Liphetoho tsa dopamine D2-receptor binding li amahanngoa le ho fokotsa matšoao ka mor'a lefu la kelello lefung la ho tšoenyeha ha sechaba (2012)

Tlhaloso: Phetolelo ea Psychiatry (2012) 2, e120; Doi: 10.1038 / tp.2012.40

S Cervenka¹, E Hedman^1,2, Y Ikoma^1,3, BOPHELO BA SEBELE¹, C Rück¹, C Halldin¹ le N Lindefors¹

¹Lefapha la Neuroscience ea Clinical, Karolo ea Psychiki, Karolinska Institutet, Stockholm, Sweden
²Lefapha la Clinical Neuroscience, Setsi sa Osher bakeng sa Bongaka bo Kopaneng le Karolo ea Psychology, Karolinska Institutet, Stockholm, Sweden
³Setsi sa Imera sa Limolek'hule, Setsi sa Naha sa Mahlale a Radiological, Chiba, Japan

Sengoloa: Ngaka S Cervenka, Lefapha la Tleliniki ea Kliniki, Karolo ea Psychiki, Karolinska Institutet, Karolinska University Hospital Solna, Moaho oa R5, 171 76 Stockholm, Sweden. Lengolo-tsoibila: [imeile e sirelelitsoe]

E amohetse 19 Hlakubele 2012; E amohetse 10 Mmesa 2012

inahaneloang

Sisteme ea dopamine e khothalelitsoe ho bapala karolo ea khatello ea kelello ea sechaba (SAD), karolo e ipapisitseng le lipatlisiso tsa limolek'hule tse bonts'ang maemo a fokotsitsoeng a matšoao a driamal dopaminergic ho bakuli ha a bapisoa le lithuto tsa taolo. Leha ho le joalo, sisteme ea dopamine ha e e-so hlahlojoe libakeng tsa boko le tsa matsoele tse khothalelitsoeng ho ba karolo ea mantlha ho pathophysiology ea SAD. Phuputsong e teng hona joale, re fetisitse maikutlo a hore maemo a extopriatal dopamine D2-receptor (D2-R) a lekantsoeng a sebelisa positron emission tomography (PET) a ka bolela phokotso ea matšoao kamora ho ba le kalafo ea boits'oaro ea kelello (CBT). Bakuli ba robong ba SAD ba ile ba hlahlojoa ba sebelisa phetoho e phahameng ea PET le radioligand e phahameng ea D2-R [¹¹C]FLB 457, pele le kamora libeke tsa 15 tsa CBT. Maemo a matšoao a ne a hlahlojoa a sebelisa subscale ea ho tšoenyeha ea Liebowitz Social Anxcare Scale (LSAS_tšoenyeha). Nakong ea phekolo, ho na le phokotso e kholo ea lipalo ea matšoao a ho tšoenyeha ka sechaba (P<0.005). Ho sebelisa tlhahlobo ea mehato e phetoang ea covariance, litlamorao tse kholo tsa nako le nako × LSAS_tšoenyeha phetoho ho bokgoni bo tlamang ba D2-R (BP_ND) li bontšitsoe (P<0.05). Phuputsong e latelang ea tikoloho le tikoloho, likamano tse fosahetseng lipakeng tsa phetoho ho D2-R BP_ND le LSAS_tšoenyeha phetoho e fumanoe bakeng sa medial prefrontal cortex le hippocampus (P Ena ke thuto ea pele ea ho tlaleha kamano e tobileng lipakeng tsa phetoho ea matšoao kamora kalafo ea kelello le letšoao la methapo ea kelello. U sebelisa sebopeho sa papiso ea motho a le mong, thuto e ts'ehetsa karolo ea sisteme ea dopamine libakeng tsa boko le lipoping tsa setho sa botona ho pathophysiology ea SAD.

Selelekela

Sisteme ea dopamine e kenella boits'oarong ba sechaba, ho ithuta le taolo ea maikutlo, ho bolela esale pele karolo ea pathophysiology ea likhathatso tsa khatello ea sechaba (SAD). Lithuto tsa ho nahana ka molek'hule li fane ka tšehetso ea mantlha bakeng sa ts'usumetso ena, ho bonts'a litekanyetso tse fokotsang tsa matšoao a driantal dopaminergic ho tsa pele le tsa postynaptically ho bakuli ha li bapisoa le lithuto tsa taolo.^{1, 2, 3} Leha ho le joalo, litholoana tse mpe le tsona li tlalehiloe.⁴ Tlhaloso e ka bang teng mabapi le ho se lumellane hona e kanna ea ba hore ha ho na lithuto tse entsoeng ho fihlela joale tse ileng tsa hlahloba tšebetso ea dopamine libakeng tsa boko kapa tsa pele, tse bonts'itseng ho nka karolo ho SAD ho latela lithuto tsa ts'ebetso ea boko (bakeng sa tlhahlobo, bona Ref. 5). Karolong e 'ngoe, sena se bile ka lebaka la mefokolo ea mokhoa, joalo ka ha molumo oa pele oa D2-receptor (D2-R) positron emission tomography (PET) radioligands joalo ka [¹¹C] raclopride ha e na tšebelisano e lekaneng bakeng sa litekanyo libakeng tse tlase tsa methapo ea kutlo tsa bongo.

