Nthenda ya ubongo yowchova njuga ndi kumwa mankhwala osokoneza bongo ndichidule ndi zotsatira zatsopano (2008)

Philos Trans R Soc Lond B Biol Sci. 2008 October 12; 363(1507): 3181-3189.

Idasindikizidwa pa intaneti 2008 July 18. do: 10.1098 / rstb.2008.0100

Marc N Potenza^1,^2,^*

Zambiri za wolemba ► Chidziwitso cha Copyright ndi License ►

Nkhaniyi yakhala wotchulidwa ndi nkhani zina mu PMC.

Kudalirika

Kutchova njuga ndi chikhalidwe chofala kwambiri cha zosangalatsa. Pafupifupi achikulire a 5% akuyerekezeredwa kuti akukumana ndi mavuto a njuga. Mtundu wovuta kwambiri wa kutchova juga, wa pathological njuga (PG), umadziwika ngati mkhalidwe wama thanzi. Maganizo awiri osagwirizana a PG adawona kuti ndiwowoneka bwino komanso wovuta kuchita. Kulingalira koyenera kwambiri kwa PG kumakhala ndi tanthauzo lofunikira ndi lingaliro. Zambiri zikuwonetsa ubale wapakati pa PG ndi zovuta zogwiritsa ntchito pazinthu kuposa zomwe zili pakati pa PG ndi kusokonekera-kovutikira. Pepala ili liziwunikanso deta ya neurobiology ya PG, lingaliranenso momwe lingakhalire ngati chizolowezi chamakhalidwe, likambirana za kukhazikika ngati chinthu chomwe chimapanga, ndikuwonetsa zomwe zapezedwa mu ubongo zomwe zikufufuza zomwe zikuchitika mu PG poyerekeza ndi omwe amadalira cocaine. Zomwe zimakhudza njira zopewera ndi kulandira chithandizo zidzafotokozedwa.

Keywords: kutchova njuga, kuzolowera, kuyendetsa moponderezedwa, kusokoneza chisokonezo, kulingalira kwa ubongo, kugwira ntchito kwa maginito olimbitsa thupi

1. Zosangalatsa, zovuta komanso kutchova njuga

Kutchova juga kumatha kufotokozedwa ngati kuyika chinthu chamtengo wapatali pachiwopsezo cha kupeza chinthu chamtengo wapatali kwambiri (Potenza 2006). Akuluakulu ambiri amatchova juga, ndipo ambiri amatero popanda kukumana ndi mavuto akulu. Komabe, mavuto a njuga pakati pa achikulire amawerengedwa mpaka 5%, ndimagulu ena (achikulire, achinyamata omwe ali ndi vuto la matenda amisala komanso omwe ali m'ndende) akuyerekeza kangapoKhumbani Et al. 1999). Kutchova juga kwachidziwitso (PG), choyimira mtundu wovuta kwambiri wa kutchova juga (onani pansipa), akuyerekeza kuchuluka kwa pafupifupi 0.5-1% (Petry Et al. 2005). Popeza kupezeka kwa kutchova juga kovomerezeka ndi kutchuka kwazaka makumi angapo zapitazi, chidwi chochulukirapo pa zovuta zakumagwiridwe ka njuga ndizoyenera (Shaffer & Korn 2002).

Palibe mpaka 1980 pomwe Kuzindikira ndi buku lamaumboni (DSM) adafotokoza njira zavuto la kutchova juga (Association of Psychiatric Association 1980). Mawu akuti 'PG' amasankhidwa m'malo mwa mawu ena (mwachitsanzo, kutchova juga) omwe anali kugwiritsidwa ntchito kwambiri panthawiyo, mwina pofuna kusiyanitsa matendawa ndi zovuta zomwe zimapangitsa kuti anthu azisala. Pamodzi ndi pyromania, kleptomania, trichotillomania komanso kuphulika kwapakatikati, PG pano imatchulidwa kuti ndi 'impulse control disorder (ICD) osati kwina kulikonse' mu DSM. Momwemonso, mu International Classization of Disways, matendawa amawerengedwa pansi pa 'Zizolowezi komanso zovuta zina' pamodzi ndi pyromania, kleptomania ndi trichotillomania. Njira zambiri zodziwira matenda omwe PG imagawana ndi omwe amadalira mankhwala osokoneza bongo (DD). Mwachitsanzo, njira zololera, kuleka, kubwereza kosalephera kapena kusiya, ndi kusokonezedwa pamagawo akuluakulu amoyo wamoyo zilipo mu njira ya PG ndi DD. Zofanana zimafikira ku phenomenological, matenda, matenda, ma genetic ndi zina zolengedwa (Goudriaan Et al. 2004; Potenza 2006; Brewer & Potenza 2008), kudzutsa mafunso ngati PG itha kukhala yodziwika ngati 'mwamakhalidwe'.

2. PG ngati osokoneza bongo

Ngati PG ikuyimira chizolowezi, iyenera kugawana ndi mawonekedwe apakati a DD. Zoyeserera zazikuluzikulu zokhudzana ndi zosokoneza bongo zakhala zikufunsidwa kuphatikiza (i) kupitiliza kuchita zinthu mosagwirizana ndi zovuta, (ii) kuchepa kudziletsa pakuchita zinthu, (iii) kuchita zolimbitsa thupi, (iv) kukakamiza kapena kuchita kulakalaka dziko lisanayambe kuchita zomwezo (Potenza 2006). Zambiri mwazinthu izi, komanso zina, monga kulekerera ndi kusiya, zimawoneka zofunikira pa PG ndi DD (Potenza 2006). Kafukufuku wokhazikika wa PG ndi DD ayenera kuthandiza kutanthauzira zomwe zimagwirizana ndi mankhwala. Ndiye kuti, mankhwalawa amatha kusokoneza kupangika kwa ubongo ndikugwira ntchito m'njira zomwe zili chapakati kapena zosagwirizana ndi njira yolowerera. Mwa kuti PG ingakhale yodalirika ngati mankhwala osokoneza bongo popanda kufananizidwa, kuyerekeza mwachindunji kwamatenda onsewa kumatha kupereka chidziwitso pazinthu zoyambira zamankhwala osokoneza bongo ndikuwongolera kukulitsa ndi kuyesa kwa mankhwala othandiza.

