Neuroimage. 2012 Oct 15; 63 (1): 40-6. doi: 10.1016 / j.neuroimage.2012.06.067. Epub 2012 Jul 6.
Clark L, Amakonda PR, Wu K, Mikalczuk R, Benecke A, Watson BJ, Egerton A, Pikisini P, Nutt DJ, Bowden-Jones H, Lingford-Hughes AR.
gwero
Dipatimenti ya Experimental Psychology, University of Cambridge, Cambridge, UK. [imelo ndiotetezedwa]
Kudalirika
Kutchova njuga (PG) ndichizolowezi chomayanjana ndi kukwezedwa komanso kukayikiridwa dopamine kukomoka. Kuchepetsa striatal dopamine D (2) / D (3) phwando kupezeka kwanenedwa kuti mumapezeka mankhwala osokoneza bongo, ndipo kungapangitse chizindikiritso chokhala pachiwopsezo chazovuta zomwe zingachitike.
Cholinga cha phunziroli chinali kuyang'ana momwe zinthu ziliri dopamine D (2) / D (3) phwando kupezeka kwa PG, komanso kuyanjana ndi kusayanjika kwamtundu. Amuna omwe ali ndi PG (n = 9) ndikuwongolera kwathanzi la amuna (n = 9) adayang'aniridwa [11C] -raclopride positron emission tomography imaging ndikutsiriza muyeso wa UPPS-P.
Panalibe kusiyana kwakukulu pakati pa magulu mu striatal dopamine D (2) / D (3) phwando kupezeka, Mosiyana ndi malipoti am'mbuyomu osokoneza bongo.
Komabe, kutengeka kokhudzana ndi kusinthasintha kwa mtima ('Urgency') kudalumikizidwa molakwika ndi [11C] -raclopride zomangika zomwe zingatheke mu gulu la PG. Kusakhala kwa kusiyana kwamagulu mu striatal dopamine kumangirira kumatanthauza kusiyanitsa pakati pa zizolowezi zamavuto ndi zosokoneza bongo. Komabe, deta yathu imawonetsa heterogeneity mu dopamine phwando kupezeka kwa zomwe zasungidwa njuga, kotero kuti anthu omwe ali ndi chidwi chachikulu chokhudzana ndi kusangalala akhoza kuwonetsa phindu kuchokera dopamine- mankhwala opangira.
Keywords: Kutchova juga, kusonkhezera, Dopamine, Neuroimaging, Kusuta, Striatum
Mfundo
► Yoyesedwa ya 11C-raclopride yomanga njuga zamatenda, chizolowezi chamakhalidwe. ► Palibe kusiyana kwamagulu mu striatal dopamine kumanga kuchokera ku zowongolera zathanzi. ► Dopamine yomanga yolumikizana molakwika ndi kusokonekera-kokhudzana ndi kusokonekera ('Urgency').
Introduction
Kuthetsa Njuga kwa Pathological (PG) ndikuwongolera kuwongolera kwa DSM-IV kwachidziwitso chazachipatala komanso kuthana ndi aetiological, zomwe zimapangitsa kubwereranso kwa PG ngati 'chizolowezi chomachita' (Bowden-Jones ndi Clark, 2011; Frascella et al., 2010). Mitundu ya Neurobiological ya mankhwala osokoneza bongo imatsindika kuchuluka kwa dopamine: mankhwala ambiri osokoneza bongo amalimbikitsa dopamine neurotransication (Di Chiara ndi Imperato, 1988), ndi kuchepetsedwa mu dopamine D2/D3 kupezeka kwa receptor kufotokozedwera kwa odwala omwe amadalira mitundu yosiyanasiyana ya mankhwala omwe amenyedwa (Fehr et al., 2008; Heinz et al., 2004; Martinez et al., 2004; Volkow et al., 1997, 2001). Sizikudziwika ngati kusintha kumeneku kukuwonetsa chifukwa chogwiritsa ntchito mankhwala kwakanthawi, kapena vuto lomwe lingakhalepo pachiwerewere. Poyenderana ndi chikhomo chosavulaza, 'kukonda mankhwala' kumalumikizidwa ndi D2/D3 kupezeka kwapatsidwa (Volkow et al., 1999), ndipo makina oimitsa kuti azikhala mwamakhalidwe azisonyeza kuti atengeka ndi mankhwala osokoneza bongo a cocaine komanso kuchepetsedwa kwa dopamine D2/D3 kupezeka kwa receptor musanafike pakudziwitsidwa kwa mankhwala (Dalley et al., 2007). Monga njira yomwe ingagwiritsidwire ntchito mankhwala omwe ali ndi vuto laukali, kafukufuku wa PG atha kuthandiza kusanthula kwazovuta mwa anthu, ndikuthandizira kuthana ndi zovuta komanso zotsatila (Verdejo-Garcia et al., 2008). Zoonadi, pali zingapo zomwe zikuwonetsa kuwunika kwa dopamine mu PG. Zolemba zotumphuka za dopamine mu madzimadzi a cerebrospinal zimalembedwa m'mavuto otchova njuga (Bergh et al., 1997; Meyer et al., 2004,, monga momwe mayankho a FMRI amayendera potengera dopamine pochita ntchito zamtundu wa juga (Chase ndi Clark, 2010; Reuter et al., 2005), ngakhale kuwongolera kwa zotsatira sikugwirizana. Kuphatikiza apo, mankhwala a dopamine-agonist a Matenda a Parkinson amawoneka kuti atha kuyambitsa njuga zosasangalatsa ngati zoyipa (Voon et al., 2009).
Positron Emission Tomography (PET) yolinganiza ndi [11C] -raclopride imapereka njira yotithandizira kufalikira kwa striatal dopamine mu ubongo wamunthu wamoyo. [11C] -raclopride yagwiritsiridwa ntchito posachedwa mu maphunziro anayi a PET kuwunika ophunzira omwe ali ndi njuga zosasinthika kapangidwe kazinthu zazikulu (monga zokhudzana ndi ntchito) (Joutsa et al., 2012; Linnet et al., 2011; O'Sullivan et al., 2011; Steeves et al., 2009). Awiri mwa maphunzirowa anali odwala omwe ali ndi Matenda a Parkinson (O'Sullivan et al., 2011; Steeves et al., 2009), pomwe sizikudziwika bwinobwino momwe kuchuluka kwa zovuta zogwirizanirana zolimbikitsira zimagwirira ntchito mogwirizana ndi neuropathology yoyamba yamatenda (Voon et al., 2009). Maphunziro enawo awiri, a PG yoyamba, onse adagwiritsa ntchito kupanga chisankho chovuta kupanga / kutchova njuga pomwe poyambira sikunali ndi ntchito yoyang'anira ma sensorimotor (Joutsa et al., 2012; Linnet et al., 2011). Phunziro limodzi lokha (Steeves et al., 2009) adapeza umboni wakuchepetsa striatal dopamine D2/D3 kupezeka kwa receptor m'gululi ndi njuga zosasangalatsa. Kafukufukuyu apenda kafukufuku woyambira Driatal dopamine D2/D3 kupezeka kwa receptor pofunafuna odwala omwe ali ndi matenda oyamba a PG, pomwe tinafotokozera kuti D2/D3 kupezeka kwa receptor kutengera maphunziro apambuyo pake osokoneza bongo.
Tinayesanso kufufuza za striatal D2/D3 kupezeka kwa receptor pokhudzana ndi kuperewera msana. Kusunthidwa kwakwezedwa kumawonedwa modalirika paliponse pazokonda zamankhwala ndi PG (Verdejo-Garcia et al., 2008,, komanso akuwonekeranso kuneneratu za chitukuko cha kugwiritsa ntchito mankhwala osokoneza bongo ndi mavuto a njuga (Slutske et al., 2005). Posachedwa tidagwiritsa ntchito UPPS-P impulsivity wadogo (Cyders et al., 2007) kuwunika mawu omaliza amtundu wa odwala omwe ali ndi PG omwe akupita ku UK Nationalavuta Njuga Clinic (UK Nationalavuta Gging Clinic (Michalczuk et al., 2011). Kusiyanitsa kwakukulu kunawonedwa pakati pa gulu la PG ndikuwongolera athanzi pazinthu zingapo za UPPS-P zophatikizira Urgency - chizolowezi chokhala osafunikira panthawi zovuta kapena zabwino za boma ('rash impulsivity') - ndi zina za 'kupapatiza' Kupanga ndi Kulephera Kupirira). Komabe, kukula kwake kwa kusiyana kwakanthawi ka Urgency kunali kwakukulu kwambiri poyerekeza ndi mbali zazifupi zomwe zimapangitsa kuti anthu azingotengera kutchovera juga makamaka chifukwa cha kutchova juga kosavomerezeka (Michalczuk et al., 2011). Poona izi, kusiyana kwathu patokha kumaunikira a priori pamasamba awiri a Urgency subs (Negative Urgency and Positive Urgency) monga olosera.