Lithuto tsa PET li bonts'itse phapang e fapaneng pakeng tsa motho ka mong maemong a matšoao a dopaminergic lithutong tsa taolo e phetseng hantle.⁶ Sena se baka phetoho lithutong moo bakuli le lithuto tsa taolo ba bapisoang, ka ho hlokahala mehlala e meholo ea mohlala ho bona phapang e nyane. Ntle le moo, liphapang tsa sehlopha maemong a biomarker ha li amane ka ho toba le khokahano ea Causal. Moralo oa liteko moo letšoao la bioloji le bonoang e le ts'ebetso ea phetoho maemong a mafu le ka nkuoa e le leano le matla ho feta tsena. Ka ts'ebeliso ea kelello, nts'etsopele ea mefuta e sebetsang ea psychotherapy e fana ka monyetla o ikhethang oa ho ntlafatsa matšoao ntle le ho kena-kenana ka ho toba le biochemistry ea boko. Bakeng sa SAD, kalafo ea boits'oaro ba kelello (CBT) e lebisa ntlafatsong ea kliniki ho fihlela ho 75% ea bakuli.^{7, 8}

Leha lithuto tse 'maloa ba batlisisa phello ea a tlhaloganyo ka boko Tshebediso ya jwalo lekanyetswa go ya ka ho sebedisa PET le tshebetso gomoso a khoheli nka litšoantšo (MRI), ditlaleho ka liphetoho neurotransmission ba' nile ba fokola. Ho eketsa tlama ho transporter ea serotonin bohareng ba mokokotlo ka mor'a likhoeli tsa 12 tsa kalafo ea psychodynamic ho bontšitsoe mokhatlong oa bakuli ba nang le khatello ea maikutlo. Ha ho phetoho e bonts'itsoeng maemong a dopamine transporter.⁹ Phuputsong e latelang e sebelisang PET le [¹¹C] WAY-100635, 5HT_1a-receptor binding e bontšitsoe ho eketseha ho bakuli ba nang le khatello e kholo ea khatello ea maikutlo ka mor'a nakoana psychodynamic psychotherapy.¹⁰ Leha ho le joalo, ho lithuto tsena kaofela ha ho kamano e ka bonts'ang lipakeng tsa phetoho maemong a biomarker le ntlafatso ea matšoao. Qetellong, thutong ea morao tjena ho bakuli ba nang le khatello ea maikutlo, ha ho na phello ea psychodynamic psychotherapy e bonts'itsoeng ho dopamine D2-R e tlamang ho striatum.¹¹ Ho fihla joale, ha ho na lithuto tse hlahlobeng phello ea CBT ho letšoao la li-neurotransmission tsa boko. Joalo ka ha CBT e le kalafo e matla e hatelletsang ho pepesetsoa maikutlo khafetsa ho ts'usumetso ea ts'abo e le ho fokotsa maemo a ho tšoenyeha (mohlala, bona Ref. 12), mofuta ona oa psychotherapy e ka ba sebaka se ts'episang haholoanyane bakeng sa ho fumana li-correo tsa neurobiological ho fetola matšoao.

Phuputsong e teng hona joale, sepheo sa mantlha e ne e le ho etsa lipatlisiso karolo ea sistimi ea dopamine ho SAD ho sebelisa moralo oa motho ka mong, ka ho hlahloba kamano pakeng tsa phetoho maemong a matšoao kamora CBT le phetoho ho dopamine D2-R e tlamang. Re boletse esale pele hore bokhoni bo tlamang ba ho eketsa (BP_ND) e tla amahanngoa ka ho khetheha le maemo a fokotsehileng a matšoenyeho maemong a sechaba. Boithuto bona bo entsoe ho sebelisoa radioligand ea holimo-khang ea D2-R antagonist radioligand [¹¹C] FLB 457,¹³ e etsang hore litekanyetso libakeng tse potileng tsa bongo tsa thahasello e khethehileng bakeng sa SAD, mme litlhahlobo li ile tsa etsoa ho sistimi e phahameng ea qeto ea tomograph PET bakeng sa ho nepahala ha anatomical.¹⁴

