Litšoantšo tsa lefutso tsa tsoelo-pele: ho amahanya dopamine le boits'oaro ho boits'oaro ba bocha (2014)

Kelello ea Brain. Sengoloa se ngotsoeng; e fumaneha ho PMC 2015 Aug 1.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

Kelello ea Brain. 2014 Aug; 89: 27-38.

E phatlalalitsoe marang-rang 2013 Oct 17. Doi: 10.1016 / j.bandc.2013.09.011

PMCID: PMC4226044

NIHMSID: NIHMS535184

Aarthi Padmanabhan¹ 'me Beatriz Luna¹

Boitsebiso ba Mongoli ► Tlhahisoleseding ea Copyright le License ►

Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Kelello ea Brain

Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.

inahaneloang

Nako ea bocha ke nako ea kholiso e tšoauoa ka liphetoho tse ngata tse amanang le methapo ea kutlo tse amang ka matla boitšoaro le tšebetso ea boko. Nako ea bocha e khahla haholo ka lebaka la lipalo tse tšosang tse bonts'a hore palo ea batho ba shoang e eketseha habeli ho isa ho tse tharo ka nako ena ha e bapisoa le bongoana, ka lebaka la tlhalo e kholo ea boits'oaro bo kotsing e hlahisoang ke ho tsitlallela ho hoholo le takatso ea maikutlo. Ntle le moo, ho na le phapang e kholo e senotsoeng litloaelong tsena tseo karolo ea tsona e anngoeng ke lintho tsa tlhaho. Tsoelo-pele ea morao-rao genetics ea limolek'hule le tšebetso e sebetsang li file monyetla o ikhethang le o monate oa ho ithuta ka tšusumetso ea mabaka a liphatsa tsa lefutso ho ts'ebetso ea boko ho motho. Le ha liphatsa tsa lefutso li sa ngolle boits'oaro bo itseng, li khetholla sebopeho le tšebetso ea liprotheine tse bohlokoa lits'ebetsong tsa methapo. Ka hona, ho ithuta tšebelisano ea genotype ka mehato ea ts'ebetso ea ts'ebetso ea ts'ebetso ea boko ho ka hlahisa leseli linakong tsa bohlokoa tsa nako ha litekanyetso tsa tlhaho ka bo-motho li hlaha. Mona re lekola lingoliloeng tsa liphoofolo le tsa batho tse lekolang motheo oa neurobiological oa nts'etsopele ea bongoaneng e amanang le dopamine neurotransmission. Dopamine e bohlokoa haholo hobane (1) karolo ea eona ho boits'oaro bo botle le boits'oaro, (2) karolo ea eona ho pathogenesis ea psychopathology e kholo, le (3) nts'etsopele e hlahisitsoeng ea dopamine signways litseleng tsa bocha. Joale re tla shebana le lipatlisiso tsa hajoale ho hlahloba karolo ea liphatsa tsa lefutso tse amanang le dopamine tšebetsong ea boko. Re khothaletsa ts'ebeliso ea genetics ea ho nahana ka sepheo sa ho hlahloba tšusumetso ea dopamine e pakeng tsa dopamine tšebetsong ea boko nakong ea bocha, re ntse re hopola meeli ea mokhoa ona.

Selelekela

Bophelong ba motho, nako ea bongoana e batla e tsamaellana le ho qala ho kena bohlankaneng kapa boroetsaneng, ha tšebetso ea bohlokoa ea neuroendocrine e baka 'me e ba teng ka tatellano e thata ea liphetoho tsa bioloji ho kenyelletsa, ho bohlokoa' meleng, thobalanong, neurochemical, neurofunctional, 'mele, pelo le pelo. (Falkner le Tanner 1986; Romeo 2003). Liphetoho tsena tsa likokoana-hloko li sebetsana le tikoloho khafetsa 'me li tšoaea nako e tlokotsing le e matla ea ntlafalo ea' mele, ea kelello le ea sechaba (Spear, 2000). Mefuta le litso tse fapaneng, ho na le boits'oaro bo lilemong tsa bocha ho kenyelletsa litlhōrō tsa maikutlo / bocha ba ho kopa hammoho le maemo a fokotsehileng a thibelo ea likotsi, a lebisang keketseho ea boits'oaro bo kotsi (Laviola, Macri et al. 2003). Keketseho e tloaelehileng ea maikutlo / ho batla lintho tse ncha li ka fetoha, ho lumella bacha ho batla boipuso ka ntle ho ntlo. Ka mantsoe a mang, likotsi tse ling li ka hlokahala ho tsamaisa phetoho ea likarolo tsa batho ba baholo sechabeng. Leha ho le joalo, boits'oaro bo itseng bo nang le litakatso tse phahameng haholo bo ka pepesetsa motho litlamorao tse mpe (Spear, 2000). Ka hona, re hlalosa ho nka kotsi e le ho nka bohato ba ho etsa lintho tse ka hlahisang melemo (hape e tsejoang e le boitšoaro bo khothalletsoang ke ts'usumetso), empa litlamorao tse mpe tse mpe. Litlamorao tsa boits'oaro bo kotsi bo hokeloang bocheng (mohlala, ho sebelisa lithethefatsi le joala, ho khanna ka mokhoa o sa tsotelleng, le thobalano e sa sireletsehang), li ka ba matla haholo ha litekanyetso tsa batho ba shoang le ba fokolloang ke bophelo li eketseha haholo ho tloha bongoaneng (Dahl 2004). Ntle le likotsi tsa kholo e tloaelehileng ea bocha, bocha hangata ke nako eo mafu a fapaneng a kelello a hlahang a kang khatello ea maikutlo, mathata a tšebeliso e mpe ea lithethefatsi, mathata a ho ja le psychoses (Pine 2002; Litho, Taylor et al. 2003; Sisk le Zehr 2005; Paus, Keshavan et al. 2008), lintlha tse behang kotsing tse sa khetholloeng ka botlalo. Ka lebaka la bopaki bona, ho bohlokoa hape hore o hlokomele hore bacha ba khona ho etsa liqeto tse holileng (Paus 2005), monahano o thetsang, 'me hangata o etsa boitšoaro bo bobe (Steinberg, Cauffman et al. 2009). Kahoo, litloaelo tse ngata tse nkang kotsi nakong ea bohlankana hangata li ba maemong a liphaello tse matla tsa maikutlo le / kapa tse batlang moputso (Casey, Getz et al. 2008; Blakemore le Robbins 2012), ho totobatsa ho ba kotsing ea tlhaho le tikoloho ea tlhaho ea tlhaho le "neuroplasticity" e sa khetholloang ka botlalo.

Leha ho na le bopaki ba keketseho e akaretsang ea ho beha boitšoaro bocheng, ka monahano oa hore motho e mong le e mong o mothating oa ho khotsofatsa le ho batla lintho tse ncha, ho na le phapang e ngata boits'oarong ba bocha e sa hlalosoang. Ka mantsoe a mang, ha bacha ba bang ba ipeha kotsing ea ho beha batho ba bang kotsing, ba bang ha ba joalo, le maemo ao ho ona batho ba bang ba kenang molemong oa ho ipeha kotsing. Lilemong tsa morao tjena, lefapha la liphatsa tsa lefutso le kopantsoe le kelello ea kelello ho hlahloba motheo oa methapo ea phapang ea boitšoaro. Mokhoa ona, o tsejoang e le 'imaging genetics', o thehiloe khopolong ea hore ts'ebetso ea boko le sebopeho li ka sebetsa e le lipakeng tsa liphatsa tsa lefutso le boits'oaro, ha mosebetsi oa boko o sebetsa haufi le genotype (Hariri le Weinberger 2003).

Tlhahlobo ena e shebana le tšusumetso ea dopamine ea neurotransmitter le mefuta e fapaneng ea liphatsa tsa lefutso tsa dopamine mekhoeng ea boits'oaro e susumetsoang bocheng. Re qala ka ho lekola lingoliloeng tse mabapi le ho nonoa ha litsamaiso tsa mantlha tsa boko - e leng lipotoloho tsa frontostriatal - le karolo ea bona boits'oarong ba bocha. Karolo ea dopamine ho fetoleng boitšoaro bo susumetsang le nts'etsopele e tsoelang pele ea ts'ebetso ea dopamine nakong ea bocha e tla tšohloa ka mor'a moo. Qetellong, re tsepamisitse maikutlo tlhahlobisong ea lithuto tsa liphatsa tsa lefutso tsa liphatsa tsa lefutso re sebelisa li-polymorphisms tse tloaelehileng tse sebetsang liphatseng tsa bohlokoa tse bontšang liphatsa tsa lefutso tse lebisang ho tlhahiso ea lipatlisiso tsa kamoso kholong ea bongoana.

