Isbeddelka ku yimaadda dopamine D2-receptor cillad ayaa la xiriirta hoos u dhigista calaamadaha ka dib marka daaweynta teraabiyada cilminafsiga (psychotherapy) ee ku saabsan xannuunada bulshada (2012)

Sharax: Cilmi-nafsi maskaxeed (2012) 2, e120; doi: 10.1038 / tp.2012.40

S Cervenka¹, E Hedman^1,2, Y Ikoma^1,3, D Radu Djurfeldt¹, C Rück¹, C Halldin¹ iyo N Lindefors¹

¹Waaxda Qeybta Neuroscience, Qaybta Maskaxeed, Karolinska Institutet, Stockholm, Sweden
²Waaxda Neuroscience, Xarunta Osher ee Daawada Isku-dhafan iyo Qeybta Cilmi-nafsiga, Karolinska Institutet, Stockholm, Sweden
³Machadka Imtixaanka Maaskariirka, Machadka Qaranka ee Radiological Sciences, Chiba, Japan

Wareysiga: Dr S Cervenka, Waaxda Dhimirka Nuujiyaanka, Qeybta Maskaxda Dhimirka, Karolinska Institutet, Jaamacada Karolinska University Solna, Dhismaha R5, 171 76 Stockholm, Sweden. E-mail: [emailka waa la ilaaliyay]

La helay 19 Maarso 2012; La aqbalay 10 Abriil 2012

aan la taaban karin

Nidaamka dopamine waxaa lagu soo jeediyey inuu door ka qaato xanuunka wacyigelinta bulshada (SAD), oo qayb ahaan ku salaysan baaritaanada sawir-baadhista sheybaarka muujinaya heerarka hoos-u-dhigista dopaminergic-ka ee bukaannada marka loo eego maadooyinka kontaroolka. Si kastaba ha noqotee, nidaamka dopamine looma baarin goobaha hore ee maskaxda iyo limbic maskaxda lagu soo jeediyey in ay noqdaan bartamaha pathophysiology ee SAD. Daraasaddan cilmibaadhista ah, waxaannu ku qiimeynaynaa in heerarka dopamine D2-receptor (D2-R) lagu qiyaaso isticmaalka sawir-shaxanka xasaasiga ah (PET) uu saadaalinayo calaamadaha la yiraahdo dabeecadda garaadka (CBT). Sagaal qof oo bukaannada SAD ah ayaa la baaray iyada oo la adeegsanayo PET-ga oo sarreeya iyo jilicsanaanta D2-R antagonist radioligand [¹¹C]FLB 457, ka hor iyo ka dib toddobaadka 15 ee CBT. Heerarka calaamadaha ayaa la qiimeeyay iyadoo la adeegsanayo walwalka hoose ee liiska cabirka Bulshada ee Liebowitz (LSAS)_anx). Markii la sii daayay, waxaa jiray hoos u dhac weyn oo laga soo qaaday calaamadaha walaaca bulshada (P<0.005). Iyadoo la adeegsanayo falanqeyn cabbiraado soo noqnoqda oo ku saabsan kala-badhnaanta, saamaynta weyn ee waqtiga iyo waqtiga × LSAS_anx isbeddel ku yimaad D2-R-ku-xirnaan kara (BP_ND) ayaa la muujiyay (P<0.05). Falanqaynta soo socota ee gobol-gobol, isku xirnaanta xun ee udhaxeysa isbeddelka D2-R BP_ND iyo LSAS_anx isbeddel ayaa laga helay kortex celcelis ee hore iyo hippocampus (P Tani waa daraasadda ugu horreysa ee lagu soo bandhigo xiriir toos ah oo u dhaxeeya isbedelka astaamaha ka dib daaweynta cilmu-nafsiga iyo calaamadaha maskaxda neurotransmission. Isticmaalka naqshadeynta isbarbardhiga shakhsi ahaaneed ee shakhsi ahaaneed, daraasaddu waxay taageertaa doorka habka dopamine ee gobollada maskaxda iyo limbic ee ku jira fayaqowrka nafsiga ee SAD.

Hordhac

Nidaamka dopamine wuxuu ku lug leeyahay dhaqanka bulshada, xakamaynta barashada iyo shucuurta, oo saadaalinta doorka ku jira jirdhiska maskaxda wacyiga bulshada (SAD). Daraasado sawir-baadhis ah oo miisaaniyadeed ayaa bixiyay taageero hordhac ah oo muujinaysa sharaxaaddan, oo muujineysa heerarka calaamadaha dopaminergic-yada ah ee labadaba horay iyo ka dib marka loo eego bukaanada marka loo eego maadooyinka kontoroolka.^{1, 2, 3} Si kastaba ha ahaatee, natiijooyinka taban ayaa sidoo kale la soo sheegay.⁴ Faahfaahin suurtogal ah oo ku saabsan isku-dheelitir la'aantaas waxay noqon kartaa in mid ka mid ah daraasadaha aan ilaa iminka samaynin ay baaritaan ku sameeyeen nidaamka dopamine ee gobollada maskaxda ama barafka hore, kuwaas oo muujiyay in ay ku lug leeyihiin SAD iyadoo lagu saleynayo daraasadaha waxqabadka maskaxda (dib-u-eegid, fiiri ref. 5). Qeyb ahaan, tani waxay sababtay xadidaadaha habka, sida jiilka kowaad ee D2-reseptor (D2-R) oo loo yaqaano "positron emission tomography (PET)" radioligands sida [¹¹C] Racsopride ayaa leh qulub aan ku filnayn cabirrada miyir-beeleedyada hoose ee mawduucyada maskaxda.