Lisebelisoa le mekhoa

Lihlooho

Bakuli ba robong ba nang le SAD ba ile ba nkuoa thutong e neng e bapisoa le CBT e neng e tsamaisoa ka kalafo ea sehlopha sa marang-rang, 'me litholoana tsa teng li tlalehiloe hosele.¹⁵ E le karolo ea thuto ea kalafo, lithuto tsohle li ile tsa botsoa ke ngaka ea mafu a kelello mme tsa fumanoa li phethahatsa maemo a DSM IV bakeng sa SAD¹⁶ sebelisa puisano e hlophisitsoeng ea bongaka bo hlophisitsoeng bakeng sa mathata a DSM-IV axis I. Comorbidity, ho kenyelletsa le lithethefatsi le tlhekefetso, e ile ea hlahlojoa ho sebelisoa lipotso tsa Mini-International Neuropsychiatric Puisano.¹⁷ Kamora ho kenyelletsoa lipatlisisong tsa PET, bakuli ba ile ba khethoa ka mokhoa o sa reroang kalafo ka mokhoa oa sehlopha kapa kalafo ka inthanete. Lithuto li ne li phetse hantle joalo ka ha ho fanoa ka tlhahlobo ea 'mele le liteko tsa mali tse tloaelo le tlhahlobo ea MRI ea boko. Lithuto tse tharo li ne li kile tsa tšoaroa ka serotonin kapa serotonin le noradrenaline reuptake inhibitors, empa ha ho le ea mong ea amohetseng kalafo ea pharmacological bakeng sa SAD nakong ea likhoeli tsa 2 pele ho thuto. Ha ho na batho ba neng ba sebelisa nikotine. Mokuli a le mong o phethile mokhoa oa ho tšoenyeha ka nako e tšoanang le agoraphobia, ho seng joalo ho ne ho se na comorbidity e neng e le teng. Bakeng sa lintlha tse ling tsa thuto, bona Lethathamo 1. Boithuto bona bo amohetsoe ke Boto ea Tlhahlobo ea Boitšoaro ba Libaka hammoho le Komiti ea Ts'ireletso ea mahlaseli sepetlele sa Karolinska, Stockholm. Litaba li kenyelelitsoe feela kamora ho fana ka tumello e ngotsoeng.

Lethathamo 1

Palo ea batho ba nang le mamello

Litekanyetso tsa matšoao

Ho kenyelletsoa thutong ea kalafo le ka mor'a kalafo, bakuli ba ile ba hlahlojoa le ngaka e laoloang ke Liebowitz Social Anxcare Scale (LSAS).¹⁸ Mofuta oa boits'oaro oa tekanyo e tšoanang (LSAS-SR)¹⁹ e ile ea phethoa ka marang-rang ka kotloloho pele le ka mor'a kalafo. LSAS e entsoe ka lipenshene tse peli, e 'ngoe e lekanyang matšoenyeho maemong a fapaneng (LSAS)_tšoenyeha), le tse ling tse lekolang tekanyo ea thibelo maemong a tšoanang (LSAS_qoba). Ha re kholoa hore ho tlama D2-R ho tla amana haholo le maemo a matšoenyeho, LSAS_tšoenyeha ke sephetho sa phapang e kholo. Maemong a 'maloa, nako pakeng tsa tekanyo ea kliniki le litlhahlobo tsa PET e ile ea eketsoa ho fihlela likhoeli tse' maloa, 'me maemong a mang tekanyo e entsoe ke lingaka tse fapaneng tsa kelello pele le ka mor'a kalafo. Ka hona, ke lintlha tsa LSAS-SR feela tse kenyellelitsoeng tlhahlobisong. PET1 e ile ea etsoa ka kakaretso ea 13 ± 14 (e bolelang ± sd) matsatsi pele ho litekanyetso tsa kalafo ea kalafo, le nako pakeng tsa litekanyetso tsa kalafo le PET 2 e ne e le matsatsi a 17 ± 15.

Treatment

Bakuli ba bararo ba ile ba fumana kalafo ea boitšoaro ea sehlopha sa boits'oaro¹² le bakuli ba tšeletseng CBT e thehiloeng inthaneteng.²⁰ Nako ea kalafo e ne e le libeke tsa 15 maemong ao ka bobeli. Phekolo e sebelisitsoeng thutong, ka mekhoa eohle ea phepelo, e ile ea latela mohlala oa CBT e hatisang bohlokoa ba boitšoaro bo botle ba ts'ireletso le polokeho le litlhaloso tse fosahetseng tsa liketsahalo tsa sechaba le tsepamiso ea kahare e le lintlha tsa SAD.^{21, 22} Motheo oa theoretical le mekhoa e reriloeng e ne e tšoana ebile e le sephetho sa mantlha ho tsoa thutong ea kalafo, eo sampole ea hona joale e neng e hapiloe, ke hore CBT e thehiloeng inthaneteng le sehlopha sa CBT li hlahisa litholoana tse tšoanang tsa kalafo.¹⁵ Palo ea Median ea li-program tse tlatsitsoeng kapa li-module tsa mefuta eohle ea phumants'o e ne e le 13 ea 15 (bolela = 11.5; sd = 3.5). Barupeluoa bohle ba ile ba pepesetsoa likarolo tsa mantlha tsa kalafo.