Khothatsoa boits'oaro bo khothalletsoang le meketjana ea pele ho bohlankana

Bopaki bo fana ka maikutlo a hore bacha ba tloaetse ho susumetsa ka tsela e fapaneng le ho feta batho ba baholo (bakeng sa litlhahlobo bona: Geier le Luna (2009; Ernst, Daniele et al. 2011)), e lebisang ho ho etsa liqeto tse fokolang ebile hangata ho ba kotsi. Moralo oa ts'ebetso ea ts'usumetso ea bohlankana o its'etleha hodima mohopolo oa hore bacha ba leeme mabapi le meputso e ka ba teng (Steinberg 2004) le ho bontša taolo ea bokhachane ea kelello (Yurgelun-Todd 2007).Casey, Getz et al. 2008; Ernst le Fudge 2009).

Striatum ea motho e amoheloa e le senotlolo sa ts'ebetso ea ts'ebetso ea ts'usumetso le boits'oaro bo hlahisang, ka ho khetheha bokhoni ba ho kopanya mekhoa e fetohileng ea tikoloho le ho ntlafatsa boits'oaro bo nepahetseng ka ho hokahana le "preortalal cortex" (PFC) ka tsela ea ho feta empa e arohaneng ka tsela e fapaneng (Alexander, DeLong et al. 1986; Postuma le Dagher 2006; Di Martino, Scheres et al. 2008) tseo e leng boitšoaro bo ikhethileng (Tekin le Cummings 2002). Li-circuits tse kholo tsa kapele-pele li sebetsa ka tsela ea likhakanyo tse thabisang ho tloha libakeng tse ka pele ho ea libakeng tse itseng tsa sepakapaka (mohlala dorsolateral PFC ho ea dorsal caudate, laterC OFC ho ventromedial caudate, medial OFC ho li-nucleus accumbens) le ho khutla ka thalamus. Li-circuits tsena tse koetsoeng ka thata li lebisa tseleng tse peli tse kholo; ka kotloloho le ka kotloloho. Tsela e tobileng, e thibelang thalamus, e kenyelletsa merero ea GABAergic ho tloha striatum ho ea ho midbrain ho ea karolong e ka hare ea globus pallidus ho ea ho thalamus. Tsela e sa tobang e na le lipakanyo tsa GABAergic ho tloha ho striatum ho ea ho globus pallidus externa ho ea subthalamic nucleus, qetellong e thabisang ea inhibitory neurons ho globus pallidus interna, e thibelang thalamus. Kahoo, boitšoaro bo ratoang bo hlahisoa ka tsela e otlolohileng mme tsela e sa tobang e sitisa liketso tse sa lakatseheng le tse tlholisang. Ka hona, ho hloka botsitso le ho sitisoa ha tšebetso ea lipotoloho tse ka pele ho ka baka tlholisano lipakeng tsa tsela tse otlolohileng le tse sa tobang, tse lebisang boits'oarong bo bobebe.

Ho fihlela sena, mehlala ea methapo ea kholo ea kholo ea bocha e khothaletsa hore ts'ebetso ea ts'usumetso ea bocha e sebetsang, e tsamaisoang ke striatum, e nang le ts'ebetso e hlokofatsang ea kelello, e tsamaisoang ke PFC, e ka baka ho se lekane hoa ts'ebetso ho melao e nepahetseng ea boitšoaro , empa boits'oaro bo sa lokang) ka ho etsa joalo bo ntlafatsa boits'oaro bo nkang kotsi bocheng (((Nelson, Leibenluft et al. 2005; Ernst, Pine et al. 2006; Casey, Getz et al. 2008), bakeng sa kakaretso ea mehlala ena bona Sturman le Moghaddam, (2011)). Ho joalo, liphuputso tse sebetsang tsa ts'ebetso ea ts'usumetso ea ts'usumetso e bonts'a phapang e kholo ea ts'ebetso le ts'ebetso ea PFC bohlankeng bo amanang le bohlankana.Bjork, Knutson et al. 2004; Ernst, Nelson et al. 2005; Galvan, Hare et al. 2006; Bjork, Smith et al. 2010; van Leijenhorst, Moor et al. 2010; Padmanabhan 2011), ka boholo ba lithuto tse tlalehang keketseho ea ts'ebetso ea ts'ebetso ea striatal, hammoho le ho fokotseha ha ho hloa mosebetsi pele. Ntle le moo, lithuto tsa khokahano e sebetsang li fana ka maikutlo a hore ho hokahanya le ho hokahana lipakeng tsa boko, ho kenyelletsa khokahano e nyane ea cortical, ho ntlafatsoa le ho sebetsa hantle haholoanyane lilemong tsa bocha, ho lebisetse khokahanong e sa sebetseng ea mesebetsi, ho matlafatsoa ha khokahano e tšehetsang liketso tse lebisitsoeng ho sepheo, le ho felisoa ha bofokoli. khokahanyo (Durston, Davidson et al. 2006; Liston, Watts et al. 2006; Ka toka, Cohen et al. 2009; Stevens, Pearlson et al. 2009; Hwang, Velanova et al. 2010). Lingoliloeng tsa batho tsa liphoofolo le tsa ka mor'a lefu li fana ka maikutlo a mangata a li-receptor tsa serotonin, dopamine, adenergic le endocannabinoids (Lidow le Rakic 1992), e phahameng ka ho fetisisang ea li-interneurons (Anderson, Classey et al. 1995; Lewis 1997; Erickson le Lewis 2002), le keketseho ea maemo a GABA (Hedner, Iversen et al. 1984). Liphetoho tsena li fetola botsitso ba maiketsetso a ho emisa tšebetso ea neuronal e ntlafatsang ts'ebetso hore e be motho e moholo. Qetellong, ho eketseha ha myelination ka cortical ho subcortical axons, liphetoho ho axon calign, pruning ea synapses le receptors, cell shrinkage, le liphetoho tsa glial (Yakovlev le Lecours 1967; Rakic, Bourgeois et al. 1986; Benes, Turtle et al. 1994; Andersen 2003) nchafatsa boko bo ntseng bo hola le ho matlafatsa le ho kopanya likhokahano tse sebelisoang haholo, ha o ntse o fokolisa kapa o tlosa likhokelo tse sebelisoang ka mokhoa o fokolang kapa o fokolang ka boiphihlelo bo ikhethileng ((Huttenlocher 1990; Jernigan, Trauner et al. 1991; Pfeff)um, Mathalon et al. 1994; Giedd, Blumenthal et al. 1999), bakeng sa tlhahlobo Bona: (Paus 2005)). Ha ho tsamaisoa hammoho, lingoliloeng tsa hajoale li totobatsa hore ho hloka tšebetso tšebetsong le ho kopanya lipakeng tsa likarolo tse ka pele le tse hlophisehileng ho kenya letsoho mohopolong o fapaneng oa bongoana (le boits'oaro bo latelang).

Dopamine

Li-circuits tsa Frontostriatal tse fanang ka lits'ebetso tse thusang, tse hlokofatsang, le tsa koloi li fetoloa haholo ke neurotransmitter dopamine (DA) (bakeng sa litlhahlobo bona (Schultz 2002; 2004 e Bohlale; Cools 2008), ka ho nolofalletsa tsela e otlolohileng ka ketso ea li-receptors tsa thabo tsa DA (D₁-ka tšoana le thibelo ea tsela e sa tsejoeng ka ketso ea li-receptors tsa inhibitory tsa DA (D₂-ba joaloka). Li-neurons tsa DA ho projeke ea "midbrain" ho ea ho li-spiny neuron tse ka hare ho NAcc le li-neuron tsa pyramidal ho PFC, ka tsela ena li fetola litefiso tsa ho thunya ha methapo ena le ho theha likamano tse matla pakeng tsa striatum le PFC (Mohau, Floresco et al. 2007). Maemo a DA a fetoloa ke lits'ebetso tse peli tse sa hlonepheng tsa ho hlohlona ha DA tse sebetsanang, (1) tonicity ea semmuso e laoloang ke ho hlaseloa hoa motheo ha li-neurons tsa DA le liphatlalatso tsa glutamatergic ho tloha libakeng tsa cortical ho ea ho striatal, le (2) ho phatloha ho hoholo ho hoholo hoa maemo a phahameng (amplitude phasic) (Mohau, Floresco et al. 2007). Mekgwa ena e mmedi ya ho supa ha DA e fumanoe e lebisa boitsong bo ikhethileng (Floresco, West et al. 2003) mme e laoloa ke li-enzyme tse tsoang hape le ho nyenyefatsa. Liketsahalo tse potlakileng tsa phasic li etsahala ho arabeloa liketsahalong tse amanang le moputso, tse ka bang lipontšo tsa bohlokoa tsa ho ruta bakeng sa ho sibolla phoso le ho fetola liphetoho tsa boitšoaro ha li arabela tikolohong (Schultz 1998). Liphetoho tse fokotsehileng litekong tsa tonic tsa DA e kanna ea ba mokhoa oa ho itukisetsa setho ho arabela lithahasellong tsa tikoloho tse amanang le moputso (Schultz 1998). Lits'ebetso tsena li sebetsa hape joalo ka ha tšebetso ea DA ea tonic e laola ho supa ha phasic ka mokhoa o thibelang mme ho bontšitsoe DA ea phasic ho ntlafatsa tšebetso ea tonic (Niv, Daw et al. 2007).

