Nako ea mokokotlo. 2012 Oct 15; 63 (1): 40-6. Doi: 10.1016 / j.neuroimage.2012.06.067. Epub 2012 Jul 6.
Clark L, Litutu PR, Wu K, Michalczuk R, Benecke A, Watson BJ, Egerton A, Pccini P, Nutt DJ, Bowden-Jones H, Lingford-Hughes AR.
mohloli o moholo
Lefapha la Psychology ea Tlhaho, Univesithi ea Cambridge, Cambridge, UK. [imeile e sirelelitsoe]
inahaneloang
Papali ea papali ea chelete (PG) ke tšebeliso ea boitšoaro bo amanang le tšusumetso e phahameng le ho belaelloa dopamine dysregulation. Fokotsoe striatal dopamine D (2) / D (3) mokamoli ho fumaneha ho tlalehiloe ho lemalloang ea lithethefatsi, 'me ho ka ba le letšoao la ho ba tlokotsing ea mafu a lemalloang.
Morero oa thuto ea hona joale e ne e le ho lekola maemo a bophelo ba basali dopamine D (2) / D (3) mokamoli ho fumaneha ho PG, le kamano ea eona le tšusumetso ea litšobotsi. Ba batona ba nang le PG (n = 9) le taolo e ntle ea banna (n = 9) ba bile ba le tlasa monahano oa [11C] -raclopride positron emission tomography imaging mme ba qetile sekala sa UPPS-P impulsivity.
Ho ne ho se na phapang ea bohlokoa lipakeng tsa lihlopha tsa striatal dopamine D (2) / D (3) mokamoli phumaneho, ho fapana le litlaleho tse fetileng tsa bokhoba ba lithethefatsi.
Leha ho le joalo, ho ts'oenyeha ho amanang le maikutlo ('Urgency') ho ne ho hokahane hampe le menyetla e tlamang ea [11C] -raclopride sehlopheng sa PG. Ho ba sieo ha phapang ea sehlopha nakong ea pelehi dopamine ho tlama ho bolela phapang lipakeng tsa bokhoba ba litloaelo le bokhoba ba lithethefatsi. Leha ho le joalo, datha ea rona e bonts'a heterogeneity ho dopamine mokamoli ho fumaneha ka disordered becha, e le hore batho ba nang le phello e phahameng e amanang le maikutlo a leholimo ba ka bonts'a melemo e fapaneng ho tloha dopaminemeriana e fanoang.
Keywords: Ho becha, ho susumetsa, Dopamine, Neuroimaging, Ho lemalla, Striatum
Lintlha-khōlō Tsa
► Ho lekantsoe 11C-raclopride e tlamang papaling ea papali ea chelete, tšibollo ea boitšoaro bo bobe. ► Ha ho phapang ea sehlopha ho dopamine e tlamang e tsoang taolong e phetseng hantle. ► Dopamine e tlamang e tsamaellanang hampe le ho susumetsoa ho amanang le maikutlo ('Urgency').
Selelekela
Pathological Gossip (PG) ke bothata ba taolo ea tšusumetso ea DSM-IV e nang le tšubuhlellano e ngata ea bongaka le tšebeliso ea lithethefatsi, e hlahisang concuptualisation ea PG e le 'tlhekefetso ea boitšoaro' (Bowden-Jones le Clark, 2011; Frascella et al., 2010). Mehlala ea Neurobiological ea ts'ebeliso ea lithethefatsi e totobatsa bothata ba dopamine: lithethefatsi tse ngata tsa tlhekefetso li matlafatsa dopamine neurotransmission (Di Chiara le Imperato, 1988), le phokotso ho dopamine D2/D3 ho fumaneha ha li-receptor ho hlalositsoe ho bakuli ba itšetlehileng ka lithethefatsi tse fapaneng tse hlekefelitsoeng (Fehr et al., 2008; Heinz et al., 2004; Martinez et al., 2004; Volkow et al., 1997, 2001). Ha ho hlake hore na liphetoho tsena li bonts'a phello ea tšebeliso ea lithethefatsi ea nako e telele kapa ho ba tsietsing ea ho lemalla. E lumellana le letšoao le nang le tšoaetso, 'ho rata lithethefatsi' ho amana le D2/D3 phumaneho ea receptor (Volkow et al., 1999), le khatello ea methapo e qobelloang ho phela ka boits'oaro e bonts'a phihlello ea boikoetliso ea koae ka potlako le ho fokotsoa ha dopamine D2/D3 ho fumaneha ha receptor pele ho ts'ebetso ea lithethefatsi (Dalley et al., 2007). E le mokhoa oa ho lemalla joala bo ka 'nang ba e-ba le chefo e sa nahaneleng, lithuto tsa PG li ka thusa ho tsoela pele ho ithuta ka mefuta ea batho ba kotsing, le ho thusa ho rarolla mathata a sesosa le sephetho (Verdejo-Garcia et al., 2008). Ka sebele, ho na le lipontšo tse 'maloa tsa dopamine dysregulation ho PG. Mats'oao a dopamine a potoloha ho mokelikeli oa "cerebrospinal" a kenelletse methating ea papali ea chelete.Bergh et al., 1997; Meyer et al., 2004), joalo ka likarabo tsa fMRI ho li-circopper tse nang le dopamine nakong ea ts'ebetso ea mesebetsi ea papali ea papali ea chelete (Chase le Clark, 2010; Reuter et al., 2005), leha tataiso ea sephetho e sa lumellane. Ntle le moo, meriana ea dopamine-agonist bakeng sa Mafu a Parkinson e bonahala e khona ho baka tšitiso ea papali ea chelete e le litlamorao (Voon et al., 2009).