Litlhahlobo tsa MR

E le karolo ea ts'ebetso ea ho kenyelletsoa, bakuli bohle ba ile ba etsa tlhahlobo ea MRI ea T1- le T2 e boima ba 1.5T GE Signa Scanner (Milwaukee, WI, USA). Setšoantšo sa T2 se ile sa hlahlojoa bakeng sa pathology ea macroscopic, mme setšoantšo sa T1 se ile sa sebelisoa tlhahlobisong e latelang ea setšoantšo.

Radiochemistry

Radioligand [¹¹C] FLB457 ke benzamide e fetotsoeng le tumellano ea 0.02nmoll^-1 bakeng sa D2 le D3 dopamine receptors ka vitro e phahameng haholo ho feta ea [¹¹C] raclopride (1-2nmoll^-1).¹³ Tšobotsi ena e lumella tlhahlobo ea libaka tsa boko tse fetelletseng moo likhahla tsa D2-R li fokolang. [¹¹C] FLB457 e ne e entsoe ka mokhoa o hlalositsoeng pejana.²³ Motsoako o kentsoeng oa PET1 le PET2 e ne e le 468 ± 16 le 465 ± 19MBq, ka ho latellana. Bakeng sa mabaka a tekheniki, tlhaiso-leseling mabapi le ts'ebetso e ikhethang le kakaretso e kenelletseng e ile ea lahleheloa ke PET1 e le 'ngoe PET2, ka ho latellana. Bakeng sa litlhahlobo tse setseng, mosebetsi o ikhethileng e ne e le 1436 ± 2348 le 658 ± 583GBqμmol^-1 bakeng sa PET1 le PET2, mme boima ba lejoala la FLB 457 e ne e le 0.41 ± 0.3 le 0.58 ± 0.6μg, ka ho latellana. Tekanyetso e kenang, ts'ebetso e itseng le boima bo ne bo sa fapana pakeng tsa kalafo ea pele le ea kalafo (P> 0.5, e kopane t-test), 'me ka bohlokoa, ho ne ho sena khokahano pakeng tsa boima le ente kapa BP_ND kapa ho fetoha hoa matšoao.

Litlhahlobo tsa PET

Litlhahlobo tsa PET li ile tsa etsoa lenaneong le phahameng la ho etsa lipatlisiso tsa tlhahlobo ea manonyeletso (LG Molecular Imaging, Knoxville, TN, USA). Pele ho tlhatlhobo ea pele ea PET, ho ile ha etsoa helmete ea samente bakeng sa thuto ka 'ngoe ka bo eona ho fokotsa motsamao oa hlooho nakong ea litekanyo. Nako pakeng tsa PET1 le PET2 e ne e le matsatsi a 146 ± 23. Nako e karolelitsoeng ea ente e ne e le 12: 24 ea PET 1 le 11: 53 ea PET2. Pele ho emisoa, ho ne ho etsoa scan ninemani ea 5-min ho lokisa bakeng sa ho fihlella le ho hasanya. [¹¹C] FLB 457 e ile ea kenngoa ka har'a mothapo oa antecubital e le lethal e le bolus mme radioactivity e lekantsoe 87mets. Bakeng sa lithuto tse peli, tlhahlobo ea bobeli e ile ea sitisoa pakeng tsa 910 le 1416s le 3361 le 3623s, ka ho latellana. Likhohlano tsena li ile tsa qheleloa ka thoko tlhahlobisong e latelang ea kinetic. Litšoantšo li ile tsa hahuoa bocha ho latela ts'ebetso e tloaelehileng ea Poisson e likarolo li tharo e kopantsoeng le ho eketsa ts'ebetso ea algorithm, e fana ka tharollo ea sefofane sa 1.5mm ka halofo-e phahameng bohareng ba tšimo ea pono.¹⁴