Sistimi ea DA e ba le phetoho e kholo ho feta lilemong tsa bocha, e loketseng boits'oaro ba bongoana ka mabaka a 'maloa. Taba ea pele, letšoao la DA le ts'ehetsa ho ithuta ho matlafatsang ha e ntse e ntlafatsa matla a li-synapses, ka tsela eo e susumetsa polasetiki. Taba ea bobeli, ho feto-fetoha ha maikutlo a DA ka ts'ebetso ea mantlha le tšusumetso ea pele li susumetsa boits'oaro bo nepahetseng le bo susumetsang bo fetoloang bocheng. Qetellong, ho hlekefetsoa ha matšoao a DA ho ameha ho pathophysiology ea mathata a amanang le neuropsychiatric a atisang ho hlaha lilemong tsa bocha (mohlala, schizophrenia, ts'ebeliso e mpe ea lithethefatsi). Lingoloa tse bontšang bolelele ba tšebetso ea DA le liphetho tsa bocha ba bocha li hlahlojoa ka botebo libakeng tse ling, (Spear 2000; Litho, Taylor et al. 2003; O'Donnell 2010; Wahlstrom, Collins et al. 2010; Wahlstrom, White et al. 2010; Luciana, Wahlstrom et al. 2012) mme e akaretsitsoe ka tlase. Boholo ba bopaki bo mabapi le tsamaiso ea DA bocheng bo tsoa mehlaleng eo eseng ea motho ea makatsang le ea litheko le liphumano li sa hlaka. Ka morero ona, lingoliloeng tse amehang li akaretsoa ka bokhutšoanyane ho totobatsa mokhoa o ka akaretsang o ka bang le phello molemong oa boitšoaro ba bocha.

Tlhōrō ea tšebetso ea li-neurbrain tsa DA e ngotsoe ka har'a mofuta oa litekanyetso (McCutcheon, White et al. 2009), ho fana ka tlhahiso ea keketseho e akaretsang ea maemo a DA. Liphuputso tse ling li hlokometse tlhōrō ea litekanyetso tsa DA tsa bonyenyane lilemong tsa bohlankana le ho fokotseha ho hoholo ha motho e moholo ((Badanich, Adler et al. 2006; Philpot, Wecker et al. 2009). Boithuto ba morao-rao bao e seng ba batho bo bonts'a hore likakanyo tse phahameng ka ho fetisisa tsa DA nakong ea bocha li ho PFC pele li theohela tlase ho ba motho e moholo (Goldman-Rakic le Brown 1982). Lithutong tsa batho ka mor'a lefu la motho, maemo a DA ho striatum a eketseha ho fihlela lilemong tsa bocha ebe a fokotseha kapa a sala a le joalo (Haycock, Becker et al. 2003). Phuputsong e 'ngoe, maemo a tsoang ho DA ho NAcc a ne a le tlase lilemong tsa bocha ha a bapisoa le ho ba motho e moholo.Cao, Lotfipour et al. 2007). Dopaminergic ho fihlelletsoa ha PFC tlhorong ea bohlankana (Rosenberg le Lewis 1995; Benes, Taylor et al. 2000), ka keketseho e kholo ka ho fetesisa ea cortical layer III, e leng tikoloho e amehang haholo ts'ebetsong ea kelello (Lewis le Gonzalez-Burgos 2000). Liphetoho tsena li etsahala ka bolelele ba li-axon ka bomong le palo e felletseng ea li-axons tse reriloeng.Rosenberg le Lewis 1994; Lambe, Krimer et al. 2000). Ho boetse ho na le keketseho ea khatello ea li-synapses pakeng tsa li-neurons tsa DA le li-neuron tsa pyramidal ka har'a karolo ea III ea cortex (Lambe, Krimer et al. 2000) hammoho le tlhoro ea khokahano ea glutamatergic ho tloha ho PFC ho ea ho NAcc, haholo ho D₁Litho tsa methapo ea kutlo (Brenhouse, Sonntag et al. 2008). Mabapi le methapo ea li-receptor, patlisiso e seng ea botho ea batho e bonts'a hore letsoalo la D₁ le D₂ li-receptors ho PFC li nyoloha ka litefiso tse fapaneng, ka D₁ segokanyi sa receptor se bonts'a litlhoro tsa pejana ho feta D₂, e phahameng ka ho fetisa bohlankana kapa botsofaling ba pele (Tseng le O'Donnell 2007). Patlisiso ea motho ea entseng lefu ea poso e fumane hore D₁ litlhaselo tsa methapo ea kutlo (receptor densities) ho pota lilemo tsa 14-18Weickert, Webster et al. 2007), ea fokotseha kamora moo. Tlhoro ea lisele tse nang le D₁ li-receptors ho PFC le tsona li ngotsoe (Andersen, Thompson et al. 2000; Weickert, Webster et al. 2007). Boemong ba striatum, litlhoro ka bobeli ba D₁ le D₂ li-receptors li etsahala bongoaneng mme li qala ho theoha boteng, li bonahala mesebetsing ea liphoofolo le ea batho (Seman, Bzowej et al. 1987; Lidow le Rakic 1992; Montague, Lawler et al. 1999; Andersen, Thompson et al. 2002). Leha ho le joalo, bopaki bo bong bo fana ka maikutlo a hore methapo ea li-receptor ea DA e theoha dorsal, empa eseng "striatum" moo maemo a lulang a le joalo ka nako ea bocha (Teicher, Andersen et al. 1995). Patlisiso mabapi le batsamaisi ba DA e sa lumellane le taba ea bohareng ba mmuso e bonts'ang phetoho e sa fetoheng ea nts'etsopele (Moll, Mehnert et al. 2000), keketseho ea bochaGalineau, Kodas et al. 2004) le litlhoro tsa bongoana (Coulter, Happye et al. 1996). Patlisiso e ngoe e khothalelitse hore lithutong, litheko tsa baeti ba DA li eketseha ho ba ngoana mme ba lule ba tsitsitse nakong ea bocha.Coulter, Happye et al. 1996; Tarazi, Tomasini et al. 1998; Galineau, Kodas et al. 2004).

Ho tlatselletsa ho rarahaneng bona, liphetoho tsa maturational mosebetsing oa DA ha li so ts'oaroe ka kotloloho boits'oarong ba bocha tse fanang ka maikutlo a hore tlhahlobo e felletseng ea ts'ebelisano ea likarolo tse fapaneng tsa tsamaiso ea DA (mohlala, li-receptors, clearance, innervation) le litlamorao tsa tsona ka kotloloho boitshwarong li nepahetse. (Spear 2011; Luciana, Wahlstrom et al. 2012). Mohlala, ho phahama ha tonic DA nakong ea bocha ho ka ama taolo ea karabelo ea phasic ho arabela tlhahisoleseling e ikhethileng kapa e ruisang (bakeng sa tlhahlobo ea bona (Luciana, Wahlstrom et al. 2012)), empa sena ha se so hlahlojoe ka matla. Ho boleloa hore mokhoa oa DA o "siling e sebetsang" bocheng bo amanang le bongoana kapa ho ba motho e moholo.Litho, Taylor et al. 2003), ka lebaka la tlhoro ea ho thunngoa ha lisele tsa midbrain DA, litekanyetso tsa tonic ka kakaretso, bolulo ba lehae, hammoho le methapo e mengata ea li-receptor. Lingoloa tsa batho ba baholo li fana ka maikutlo a hore ho eketseha ha lipontšo tsa DA ka tsamaiso ea DA kapa agonists ea DA ho eketsa boitšoaro bo batlang bo sa tloaelehang le ba ho hlahloba, athe ho fokotsa DA ho saena le bahanyetsi ho emisa boits'oaro bo joalo (Pijnenburg, Honig et al. 1976; Fouriezos, Hansson et al. 1978; Le Moal le Simone 1991). Liphumano tsena tsa pejana li supa mohlala oa tšebetso ea DA ea lilemong tsa bocha moo bophahamo ba DA bo phahamisitsoeng bo lebisang tšusumetsong e phahameng, kapa boits'oaro bo ts'oanang-ka lebaka la ts'ebetso e ntseng e eketseha ea tsela e tobileng le thibelo ea tsela e sa tobang. Bopaki bo bong bo amanang le DA bo fetotsoeng lilemong tsa bocha ho ea boits'oarong bo fana ka maikutlo a hore litoeba tsa bongoaneng li bonts'a litlamorao tse matlafatsang ho lithethefatsi tse susumetsang ho lokolloa ha DA, joalo ka joala, nicotine, amphetamines le cocaine (Adriani, Chiarotti et al. 1998; Laviola, Adriani et al. 1999; Adriani le Laviola 2000; Badanich, Adler et al. 2006; Shram, Funk et al. 2006; Frantz, O'Dell le al. 2007; Mathews le McCormick 2007; Brenhouse le Andersen 2008; Varlinskaya le Spear 2010). Bacha ba boetse ba bonts'a karabelo e fokotsehileng ea lintho tse hlekefetsoang (ke hore, likarabo tse bobebe tsa ho tlohela chelete, litlamorao tsa psychomotor) (Spear 2002; Doremus, Brunell et al. 2003; Levin, Rezvani et al. 2003) le kutloelo-bohloko e eketsehileng ho bahanyetsi ba DA receptor (Spear, Shalaby et al. 1980; Spear and Brake 1983; Teicher, Barber et al. 1993). Patlisiso ho mehlala ea batho ba baholo le liphoofolo e bontšitse hore maemo a mahareng a ho supa ha DA ho PFC le striatum hoa hlokahala bakeng sa ts'ebetso e nepahetseng, kamora karabelo ea karabelo ea sebopeho sa U-moetsi oa Jerkes-Dodson e nang le sebopeho sa U.Robbins le Arnsten 2009; Liphoso le D'Esposito 2011). Kamora mohlala ona, maemo a DA a eketsehileng bocheng a ka feta moputso o hlokahalang bakeng sa ts'ebetso e phethahetseng (Wahlstrom, Collins et al. 2010; Wahlstrom, White et al. 2010). DA ho supa lilemong tsa bocha le eona e ka ba le tšusumetso le ho susumetsoa ke phapang ea maemo a tlase a tsamaiso ea subcortical e amanang le cortical, le ho se leka-lekane ha bokong ba bongoana bo tsamaisoang ke ho saena le ho sa sebetse hantle meralong e tsamaisoang ke PFC (Litho, Taylor et al. 2003; Ernst, Pine et al. 2006).

