Faʻataʻotoga Faʻaleagaina ma le Faʻalavelave, mai le Mamanu Manuʻa i Endophenotypes: O le Toe Fuataina o Tala (2010)

Neuropsychopharmacology. Feb 2010; 35(3): 591–604.

Lolomi i luga ole laiga Nov 25, 2009. doi:  10.1038 / npp.2009.185

PMCID: PMC3055606

O lenei tusiga ua taua e isi tusiga i le PMC.

lē faʻatino

Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive–compulsive disorder (OCD), obsessive–compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field.

uputatala: fa'amalosi, fa'amalosi, endophenotypes, serotonin, dopamine

FAATOMUAGA

A'o gaioi ma uiga fa'amalosi pe fa'amalosi e mafai ona saofagā patino i le fatufatua'i ma le tumau ma e masani lava i le fetuutuuna'i o amio a le tagata, o le fa'aletonu o le fa'atonutonuina o le fa'alavelave po'o le fa'amalosi e ono feso'ota'i ma a'afiaga leaga ma e iai sona aoga i le atina'eina o le mafaufau. O le impulsivity e mafai ona faauigaina o le 'se faʻaalia i le vave, le fuafuaina o tali i totonu poʻo fafo faʻaosofia ma le faʻaitiitia o le manatu i taunuuga le lelei o nei tali i le tagata faʻamalosi poʻo isi' (Chamberlain ma Sahakian, 2007; Potenza, 2007b). I se fa'atusatusaga, o le fa'amalosi e fa'atusalia ai le fa'aalia o le fa'atinoina o ni gaioiga fa'aleaogaina i se faiga masani po'o le fa'ata'ita'iga e puipuia ai a'afiaga leaga, e o'o atu ai i le fa'aletonu o galuega (WHO, 1992; Hollander ma Cohen, 1996; Chamberlain 'ua al, 2006b). These two constructs may be viewed as diametrically opposed, or alternatively, as similar, in that each implies a dysfunction of impulse control (Stein ma Hollander, 1995). O mea ta'itasi e ono a'afia ai suiga i totonu o le tele o fa'agasologa o neural, e aofia ai le fa'alogo, fa'aaliga, ma le fa'amaopoopoina o tali fa'amalosi po'o le mafaufau.

O faʻataʻitaʻiga Neuroanatomical o loʻo faʻaalia ai le i ai o le 'faʻamalosi' ma le 'impulsive' cortico-striatal circuits eseese ae fesoʻotaʻi, faʻavasegaina e neurotransmitters (Robbins, 2007; Brewer ma Potenza, 2008). In the compulsive circuit, a striatal component (caudate nucleus) may drive compulsive behaviors and a prefrontal component (orbitofrontal cortex, OFC) may exert inhibitory control over them. Similarly, in the impulsive circuit, a striatal component (ventral striatum/nucleus accumbens shell) may drive impulsive behaviors and a prefrontal component (anterior cingulate/ventromedial prefrontal cortex, VMPFC) may exert inhibitory control. Thus, in this model, there exist at least two striatal neural circuitries (one compulsive and one impulsive) that drive these behaviors, and two corresponding prefrontal circuitries that restrain these behaviors. Hyperactivity within the striatal components or abnormalities (presumably hypoactivity) in the prefrontal components may thus result in an increased automatic tendency for executing impulsive or compulsive behaviors, depending on the sub-component afflicted. Other possible abnormalities within cortico-striatal circuits (eg related to diminished striatal activation to rewards) may also contribute to seemingly impulsive or compulsive behaviors during engagement in reward-related behaviors. These pathologies can be explored using tasks of cognitive performance that tap into these specific functions and/or by functional imaging studies that measure activity within these neural systems. Overlap between these functional systems, so that what starts out as a problem in the impulsive circuit may end up as a problem in the compulsive circuit and vice versa, may contribute toward the impulsive–compulsive diathesis model proposed by Hollander ma Wong (1995) (Brewer ma Potenza, 2008).

O lo'o i ai ni fa'aletonu o le mafaufau lea e foliga mai ai amioga fa'atopetope ma fa'amalosi, a itiiti mai i fa'afitauli fa'apitoa, e avea ma mea e sili ona fa'aleagaina. O nei fa'afitauli e masani ona fa'atupuina, o lo'o fa'avasegaina i le tele o vaega fa'ama'i o le DSM-IV-TR (APA), e aofia ai ma'i fa'apitoa-fa'amalosi (OCD), fa'aletonu o le tino, ma'i o Tourette, trichotillomania, fa'ama'i fa'aletonu le mafaufau (ADHD), taaloga faitupe, ma vaisu (SA). O le mea e fiafia i ai, o le autism o loʻo faʻaalia i amioga faʻamalosi e lua (e pei o se tasi o vaega autu e tolu) faʻapea foʻi ma amioga faʻafefe (e pei o se tasi o faʻailoga e fesoʻotaʻi).

I le masani ai, o fa'alavelave fa'amalosi ma fa'alavelave e va'aia i pito fa'afeagai o se itu e tasi; o le mea muamua e faaosofia e le manao e aloese mai le afaina ae o le mea mulimuli e ala i amioga saili taui. Ae ui i lea, o faʻamaoniga faʻamaonia mai suʻesuʻega faʻaliliuga o loʻo taʻu mai ai o le fefaʻasoaaʻi faʻatasi i le faʻaleagaina o amioga, masalo e mafua mai i le toilalo i le 'pito i lalo' le pulea o le cortical circuits fronto-striatal circuits, poʻo se isi mea mai le soona gaioi i totonu o striatal circuitry, e mafai ona faʻavaeina faʻalavelave faʻalavelave ma faʻalavelave faʻalavelave. . O le mea lea, nai lo le faʻafeagai polar, o le faʻamalosi ma le impulsivity e mafai ona faʻatusalia ai mea taua faʻapitoa e tofu sao i tulaga eseese i nei faʻafitauli.

O le tele o nei faʻafitauli e masani ona tupu faʻatasi, pe i totonu o le tagata lava e tasi poʻo le faʻapipiʻiina i totonu o aiga, e faʻaalia ai le avanoa e fefaʻasoaaʻi pathophysiological mechanisms (Loia 'ua al, 2007b). E le gata i lea, o loʻo i ai faʻamaoniga o le faʻaogaina o togafitiga-tali i nisi o faʻafitauli. OCD e masani ona tali atu i le serotonin reuptake inhibitors (SRIs; clomipramine ma SRIs filifilia, SSRIs) ma SSRIs faʻatasi ma vailaʻau antipsychotic (Finepa 'ua al, 2005). Antipsychotics o loʻo faʻatusalia togafitiga muamua mo Tourette's syndrome, ma o le mea lea, e manaia ai le latou tuʻufaʻatasia ma SSRI o loʻo faʻaalia ai le sili atu le aoga i le OCD e fesoʻotaʻi ma le tic.Bloch 'ua al, 2006). O faʻamalosi e fesoʻotaʻi ma faʻamaʻi autistic e mafai foi ona tali atu i le SSRI maualalo ma le antipsychotics (Kolevzon 'ua al, 2006). Trichotillomania e mafai ona tali atu i SRIs ma antipsychotics, e ui o le faʻamaoniga i suʻesuʻega faʻatonutonu e manaʻomia (Chamberlain 'ua al, 2007d). O le ADHD, i le isi itu, e tali atu i inhibitors reuptake noradrenergic faʻapea foʻi ma vailaʻau dopaminergic (faʻataʻitaʻiga amphetamine), taʻaloga faʻamaʻi, ma faʻafitauli o le faʻaaogaina o vailaʻau e mafai foi ona faʻasoa se tali faʻafomaʻi i tagata tetee opiate (Fale faʻatau 'ua al, 2008).