Njira ndi zipangizo
ophunzira
Amuna asanu ndi anayi odzipereka omwe ali ndi PG (azaka zakubadwa zaka 35.3, sd 9.0, osiyanasiyana 25-49) adafaniziridwa motsutsana ndi zowongolera zisanu ndi zinayi za amuna (zaka zakubadwa 37.2, sd 5.6, osiyanasiyana 30-46). Phunziro la PG la khumi lidalembedwa koma silikupezeka kuti liwunikidwe chifukwa cha kulephera kwa radiochemistry. Zoyeserera zoyambira zodzifunira zidadziwika kuchokera m'maphunziro awiri am'mbuyomu (Egerton et al., 2010; Stokes et al., 2010) pogwiritsa ntchito nkhokwe yachidziwikire ya sclopride scans yomwe imachitikira ku MRC Clinical Sciences Center, ndipo sizinasiyana ndi gulu la PG pazaka (t16 = 0.53, p = .602). Omwe atenga nawo mbali mu PG adaphunzitsidwa mpaka kusukulu yasekondale ndi ziyerekezo za IQ pamiyeso yabwinobwino (Wechsler Adult Scale for Intelligence: mean 116, sd 10.8; National Adult Reading Test: mean 117, sd 5.7); Ntchito yam'mbuyomu imawonetsa kulumikizana kosagwirizana pakati pamawonekedwe anzeru ndi ma dopamine. Odzipereka onse adapereka chidziwitso cholemba phunziroli, chomwe chidavomerezedwa ndi a Hammersmith Research Ethics Committee ndi Administration of Radioactive Substances Advisory Committee, UK.
Otsatira a PG adalandidwa kuchokera ku chipatala cha Nationalavuta Njuga Clinic, Central North West NHS Foundation Trust. Othandizira asanu ndi mmodzi anajambulidwa atatsala pang'ono kuchita, kapena, maphunziro khumi olimbitsa thupi ndipo atatuwo anali atamaliza kumene chithandizo. Onse 9 odzipereka anali ndi mbiri yaposachedwa ya kutchova juga. Kuzindikira kwa DSM-IV kwa PG kwatsimikiziridwa ndi Massachusetts Gcane Screen (MAGS; kutanthauza 9.8, sd 2.2, range 5-12) (Shaffer ndi al., 1994), yoyendetsedwa ndi katswiri wama psychologist panthawi yoyambitsa chithandizo. Kuzindikira kunaphatikizidwa ndi vuto la Kutchova Juga Kokulumikizana (Ferris ndi Wynne, 2001), sikelo yodzidziwitsa yomwe imaperekedwanso koyambirira kwa chithandizo (kutanthauza 18.4, sd 5.7, range 8-24; mphambu wa 8 kapena pamwambapa akuwonetsa vuto la kutchova juga). Kuchedwa pakati pakuwunika kwachipatala ndi PET scan kunali miyezi 2-8 mwa omwe anali nawo pa 8/9, ndi miyezi 23 mu PG imodzi yomwe idasankhidwa atalandira chithandizo. Matenda okhudzana ndi matenda amisala adayesedwa mwa omwe amatenga nawo mbali ndi PG poyankhulana mwadongosolo pogwiritsa ntchito ICD-10, molumikizana ndi mtundu wapakompyuta wa Mini International Neuropsychiatric Mafunso (e-MINI v2.0; Medical Outcome Systems, Jacksonville, Florida) (Sheehan et al., 1998). Anthu awiri odzipereka anali ndi mbiri yakale yovuta yayikulu, ndipo munthu m'modzi wodzipereka adakwanitsa kuthana ndi mavuto apadzikoli. Wodzipereka adakwaniritsa zomwe zidadalira kale mowa, ndipo wachiwiri adakumana ndi njira zomwe zidadalira kudalira kwa cannabis. Othandizira anayi anali osuta fodya panthawiyi panthawi yomwe akulemba maphunziro (Fagerstrom Nicotine Dependence Scale scores from 6 to 12). Njira zochotseredwa pagulu la PG zinali: mbiri ya matenda amitsempha, kuvomereza kwam'mbuyomu kwam'maganizo, mankhwala aposachedwa a mankhwala ndi matenda ofunika m'thupi. Mwakutero, ma comorbidities opezeka amisala sanali okhazikika okwanira kufuna chithandizo chamankhwala. Onse omwe anali nawo pa chiwonetserochi adayesedwa kale ndi dokotala wamisala kuti asatenge mavuto apano kapena am'mbuyomu ofunika, komanso kudalira zinthu monga kufotokozedwera ndi DSM-IV, kudwala kwambiri, kusokonezeka kwa mitsempha m'mbuyomu kapena kugwiritsa ntchito kale mankhwala a psychotropic.
Zochita kutchova juga zidayesedwa mwa omwe anali nawo pa PG ogwiritsa ntchito zinthu 1-3 pa Screen Oaks Gossip (Lesieur ndi Blume, 1987). Ophunzira asanu ndi mmodzi adaganizira zamagetsi zamagetsi zamagetsi ('Fixed Odds Betting terminals') kuimira mtundu wawo wamavuto wa njuga; atatu onse otsala amawona kubetcha masewera (pamahatchi), poker / intaneti, ndi masewera a kasino kukhala ovuta kwambiri. Pakuyerekeza kuchuluka kwakukulu kwa ndalama zotchova juga tsiku limodzi, asanu adalipira ngongole ya £ 1,000- £ 10,000, ndipo anayi adalipira kupitilira $ 10,000. Atafunsidwa za ngongole zokhudzana ndi kutchova juga, wotchova njuga m'modzi anakana kupereka chidziwitso cha ngongole, wotchova njuga mmodzi sananene ngongole chifukwa chogwiritsa ntchito ndalama zake, ndipo ngongole zomwe zilipo masiku asanu ndi awiriwo kuyambira pa $ 4000- £ 35,000 (amatanthauza £ 15,714).
Ophunzira adamaliza UPPS-P Impulsive Behaeve Scale (Cyders et al., 2007), funso lokhala ndi mafunso lokhala ndi zinthu 59 lomwe lili ndi ma subscales asanu omwe akuyesa Kuchita Zachangu (mwachitsanzo "Nthawi zina ndikakhumudwa, sinditha kusiya zomwe ndikuchita ngakhale zikundipweteka kwambiri"), Posachedwa ( Mwachitsanzo “Ndikasangalala kwambiri, ndimaona ngati sindingathe kudziletsa kuti ndisapitirire”), (kusowa) Kukonzekera (monga “Nthawi zambiri ndimapanga malingaliro anga mwa kulingalira mosamala” - kulowetsa molakwika), (kusowa) Khama (mwachitsanzo. "Ndimaliza zomwe ndiyamba" - kutsitsa molakwika) ndi Kufunafuna Kumva (mwachitsanzo "Ndingasangalale ndikamachita masewera othamanga kwambiri kutsika phiri"). Sitinathe kupeza zambiri za UPPS-P kuchokera kwa omwe amadzipereka pakuwongolera database.
Kutenga kwa chithunzi ndi kukonza
Zoyesa zonse za PET zidapezeka pogwiritsa ntchito sikani ya ECAT HR + 962 (CTI / Seimens) yokhala ndi gawo la axial la 15.5 cm. [11C] -raclopride idaperekedwa ngati jakisoni wolowetsa bolus kwa odzipereka a PG, komanso kwa odzipereka olamulira ngati cholumikizira choyambirira chotsatira ndikulowetsedwa kosalekeza, ndikulowetsedwa kwa 85 min pazithunzi zinayi zochokera ku Egerton et al. kuphunzira (2010) ndi 100 min pazithunzi zisanu zochokera ku Stokes et al. kuphunzira (2010). Kujambula kofalitsa kwa 10 min kunkachitika musanayese kutulutsa kulikonse kuti athe kuyeza ndikukonzekera kuchepa kwa minofu. Zoyeserera zakutulutsa mwamphamvu zidapezedwa pamitundu itatu pogwiritsa ntchito njira yofananira (20 mafelemu nthawi yopitilira 60 min kwa omwe akutenga nawo mbali pa PG, 28 mafelemu a nthawi yopitilira 85 min ya Egerton et al. (2010) skani ndi 38 mafelemu a 100 mphindi za Stokes et al. (2010) scans). Kwa otenga nawo mbali pa PG, kujambulidwa kwawo kunakhudzana ndikuwonetsedwa kwa zithunzi zosaloŵererapo kuphatikiza malo, zinthu zapakhomo ndi njira zosasinthika, koma popanda zofunika zamagalimoto (ochita nawo masewerawa anangotseredwa kamodzi).