Leha ho na le tlhoko e akaretsang ea ts'oaetso ea DA le lits'ebetso tse akaretsang tsa bohlankana, ho na le phapang e le 'ngoe e ka sebelisoang ho saena hoa DA, le boits'oaro bo susumetsoang ke DA, mohlomong ka lebaka la motsoako oa liphatsa tsa lefutso le tikoloho (Depue le Collins 1999; Frank le Hutchison 2009). Ho utloisisa mofuta oa liphapang tsena ka bomong ho ka ba le matla a maholo a ho rera esale pele. Mohlala, bacha ba nang le maemo a phahameng a lipalo tsa DA tsa tonic, litheko tse phahameng tsa DA receptor, le litheko tse tlase tsa DA clearance le nyenyefatso li ka etsa boits'oaro bo fetotsoeng ke DA (mohlala: ho natefeloa / ho batla bocha) ka tekanyo e kholo ho feta lilemong tsa bocha tse nang le lipalo tsa DA tse theotsoeng le phumaneho (Bakeng sa tlhahlobo ea bona (Luciana, Wahlstrom et al. 2012)). Lits'oants'o tsena tse kholo li ipapisitse le lithuto tsa khale tsa batho ba baholo tse totobatsang bohlokoa ba boemo ba motheo ba tsamaiso ea DA - bo fapaneng ka bomong. Mohlala, ho eketsa maemo a DA ho batho ba nang le maemo a phahameng a DA ho sitisa ts'ebetso ea kelello, (mohlomong ho ba sutumelletsa ka holim'a tlhoro ea "curve" ea inverated) athe ntlafatso e bonoa ho batho ba nang le maemo a tlase a tlase (ba a sutumelletsa haufi le sehloho sa curve) (Mattay, Goldberg et al. 2003; Apud, Mattay et al. 2007; Cools, Frank et al. 2009). Le ha mohlala ona o le bonolo, re sebelisa sena e le moralo oa ho ithuta lintlha tsa lefutso tse tsamaisang mosebetsi oa DA le hore na lintlha tsena li ka sebelisana joang le liphetoho tse tloaelehileng holima ntlafatso. Kamora mohlala ona, ho a khonahala hore liphapang tsa mantlha tsa batho ba lilemong tsa bocha li tla fapana ka ho fapana le ho ba motho e moholo ka lebaka la ho holofala tsamaisong ea DA.

Ntlafatso ea Kofuto ea Ntlafatso

Ka mokhoa o nepahetseng, ho khetholla sebopeho sa methapo ea methapo kholisong ea batho ho phephetsa, hobane lithibelo tsa bongaka le tse ling tse hlaselang (ke hore, PET) hangata li ka se sebelisoe ho ithuta ho nts'etsapele baahi. Boitekong ba ho nts'etsapele "hypotheses" e sebetsanang le litekanyetso tsa tšibollo ea DA tšebetsong ea boko, boiteko ba morao-rao bo shebile ho tseba phapang e teng liphatseng tsa lefutso la motho e amang ka kotloloho mosebetsi oa liprotheine le tšebetso ea boko le tsamaiso ea methapo ea methapo. Bafuputsi ba sebelisitse mehato e sebetsang ea sebopeho le sebopeho e le lipapatso tse bohareng ho utloisisa hantle tšusumetso ea phapang ea liphatsa tsa lefutso boits'oarong ba motho (Hariri le Weinberger 2003). Mokhoa ona o thehiloe khopolong ea hore litšusumetso tsa liphatsa tsa lefutso ho boelana le liphetoho tsa maemo a selefouno le litsamaiso tsa tšebetso bokong. Ho joalo, boithuto ba tšusumetso ea liphatsa tsa lefutso ka tšebetso ea boko kapa "liphatsa tsa lefutso" bo se bo fane ka leseli le lemohileng ka tšusumetso ea phapang e bakoang ke liphatsa tsa lefutso ho 'mele oa boko (mohlala (Hariri le Weinberger 2003; Brown le Hariri 2006; Drabant, Hariri et al. 2006; Hariri le Lewis 2006)). Leha ho le joalo bona: (Flint le Munafo 2007; Walters le Owen 2007; Kendler le Neale 2010) bakeng sa meeli le ho nahanisisa ka mokhoa ona. Taba ea ho nahana ka liphatsa tsa lefutso ke hore, ka lisebelisoa tsa eona tsa tlhahlobo tse makatsang le bokhoni ba eona ba ho fumana tlhaiso-leseling e qaqileng le e sebetsang, ho nahana ka bokong ho na le tšepiso e ikhethang ea ho hokahanya litlamorao tsa liphatsa tsa lefutso ho boits'oaro. Ha ho nahanoa hore nts'etsopele ea sistimi ea DA e ka ama batho ba bang ho feta ba bang le hore liphetho tsa liphatsa tsa lefutso li kanna tsa se emele, 'me tsa fetoha ka nako eohle ea bophelo, ho ithuta tšusumetso ea ho fapana hoa tsamaiso ea DA holima nts'etsopele ea boko e na le monyetla o moholo oa ho hlakisa. motheo oa biolo oa liphapang tsa motho ka mong boits'oarong le kotsi ea ho holisa psychopathology.

Mefuta e sa tšoaneng ea liphatsa tsa lefutso e amanang le liprotheine tse fapaneng tse amanang le DA e kile ea amahanngoa le phapang pakeng tsa motho ka mong tšebetsong ea sebopeho sa frontostriatal (mohlala (Bertolia, Blasi et al. 2006; Drabant, Hariri et al. 2006; Yacubian, Sommer et al. 2007; Dreher, Kohn et al. 2009; Marena, Roelofs et al. 2010), hape le phapang e teng lithutong tsa boits'oaro tse amanang le boithuto ba bongoana ho kenyelletsa ho ba le bohlasoa, ho batla lintho tse ncha, litšobotsi tse mabifi, ts'ebetso ea motsamaisi, ts'ebetso ea ts'usumetso, ts'ebeliso e mpe ea lithethefatsi, le etiology ea lefu la neuropsychiatric joalo ka lefu la schizophrenia, ADHD le lefu la Parkinson ((Karayiorgou, Altemus et al. 1997; Eley, Lichtenstein et al. 2003; Enoke, Schuckit et al. 2003; Lee, Lahey et al. 2007), bakeng sa tlhahlobo bona (Nemoda, Szekely et al. 2011)). Likarolong tse latelang re hlahloba lithuto tse natefisang tsa li-polymorphism tse sebetsang liphatseng tsa lefutso tse susumetsang ho saena hoa DA. Re tla tšohla lithuto ka bobeli ba li-polymorphisms tsa li-single tsa nucleotide (SNP) le li-polymorphisms tse fapaneng tsa nucleotide. Re shebana ka kotloloho le ho nahana ka lipatlisiso tsa liphatsa tsa lefutso tse sebelisang mohopolo o sebetsang le oa sebopeho sa matla a matla a sefahleho (MRI le fMRI). E le bopaki ba litloaelano tsa boits'oaro le mefuta e amanang le DA li hlahlobisisitsoe ka botebo libakeng tse ling (mohlala (Nemoda, Szekely et al. 2011; Cormier, Muellner et al. 2013), re shebana feela le lipatlisiso tsa lipatlisiso tsa liphatsa tsa lefutso. Leha tlhahlobo ena e shebile nts'etsopele ea maemo a tloaelehileng, re akaretse lipatlisiso tsa mantlha tsa lipatlisiso tsa tsoelopele tsa lipono tsa liphatsa tsa lefutso ho tsa bobeli tsoelo-pele le mathata a nts'etsopele a amang DA (joalo ka schizophrenia le ADHD) ho Lethathamo 1.