3. Makina a Neurotransmitter ndi PG

Ma neurotransmitters apadera adapangidwa kuti agwirizane ndi mitundu yosiyanasiyana ya PG. Kutengera maphunziro a PG ndi / kapena kusokonezeka kwina, Noradrenaline yakhala ikuwunikidwa mu ICD kuti ikhale yofunikira kwambiri pazinthu zosangalatsa komanso kusangalala, serotonin poyambitsa kukhazikika ndi kusiya, dopamine kuti ipereke mphotho ndi kulimbikitsa, ndi ma opioids osangalatsa kapena okakamiza. Izi ndi machitidwe ena amawonedwa pansipa.

(a) Noradrenaline

Kafukufuku yemwe adachitika mu 1980s adayerekezera amuna omwe ali ndi PG ndi omwe alibe ndikupeza milingo yayikulu ya noradrenaline kapena metabolites ake mu mkodzo, magazi kapena magazi a cerebrospinal fluid m'mbuyomu (Roy Et al. 1988), ndi miyeso ya noradrenergic yolumikizidwa ndi miyeso yopitilira muyeso (Roy Et al. 1989). Kutchova juga kapena machitidwe okhudzana nawo adalumikizidwa ndi kudziyimira pawokha, kusewera pachinko ndi kasino wakuda uliwonse wogwirizana ndi kukweza kwa mtima ndikuwonjezeka kwa miyeso ya noradrenergic (Shinohara Et al. 1999; Meyer Et al. 2000). Panthawi ya kasino njuga njuga, kugunda kwamtima ndi miyambo ya noradrenergic imakwezedwa pamlingo waukulu mwa abambo omwe ali ndi mavuto a njuga poyerekeza ndi omwe alibe (Meyer Et al. 2004). Kuphatikiza pa gawo lomwe lingachitike pakukondweretsa kapena kusangalala, Noradrenaline ikhoza kukhala yokhudzana ndi mbali zina za PG. Mwachitsanzo, zochitika za noradrenergic zimakhudza ntchito ya preortal cortical function ndi njira yothandizira chidwi chaposachedwa, komanso mankhwala (mwachitsanzo, mayendedwe a noradrenaline inhibitor atomoxetine ndi alpha-2 adrenergic agonists clonidine ndi guanfacine) omwe amagwiritsa ntchito ma adrenergic -deficit hyperacaction disorder ndi matenda ena amisala (Arnsten 2006). Mankhwala a Adrenergic adawonetsedwa kuti amathandizira mbali zina za kayendetsedwe kazovuta mu maphunziro a nyama ndi anthu (Chamberlain & Sahakian 2007). Zomwe apezazi zikuwonetsa maudindo angapo omwe angachitike mu ntchito ya adrenergic ku PG ndi chithandizo chake, ndipo kufufuza kwina kukufunika m'derali kuti tionenso momwe zingathekere.

(b) Serotonin

Pachikhalidwe, ntchito ya serotonin imawerengedwa kuti ndi yofunika kwambiri pakulamulira kuwongolera kusokonekera. Anthu omwe ali ndi vuto lofooka la chipatala, omwe ali ndi PG (Nordin & Eklundh 1999) kapena kuchita chipongwe (Linnoila Et al. 1983), awonetsa kuchepa kwa serotonin metabolite 5-hydroxy indoleacetic acid. Anthu omwe ali ndi PG kapena zovuta zina kapena zikhalidwe zomwe zimadziwika ndi chiwongolero chosayendetsa bwino (mwachitsanzo, kupsa mtima) zimawonetsa mayendedwe osiyanasiyana komanso zamankhwala amodzi pamankhwala osokoneza bongo a serotonergic kuposa momwe zimakhalira ndi maphunziro oyendetsa bwino. Anthu omwe ali ndi PG adanenetsa kuti cholinga-chlorophenylpiperazine (m-CPP), agonist yochepa ya serotonin yomwe imamangiriza ku angapo 5HT₁ ndi 5HT₂ ma receptor omwe ali ndi mgwirizano wapamwamba wa 5HT_2c receptor (DeCaria Et al. 1998; Pallanti Et al. 2006). Kuyankha uku kunali kosiyana ndi kwa oyang'anira nkhani ndipo anali ofanana ndi ziwonetsero zambiri zomwe zidanenedwapo kale ndi anthu osagwirizana, okhala pamalire ndi anthu omwe adamwa mowa atalandira mankhwalawo. Kuyankha kwa Prolactin ku m-CPP kumasiyanitsanso magulu a PG ndi oyang'anira, ndikukwera kwambiri komwe kumawonedwa kale.

Serotonergic probes yakhala ikugwiritsidwa ntchito molumikizana ndi kuganiza kwa ubongo mwa anthu omwe ali ndi vuto losokoneza. Mwa anthu omwe ali ndi mkwiyo wosakakamiza poyerekeza ndi omwe alibe, kuyankha kokhazikika mu ventromedial prefrontal cortex (vmPFC) kumawoneka poyankha m-CPP (yatsopano Et al. 2002) kapena osazungulira agonist fenfluramine (Wokhulupirira Et al. 1999), zogwirizana ndi zomwe zapezeka mu zidakwa (Wokhalamo Et al. 1997). Kafukufuku wofanana sanachitikebe mpaka pano ku PG, ngakhale kuti kufufuza kwina kwapangitsa ntchito ya vmPFC ku PG (onani pansipa).