Fa'ailoaina o le mafua'aga ma le a'afiaga, fa'aaoga na'o fa'amatalaga a le falema'i, e ono fa'afememea'i ona o le tele o fa'ailoga e feso'ota'i ai vaega o lo'o tutupu i totonu o fa'afitauli faigata o le mafaufau. O le mea moni, o lenei vaega o faʻafitauli e faʻaalia i le tele o le phenotypic heterogeneity ma faʻapipiʻi. Mo se faʻataʻitaʻiga, o nisi o mataupu e iai le autism e leai ni faʻamaoniga o le ADHD poʻo le faʻamalosi, o isi e faʻaalia le ADHD, o isi OCD, ae o isi o loʻo faʻaalia amioga faʻasolosolo e le pei o le OCD. O su'esu'ega fa'aliliuga e su'esu'e mai le va'aiga o faiga fa'avae, ma e ono mafai ai ona fa'ailoa sao o neural e fa'aosoina ai vaega fa'apitoa ole fa'aletonu ole mafaufau. Endophenotypes e mafai ona fuaina, fa'aleaganu'u uiga, fa'ata'ita'iga o lo'o tu i se tulaga vaeluagalemu i le va o le fa'ama'i phenotype ma le fa'ama'i-a'afia genotype. O ia 'fa'ata'ita'iga vavalo' o lo'o fa'apea e sili atu ona feso'ota'i ma le fa'alavelave fa'aletagata mo fa'afitauli o le mafaufau polygenic nai lo amioga fa'aalia ile falema'i (Gottesman ma Gould, 2003; Chamberlain ma Menzies, 2009). Endophenotypic faʻataʻitaʻiga o faʻamaʻi atonu e fesoasoani mo le faʻamalamalamaina o lo tatou malamalama i le faʻavae faʻavae o faʻafitauli faigata o le faiʻai ma faʻapea mo le faʻamalamalamaina o le faʻavasegaina o suʻesuʻega. I le taimi nei, o faʻalavelave faʻalavelave ma faʻalavelave faʻalavelave o loʻo faʻavasegaina i totonu o vaega eseese DSM-IV. A'o iloiloina e le American Psychiatric Association le toe fa'avasegaina o le OCD, fa'alavelave popole ma fa'alavelave fa'alavelave (ICDs) mo le toe iloiloga o le DSM-V (Finepa 'ua al, 2007a), ua o'o i le taimi e toe iloilo ai faiga fa'avae o nei fa'afitauli.

I lenei iloiloga faʻamatalaga, matou te mafaufau i le neural ma neuropsychological mechanisms e fesoʻotaʻi ma gaioiga faʻamalosi ma faʻamalosi ma a latou sao i faʻataʻitaʻiga o faʻalavelave faʻalavelave ma faʻalavelave. Matou te tuʻufaʻatasia suʻesuʻega talafeagai mai le tele o faʻamatalaga faʻaopoopo, e aofia ai suʻesuʻega faʻaliliuga talu ai nei ma e leʻi faʻasalalauina, suʻesuʻega endophenotypic tagata, ma faʻataʻitaʻiga togafitiga, e aofia ai galuega faifaipea mai a tatou lava iunite i Peretania ma le Iunaite Setete. O la matou suʻesuʻega e taulaʻi i le suʻesuʻeina o le tutusa, faʻapitoa faʻapitoa, cortico-striatal neural projections mai le OFC i le medial striatum (caudate nucleus), faʻatulagaina e faʻamalosi ai le gaioiga, ma mai le cingulate / VMPFC i luma i le ventral striatum (nucleus accumbens shell), fuafuaina. e fa'aoso le fa'alavelave, ma le felafolafoa'i i le va oi latou (Robbins, 2007; Brewer ma Potenza, 2008) (Ata 1).

Ata 1  

Compulsivity ma le impulsivity: sui neural faiga e saofagā i le mafaufau faaletonu. E ui lava o faʻalavelave faʻalavelave ma faʻalavelave faʻalavelave e mafai ona manatu o ni faʻafeagai polar, o le toilalo i le faʻaogaina o le cortical controls fronto-striatal neural circuits e mafai ona faʻavaeina uma. ...

I le faʻaaogaina o nei faʻamatalaga, matou te taumafai e faʻatalanoaina fesili autu e aofia ai: (i) o le a le tele o le faʻamalosia ma le le mautonu e saofagā i nei faʻafitauli, (ii) o le a le tele latou te faʻalagolago i le fefaʻasoaaʻi poʻo le vavae ese o neural circuitry, (iii) o le a le mediating monoaminergic faiga, (iv) pe i ai ni vaega o amioga fa'amalosi po'o le fa'amalosi e iai so'o se aoga fa'apitoa e feso'ota'i ma togafitiga fa'afoma'i, ma (v) pe iai se fa'ata'ita'iga tu'ufa'atasi e fa'aogaina atoatoa nei fa'amaumauga? Matou te taulaʻi atu foʻi i faʻamoemoega mo suʻesuʻega i le lumanaʻi matou te talitonu e sili atu ona manuia le alualu i luma o le fanua.

FA'ATA'ITA'IGA FA'ALILIUINA O LE FA'ASA'O'OGA MA LE FA'ASAO

O suʻega neurocognitive faʻamoemoe e mafai ona faʻamalamalamaina le auala e faʻaogaina ai e le vailaʻau faʻamaʻi a latou aʻafiaga aoga ma mo le vavalo o taunuʻuga o falemaʻi (Chamberlain 'ua al, 2007e; Brewer ma Potenza, 2008). O le faʻaaogaina o galuega maʻaleʻale ma le faʻapitoa o le neurocognitive, o le impulsivity ma le faʻamalosia e mafai ona vaevaeina i ni vaega faʻapitoa neurobiologically eseese ma faʻatusatusa i totonu o tagata soifua ma manu faʻataʻitaʻi, faʻatasi ai ma vaega faʻapitoa e aʻafia ai vaega e le mafai ona faʻaogaina o le fronto-striatal circuitry (Winstanley 'ua al, 2006).