Tlhahlobo ea litšoantšo

Litšoantšo tsa PET li ile tsa lokisoa hore motsamao oa hlooho o sebelisoe ka sebopeho sa tokiso ea setlamo ka sebopeho,²⁴ ka sebopeho se seng le se seng sa setšoantšo se sebetsa e le pontšo ho se latelang. Litšoantšo tsa T1 MR li ile tsa fetisetsoa moketjaneng oa ka ntle oa ntlo - sefofane sa kamora morao. Melao ea lithahasello (ROIs) e ile ea hlalosoa ka nepo ho MRI bakeng sa thuto ka 'ngoe ka bo eona, ho sebelisoa software ea Human Brain Atlas²⁵ (Setšoantšo sa 1). Mebuso e khethiloeng e ne e le amygdala, hippocampus le li-cortices tsa pele, tse thehiloeng ho karolo ea bona e reriloeng ho SAD,⁵ mme li-ROI li ile tsa hlalosoa li sebelisa tataiso e neng e hatisitsoe pele.^{26, 27} Cortex ea pele e ne e arotsoe ka libaka tsa dorsolateral, medial and orbitof Pambal.²⁷ Likarolo tsa litereke ha lia ka tsa hlahlojoa, e le kamano e phahameng ea [¹¹C] FLB 457 ha e lumelle ho lekana kahare ho sebopeho sa liteko tsa PET, ka hona e thibela lipalo tse nang le moelelo tsa tlamo ea radioligand.²⁸ Li-MRIs li ile tsa aroloa hore e be ntho e putsoa, lintho tse tšoeu le mokelikeli oa k'holeseterole, 'me tsa ngolisoa ka ho hlaka ho e' ngoe ea litšoantšo tse peli tsa PET li sebelisa SPM5 Litekanyetso tsa phetoho tse fumanoeng li ile tsa sebelisoa ho kenya ts'ebetsong li-ROI litšoantšong tse matla tsa PET ho hlahisa li-curve tsa ts'ebetso ea nako (TACs). Bakeng sa libaka tse ka pele tsa cortical, ho ne ho kenyelletsoa voxels feela ea karolo e putsoa ea ROI. Hape khalemelo e sebetsang ea bophahamo ba molumo o sebelisang mokhoa oa Meltzer e ile ea sebelisoa bakeng sa libaka tsena ho qoba tšitiso e tsoang ho li-voxels tsa CSF tse haufi.²⁹ Ts'ebetso ea litšoantšo e entsoe ho SPM5 e sebetsang ho Matlab R2007b (MathWorks, Natick, MA, USA).

Setšoantšo sa 1

(a-c) Magnetic resonance litšoantšo tse nang le libaka tsa lithahasello tsa amygdala (khubelu), hippocampus (mosehla), dorsolateral prefrontal cortex (cyan), medial prefrontal cortex (blue) le orbitof Pambal cortex (botala). (d-f) Litšoantšo tse akaretsang tsa [¹¹C] FLB (Hape …)

BP_ND e ile ea balelloa ho tsoa ho li-TACs ho sebelisa mofuta o bonolo oa li-tishene tsa seteraeke (SRTM), e nang le "cerebellum" ho joalo ka litšupiso. Boemong bona, BP_ND e emela karolelano ea mahlakore a radioligand a tlameletsoeng ka ho lekana le radioligand e ke keng ea khoneha lithong.³⁰ SRTM pele e ne e netefalitsoe bakeng sa [¹¹C] FLB 457.²⁸ Kaha re ne re sena hypothesis ea litla-morao tse kenelletsang ho dopaminergic neurotransuction ho SAD, BP_ND bakeng sa libaka tsohle li ile tsa baloa li sebelisa li-TAC tse karolelano ea libaka bakeng sa mahlakore a nepahetseng le a leqele bakeng sa ho ntlafatsa lipalo tsa TAC.

Tlhahlobo ea statistical

Liphetoho linthong tsa LSAS le D2-R BP_ND ba ile ba hlahlojoa ba sebelisa lipara t-etona. Litloaelano lipakeng tsa D2-R BP_ND 'me lintlha tsa LSAS motheong oa motheo li ne li baloa li sebelisa likarolo tse ling, ho laola lilemo. Kamano lipakeng tsa liphetoho tse tlamang D2-R e tlamang le liphetoho LSAS_tšoenyeha lintlha li ile tsa hlahlojoa ho sebelisoa tlhahlobo ea khafetsa ea covariance, ka nako le sebaka joalo ka likarolo le litaba tsa LSAS_tšoenyeha liphesente lia fetoha e le covariate. Litlhahlobo tsa bobeli li ile tsa etsoa bakeng sa LSAS_qoba 'me likhakanyo tse peli li kopantsoe. Kamora moo, li-coefficients tsa amanang le tsona li ile tsa balelloa pakeng tsa phetoho ea liperesente ho D2 BP_ND le phetoho liperesente ho LSAS_tšoenyeha lintlha. A post-hoc tlhahlobo, batho ka bomong ba ile ba aroloa ho ba ba arabelang (Phokotso ea matšoao a 50% le ba sa arabeng, le phapang ea lihlopha ho BP_ND boleng bo ile ba batloa ho sebelisoa tlhahlobo e le 'ngoe ea phapang. Bakeng sa liteko tsohle, liphetho li ne li nkuoa e le tsa bohlokoa ho P<0.05. Tlhahlobo ea lipalo-palo e entsoe ho sebelisoa PASW 18 (SPSS, Chicago, IL, USA).