DA Receptor gen (DRD1, DRD2, le DRD4)

Kabo ea bobeli ba D₁- (D₁ le D₅) le D₂ (D₂, D₃, D₄Li-receptors tse joalo ka bokong li fella ka ho tsitsisa ha mahlasipa a maqhubu a mothofatso, a fanang ka tšusumetso e matla ts'ebetsong le ho hokahaneng ha pele, ka letsoalo le leholo la li-receptors ho ba striatum. Ka bobeli D₁ le D₂Li-receptors tse kang G ke protheine e kopantsoeng, 'me e sebeletsa likarolo tse hanyetsanang, e ntseng e eketseha le ho thibela cyclic adenosine monophosphate ka ho latellana, ka tsela eo e thabisa kapa e sitisa ts'ebetso ea methapo. D₁ le D₂ Li-receptor ka hona li na le likarolo tse tlatsetsang. D₁ ho hlohlelletsa li-receptors ho lumella ho bolokoa ha tlhahisoleseling inthaneteng le ho tsitsisa linaha tse sebetsang, le D₂ receptor binding e kenella ho ntlafatseng ha tlhaiso-leseling ea tlhahisoleseling le ho lumella phetoho lipakeng tsa linaha tse sebetsang (Seamans, Durstewitz et al. 2001; Durstewitz le Seamans 2002; Li-Seamans le Yang 2004). D₁ li-receptors li ngata haholo tseleng e otlolohileng, li-neurons tse thabisang tsa GABAergic ha li araba boitšoaro bo ratoang, le D₂ tseleng e sa tobang, e thibelang li-neurons tsa GABAergic le ho fokotsa phello ea tsela e sa tsejoeng. Keketseho ho bobeli ba D₁ le D₂ li-receptors, joalo ka ha li bonoa lilemong tsa bocha ka hona li ka ba le phello e thabisang bokong, tse ka hlahisang keketseho ea boits'oaro bo its'epileng ho DA (joalo ka moputso le ho batla bocha).

Ho PFC, D₁ li-receptors li sebetsa liseleng tse glutamatergic pyramidal, ho eketsa ho thunya ho amanang le mosebetsi (Farde, Halldin et al. 1987; Goldman-Rakic 1990; Lidow, Goldman-Rakic et al. 1991). Ka nako e ts'oanang, D₁ ts'ebetso ea li-receptor mabapi le maqhubu a sebaka sa GABAergic (inhibitory) e thusa ho thibela litlatsetso tse sa utloahaleng tsa glutamatergic (Durstewitz, Baseket et al. 2000). Patlisiso e lekanyelitsoeng e lekotse li-polymorphisms tsa D₁mofuta oa mofuta oa (DRD1) mabapi le sebopeho sa boko / mosebetsi. Phuputso e 'ngoe e sebelisang batho ba baholo e bonts'a khokahano e fetotsoeng ea pele-pele ea parietal nakong ea mosebetsi oa memori o sebetsang ho bakuli ba schizophrenic ba khethiloeng bakeng sa DRD1 Dde I single nucleotide polymorphism e entsoeng ka sebaka sa A ho G ho 50 UTR (Tura, Turner et al. 2008). H heterozygotes, ba ekelitseng D₁ li-receptors, li bonts'itse ho hira ha DLPFC ho amanang le AA homozygotes, ea entseng likarolo tse ngata tsa boko. Liphumano tsena li tsamaellana le mosebetsi o mong o fanang ka tlhahiso ea hore sephetho sa taolo ea DA pele se etsa hore ho be le ts'ebetso e ntlafalitsoeng ea tlhokomeliso le ho saena pele ho pele (mohlala (Egan, Goldberg et al. 2001; Mattay, Goldberg et al. 2003)).

D₂ receptor, e hlalosoang haholo ho striatum e amanang le PFC, e fana ka tšusumetso e matla ho khokahano ea pele ho maqhubu ka ho thibela lits'oants'o tse nyarosang le tse thibelang mekhoa e thibelang (Cepeda le Levine 1998; Goto le Mohau 2005). D₂ li-receptors li na le li-isoforms tse peli tse ikhethileng, isoform e khutšoane (D₂-S) e sebetsa e le "presynaptic autoreceptor", e thibelang ho lokolloa ha DA, athe isoform e telele (D₂-L) e sebetsa haholo ho thibela cell cell ea posta (Centonze, Grande et al. 2003). E theohile D₂ Ts'ebetso ea autoreceptor e eketsa tokollo ea DA le batho ka bomong ba fokotsehileng D₂-S e bonts'a ho eketsa ho batla botjha le ho fumana moputso hape (Zald, Cowan et al. 2008; Pecina, Mickey et al. 2012). Liprothoriamo tse sebetsang liphatseng tsa lefutso tse etselitsoeng D₂ receptor (DRD2) e susumetsang tšibollo ea mRNA ea protheine, 'me qetellong ts'ebetso ea eona e fumanoe ho kenyeletsa, −141 C Ins / Del, Ser311Cys, Taq1A ANKK1, Taq1B, C957T, rs12364283, rs2283265 le rs1076560 (Zhang, Bertolia et al. 2007). Li-polymorphisms tse susumetsang D₂ ho tlama ho kenyelletsa mofuta wa DRD2 / ANNK1 TaqIA, e leng phepelo ea bolelele ba polymorphism e hlahisang mofuta oa Glu to Lys amino acid ho gene ea ANNK1 e haufi, le −141C Ins / Del SNP e sebakeng sa promotor sa mofuta oa DRD2. Talele ea TaqI A1 le Del allele li amahanngoa le ho fokotseha ha litlamo tsa D2 (Arinami, Gao et al. 1997; Noble 2000), leha thuto e le 'ngoe e bontša heterosis ea molek'hule ka polymorphism ea TaqIA, e nang le D e fokotsehileng₂ letsoalo ho heterozygotes ho amanang le homozygotes (Pohjalainen, Nagren et al. 1999). Kahoo, liqoso tsa Del le A1 li amahantsoe le ho eketseha ha meputso ho li-ventral striatum ka ho ba motho e moholo (Cohen, Young et al. 2005; Forbes, brown et al. 2009). Allele ea A1 e boetse e amahanngoa le ts'ebetso e fokotsehileng ea ts'ebetso ea pele le ho hokahanya lits'ebetsong tse ka pele nakong ea phetoho ea mosebetsi (Stelzel, Basten et al. 2010).

Ho fapana le lipatlisiso tsa batho ba baholo, lithuto tse 'maloa tse sebelisang barupeluoa feela ba lilemong tsa bocha li fumane hore alamo ea A1 e amana le ho fokotsa meputso maemong a morao (Stice le Dagher 2010) le dorsal (Stice, Spoor et al. 2008) striatum. Bocheng, ha ho ba le khatello e phahameng ea D₂ li-receptors, kamano lipakeng tsa ts'ebetso ea boko le D₂ ho fumaneha ha li-receptor ho ka tsamaisana le liphumano tsa pejana tse sebelisang ts'ebetso ea meriana e lebisang ho D₂ receptors (Kirsch, Reuter et al. 2006; van der Schaaf, van Schouwenburg et al. 2012), ho fana ka maikutlo a hore na lilemo li tla sebelisana le mofuta ofe ha li bapisoa le liteko tsa 'mele.