O faʻamaumauga e faʻaalia ai o le impulsivity e mafai ona maua mai i se tasi pe sili atu faʻapitoa neurocognitive masini. O nei mea e aofia ai le faʻaalia o le faʻamaʻiina o le afi muamua, fuaina i le taimi e faʻaalia ai le faailo (SSRT) galuega (Aron ma Poldrack, 2005), fa'atalanoaina i tagata soifua e ala i le fa'agaoioia o le pito i lalo taumatau pito i luma (RIF) cortex ma ona so'otaga fa'asolo (subcortical connections).Rubia 'ua al, 2003) ma fa'aogaina i isumu ma tagata soifua e le norepinephrine (Chamberlain 'ua al, 2006c, 2007a; Cottrell 'ua al, 2008), ae le o le serotonin (Clark 'ua al, 2005; Chamberlain 'ua al, 2006d). O le isi itu e aofia ai le faigata i le tolopoina o le faamalieina ma le filifilia vave o taui laiti e ui lava i taunuuga le lelei mo se taimi umi, e fuaina i le faia o faaiuga po o taaloga faitupe e pei o le Cambridge Gambling Task (CANTAB), faʻatalanoaina e ala ile orbitofrontal ma fesoʻotaʻiga cortical circuitry i lalo ole serotonergic modulation (Rogers 'ua al, 1999b), ma le fa'asologa o le subcortical i lalo o le pule fa'atasi dopaminergic ma serotonergic (Winstanley 'ua al, 2006). O le vaega lona tolu e aofia ai le le lava o faʻataʻitaʻiga faʻamatalaga aʻo leʻi faia se filifiliga, fuaina i faʻamatalaga faʻataʻitaʻiga galuega e pei o le Reflection Task (Clark 'ua al, 2006) ma atonu o le 5-Choice Serial Reaction Time Task (5-CSRTT) (Robbins, 2002) (Laulau 1).

Laulau 1  

Vaevaeina o le Impulsivity ma le Compulsivity e tusa ai ma Neurocognitive Domains: Galuega ma Neural/Neurochemical Correlates.

O le fa'amalosia, masalo, e le malamalama lelei. Fa'aletonu i (i) a'oa'oga feliua'i (fa'atusa o le mafai ona fetuutuuna'i amioga pe a mae'a fa'amatalaga le lelei, fuaina i galuega fa'aa'oa'oga fa'afesuia'i fa'apitoa) ma le (ii) fa'aopoopoina (ED) le fa'amanino o le seti, e mafai ona tofu sao i lona fa'aaliga (Aso 'ua al, 1996; Clarke 'ua al, 2005). O fa'aletonu uma e lua o lo'o fa'atusalia ai le fa'aletonu o le mafaufau, ae e foliga mai o lo'o fa'amalieina e ala eseese neural circuitry.

O le toe fa'afo'isia a'oa'oga e fa'aletonu ona o manu'a i le OFC (ae le o le dorsolateral prefrontal cortex, DLPFC) i ituaiga eseese (Aso 'ua al, 1996; Berlin 'ua al, 2004; Hornak 'ua al, 2004; Boulougouris 'ua al, 2007). I tagata soifua, o le OFC e faʻagaoioia filifilia i le taimi o aʻoaʻoga fesuiaʻi (Hampshire ma Owen, 2006). I se faʻatusatusaga, o faʻamaʻi i le pito i tua o le PFC e faʻaleagaina ai le ED set-shifting i primates (Aso 'ua al, 1996), ma i tagata soifua o le faʻatinoina o le galuega e fesoʻotaʻi ma le faʻagaioiina o le faʻaogaina o le ventrolateral prefrontal cortex (VLPFC) (Hampshire ma Owen, 2006) (Laulau 1).

O loʻo iai nei le tele o faʻamaoniga e fesoʻotaʻi ai le fesuiaʻiina o aʻoaʻoga ma le 5-HT masini, e aofia ai i rodents (Masaki 'ua al, 2006; Boulougouris 'ua al, 2008; Lapiz-Bluhm 'ua al, 2009), tagata e le o tagata soifua (Clarke 'ua al, 2004, 2005; Walker 'ua al, 2009), ma tagata soifua (malae 'ua al, 1994; Rogers 'ua al, 1999a; Evers 'ua al, 2005) faʻavae i luga o vailaʻau, neurochemical ma togafiti meaʻai, ma faʻamaoniga o polymorphisms kenera i manuki rhesus (Izquierdo 'ua al, 2007). E masani lava, faʻaitiitia le serotonin faiʻai, aemaise i vaega faʻapitoa e pei ole OFC (eg Clarke 'ua al, 2004), e fa'aleagaina ai le a'oa'oina o suiga. Ua fa'aalia fo'i le fa'aletonu o le a'oa'oina o suiga fa'aleaganu'u ole 5-HT-2A.Boulougouris 'ua al, 2008). O le 5-HT6 antagonist faʻafeiloaʻi ua faʻaalia foi e faʻaleleia uma le aʻoaʻoina o le suiga ma le suiga o le mafaufau i isumu (Hatcher 'ua al, 2005). Ae ui i lea, o loʻo i ai ni faʻaletonu e maua ai aʻafiaga i le toe faʻafoʻiina o aʻoaʻoga, e masani lava pe a maeʻa le faʻaitiitia o le tryptophan, i tagata soifua (Talbot 'ua al, 2006) ma pusi (van der Plasse ma Feenstra, 2008), ma le faaletonu o le serotonin transporter i isumu e foliga mai e le afaina ai le fesuiaʻiina o avanoa faigofie (Homberg 'ua al, 2007).

5-HT2 FAITAU FA'AALI'I E MAFAI ONA FA'A'ALI'I UIGA FA'ASA'I.

Ole tele ole 5-HT faʻafeiloaʻi ua faʻaalia lea o loʻo faʻavaeina ai ni liga faʻapitoa. O faʻamaoniga muamua mai suʻesuʻega a manu ma tagata e taʻu mai ai se galuega mo 5-HT2 talipupuni i amioga faʻamalosi. O isumu Transgenic e leai ni 5-HT2C faʻafeiloaʻi e atiaʻe amioga faʻamalosi e fai ma faʻataʻitaʻiga talafeagai mo OCD (Chou-Green 'ua al, 2003). Ae ui i lea, o loʻo i ai se faʻamatalaga manino o faʻamaumauga na maua mai i lenei sauniuniga faʻavae ma isi faʻamatalaga, atonu ona o le le faʻamalamalamaina o le faʻatulagaina o taui i le sauniuniga transgenic, ona o faʻamatalaga faʻafomaʻi lata mai o loʻo faʻaalia ai le faʻafeagai o le mauaina o le 5-HT2C receptor activation e fesoʻotaʻi ma le faʻateleina o le faʻamalosi. O le mea lea, i se faʻataʻitaʻiga T-paso faʻataʻitaʻiga a le OCD, Tsaltas 'ua al (2005) na maua ai o le faʻaaogaina o le m-chlorophenylpiperazine (mCPP), o se vailaʻau faʻafefiloi serotonin faʻatasi ma aʻafiaga malosi 5-HT2C agonist, faateleina faʻaauau poʻo le faʻamalosia o le tali atu, ae o le togafitiga faʻasolosolo ma se SSRI (fluoxetine), ae le o se benzodiazepine poʻo le desipramine, na faʻaumatia ai aʻafiaga o le mCPP. O le luʻitau ma le 5-HT1B receptor agonist naratriptan e leai se aʻafiaga i le faʻamalosi i totonu o lenei faʻataʻitaʻiga, e fautuaina ai se galuega faʻapitoa mo le 5-HT2C receptor, lea e mafai ona faʻatulafonoina i lalo ole togafitiga SSRI. I tagata ma'i OCD, fa'alavelave fa'afoma'i lu'i ma le mCPP fa'ateleina fa'ailoga OCD (Loia 'ua al, 1991b). O lenei aafiaga na faʻaitiitia foʻi e ala i togafitiga muamua ma le fluoxetine (Loia 'ua al, 1991a) ma le clomipramine (Zohar 'ua al, 1988). E le gata i lea, e tusa ai ma nei suʻesuʻega, Boulougouris 'ua al (2008) na maua ai o le 5-HT2C fa'afeagai talitali fa'aleleia le a'oa'oga fa'aliliu. I le isi itu, o le faʻagaoioia o faʻamaʻi muamua 5-HT2A ua faʻatulagaina e faʻavaeina ai le aʻafiaga o le SSRIs (Westenberg 'ua al, 2007). E mafai ona fa'ateleina amioga fa'amalosi i tagata gasegase e maua i le schizophrenia, ma ua fa'ailoa mai e tupu lenei mea e ala i le malosi o le 5-HT2A antagonism (Poyurovsky 'ua al, 2008), e ui lava o le dopamine (DA) antagonism o loʻo faʻatusalia se isi auala e mafai. E le gata i lea, o antipsychotics lona lua ma le muamua o loʻo faʻaalia le aoga faʻapitoa pe a tuʻufaʻatasia ma SSRI i le OCD (Fineberg ma Gale, 2005), masalo e ala i le faʻateleina o gaioiga a le DA i totonu o le pito i luma (Faʻatau 'ua al, 2004).