Results

Liphetoho maemong a matšoenyeho a sechaba le D2-R BP_ND

Bakuli bohle ba ile ba ntlafala kamora kalafo, mme phetoho ea palo eohle ea LSAS hammoho le matšoenyeho le lithuso tsa phemelo li ne li le bohlokoa ka lipalo (Lethathamo 2). Ho ne ho se na phapang phetoho ea LSAS lipakeng tsa bakuli ba fumanang kalafo ea sehlopha le bakuli ba tšoaroang ka marang-rang, ekaba ka kakaretso eohle kapa bakeng sa subscales (P> 0.74). Nakong ea kalafo kamora 'kalafo, barupeluoa ba bane (44%) ha ba sa kopana le litekanyetso tsa tlhahlobo ea SAD. Boemong ba sehlopha, phapang ea kalafo e tlamang ea D2-R le kalafo ea kamora 'kalafo ha ea ka ea fihlela boleng ba lipalo bakeng sa libaka life kapa life, joalo ka ha ho hlahlojoa ho sebelisoa lipara t-eteteLethathamo 2). Leha ho le joalo, tataiso le boemo ba phetoho li bonts'a phapang e fapaneng e fapaneng, e ileng ea thusa ho kopants'oa ha melaetsa e lumellanang le phetoho ea matšoao.

Lethathamo 2

D2-receptor-binding-binding e tlamang le matšoao a matšoao pele le ho phumala

Litloaelano lipakeng tsa D2-R BP_ND phetoho le phetoho ea matšoenyeho a sechaba

Boitekong bo pheta-phetoang ba covariance, litlamorao tsa bohlokoa tsa nako le nako tsa pontšo ea li-tokiso li bonts'itsoe LSAS_tšoenyeha (F = 7.61, P= 0.028 le F = 7.77, P= 0.027). Tlhahlobisong e latelang ea tikoloho le tikoloho, khokahano e mpe pakeng tsa phetoho ho D2-R BP_ND le LSAS_tšoenyeha phetoho e bonts'itsoe bakeng sa cortex ea dorsolateral pele.r= -0.78, P= 0.013), "cortex" e tlang pele ho kalafor= -0.82, P= 0.007) hammoho le bakeng sa hippocampus (r= -0.81, P= 0.008; Setšoantšo sa 2). Liphakanyo tse ho medial prepaleal cortex le hippocampus li pholohile khalemelo ea Bonferroni (e fetotsoe P-ba bohlokoa <0.01). Libakeng tsena, ba arabelang ba bontšitse keketseho ea tlamo (5.0% le 9.5%, ka ho latellana, n= 4), athe ba neng ba sa arabe ka karolelano ba bontšitse ho fokotseha (−8.6% le −8.3%, n= 5). Leha ho na le batho ba fokolang sehlopheng ka seng, phapang ena e ne e le bohlokoa ho MFC (P= 0.003) le boemo ba maemo a bohlokoa bakeng sa hippocampus (P= 0.097). Ha ho na tšusumetso e kholo ea phetoho ea nako kapa ea nako ea pontšo ho tokiso ea thibelo. Phapang ena ea litlamorao lipakeng tsa subscales e ile ea bonts'oa hape hobane ha ho kopanya sekala tse peli e le covariate, litla-morao tsa maemo li ile tsa bonoa bakeng sa nako (F = 3.93, P= 0.088) le nako ea tšebelisano bakeng sa nako ea phetoho ea x = (F = 3.74, P= 0.095).

Setšoantšo sa 2

Scatterplots e bonts'a likamano lipakeng tsa phetoho ho Liebowitz Social Anxcare Scale (LSAS) lintlha tsa ho tšoenyeha le dopamine D2-receptor-binding mohlomong (BP) ho dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MFC) le hippocampus (HIP). (Hape …)

Likahare tsa pele le tsa kalafo pakeng tsa D2-R BP_ND le matšoenyeho a sechaba

Ho ne ho se na kamano pakeng tsa D2-R BP_ND le LSAS_tšoenyeha kapa LSAS_qoba lintlha pele ho nako, kapa ho kula, kamora ho laola lilemo.