Daraasadaha PET waxay muujiyeen isbeddel shakhsiyeed oo isbarbar dhigaya heerarka dopaminergic ee mawduucyada ilaalinta caafimaadka leh.⁶ Tani waxay ka dhigan tahay barashada daraasadaha maaddooyinka bukaanka iyo maareynta kiisaska la barbardhigo, maaddaama tirada weyn ee tirooyinka loo baahan yahay si loo ogaado kala duwanaanta yar. Intaas waxaa dheer, kala duwanaanta kooxaha ee heerarka biomarker ma si toos ah u dardar galinayaan xiriirka calaamadaha cudurka. Naqshad tijaabo ah oo calaamadda bayoolajiga loo arko inay tahay isbedel ku dhaca cudurka cudurada ayaa loo tixgelin karaa istaraatijiyad xooggan oo ka mid ah arrimahan. Daaweynta maskaxda, horumarinta qaababka wax ku oolka ah ee daaweynta cilminafsiga waxay bixisaa fursad gaar ah si loo hagaajiyo calaamadaha aan si toos ah u faragelin maskaxda maskaxda. SAD, daaweynta dabeecadda garaadka (CBT) waxay horseedaysaa hagaajinta xarumaha illaa illaa 75% bukaanada.^{7, 8}

Inkasta oo dhowr baaritaan ay baaritaan ku sameeyeen saameynta daaweynta nafsaaniga ah ee dhaqdhaqaaqa maskaxda sida loo qiimeeyay iyada oo la adeegsanayo PET iyo MRI, shaqeyntiisuna waxay ku yar yihiin isbeddelka neurotransmission. Kordhinta culeyska xambaarsan serotonin-ga ee fareemka ka dib markii bilihii 12 ee daaweynta cilmi-nafsiga ee psychodynamic lagu muujiyay koox hoose oo bukaanka qaba niyad-jabka. Wax isbeddel ah lama muujin heerarka cabbiraha dopamine.⁹ Daraasad xiga oo la adeegsanayo PET iyo [¹¹C] WAY-100635, 5HT_1a- Xakamaynta gardarrada ayaa lagu muujiyey inay kordhinayso bukaanada qaba xanuunka weyn ee niyadjabka ka dib marka la yiraahdo psychotherapy psychotherapy.¹⁰ Si kastaba ha ahaatee, daraasadahan midkoodna xiriirka ayaa la muujin karaa inta u dhaxaysa isbeddelka heerarka noolol-biyomarkerka iyo hagaajinta calaamadaha. Ugu dambeyntiina, daraasad dhowaan lagu sameeyay bukaanada qaba niyad-jabka, wax saameyn ah uma leh daaweynta cilminafsiga ee cilmi-nafsiga ee psychodinamic ayaa lagu muujiyey dopamine D2-R oo ku xiran qallooca.¹¹ Ilaa hadda, daraasad cilmi baaris ah ayaa baadhis ku samaysay saameynta CBT-da on calaamadaha neurotransmission maskaxda. Maadaama ay CBT tahay daaweyn degdeg ah iyada oo xoogga la saarayo soo noqnoqoshada soo noqoshada ee cabsida cabsida leh si loo yareeyo heerarka welwelka (tusaale ahaan, fiiri ref. 12), qaabkan daaweynta nafsaaniga ah wuxuu noqon karaa meel lagu kalsoonaado oo lagu ogaanayo xiriirka neurobiological ee isbeddelka astaamaha.