Popeza deta yomwe ikuwonetsa gawo lofunikira la ntchito ya serotonin ku PG ndikuyambitsa dyscontrol, mankhwala a serotonergic amafufuzidwa pochiza PG (Brewer Et al. 2008). Serotonin reuptake inhibitors amawonetsa zotsatira zosakanikirana. M'malo ochepa, oyesedwa ndi placebo, akhungu la kawiri, poyeserera khungu la fluvoxamine, manja ndi malo a placebo anali osiyana kwambiri ndi theka lachiyeso, pomwe mankhwala osokoneza bongo amakhala apamwamba kuposa placebo (Hollander Et al. 2000). Chiyeso chaching'ono cholamulidwa ndi placebo sichinasiyanitse pakati yogwira fluvoxamine ndi placebo (White Et al. 2002). Momwemonso, kafukufuku wina wosasankhidwa, wolamulidwa, wamaso awiri wopatsirana paroxetine adawonetsa kupambana kwa yogwira mankhwala kuposa placebo (Kim Et al. 2002), pomwe kafukufuku wamkulu, wapakatikati, wosasinthika, wowongoleredwa ndi khungu, sanapeze kusiyana kwakukulu pakati pa mankhwala omwe amagwiritsidwa ntchito ndi placebo (Grant Et al. 2003). Mayeserowa oyambilira nthawi zambiri sanali kupatula anthu omwe ali ndi vuto la matenda amisala. Chiyeso chaching'ono, chowonekera poyera cha escitalopram chotsatiridwa ndi kuleka kwakhungu kwamaso chinachitidwa mwa anthu omwe ali ndi PG komanso mavuto obwera chifukwa cha nkhawa (Grant & Potenza 2006). Panthawi yotseguka, zilembo ndi nkhawa zinayamba kuyenda bwino. Kusintha kwadzidzidzi kwa placebo kunalumikizidwa ndikuyambiranso kwa kutchova njuga ndi nkhawa, pomwe kusinthasintha kwa mankhwala ogwira ntchito kumalumikizidwa ndi mayankho okhazikika. Ngakhale zinali zoyambirira, zomwe zapezazi zikuwonetsa kuti pali kusiyana pakati pa anthu omwe ali ndi PG, komanso kuti kusiyana kumeneku kuli ndi tanthauzo lofunikira pakuyankhidwa.

(c) Dopamine

Dopamine imakhudzidwa pakupindulitsa ndikulimbikitsa machitidwe ndi kusuta kwa mankhwala osokoneza bongo (Nestler 2004). Komabe, maphunziro ochepa adafufuza mwachindunji gawo la dopamine mu PG. Zotsatira zopatsa chidwi zanenedwa za miyeso ya cerebrospinal fluid ya dopamine ndi metabolites ake ku PG (Bergh Et al. 1997; Nordin & Eklundh 1999). Momwemonso, kafukufuku wina wam'maselo oyamba a PG adapangitsa chidwi cha TaqA1 cha dopamine receptor gene DRD2 chimodzimodzi ku PG, kugwiritsa ntchito mankhwala osokoneza bongo komanso mavuto ena amisala (Kutengera 1998). Kafukufuku wakale wama genetic a PG nthawi zambiri amaphatikiza kufooka kwa njira monga kusowa kwa mayendedwe amtundu kapena mafuko ndi kuwunika kosakwanira kofufuzira, komanso kafukufuku wotsatira wogwiritsa ntchito njira zowongolera mtundu / fuko ndikupeza kufufuza kwa DSM-IV sikunawone kusiyana mumalingaliro amtundu wa TaqA1 mu PG (da Silva Lobo Et al. 2007). Zolemba zowunikidwa ndi anzanu zomwe zimakhudza maphunziro a PG komanso kufufuza njira za dopamine (kapena zina) pogwiritsa ntchito njira zochokera ku ligand kulibe, ndipo kafukufuku wotereyu akuimira gawo lofunikira lakufufuzira mtsogolo.

PG ndi ma ICD ena awonedwa mwa anthu omwe ali ndi matenda a Parkinson (PD), matenda omwe amadziwika ndi kuchepa kwa dopamine ndi machitidwe ena (Jellinger 1991; Potenza Et al. 2007). Omwe ali ndi PD amathandizidwa ndi mankhwala omwe amalimbikitsa ntchito ya dopamine (mwachitsanzo, levodopa kapena dopamine agonists, monga pramipexole kapena ropinirole) kapena kulowererapo (mwachitsanzo kukondoweza kwa ubongo) komwe kumalimbikitsa kulumikizana kwa neurotransmission kudzera m'magawo okhudzana ndi (Lang & Obeso 2004). Mwakutero, ma ICD mu PD amatha kutuluka kuchokera ku pathophysiology ya chisokonezo, chithandizo chake, kapena kuphatikiza kwina. Kafukufuku awiri adafufuza ma ICD mwa anthu mazana angapo omwe anali ndi PD (Onani Et al. 2006; Weintraub Et al. 2006). Ma ICD adalumikizidwa ndi gulu la dopamine agonists osati othandizira ena, ndipo anthu omwe ali ndi ma ICD anali achichepere ndipo anali ndi mibadwo yakale koyambirira kwa PD. Anthu omwe alibe komanso opanda ma ICD amakhalanso osiyana pazinthu zina zokhudzana ndi kusokonekera kwa chiwongolero champhamvu. Mu kafukufuku wina, iwo omwe ali ndi ICD anali ndi mwayi wokhala ndi ICD mtundu wa PD usanayambike (Weintraub Et al. 2006). Mwanjira ina, maphunziro a PD omwe alibe ndi PG popanda kusiyanasiyana adasiyanitsidwa ndi njira zochititsa chidwi, kufunafuna zatsopano komanso uchidakwa wa banja kapena banja (Onani Et al. 2007). Kupereka kotheka kwa kusiyana kumeneku komanso kusintha kwa zinthu zina kumatsimikiziranso kulingaliridwa pakufufuza kwa ma pathophysiologies a mankhwala othandizira ma ICD a PD. Ngakhale anecdotal ndi nkhani yotsatizana ikusintha momwe ICD imayambira ndi discontinuation kapena kuchepa kwa dopamine agonists (Mamikonyan Et al. 2008), maphunziro awa ndi oyambilira mwachilengedwe ndipo amafunsidwa ndi mayesero ena osasunthika. Kuphatikiza apo, odwala ena sangalole mlingo waukulu wa levodopa omwe amawongolera zizindikiro za PD pomwe ena amatha kugwiritsa ntchito mankhwalawa (Giovannoni Et al. 2000; Evans Et al. 2005). Pamodzi, izi zikuwonetsa kuti kafukufuku wofunikira akufunika mu pathophysiologies of and chithandizo cha ma ICD mu PD.