D₄ receptor ke D₂-joalo ka eona ebile e hlahisoa ho li-neurons tsa postynaptic striatal neurons le li-affliente tsa pele tsa synaptic corticostriatal glutamatergic. Bopaki bo fokolang bo fana ka maikutlo a hore D₄ li-receptors li nts'etsapele joalo ka D₂ li-receptors (tse nang le tlhoro ea bohloka bongoaneng 'me hamorao li theoha ho ba motho e moholo) (Tarazi, Tomasini et al. 1998). Mofuta (DRD4) dikhoutu tsa D₄ receptor e na le li-polymorphism tse 'maloa tse sebetsang, tseo 48-base pair VNTR ho exon 3 e hlahisang khafetsa tlhahlobo -ngong ea 7 kapa 4-frequency, e ithutoa khafetsa. Motsoako o pheta-pheta oa 7 o amahanngoa le thibelo e fokotsehileng ea postynaptic ea DA, ka lebaka la phokotso ea phokotso ea cAMP, e lebisang ho disinhibition ea li-neurons tsa striatal (Asghari, Sanyal et al. 1995; Seeger, Schloss et al. 2001), hape e amahantsoe le ho eketseha hape ha moputso ho amanang le moputso ho li-ventral striatum, tse amanang le allele ea 4Schoots le Van Tol 2003; Forbes, brown et al. 2009; Stice, Yokum et al. 2012). A SNP ho DRD4 gene (rs6277, −521 SNP) e hlahisa phokotseho ea 40% ho sengolo sa RNA bakeng sa mong ka T-allele ho C-allele (Okuyama, Ishiguro et al. 1999), leha thuto e 'ngoe e sa fumane phapang (Kereszturi, Kiraly et al. 2006). Ho fihla joale, phuputso e 'ngoe e nahanneng e tlaleha hore batho ka bomong ba sa boneng hantle bakeng sa pontšo ea C allele ba ekelitse morusu PFC / activation cingrate nakong ea ts'ebetso ea boholo ba meputso (Camara, Kramer et al. 2010). Ke DRD4 VNTR feela e ithutileng ho nts'etsopele ea baahi, ho kopanya 7-repeat allele e fokotseng botenya ba cortical ho PFC ea bana (Shaw, Gornick et al. 2007), ts'ebetso e matlafatsang ea ts'usumetso ho bana le ho bacha e le mookameli oa matšoenyeho ho bacha (Perez-Edgar, Hardee et al. 2013), le ho fokotsa ts'ebetso ho meputso ea lijo e le motsamaisi oa phaello ea boima ho bacha (Stice, Yokum et al. 2010). Litlamorao tsa polymorphism ena tšebetsong ea boko bocheng, ka hona e ka tšoana le liphetho tsa batho ba baholo.

Ka kopanelo, lithuto tsena li bonts'a hore mefuta e fapaneng ea tšebetso ea liphatsa tsa lefutso tsa DA e susumetsa tšebetso ea boko ba pele ho bana, bacha le batho ba baholo ka thoko. Leha ho le joalo, ha ho na lithuto tse fihlang ho fihlela joale tse ileng tsa hlahloba tšusumetso ea li-polymorphisms tsena ho ntlafatseng. Patlisiso ea hajoale e bontša hore D₁ le D₂ li-receptor densities li phahame haholo bongoaneng, ho fana ka maikutlo a hore letsoalo la receptor le phahame haholo lilemong tsa bocha tse amanang le ho ba motho e moholo. Ho latela mohlala o kentsoeng ka U, e eketsehile D₁ le D₂ ho fumaneha ha li-receptor ho ka etsa hore tlholisano e eketsehe lipakeng tsa tsela e otlolohileng le e sa tobang e ka eketsoang le ho feta lilemong tsa bocha tse nang le boteng bo phahameng ba ho amohela lintho tse fumanehang motheong oa motheo.

Mefuta ea DA ea inactivation (COMT, DAT1)

Mesebetsi ea Polymorphism ho COMT Gene

Catechol-O methyltransferase (COMT), enzyme ea catecholamine catabolism, e bohlokoa ho laola phetoho ea DA ho PFC moo batsamaisi ba DA ba haellang (Hong, Shu-Leong et al. 1998; Matsumoto, Weickert et al. 2003). Ka har'a mofuta oa COMT (COMT) ke mofuta o le mong oa nucleotide polymorphism (SNP) o hlahisang methionine (o ile a kopana) ho boleng (Seq) ho codon 158 (Tunbridge 2010). The TLTV allele e amahanngoa le ts'ebetso e phahameng ea enzymatic mme ka hona maemo a tlase a synaptic dopamine, athe a Tla kopana allele ho fella ka hore re ka etsa karolo e le 'ngoe ho tse tharo ea enzyme e fokolang mme ka lebaka leo, dopamine e phahameng haholo (Chen, Lipska et al. 2004). Heterozygotes e bonts'a maemo a mahareng a COMT ts'ebetso. Leha a hlahisitsoe hofihlela ho PFC, the COMT val158met polymorphism e boetse e amahanngoa le litlamorao tse theohelang mosebetsing oa Midbrain DA (Meyer-Lindenberg, Kohn et al. 2005).

The COMT val158met SNP e ithutile haholo molemong oa ts'ebetso ea pele-nakong ea ts'ebetso ea kelello (Egan, Goldberg et al. 2001; Horses, Volavka et al. 2002; Malhotra, Kestler et al. 2002; Goldberg, Egan et al. 2003; Mattay, Goldberg et al. 2003; Litaemane, Briand et al. 2004) ho kenyelletsa memori ea ho sebetsa, thibelo ea karabelo, ho feto-fetoha ha maemo le ts'ebetso ea moputso. Bopaki bo fana ka maikutlo a hore batho ba nang le o ile a kopana allele bontsa mosebetsi o mongata oa cortical (mohlala (Egan, Goldberg et al. 2001; Mattay, Goldberg et al. 2003; Meyer-Lindenberg, Kohn et al. 2005)) le keketseho e amanang le moputso ts'ebetsong ea ts'ebetso ea "striatal activation"Yacubian, Sommer et al. 2007; Dreher, Kohn et al. 2009) amanang le batho ba nang le Seq allele. Ntle le moo, maemo a DA a ntseng a eketseha a sebetsana le COMT val158met SNP e lumellanang le mohlala oa U oa ho beha o ile a kopana batho ba bonts'ang ts'ebetso ea cortical e fokotsehileng nakong ea mesebetsi ea taolo ea kelello Seq batho ba bonts'ang lintlafatso (Mattay, Goldberg et al. 2003; Apud, Mattay et al. 2007). Ho ipapisitse le bopaki bona, ho boleloa hore bacha, ba eketsehileng maemo a DA a amanang le batho ba baholo, ba ka latela mohlala o tšoanang le ts'ebetso ea COMT genotype e le lithuto tsa meriana ho batho ba baholo. Sena ke bacha ba nkileng o ile a kopana allele e ka feta litheko tse nepahetseng, tse ka lebisang ts'ebetsong e fokolang ea cortical, e amanang le Seq (Wahlstrom, Collins et al. 2010; Wahlstrom, White et al. 2010). Ho a khonahala hore liphapang tsa batho ka bomong li hlahisoa ka mokhoa o fapaneng e le ts'ebetso ea setho sa DA ho ntlafatso e thehiloeng ho genotype (mohlala Seq allele e ka fana ka monyetla o lekanyelitsoeng oa ts'ebetso ea kelello ho tloha nts'etsopele, ha maemo a DA a phahame ho feta ho batho ba baholo. Leha ho le joalo, lipatlisiso tse fokolang li lekotse tšusumetso ea COMT val158met polymorphism bokong ba bocha, 'me lithuto tsena tsa mantlha li tsoakane' me li hloka ho phetoa. Nakong ea ts'ebetso ea memori ea ho sebetsa ea pono ea batho ba pakeng tsa 6 le 20,Dumontheil et al. (2011), e bontšitse hore ts'ebetso libakeng tse ka pele le tsa parietali e eketsehang ho ntlafala ho batho ka bomong ba homozygous bakeng sa Seq allele, empa ha ho joalo o ile a kopana bajari, fana ka maikutlo a lietsahala nts'etsopele ea ts'ebeliso ea kelello ho batho ba nang le Seq allele. Val/Seq homozygotes e boetse e bontšitse ho fokola hanyane ka hanyane molemong oa ntlafatso holima nts'etsopele ea kamora parietal cortex, mohlomong e bonts'a ho poma butle le ho se sebetse hantle ha ts'ebetso ea cortical. COMT litlamorao bocha bo fumanoe hape lithutong tsa khokahano ea sebopeho le tšebetso, le bacha ba nang le Seq allele show o ile a kopana (Thomason, Waugh et al. 2009; Thomason, Dougherty et al. 2010), leha lithuto tsena li ne li sa ntlafatsoe ntle le lihlopha tsa batho ba baholo. Qetellong, phuputso e le 'ngoe e tlohang bophelo bohle (ho tloha lilemong tsa 6-84) e bonts'itse molumo oa litaba oa bohlooho o theohileng ho ventral PFC ho met / Kopana batho ka bomong ba amanang le boleng / boleng empa ha ho lilemo ka lipuisano tsa genotype (Williams, Gatt et al. 2008).