Daraasadani, ujeedada koowaad waxay ahayd in la baaro doorka dopamine ee SAD iyada oo la adeegsanayo isbarbardhigga isbarbardhiga shakhsiyeed, iyada oo la baarayo xiriirka ka dhexeeya isbedelka heerarka astaamaha ka dib CBT iyo isbedelka dopamine D2-R. Waxaan saadaalinnay in korodhka ballaarinta (BP_ND) ayaa si gaar ah loola xiriiri karaa heerarka walaaca ee hoos u dhaca xaaladaha bulshada. Daraasaddan waxaa lagu fuliyay iyadoo la adeegsanayo jilicsanaanta D2-R antagonist radioligand [¹¹C] FLB 457,¹³ taas oo u sahli karta cabbiraadda gobollada maskaxda ee maskaxda ee danta gaarka ah ee SAD, baaritaankana waxaa lagu qabtey nidaam cilmi-baaris oo qotodheer oo ku salaysan kombuyuutarka PET si loo kordhiyo qiyaasta anatomical.¹⁴

Qalabka iyo hababka

maadooyinka

Sagaal bukaan oo qaba SAD ayaa la qorey daraasaddan marka la barbardhigo CBT oo lagu maamulo daaweynta kooxeed ee internetka, natiijooyinka kuwaas oo laga soo wariyay meelo kale.¹⁵ Iyadoo qayb ka ah daraasadda daaweynta, maadooyinka oo dhan ayaa wareysi dhakhtarka sare ee dhimirka iyo waxaa la ogaaday inay buuxinayaan shuruudaha DSM IV ee SAD¹⁶ iyadoo la adeegsanayo wareysiga Rugta ee Qaabilsan Xeeladaha DSM-IV ee I xanuunada. Dulqaadashada, oo ay ku jiraan daroogada maandooriyaha iyo xadgudubka, ayaa la qiimeeyey iyada oo la adeegsanayo Wareysiga Maqalka ee "Min-International Neuropsychiatric".¹⁷ Ka dib markii lagu darey baaritaanka PET, bukaanka ayaa loo kala soocay daaweynta qaabka kooxeed ama daaweynta internetka. Mawduucyada caafimaadku waxay ahaayeen kuwo caafimaad qaba sida lagu ogaado baaritaanka jirka iyo baaritaanka joogtada ah ee dhiigga iyo sidoo kale baaritaanka MRI ee maskaxda. Saddex maaddo hore ayaa lagu daaweeyay serotonin ama serotonin iyo daawada noradrenaline inhibitor, laakiin qofna ma helin daaweyn daawo ee SAD inta lagu jiro bilaha 2 ka hor daraasaddan. Ma jiraan wax nicotine ah. Hal bukaan ah ayaa soo buuxiyay shuruudaha isbedelka argagax ee isdaba jooga ah ee agorafobiya, haddii kale ma jiro wax isdaba joog ah. Mabaadiida mawduucyada dheeraadka ah, eeg Shaxda 1. Daraasadan waxaa ansixiyay Guddiga Dib u Eegista Anshaxa iyo sidoo kale Guddiga Badbaadinta Raadinta ee Isbitaalka Karolinska, Stockholm. Mawduucyada waxaa lagu daray kaliya ka dib markii ay qoraal ku siiyeen ogolaansho wargalin ah.

Shaxda 1

Noocyada Bukaanka

Qiimaynta calaamadaha

Marka lagu daro daraasadda daaweynta iyo daaweynta ka dib, bukaanada waxaa lagu qiimeeyaa cabirka Dhibaatada Bulshada ee Liebowitz (LSAS).¹⁸ Nooca is-qiimeynta ee miisaanka isku midka ah (LSAS-SR)¹⁹ waxaa si dhammeystiran loo soo dhajiyay internetka kahor iyo kadib daaweyn. LSAS waxay ka kooban tahay labo qiyaasood, hal cabbir cabbir ah oo ku saabsan xaalado kala duwan (LSAS_anx), iyo kuwa kale ee qiimeynaya heerka ka fogaanshaha isla xaaladahaas (LSAS_avoider). Sida aynu ku dhigno in D2-R xidhitaanku ku xirnaan doono heerarka walwalka, LSAS_anx wuxuu ahaa isbeddelka natiijada danta guud. Xaalado badan, wakhtiga u dhexeeya qiimeynta rugta caafimaadka iyo baaritaanka PET ayaa la kordhiyey illaa dhowr bilood, mararka qaarkoodna qiimeynta waxaa sameeyay dhakhaatiirta kala duwan kahor iyo kadib daaweyn. Sidaa darteed, kaliya dhibcaha LSAS-SR ayaa lagu daray falanqaynta. PET1 waxaa lagu sameeyay celcelis ahaan 13 ± 14 (celcelis + sd) maalmo kahor qiimeynta daaweynta ka hor, iyo waqtiga u dhaxeeya qiimeynta dib u dhigista iyo PET 2 wuxuu ahaa 17 ± 15 maalmood.