Zoyeserera zonse zamphamvu zidakonzedwa kuti mutu uzigwiritsa ntchito chimango pogwiritsa ntchito chimango (FBF)Montgomery et al., 2006). Njirayi idagwiritsidwa ntchito pazithunzi zonse kuti apange chithunzi champhamvu cha FBF, chomwe chimasinthidwa ndikugwiritsa ntchito mawonekedwe a chidwi (ROI), chowonjezeredwa ndi kuwunika kotsimikizika kwa voxelwise.
Kufufuza kwa ROI
Ma striatal ndi cerebellar ROIs amatanthauziridwa pogwiritsa ntchito chithunzithunzi chomwe chimapangidwa pazigawo zitatu zogwira ntchito za striatum; limbic, Associative ndi sensorimotor striatum, ndi cerebellum monga gawo lothandiza. Magawo a striatal ndi anomeous ku ventral striatum (limbic striatum), pre-commissural dorsal putamen, pre-commissural dorsal caudate and post-commissural dorsal caudate (Association striatum) and post-commissural putamen (sensorimotor striatum) (Martinez et al., 2003). Template ya [11C] -raclopride template idasinthidwa kukhala malo a PET a chithunzi chilichonse chowongoleredwa ndi FBF (chopangidwa kuchokera ku chithunzi chilichonse cholimbikitsa cha FBF pogwiritsa ntchito mapulogalamu apanyumba olembedwa ku Matlab (mtundu wa 5; The MathWorks, Inc, Natick, Mass) )) mkati mwa SPM5 (www.fil.ion.ucl.ac.uk/spm) ndipo matform opanga mapindikidwe adagwiritsidwa ntchito pa ma atlas. Chithunzi chowonongeka cha striatal atagwiritsidwa ntchito kuyesa kuwerengera kuchokera pamitundu yozama [11C] -raclopride zithunzi za PG scans, komanso kuchokera pamalonda olemera okhwima omwe amawonjezera chithunzi chowongolera, pogwiritsa ntchito kusanthula pulogalamu ya 8.0 (www.analyzedirect.com). Kwa PG scans, [11C] -raclopride BPND Malangizo, mulingo wa radioligand womangika mosiyanasiyana ndi wamagamu osagwiritsidwa ntchito mwazigawoInnis et al., 2007,, adawerengedwa pogwiritsa ntchito mtundu wosavuta wa minofu yolumikizira ndi cerebellum ngati minofu yolankhulira yogwiritsira ntchito pulogalamu yanyumba yolembedwa ku Matlab. Pakuwongolera makina, [11C] -raclopride BPND mawerengeredwe amawerengedwa ngati kuchuluka kwa ziwerengero zakubadwa mpaka ziwerengero za cerebellar, kuchotsera 1, munthawi yokhazikika ya boma. Nthawi yolimba yokhazikitsira kulowetsedwa kwa bolus imadziwika kuti imayambira pa 39 min post-jekeseni ndikupitilira mpaka kumapeto kwa sikani, kutengera kuyerekezera kwakanthawi koyenera kakhazikitsidwe kakhazikika (Watabe et al., 2000).
Kusanthula kwa Voxelwise
Pazosankha zodzipereka za PG, zithunzi za parametric [11C] -raclopride zidapangidwa kuchokera pazithunzi zosunthika zomwe zimagwiritsa ntchito mtundu wosavuta wazolumikizira ndi cerebellum ngati cholembera chomwe chimagwiritsa ntchito pulogalamu yanyumba yolembedwa ku Matlab. Pazowongolera zodzipereka, zithunzi zoyeserera zidapangidwa kuchokera kudziko lolemera lowonjezera kuwonjezera zithunzi pogwiritsa ntchito algebra yazithunzi mkati mwa SPM5 pogawa kuwerengera kwa voxel iliyonse ndikuwerengera kwa cerebellar ndikuchotsa imodzi. Zithunzi zonse za parametric zidasinthidwa kukhala template ya [11C] -raclopride PET pogwiritsa ntchito matrix osokonekera omwe amapangidwa ndikusintha kwa munthu payekha pazithunzi. Zithunzi zosinthidwa mwazomwe zimasinthidwa mkati mwa SPM5 pogwiritsa ntchito kernel yosalala ya 6 mm.
Kusanthula kusanthula
Kusiyana kwamagulu mukukakamizidwa komanso BP yachigawoND zofunikira zimayesedwa pogwiritsa ntchito kusanthula kwa multivariate kwa kusiyanasiyana (MANOVA), komwe kumayendetsedwa mu SPSS 15 (SPSS, Chicago, Illinois). Maubwenzi apakati pa Urgency ndi BPND mfundo zimayesedwa pogwiritsa ntchito zosakanikirana zofananira, kuwongolera zaka chifukwa cholimbikitsidwa ndi msinkhu pa PET miyeso ya D2/D3 kupezeka kwa ma receptor ngakhale atakulaBackman et al., 2000; Kim et al., 2011). Chiwerengero cha Bonferroni chomwe chidakonzedwa p <.00625 chidakwaniritsidwa pakuwunika kophatikizana, kusintha kwa zigawo zinayi za striatal (chonse, limbic, Associative, sensorimotor) ndi masikelo awiri a Urgency. Pakufufuza kwamawu, kulumikizana pakati pa Urgency ndi [11C] -raclopride kumangako kunayesedwa pogwiritsa ntchito kuwunika kambiri mkati mwa SPM5, kumangolekezera ku striatum, ndikuphatikizanso zaka zongodzipereka ngati covariate. Mulingo wokhazikika wa masango p <0.05 wokhala ndi kukula kwa masango opitilira ma voxels khumi udagwiritsidwa ntchito pakuwerengera.
Results
Pa sikelo ya UPPS-P yokhazikika, panali zovuta zazikulu pagulu (Wilks 'lambda = 0.21, F (5,11) = 8.44, p = .002) ndi gulu la PG lomwe limakwera kwambiri kuposa kuwongolera koyenera pa Negative Changu (F1,15 = 43.0, p <.001), Posachedwa Mwachangu (F1,15 = 17.4, p = .001), ndi (kusowa kwa) Planning (F1,15 = 4.95, p = .042) ndalama zochepa. Mogwirizana ndi lipoti lathu laposachedwa pagulu lowonjezera la PG lomwe lidatumizidwa kuchipatala chomwecho (Michalczuk et al., 2011,, kukula kwake kunali kwakukulu pamitundu iwiri ya Urgency (onani Gulu 1). Panalibe kusiyana kwakukulu pakati pa magulu pa (kusowa kwa) Kupirira (F1,15 = 0.59, p = .455) ndi Kufunafuna Kumva (F1,15 = 0.76, p = .398).
Striatal dopamine D2 / 3 cholandirira cholumikizira kuthekera ndi mbali zina zakukakamizidwa mu Pathological Gamblers and Health Controls, ndimphamvu zazikulu zotchedwa Cohen's d.
Kufufuza kwa ROI
Panalibe kusiyana kwamagulu onse mu [11C] -raclopride BPND values (Wilks 'lambda = 0.59, F (4,13) = 2.22, p = .124), popanda kusiyana mu striatum yonse (F1,16 = 0.22, p = .64) kapena mulimonse mwa magawo atatu a striatal (limbic F1,16 = 0.02, p = 0.879; wothandizana ndi F1,16 = 0.54, p = 0.473; chojambulira F1,16 = 0.05, p = .819) (onani Mkuyu 1 ndi Gulu 1).
[11C] -raclopride yomanga yolimba (BPND) pagawo lonse la striatum la chidwi (mayiko awiri) komanso magawo olimbitsa thupi, pamilandu yokhala ndi Njuga ya Pathological komanso zowongolera zathanzi.