Positron Emission Tomography (PET) e nahanang ka [11C] -raclopride e fana ka mokhoa oa ho pheta phetisetso ea driamine ea striatal dopamine bokong ba motho bo phelang. [11C] -raclopride e sa tsoa sebelisoa lithutong tse 'ne tsa PET ho nka karolo ha barupeluoa ba sa ts'oane le ho becha ka meralo e matla (e amanang le mosebetsi).Joutsa et al., 2012; Linnet et al., 2011; O'Sullivan et al., 2011; Steeves et al., 2009). Tse peli tsa lithuto tsena li ne li le ho bakuli ba nang le Mafu a Parkinson (O'Sullivan et al., 2011; Steeves et al., 2009), moo ho sa tsejoeng hore na mefuta ea lits'oaetso tsa taolo ea ts'usumetso e amanang le tsona e sebetsa joang ka nepo ea neuropathology ea lefu (Voon et al., 2009). Lithuto tse ling tse peli, PG ea mantlha, ka bobeli ba sebelisitse liqeto tse boima tsa ho etsa liqeto / ho becha moo sekepe sa motheo se neng se kenyelletsa mosebetsi oa taolo ea sensorimotor (Joutsa et al., 2012; Linnet et al., 2011). Phuputso e le 'ngoe feela (Steeves et al., 2009) fumana bopaki ba dopamine D e fokotsitsoeng2/D3 fumaneha ka bongata sehlopheng se nang le papali ea chelete. Phuputso e teng hona joale e hlahlobile baster striatal dopamine D2/D3 ho fumaneha ha li-receptor ho bakuli ba batlang kalafo ba nang le tlhahlobo ea mantlha ea PG, moo re faneng ka maikutlo a hore phokotso ea D2/D3 ho fumaneha ha li-receptor ho ipapisitse le boithuto ba pele ho tlhekefetso ea lithethefatsi.
Re boetse re batla ho lekola striatal D2/D3 ho fumaneha ha receptor mabapi le tšusumetso ea boitšoaro. Ho ts'oaroa ho hoholo ho bonoa ka ts'epahalo ho litheko tsa lithethefatsi le PG (Verdejo-Garcia et al., 2008), hape e bonahala e bolela esale pele kholo ea tšebeliso ea lithethefatsi le mathata a papali ea chelete (Slutske et al., 2005). Haufinyane re sebelisitse sekala sa impulsivity sa UPPS-P (Cyders et al., 2007) ho hlahloba litlatsetso tse tlase tsa ho hloka toka ho ahang ho bakuli ba nang le PG ba eang Kliniki ea Naha ea Ho Becha ea Matekoane ea UK (Mikalczuk et al., 2011). Ho ile ha bonoa liphapang tsa bohlokoa lipakeng tsa sehlopha sa PG le taolo e phetseng hantle litsing tse 'maloa tsa lithuso tsa UPPS-P ho kenyelletsa Urgency - tšekamelo ea ho se ts'oenyehe nakong ea maemo a mabe kapa a nepahetseng a maikutlo (' rash impulsivity ') - le likarolo tsa' ho fokola 'ha batho (Ho hloka Moralo le ho haelloa ke mamello). Leha ho le joalo, boholo ba litlamorao bakeng sa phapang ea Urgency bo ne bo phahame haholo ho feta litšobotsi tse patisaneng tsa ho se ts'oanehe, ho hlahisa sephetho sa hore ho susumetsa ho amanang le maikutlo ho bohlokoa ka ho khetheha maemong a papali ea chelete e sotlehileng (Mikalczuk et al., 2011). Ka lebaka la lipatlisiso tsena, liphapang tsa rona ka bomong lia sekaseka a priori ho li-subscales tse peli tsa Urgency (Negative Urgency and Positive Urgency) joalo ka baetapele.
Mekhoa le thepa
barupeluoa ba
Baithaopi ba robong ba banna ba nang le PG (lilemo tse bolelang lilemo tse 35.3, sd 9.0, range 25-49) ba ile ba bapisoa le taolo e robong ea banna e phetseng hantle (e bolelang lilemo tse 37.2, sd 5.6, range 30-46). Taba ea leshome ea PG e ile ea hiroa empa ha e fumanehe bakeng sa tlhahlobo ka lebaka la ho hloleha ha radiochemistry. Litekanyetso tsa motheo tsa taolo ea baithaopi li fumanoe liphuputsong tse peli tse fetileng (Egerton et al., 2010; Stoke et al., 2010) o sebelisa database e tloaelehileng ea sclopride scans e tšoaretsoeng Setsing sa Tleliniki ea MRC, mme e ne e sa fapana le sehlopha sa PG ka lilemo (t16 = 0.53, p = .602). Barupeluoa ba PG ba ile ba rutoa ho isa bonyane boemong ba sekolo se phahameng ka likhakanyo tsa IQ maemong a phetseng hantle (Wechsler Adult Scale for Intelligence: e bolelang 116, sd 10.8; Teko ea Naha ea Batho ba baholo ea ho Bala: bolela 117, sd 5.7); Mosebetsi oa nakong e fetileng ha o bontše kamano e ts'oanang lipakeng tsa bohlale le maemo a tlamang a dopamine. Baithaopi bohle ba fane ka tumello e ngotsoeng e nang le tsebo bakeng sa thuto, e ileng ea amoheloa ka bobeli ke Komiti ea Boitšoaro ea Liphuputso ea Hammersmith le Tsamaiso ea Komiti ea Boeletsi ea Lintho tsa Radioactive, UK.