Daaweynta

Saddex bukaan ayaa heley teraabiyada kooxda dabiiciga ah¹² iyo lix bukaan oo ku salaysan CBT-da internetka.²⁰ Muddada daaweynta waxay ahayd 15 toddobaadyo labada xaaladoodba. Daaweyntii loo adeegsaday daraasaddan, qaababka gudbinta labadaba, waxay raaceen habka CBT-ga oo muujinaya muhiimada looga hortagayo iyo dabeecadaha badbaadada iyo sidoo kale si xun u dhicin dhacdooyinka bulshada iyo diiradda gudaha si loo ilaaliyo arrimo SAD.^{21, 22} Nidaamka aasaasiga ah iyo hababka la soo jeediyey waxay isku mid ahaayeen iyo raadintii ugu weyneyd ee daraasadda daaweynta, oo laga soo qaatay shaybaarkaan la soo ururiyey, waxay ahayd in CBT-da ku salaysan Internet-ka iyo kooxda CBT ay saameyn ku yeelato daaweyn isku dhigma.¹⁵ Tirada dhexdhexaadinta casharrada la dhamaystiray ama modules ee labada nooc ee gudbinta labadaba waxay ahaayeen 13 ee 15 (macnaha = 11.5; sd = 3.5). Dhamaan kaqeybgalayaashu waxay soo gaadheen qaybaha ugu muhiimsan ee daaweynta.

Imtixaannada MR

Iyadoo qayb ka ah hannaanka ka mid noqoshada, dhammaan bukaanada waxay sameeyeen baaritaan lagu sameeyo T1-iyo T2-miisaanka MRI iyada oo la adeegsanayo 1.5T GE Signa Scanner (Milwaukee, WI, USA). Sawirka sheyga T2 ayaa la kormeeray maadada macroscopic, iyo sawirka T1 ayaa loo isticmaalay falanqaynta sawirada dambe.

Rugta sheyga

Radioligand [¹¹C] FLB457 waa benzamide la beddelay iyada oo xidhiidhsanaanta 0.02nmoll^-1 loogu talagalay dukaamada D2 iyo D3 dopamine in vitro taas oo aad uga sarreeya tan [¹¹C] raclopride (1-2nmoll^-1).¹³ Qaabkani waxa uu u oggolaanayaa in lagu baaro gobollada maskaxda ee miyir-qabadka halkaas oo D2-R cufnaanta ay yar tahay. [¹¹C] FLB457 waxaa loo soo saaray sidii hore loogu sharraxay.²³ Qaadashada la isku duro ee PET1 iyo PET2 waxay ahayd 468 ± 16 iyo 465 ± 19MBq, siday u kala horreeyaan. Sababo farsamo, macluumaad ku saabsan waxqabad gaar ah iyo isku-darka guud ee la isku duro ayaa lumay hal PET1 iyo hal PET2, siday u kala horreeyaan. Wixii imtixaannada soo haray, celceliska waxqabadka gaarka ah wuxuu ahaa 1436 ± 2348 iyo 658 ± 583GBqμmol^-1 loogu talagalay PET1 iyo PET2, iyo tiro badan oo laysku duro FLB 457 wuxuu ahaa 0.41 ± 0.3 iyo 0.58 ± 0.6μg, siday u kala horreeyaan. Qiyaasta laysku duro, waxqabadyada gaarka ah iyo kobcinta looma kala duwanaan inta u dhexeysa kahor iyo dib u-qabashada (P> 0.5, oo la isku daray t-test), iyo muhiimad ahaan, ma jiro isku xirnaan inta u dhaxaysa cirbadda laysku muday iyo BP_ND ama isbedelka astaamaha.

Baadhista PET

Baaritaannada PET ayaa lagu sameeyay nidaam shay-baara oo sareeya (Siemens Molecular Imaging, Knoxville, TN, USA). Ka hor inta aan baaritaanka PET ee ugu horreeya, koofiyada naqaska waxaa loo sameeyay maado kasta si shakhsiyan ah si loo yareeyo dhaqdhaqaaqa madaxa inta lagu jiro cabbiraadda. Waqtiga u dhexeeya PET1 iyo PET2 waxay ahaayeen maalmo 146 ± 23. Waqtiga caadiga ah ee duritaanka waa 12: 24 loogu talagalay PET 1 iyo 11: 53 loogu talagalay PET2. Ka hor inta aan la saarin, 5-min scan ayaa la sameeyay si loo saxo xajinta iyo kala firdhinta. [¹¹C] FLB 457 ayaa lagu duray xididka dareen-celinta sida xajmiga xajmiga iyo raajo-qaadidda ayaa lagu qiyaasey 87min. Laba maadi, imtixaanka labaad ayaa la kala dhexdhexaadiyay 910 iyo 1416s iyo 3361 iyo 3623s, siday u kala horreeyaan. Dhexdhexaadintan waxaa laga reebay falanqaynta xiga ee xigta. Sawirrada waxaa dib loo cusbooneysiiyey iyadoo la adeegsanayo Goobta caadiga ah ee saddexda qiyaasood ee loo yaqaan "Poisson" ee qiyaasta ugu sarreeya ee la yiraahdo "algorithm", taas oo ka dhigaysa xallinta qulqulka 1.5mm kala badh ugu badnaan bartamaha aragga.¹⁴

