JAMA Psychiatry. 2019 May 1. doi: 10.1001/jamapsychiatry.2019.0801.
Pizzagalli DA1,2, Berretta S1,2, Wooten D1,3, Goer F2, Pilobello KT2, Kumar P1,2, Murray L2, Beltzer M2, Boyer-Boiteau A2, Alpert N1,3, El Fakhri G1,3, Mechawar N4, Vitaliano G1,2, Tureki G4, Normandin M1,3.
Abstract
Ukubaluleka:
Ukuphazamiseka okukhulu koxinzelelo (MDD) kunokubandakanya ukuncitshiswa kwe-dopamine (DA). Umthuthi we-DA (DAT) ulawula ukukhutshwa kwe-DA kunye ne-neurotransmission kwaye unovelwano kumanqanaba e-DA, kunye nezifundo zangaphambili (kubandakanywa nezo zibandakanya uxinzelelo olungenakuphepheka) olubonisa ukuba ubuninzi be-DAT buyancipha xa ukubonakaliswa kwe-DA kuncitshisiwe. Nangona idatha ye-preclinical, ubungqina be-DAT encitshisiweyo kwi-MDD ayigqibeki.
Injongo:
Ukusebenzisa i-DAT positron emission tomography (PET) tracer ekhethiweyo kakhulu ([11C] altroropane), ukufumaneka kwe-DAT kwaphandwa kubantu abane-MDD ababengathathi mayeza. Amanqanaba enkcazo ye-DAT aye avavanywa kwizicubu ze-postmortem ezivela kubaxhasi abane-MDD abasweleke ngokuzibulala.
Uyilo, ukuseta, kunye nabathathi-nxaxheba:
Olu pho nonongo lwe-PET lwe-cross-sectional lwenziwa kwiSibhedlele saseMcLean (eBelmont, Massachusetts) kunye neMassachusetts General Hospital (Boston) kwaye babhalisa abantu abalandelelanayo kunye ne-MDD abangazange bathathe amayeza kunye nolawulo lwabantu oluhambelana nolawulo olunempilo phakathi kukaJanuwari 2012 no-Matshi 2014. Izicubu zobuchopho zafunyanwa. ukusuka Douglas-Bell Canada Brain Bank. Kwicandelo le-PET, abantu be-25 abane-MDD yangoku abangazange bathathe amayeza kunye ne-23 yolawulo oluphilileyo oluqeshwe kwiSibhedlele saseMcLean lubandakanyiwe (zonke zinikezelwe idatha esebenzayo). Kwicandelo le-postmortem, abantu be-15 abanokudakumba kunye ne-14 yolawulo olunempilo baqwalaselwa.
Ukungenelela:
PET scan.
Iziphumo eziPhambili kunye neMilinganiselo:
I-striatal kunye ne-midbrain yengqondo ebophelelayo ye-DAT enokubakho iye yavavanywa. Kwicandelo le-postmortem, i-tyrosine hydroxylase kunye namanqanaba e-DAT ahlolwe kusetyenziswa ama-blots aseNtshona.
iziphumo:
Xa kuthelekiswa nolawulo lwezempilo lwe-23 (abafazi abayi-13 [56.5%]; iminyaka yobudala [SD], i-26.49 [7.26] iminyaka), abantu abangama-25 abane-MDD (abafazi abayi-19 [76.0%]; kuthetha ubudala [SD], 26.52 [5.92] iminyaka) ibonise i-vivo ephantsi kakhulu kwi-DAT ekhoyo kwi-putamen ye-bilateral kunye ne-ventral tegmental area (uluhlu lwe-Cohen d, -0.62 ukuya ku-0.71), kwaye zombini ukunciphisa kwandiswa ngamanani anyukayo ee-depressive episodes. Ngokungafaniyo nolawulo olusempilweni, iqela le-MDD aliphumelelanga ukubonisa ukuncitshiswa okunxulunyaniswa neminyaka ekufumanekeni kwe-DAT yokubulala, nabantu abancinci abane-MDD ababonakali kulawulo oludala olusempilweni. Ngaphezu koko, ukufumaneka kwe-DAT kwindawo ye-ventral tegmental yayiphantsi kakhulu kubantu abane-MDD abaye babika ukuba baziva bevalelwe kwiimeko ezixinzelelekileyo. Amanqanaba aphantsi e-DAT (kunye ne-tyrosine hydroxylase) kwi-putamen ye-MDD xa kuthelekiswa nokulawulwa okunempilo kwaphindwa kuhlalutyo lwe-postmortem (uluhlu lwe-Cohen d, -0.92 ukuya ku-1.15).
Iziphetho kunye nokuDibana:
Ingxaki enkulu yokudakumba, ngakumbi ngeziqendu eziphindaphindiweyo, ibonakala ngokuncipha kwentetho ye-DAT, enokubonisa ukuthotywa kwembuyekezo ngenxa yokubonakaliswa okuphantsi kwe-DA kwiindlela ze-mesolimbic.
PMID: 31042280
PMCID: PMC6495358
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