Pakati pa gulu la PG, kulumikizana mosasamala (kufananizira zaka) kunawonedwa pakati pa Negative Urgency ndi [11C] -raclopride BPND Makhazikitsidwe munthawi yonseyi (Mkuyu 2A), komanso magawo ogwirizana komanso oyanjana a striatum, iliyonse yomwe inali yofunika kwambiri pamlingo wokonzedwa ndi Bonferroni (onani. Gulu 2). Posakhazikika Urgency adalumikizidwa molakwika ndi BPND Makhazikitsidwe munthawi yonseyi (Mkuyu 2B), ndi kugawa koyanjana, pamalo oyikika. Negative Urgency ndi Positive Urgency anali okha ogwirizana pakati (57% anagawana mosiyanasiyana mu PG, 81% amagawana zosiyana muzowongolera). Maubwenzi apakati pa Urgency ndi BPND sizinafotokozeredwe momveka bwino kupezeka kwa osuta anayi mgulu la PG: osuta (motsutsana ndi PG osasuta) adawonetsa kusiyanasiyana kwakanthawi pazambiri za Urgency (Urative Urgency mean = 39.0 vs 38.4; Positive Urgency mean = 38.8 vs 37.0) ndi BPND values (limbic striatum amatanthauza = 2.20 vs 2.24). Popanda zaka zimaphatikizidwa monga kusiyanasiyana pang'ono, BPND makonzedwe anakhalabe ofunikira ku Negative Urgency (yonse r9 = .875, p = .002; limbic r9 = −.846, p = .004; wothandizana naye r9 = −.868, p = .002) koma zolumikizana motsutsana ndi Positive Urgency sizinatanthauze pazomwe zakonzedwa (chonse r9 = −.703, p = .035; wothandizana naye r9 = = 738, p = .023). Zambiri pa Vuto la Kutchova Juga Severity Index (PGSI) zidalumikizidwa molakwika ndi BPND Makhalidwe mu striatum othandizira (tsankho rho = -881, p = .004) koma sanali ofunika popanda zaka zophatikizidwa ngati kusiyanasiyana pang'ono (r9 > - 0.45, p> 0.22). PGSI idalumikizidwa kwambiri ndi Positive Urgency (r9 = .916, p <.001) koma osati kwenikweni ndi Negative Urgency (r9 = .627, p = .071).
Kugwirizana mu Pathological Gambler pakati pa [11C] -raclopride BPND chonse striatum ndi UPPS-P Negative Urgency (A) ndi Positive Urgency (B). C: Chigwirizano cha Quadratic pakati pa [11C] -raclopride BPND mu limbic striatum ndi Negative Urgency mu zojambulazo ...
Zogwirizanitsa mwapang'onopang'ono (zolamulira zaka) mu Pathological Gambler pakati pa [11C] -raclopride BPND m'magawo achidwi ndi chidwi Urgency (Zosasangalatsa, Zabwino). Ma mfundo molimba mtima anali ofunikira pambuyo pa Bonferroni ...
BPND mfundo sizinagwirizane kwambiri ndi njira Zachangu m'gulu lolamulira (r = - 0.36 mpaka 0.31, p> 0.42). Zowonadi, za ubale wapakati pa Negative Urgency ndi BPND mu limbic striatum, kuyesedwa kwachindunji kwa kusiyana pakati pa zophatikizika zophatikizika kunatsimikizira ubale wolimba mu gulu la PG poyerekeza ndi zowongolera (Fisher's r to z transformation; z = 2.03, p = .043), ngakhale mayeso ofanana mu striatum yonse ya Negative Urgency (z = 1.48, p = .139) ndi Positive Urgency (z = 0.97, p = .332) sizinali zofunikira. Popeza kuchuluka kwa gululi kukuwonjezeka pakukhudzidwa kwamphamvu mu gulu la PG, tinayesetsanso kusanthula kwaposachedwa poyesa ubale wa quadratic pakati pa Urgency ndi [11C] -raclopride BPND patsamba lozunguliridwa, poyerekeza lipoti laposachedwa la ubale wa 'unverted U' pakati pa porral striatal raclopride womangira ndi mkhalidwe Wobwereza Kufuna odzipereka athanzi (Gjedde et al., 2010). Pobwezeretsa [11C] -raclopride mfundo zomangirira mu limbic striatum (kudalira kosiyanasiyana) ku Negative Urgency (predictor variable), mtundu wonsewo sunakwaniritse tanthauzo (F (2,14) = 3.65, p = .053) koma panali zotsatira zazikulu za mawu a quadratic (β = - 4.07, t = - 2.21, p = .045) (Mkuyu 2C). Zotsatira za quadratic sizinawonedwe Pazachangu Posachedwa mu limbic striatum (β = - 2.30, t = - 1.40, p = .183), kapena mu striatum yonse (Negative Urgency: β = - 3.10, t = - 1.56, p Kufulumira Kwambiri: β = - 141, t = - 1.75, p = .1.06). Kuyesera mwachindunji kubwereza zotsatira za quadratic za Sensation Kufunafuna limbic striatum kunalinso kosafunikira (β = 306, t = 1.35, p = .0.44).
Kusanthula kwa Voxelwise
Kufanizira kwamagulu osalongosoka sikunatsimikizire kuti panali kusiyana kwakukulu mu [11C] -raclopride yomanga pakati pa PG ndi zowongolera. Kuponderezedwa kwa voxelwise motsutsana ndi Negative Urgency mu gulu la PG kunatsimikizira kulumikizana kosagwirizana ndi [11C] -raclopride yolumikizira mbali ziwiri zomwe zimachokera ku ventral putamen kupita kumutu wa caudate kumanja (pachimake chimagwirizanitsa: x = 10, y = 17 , z = - 5, masango kukula = 227, p <0.001 tsango lokonzedwa) ndi thupi lamanzere la caudate (pachimake chimagwirizanitsa: x = - 10, y = 13, z = 2, kukula kwa masango = 103, p = tsango la 0.001 kukonzedwa). Kuponderezedwa motsutsana ndi Positive Urgency kunapangitsa kuti mayiko awiri azikhala pakati pa ma nucleus accumbens ndi ma ventral putamen kupita ku thupi la caudate kumanja (pachimake chimagwirizanitsa: x = 21, y = 15, z = - 5, kukula kwa masango = 409, p <0.001 masango adakonzedwa) ndi caudate yamanzere ndi putamen (chimagwirizanitsa: x = - 25, y = 13, z = - 2, kukula kwa masango = 297, p <tsango la 0.001 lokonzedwa) (onani Mkuyu 3). Kuti tiwone momwe izi zikugwirizanira ndi kukhudzidwa komwe kumayenderana ndi kusokonekera, tinalowanso (kusowa) Kukonza ngati woneneratu wa [11C] -raclopride binder; palibenso ma voxels apamwamba omwe adapezeka.
Zotsatira za rexelwise regression ya [11C] -raclopride BPND mu Pathological Gamblers, akuwonetsa kuyanjana ndi Negative Urgency (A) (y = +15, z = - 5) ndi Positive Urgency (B) (y = +15, ...
Kukambirana
Sitinapeze kusiyana kwa striatal dopamine D2/D3 kupezeka kwa ma receptor pakati pa amuna omwe ali ndi PG kupita ku katswiri wa chithandizo chamankhwala, ndi kayendetsedwe kabwino kaimuna. Kuphatikiza pa kukwaniritsa wonse striatal D2/D3 kupezeka kwa receptor, kuwunika kwa ROI kunayang'ananso kupezeka kwa receptor m'magawo atatu ogwira ntchito a striatum. Kugawika kwa limbic kumakhala ndi ma nyukiliya obisika, polira putamen ndi porral caudate, ndipo amakhudzidwa kwambiri m'mavuto osokoneza bongo kuphatikizira kutchova njuga kosafunikira (Linnet et al., 2011; O'Sullivan et al., 2011; Steeves et al., 2009). Kupenyerera kwathu kopanda kusiyana mu zoyambira striatal dopamine D2/D3 kupezeka kwa receptor pakati pa ochita nawo PG ndikuwongolera kumagwirizana ndi maphunziro awiri aposachedwa a [11C] -raclopride omwe adawunika kusintha kumumanga pomwe maphunziro a PG adagwira ntchito zosiyanasiyana popanga zisankho / kutchova njuga (Joutsa et al., 2012; Linnet et al., 2011), komanso kafukufuku wachitatu wa PET wofanizira odwala omwe ali ndi Matenda a Parkinson omwe ali ndi zovuta zowongolera kuphatikiza PG, pakuwona zithunzi zokhudzana ndi mphotho (O'Sullivan et al., 2011). Sitinathe kulimbikitsa kuchepetsa BPND mfundo zomwe Steeves et al (2009) milandu 7 yokhala ndi Matenda a Parkinson, okhala ndi dopamine-agonist omwe adayambitsa PG. Tiyenera kudziwa kuti zoyambira zawo zoyambira zimakhudza kusankha kwamagalimoto (kusankha pakati pa makhadi anayi opanda mayankho opanda tanthauzo), zomwe zitha kupotoza kuyerekezera kwakupezeka koyambira (Egerton et al., 2009).