Barupeluoa ba PG ba ile ba hloaea ho tsoa Setsing sa Naha sa Papali ea Papali ea Mathata, Central North West NHS Foundation Trust. Baithaopi ba tšeletseng ba ile ba bonts'oa nakoana pele, kapa nakong ea thupelo e leshome ea kalafo ea boits'oaro 'me ba bararo ba sa tsoa qeta kalafo. Baithaopi bohle ba robong ba ne ba le nalane ea morao tjena ea papali ea papali ea chelete. Tlhahlobo ea DSM-IV ea PG e netefalitsoe ke Massachusetts Gamb Screen (MAGS; bolela 9.8, sd 2.2, range 5-12) (Shaffer et al., 1994), e tsamaisoe ke setsebi sa kelello nakong ea ho qala kalafo. Tlhahlobo ena e ile ea kopantsoe le bothata ba papali ea bothata ba papali ea chelete.Ferris le Wynne, 2001), sekala sa ho itlaleha se fanoeng le qalong ea kalafo (bolela 18.4, sd 5.7, range 8-24; lintlha tsa 8 kapa tse kaholimo li bontša bothata ba papali ea chelete). Ho lieha pakeng tsa tlhahlobo ea bongaka le tlhatlhobo ea PET e bile likhoeli tse 2-8 ho barupeluoa ba 8/9, le likhoeli tse 23 ho PG e le 'ngoe e ileng ea hlahlojoa kamora' kalafo. Likokoana-hloko tsa mafu a kelello li ile tsa hlahlojoa ho barupeluoa ba PG ka lipotso tse hlophisitsoeng hantle tse sebelisang ICD-10, hammoho le mofuta oa k'homphieutha oa Mini International Neuropsychiatric Interview (e-MINI v2.0; Medical Outcome Systems, Jacksonville, Florida) (Sheehan et al., 1998). Baithaopi ba babeli ba ne ba e-na le nalane e fetileng ea bokuli bo sithabetsang, 'me moithaopi a le mong o ile a kopana le maemo a ho tepella ho hoholo hona joale le bophelong. Moithaopi a le mong o ile a kopana le litekanyetso tsa ho itlhahisa a joala nakong e fetileng, 'me ea bobeli e ile ea kopana le litekanyetso tsa pele tsa ts'ebeliso ea cannabis. Baithaopi ba bane e ne e le batho ba tsubang ba tsubang nakong ea ho hloa thuto (Fagerstrom Nicotine Dependence Scale scale ho tloha 6 ho isa 12). Litekanyetso tsa ho lelekoa ha sehlopha sa PG e ne e le: nalane ea bokuli ba methapo, tumello ea kelello ea nakong e fetileng, pharmacotherapy ea hona joale le bokuli ba bohlokoa ba 'mele. Kahoo, li-comorbidities tsa kelello tse bonoang li ne li sa tsitsa ka ho lekaneng ho hloka ts'ebetso ea bongaka. Bohle ba neng ba nkile karolo taolong ba kile ba hlahlojoa ke ngaka ea mafu a kelello ho khetholla mathata a teng a bophelo ba kelello ba morao-rao kapa ba nakong e fetileng, le ts'ehetso ea litheko joalo ka ha ho hlalositsoe ke DSM-IV, bokuli bo tebileng ba 'mele, mathata a methapo ea methapo kapa ts'ebeliso ea pele ea meriana ea psychotropic.
Mesebetsi ea papali ea papali ea chelete e ile ea hlahlojoa ho litho tsa PG ba sebelisang lintho 1-3 ho Screen Oaks Gurb Screen (Lesieur le Blume, 1987). Barupeluoa ba tšeletseng ba ile ba nahana ka mechini ea lipapali tsa elektroniki ('Fixed Odds Betting terminals') ho emela mofuta oa bona oa mathata oa papali ea chelete; ba bararo ba setseng ba nka ho becha ha lipapali (lipere), marang-rang a marang-rang / li-blackjack, le lipapali tsa lipapali tsa papali ea papali ea chelete (roulette) e le bothata haholo. Ka tekanyo ea chelete e ngata ka ho fetisisa e ts'oeroe ka letsatsi le le leng, ba bahlano ba ile ba amohela bin ea £ 1,000- £ 10,000 bin, 'me ba bane ba ile ba lumellana ho feta $ 10,000. Ha a botsoa ka likoloto tse amanang le papali ea chelete, motlalehi a le mong o ile a hana ho fana ka leseli la mokoloto, motho ea betang a le mong o ile a re ha a na sekoloto ka lebaka la tšebeliso ea chelete ea hae, le mokoloto o teng ho tse supileng tse setseng ho $ 4000- £ 35,000 (ho bolela hore ke $ 15,714).
Barupeluoa ba qetile karolo ea UPPS-P Impulsive Behaeve Scale (Cyders et al., 2007), lenane la lipotso tse 59 tse itlalehang ka boeena le li-subscales tse hlano tse lekolang ho potlaka ho hobe (mohlala: "Ka linako tse ling ha ke ikutloa ke hloname, ho bonahala eka ha ke emise seo ke se etsang leha se nkutloisa bohloko le ho feta"), Positive Urgency ( Mohl. “Ha ke thabile haholo, ke utloa eka nke ke ka ithiba hore ke se ke ka fetella”), (lack of) Planning (mohl. “Hangata ke etsa qeto ka ho beha mabaka ka hloko” - negative loading), (lack of) Mamello (mohl. “Ke phethela seo ke se qalang” - ho kenya lintho hampe) le Ho Batla Boikutlo (mohlala: “Ke ne ke tla natefeloa ke maikutlo a ho thelelisa ka lebelo le tlase haholo letsoapong le phahameng la thaba”). Ha rea atleha ho fumana lintlha tsa UPPS-P ho tsoa ho e mong oa baithaopi ba taolo ea database.
Ho fumana litšoantšo le ho e lokisa
Lisebelisoa tsohle tsa PET li fumanoe ho sebelisoa sekena sa ECAT HR + 962 (CTI / Seimens) se nang le axial field ea pono ea 15.5 cm. [11C] -raclopride e ne e sebelisoa e le ente e kenang methapong ea bolus bakeng sa baithaopi ba PG, le bakeng sa baithaopi ba taolo joalo ka tšubuhlellano ea pele e kenang methapong e lateloang ke ho tšeloa khafetsa, ka bolelele ba infusion ea 85 min bakeng sa lisene tse 'ne ho tsoa ho Egerton et al. boithuto (2010) le 100 min bakeng sa litekanyetso tse hlano ho tsoa ho Stokes et al. boithuto (2010). Sesepa sa phetisetso ea metsotso e 10 se ile sa etsoa pele ho scan ninemanga e 'ngoe le e' ngoe ho lekanya le ho lokisa bakeng sa ho fokotsa lisele. Lits'ebetso tse matla tsa ho tsoa moeeng li fumanoe ka mekhahlelo e meraro e sebelisang mokhoa o tloaelehileng oa ho fumana (liforeimi tse 20 tse fetang 60 min bakeng sa bankakarolo ba PG, liforeimi tse 28 tse fetang 85 min bakeng sa Egerton et al. (2010) Scans le liforeimi tsa 38 tse fetang metsotso ea 100 bakeng sa Stokes et al. (2010) scans). Bakeng sa barupeluoa ba PG, sekepe sa bona se ne se kenyelletsa tlhahiso ea litšoantšo tse sa nke lehlakore ho kenyelletsa naha, lintho tsa ntlo le lipaterone tse sa sebetseng, empa ntle le tlhokahalo ea makoloi (barupeluoa ba ne ba fuputsoa hanngoe feela).