Puisano

Thutong ena, re ile ra lekola karolo ea sistamine ea extopriatal dopamine SAD, ka ho hlahloba liphetoho dopamine D2-R e le ts'ebetso ea phetoho ea matšoao kamora CBT. Habohlokoa, sepheo sa thuto ena e ne e se ho hlahloba litlamorao tsa kalafo ea kelello ho D2-R binding ho SAD, kaha sena se ka kenyelletsa tšebeliso ea boemo ba taolo. Sebakeng seo, CBT e sebelisitsoe e le sesebelisoa sa ho fetola boemo ba lefu boo e seng ba meriana. Ka lebaka leo, kamano pakeng tsa phetoho ea matšoao a lipontšo le liphetoho tse tlisoang ke li-receptor binding e bile sephetho sa mantlha, ho fapana le ho fetoloa le ho khutlisetsoa ka bongata sehlopheng sa sehlopha. Ka hona, athe phapano ea karolelano mahareng a PET1 le PET2 e ne e le kahare ho phapano ea teko e bonts'itsoeng pejana bakeng sa [¹¹C] FLB 457,³¹ phetoho e kopanetsoeng e fapaneng e ne e lekane bakeng sa tlhahlobo e lumellanang. U sebelisa moralo o ts'oanang, liphetoho ho D1-receptor binding li sa tsoa bontšoa hore li amana le ntlafatso ea bokhoni ba ho hopola kamora ho sebetsa koetliso ea memori,³² 'me joale re qala ho bonts'a kamano e tobileng lipakeng tsa phokotso ea matšoao kamora ho phekoloa ka kelello le phetoho ho letšoao la methapo ea kelello.

Karolo ea sisteme ea dopamine boits'oarong ba sechaba e bonts'itsoe lipatlisisong tsa liphoofolo le lithutong tsa batho. Boithuto ba ho nahana ka molek'hule bo bontšitse khokahano e mpe lipakeng tsa matšoao a makhopho a DA le litšobotsi tsa botho hammoho le mehato e fapaneng ea ho ikamahanya le maemo le maemo a tlase sechabeng.^{33, 34, 35, 36, 37, 38, 39} Haufinyane tjena, re atolositse moeli ona oa lipatlisiso ka ho bonts'a kamano e lipakeng tsa takatso ea sechaba le D2-R e tlamang moetlo oa medial temporal joalo ka ha ho lekantsoe ho sebelisoa [¹¹C] FLB 457.⁴⁰ Sebakeng sa motho e mong le e mong, litšobotsi tsena li ka shejoa ho bontša ho ikokobelletsa sechaba ho fapana le taolo ea sechaba,⁴⁰ mme diphetho ka hona li etsa lipatlisiso tsa sejoale-joale mabapi le litoeba le litheko tsa batho bao e seng batho moo dopaminergic neurotransmission e amanang le boholo ba boitšoaro bo ikokobelletsang.^{41, 42, 43, 44} Ho khahlisang haholo ke thuto eo Morgan et al a.,⁴⁴ moo D2-R e tlamehang ho litšoene e bonts'itsoe e fetoha ts'ebetso ea maemo a hloahloa ha liphoofolo li tloha ho motho ka mong ho ea matlong a sechaba. Ho hlokomela kamano pakeng tsa phetoho ho D2-R matšoao a tlamang a setjhaba le kopane le mela e mengata ea lipatlisiso mme ho ka talingoa e le ts'ehetso ea khokahano e khothalelitsoeng pakeng tsa tekanyo e ikokobelitseng ea boits'oaro ba motho le SAD.⁴⁵ Ho ikamahanya ha tsona ho ne ho se bohlokoa bakeng sa LSAS_qoba, e ka hlalosoang ke mofuta o makatsang oa boiketsetso. Mohlala, thibelo e fokotsehileng ea boits'oaro bo bolokehileng ha e lebelloe ho hlahisa khatello e tlase.²¹

Lithuto tsa SPECT li kile tsa bonts'a pele dopamine D2-R e tlamang ho striatum ho bakuli ba 10 ba nang le SAD, hammoho le sampole ea 7 e nang le comorbid OCD ha e bapisoa le lithuto.^{1, 2} Ka lehlakoreng la Presynaptic, ho tlama dopamine transporter e tlase ho bontšitsoe ho bakuli ba 11.³ Phuputsong e sa tsoa feta e sebelisitsoeng PET, ha ho phapang e ileng ea bontšoa ho fumaneha ha D2-R, ebang ke motheo kapa kamora phephetso ea amphetamine, hape ho ne ho sena phapang ea ho tlama ho phepelo ea dopamine (n= 15, 12 le 12, ka ho latellana).⁴ Leha ho le joalo, ha ho le e 'ngoe ea lithuto tsena e ileng ea lekola li-receptor tsa dopamine libakeng tsa boko bo fetisisang.