Zovuta zingapo zingatengedwe pazomwe tidapeza mu PG. Choyamba, kuchepetsedwa kwa dopamine D2/D3 kupezeka kwa receptor komwe kumafotokozedwapo ogwiritsa ntchito mankhwalaFehr et al., 2008; Heinz et al., 2004; Martinez et al., 2004; Volkow et al., 1997, 2001) itha kuthandizidwa ndi mankhwalawa a neuroadaptive kapena neurotoxic a mankhwalawo, ndipo osagwirizana ndi chiopsezo chokhala pachiwopsezo chamavuto osokoneza bongo. Zogwirizana ndi nkhaniyi, D2 kupezeka kwa ma receptor kunaphatikizana ndi nthawi yayitali yozunza mwanthawi yofanizira woyeserera (Nader et al., 2006). Kutanthauzira kwina ndikuti kuchepetsedwa kwa kumanga kwa dopamine kungaimire chiopsezo cha kusuta kwa mankhwala omwe amapezeka osati fotokozerani ku PG ngati chizolowezi chakhalidwe. Kupezeka kwa dopamine receptor kupezeka kunanenedwapo kale mu kunenepa kwambiri (Wang et al., 2001), monga munthu wina ofuna kusintha. Zachidziwikire, zomwe tapeza sizimalepheretsa kusintha kwa ma neurotransmitter ena mu PG, monga glutamate, GABA kapena serotonin (Leeman ndi Potenza, 2012,, kapena amasintha mbali zina pamatenda a dopamine monga kumasulidwa (Linnet et al., 2011), bwerezaninso (Cilia et al., 2010) kapena kagayidwe (Bergh et al., 1997). Chachiwiri chazidziwitso kuchokera pazomwe tapeza ndikuti kumasulidwa kwa dopamine kosonkhezeredwa ndi magawo a kupambana ndi kutaya zomwe akumana nazo omwe amatchova njuga (mwachitsanzo. Zald et al., 2004) sizingakwanire kuyendetsa bata D2/D3 kupezeka kwapatsidwa.
Komabe, mkati mwa gulu la otchova njuga, [11C] -raclopride binder anali olumikizana molakwika ndi impulsivity, chinthu chokhazikitsidwa chomwe chingayike kubweretsa njuga (Slutske et al., 2005) ndi zovuta zogwiritsa ntchito mankhwala (Ersche et al., 2010). Mbali yofulumira yomwe timazindikira kuti ndi yolosera za striatal dopamine kumanga inali Urgency (kapena 'kukwiya mwachangu'), chizolowezi chofuna kuchita zinthu mopupuluma munthawi yayikulu. Kufanizira kwazomwe zikuchitika pakompyuta ya Urgency kunapereka kukula kwakukulu kuposa 'kupyapyala' (mwachitsanzo, kusowa mapulani, kusapirira), komwe kunawonedwanso pagulu lalikulu lomwe lidayambika kuchokera kumalo omwewoMichalczuk et al., 2011). Kuperewera kwa subscale yokonzekera sikunanenere za striatal dopamine yomanga pakuwunika kwa voxelwise. Zambiri zadzidzidzi zimalosera kusinthaku kukhala njuga yamavuto, kugwiritsa ntchito mankhwala osokoneza bongo komanso zizolowezi zina zowopsa pamasampulu amakalasi (Cyders ndi Smith, 2008). Zochepa ndizodziwika pokhudzana ndi maubongo omwe amayendetsa gawo ili la kunyengerera, ngakhale kuti kafukufuku waposachedwa wamatsenga waposachedwa adati liphatikizidwe la Urgency ndi magawo a GABA mu dorsolateral prefrontal cortex (Mnyamata et al., 2011), ndi data phula ikuwonetsa kuwongolera kwa ma striatal dopamine mwa cortical GABA (Matsumoto et al., 2005). Mu gulu la PG, zonse zoyipa komanso zabwino za Urgency zidanenedweratu striatal dopamine D2/D3 kupezeka kwa receptor. Maubwenzi awa adawonedwa mu striatal ROI komanso limbic (Negative Urgency) komanso oyanjana (onse Negative and Positive Urgency) magawo a striatal, ndipo adatsimikizika pakuwunika kwa voxelwise. Zowopsa ndi Zabwino Zazadzidzidzi zinali zokhudzana, komabe sizikudziwika ngati odwala omwe ali ndi PG nawonso ali pachiwopsezo chokhala ndi chiyembekezo (mwachitsanzo, euphoria) komanso chosalimbikitsa (mwachitsanzo, kusowa nkhawa, kuvutika maganizo) zimayambitsa nkhawa (Blaszczynski ndi Nower, 2002; Stewart ndi Zack, 2008).
Chiyanjano pakati pa kupezeka kwa Urgency ndi dopamine receptor sichinawonekere pagulu laling'ono la oyendetsa bwino omwe ayesedwa pano. Zowonadi, cholowa cha Negative Urgency mu limbic striatum chinali champhamvu kwambiri mgulu la PG kuposa zoyendetsera. Mwa anthu omwe amadalira methamphetamine, striatal D2/D3 kupezeka kwa receptor kunaphatikizidwanso molakwika ndi kusokonezeka kwa mkhalidwe (Lee ndi al., 2009). Poyerekeza lipoti laposachedwa mu ophunzira omwe ali ndiumoyo omwe akuwonetsa ubale wapakati pa mgwirizano wa pakati [11C] -raclopride binding and the Srance UkufunaGjedde et al., 2010), tidayesa kusanthula kwa post-hoc kuti tiyese zotsatira zofananira za Urgency mu zitsanzo zathu za PG ndikuwongolera athanzi. Tidayesanso kusintha kwa 'inverted U' (kapena Yerkes-Dodson) mu miyendo, ngati ntchito ya Negative Urgency. Izi zikusonyeza kuti onse okwera ndi kutsika kochepa kokhudzana ndi kukhudzika kumalumikizidwa ndi kutsika kwa striatal raclopride binder, ndikuti BPND ndichabwino kwambiri pakatikati kagawidweko.
M'mawu ake, adatsitsa BPND zitha kuwonetsa kuchepa mu mawu a striatal D2/D3 dopamine receptors ndi / kapena kuwonjezeka kwamankhwala a daptamine ya synaptic. Kafukufuku wogwiritsa ntchito alpha-methyl paratyrosine (AMPT) kuti athetse dopamine m'maphunziro omwe amadalira cocaine adawonetsa kuchepa kwa kupezeka kwa receptor kuphatikiza ndi kuchepa milingo ya dopamine ya extracellular pansi pazoyambira (Martinez et al., 2009). Komabe, ntchito yoyamba ku PG yawonetsa kutulutsidwa kwa ntchito zokhudzana ndi dopamine mu gawo la omwe akutenga nawo gawo pa PG omwe anasimba chisangalalo chokhudzana ndi ntchito (Linnet et al., 2011). Ndizotheka kuti BP yotsikaND m'malo otsika mumatha kuyendetsedwa ndi D2 / D3 receptor, pomwe BP yotsikaND mu kwambiri kukakamiza akhoza kuyendetsedwa ndi kupezeka kwa receptor kupezeka komanso okwera extracellular dopamine (Gjedde et al., 2010). Kuchuluka kwa kutulutsidwa kwa dopamine kungathenso kugwirizanitsidwa ndi kupezeka kwapansi pa lamulo la (midbrain) kupezeka kwa autoreceptor, monga momwe wapezeka ndi [18F] -fallypride ligand (Buckholtz et al., 2010). Pazomwe zilipo, kusamala kwina kumakhala koyenera chifukwa chakuti mawu akuti quadratic adayendetsedwa makamaka ndi omwe anali ndi mbali ya PG akugwera kudzanja lamanzere, kutsika miyendo, kuphatikizidwa ndi kusiyana kotchulidwa mu gululi. Kuti timvetse bwino za maubwenzi awa, maphunziro owonjezera amafunikira kugwiritsa ntchito zolemba zingapo za dopamine pantchito yonse yopanda chidwi, koma titha kuvomereza kuti maphunziro amtsogolo azilingalira za mayendedwe amtunduwu ndi ma quadratic payekha panjira yonse ya dopamine.