Lits'oants'o tsohle tse matla li ile tsa lokisoa bakeng sa ho tsamaea ha hlooho ho sebelisoa foreimi ka foreimi (FBF) realignment (Montgomery et al., 2006). Ts'ebetso ena e ile ea sebelisoa ho liforeimi tsohle ho hlahisa setšoantšo se matla sa FBF se ntlafalitsoeng, se neng se hlahlobisisoa ho sebelisoa tlhahlobo e ikemetseng ea boits'oaro (ROI), e tlatselletsoang ke tlhahlobo e netefatsang ea voxelwise.
Tlhahlobo ea ROI
Li-ROI tsa Striatal le cerebellar li hlalositsoe ka ho sebelisa atlas e nang le likarolo tse tharo tse sebetsang tsa striatum; limbic, Associative and sensorimotor striatum, le cerebellum e le sebaka sa ho buoa. Likarolo tsa striatal li anomeous ho anthians ea ventral striatum (limbic striatum), pre-commissural dorsal putamen, pre-commissural dorsal caudate and post-commissural dorsal caudate (Associated striatum) le post-commissural putamen (sensorimotor striatum) (Martinez et al., 2003). Setempe sa [11C] -raclopride se ile sa fetoloa sebakeng sa PET sa setšoantšo ka seng se ntlafalitsoeng sa FBF (se hlahisitsoeng ho tsoa ho setšoantšo se seng le se seng se matla sa FBF se sebelisang ho software ea ntlo e ngotsoeng Matlab (mofuta oa 5; The MathWorks, Inc, Natick, Mass )) kahare ho SPM5 (www.fil.ion.ucl.ac.uk/spm) mme matrix ea deformation e ileng ea latela e ile ea sebelisoa ho atlas. Sefofane se senyehileng sa "striatal atlas" se sebelisitsoe ho etsa sampole ea lipalo ho tsoa linthong tse matla tsa [11C] -raclopride bakeng sa sekhahla sa PG, le ho tsoa setulong se boima sa boemo bo tsitsitseng bakeng sa likhakanyo tsa taolo, ho sebelisoa software ea Hlahloba 8.0 (www.analyzedirect.com). Bakeng sa scann ea PG, [11C] -raclopride BPND boleng, karo-karolelano ea radioligand e tlameletsoeng ka ho khetheha ho ligand e sa senyeheng ka har'a lithane tsa phetisetso ea "cerebellar"Innis et al., 2007), li ne li baloa li sebelisa mofuta o bonolo oa litšupiso tsa setifikeiti le "cerebellum" joalo ka setene se sebelisitsoeng ho software ea ntlo e ngotsoeng ho Matlab. Bakeng sa scans ea taolo, [11C] -raclopride BPND litekanyetso li baliloe e le karolelano ea lipalo tsa pelehi ho lipalo tsa cerebellar, minus 1, ka nako e tsitsitseng ea mmuso. Nako e tsitsitseng ea mmuso bakeng sa sekhahla sa bolus infusion e hlalositsoe e le ho qala ka metsotso e 39 kamora ho entoa le ho tsoela pele ho fihlela qetellong ea scan, ho ipapisitsoe le likhakanyo tsa nako e nepahetseng ea ho theha mmuso o tsitsitseng (Watabe et al., 2000).
Tlhahlobo ea Voxelwise
Bakeng sa litlhahlobo tsa boithaopo tsa PG, litšoantšo tsa parametric [11C] -raclopride li hlahisitsoe ho tsoa litšoantšong ka bonngoe tse sebelisang mokhoa o nolofalitsoeng oa lisele tsa 'mele le cerebellum joalo ka lesela le sebelisang software ea ntlo e ngotsoeng Matlab. Bakeng sa litekanyetso tsa baithaopi ba taolo, litšoantšo tsa parametric li entsoe ho tloha boemong bo ikemetseng bo eketsang litšoantšo tse sebelisang algebra ea setšoantšo ka hare ho SPM5 ka ho arola lipalo tsa voxel ka 'ngoe ka lipalo tsa cerebellar le ho tlosa e le' ngoe. Litšoantšo tsohle tsa parametric li ile tsa hlophisoa hore e be template ea [11C] -raclopride PET e sebelisang matrix ea deformation e hlahisoang ke phetoho ea sebaka sa motho ka mong ea eketsang litšoantšo ho template. Litšoantšo tse tloaelehileng tsa parametric li ile tsa ntlafatsoa kahare ho SPM5 ho sebelisoa kernel ea 6 mm e boreleli.
Tlhahlobo ea statistical
Phapang ea sehlopha ho impulsivity le BP ea tikolohongND boleng bo ile ba hlahlojoa ho sebelisoa tlhahlobo ea multivariate ea variance (MANOVA), e kenngoeng ho SPSS 15 (SPSS, Chicago, Illinois). Likamano lipakeng tsa Urgency le BPND boleng bo ile ba hlahlojoa ho sebelisoa li-coefficients tsa nakoana, ho laola lilemo ho fuoe tšusumetso e matla ea lilemo holima methati ea PET ea D2/D3 ho fumaneha hapeBackman et al., 2000; Kim et al., 2011). Sekhahla sa lipalo-palo se lokisitsoeng sa Bonferroni sa p <.00625 se kentsoe tšebetsong bakeng sa litlhahlobo tsa khokahano, se hlophisang libaka tse nne tsa seteraeke (kakaretso, limbic, Associative, sensorimotor) le likala tse peli tsa Potlako. Bakeng sa tlhahlobo ea voxelwise, likamano lipakeng tsa Urgency le [11C] -raclopride binding li ile tsa hlahlojoa ho sebelisoa tlhahlobo e mengata ea khatello kahare ho SPM5, e thibetsoe ho striatum, hape ea kenyelletsa lilemo tsa boithaopo joalo ka covariate. Sekala se lokisitsoeng sa sehlopha sa p <0.05 se nang le boholo ba sehlopha se fetang li-voxels tse leshome se sebelisitsoe bakeng sa lipalo-palo.
Results
Ho UPPS-P sekhahla sa khatello ea maikutlo, ho bile le phello e akaretsang ea sehlopha (Wilks 'lambda = 0.21, F (5,11) = 8.44, p = .002) le sehlopha sa PG se ipehileng holimo haholo ho feta taolo e phetseng hantle ho Negative Potlako (F1,15 = 43.0, p <.001), Potlako e Potlakileng (F1,15 = 17.4, p = .001), le (ho haella ha) Planning (F1,15 = 4.95, p = .042) liphallelo. Ho latela tlaleho ea rona ea haufinyane sehlopheng se atolositsoeng sa PG se hiriloeng tleliniking e le 'ngoe (Mikalczuk et al., 2011), boholo ba litlamorao bo ne bo le boholo ho li-subscales tse peli tsa Urgency (bona Tafole 1). Ho ne ho se na phapang e kholo lipakeng tsa lihlopha ho (tlhokeho ea) Tiisetso (F1,15 = 0.59, p = .455) le Boikutlo ba ho Batla (F1,15 = 0.76, p = .398).