Mesebetsi ea Polymorphism ho DAT1 Gene

Sephethephethe sa DA (DAT) se hlahisoa haholo lithutong mme se ikarabella bakeng sa ho pheta-pheta ha DA, ho hlakola DA ho tsoa sebakeng se kantle ho naha kamora ho lokolloa (Jaber, Bloch et al. 1998). The polymorphism ea VNTR ho gene e khoutang bakeng sa DAT (DAT1 or SLC6A3) e baka lits'oantso lipakeng tsa 3 le 13 tse pheta-phetoang tsa tatellano ea li-40-base tse latellanang sebakeng sa eona sa 3 'untranslated (Vandenbergh, Persico et al. 1992) ha li-coding sebakeng se fapaneng ha li fumanehe seoelo. Sekhahla sa marang-rang se kopantseng sa marang-rang bakeng sa li-allels tse tloaelehileng tse pheta-phetoang (9-repe and 10-uphinda) se fokola haholo bakeng sa alamo ea phepelo ea 9 ho feta polelo ea phetisetso ea 10, e hokahanyang 9-e phetang allele ka polelo e fokotsoeng ea DAT le synaptic e kholo ea striatal DA (Fuke, Suo et al. 2001; Mill, Asherson et al. 2002; VanNess, Owens et al. 2005), leha lithuto tse ling li hlahisitse se fapaneng (Mill, Asherson et al. 2002; van de Giessen, de Win et al. 2009). Polelo ea tlase ea DAT e fokotsa ho hlakoloa ha DA ka tsela eo ho eketsang maemo a DA (Cagniard, Balsame et al. 2006; Cagniard, Beeler et al. 2006). Patlisiso ea FMRI e kopanya alamo ea 9R khafetsa le ho eketseha ha meputso ho striatum (Yacubian, Sommer et al. 2007; Dreher, Kohn et al. 2009; Forbes, brown et al. 2009). Le ha DAT e hlalosoa haholo-holo ka har'a striatum, bopaki bo amahanya allele ea 9-pheta-pheta le ts'ebetso e eketsehang ea ventral ea striatal le dorsomedial PFC nakong ea ts'ebetso ea memori ea ho ntlafatsa le ho chencha mesebetsi (Marena, Roelofs et al. 2010; Garcia-Garcia, Barcelo et al. 2010), le ho eketsa ts'ebetso ea PFC nakong ea taolo ea thibelo, e ileng ea hlalosoa e le ts'ehetso ea taolo e ntlafalitsoeng ea thibelo (Congdon, Lesch et al. 2008; Congdon, Constable et al. 2009). Lithuto tsa nts'etsopele li sebelisa DAT1 polymorphism e fana ka maikutlo a hore ka tloaelo bacha ba ntseng ba hola ba nang le 9-repeat allele ba bonts'itse ts'ebetso ea libaka tse etellang pele le tsa maemo nakong ea taolo ea thibelo (Braet, Johnson et al. 2011), le moputso oa bolepi esale pele (Paloyelis, Mehta et al. 2012). Liphetho tsena li fana ka maikutlo a hore mofuta oa genotype oa DAT1 o ka ba le tšusumetso molemong oa bongoaneng - 'moho o pheta-phetang oa 9 o bakang ho fokotseha ha maikutlo le boiphetetso bo botle ho feta ho ba motho e moholo. Ho ka etsahala hore nakong ea bocha, ha maemo a DA a fetelletseng a le teng, batho ka bomong ba tsamaeang le 9-repeat allele ba na le ts'ebetso e kholo ea ho fumaneha ha synaptic DA, e ka bang le litlamorao tse fapaneng le ts'ebetso ea boko ho feta ho ba motho e moholo.

Litšebelisano tsa Gene-Gene

Patlisiso ea liphatsa tsa lefutso e tsepamisitse maikutlo ho li-polymorphisms tse sa sebetseng lijini tsa mokhethoa. Ho rarahana ha sistimi ea DA, litekanyetso tse fapaneng tsa phetoho ea likarolo tse fapaneng tsa sistimi, tšebelisano ea likarolo tse fapaneng tsa sisteme, le tšebelisano ea tsamaiso ea DA ka mekhoa e meng ea boko, e fana ka maikutlo a hore liphetho tsa liphatsa tsa lefutso ha li ikemele kapa dichotomous. Bafuputsi ba sa tsoa qala ho ithuta litšebelisano lipakeng tsa litlamorao tsa mefuta e mengata. Ha ho fanoa ka bopaki ba hore likarolo tse fapaneng tsa tsamaiso ea DA lia phahamisoa kapa li fetotsoe lilemong tsa bocha le hore litlamorao tsa lefutso le le leng li ka hlaha ka tsela e fapaneng bokong ba bocha, ho ka etsahala hape hore litšebelisano tsa liphatsa tsa lefutso li fapane bokong ba bocha ho feta bokong ba batho ba baholo. Ho nka boholo ba phello e tšoanang ea polymorphism ka 'ngoe, lithuto tsa pejana li bontšitse litlamorao ho ts'ebetso ea boko e le ts'ebetso ea tšebelisano lipakeng tsa liphatsa tsa lefutso (Bertolia, Blasi et al. 2006; Yacubian, Sommer et al. 2007; Bertolia, Di et al. 2008; Dreher, Kohn et al. 2009). Mohlala, lithuto tsa pejana li bontšitse litlamorao tsa COMT val158met SNP le DAT1 3'VNTR nakong ea tebello ea moputso le mehato ea sephetho sa ts'ebetso ea moputso ho PFC le striatum, ho tlaleha ts'ebetso e eketsehileng e amanang le genotypes e entseng hore DA e fumanehe (Yacubian, Sommer et al. 2007; Dreher, Kohn et al. 2009). Leha ho le joalo, ka lebaka la mehlala e sa lekanyetsoang ea lipampiri, lithuto tsena li hlahlobisitse li-polymorphism habeli feela joaloka hanngoe. Haufinyane tjena, bafuputsi ba fumane tšusumetso ea liphatsa tse 'maloa tsa DA tšebetsong ea boko nakong ea ts'ebetso ea meputso ba sebelisa "lintlha tse ngata tsa sehlopha" (Plomin, Haworth et al. 2009), ho abela morupeluoa e mong le e mong lintlha tse kenyelletsoang ho ipapisitse le maemo a lekanang le a ho supa ha DA. Morero o ka morao ho mokhoa ona ke hore ho kopanya liphatsa tsa lefutso tse sebetsang hantle ka lintlha tse fumanehang tsa boemo bo holimo ho ka hlalosa ho fapana ho feta ha loci e le 'ngoe e ka bang le litlamorao tse seng tsa bohlokoa. Patlisiso ena e kopantseng genTypX, DAT1, le DA receptor genotypes e bonts'itse ts'ebetso ea "portral striatal reacition" e le mosebetsi oa ho eketsa ho supa ha DA ho ba motho e moholo.Nikolova, Ferrell et al. 2011), le ho qaqea le ho ts'oara lilemong tsa bocha.Stice, Yokum et al. 2012) nakong ea kamohelo ea meputso ea chelete. Ho pheta liphumano tsena le tlhahlobo ea tšebelisano ea liphatsa tsa lefutso mabapi le nts'etsopele hoa hlokahala hore re utloisise hantle litlamorao tsa genotype.

Mehopolo le Litataiso tsa Bokamoso bakeng sa lithuto tsa Imaging Genetics

Motheo oa liphatsa tsa lefutso o rarahaneng o ka bakoa ke ho fapana ho fapaneng liphatseng tsa liphatsa tsa lefutso le tšebelisano ea bona le ba bang le tikoloho. Bongata ba lipatlisiso tsa liphatsa tsa lefutso bo lebisitse tlhokomelo likamanong tse lipakeng tsa ts'ebetso ea boko le tšebetso e le 'ngoe kapa tse' maloa tsa liphatsa tsa lefutso. Ntle le moo, hobane lithuto tsa neuroimaging li hloka lihlopha tse arolelanoang ka mokhoa o tšoanang, lipatlisiso tsa liphatsa tsa lefutso li shebane haholo le litlatsetso tse phahameng tse atisoeng hantle ka har'a baahi ka hona li ba le litlamorao tse ntle kapa tse sa nke lehlakore. Bothata ba mokhoa ona ke hore mefuta ena e hlalosa karolo e fokolang feela ea phapang ea mathata a tebileng kapa litšobotsi tse ling. Ka hona, sepheo sa mantlha sa ho nahana ka liphatsa tsa lefutso ha se ho fumana lihokela tsa lefutso, empa ke ho utloisisa hofetisisa moko-taba oa boitšoaro bo rarahaneng.