FA'AIGA FA'AMA'IA'I O LE FA'A'OA'OGA MA LE FA'ASA'I; LIGANDS RECEPTOR

I faʻataʻitaʻiga manu, o se faʻalavelave faʻafefe i le va o aʻafiaga o le 5-HT2A ma le 5-HT2C faʻataʻitaʻiga antagonists i luga o fuataga o le impulsivity ma le faʻamalosi ua matauina. I luga o le 5-CSRTT, o le pulega faʻapitoa o le 5-HT2C receptor antagonist (SB24284) faʻateleina le faʻaleleia o le impulsivity e masani ona matauina pe a maeʻa le faʻaitiitia o le 5-HT i le lalolagi na gaosia e le intracerebroventricular administration o le 5,7-dihydroxytryptamine; o se faʻaleleia tutusa o le SB24284 i le impulsivity na vaaia i isumu faʻafefe (Winstanley 'ua al, 2004). I se faʻatusatusaga, o le faʻaogaina o le faʻaogaina o le 5-HT2A receptor antagonist (M100907) sa i ai ni gaioiga faʻafeagai, toe faʻaleleia le impulsivity i le faʻaogaina ma le 5-HT-depleted rats. O nei aʻafiaga eseese o le 5-HT2A ma le 5-HT2C antagonists na faʻataʻitaʻiina e le faʻaogaina o vailaʻau i totonu o le nucleus accumbens, ae le o le mPFC, i manu faʻamaʻi (Cottrell 'ua al, 2008). Ae ui i lea, i fesuiaiga o le 5-CSRTT, na mafai ona iloa le faʻaitiitia o le faʻaitiitia o le impulsivity i le maeʻa ai o le intra-mPFC infusion o le 5-HT2A receptor antagonist. O suʻesuʻega mulimuli na ogatasi ma faʻamatalaga e faapea, i le faitau aofaʻi o isumu Lister hooded, e masani lava o manu sili ona faʻamalosi e sili atu le maualuga o le 5-HT i le mPFC, e faʻaalia ai o eseesega o tagata taʻitoʻatasi ma faʻaitulagi faʻapitoa o ni iloiloga taua i le malamalama i le sootaga i le va o le 5-HT ma le faʻaleagaina o amio.

O aʻafiaga o le 5-HT manipulations tutotonu i luga o le impulsivity e tu i se eseesega ma a latou gaioiga i luga o galuega faʻalogo. taʻitasi i le 5-CSRTT. E tele pepa na matauina pe leai ni aʻafiaga poʻo le faʻaleleia moni o le saʻo lelei pe a faʻaleleia amioga faʻafefe (Harrison 'ua al, 1997) poʻo le maeʻa togafitiga faʻatasi ma faʻalavelave faʻapitoa poʻo intra-PFC 5-HT2A faʻafeiloaʻi e pei ole ketanserin poʻo M100907 (Passetti 'ua al, 2003; Winstanley 'ua al, 2003) faʻapea foʻi ma le 5-HT1A receptor agonist 8-OHDPAT (Winstanley 'ua al, 2003). O nei su'esu'ega e fetaui lelei ma le manatu e fa'apea o le taofiofia o le pulea o amioga fa'atopetope ma le fa'aogaina o le gaioiga e na'o le tu'ufa'atasia i lenei tulaga fa'ata'ita'iga ma fa'ailoa mai o le a leai se va'aiga faigofie i le va o ia fa'ama'i e pei o le ADHD.

O se elemene faaopoopo o le lavelave e faʻaalia pe a mafaufau i aʻafiaga o nei lava vailaʻau i luga o fua o le faʻamalosi. Fa'aaogaina o se su'ega fa'asolosolo fa'asolosolo fa'asolosolo fa'asolosolo e ma'ale'ale i manu'a o le OFC (Boulougouris 'ua al, 2007), na maua ai le 5-HT2C antagonism talitali (faia e le pulega faʻapitoa) faʻafaigofie a'oa'oga fesuia'i. M1000907 na i ai le fa'afeagai a'afiaga o le fa'aleagaina (Tsaltas 'ua al, 2005). Manatua e tusa ai ma le toe faʻaleleia, e faʻafeagai ma mea na maua mo fuataga o le impulsivity. O faʻaleleia tutusa o le toe faʻafoʻiina o aʻoaʻoga ina ua maeʻa togafitiga ma le 5-HT2C antagonist na maua foi ina ua maeʻa le faʻapipiʻiina i totonu o le OFC (Boulougouris, Glennon, Robbins, faʻamatalaga e leʻi faʻasalalau) (Laulau 2).