Falanqaynta sawir

Sawirada PET ayaa lagu saxay dhaqdhaqaaqa madaxa iyada oo la adeegsanayo hanaanka qaabeynta qaab-dhismeedka,²⁴ iyada oo qaab kasta oo sawir ahaan loo adeegsanayo tixraac ku xiga. Sawirro sawirro ah ayaa lagu soo rogay baqshadda hore - dusha sare ee hawada. Gobollada xiisaha (ROIs) ayaa manhajka loo qoondeeyey maaddo kasta si shakhsiyan ah, iyada oo la adeegsanayo software Brain Atlas software²⁵ (Jaantuska 1). Gobollada la doortay waxay ahaayeen amygdala, hippocampus iyo kilinaan horay loo soo doortay, oo ku salaysan doorka ay soo jeediyeen ee SAD,⁵ iyo ROIs ayaa lagu qeexay isticmaalka tusmooyinka hore loo daabacay.^{26, 27} Kortex doorbidu wuxuu u qaybsamaa gobollada dorsolateral, medial iyo orbitofrontal.²⁷ Gobolada Striatal lama qiimeynin, sida xiriirka sare ee [¹¹C] FLB 457 uma oggolaanayso in loo simo si siman ee ku jira tijaabada PET, taas oo ka hortagaysa xisaabinta macnaha leh ee radioligand xidhaya.²⁸ MRIs waxaa loo kala qaybiyey maaddada cawska, caddaanka cad iyo dheecaanka cerebrospinal, iyo iskudubarid kasta oo ka mid ah laba sawir oo PET ah oo isticmaalaya SPM5. Xuduudaha isbeddelka ee la helay ayaa loo isticmaalay si markaa loo adeegsado ROI ee sawirada PET ee firfircoon si loo abuuro curiska waqtiga firaaqada (TACs). Goobaha xuduudaha ee hore, kaliya voxels oo ka tirsan qaybta miisaanka miisaanka ayaa lagu daray ROI. Sidoo kale, habka loo yaqaan 'Meltzer' ayaa loo adeegsadey gobolladan si looga fogaado inay saameyn ku yeelato xeeladaha CSF ee deriska ah.²⁹ Hawlgalka sawirka waxaa lagu sameeyay SPM5 oo ku shaqeyneysa Matlab R2007b (MathWorks, Natick, MA, USA).

Jaantuska 1

(a-c) Sawirada xasaasiyadeed ee magnetka leh gobollada danaha amygdala (casaanka), hippocampus (jaalle), kortext horjeeda hore (cyan), kortex celcelis ahaan medial (buluug) iyo kortex orbitofrontal (cagaaran). (d-f) Sawirada soo koobay ee [¹¹C] FLB (inbadan…)

BP_ND waxaa lagu xisaabiyey TACs iyadoo la adeegsanayo habka loo yaqaan 'tie-ka' (SRTM), oo la yiraahdo cerebellum sida tixraaca. Xogtaan, BP_ND waxay ka dhigan tahay saamiga isku midka ah ee shaybaarkiisa gaarka ah ee ku xiran shucaaca ee ku salaysan unugyada aan loo naqshadeeyn karin ee unugyada.³⁰ SRTM hore ayaa loo ansixiyey [¹¹C] FLB 457.²⁸ Maadaama aysan jirin wax isbeddel ah oo ka dhexeeya kala duwanaanshaha dhinaca ka qayb qaadashada dopaminergic neurotransmission ee SAD, BP_ND sababtoo ah dhammaan gobollada waxaa lagu xisaabiyaa iyadoo la adeegsanayo TACs-ka celcelis ahaanta ee dhinacyada saxda ah iyo bidix si loo wanaajiyo tirakoobka TAC.

Falanqaynta tirakoobka

Isbedelada dhibcaha LSAS iyo D2-R BP_ND ayaa la qiimeeyay iyada oo la isticmaalayo lamaane t- ugu dambeyntii. Ururada u dhexeeya D2-R BP_ND iyo natiijooyinka LSAS ee aasaasiga ah waxaa lagu xisaabiyaa iyadoo la isticmaalayo is-dhex-galka qaybaha, xakamaynta da'da. Xidhiidhka ka dhexeeya isbeddelada D2-R gobolka iyo isbedelka LSAS_anx buundooyinka waxaa lagu qiimeeyay iyadoo la adeegsanayo falanqayno isdabajoog ah oo ku saabsan isweydaarsiga, iyada oo waqti iyo gobolba loo eegayo arrimo gudaha ku lug leh iyo LSAS_anx boqolkiiba isbeddel ahaan sida isweydaarsi. Falanqaynta labaad ayaa loo sameeyey LSAS_avoider iyo labada qiyaasood ee isku dhafan. Kadibna, isku dheelitirnaanta xidhiidhka ayaa lagu xisaabiyey inta u dhaxaysa isbedelka boqolkiiba ee D2 BP_ND iyo boqolkiiba isbedelka LSAS_anx dhibcaha. In a ka dib falanqaynta, shakhsiyaadka ayaa loo qaybiyey dadka wax ka qabta (50% hoos u dhigista calaamadaha) iyo kuwa aan ka jawaabin, iyo kala duwanaanshaha kooxda isbedelka BP_ND qiyamka waxaa lagu sharaxay iyadoo la isticmaalayo falanqeyn hal dhinac ah oo kala duwan. Dhamaan imtixaanada, natiijooyinka waxaa loo tixgeliyey inay muhiim tahay P<0.05. Falanqaynta tirakoobka waxaa lagu sameeyay iyadoo la adeegsanayo PASW 18 (SPSS, Chicago, IL, USA).