Striatal dopamine D2 / 3 receptor e matlafatsang menyetla le likarolo tsa ho se ts'oenyehe ho Bacha ba Papali le Taolo e phetseng hantle, ka boholo ba litlamorao bo tlalehiloeng e le Cohen's d.
Tlhahlobo ea ROI
Ha ho na phapang e kholo ea sehlopha ho [11C] -raclopride BPND values (Wilks 'lambda = 0.59, F (4,13) = 2.22, p = .124), ho se na phapang ho striatum ka kakaretso (F1,16 = 0.22, p = .64) kapa ho efe kapa efe ea likarolo tse tharo tsa striatal (limbic F1,16 = 0.02, p = 0.879; motsoalle F1,16 = 0.54, p = 0.473; kutlo ea F1,16 = 0.05, p = .819) (bona Setšoantšo sa 1 'me Tafole 1).
[11C] -raclopride e nang le bokhoni ba ho ikatisa (BPND) bakeng sa sebaka ka kakaretso sa "striatum" se khahlisang (likamano tse peli) le karohano ea maoto le matsoho, bakeng sa linyeoe ka bomong tse nang le Pathological Gambing le taolo e phetseng hantle.
Ka har'a sehlopha sa PG, likhokahano tse mpe (ho khetholla lilemo) li ile tsa bonoa pakeng tsa Negative Urgency le [11C] -raclopride BPND boleng maemong a akaretsang a litaba (Setšoantšo sa 2A), le likarolo tse matla le tse kopanyang tsa striatum, e 'ngoe le e' ngoe ea eona e ne e le bohlokoa ho boemo ba tokiso ea Bonferroni (bona Tafole 2). Positive Urgency e ne e amana hantle le BPND boleng maemong a akaretsang a litaba (Setšoantšo sa 2B), le karohano ea likamano tse haufi, monyako o lokisitsoeng. Urgency Negative Urgency le Positive ntle ka boyona e ne e amana-tekano (57% phapano e arolelanoeng ho PG, 81% fapana ka taolo). Likamano lipakeng tsa Urgency le BPND ho ne ho sa hlalosoe ka botlalo boteng ba batho ba tsubang ba bane sehlopheng sa PG: batho ba tsubang (khahlano le batho bao e seng batho ba tsubang ba PG) ba bonts'itse liphapang tse fokolang tsa lintlha tsa Urgency (Negative Urgency mean = 39.0 vs 38.4; Positive Urgency mean = 38.8 vs 37.0) le BPND values (limbic striatum e bolela = 2.20 vs 2.24). Ntle le lilemo li kenyelelitsoe joalo ka phapano ea karoloana, BPND litokisetso li lula li le bohlokoa bakeng sa Negative Urgency (ka kakaretso r9 = = 875, p = .002; limbic r9 = = 846, p = .004; kopantseng r9 = −.868, p = .002) empa likamano tse khahlano le Positive Urgency ha lia fihlela bohlokoa moeling o lokisitsoeng (ka kakaretso r9 = = 703, p = .035; kopantseng r9 = = 738, p = .023). Lintlha tse mabapi le Bothata ba Papali ea Papali ea Bothata ba ho becha (PGSI) li ne li hokahane le BPND litekanyetso ho striatum e kopantsoeng (rho = karolo.881, p = .004) empa li ne li se bohlokoa ntle le lilemo li kenyelelitsoe joalo ka phapano ea karolo (r9 > - 0.45, leq> 0.22). PGSI e ne e hokahane haholo le Positive Urgency (r9 = .916, p <.001) empa eseng haholo ka Urative Urgency (r9 = .627, p = .071).
Likhohlano ho Pathological Gambler pakeng tsa [11C] -raclopride BPND ka kakaretso striatum le UPPS-P Negative Urgency (A) le Positive Urgency (B). C: Kamano ea Quadratic pakeng tsa [11C] -raclopride BPND ka limbic striatum le Negative Urgency ho tse kenyellelitsoeng ...
Li-co-efficients tse kopanetsoeng (ho laola lilemo) ho Pathological Gambler pakeng tsa [11C] -raclopride BPND dikarolong tsa striatal tsa khahleho le tšobotsi ea Urgency (Negative, Positive). Melao e ngotsoeng ka makhethe e ne e bohlokoa haholo ka lipalo kamora Bonferroni ...
BPND litekanyetso li ne li sa tsamaellane haholo le mehato ea Potlako sehlopheng sa taolo (r = - 0.36 ho 0.31, p> 0.42). Ho joalo, bakeng sa kamano lipakeng tsa Taba ea Potlako le BPND limbic striatum, teko e tobileng ea phapang lipakeng tsa li-co-efficients tsa khokahano e netefalitse kamano e matla sehlopheng sa PG ha e bapisoa le litsamaiso (Fisher's r to z phetoho; z = 2.03, p = .043), leha liteko tse lekanang ho striatum ka kakaretso ea Negative Urgency (z = 1.48, p = .139) le Positive Urgency (z = 0.97, p = .332) li ne li se bohlokoa. Ha ho fanoa ka keketseho ea sehlopha mabapi le maikutlo a amanang le maikutlo sehlopheng sa PG, re boetse ra etsa tlhahlobo ea post-hoc ho leka kamano ea quadratic lipakeng tsa Urgency le [11C] -raclopride BPND sampole e kentsoeng, ka lebaka la tlaleho ea haufinyane ea kamano ea 'inverted U' lipakeng tsa ventral striatal raclopride e tlamang le tšusumetso ea ho Batla baithaopi ba phetseng hantle (Gjedde et al., 2010). Ha re hatella boleng ba [11C] -raclopride bo tlamang ho limbic striatum (mofuta o itšetlehileng ka eona) ho Negative Urgency (predictor variable), mohlala ka kakaretso ha oa ka oa fihlela bohlokoa (F (2,14) = 3.65, p = .053) empa ho ne ho na le phello e kholo ea lentsoe la quadratic (β = - 4.07, t = - 2.21, p = .045) (Setšoantšo sa 2C). Litholoana tsena tsa quadratic ha lia ka tsa bonoa bakeng sa Potlako e Potlakileng ho limbic striatum (β = - 2.30, t = - 1.40, p = .183), kapa ho striatum ka kakaretso (Taba e potlakileng: β = - 3.10, t = - 1.56, leq Potlako e Potlakileng: β = - 141, t = - 1.75, p = .1.06). Boiteko bo tobileng ba ho pheta phello ea quadratic bakeng sa Sensation Ho batla limbic striatum le eona e ne e se ea bohlokoa (β = 306, t = 1.35, p = .0.44).