Laulau 2  

Aafiaga Eseese o le 5-HT2C ma le 5-HT2A Receptor Antagonists i Iole Faʻataʻitaʻiga o le Impulsivity ma le Compulsivity

E tusa lava po o le a le faʻamalamalamaina saʻo o le masini, o nei faʻamatalaga faʻamaʻi faʻamaʻi vavae ese nei ituaiga o le impulsivity ma le faʻamalosia, fautua mai. latou te le mafaia fa'alagolago i se faiga masani o le taofiofia o amioga. E le mafai ona faigofie ona fa'amatalaina le fa'amavaega i tulaga o eseesega i ituaiga, vaila'au, po'o fua ole fa'afeagai tali fa'aaogaina po'o le ituaiga o fa'aosofiaga fa'aaogaina; e tatau ona fa'alagolago i galuega-ona o galuega uma e lua e mana'omia ai le fa'alavelave tali mo le fa'atinoina lelei. O le mea lea, matou te fa'ai'uina o lo'o i ai se isi itu o fa'agasologa o lo'o fa'atinoina e le galuega, lea e fa'avasega ai. O nei fa'ai'uga e fa'aalia ai fo'i o le impulsivity ma le compulsivity o lo'o tu'ufa'atasia ma felagolagoma'i, tu'uina atu le lagolago i le fa'ata'ita'iga fa'amalosi-fa'amalosi diathesis (Hollander ma Wong, 1995). Latou te fautua mai foi o le impulsivity ma le compulsivity e mafai ona vavaeeseina e le filifilia o le 5-HT2 receptor ligands ma faʻaalia i ni faʻaoga fou a le falemaʻi mo ia sui. Ae ui i lea, o le a taua le foia pe faʻafefea ona fetaui nei faʻamaumauga ma le suʻesuʻega faifaipea o le faʻaitiitia o le 5-HT i le OFC e faʻaleagaina ai le aʻoaʻoina o mea faitino i manuki marmoset (Clarke 'ua al, 2004, 2005; Yucel 'ua al, 2007). E le gata i lea, e foliga mai o nei aʻafiaga e foliga mai e faʻafeagai o loʻo faʻatalanoaina e ala i auala eseese neural: i le tulaga o le impulsivity, e ala i faʻataʻitaʻiga mai le infralimbic VMPFC (eria 25), o se eria e matuaʻi faʻamalosia e le 5-HT2A receptors ma e matua aʻafia i le aʻafiaga. tulafono faatonutonu, agai i le atigi o le nucleus accumbens (Vertes, 2004) ma, i le tulaga o le faʻamalosi, i fesoʻotaʻiga i le va o le OFC ma le caudate nucleus (poʻo le dorsomedial striatum i le iole) (Schilman 'ua al, 2008).

FA'AVAEINA FA'AVAE FA'AMATALAGA MA LE FA'ASA'OGA FA'A'OGA O GALUEGA NEUROPSYCHOLOGICAL.

O fa'alavelave fa'alavelave ma fa'alavelave e masani ona aofia ai le fa'aitiitia o le malosi e fa'atuai pe taofia ai mafaufauga po'o amioga fai soo. O le mea lea, o faʻafitauli e taofiofia pe faʻalavelaveina amioga le talafeagai e mafai ona faʻavaeina uma faʻamaʻi faʻamalosi ma faʻamalosi (Chamberlain 'ua al, 2005; Stein 'ua al, 2006). O le ADHD o se faʻafitauli o le vave amataina e faʻaalia i le le lelei o le mafaufau, gaioiga faʻamalosi ma le faʻaleagaina malosi i le faʻalavelave afi e pei ona fuaina i galuega e pei o le SSRT (Aron 'ua al, 2003; Lijffijt 'ua al, 2005). O le faʻaaogaina o mea e faʻaleleia ai le mafaufau e pei o le atomoxetine ma le methylphenidate e faʻaleleia ai faʻamaoniga ma faʻaleleia le paʻu o le SSRT i tagata matutua e iai le ADHD, atonu e galue e ala i le faateleina o le noradrenergic (poʻo le dopaminergic) neurotransmission (Chamberlain 'ua al, 2007a).

O suʻesuʻega i tagata maʻi OCD na faʻaalia ai le faaletonu o le SSRT ma le le lelei o le faʻatinoga i galuega ED-shifting (Chamberlain 'ua al, 2006a, 2007c; Menzies 'ua al, 2007a), e fa'aalia uma ai sao fa'amalosi ma fa'amalosi i le ma'i. O aiga e le'i a'afia i le tikeri muamua o le OCD probands e tutusa o latou faaletonu i galuega SSRT ma ED-shifting (Chamberlain 'ua al, 2007c) ma faʻapea e foliga mai e faʻaalia tutusa tulaga o le faʻaogaina o le afi ma le faʻaogaina o le mafaufau, e ui lava i le leai o ni faʻamaoniga o le OCD. I le faʻatusatusaina o le OCD, o le faʻaaogaina o se suʻega suʻega neurocognitive tutusa i tagata taʻitoʻatasi e maua i le trichotillomania na faʻaalia ai se faʻafitauli sili atu ma le filifilia i le faʻalavelave afi, e ogatasi ma lona DSM-IV faʻavasegaina o se ICD (Chamberlain 'ua al, 2006b, 2007b). O le MRI atoa o le faiʻai i le trichotillomania e leʻi faʻaaogaina na faʻaalia ai le faʻateleina o le lanu efuefu i le itu tauagavale ma le tele o vaega o le cortical (Chamberlain 'ua al, 2008b). Faʻateleina mea efuefu i itulagi striatal ua lipotia foi i suʻesuʻega o Tourette syndrome (Bohlhalter 'ua al, 2006; Garraux 'ua al, 2006) ma le OCD (Menzies 'ua al, 2008a). I le isi itu, o tagata gasegase e maua i le Tourette's syndrome na maua e fefaʻasoaaʻi le faʻaogaina o le mafaufau ma e sili atu le faʻaleagaina nai lo tagata OCD i le faia o filifiliga, ae faʻaitiitia le faʻaleagaina i se galuega o le faʻalavelave afi (Watkins 'ua al, 2005), e ui lava o se isi suʻesuʻega suʻesuʻega talavou ma Tourette e leʻi maua ai faʻamaoniga o le faʻaleagaina o le aʻoaʻoina o taui pe a faʻatusatusa i faʻatonuga i luga o se galuega faitupe (Crawford 'ua al, 2005). Li 'ua al (2006) na le mafai ona faʻaalia le faʻaletonu o galuega pe a faʻatusatusa i faʻatonuga ile SSRT ile 30 tamaiti e maua i le maʻi o Tourette.

O le faʻapipiʻiina o le faʻamalosi ma le faʻamalosi tali atu i totonu ole OCD e tulaʻi mai ai le fesili pe o le impulsivity e masani ona faʻamalosia ai le faʻamalosi, ma faʻapea pe mafai ona faʻaalia le faʻamalosia o le pathological. e aunoa ma impulsivity afi. Afai o lea, o a fa'afitauli e ono fa'aalia ai le 'mama' fa'amalosi? O tagata taʻitoʻatasi o loʻo i ai le faʻafitauli faʻapitoa-faʻamalosi faʻapitoa faʻatasi ma le OCD na faʻaalia le faʻateleina o le faʻaleagaina aemaise lava ile vaega ole suiga ole ED. O lea su'esu'ega o lo'o ogatasi ma le fa'ata'ita'iga a le falema'i o le mata'utia-fa'amalosi uiga fa'aletonu, lea e fa'aalia i le tele o le mafaufau ma le fa'aletonu o amioga, ae e le aofia ai amioga fa'asolosolo (fa'ailoilo po'o le fa'amalosi). O le mea lea, o le faʻalavelave faʻalavelave faʻapitoa e mafai ona avea ma faʻamaʻi faʻapitoa-faʻamalosi (Finepa 'ua al, 2007b). O su'esu'ega fa'amaonia e fa'aaoga ai tagata ta'ito'atasi e le o fa'ama'i OCPD e fa'afeiloa'ia.