Natiijooyinka

Isbedelada heerarka walaaca bulshada iyo D2-R BP_ND

Dhammaan bukaannada ayaa la hagaajiyey daaweynta ka dib, iyo isbedelka guud ee dhibcaha LSAS iyo sidoo kale walwalka iyo ka-hortagga hoos-u-dhigidda ayaa ahaa mid aad u muhiim ah (Shaxda 2). Ma jirin wax isbeddel ah oo ku yimid isbeddelka LSAS ee u dhexeeya bukaannada qaadaya daaweynta kooxeed iyo bukaannada lagu daaweeyo internetka, ama miisaankoo dhan ama qiyaasta hoose (P> 0.74) Daaweynta ka dib, afar (44%) kaqeybgalayaashu ma aysan buuxin shuruudaha lagu ogaanayo cudurka SAD. Heer kooxeed, farqiga u dhexeeya D2-R-ku-xirnaanta hore iyo dib-u-qaadista ma gaarin muhiimadda tirakoobka mid ka mid ah gobollada, sida lagu qiimeeyay iyadoo la adeegsanayo isku-darka t- ugu dambeyn (Shaxda 2). Si kastaba ha ahaatee, jihada iyo heerka isbeddelka ayaa muujiyey isbadal wayn oo dhexdhexaad ah, taas oo awood u yeelatay xisaabinta isirrada macnaha leh ee isbedelka astaamaha.

Shaxda 2

D2-ka-qaadista-kartida iyo calaamadaha calaamadaha horey u-qabashada iyo dib u-qabashada

Ururada u dhexeeya D2-R BP_ND isbedelka iyo isbedelka walaaca bulshada

Falanqaynta tallaabooyinka soo noqnoqda ee khilaafka, saameeynta weyn ee waqtiga iyo waqtiga × Isbeddelka dhibcaha calaamaduhu waxay muujiyeen LSAS_anx (F = 7.61, P= 0.028 iyo F = 7.77, P= 0.027). Falanqaynta xigta ee gobol-ku-xigga, xiriirka xun ee u dhexeeya isbedelka D2-R BP_ND iyo LSAS_anx isbeddelka ayaa lagu muujiyay kortulo prefrontal ah (r= -0.78, P= 0.013), kortex celcelis ahaan medial (r= -0.82, P= 0.007) iyo sidoo kale hippocampus (r= -0.81, P= 0.008; Jaantuska 2). Isku xirnaanta kortex celinta hore ee hareeraheeda iyo hippocampus ayaa ka badbaaday habdhaqanka Bonferroni (oo la hagaajiyay P-qeyr <0.01). Gobolladan, jawaab bixiyayaashu waxay muujiyeen koror ku xidhan (5.0% iyo 9.5%, siday u kala horreeyaan, n= 4), halka dadka aan ka jawaabin celceliska ay muujiyeen hoos u dhac (-8.6% iyo -8.3%, n= 5). In kasta oo kooxo yar oo koox kasta ah, farqigaas ayaa muhiim u ahaa MFC (P= 0.003) iyo heerarka isbeddelka ee hippocampus (P= 0.097). Wax saameyn ah kuma yeelanin wakhti ama wakhti isbeddel x Farqiga Tani waxay saameyn ku yeelaneysaa saameynta heerarka hooseeya (F = 3.93, P= 0.088) iyo mudada isdhexgalka ee waqtiga isbedelka (F = 3.74, P= 0.095).

Jaantuska 2

Iskudhicirro muujinaya xiriirka ka dhexeeya isbeddelka Dhibaatooyinka Dhibaatada Bulshada ee Liebowitz (Scale) iyo dopamine D2-qabasho-qabasho (BP) ee koontada hore ee dorsolateral-ka (DLPFC), kortelka hore ee saxada ah (MFC) iyo hippocampus (HIP). (inbadan…)

Isku xirnaanshaha hore iyo isudheellitirka ka dhexeeya D2-R BP_ND iyo walaaca bulshada

Ma jiro xidhiidh kudhexeeya D2-R BP_ND iyo LSAS_anx ama LSAS_avoider dhibcaha ka hor ama ka-dib-u-qabashada, ka dib markii la xakameeyo da'da.