Ka lithuto tsa Tshebediso ya boko, e mong oa se fumaneng ho fetisisa replicated e eketsehileng Tshebediso ya ka amygdala ka lebaka la ho susumetsa ba tšoha ea sechaba^{46, 47, 48} empa, ho hlokometsoe, liphetho tse mpe le tsona li tlalehiloe.^{49, 50} Likarolo tse ling tse bontšang tšebetso e fetotsoeng ho SAD li kenyelletsa hippocampal le pele ho li-cortices.^{5, 46, 47, 51, 52, 53} Bakeng sa cortex ea medial prefrontal cortex, karolo e tobileng ho lekola tlhahlobo ea sechaba e bontšitsoe ho bakuli ba SAD^{51, 52} mme sebaka sena se boetse se kenelletse ho timelleng hoa tšabo.^{54, 55} Phetisetso ea dopaminergic ka hippocampus e bonts'itse ho kenya letsoho ts'ebetsong ea memori lipatlisisong tsa liphoofolo le lithutong tsa ho nahana ka limolek'hule.^{56, 57, 58, 59} Ha ho nkuoa hammoho, liphumano tsa hona joale tsa khokahano pakeng tsa ts'ebetso ea dopaminergic libakeng tsa hippocampus le libakeng tsa pele tsa cortical li ka amana le karolo ea libaka tsena ho ithuteng le litekong tsa sechaba.

Sekhahla se ka sehloohong sa thuto ena ke boholo ba sampole e nyane. Le ha bakuli ba 126 kaofela ba kenyellelitsoe thutong ea kalafo.¹⁵ bakeng sa thuto ea hona joale re sebelisitse litekanyetso tse kenyelletsoeng haholoanyane tsa ho kenyelletsa sepheo sa ho qoba litlamorao tse fumanehang mabapi le ho fumaneha ha D2-R, mohlala ka tšebeliso ea meriana e kopaneng ea litlhare kapa nikotini. Ho feta moo, bakuli ba bang ba ile ba lahleha ka lebaka la mathata a nako. Taba ea bobeli, re ke ke ra tseba hore na liphetoho li BP_ND li bakiloe ke liphetoho matsatsing a letsoalo la receptor kapa tumellano e bonahalang e le teng, hobane liparamente tsena li ke ke tsa aroloa ho latela tekanyo e le 'ngoe ea PET.³⁰ Har'a lintho tse susumetsang tšebelisano-'mōtoana, maemo a dopamine a tsoang morao a bontšitse hore a ama [¹¹C] FLB 457 e tlamang,^{60, 61, 62} leha ho le joalo, lithuto tse ling li bile mpe.^{63, 64} Lifeme, moo litekanyetso tsa methapo ea kutlo li fumanehang habonolo, ho lokolloa ha DA ho hlokometsoe ho arabela ts'usumetso e sithabetsang.^{65, 66} Leha lithuto li sebelisa litlhahlobo tse ngata tsa PET ka ts'ebetso e fapaneng ea [¹¹C] FLB 457 e bontšitse hore li-recensor density account li thusa haholo ho fapana ho BP_ND,⁶⁷ ho ke ke ha qheleloa ka thoko hore phapang e teng maemong a dopamine ea nako e telele e ka ikarabella bakeng sa mekhatlo e hlokometsoeng, mohlala, e bonts'a tšebetso e phahameng ea DA nakong ea tlhahlobo ho bakuli ba ntlafatsang hanyane kamora kalafo.

Qetellong, liphetho tse tsoang thutong ena ea pele li bonts'a hore liphetoho tsa polasetiki tsamaisong ea dopamine li ka fokotsa matšoao a ho tšoenyeha ho bakuli ba SAD kamora kalafo le CBT. Boithuto bona bo tšehetsa karolo ea sisteme ea dopamine ho SAD, mme e bonts'a hore papiso ea motho a le mong e ka ba mokhoa o ts'episang oa ho khetholla li-biomarkers tsa boko bakeng sa mafu a kelello.

lumela hore baa fokola

Boithuto bona bo tšehelitsoe ke Söderström Königska Stiftelsen, Boto ea Naha ea Bophelo le Boiketlo, Stockholm County Council le Psykiatrifonden. Basebetsi ba Setsing sa Karolinska PET le ba Lefapha la Psychiki ea Inthanete Sepetleleng sa Karolinska University Huddinge ba lebohile ka kananelo.

Notes

Bangoli ba phatlalatsa hore ha ho na likhohlano tsa thahasello.

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