NEUROCOGNITIVE ENDOPHENOTYPES, OCD, MA LAVA

E ui o galuega neurocognitive e mafai ona faʻaaogaina e faʻamaonia ai vaega faʻapitoa o le neuropsychological, e mafai ona faʻaogaina le neuroimaging faʻapitoa e vaʻaia ai mea faʻapitoa faʻapitoa ma neural circuits e mafua ai le lamatiaga o le gasegase mo se maʻi. E ala i le tuʻufaʻatasia o le neurocognitive ma le faʻatulagaina o le MRI, faʻaaogaina se suʻesuʻega multivariate atoa-faiʻai (tekinolosi o sikuea pito itiiti, McIntosh ma Lobaugh, 2004) ma se su'ega fa'aliliuga fou, Menzies 'ua al (2007a) fa'ailoaina a'afiaga fa'aleaiga i luga o le fa'atinoga i luga o se galuega fa'atosina afi (le SSRT) e feso'ota'i ma suiga i le tele o nofoaga fa'apitoa. O gasegase uma o le OCD ma o latou aiga tulaga muamua e le afaina faʻaalia le faʻaleagaina o le faʻaogaina o le afi, faʻasinoina e ala i le umi umi o le SSRT ma le umi umi na fesoʻotaʻi ma le faʻaitiitia o le lanu efuefu i le OFC ma le RIF cortex (ituaiga masani e fesoʻotaʻi ma le OCD ma le SSRT faʻagaoioia, faasologa) ma faʻateleina le lanu efuefu i totonu. vaega o le striatum, cingulate, ma parietal cortex. O nei faʻaiʻuga e finau mo le faʻasologa muamua o le MRI endophenotype-mediating aiga, ma atonu o le kenera, lamatiaga mo le faʻaogaina o le OCD. O su'esu'ega i le lumana'i e mafai ona su'esu'e lelei mo a'afiaga fa'apitoa i le fesuisuia'i i ia fa'ata'ita'iga vaeluaga, e fai ma sui i mamanu fa'atasi masani, mo le su'esu'eina o alale'a faigofie.

O suʻesuʻega i le SSRT, o se faʻamaʻi faʻamaʻi-e le o se galuega faʻapitoa o le faʻaogaina o le afi, faʻatupuina le avanoa e ono le faʻatapulaʻaina se endophenotype i le OCD, ae faʻaopoopo e fesoʻotaʻi ma isi faʻalavelave i totonu, ma atonu i fafo, o faʻalavelave faʻalavelave-faʻamalosi. alaleo. Mo se faʻataʻitaʻiga, o tagata taʻitoʻatasi e iai le ADHD ma o latou aiga e foliga mai e faʻaleagaina i galuega faʻasaina afi (Crosbie ma Schachar, 2001), ae e leʻi manino pe tutusa pe eseʻesega faʻapitoa o le faʻaleagaina mo i latou e iai aʻafiaga faʻale-aiga mo le ADHD pe ese mai tagata e iai aʻafiaga faʻapitoa mo le OCD.

O le fesoʻotaʻiga i totonu-mataupu i le va o le faʻaitiitia o voluma efuefu i totonu o pito i luma o le cortex ma le faʻateleina o voluma i totonu o le striatum e faʻaalia i faʻataʻitaʻiga faʻapitoa OCD na maua mai suʻesuʻega faʻataʻitaʻiga vave (Baxter 'ua al, 1987) ma mulimuli ane suʻesuʻega faʻatulagaina ma faʻatinoga MRI (mo iloiloga vaʻai, Menzies 'ua al, 2008a). Sa'ili'ili muamua mai se su'esu'ega mulimuli ane e fa'aaoga ai ata fa'asalalau i totonu o tagata o le aiga OCD (Menzies 'ua al, 2008b) faʻamaonia faʻamaoniga o faʻalavelave paʻepaʻe i totonu ole faiʻai faʻatasi e aofia ai le itu taumatau pito i luma (latalata i luma o le cingulate cortex, ACC) ma le itu taumatau pito i lalo parietal (latalata i le parietal cortex) sone, e fetaui ma taunuuga mai se suʻesuʻega muamua e aofia ai maʻi OCD (Szeszko 'ua al, 2005). Ae ui i lea, e ala i le faʻalauteleina o lenei suʻesuʻega e aofia ai tagata o le aiga OCD e leʻi aʻafia, ua matou faʻatulagaina nei suʻesuʻega e mafai ona avea ma endophenotypes paʻepaʻe mo OCD (Menzies 'ua al, 2008b).

I le faʻaopoopoga i faʻalavelave faʻaletonu o le faiʻai i tagata mamaʻi ma le OCD ma o latou aiga, o suʻesuʻega ua amata ona suʻesuʻeina le amio saʻo o le fronto-striatal circuitry e faʻaaoga ai fMRI paradigms faʻatulagaina mo lenei faʻamoemoe. I le faʻaaogaina o le fMRI cognitive flexibility paradigm, na faʻaalia ai o tagata mamaʻi ma le OCD ma o latou aiga e leʻi aʻafia i le tikeri muamua na faʻaalia i lalo o le faʻaogaina o le OFC pito i tua i le taimi o le fesuiaiga o tali; na latou fa'apea fo'i e le fa'agaoioia vaega pito i tua o le PFC i le taimi o suiga ole ED i tulaga masani (Chamberlain 'ua al, 2008a).

Faʻatasi, o nei suʻesuʻega o loʻo faʻaalia ai o le neuroimaging techniques e mafai ona maua ai se punaoa mauoa o sui endophenotypes mo OCD. O fa'ai'uga e fetaui lelei ma a'oa'oga e a'afia ai le fa'ato'ilaloina o le pito i lalo i lalo o le fa'aogaina o amioga fa'atalanoa. Latou te fautua mai o le faʻalavelave faʻalavelave faʻalavelave ma tu ma aga faʻamalosi e faʻaalia ai le OCD o loʻo faʻatasi ma le tele o faʻataʻitaʻiga masani agaʻi atu i amioga maʻaʻa ma le faʻaleagaina lea e fefaʻasoaaʻi i tagata e le o aʻafia i le aiga. O lea la, o fa'afitauli i le 'fa'ato'ilaloina o le mafaufau ma le fetuutuuna'i' e ono mafua ai ona saofagā i le atina'eina o fa'ailoga o le OCD. O galuega i le lumana'i e tatau ona su'esu'e pe mafai ona fa'amanino lelei lenei faiga i isi fa'afitauli i luga ole alaleo fa'amalosi. Ole taua ole falema'i ole endophenotypes e mana'omia se su'esu'ega fa'aopoopo e iloa ai pe (ma pe fa'afefea) aiga e le'i a'afia o lo'o fa'asoa fa'ailoga uiga ma fa'ailoga OCD e mafai ona 'ese'ese mai fa'atonuga ole OCD. E mana'omia le fa'aleleia atili o auala e mafai ai e a'afiaga o le si'osi'omaga ona fa'atupuina ai le OCD i tagata fa'ama'i, ma pe fa'afefea fo'i ona fesoasoani togafitiga e fa'aleleia ai le amataga o fa'ama'i.