Monga zoperewera zina za kafukufukuyu, kukula kwamagulu athu kunali kocheperako chifukwa chake kafukufukuyu sanapatsidwe mphamvu zokwanira kuti azindikire kukula kwakanthawi. Kutengera kukula kwa zotsatira za striatum yonse (Cohen's d = 0.22), magulu awiri osachepera 350 omwe akutenga nawo mbali adzafunika kuti azindikire kusiyana kwakukulu. Chachiwiri, kugwiritsa ntchito njira zowongolera kuchokera ku nkhokwe zachizolowezi kunapangitsa kuti pakhale zovuta zazing'ono pakati pamagulu awiriwa: maphunziro a PG adawonetsedwa ndi zithunzi zosalowerera poyerekeza (ngakhale kulibe yankho), ndipo maphunziro a PG adalandira jekeseni wa bolus pomwe zowongolera zidalandira bolus kuphatikiza kulowetsedwa. Ntchito isanachitike ikuwonetsa kuti [11 C] -raclopride zomangira zomwe zimapangidwa ndi bolus njira yokhayo ndizofanana ndi mfundo zomangika zomwe zimapangidwa ndi bolus-infusion mu odzipereka omwewo (Carson et al., 1997; Ito et al., 1998). Mu gulu la PG, padali kuchuluka kwa heterogeneity munthawi ya Scan wachibale chithandizo (ambiri koma si onse omwe adafufuzidwa chisanachitike chithandizo), ndipo psychiatric comorbidities idalipo mwa ophunzira anayi. Kafukufuku wa Post-hoc adawonetsa kuti zotsatira zathu sizinali chifukwa cha kusuta (Busto et al., 2009; cf Fehr et al., 2008). Psorchiatric comorbidities ndiyotchuka kwambiri mu PG (Kessler et al., 2008) ndikuphatikizidwa kwa milandu yotere kumapangitsa kuti zomwe tikupeza ndizofanana.
Pankhani ya kachipatala, ndizodziwika kuti pomwe dopamine agonist pramipexole ndi gawo la agonist aripiprazole akhala akuthandizira poyambitsa kutchova juga kosagwirizana (Smith et al., 2011; Voon et al., 2009), dopamine D2 antepton antagonists monga olanzapine mpaka pano alephera kuwonetsa kuyeserera kwathunthu pakuyesedwa kwa mankhwala a PG (Fong et al., 2008; McElroy et al., 2008). M'magulu a ophunzira omwe ali ndiumoyo wathanzi, kupezeka kwa dopamine koyambira kumapangitsa zochitika za dopaminergic othandizira malinga ndi mtundu wa in Uver (Cools ndi D'Esposito, 2011), potero zomwe tapeza zakusagwirizana kwa dopamine m'matenda osokoneza bongo amatanthawuza kuti anthu omwe ali ndi chidwi chokhudzidwa kwambiri atha kuwonetsa mapindu amasiyana ndi mankhwala ochokera ku dopamine. Mwachitsanzo, ngati otsika [11 C] -raclopride omangika pamasewera otchova juga amayamba chifukwa cha kuchuluka kwa synaptic dopamine (Gjedde et al., 2010), awa akhoza kuyankha mwapadera dopamine blockade. Maubale omwe amakumana nawo ndi kusiyanasiyana kwamunthu kumatanthawuza kuti njira zambiri zaku dopaminergic zitha kugwira ntchito povutitsa ena (Buckholtz et al., 2010; Cilia et al., 2010; Gjedde et al., 2010).
Kulankhulidwa
L Clark alengeza zaulangizi wa Cambridge Cognition plc. AR Lingford-Hughes alandila ulemu kuchokera kwa Janssen-Cilag, Pfizer, Servier, komanso ku Britain Association for Psychopharmacology. Wapereka upangiri ku NET Device Corp, walandila ndalama zofufuzira kuchokera kwa Archimedes, Lundbeck, Pfizer ndi Schering, ndipo ali ndi zopereka zofufuzira ndi GlaxoSmithKline. DJ Nutt adatumikira m'mabungwe olangiza a Lundbeck, Servier, Pfizer, Reckitt Benkiser, D&A Pharma, ndipo alandiranso honaria kuchokera ku Bristol Myers Squibb, Glaxo Smith Kline ndi Schering-Plow. Adalandira ndalama zofufuzira kuchokera ku P1vital, amagawana nawo P1vital, ndipo amalandila ulemu wolemba kuchokera kwa Sage. AR Lingford-Hughes ndi DJ Nutt onse ndi mamembala a Lundbeck International Neuroscience Foundation. Dr Stokes, Dr Wu, Ms Michalczuk, Ms Benecke, Dr Egerton, Dr Watson, Dr Piccini ndi Dr Bowden-Jones alibe ndalama zoti anganene.
Kuvomereza
Ntchitoyi idathandizidwa ndi Medical Research Council yopereka G0802725 ku LC ndi HBJ, ndi G0400575 kwa DJN ndi ALH. Chipatala cha Dziko Lonse Cha Njuga chikuthandizidwa ndi Fund Yoyeserera Njuga. Ntchitoyi idatsirizidwa mu Behavioral and Clinical Neuroscience Institute, mothandizidwa ndi mphotho ya mgwirizano kuchokera ku MRC ndi Wellcome Trust (wotsogolera: TW Robbins). Zambirizi zidawonetsedwa pamsonkhano wa chirimwe wa Britain Association for Psychopharmacology, Harrogate, UK (Julayi 2011).
Zothandizira
Backman L., Ginovart N., Dixon RA, Wahlin TB, Wahlin A., Halldin C., Farde L. Akuluakulu okhudzana ndi ukalamba wogwirizana ndi kusintha kwa machitidwe a striatal dopamine. Am. J. Psychiatry. 2000; 157: 635-637. [Adasankhidwa]
Bergh C., Eklund T., Sodersten P., Nordin C. Anasinthika ntchito ya dopamine mu njuga zamatenda. Psychol. Med. 1997; 27: 473-475. [Adasankhidwa]
Blaszczynski A., Nower L. A njira yanjira yamavuto ndi njuga zamatsenga. Kuledzera. 2002; 97: 487-499. [Adasankhidwa]
Bowden-Jones H., Clark L. Pathological Kutchova Juga: kusinthika kwa mitsempha ndi zamankhwala. Br. J. Psychiatry. 2011; 199: 87-89. [Adasankhidwa]
Mnyamata F., Evans CJ, Edden RA, Lawrence AD, Singh KD, Husain M., Sumner P. Dorsolateral premaal gamma-aminobutyric acid mwa amuna amaneneratu zakusiyana pakati pa kukakamira kosafunikira. Biol. Psychiatry. 2011; 70: 866-872. [Adasankhidwa]
Buckholtz JW, Treadway MT, Cowan RL, Woodward ND, Li R., Ansari MS, Baldwin RM, Schwartzman AN, Shelby ES, Smith CE, Kessler RM, Zald DH Dopaminergic network kusiyana pakukhudzidwa ndi anthu. Sayansi. 2010; 329: 532. [Adasankhidwa]
Busto UE, Redden L., Mayberg H., Kapur S., Houle S., Zawertailo LA Dopaminergic zochitika mu osuta omwe ali ndi nkhawa: kafukufuku wa positron emission tomography. Sinthani. 2009; 63: 681-689. [Adasankhidwa]
Carson RE, Breier A., de Bartolomeis A., Saunders RC, Su TP, Schmall B., Der MG, Pickar D., Eckelman WC Quanifying of amphetamine-ikiwa chifukwa cha [11C] kumanga mendulo ndi kulowetsedwa kosalekeza. J. Cereb. Magazi Olowera Magazi. 1997; 17: 437-447. [Adasankhidwa]
Chase HW, Clark L. Kutchova njuga kuneneratu kuyankha kwapakati pa zotsatira zaposachedwa. J. Neurosci. 2010; 30: 6180-6187. [Adasankhidwa]
Cilia R., Ko JH, Cho SS, van Eimeren T., Marotta G., Pellecchia G., Pezzoli G., Antonini A., Strafella AP Yachepetsa kuchuluka kwa ma transporter a dopamine mu ventral striatum ya odwala omwe ali ndi matenda a Parkinson komanso njuga zamatenda. Neurobiol. Dis. 2010; 39: 98-104. [Adasankhidwa]