Kaha li-polymorphism tsa lefutso tse le 'ngoe li na le litlamorao tse nyane ho boits'oaro bo fapaneng le bo boholo ba boithuto, boithuto ba tšusumetso ea mefuta e fapaneng ea ts'ebetso ea ts'ebetso ea boko bo hloka kutloelo-bohloko e matla le ts'epahalo ea mehato e fumanoeng. Lithuto tsa genetics tse entsoeng li lokela ho sebelisa litekanyetso tse hlalositsoeng hantle le ka mokhoa o hlakileng (ke hore, mesebetsi ea fMRI e sebelisitsoeng ka ts'epo le ka matla e ka etsa lits'ebetso tsa ts'ebetso ea boko le ho bonts'a phapano ho barupeluoa. fMRI ke e 'ngoe ea mekhoa e tloahelehileng ka ho fetisisa ea ho lekanya ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea sepakapaka le ea nakoana, empa ho latela hore ke tekanyo e sa tobang ea ts'ebetso ea boko, e bonts'ang phetoho e amanang le paradigm ea ts'ebeliso ea metabolic (Logothetis, Pauls et al. 2001), tlhaloso ea liphetho tsa liphatsa tsa lefutso e lekanyelitsoe. Kahoo, ho kopanya mekhoa ea multimodal e lekanyang ts'ebetso ea sebopeho le sebopeho maemong a fapaneng a liqeto tsa sepakapaka le tsa nakoana le ho theha mehato e lekaneng ea maemo a tikoloho ho ka ba molemo molemong oa ho utloisisa liphetho tsa liphatsa tsa lefutso tšebetsong ea boko (Bigos le Hariri 2007; Fisher, Munoz et al. 2008; Nemoda, Szekely et al. 2011). Patlisiso ea liphatsa tsa lefutso e tla boela e rue molemo mosebetsing oa ho fetolela, ho ithuta tšusumetso ea liphatsa tsa lefutso ho batho ka bobeli le mehlala ea liphoofolo tse fetotsoeng liphatsa tsa lefutso ka ho sebelisa mekhoa e ts'oanang ea boits'oaro / neurofunctional phenotypes (Casey, Soliman et al. 2010). Leha ho na le meeli ea ho fetolela boits'oaro ba batho ho liphoofolo, boithuto bo sebelisang liphatsa tsa lefutso tse fetotsoeng liphatsa tsa lefutso tsa mofuta oa bohlokoa oa DA, ho kenyeletsoa COMT 'me DA mefuta ea li-receptor e bontšitse litlamorao tse tšoanang tsa kelello le boits'oaro bo tšoanang le ba batho (bakeng sa tlhahlobo bona (Casey, Soliman et al. 2010)). Kahoo, ho ka etsahala hore liphetho tsa liphatsa tsa lefutso bokong le tsona li ka bonts'a mefuta e fapaneng ea mefuta eohle. Ntle le moo, mefuta ea liphoofolo e tsoetseng pele e na le monyetla oa ho phela nako e khuts'oane le taolo e matla ea tikoloho.

Mokhoa o mong oa ho ntlafatsa ho ts'epahala lipatlisisong tsa ho nahana ka tšebeliso ke ho sebelisa mehlala e mehlala e fanang ka matla a ho fumana litlamorao tse nyane ho isa ho tse mahareng. Litlaleho tsa pele li boletse hore kamano ea ts'ebetso ea boko ho genotype e kanna ea lumella hore litlamorao tsa gene li bonoe ho barupeluoa ba fokolang ho feta lithuto tse tloaelehileng tsa boits'oaro. Ka mohlala,Munafo et al. (2008) o entse tlhahlobo ea meta ea lithuto tse tlalehileng litloaelano lipakeng tsa polanor ea VNTR ho genot transporter gene (5-HTTLPR) le ts'ebetso ea amygdala mme o khothalelitse hore tlhahlobo ea liphatsa tsa lefutso e tla hloka sampole e felletseng ea barupeluoa ba 70 ho fihlella matla a .8 bakeng sa matla a alpha a .05. Ho nka karolelano ea likarolo tse ling, sena se ka fella ka hore ho be le sehlopha se ka bang 30-35 ka sehlopha ka seng. Ka mokhoa o ts'oanang, ba bang ba khothalelitse hore mehlala ea sampole ea lithuto tse fetang 25 sehlopheng ka seng li hlokahala bakeng sa lithuto tse akaretsang tsa FMRI e le hore ho be le ts'episo e lekaneng (Thirion, Pinel et al. 2007). Meta -ens e lekola hore na boholo ba lipatlisiso tsa lipatlisiso tsa liphatsa tsa lefutso tse fetileng le boholo ba mehlala e loketseng bakeng sa bokamoso bo netefalitsoe ke lithuto tsa polymorphisms tsa DA-gene (Munafo, Bowes et al. 2005; Barnett, Scoriels et al. 2008). Leha ho le joalo, ho bohlokoa hape ho hopola hore tlhahlobo ea meta hangata e na le khethollo, hobane lithuto tse fumanoeng li sa fumanehe hangata li sa phatlalatsoe. Ho ka etsahala hore boholo ba sampole bo tla tlameha ho eketsoa e le hore bo pheta liphetho tse fetileng le ho hlahisa liteko tse nepahetseng tsa boholo ba phello ea li-polymorphisms tse fapaneng.

Kakaretso / Liphetho

Ho sitoa ho laola boits'oaro khafetsa le ho eketseha ha maikutlo ho phehella bocheng, ho lebisang keketseho ea boits'oaro bo nkang boits'oaro. Leha litloaelo tsena li ka tsamaisoa ke lintho tseo e seng tsa tlhaho, re tlameha ho supa mekhoa e tataisang nts'etsopele ea tlhaho hore re utloisise litlamorao tsa eona. Bopaki bo supa kholisong e tsoetseng pele ea lits'ebetso tsa boko ho kenyeletsa le PFC le boemo bo phetseng nakong eohle ea bongoaneng le bohlankana. Lits'ebetso tsena li ts'ehetsa boits'oaro bo susumetsoang ka tšusumetso mme li ka kenya letsoho tlokotsing ea ho hlaha ha psychopathology. PFC le striatum e ts'ehetsa boits'oaro bo susumetsang bo tsamaisanang le likamano tsa bona tse ikhethileng, tse fetotsoeng ke tšebetso ea DA. Ho fumaneha ha DA le ho supa ho eketsoa nakong ea bohlankana 'me ho ka khothaletsa ho batla bocha ka mokhoa o ikamahantseng le maemo ho fumana litsebo tse tšehetsang pholo ea batho ba baholo. Leha ho le joalo, maemo a DA a feteletseng lithutong tsa botsitso le PFC lilemong tsa bocha a ka etsa hore batho ba be le maikutlo a eketsehileng a ho fumana moputso hammoho le taolo e mpe ea boitšoaro bo tsosang takatso, ka ho etsa joalo ba eketsa tlokotsi bakeng sa boits'oaro bo bobe. Leha maemo a akaretsang a phetoho ea maturational ho DA, ho na le phapang e kholo mekhoeng ea bocha, e hlahisang lipotso ka mekhoa ea tlhaho e entseng tlholeho ena, moeli oa lipatlisiso o sa ntseng o lokela ho hlahlojoa. Polelo ea Gene ke e 'ngoe ea mehloli ea mantlha ea ho fapana, ho sebetsa ka methapo ea methapo ea methapo le methapo ho hlahisa liketsahalo tse rarahaneng tse bonahatsang ts'ebetsong ea boits'oaro le ho se sebetse hantle. Boholo ba lipatlisiso tsa liphatsa tsa lefutso ho tla fihlela kajeno bo shebile liphapang lipakeng tsa genotypes ka botsofaling kapa lihlopheng tse arohaneng, leha ho na le bopaki bo ntseng bo hola ba hore lits'ebetso tsa boko li tsoela pele ho hlophisoa bocha nakong ea bophelo le hore liphetho tsa liphatsa tsa lefutso li ka bonahala ka mekhahlelo e fapaneng. Ho khetholla mofuta oa li-trajectories tsena tse fetohang ho tla ba molemo ho ho feta thutong ea kelello ho feta ho lekanya phapang ea methati ka har'a lihlopha tsa lilemo. Patlisiso e fokolang ea ho nahana ka liphatsa tsa lefutso (ke hore (Dumontheil, Roggeman et al. 2011) e khothalelitse hore tataiso ea liphetho tsa liphatsa tsa lefutso ts'ebetsong ea boko e ka fetoha holim 'a ntlafatso ha lits'ebetso tsa boko li hlophisa bocha. Mosebetsi oa lipono tsa bokamoso bo tlang o lokela ho ithuta liphetho tsa liphatsa tsa lefutso ho ntlafatso (le nako ea bophelo), ka mokhoa o hlakileng. Sena se ka ba le litlamorao tse matla bakeng sa ho utloisisa ts'ebetso ea kotsi ea kotsi ea bongoana nakong ea bocha, ho lemoha ho ba kotsing ea ho hlaha ha psychopathology, ho nts'etsapele kalafo e tobileng ea lilemo, le ho khetholla litsela tse lebisang liphellong tsa botsofaling.

Lintlha-khōlō Tsa

Litsamaiso tse ka pele tse nang le boitšoaro bo susumetsang ha li lilemong tsa bocha
Sisteme ea dopamine e hlophisoa bocha bocha ho feta bohlankana
Matšoao a ho etsa liphatsa tsa lefutso a ka sebelisoa ho ithuta motheo oa tlhaho le phapang e teng tšebetsong ea boko
Ho kenyelletsa liphatsa tsa lefutso ho ka ba molemo ho ithuta tšusumetso ea dopamine bohlankaneng

Mongolo o botlaaseng ba leqephe

Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.

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