ICDS MA FAAATAITAI O TAUI

I le faʻatusatusaina o faʻalavelave faʻamalosi e pei ole OCD, o nisi ICDs, e pei ole pathological gambling, e faʻaalia e ala i le filifilia o le faʻamalieina mo taimi pupuu e tusa lava po o a taunuuga leaga umi. Berlin 'ua al (2008) faʻatusatusa tagata taʻitoʻatasi ma e aunoa ma se taʻaloga faʻapitoa i luga o se maʻa neuropsychological filifilia (Berlin 'ua al, 2008). O tagata taʻitoʻatasi o loʻo i ai taaloga faʻapitoa e sili atu le maualuga o latou togi i luga o faʻamatalaga a le tagata lava ia o le impulsivity e pei o le Barratt Impulsivity Scale i le averesi e sili atu le vave faʻatatau o le taimi (taimi faʻatauvaʻa) pe a faʻatusatusa i faʻataʻitaʻiga ma faʻaalia le paʻu na fuaina i se fesili i luma o amioga e faʻatatau e atagia ai le muamua. - fa'aletonu le tino. O mataupu e maua i taaloga faitupe ma'i na fa'aalia ai fo'i le le lelei o le faia o fa'ai'uga i le Iowa Gamble Task (Mulimuli 'ua al, 1994) ma fa'aletonu o fuafuaga fa'apitoa (fa'ata'ita'iga i luga o Fuafuaga Fa'ava-o-malo ma Toto'a a Cambridge su'ega a le CANTAB), fa'aaafia ai le ta'amilosaga muamua e aofia ai le OFC/VMPFC itulagi. E ese mai le OCD (Watkins 'ua al, 2005; Chamberlain 'ua al, 2006b), o le suia o seti e le'i afaina i taaloga faitupe. Ae ui i lea, o isi suʻesuʻega o loʻo faʻaalia ai o tagata taʻitoʻatasi o loʻo maua i taaloga faitupe faʻamaʻi e maualuga le togi i luga o fuataga patino o le faʻamalosi poʻo le aloese mai le afaina, ma o fua o le impulsivity ma le faʻamalosi e mafai ona suia i le taimi (faʻataʻitaʻiga, i le taimi o togafitiga (Potenza, 2007a; Paʻepaʻe 'ua al, 2009). O nei suʻesuʻega o loʻo fautua mai ai o le impulsivity ma le faʻamalosi e le faʻafeagai faʻatasi ma fefaʻasoaaʻi se fesoʻotaʻiga lavelave, faʻapitoa, faʻatasi ai ma faʻafitauli faʻapitoa e faʻaalia ai le sili atu o le tasi faufale i luga o le isi e ono suia i se tulaga faʻaletino.

Loia 'ua al (2007a) fa'atusatusa vaega e tolu o tausaga-ma le itupa-tutusa tagata ta'ito'atasi, e aofia ai le pathological gambling (teletele impulsive) ma le OCD ma autism (teletele fa'amalosi) fa'aletonu, fa'aaogaina se maa o falema'i, mafaufau, ma galuega fa'ata'ita'iga. I le taimi o le faʻatinoina o tali-faʻalavelave galuega (go / leai-go) e masani ona faʻagaoioia fronto-striatal circuitry, o vaega uma e tolu o alaleo-faʻafitauli na faʻaalia ai le faʻaogaina o le fMRI faʻaletonu i le pito i tua (cognitive) ma le ventral (lagona) itulagi o le ACC pe a faʻatusatusa i pulega maloloina. . E leai se eseesega tele o faatinoga i le va o vaega e fa. Ae ui i lea, o suʻesuʻega i le va o vaega na faʻaalia ai le faʻaitiitia o le faʻagaioiina o le ACC i totonu o vaega uma e tolu e faʻatatau i le soifua maloloina. O le mea lea, i le taimi o le faʻalavelave faʻalavelave, o faʻalavelave faʻamalosi ma faʻalavelave faʻafuaseʻi na faʻaalia i le faʻaitiitia o le faʻaogaina o le ACC, lea e ono fesoasoani i le le mafai ona faʻalavelaveina amio faʻamalosi i luga o nei faʻafitauli.

Ina ua faʻamaopoopoina faʻataʻitaʻiga a le tagata taʻitoʻatasi o le ACC ventral ma fua o le impulsivity poʻo le faʻamalosi, faʻalavelave faʻapitoa i le va-vaega eseesega na aliaʻe. I totonu o le vaega o taaloga faitupe, o le faateleina o le ACC / ventral striatum activation e fesoʻotaʻi lelei ma faʻataʻitaʻiga faʻapitoa o le faʻateleina o amioga suʻesuʻe taui (e pei ona fuaina e le TCI Impulsiveness ma le Aofaʻi Faʻaleagaina, NEO-FFI Extraversion, Aofaʻi Taimi, ma le Iowa Gambling Task ). E le gata i lea, o tagata taaalo ma le faʻateleina o le faʻagaoioia i le ventral ACC (ituaiga 25) na faʻaalia ai le maualalo o togi faʻamalosi i galuega o le suʻeina o le mafaufau (faʻamaeʻaina tulaga ID / ED). I le faʻatusatusaga, i le autistic (faʻamalosi) vaega, faʻateleina le ACC / ventral striatum gaioiga faʻatasi ma le faʻateleina o le mamafa o faʻamalosi faʻalavelave faʻalavelave (faʻamalosia) mausa, ma faʻateleina le faʻagaoioia i totonu o vaega tutusa o le ventral ACC (area 25) faʻatasi ma le faʻateleina o le faʻamalosi (ID / ED suiga aofaʻi o mea sese ua fetuʻunaʻi) ma faʻaitiitia le impulsivity i luga o le Taimi Fuafuaga galuega.

O lenei 'lua-dissociation' o loʻo taʻu mai ai i le pathological gambling ma autism, o loʻo iai le eseesega i le neuromodulation aʻafiaga i luga o auala corticostriatal ventral i le taimi o le faʻasaina o amioga, lea i le pathological taaloga faitupe e mafai ona faʻaosoina le impulsivity ma i le autism drive compulsivity. O loʻo faʻamanatuina foʻi faʻamaumauga mai isumu o loʻo faʻamatalaina i se isi mea iinei o loʻo faʻaalia ai aʻafiaga faʻafeagai o le 5-HT2C ma le 5-HT2A faʻafefe talitali i luga o le impulsivity i le 5-CSRTT ma le faʻamalosi (spatial serial reversal learning) (Tsaltas 'ua al, 2005; Boulougouris 'ua al, 2007)—ma faʻapea foʻi ma suʻesuʻega faʻalua faʻalua a Carli 'ua al-o le faʻaogaina o le 5-HT1A agonist i totonu o le infralimbic e faʻaitiitia ai amioga faʻamalosi (i luga o le 5-CSRTT) e aunoa ma le aʻafiaina o le tali atu, faʻatasi ai ma le 5-HT2A antagonist o loʻo i ai le faʻafeagai (Chambers 'ua al, 2004). Faʻatasi, o nei suʻesuʻega o loʻo fautua mai ai o le neural circuitry tutusa e mafai ona faʻaosoina uiga faʻamalosi pe faʻamalosi o amioga a tagata ma o le 5-HT subtypes i le VMPFC (5-HT2A) ma le OFC (5-HT2C), ma le faʻaletonu o le ACC, e mafai ona i ai se galuega i totonu. le toilalo o le faʻalavelave tali i faʻalavelave faʻafuaseʻi (pathological gambling) ma faʻalavelave faʻalavelave (OCD, autism).