(d) Ma opioids

Ma opioid akhala akukumana ndi njira zosangalatsa komanso zopindulitsa, ndipo ntchito ya opioid imatha kukopa ma neurotransication munjira ya mesolimbic yomwe imachokera ku malo a gawo la ventral mpaka ku nucleus accumbens kapena ventral striatum (Spanagel Et al. 1992). Pamaziko azotsatira izi ndi kufanana pakati pa PG ndi zosokoneza, monga kudalira mowa, otsutsana ndi opioid adawunikiridwa pochiza PG ndi ma ICD ena. Malo oyesedwa ndi placebo, akhungu awiri, osawerengeka adayesa momwe ntchito ikuyendera ndi kulekerera kwa naltrexone ndi nalmefene. Mkulu mlingo naltrexone (pafupifupi kumapeto kwa kuphunzira = = 188mgd^-1; kuchuluka mpaka 250mgd^-1) anali wamkulu kuposa placebo pochiza PG (Kim Et al. 2001). Monga kudalira mowa, mankhwalawa adawoneka othandizira makamaka kwa anthu omwe ali ndi chidwi chofuna kutchova juga nthawi yoyamba. Komabe, mayesero amtundu wa chiwindi amawonetsedwa mu 20% ya maphunziro omwe amalandila mankhwala ogwiritsira ntchito nthawi yayifupi. Nalmefene, wotsutsana ndi opioid wosagwirizana ndi kuwonongeka kwa chiwindi, adayesedwa pambuyo pake (Grant Et al. 2006). Nfumufene inali yapamwamba kuposa placebo, ndipo zolakwika zokhudzana ndi chiwindi sizinawonedwe. Mlingo womwe umawonetsa kuyenera kwambiri ndi kulolera unali 25mgd^-1 Mlingo, womwe ndi wofanana ndi 50mgd^-1 Mlingo womwe umagwiritsidwa ntchito pochiza mowa kapena kudalira kwa opiate. Kawuniwuni wotsatira wa zotsatira za mankhwalawa mu PG kulandira olimbana ndi opioid adazindikira mbiri yakale ya zakumwa zoledzera monga zomwe zimagwirizanitsidwa kwambiri ndi mayankho abwino a mankhwala, kupeza komwe kumagwirizana ndi zolemba zamowa (Grant Et al. 2008). Kukula kwazinthu zina zomwe zimagwirizanitsidwa ndi yankho la chithandizo kwa okhudzana ndi opioid mu zakumwa zoledzeretsa (mwachitsanzo, kusiyanasiyana kwa jini komwe kumalembera μ-opioid receptor; Oslin Et al. 2003) kukulira ku chithandizo cha kufufuza kwa PG kwawunikira mwachindunji.

(e) Glutamate

Glutamate, neurotransmitter yosangalatsa kwambiri, wayikika panjira zolimbikitsira komanso kugwiritsa ntchito mankhwala osokoneza bongo (Chambers Et al. 2003; Kalivas & Volkow 2005). Kutengera ndi izi komanso zomwe zapezedwa zikuwonetsa udindo wa kuchiritsa kwa glutamatergic mu ma ICD ena (Ziphuphu Et al. 2007), wothandizirana ndi glutamatergic modulating N-acetyl cysteine anafufuzidwa pochiza PG (Grant Et al. 2007). Kapangidwe kake ka kafukufukuyu kanakhudzana ndi zolemba zowonekera poyera zomwe zimatsatiridwa ndikusiyidwa kwamaso kawiri. Pa gawo lotseguka, chizindikiritso cha kutchova juga chinayamba bwino. Kutsatira kuleka kwa khungu kwamaso awiri, kusintha kunasungidwa mu 83% ya omwe amayankha mosasankha kwa mankhwala omwe amagwira ntchito poyerekeza ndi 29% ya omwe adasinthidwa mwangozi. Izi zowerengera zoyambirira zikuwonetsa kufunikira kwa kafukufuku wowonjezera mu zopereka za glutamatergic ku PG ndi chithandizo chamankhwala a glutamatergic pamankhwala ake.

4. Njira zama Neural

Kafukufuku wocheperako adasanthula momwe zochita za ubongo zimasiyanirana mwa anthu omwe ali ndi PG kapena ma ICD ena poyerekeza ndi omwe alibe. Kafukufuku woyamba wogwira ntchito wa maginito (fMRI) woyeserera adafufuza za anthu omwe ali ndi PG (Potenza Et al. 2003b). Powona matepi a juga komanso musanayambike kuchitapo kanthu chifukwa cha zoyeserera kapena zam'maganizo, oyendetsa njirayo (PGers) poyerekeza ndi omwe amasangalatsa amawonetsa kusintha kochepa kwa magazi a oxygen (amadalira) Bold ganglionic ndi kumbali yamatumbo a ubongo. . Kusiyana kwapakati pagulu sikunawonedwe panthawi yachimwemwe kapena chosangalatsa cha videotape panthawi yanthawi yowonerera, ndipo zomwe zapezazi ndizosiyana ndi maphunziro aanthu omwe ali ndi vuto lodzikakamiza, omwe nthawi zambiri amawonetsa kukhudzidwa kwa zigawo izi panthawi yopanga maphunziro. (Bakuman & Rauch 1996). Munthawi yomaliza yowonera matepi, nthawi yomwe amalimbikitsa kutchova juga mwamphamvu kwambiri, amuna omwe ali ndi PG poyerekeza ndi omwe anali osadziwika kwambiri adawonetsa kusintha kwakukulu kwa chizindikiro cha BOLD mu vmPFC. Zotsatira izi zikuwoneka zogwirizana ndi zomwe zimachokera ku maphunziro a kusokonekera kwa chiwongolero champhamvu pamagawo ena azikhalidwe, makamaka nkhanza (Wokhulupirira Et al. 1999; yatsopano Et al. 2002) ndikusankha zochita (Bechara 2003).