Cools R., D'Esposito M. Zochita zofananira ndi mawonekedwe a U pamachitidwe okumbukira anthu ndikuwongolera kuzindikira. Chiwawa. Psychiatry. 2011; 69: e113 – e125. [Adasankhidwa]
Ma Cyders MA, Smith GT Emotion-to dispositions to Rash action: zabwino ndi zoyipa changu. Psychol. Bull. 2008; 134: 807-828. [Adasankhidwa]
Cyders MA, Smith GT, Spillane NS, Fischer S., Annus AM, Peterson C. Kuphatikiza kwamphamvu ndi malingaliro abwino kuti alosere zinthu zowopsa: chitukuko ndi kutsimikizika kwa muyeso wodalirika. Psychol. Ganizirani. 2007; 19: 107-118. [Adasankhidwa]
Dalley JW, Fryer TD, Brichard L., Robinson ES, Theobald DE, Laane K., Pena Y., Murphy ER, Shah Y., Probst K., Abakumova I., Aigbirhio FI, Richards HK, Hong Y., Baron JC, Everitt BJ, Robbins TW Nyukiliya yomwe imasonkhanitsa D2 / 3 receptors imalosera zamtunduwu ndi kulimbikitsidwa kwa cocaine. Sayansi. 2007; 315: 1267-1270. [Adasankhidwa]
Di Chiara G., Imperato A. Mankhwala osokoneza bongo omwe anthu amawagwiritsa ntchito amakonda kuwonjezera chiwonetsero cha dopamine m'matumbo a mesolimbic oyendetsera makoswe momasuka. Proc. Natl. Acad. Sayansi. USA 1988; 85: 5274-5278. [Adasankhidwa]
Egerton A., Mehta MA, Montgomery AJ, Lappin JM, Howes OD, Reeves SJ, Cunningham VJ, Grasby PM The dopaminergic maziko a machitidwe a anthu: kuwunikira maphunziro a kulingalira kwamolekyulu. Neurosci. Biobehav. Rev. 2009; 33: 1109-1132. [Adasankhidwa]
Egerton A., Shotbolt JP, Stokes PR, Hirani E., Ahmad R., Lappin JM, Reeves SJ, Mehta MA, Howes OD, Grasby PM pachimake cha anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: Phunziro la [11C] raclopride PET. Chikhulupiriro. 2010; 50: 260-266. [Adasankhidwa]
Ersche KD, Turton AJ, Pradhan S., Bullmore ET, Robbins TW Mankhwala osokoneza bongo a endbhenotypes: okopa chidwi ndi mikhalidwe yosaka chidwi. Biol. Psychiatry. 2010; 68: 770-773. [Adasankhidwa]
Fehr C., Yakushev I., Hohmann N., Buchholz HG, Landvogt C., Deckers H., Eberhardt A., Klager M., Smolka MN, Scheurich A., Dielentheis T., Schmidt LG, Rosch F., Bartenstein P., Grunder G., Schreckenberger M. Association of low striatal dopamine d2 receptor kupezeka ndi chidaliro cha chikonga chofanana ndi chomwe chimawonedwa ndi mankhwala ena ozunza. Am. J. Psychiatry. 2008; 165: 507-514. [Adasankhidwa]
Ferris J., Wynne H. Canadian Center on Abuse; Ottawa, Ontario: 2001. Chingwe cha Mavuto Akubera ku Canada.
Fong T., Kalechstein A., Bernhard B., Rosenthal R., Rugle L. Chiyeso cham'maso chokhazikika m'maso. Pharmacol. Biochem. Behav. 2008; 89: 298-303. [Adasankhidwa]
Frascella J., Potenza MN, Brown LL, kulera kwa ana Kugawidwa kwa bongo komwe kumatsegulira njira zolaula: kuphatikiza chizolowezi chatsopano? Ann. NY Acad. Sayansi. 2010; 1187: 294-315. [Adasankhidwa]
Gjedde A., Kumakura Y., Cumming P., Linnet J., Moller A. Makina osakanikirana pakati pa mawonekedwe a dopamine receptor pakupezeka kwa striatum ndi kufunafuna. Proc. Natl. Acad. Sayansi. USA 2010; 107: 3870-3875. [Adasankhidwa]
Heinz A., Siessmeier T., Wrase J., Hermann D., Klein S., Grusser SM, Flor H., Braus DF, Buchholz HG, Ground G., Schreckenberger M., Smolka MN, Rosch F., Mann K ., Bartenstein P. Correlation pakati pa dopamine D (2) zolandilira mu ventral striatum ndi chapakati kukonzanso zakumwa zoledzeretsa ndikukhumba. Am. J. Psychiatry. 2004; 161: 1783-1789. [Adasankhidwa]
Innis RB, Cunningham VJ, Delforge J., Fujita M., Gjedde A., Gunn RN, Holden J., Houle S., Huang SC, Ichise M., Iida H., Ito H., Kimura Y., Koeppe RA , Knudsen GM, Knuuti J., Lammertsma AA, Laruelle M., Logan J., Maguire RP, Mintun MA, Morris ED, Parsey R., Price JC, Slifstein M., Sossi V., Suhara T., Votaw JR, Wong DF, Carson RE Consensus nomenclature ya mu vivo poganiza kuti ma radioligands asintha. J. Cereb. Magazi Olowera Magazi. 2007; 27: 1533-1539. [Adasankhidwa]
Ito H., Hietala J., Blomqvist G., Halldin C., Farde L. Kufanizira kwa kanthawi kocheperako komanso njira yolowerera yolumikizira kwa kuchuluka kwa PET kwa [11C] kumanga ma raclopride. J. Cereb. Magazi Olowera Magazi. 1998; 18: 941-950. [Adasankhidwa]
Joutsa J., Johansson J., Niemela S., Ollikainen A., Hirvonen MM, Piepponen P., Arponen E., Alho H., Voon V., Rinne JO, Hietala J., Kaasinen V. Mesolimbic dopamine kumasulidwa kulumikizidwa kuwonetsa kuzunzika kwa njuga zamatenda. Chikhulupiriro. 2012; 60: 1992-1999. [Adasankhidwa]
Kessler RC, Hwang I., LaBrie R., Petukhova M., Sampson NA, Winters KC, Shaffer HJ DSM-IV njuga zamatenda mu National Comorbidity Survey Replication. Psychol. Med. 2008; 38: 1351-1360. [Adasankhidwa]
Kim JH, Son YD, Kim HK, Lee SY, Cho SE, Kim YB, Cho ZH Zotsatira za ukalamba pa dopamine D (2) receptor kupezeka kwa magawo a striatal: Kafukufuku wapamwamba wa positron emission tomography. EUR. Neuropsychopharmacol. 2011; 21: 885-891. [Adasankhidwa]
Lee B., London ED, Poldrack RA, Farahi J., Nacca A., Monterosso JR, Mumford JA, Bokarius AV, Dahlbom M., Mukherjee J., jpg RM, Brody AL, Mandelkern MA Striatal dopamine d2 / d3 receptor deptamine yafupika pakudalira kwa methamphetamine ndipo imalumikizidwa ndi kusakhazikika. J. Neurosci. 2009; 29: 14734-14740. [Adasankhidwa]
Leeman RF, Potenza MN Kufanana ndi kusiyana pakati pa kutchova juga kwazomwe zimayambitsa matenda osokoneza bongo: kuyang'ana kwambiri pakupunthwa komanso kukakamizidwa. Psychopharmacology (Berl) 2012; 219: 469-490. [Adasankhidwa]
Lesieur HR, Blume SB The South Oaks Gossip Screen (SOGS): chida chatsopano chodziwitsira otchova njuga. Am. J. Psychiatry. 1987; 144: 1184-1188. [Adasankhidwa]
Linnet J., Moller A., Peterson E., Gjedde A., Doudet D. Dopamine kumasulidwa mu ventral striatum nthawi ya Iowa Masewera a Masewera a Task akugwirizana ndi kuchuluka kwamasewera osangalatsa mu njuga zamatenda. Kuledzera. 2011; 106: 383-390. [Adasankhidwa]
Martinez D., Slifstein M., Broft A., Mawlawi O., Hwang DR, Huang Y., Cooper T., Kegeles L., Zarahn E., Abi-Dargham A., Haber SN, Laruelle M. Imaging mesolimbic kufalitsa dopamine ndi positron umuna tomography. Gawo II: amphetamine-inachititsa dopamine kumasulidwa mu magawo ogwirira ntchito a striatum. J. Cereb. Magazi Olowera Magazi. 2003; 23: 285-300. [Adasankhidwa]