Tlhahlobo ea Voxelwise
Papiso ea sehlopha sa voxelwise ha e netefatse phapang e kholo ho [11C] -raclopride e tlamang pakeng tsa PG le taolo. Phokotso ea voxelwise khahlano le Negative Urgency sehlopheng sa PG e netefalitse kamano e fapakaneng le [11C] -raclopride e tlamang libakeng tse kopaneng ho tloha ho ventral putamen ho ea hloohong ea caudate ka lehlakoreng le letona (tlhoro e hokahanya: x = 10, y = 17 , z = - 5, cluster size = 227, p <0.001 cluster corrected) le mmele wa leqele wa caudate (tlholisano e hodimo: x = - 10, y = 13, z = 2, cluster size = 103, p = 0.001 cluster lokisitsoe). Phetohelo khahlano le Positive Urgency e hlahisitse tsepamiso tsa linaha tse peli ho tloha ho li-nucleus accumbens le ventral putamen ho ea ho 'mele oa caudate ka lehlakoreng le letona (tlholisano ea tlhoro: x = 21, y = 15, z = - 5, cluster size = 409, p <Sehlopha sa 0.001 se lokisitsoe) le caudate le putamen ka ho le letšehali (litlhokahalo tsa tlhoro: x = - 25, y = 13, z = - 2, cluster size = 297, p <0.001 cluster corrected) (bona Setšoantšo sa 3). Ho lekola botebo ba lihokelo tsena ho li-impulsivity tse amanang le maikutlo, re boetse ra kena (ho hloka) Ho hlophisa joalo ka moetapele oa [11C] -raclopride tlamo; ha ho na li-voxels tse phahameng haholo tse fumanoeng.
Liphetho tsa regxelwise regression ea [11C] -raclopride BPND ho Pathological Gamblers, ho bonts'a kamano e mpe le Negative Urgency (A) (y = +15, z = - 5) le Positive Urgency (B) (y = +15, ...
Puisano
Ha rea hlokomela hore ho na le phapang pakeng tsa dopamine D2/D3 ho fumaneha ha li-receptor lipakeng tsa banna ba nang le PG ba eang litšebeletso tsa bongaka tsa bongaka, le taolo e phetseng hantle ea banna ba lilemo li. Ntle le ho quantifying kakaretso striatal D2/D3 ho fumaneha ha li-receptor, tlhahlobo ea ROI e boetse e lekekile ho fumaneha ha li-receptor ka likarolo tse tharo tse sebetsang tsa striatum. Karolo ea maoto le letsoho e kenyelletsa li-bokellase tsa "nucleus putamen", "ventral putamen" le "ventral caudate".Linnet et al., 2011; O'Sullivan et al., 2011; Steeves et al., 2009). Ho hlokomela ha rona ha ho na phapano ea mantlha dopamine D2/D3 ho fumaneha ha li-receptor lipakeng tsa barupelli le taolo ea PG ho tsamaisana le lithuto tse peli tsa morao-rao tsa [11C] -raclopride tse ileng tsa lekola phetoho ea ho tlama ha lithuto tsa PG li etsa mesebetsi e fapaneng ea ho etsa liqeto / ho becha (Joutsa et al., 2012; Linnet et al., 2011), mme ka thuto ea boraro ea PET e bapisang bakuli ba nang le Mafu a Parkinson ba nang le mathata a taolo a se nang tšusumetso a kenyeletsang PG, nakong ea ho shebella litšoantšo tse amanang le moputso (O'Sullivan et al., 2011). Ha rea khona ho tiisa phokotso ea BPND litekanyetso tse tlalehiloeng ke Steeves et al (2009) maemong a 7 a nang le Lefu la Parkinson, le nang le dopamine-agonist e susumelletsang PG. Re lokela ho hlokomela hore metheo ea bona ea mantlha e ne e kenyelletsa khetho ea makoloi (khetho ea serial lipakeng tsa mekato e mene ea likarete e nang le maikutlo a se nang moelelo), e ka sothelang likhakanyo tsa boteng ba mantlhaEgerton et al., 2009).
Litšireletso tse ngata tse ka 'nang tsa hlaha li ka fumanoa ho seo re se fumaneng ho PG Taba ea mantlha, fokotsa-dopamine D2/D3 phihlello ea receptor e hlalositsoeng pele ho basebelisi ba lithethefatsi (Fehr et al., 2008; Heinz et al., 2004; Martinez et al., 2004; Volkow et al., 1997, 2001) e ka tsamaisoa ke matla a marang-rang a nuroadaptive kapa neurotoxic ea lithethefatsi ka boeona, 'me e se ke ea tsamaellana le tlokotsi ea boteng ba mafu a lemallo. Tumellanong le ak'haonte ena, D2 ho fumaneha ha "receptor" ho ne ho amana hantle le nako ea tlhekefetso e matlafatsang mohlaleng oa liteko oa tekanyetso (Nader le al., 2006). Tlhaloso e 'ngoe ke hore phokotso ho tlama dopamine ho ka emela sesosa sa kotsi ea ts'ebeliso ea lithethefatsi e joalo eseng akaretsa ho PG e le tšibollo ea boitšoaro. Phokotso ea ho fumaneha ha dopamine receptor ho tlalehiloe pele ho botenya (Wang et al., 2001), joalo ka temallo e 'ngoe ea boitlamo ba mokhethoa. Ho joalo, seo re se fumaneng ha se hanelle monyetla oa ho fetola mekhoa e meng ea neurotransmitter ho PG, joalo ka glutamate, GABA kapa serotonin (Leeman le Potenza, 2012), kapa ehlile e fetoha likarolong tse ling tsa phetisetso ea dopamine joalo ka tokollo (Linnet et al., 2011), hlakola (Cilia et al., 2010) kapa metabolism (Bergh et al., 1997). Taba ea bobeli ho seo re se fumaneng ke hore tlhahiso ea dopamine e hlahisoang ke kemiso ea nako e telele ea ho hapa le ho lahleheloa ke boiphihlelo ba papali ea chelete (mohlala, Zald et al., 2004) e kanna ea se ke ea lekana ho theola maemo a tlase a D2/D3 ho fumaneha ha receptor.