Ngakhale maphunziro ena oyerekeza adakhala ndi chidwi ku zigawo za PG (Crockford Et al. 2005), kafukufuku wambiri wawona kusiyana mu vmPFC ntchito mu PG. Kafukufuku wokhudza kuwongolera kuzindikira pogwiritsa ntchito chochitika chokhudzana ndi chochitika cha Stroop color-mawu osokoneza ntchito adapeza kuti amuna omwe ali ndi PG poyerekeza ndi omwe alibe adasiyanitsidwa kwambiri ndi kusintha kocheperako kwa chizindikiro cha BOLD kumanzere kwa vmPFC kutsatira kuwonetsa kwa zoyipa zoyipa (Potenza Et al. 2003a). Pochita FMRI Stroop paradigm yomweyi, anthu omwe ali ndi vuto la kupuma omwe adasiyanitsidwa kwambiri ndi maulamuliro m'dera lomwelo la vmPFC (Blumberg Et al. 2003,, ndikuwonetsa kuti zinthu zina zomwe zimafala pamavuto (mwachitsanzo, kuwongolera kusawongolera, kusakhazikika pamalingaliro) zimagawana gawo la neural pamalire azizindikiro. Mofananamo, anthu omwe amadalira mankhwala omwe alibe kapena osagwirizana ndi PG adawonetsa kutsegula pang'ono kwa vmPFC kuposa omwe adayang'anira nkhani mu 'kuwunika' njuga poyesa kusankha zochita (Tanabe Et al. 2007).

Kafukufuku wina wa FMRI, anthu omwe ali ndi PG poyerekeza ndi omwe sanayesere kuyambitsa vmPFC panthawi yongoyerekeza kutchova njuga poyerekeza kupambana ndi kutaya zinthu, ndipo kusintha kwa chizindikiro cha BOLD mu vmPFC kumakhudzana kwambiri ndi kusuta kwa njuga pakati pa PGers (Zosintha Et al. 2005). Mu kafukufuku omwewo ndikugwiritsa ntchito kusiyanasiyana, njira yofananira yakuchepa idawonedwa ku PGers mu ventral striatum, dera laubongo lomwe lili ndi dopaminergic innervation ndipo ndilofala kwambiri pakukhudzidwa kwa mankhwala osokoneza bongo ndikuwongolera mphotho (Everitt & Robbins 2005). Kutengera ndi ntchito za anyani (Schultz Et al. 2000), kafukufuku wokhudzana ndi kulandira mphotho mwa anthu agwirizanitsa kutsegulira kwa ma ventral streatum ndikuyembekeza kugwira ntchito yolipirira ndalama komanso kutsegula kwa vmPFC ndikulandila mphotho yazandalama (Knutson Et al. 2003). Izi zikuwoneka zofunikira makamaka pakuwongolera mphotho yomweyo popeza kusankha kwakanthawi kochedwa kumaphatikizanso ndi ma dorsal cortical network (McClure Et al. 2004). Kutchova njuga wakuda poyerekeza ndi kusewera Blackjack kwa mfundo kumalumikizidwa ndi kuchititsa kwakukulu kwa corticostriatal ku PGers (Hollander Et al. 2005). Komabe, kafukufukuyu sanaphatikizepo maphunziro opanda PG ndipo motero sanafufuze momwe maphunziro a PG amasiyana ndi omwe alibe vutoli. Kupezeka kwa kuchepa kwa magwiridwe antchito am'mimba mwa PGers mu njira yongoyeserera njuga (Zosintha Et al. 2005) imagwirizana ndi zomwe zapezeka kuchokera ku maphunziro a kuyembekezera mphoto kwa anthu omwe ali ndi vuto lotere kapena akuwoneka kuti ali pachiwopsezo cha zovuta izi. Mwachitsanzo, kuchepa kocheperako kwa zosowa zapakati panthawi yomwe akuyembekezera mphoto yazandalama zanenedwa mwa anthu omwe amadalira mowa (Hommer 2004; Tsekani Et al. 2007) kapena kudalira cocaine (CD; Pearlson Et al. 2007) komanso mu achinyamata poyerekeza ndi akulu (Bjork Et al. 2004) ndi omwe ali ndi banja loledzera poyerekeza ndi omwe alibe (Wokhalamo Et al. 2004). Zonsezi, izi zikuonetsa kuti kuchepa kwa mphamvu ya makina olowera mkati mwazomwe akuyembekeza magwiridwe a mphotho atha kuyimira njira yayikulu yapakati yogwiritsa ntchito mankhwala osokoneza bongo komanso ma ICD.

5. Kulimbikitsa chidwi mu PG ndi CD

Kulimbikitsidwa kwamtima kapena kukhumba mayiko nthawi zambiri amatsogolera kuchita zinthu zovuta monga kutchova juga kwa PGers kapena kugwiritsa ntchito mankhwala osokoneza bongo. Mwakutero, kumvetsetsa kwamgwirizano wamatumbo a maboma awa kumakhala ndi tanthauzo lofunikira muchipatala (ndalama Et al. 2006). Malinga ndi sayansi, maphunziro a njira zofananira, monga kukhumba mayiko mwa anthu omwe ali ndi PG kapena iwo omwe ali ndi DD, atha kufotokoza bwino zomwe zili pachiwonetsero cha zovuta zomwe zimayambitsa zovuta, popanda zotsatira za kuwonekera kwa mankhwala osokoneza bongo kapena owopsa.