Martinez D., Broft A., Foltin RW, Slifstein M., Hwang DR, Huang Y., Perez A., Frankle WG, Cooper T., Kleber HD, Fischman MW, Laruelle M. Cocaine amadalira komanso kupezeka kwa d2 magawo othandizira a striatum: ubale ndi njira yofunafuna cocaine. Neuropsychopharmacology. 2004; 29: 1190-1202. [Adasankhidwa]
Martinez D., Greene K., Broft A., Kumar D., Liu F., Narendran R., Slifstein M., Van Heertum R., Kleber HD Otsika otsika a dopamine kwa odwala omwe amadalira cocaine: zomwe zapezedwa ndikuganiza kwa PET of D (2) / D (3) receptors kutsatira pachimake dopamine kufooka. Am. J. Psychiatry. 2009; 166: 1170-1177. [Adasankhidwa]
Matsumoto M., Togashi H., Kaku A., Kanno M., Tahara K., Yoshioka M. Cortical GABAergic yokhudza kayendedwe ka dopaminergic pamavuto am'maganizo mu rat dorsolateral striatum. Sinthani. 2005; 56: 117-121. [Adasankhidwa]
McElroy SL, Nelson EB, Welge JA, Kaehler L., Keck PE, Jr. Olanzapine pothana ndi juga ya pathological: kuyesedwa kosasankhidwa kwa malo. J. Clin. Psychiatry. 2008; 69: 433-440. [Adasankhidwa]
Meyer G., Schwertfeger J., Exton MS, Janssen OE, Knapp W., Stadler MA, schedulelowski M., Kruger TH Neuroendocrine poyankha kutchova njuga pamasewera ovuta. Psychoneuroendocrinology. 2004; 29: 1272-1280. [Adasankhidwa]
Michalczuk R., Bowden-Jones H., Verdejo-Garcia A., Clark L. Kuthamangitsidwa ndi kupotozedwa kwamalingaliro muotchovera njuga opita ku chipatala cha UK National vuto Njuga: lipoti loyambirira. Psychol. Med. 2011; 41: 2625-2635. [Nkhani yaulere ya PMC] [Adasankhidwa]
Montgomery AJ, Thielemans K., Mehta MA, Turkheimer F., Mustafovic S., Grasby PM Kuwongolera koyenda kwamutu pamaphunziro a PET: kufananizira njira. J. Nucl. Med. 2006; 47: 1936-1944. [Adasankhidwa]
Nader MA, Morgan D., Gage HD, Nader SH, Calhoun TL, Buchheimer N., Ehrenkaufer R., Mach RH PET poganiza za dopamine D2 receptors panthawi yodzilamulira cocaine wodwala mu nyani. Nat. Neurosci. 2006; 9: 1050-1056. [Adasankhidwa]
O'Sullivan SS, Wu K., Politis M., Lawrence AD, Evans AH, Bose SK, Djamshidian A., Lees AJ, Piccini P. Cue-omwe amachititsa kuti striatal dopamine amasulidwe mu zomwe zimachitika chifukwa cha matenda a Parkinson. Ubongo. 2011; 134: 969-978. [Adasankhidwa]
Reuter J., Raedler T., Rose M., Hand I., Glascher J., Buchel C. Njira zachiwerewere zimagwirizanitsidwa ndi kuyambitsa kachitidwe ka mphotho ya mesolimbic. Nat. Neurosci. 2005; 8: 147-148. [Adasankhidwa]
Shaffer HJ, LaBrie R., Scanlan KM, Cummings TN Matenda a Kutchova Njuga pakati pa achinyamata: Massachusetts Ginja Screen (MAGS) J. Gambl. Stud. 1994; 10: 339-362.
Sheehan DV, Lecrubier Y., Sheehan KH, Amorim P., Janavs J., Weiller E., Hergueta T., Baker R., Dunbar GC Mafunso a Mini-International Neuropsychiatric Mafunso (MINI): kukhazikitsa ndi kutsimikizira kwa mtundu wofufuza wodalirika kuyankhulana kwamisala kwa DSM-IV ndi ICD-10. J. Clin. Psychiatry. 1998; 59 (Suppl. 20): 22-33. [Adasankhidwa]
Slutske WS, Caspi A., Moffitt TE, Poulton R. Umunthu ndi kutchova juga: kafukufuku woyembekezeredwa wa gulu lobadwira la achinyamata. Arch. Gen. Psychiatry. 2005; 62: 769-775. [Adasankhidwa]
Smith N., Kitchenham N., Bowden-Jones H. Kutchova njuga kwachilombo ndi chithandizo cha psychosis ndi aripiprazole: malipoti a milandu. Br. J. Psychiatry. 2011; 199: 158-159. [Adasankhidwa]
Steeves TD, Miyasaki J., Zurowski M., Lang AE, Pellecchia G., Van Eimeren T., Rusjan P., Houle S., Strafella AP Kuchulukitsa kwa striatal dopamine ku Parkinsonia odwala ndi njuga yamatenda: [11C] raclopride PET kuphunzira. Ubongo. 2009; 132: 1376-1385. [Adasankhidwa]
Stewart SH, Zack M. Development ndi kuwunika kwa ma psychometric a mafunso osokoneza bongo atatu apa njuga. Kuledzera. 2008; 103: 1110-1117. [Adasankhidwa]
Stokes PR, Egerton A., Watson B., Reid A., Breen G., Lingford-Hughes A., Nutt DJ, Mehta MA Chofunika amatsika kutsogolo komanso kwakanthawi [11C] -raclopride kumanga pambuyo pa vuto la THC. Chikhulupiriro. 2010; 52: 1521-1527. [Adasankhidwa]
Verdejo-Garcia A., Lawrence AJ, Clark L. Impulsivity ngati chisonyezo chokhala pachiwopsezo cha zovuta zogwiritsa ntchito mankhwala osokoneza bongo: kuwunikira zomwe zapezedwa kuchokera ku kafukufuku yemwe ali pachiwopsezo chachikulu, otchova njuga pamavuto komanso maphunziro azachipembedzo. Neurosci. Biobehav. Rev. 2008; 32: 777-810. [Adasankhidwa]
Volkow ND, Wang GJ, Fowler JS, Logan J., Gatley SJ, Hitzemann R., Chen AD, Dewey SL, Pappas N. Adawonjezera kuyankha kwa driamal dopaminergic m'madongosolo omwe adatsamira pa cocaine. Zachilengedwe. 1997; 386: 830-833. [Adasankhidwa]
Volkow ND, Wang GJ, Fowler JS, Logan J., Gatley SJ, Gifford A., Hitzemann R., Ding YS, Pappas N. Kulosera kwa kulimbikitsa mayankho ku psychostimulants mwa anthu mwa milingo ya dopamine D2 receptor. Am. J. Psychiatry. 1999; 156: 1440-1443. [Adasankhidwa]
Volkow ND, Chang L., Wang GJ, Fowler JS, Ding YS, Sedler M., Logan J., Franceschi D., Gatley J., Hitzemann R., Gifford A., Wong C., Pappas N. Otsika otsika a ubongo dopamine D2 receptors mu methamphetamine abusers: mayanjano ndi metabolism mu orbitof mbeleal cortex. Am. J. Psychiatry. 2001; 158: 2015-2021. [Adasankhidwa]
Voon V., Fernagut PO, Wickens J., Baunez C., Rodriguez M., Pavon N., Juncos JL, Obeso JA, Bezard E. Kukhalitsa kwa dopaminergic mu matenda a Parkinson: kuchokera ku dyskinesias mpaka kukakamiza kuwongolera zovuta. Lancet Neurol. 2009; 8: 1140-1149. [Adasankhidwa]
Wang GJ, Volkow ND, Logan J., Pappas NR, Wong CT, Zhu W., Netusil N., Fowler JS Brain dopamine ndi kunenepa kwambiri. Lancet. 2001; 357: 354-357. [Adasankhidwa]
Watabe H., Endres CJ, Breier A., Schmall B., Eckelman WC, Carson RE Kuyeza kwa kutulutsidwa kwa dopamine ndi kulowetsedwa kosalekeza kwa [11C] raclopride: kukhathamiritsa ndi kulingalirananso kwa phokoso. J. Nucl. Med. 2000; 41: 522-530. [Adasankhidwa]
Zald DH, Boileau I., El-Dearedy W., Gunn R., McGlone F., Dichter GS, Dagher A. Dopamine kufalitsa mu striatum yaumunthu panthawi yogwira ntchito yolipira ndalama. J. Neurosci. 2004; 24: 4105-4112. [Adasankhidwa]
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