Leha ho le joalo, ka har'a sehlopha sa ba bechang, [11C] -raclopride binding e ne e tsamaellana hampe le ho qobelloa, ntho e neng e ipehile kotsing ea ho becha ka bothata (Slutske et al., 2005) le mathata a tšebeliso ea lithethefatsi (Ersche et al., 2010). Karolo ea tšusumetso eo re e khethollang e le ho reroa ha dopamine e tlamang e ne e le Urgency (kapa 'rash impulsiveness'), tloaelo ea ho etsa liketso tse potlakileng tlasa maemo a tebileng a maikutlo. Ho bapisoa ha maemo joalo ka tšohanyetso tšimong ea Urgency ho hlahisitse boholo bo matla ho feta 'ho ts'oaroa ke letho' (ke ho hloka moralo, ho hloka mamello), e ileng ea boela ea bonoa sehlopheng se seholo se hapuoe ho tloha maemong a tšoanang a kliniki (Mikalczuk et al., 2011). Ho haella ha subscale ea ho hlophisa ha hoa ka ha bolela esale pele hore dopamine e tla tiisa tlhatlhobo ea voxelwise. Lipalo tsa tšohanyetso li bolela phetoho lipakeng tsa papali ea chelete ea tšebeliso ea chelete, tšebeliso e mpe ea lithethefatsi le boits'oaro bo bong bo kotsi masampeng a koleche (Cyders le Smith, 2008). Ha ho tsejoe haholo ka lits'ebetso tsa boko tse laolang tšusumetso ena, le ha ho le joalo lipatlisiso tsa morao-rao tsa "coson" tse nang le bokhoni ba ts'ebetso li tlalehiloe ka litaba tsa Urgency le maemo a GABA ho dorsolateral prefrontal cortex (Moshanyana et al., 2011), le data ea litoeba e bonts'a taolo ea litekanyetso tsa dopamine ka cortical GABA (Matsumoto et al., 2005). Sehlopheng sa PG, likarolo tse peli tse mpe le tse ntle tsa Urgency li boletse esale pele driamine dopamine D2/D3 ho fumaneha ha receptor. Likamano tsena li ile tsa bonoa ho "striatal ROI" hammoho le limbic (Negative Urgency) le Associative (bobeli Negative and Positive Urgency), mme li netefalitsoe tlhahlobisong ea voxelwise. Lintlha tse mpe le tse nepahetseng tsa tšohanyetso li ne li amana ka kotloloho, le ha ho ntse ho sa hlaka hore na bakuli ba nang le PG ka tsela e tšoanang ba kotsing ea maikutlo (mohlala, euphoria) le maikutlo a mabe (mohlala, ho sithabela maikutlo, khatello ea maikutlo) ho baka maikutlo (Blaszczynski le Nower, 2002; Stewart le Zack, 2008).
Kamano pakeng tsa ho fumaneha ha Urgency le dopamine receptor ha ea ka ea bonahala sehlopheng se senyenyane sa taolo e phetseng hantle e lekiloeng mona. Ehlile, coeffanele bakeng sa Negative Urgency ho limbic striatum e ne e le matla haholo sehlopheng sa PG ho feta taolo. Bathong ba nang le methamphetamine ba its'epahalle, striatal D2/D3 ho fumaneha ha receptor ho ne ho boetse ho hokahanngoa hampe le tšusumetso ea tšobotsi (Lee le al., 2009). Ka lebaka la tlaleho ea moraorao ho barupeluoa ba phetseng hantle ba bonts'itseng kamano e pakeng tsa maqhubu a pakeng tsa [4NUMXC] -racloprideGjedde et al., 2010), re ile ra etsa tlhahlobo ea post-hoc ho leka sephetho se ts'oanang sa tšohanyetso ea sampole ea rona ea PG le taolo e phetseng hantle. Re qopile phello ea "inverted U" (kapa Yerkes-Dodson) ho limbic striatum, e le ts'ebetso ea Negative Urgency. Sena se bontša hore ka bobeli ba phahame 'me maemo a tlase a khatello ea maikutlo a amanang le ho feto-fetoha ha maikutlo a amanang le khatello e tlase ea striatal raclopride, le hore BPND e nepahetse bohareng ba phetiso.
Ha e le hantle, BP e theotsoeND e ka bonts'a ho fokotseha ha polelo ea striatal D2/D3 dopamine receptors le / kapa keketseho ea litekanyetso tsa dopamine tsa synaptic. Phuputso e sebelisang alpha-methyl paratyrosine (AMPT) ho fokotsa dopamine lithutong tse itšetlehileng ka koae e bontšitse hore ho fumaneha ha receptor hammoho le e fokotsehile maemo a dopamine ea extracellular tlasa maemo a motheoMartinez et al., 2009). Leha ho le joalo, mosebetsi oa pele ho PG o bonts'itse ts'ebetso ea dopamine e amanang le mosebetsi ka har'a sehlopha sa barupeluoa ba PG ba tlalehileng thabo e amanang le mosebetsi (Linnet et al., 2011). Ho ka nahanoa hore BP e tlaseND maemong a tlase e ka tsamaisoa ke ho fokotseha ha li-D2 / D3, athe BP e tlaseND maemong a phahameng a ho tsamaisoa ho ka tsamaisoa ke ho fumaneha ha receptor ka bobeli le dopamine e phahameng ea extracellular (Gjedde et al., 2010). Keketseho ea tokollo ea dopamine e kanna ea amahanngoa le phello e tlase ea taolo ea (midbrain) phumaneho ea autoreceptor, joalo ka ha e fumanoe ka [18F] -fallypride ligand (Buckholtz et al., 2010). Ho data ea hona joale, tlhokomeliso e itseng e pakoa ke taba ea hore nako ea quadratic e ne e tsamaisoa haholo ke barupeluoa ba PG ba oelang ka letsohong le letona, ba theoha le matsoho, hammoho le phapang e boletsoeng sehlopheng seo. Ho hlakisa likamano tsena, lithuto tse tsoelang pele li hlokahala ho hira matšoao a mangata a ts'ebetso ea dopamine maemong ohle a ferekanyang, empa re ne re ka khothaletsa hore lithuto tsa nako e tlang li nahane ka liphapang tsa motsamao oa maoto le oa quadratic ka har'a tsela ea dopamine.