Dood

Daraasaddan, waxaanu qiimeynay doorka nadaamka dopamine-ka ee miyir-beelka ee SAD, isagoo baaraya isbeddelka ku dhaca dopamine D2-R oo ku xiran sida shaqeynta calaamadaha isbeddelka ka dib CBT. Muhiimadda, ujeeddada daraasadani ma ahan in la baaro saameynta daaweynta nafsiga ah ee ku saabsan D2-R ee ku xiran SAD, sababtoo ah waxay taasi keenaysaa isticmaalka xaalad xakamayneed. Taa baddalkeeda, CBT waxaa loo isticmaalay qalab si loogu badalo gobolka cudurada aan farmasiga ahayn. Sidaa awgeed, isku-dhafka isbeddelka dhibcaha astaamaha iyo isbeddelka ku-xirnaanshaha aqbalaadda wuxuu ahaa natiijada asaasiga ah, halkii laga beddelan lahaa isbeddelka horey iyo ka-hor-celinta heer kooxeed. Si kastaba ha ahaatee, halka celceliska dhexdhexaadinta u dhexeeya PET1 iyo PET2 ay ku jirtay gudaha isbeddelka imtixaanka hore loo soo bandhigay [¹¹C] FLB 457,³¹ isbedelka isdhexgalka ee isbedelka ayaa ahaa ku filan falanqaynta isku xirnaanta. Isticmaalka naqshad la mid ah, isbeddelka ku-xirnaanta D1-receptor ayaa dhowaan lagu muujiyay in ay la xiriirto hagaajinta awoodda xasuusta shaqada ka dib markii tababbarka xusuusta ee shaqada,³² oo hadda waxaan marka hore muujinnaa xidhiidh toos ah oo ka dhexeeya calaamadaha dhimirka ka dib marka la daweeyo teraabiyada cilminafsiga iyo isbedelka astaamaha maskaxda neurotransmission.

Doorka habka dopamine ee dhaqanka bulshada ayaa lagu muujiyay cilmi baarista xayawaanka iyo cilmiga bini-aadamka. Daraasadaha sawir-baadhista meco-du waxay muujiyeen is-afgarad aan kala-dhexeeyn oo u dhexeeya calaamadaha DA iyo shakhsiyaadka shakhsi ahaaneed ee shakhsi ahaaneed iyo sidoo kale tallaabooyin kala duwan oo ku saleysan bulsho iyo xaalad bulshadeed oo hooseeysa.^{33, 34, 35, 36, 37, 38, 39} Dhawaan, waxaan sii dheereynay khadkaan cilmi-baarista iyadoo la muujinayo xiriirka u dhexeeya rabitaanka bulshada iyo D2-R ee ku xiran lobe dhex-dhexaad ah sida lagu cabbiro isticmaalka [¹¹C] FLB 457.⁴⁰ In domainka shakhsi ahaaneed, sifooyinka shakhsi ahaaneed ayaa loo arki karaa si ay u muujiyaan soo gudbinta bulshada iyaga oo ka soo horjeeda xukunka bulshada,⁴⁰ iyo natiijooyinka sidaas awgeed waxa lagu soo bandhigay cilmi baaris ku saabsan jiirka iyo mabaadi'da aan dadka ahayn ee dopaminergic neurotransmission lala xiriiriyay qiyaasta habdhaqanka madax-bannaanida.^{41, 42, 43, 44} Danta gaar ahaaneed waa daraasadda ay sameysay Morgan al et.,⁴⁴ halkaas oo D2-R ku xiran yihiin daanyeero la muujiyay in ay isbeddelaan sida shaqeynta darajo heer sare ah sida xayawaanka ay u guureen shakhsi ahaan ilaa guryaha bulshada. Xaqiijinta xiriirka ka dhexeeya isbedelka D2-R calaamadaha iyo calaamadaha cilladda bulshada waxay la socotaa tiirarka cilmi baarista waxaana loo arki karaa inay yihiin taageerada xiriirka la soo jeediyay ee u dhaxeeya qiyaasta xukunka ee habdhaqanka dadka iyo SAD.⁴⁵ Xidhiidhku maaha mid muhiim u ah LSAS_avoider, kaas oo laga yaabo in lagu sharaxo dabeecadda ka sii badan ee dabeecadda ka fog. Tusaale ahaan, ka-hortagga ka-hortagga dabeecadaha nabdoon ee la ilaaliyo looma filna inay keenaan walaac yar.²¹

Daraasadaha SPECT waxay horey u muujiyeen dopamine D2-R oo ku xiran bukaanka 10 ee SAD, iyo sidoo kale muunad 7 oo la socota OCD oo la barbar dhigo maadooyinka.^{1, 2} Dhinaca daawada loo yaqaan 'presynaptic,' waxaa lagu soo bandhigay bukaanka 11 hooseeya.³ Daraasad cusub oo cusub oo la adeegsanayo PET, wax isbeddel ah laguma soo bandhigin D2-R, ama mid ka mid ah asaasiga ama ka dib tartamidda amphetamine, sidoo kale ma jirin wax isbeddel ah oo ku xiran gaadiidka dopamine (n= 15, 12 iyo 12, siday isugu xigaan).⁴ Hase yeeshee, midkoodna daraasaddan ayaa lagu qiimeeyay dopamine reseptors ee gobollada maskaxda ee extrastriatal.