Kuti tifufuze, tinagwiritsa ntchito zomwe tapeza mu maphunziro athu ofufuza za kutchova njuga ku PG (Potenza Et al. 2003b) ndikukhumba mankhwala osokoneza bongo mu CD (Wexler Et al. 2001). Monga phunziroli lathu la njuga limakhudza maphunziro a amuna okhaokha, tidangoleketsa kusanthula kwa amuna, kupereka zitsanzo kuphatikizapo 10 PG maphunziro ndi ma 11 otchova juga (C_PG maphunziro) omwe adaonera njuga, makapu achisoni komanso osangalala nthawi ya fMRI, ndi 9 CD nkhani ndi 6 osagwiritsa ntchito mankhwala oyerekeza cocaine (C_CD nkhani) omwe adawona zoziziritsa kukhosi, zachisoni komanso zosangalatsa, monga tafotokozera kale. Tidasanthula motere momwe ma activation a ubongo mumagwiridwe ndi zolimbikitsira amalingaliro anali ofanana kapena osiyana mu chizolowezi chamakhalidwe ngati PG poyerekeza ndi CD yosokoneza bongo. Tidawerengera kuti zigawo zaubongo zomwe ntchito yake idapangidwa ndi kuwonetsedwa kwa cocaine, monga frontal ndi anterior cingate cortex, titha kutengapo gawo pokana zokonda za cocaine za CD komanso zofuna za juga ku PG.

Tidagwiritsa ntchito njira ya voxel yozikika popereka tanthauzo lambiri m'mibadwo ya p-mapu omwe amadziwika mosiyanasiyana momwe magwiridwe antchito am'mutu amathandizira amasiyana ndi omwe amawongolera njuga ndi magulu a cocaine pakuwona zamankhwala osokoneza bongo, okondwa komanso achisoni (Wexler Et al. 2001; Potenza Et al. 2003b). Pa gulu lililonse lomwe likuwona mtundu uliwonse wa tepi, tidatulutsa a t-kupanga kuyerekezera nthawi yowonera poyerekeza ndi zoyambira ndi zaposachedwa tepi. Chotsatira, pamtundu uliwonse wa tepi, tidatulutsa t-posiyana ndi machitidwe omwe machitidwe omwe anakhudzidwa (mwachitsanzo PG) adasiyana ndi kuwongolera kwawo (mwachitsanzo C_PG), kupanga PG-C_PG kusiyanitsa. Kenako, tinasiyanitsa momwe magulu omwe anakhudzidwa adasiyanirana ndi kuwongolera pazosinthazi ((PG-C. C_PG) - (CD-C_CD); tebulo 1a, onani chithunzi 1A pazinthu zowonjezera zamagetsi). At p<0.005 ndikugwiritsa ntchito tsango la 25 kukulitsa stringency (Friston Et al. 1994), kusiyana komwe kumayenderana ndi kusokonekera pakati pamagulu omwe akukhudzidwa ndi osakhudzidwa kunawonedwa pakuwona matepi osokoneza bongo (tebulo 1a; onani chithunzi 1A pazinthu zowonjezera zamagetsi) koma osati zomvetsa chisoni kapena zosangalatsa (sizinawonetsedwe). Madera a ventral and dorsal anterior cingulate and right inferior parietal lobule adadziwika pazowonera, ndikuchepetsa kwa ntchito mu (PG-C_PG) poyerekeza ndi CD (CD-C_CD) kufanizira. Zomwe gulu laling'ono-pamutu pazosinthazi zalembedwa (tebulo 1a). The anterior cingulate cortex, gawo laubongo lophatikizika mu magwiridwe antchito ndikuwongolera kuzindikira mwaumoyo (Chitsamba Et al. 2000) ndi CD CD (Golide Et al. 2007,, yawonetsedwa kuti iyambitse ntchito pakupanga cocaine (Kusamalira ana Et al. 1999). Cocaine makina amayambitsa makina anterior (Febo Et al. 2005), komanso nthawi komanso njira ya makonzedwe a cocaine amachititsa kuti ntchito ya cocaine ikhale kunja (Harvey 2004). Kusiyana kwa ma parietal lobule otsika kwambiri pamagulu a maphunziro kumawonetsa kusiyana kwakukulu mu mayankho a neural a magulu owongolera pamasewera a juga ndi makaseti a cocaine. The parietal lobule otsika kwambiri adayikiridwa poyankha zoletsa zamavuto a lamulo (Menon Et al. 2001; Garavan Et al. 2006). Chifukwa chake, zomwe apezazi zikuwonetsa kuti kuyang'ana matepi amitundu yosiyanasiyana (monga kufotokozera kwa chikhalidwe chosagwirizana ndi anthu (kutchova njuga) poyerekeza ndi ntchito yosavomerezeka (yogwiritsa ntchito cocaine)) zimagwirizanitsidwa ndi kuyambitsa kusiyanasiyana komwe kumayendetsa mbali za ubongo zomwe zikugwira nawo kuyankha pakati zoletsa.

Kutsegula kwa ubongo mu PG ndi CD poyerekeza ndi maphunziro.