E le meeli e meng ea thuto ea hajoale, boholo ba sehlopha sa rona bo ne bo le nyane mme ka hona thuto e ne e sa fuoa matla a lekaneng ho fumana boholo ba litlamorao. Ho ipapisitsoe le boholo ba sephetho sa striatum ka kakaretso (Cohen's d = 0.22), ho tla hlokahala lihlopha tse peli tsa bonyane barupeluoa ba 350 ho fumana phapang ea lipalo. Taba ea bobeli, ts'ebeliso ea lits'oants'o tse nepahetseng ho tsoa polokelongtshedimosetsong e tloaelehileng e hlahisitse liphapang tse nyane tsa ts'ebetso lipakeng tsa lihlopha tsena tse peli: lithuto tsa PG li hlahisitsoe ka litšoantšo tse sa nke lehlakore nakong ea scan ea bona (leha ho sena tlhoko ea karabelo), mme lithuto tsa PG li ile tsa fumana ente ea bolus athe litsamaiso li amohetse bolus le infusion. Mosebetsi oa pejana o bonts'a hore litekanyetso tsa [11 C] -raclopride tse tlamang tse hlahisoang ke bolus feela li batla li ts'oana le litekanyetso tse tlamang tse hlahisoang ke mokhoa oa bolus-infusion ho baithaopi ba tšoanang (Carson et al., 1997; Ito et al., 1998). Ho barupeluoa ba PG, ho ne ho e-na le tekanyo ea heterogeneity ka nako ea tlhahlobo ea scan ninning le kalafo (haholo empa eseng bohle ba neng ba filoe kalafo ea kalafo ea kalafo e tlang pele), mme li-comorbidities tsa kelello li ne li le teng ho barupeluoa ba bane. Tlhahlobo ea kamoso ea ho-hoc e bontšitse hore bonyane litlamorao tsa rona ha li bakoe ke boemo ba ho tsuba (Busto et al., 2009; cf Fehr et al., 2008). Psorchiatric comorbidities ehlile e atile haholo ho PG (Kessler et al., 2008) le ho kenyelletsoa ha linyeoe tse joalo ho ntlafatsa ho fumanwa ha rona.
Mabapi le ts'ebeliso ea bongaka, ho a hlokomeleha hore le ha dopamine agonist pramipexole le karolo e itseng ea agonist aripiprazole li bile le tšusumetso ho qalisoeng ha papali ea chelete e senyehileng (Smith et al., 2011; Voon et al., 2009), dopamine D2 bahanyetsi ba li-receptor ba kang olanzapine ha ba so ka ba atleha ho bonts'a katleho ea liteko tsa kalafo tsa PG (Fong et al., 2008; McElroy et al., 2008). Har'a lihlopha tsa bankakarolo ba phetseng hantle, tlhaiso ea dopamine ea mantlha e susumetsa ketso ea li-dopaminergic agents ho latela mofuta oa inverted U (Cools le D'Esposito, 2011), 'me ka hona liphuputso tsa rona tsa ho se ts'oanehe ha dopamine dysregulation ho papali ea chelete e sa sebetseng li fana ka maikutlo a hore batho ba nang le khatello e matla ea maikutlo ba ka bonts'a melemo e fapaneng ea meriana e thehiloeng ho dopamine. Mohlala, haeba tlamo e tlase ea [11 C] -raclopride ho bapapali ba papali ea chelete e phahameng e bakoa ke keketseho ea synaptic dopamine (Gjedde et al., 2010), batho bana ba kanna ba arabela ka khetho ho dopamine blockade. Kamano ea li-quadratic le liphapang tsa motho ka mong e fana ka maikutlo a hore mekhoa e mengata ea dopaminergic e ka sebetsa mesebetsing ea khatello ea bokhoba (Buckholtz et al., 2010; Cilia et al., 2010; Gjedde et al., 2010).
Litlhaloso
L Clark o phatlalatsa boeletsi bakeng sa Cambridge Cognition plc. AR Lingford-Hughes o fumane honaria ho tsoa ho Janssen-Cilag, Pfizer, Servier le ho Mokhatlo oa Borithane oa Psychopharmacology. O fane ka boeletsi ho NET Device Corp, o fumane chelete ea ho etsa lipatlisiso ho tsoa ho Archimedes, Lundbeck, Pfizer le Schering, mme o na le lithuso tsa lipatlisiso le GlaxoSmithKline. DJ Nutt o sebelitse libotong tsa boeletsi bakeng sa Lundbeck, Servier, Pfizer, Reckitt Benkiser, D&A Pharma, hape o amohetse honaria ho tsoa ho Bristol Myers Squibb, Glaxo Smith Kline le Schering-Plow. O fumane chelete ea ho etsa lipatlisiso ho P1vital, o na le likhetho tsa kabelo le P1vital, mme o fumana honary ea bohlophisi ho Sage. AR Lingford-Hughes le DJ Nutt ka bobeli ke litho tsa Lundbeck International Neuroscience Foundation. Ngaka Stokes, Ngaka Wu, Mme Michalczuk, Mme Benecke, Ngaka Egerton, Ngaka Watson, Ngaka Piccini le Ngaka Bowden-Jones ha ba na tjantjello ya tjhelete eo ba ka e phatlalatsang.
lumela hore baa fokola
Mosebetsi ona o tšehelitsoe ke lithuso tsa Lekhotla la Patlisiso ea tsa bongaka G0802725 ho LC le HBJ, le G0400575 ho DJN le ALH. Cliniki ea Bothata ba Papali ea Mathata e tšehetsoa ke Letlole la Papali ea Papali ea Chelete. Morero o phethetsoe ka har'a Behavioral and Clinical Neuroscience Institute, o tšehelitsoeng ke moputso oa tumellano e tsoang ho MRC le Wellcome Trust (motsamaisi: TW Robbins). Lintlha li hlahisitsoe Kopanong ea Brithani ea Psychopharmacology lehlabula, Harrogate, UK (Phupu 2011).
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