Daraasadaha waxqabadka maskaxda, mid ka mid ah natiijooyinka ugu soo noqnoqoday ayaa kor u kacaya firfircoonida amygdala iyada oo wax laga qabanayo dareenka bulshada ee cabsida leh^{46, 47, 48} laakiin gaar ahaan, natiijooyin xun ayaa sidoo kale la soo sheegay.^{49, 50} Gobollada kale ee muujinaya firfircoonida isdhexgalka ee SAD waxaa ka mid ah xarumaha hippocampal iyo prefrontal.^{5, 46, 47, 51, 52, 53} Guryaha hore ee saxda ah, kaalin gaar ah oo lagu kormeerayo qiimeynta bulshada ayaa lagu muujiyay bukaanka SAD^{51, 52} iyo gobolkani sidoo kale waxaa lagu soo koobay cabsida cabsida.^{54, 55} Daafka Dopaminergic ee Hippocampus ayaa muujiyay inuu ku lug yeelanayo hawlaha xasuusta ee cilmi-baarista xoolaha iyo sidoo kale daraasado sawir-gacmeedka ah.^{56, 57, 58, 59} Isku soo wada duub, natiijooyinka xaadirka ah ee xiriirka ka dhexeeya shaqada dopaminergic ee hippocampus iyo gobollada xuduudaha horay loo soo marin karaa waxay la xiriiri karaan doorka gobolladan ee waxbarashada iyo qiimeynta bulshada.

Xaddidaadda ugu horeysa ee daraasaddan waa mugga yar ee saamiga. Inkastoo wadarta bukaanada 126 lagu darey daraasadda daaweynta,¹⁵ ee daraasaddan xaadirka ah waxaanu adeegsanay shuruudo aad u adag si aan uga fogaano saameynta halista ah ee ku jirta helitaanka D2-R, tusaale ahaan isticmaalka daaweynta farmasiga ah ama daaweynta nikotiinka. Intaa waxaa dheer, bukaanno qaar ayaa lumay sababtoo ah caqabadaha waqtiga. Marka labaad, ma ogaan karno in isbeddelka ku dhacay BP_ND waxay u sabab yihiin isbeddelada cufnaanta maqnaashaha ama il-qabad muuqda, maadaama maadooyinkan aan la kala saari karin iyada oo ku saleysan hal qiyaasta PET.³⁰ Calaamadaha saameynaya ishaarada muuqda, heerarka dopamin ee endogenous ayaa muujiyay in ay saameeyaan [¹¹C] FLB 457 qasab,^{60, 61, 62} Si kastaba ha ahaatee, daraasado kale ayaa ahaa mid xun.^{63, 64} Jiirka, halkaasoo heerarka neurotransmitter ay badanaa la heli karo, korodhka DA-da ayaa la arkay iyada oo laga jawaabayo dareemayaasha cadaadiska.^{65, 66} Inkastoo daraasado ku shaqeynaya imtixaano badan oo PET ah oo leh hawlo gaar ah oo ka mid ah [¹¹C] FLB 457 waxay muujisay in cufnaanta cirfiidaanka ee xisaabteeda badankeeda kala duwanaanshaha BP_ND,⁶⁷ laguma saari karo in farqiga u dhaxeeya heerarka dopamine ee endogeley ay qayb ahaan ka xisaabtami karaan ururada la arkay, tusaale ahaan soo noqnoqoshada falcelinta DA inta lagu jiro nidaamka baaritaanka ee bukaanka leh horumarin yar oo daaweyn ka dib.

Gebogebadii, natiijooyinka ka soo baxay daraasaddan hordhaca ahi waxay muujinaysaa in isbeddelka balaastigga ee nidaamka dopamine uu hoos u dhigo calaamadaha walwalka ee SAD bukaanka ka dib marka la daaweeyo CBT. Daraasadu waxay taageertaa doorka habka dopamine ee SAD, waxayna muujineysaa in isbarbardhiga shakhsi ahaaneed uu noqon karo hab lagu kalsoonaan karo oo lagu aqoonsanayo biomarkers maskaxda ee xanuunka dhimirka.

Mahadnaq

Daraasadan waxaa taageeray Söderström Königska Stiftelsen, Golaha Qaranka ee Caafimaadka iyo Daryeelka Caafimaadka, Stockholm County Council iyo Psykiatrifonden. Shaqaalaha Xarunta Karininska PET iyo qaybta maskaxda ee internetka ee Isbitaalka jaamacadda Karolinska Huddinge ayaa mahad leh.

Notes

Qorayaashu ma sheegaan khilaafka danta.

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