Tidayesanso zigawo zamaubongo zomwe zimakonda cocaine zokhumba ndi kutchova juga, ndikuganiza kuti titha kuzindikira zigawo za ubongo zomwe zakhala zikukhudzidwa mofananamo mu CD ndi PG, monga kuchepa kuyambitsa kwa ventral striatum pokonzanso mphotho komwe yakhudzidwa poyerekeza ndi nkhani zowongolera (Zosintha Et al. 2005; Pearlson Et al. 2007). Pa gulu lililonse lomwe likuwona mtundu uliwonse wa tepi, tidatulutsa a t-kupanga kuyerekezera nthawi yowonera ndi masamba oyamba Chotsatira, pamtundu uliwonse wa tepi, tidapanga t-mapu omwe amawonetsa zodetsa nkhawa m'magulu odwala ndi kusiyanitsa gulu lililonse la odwala ndi kayendetsedwe kake, ndikupanga PG-C_PG ndi CD-C_CD kusiyanitsa. Kuyerekeza kopangidwa ndi makompyuta pazipata zazikulu zotsatizana (p<0.005, p<0.01, p<0.02 ndi p<0.05) adapangidwa kuti azindikire zigawo zomwe PG-C_PG ndi CD-C_CD kusiyanitsa kunawonetsa zomwezi. Gulu lililonse p-mapu adagwiritsidwa ntchito kuti azindikire zigawo zaubongo zomwe zikuthandizira izi. Palibe magawo aubongo omwe adadziwika omwe amagwiritsa ntchito njirayi pamankhwala osokoneza bongo, okondwa komanso achisoni. Monga momwe maphunziro athu am'mbuyomu adawonetsera kuti nthawi yoyang'ana patepi, isanayambike kuyankhidwa kwamphamvu / yokhudzidwa, idalumikizidwa ndi kusiyana kwakukulu pakati pamagulu poyankha mavidiyo owonetsa (Wexler Et al. 2001; Potenza Et al. 2003b), tinachita zofanizira zikuyang'ana nthawi yoyambira kuwonera tepi poyerekeza ndi chiyambi cha tepi isanakwane. Njirayi idazindikira madera angapo aubongo (tebulo 1b; onani chithunzi 1B pazinthu zowonjezera zamagetsi) kuwonetsa kusintha kofananako pakati pazosiyanitsa pakati pa nkhani zowonera ndi zowongolera pakuwona matepi oyenerera, ndipo palibe zigawo zomwe zidadziwika poyerekeza matepi achisoni kapena achimwemwe (osawonetsedwa).

Madera aubongo omwe adawonetsedwa kuti akuwonetsa njira zomwe zimakhazikika mu magulu omwe adachita chidwi ndi osagwiritsa ntchito mankhwala osokoneza bongo amaphatikiza zigawo zomwe zimathandizira pakukhudza mtima, kulimbikitsa mphoto ndi kusankha, kuyimitsa mayankho, ndi kuchititsa anthu kugwiritsa ntchito mankhwala osokoneza bongo. Nthawi zambiri, zigawozi zinkakhazikitsidwa mu mitu yolamulira koma osati mwa omwe adawaletsa. Kuchepa kocheperako kwa zochitika zapaderadera kumawonedwa mu maphunziro omwe adawonetsedwa poyerekeza ndi maphunziro owongolera, zogwirizana ndi zomwe zapezeka pazogwiritsa ntchito mphotho mu magulu a PG ndi ma CD (Zosintha Et al. 2005; Pearlson Et al. 2007). Zigawo za Ventral za preortal cortex, makamaka orbitof mbeleal cortex, zakhala zikuwoneka bwino pakuwongolera mphotho (Schultz Et al. 2000; Knutson Et al. 2003; McClure Et al. 2004,, ndipo dera loumbika likuganiza kuti lingayambitse pomwe chidziwitso chofunikira chikuwongolera zochita kapena ngati kusankha kumaphatikizapo kuponderezedwa kwa mayankho omwe adalandilidwa kale (Elliott Et al. 2000). Madera am'mbali mwa cortex yam'kati mwa preralal preortal cortex, monga gawo laling'ono lakutsogolo, amawonedwanso kuti ndi ofunikira kwambiri poyankha zoletsa komanso kuwongolera mosavutikira (Chamberlain & Sahakian 2007). Madera ena aubongo omwe machitidwe awo ogwiritsira ntchito adasiyanitsa anthu omwe ali osokoneza bongo komanso omwe sanachite chizolowezi chaphunziro pano apezekanso pankhani yolamulira. Mwachitsanzo, mu gulu la Go / NoGo paradigm lomwe limaphatikizapo maphunziro athanzi, chikhazikitso, chodziwika bwino ndi cholembera kwanyumba chinagwiritsidwa ntchito pakukonza zolakwika ndi orbitof mbeleal cortex ndi girus ya lingual panthawi yovuta yankho (Menon Et al. 2001). Kugwiritsira ntchito ntchito mkati kumathandizanso kukulitsa chikumbumtima ndipo motero kumatha kuchititsa anthu kusankha zochita kuti athetse vuto lawo (Craig 2002; Naqvi Et al. 2007). Kulephera kwa anthu omwe adayamba kugwiritsa ntchito mankhwala osokoneza bongo kuti akwaniritse madera amenewa poyambira kuyankha ku zinthu zomwe zimayambitsa ngozi kungapangitse kuti asadziletse komanso kugwiritsa ntchito mankhwala osokoneza bongo. Izi zakwaniritsidwa zili ndi tanthauzo pazotsatira zamankhwala kwa onse PG komanso osokoneza bongo. Mwachitsanzo, kuwonongeka kwa insula kumagwirizanitsidwa ndi kubetcha kosavomerezeka monga zikuwonetsedwera kulephera kusintha ma bets mokhudzana ndi zovuta zakupambana, ndipo chifukwa chake zovuta zomwe zimapangitsa kukhala ndi vuto ndi PG (Clark Et al. 2008). Kuphatikiza kwamatumbo a costrate pakuwona mavidiyo a cocaine kumalumikizidwa ndi zotsatira zamankhwala mu nkhani za CD, ndi omwe adatha kukana kuwonetsa kwambiri gawo ili laubongo (ndalama Et al. 2006). Chifukwa chake, ngakhale zotsatirazi ziyenera kuonedwa ngati zoyambirira zimaperekedwa pamalingaliro ang'onoang'ono a gulu lililonse la maphunziro, zomwe zapezazo zimakwaniritsa zolemba zazikulu za PG, kusokoneza bongo, chiwongolero chazomwe zimayambitsa komanso ma neural correlates a zotsatira zamankhwala osokoneza bongo. Kafukufuku wowonjezereka omwe akuphatikizapo zitsanzo zazikulu komanso zosiyana siyana amafunika kuti akwaniritse izi.

