247–1256. [E fetotsoe]
13. Ebert D, Feistel H, Loew T, Pirner A (1996) Dopamine le khatello ea maikutlo - striatal dopamine D2 receptor SPECT pele le kamora kalafo ea antidepressant. Psychopharmacology (Berl) 126: 91-94. [E fetotsoe]
14. Meyer JH, McNeely HE, Sagrati S, Boovariwala A, Martin K, et al. (2006) receptor e phahamisitsoeng ea putamen D (2) e tlamang e ka bakang khatello ea maikutlo e kholo ka ho khutla ha koloi: thuto ea [11C] ea raclopride positron emission tomography. Am J Psychiatry 163: 1594-1602. [E fetotsoe]
15. Parsey RV, Oquendo MA, Zea-Ponce Y, Rodenhiser J, Kegeles LS, et al. (2001) Dopamine D (2) phumano ea li-receptor le tlhahiso ea dopamine ea amphetamine maemong a sithabetsang a khatello ea maikutlo. Biol Psychiatry 50: 313–322. [E fetotsoe]
16. Yang YK, Yeh TL, Yao WJ, Lee IH, Chen PS, et al. (2008) Phumano e kholo ea barekisi ba dopamine ho bakuli ba nang le khatello ea maikutlo e kholo-e leng thuto ea bobeli ea isotope. Psychiatry Res 162: 230–235. [E fetotsoe]
17. Konarski JZ, Kennedy SH, McIntyre RS, Rafi-Tari S, Soczynska JK, et al. (2007) Kamano pakeng tsa metabolism ea boko ea tikoloho, ho teba ha bokuli le lilemo ho lithuto tse tepelletseng. Psychiatry Res 155: 203-210. [E fetotsoe]
18. Paillere Martinot ML, Martinot JL, Ringuenet D, Galinowski A, Gallarda T, et al. (2011) metabolism ea bongoana ea motheo ho khatello ea maikutlo le karabelo ho matla a matla a khoheli a transcranial. Neuropsychopharmacology 36: 2710-2719-XNUMX. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
19. MB ea pele (2012) Puisano e hlophisitsoeng ea Kliniki bakeng sa Lits'oaetso tsa DSM-IV-TR Axis I, Patlisiso ea Phuputso, Khatiso ea Bakuli: Setsi sa Psychiatric sa New York.
20. Hamilton M (1960) Tekanyo ea tekanyo ea khatello ea maikutlo. J Neurol Neurosurg Psychiatry 23: 56–62. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
21. Montgomery SA, Asberg M (1979) Sekhahla sa khatello ea maikutlo se secha se etselitsoe ho ela hloko liphetoho. Br J Psychiatry 134: 382-389. [E fetotsoe]
22. Fekadu A, Wooderson S, Donaldson C, Markopoulou K, Masterson B, et al. (2009) Sesebelisoa sa multidimensional sa ho felisa ho hanyetsa kalafo ha ho tepella maikutlo: mokhoa oa ho chechisa Maudsley. J Clin Psychiatry 70: 177-184. [E fetotsoe]
23. Ruhe HG, van RG, Spijker J, Peeter FP, Schene AH (2012) Mekhoa ea mekhahlelo ea kalafo e thibelang khatello ea maikutlo. Tlhahlobo e hlophisehileng. J Tlala Disord 137: 35–45. [E fetotsoe]
24. Booij J, Korn P, Linszen DH, van Royen EA, et al. (1997) Tlhahlobo ea tokollo ea dopamine ea endo native ka phephetso ea methylphenidate sebelisa iodine-123 iodobenzamide single-Photon emission tomography. Euro J Nucl Med 24: 674-677. [E fetotsoe]
25. Boot E, Booij J, Zinkstok JR, Linszen DH, Baas F, et al. (2010) Striatal D (2) receptor e tlamang ho 22q11 Deletion syndrome: thuto ea [123I] IBZM SPECT. J Psychopharmacol 24: 1525–1531. [E fetotsoe]
26. Kaasinen V, Aalto S, Nagren K, Rinne JO (2004) Liphetho tsa dopaminergic tsa caffeine ho batho striatum le thalamus. Neuroreport 15: 281–285. [E fetotsoe]
27. Nevo I, Hamon M (1995) Neurotransmitter le methapo ea methapo e amanang le tšebeliso e mpe ea joala le bokhoba ba tahi. Neurochem Int 26: 305-336. [E fetotsoe]
28. Booij J, Tissingh G, Boer GJ, Speelman JD, Stoof JC, le al. (1997) [123I] FP-CIT SPECT e bonts'a ho theoha ho hlakileng ha lets'oa la sephethephethe la striatal dopamine ho lefu la Parkinson le pele. J Neurol Neurosurg Psychiatry 62: 133-140 (Khatisitsoeng) [Tlhahiso ea mahala ea PMC] [E fetotsoe]
29. Rinne JO, Hietala J, Ruotsalainen U, Sako E, Laihinen A, et al. (1993) Ho fokotseha ha letsoalo la batho ba dopamine D2 receptor le botsofaling: thuto ea PET e nang le [11C] raclopride. J Cereb flow flow Metab 13: 310–314. [E fetotsoe]
30. Mokoetlisi BC (2011) Likarabo tsa khatello ea maikutlo le sistamine ea mesolimbic dopamine: maemo a sechaba le phapang ea thobalano. Horm Behav 60: 457-469. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
31. Kapur S, Zipursky RB, Remington G (1999) Litlamorao tsa tleleniki le mohopolo oa 5-HT2 le D2 receptor ho lula ha clozapine, risperidone, le olanzapine ho schizophrenia. Am J Psychiatry 156: 286-293. [E fetotsoe]
32. Tauscher J, Hussain T, Agid O, Verhoeff NP, Wilson AA, et al. (2004) Ho lula ka ho lekanang ha dopamine D1 le D2 receptors ka clozapine: phapang ho tsoa ho li-antipsychotic tse ling tsa atypical. Am J Psychiatry 161: 1620-1625. [E fetotsoe]
33. Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F (2004) Karolo ea kalafo ea li-receptors tsa 5-HT1A le li-5-HT2A ka khatello ea maikutlo. J Psychiatry Neurosci 29: 252-265. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
34. Hori H, Kunugi H (2012) Ho sebetsa ha pramipexole, dopamine receptor agonist, joalo ka kalafo e kopaneng ho tepelleng e hanyetsanang le kalafo: teko e bulehileng-label. SaenseWorldJournal 2012: 372474. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
35. Izumi T, Inoue T, Kitagawa N, Nishi N, Shimanaka S, et al. (2000) Ho bula kalafo ea pergolide ea khatello ea maikutlo e ka reroang le ho ts'oaroa ha heterocyclic. J Tlala Disord 61: 127–132. [E fetotsoe]
36. Leentjens AF, Koester J, Fruh B, Shephard DT, Barone P, le al. (2009) Phello ea pramipexole maikutlong le matšoao a susumetsang ho lefu la Parkinson: tlhahlobo ea litlhahlobo tsa lithuto tse laoloang ke "placebo". Kliniki Ther 31: 89-98. [E fetotsoe]
37. Farahani A, Correll CU (2012) Na li-antipsychotic kapa li-antidepressants lia hlokahala bakeng sa khatello ea kelello? Tlhahlobo e hlophisehileng le tlhahlobo ea meta ho bapisa liteko tsa kalafo ea kalafo kapa antipsychotic le kalafo e kopaneng. J Clin Psychiatry 73: 486-496. [E fetotsoe]
38. Wijkstra J, Lijmer J, Burger H, Geddes J, Nolen WA (2013) Phekolo ea meriana bakeng sa khatello ea maikutlo. Database ea Cochrane Syst Rev 11: CD004044. [E fetotsoe]
39. Corya SA, Williamson D, Sanger TM, Briggs SD, Case M, et al. (2006) Papiso e sa sebetseng, e kopantsoeng habeli ea motsoako oa olanzapine / fluoxetine, olanzapine, fluoxetine le venlafaxine ho khatello ea maikutlo e hanyetsanang le kalafo. Ho sithabela maikutlo ho sithabetsang 23: 364–372. [E fetotsoe]
40. Nelson JC, Papakostas GI (2009) Atypical antipsychotic augmentation boteng bo boholo ba khatello ea maikutlo: tlhahlobo ea meta-liteko tsa liteko tse laoloang ke placebo. Am J Psychiatry 166: 980-991. [E fetotsoe]
41. Vallone D, Picetti R, Borrelli E (2000) Sebopeho le ts'ebetso ea li-receptor tsa dopamine. Neurosci Biobehav Rev 24: 125–132. [E fetotsoe]
42. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN (1990) D1 le D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Mahlale 250: 1429–1432. [E fetotsoe]
43. Ikemoto S, Glazier BS, Murphy JM, McBride WJ (1997) Karolo ea dopamine D1 le li-receptor tsa D2 ka har'a li-nucleus tse bokellaneng moputsong oa bohanyetsi. J Neurosci 17: 8580-8587. [E fetotsoe]
44. Pizzagalli DA, Holmes AJ, Dillon DG, Goetz EL, Birk JL, et al. (2009) Karabelo ea "caudate" le "nucleus" e fokotsang karabelo ea ho fumana moputso ho batho ba sa hlophisehileng ba nang le bothata bo boholo ba khatello ea maikutlo. Am J Psychiatry 166: 702-710. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
45. Smoski MJ, Felder J, Bizzell J, Green SR, Ernst M, et al. (2009) fMRI ea liphetoho mabapi le khetho ea moputso, tebello ea maikutlo, le karabelo ho moferefere o moholo oa khatello ea maikutlo. J Tlala Disord 118: 69-78. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
46. ​​Plaven-Sigray P, Gustavsson P, Farde L, Borg J, Stenkrona P, et al. (2014) Phumano ea Dopamine D1 receptor e amana le boitšoaro ba sechaba: Boithuto ba positron emission tomography. Neuroimage 102P2: 590-595. [E fetotsoe]
47. Abi-Dargham A, Simpson N, Kegeles L, Parsey R, Hwang DR, et al. (1999) Lithuto tsa PET tsa tlholisano e tlamang pakeng tsa dopamine ea endo native le radiotracer ea D1 [11C] NNC 756. Synfall 32: 93–109. [E fetotsoe]
48. Palner M, McCormick P, Parkes J, Knudsen GM, Wilson AA, et al. (2010) Systemic catechol-O-methyl fetisa inhibition e thusa D1 agonist radiotracer R- [11C] SKF 82957. Nucl Med Biol 37: 837-843. [E fetotsoe]
49. Yamada M, Yasuhara H (2004) K'hemistri ea Clinical ea li-inhibitors tsa MAO: polokeho le bokamoso. Neurotooticology 25: 215–221. [E fetotsoe]
50. Devoto P, Flore G, Pira L, Longu G, Gessa GL (2004) Mirtazapine-induced corelease of dopamine and noradrenaline from noradrenergic neurons in the medial prefrontal and occipital cortex. Euro J Pharmacol 487: 105–111. [E fetotsoe]
51. Nakayama K, Sakurai T, Katsu H (2004) Mirtazapine e eketsa tlhahiso ea dopamine ka cortex ea pele pele ke ts'ebetso ea li-receptor tsa 5-HT1A. Brain Res Bull 63: 237–241. [E fetotsoe]