6. Zotsatira ndi zotsatila zamtsogolo

Ngakhale kupita patsogolo kwakukulu pakumvetsetsa kwathu PG pazaka khumi zapitazi, mipata yayikulu idatsalira pakumvetsetsa kwathu. Maphunziro azachilengedwe ambiri mpaka pano ali ndi zitsanzo zazing'ono za abambo kapena amuna okhaokha, zomwe zikuwonetsa kukhudzana ndi zomwe zapezeka, makamaka kwa azimayi. Kusiyana kogonana pamakhalidwe otchova juga kwanenedwa onse pokhudza mitundu yamavuto amtundu wa njuga kwa akazi poyerekeza ndi amuna komanso njira za kakulidwe ka mavuto a njuga (Potenza Et al. 2001). Mwachitsanzo, chochitika cha 'telescoping', njira yofotokoza chithunzi cha nthawi yoyambira pakati pa kuyambika ndi zovuta pamagulu azikhalidwe, adayamba kufotokozedwa za zakumwa zoledzeretsa, zaposachedwa kwambiri za DD, komanso zaposachedwa zovuta ndi PG (Potenza Et al. 2001). Popeza kusiyana komwe kumakhala koyenera m'chipatala, mayeso omwe ali pachiwonetsero cha PG ayenera kuganizira zomwe zimapangitsa kugonana. Mofananamo, magawo osiyanasiyana a matenda amtundu wa juga amayenera kuganiziridwa pakufufuza kwachilengedwenso, chifukwa cha kuchuluka kwa zinthu zomwe zimapangitsa kuti mitsempha ikhale yofanana (mwachitsanzo, panjira yotsutsana ndi dorsal striatum) momwe zimakhalira zikuyenda kuchokera ku buku lambiri kapena lokakamiza kuzolowera kapena lokakamizika (Everitt & Robbins 2005; Chambers Et al. 2007; Belin & Everitt 2008; Brewer & Potenza 2008). Zowunikira zowonjezerapo zimaphatikizapo chikhalidwe cha kukakamizidwa komanso ubale wake ndi ma ICD komanso mankhwala osokoneza bongo. Ndiye kuti, ndizotheka kuti kugwiritsa ntchito mankhwala osokoneza bongo kumatha kubweretsa kutchova juga yambiri, kutchova njuga kambiri kungayambitse kugwiritsa ntchito mankhwala osokoneza bongo, kapena kuti zinthu zodziwika monga kunyengerera zimatha kuyambitsa kwambiri gawo lililonse. Kulongosola izi mwazinyama ndi zenizeni zenizeni zimayimira cholinga chachipatala komanso sayansi (Dalley Et al. 2007). Popeza kuti kusunthidwa ndi ntchito zovuta kupanga (Moeller Et al. 2001), kumvetsetsa momwe magawo ake amagwirizanirana ndi ma pathophysiologies a komanso mankhwala a PG ndi mankhwala osokoneza bongo ndikofunikira. Pomaliza, PG ndiwophunziridwa bwino kwambiri kagulu ka ma ICD omwe pano amakhala m'magulu azidziwitso. Kafukufuku wowonjezereka amafunikira kuma ICD ena ndi ma neurobiology awo, kupewa ndi kulandira chithandizo, makamaka chifukwa zovuta izi zimalumikizidwa ndi zolemba za psychopathology yayikulu ndipo zikuwoneka kuti sizipezeka kawirikawiri pazovuta zamankhwala.Grant Et al. 2005).

Kuvomereza

Bruce Wexler ndi Cheryl Lacadie adathandizira pantchito yolingalira zamaginito yomwe idaperekedwa. Zothandizidwa pang'ono ndi: (i) National Institute on Abuse Abuse (R01-DA019039, R01-DA020908, P50-DA016556, P50-DA09241, P50DA16556, P50-AA12870) ndi National Institute of Alcohol Abuse and Alcoholism (RL1-AA017539 , P50-AA015632), ndi National Center for Research Resources (UL1-RR024925); (ii) Kafukufuku wa Zaumoyo Azimayi ku Yale; (iii) Ofesi Yofufuza Zaumoyo wa Akazi; ndi (iv) Department of Veterans Affairs ku US VISN1 MIRECC ndi REAP.

Kulankhulidwa. Dr Potenza akuti alibe zovuta zilizonse pazaka 3 zapitazi kuti anene zokhudzana ndi lipotilo. Dr Potenza walandila chithandizo chandalama kapena chipukuta misozi chifukwa cha izi: Dr Potenza amafunsira kwa Boehringer Ingelheim ndipo ndiupangiri wawo; adafunsira ndipo ali ndi zokonda zachuma ku Somaxon; walandila thandizo lofufuza kuchokera ku National Institutes of Health, Veteran's Administration, Mohegan Sun, ndi Forest Laboratories, Ortho-McNeil ndi Oy-Control / Biotie asatayike; watenga nawo mbali pakufufuza, kutumiza kapena kuyankhulana patelefoni zokhudzana ndi mankhwala osokoneza bongo, ma ICD kapena mitu ina yazaumoyo; afunsira maofesi azamalamulo ndi Federal Public Defender's Office pankhani zokhudzana ndi ma ICD; yachita kuwunika kwa mabungwe a National Institutes of Health ndi mabungwe ena; wapereka zokambirana m'malo opitilira muyeso, Kupitiliza zochitika za Medical Medical ndi malo ena azachipatala kapena asayansi; wapanga mabuku kapena mitu yamabuku ofalitsa ofotokoza zaumoyo; ndipo imapereka chithandizo chamankhwala ku Connecticut department of Mental Health and Addiction Services Vuto Kutchova Njuga.

Mawu a M'munsi

Mgwirizano wina wa 17 ku Nkhani Yokambirana pazokambirana 'Kusowa kwa ubongo: zatsopano zatsopano.'

Zowonjezera Zowonjezera

Chithunzi 1A:

Dinani apa kuti muwone.^{(541K, tif)}

Chithunzi 1B:

Dinani apa kuti muwone.^{(666K, tif)}

Nthano ya chithunzi:

Dinani apa kuti muwone.^{(48K, doc)}

Zothandizira

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