TAUI, FAAMAOTI, MA TA

O auala a le DA i le mesolimbic system o loʻo i ai se galuega taua i le taui ma le faʻamalosia (Poto, 2002). I faʻafitauli o le faʻaogaina o le manaʻo, faʻateleina le faʻagaioiina o le ACC i le taimi o le faʻalavelave tali e mafai ona fesoʻotaʻi ma le faʻateleina o amioga saili taui. O faʻaiʻuga muamua e taʻu mai ai o tagata taaalo faʻamaʻi e itiiti le maaleale i le taui i luga o le TCI taui faʻalagolago i suʻesuʻega nai lo le faʻatonutonuina o le soifua maloloina ma saili maualuga maualuga o le faʻaosofia (sailiga fou) (Berlin 'ua al, 2008). Ae ui i lea, o isi suʻesuʻega o mataupu e iai le pathological gambling ua maua ai le faʻaitiitia o le faʻagaoioia o le ACC, aemaise lava i lona vaega o le manava, i le taimi o le manava ma faʻataʻitaʻiga o le mafaufau (Potenza 'ua al, 2003a, 2003b). E tusa ai ma faʻalavelave faʻalavelave, o le faʻamaopoopo lelei i le va o le faʻateleina o le faʻaogaina o le ACC i le taimi o le tali-faʻalavelave galuega ma le faʻateleina o le faʻamalosia i tulaga ID / ED ma le aofaʻi o mea sese ua fetuʻunaʻi e mafai ona atagia mai ai le faʻateleina o le gaioiga o le dopaminergic mai se paʻu, e tusa ai ma se faʻataʻitaʻiga DA mesolimbic o le OCD (Ioelu, 2006).

O le faʻataʻitaʻiga, faʻalavelave faʻafuaseʻi ma faʻasolosolo faʻaosofia o ala mesolimbic DA e mafai ona 'faʻaalia' le faiga o taui ma taʻitaʻia ai le faʻateleina i le sailia o taui (Robinson ma Berridge, 1993), lea, pe a tuʻufaʻatasia ma le le lelei o le faʻaogaina o le faʻaogaina o le faʻamaʻi muamua-cortex-mediated, e mafai ona faafaigofieina amioga a le DA ma e foliga mai e faaosofia. O le tele o le faʻamalolo ma le faʻamalosia o le DA e ono faʻaumatia ai faleoloa a le DA ma taʻitaʻia ai le anhedonia ma le atuatuvale (Koob ma Le Moal, 1997). O le mea moni, i le faʻaaogaina o vailaʻau, faʻaitiitia le gaioiga o le mesolimbic / mesocortical DA system, e pei ona fuaina i faamaumauga electrophysiological ma i vivo microdialysis, fa'ateleina pe a uma le fa'atuputeleina o vaila'au. E ono fa'atupu ai se fa'anaunauga (fa'amalosi) e su'e ni taui sili atu e 'fa'atumu' le fa'aletonu o le DA. O le faʻataʻitaʻiga o le faʻaitiitia o le D2-pei o le faʻaogaina o le faʻaogaina o le cocaine masani, e ala ile PET imaging (Volkow 'ua al, 1999), e fautua mai ai i lalo tulafono faatonutonu e tali atu ai i le maualuga o le postsynaptic DA concentrations, e ogatasi ma le manatu o se faiga faʻaletonu o le DA pe a uma ona faʻaosofia le faʻamalosia o le tuʻuina atu o le DA. O le mea lea, o le a le mea e amata i le faʻateleina o le tuʻuina atu o le DA e taʻitaʻia ai le faʻateleina o le gaioiga o le ACC ma faʻateleina le sailia o taui (Poto, 2002) e mafai ona faʻamutaina o se taʻavale faʻamalosi agai i le maualuga o le maualuga o le faʻamalosia o taui e toe faʻafoʻisia ai se faʻafitauli o le DA. O lenei ta'avale fa'amalosi e mafai ona fa'ateleina ona o le le lava o le fa'atonuina o lagona ma le faia o fa'ai'uga, e feso'ota'i atu i le orbitofrontal, ventromedial prefrontal, ma le ACC (Adinoff, 2004). Ae ui i lea, o le maualuga o lenei manatu e fesoʻotaʻi ma ICD faʻapitoa e manaʻomia ai suʻesuʻega tuusaʻo.

FA'ASA'OGA MECANISMO O LE PULE FAATASI, TAUI, MA LE DA

O faʻataʻitaʻiga o le faʻamalosi ma le faʻamalosi e maua ai se paleni i le va o le 5-HT (2A, 2C) gaioiga faʻafeiloaʻi i vaega o le VMPFC / OFC e faʻatonutonu vaega o le faʻasaina o le tali, ma le leo DA i totonu o faʻamaufaʻailoga e fesoʻotaʻi ai le ventral ACC ma le ventral striatum / nucleus accumbens faʻatonutonu taui ma le faʻamalosia. amio. O le neurotransmission a le DA, aemaise le faʻamalologa faʻapitoa, i totonu o le nucleus accumbens ua fesoʻotaʻi ma le sailia o taui ma le faʻamalosia (Schultz, 2002). Faʻasalaga faʻafuaseʻi (tupe leiloa) ua tuʻuina atu e mafua ai le paʻu i totonu o le gaioiga o le dopaminergic, faʻaliliuga aʻoaʻoga, ma le faʻaitiitia o le sailia o taui (taʻutino 'ua al, 2007). Pro-dopamanergic vailaʻau, e aofia ai levo-dopa ma pramipexole (o le D2-pei o le DA receptor agonist), ua fesoʻotaʻi ma le suia o le suiga o aʻoaʻoga i faʻasalaga faʻafuaseʻi ma ICDs i tagata mamaʻi e maua i le maʻi o Parkinson (Cools, 2006; Fufulu 'ua al, 2006). Pramipexole ua fesoʻotaʻi foʻi ma le faʻaleagaina o le mauaina o amioga e faʻatatau i taui i tagata soifua maloloina, e ogatasi ma faʻamaumauga o loʻo fautua mai ai o le faʻailoga a le DA e talafeagai i le faʻamalosia o gaioiga e tau atu i taui (Pizzagalli 'ua al, 2008). Ae ui i lea, o isi faʻamatalaga o loʻo faʻaalia ai o le pramipexole, pe a tuʻuina atu i tagata matutua soifua maloloina, e le suia ai amioga faʻamalosi, faʻamalosi, poʻo mea faʻapipiʻi e aofia ai le tuai-paʻu, faʻalavelave faʻalavelave, faʻalavelave tali, poʻo le faʻatumauina (Hamidovic 'ua al, 2008). E le gata i lea, o le olanzapine, o se vailaʻau faʻatasi ai ma mea faʻatauvaʻa i le D2-pei o le faʻafeiloaʻiga o le aiga o DA, e leʻi faʻaalia le maualuga i le placebo i ni faʻataʻitaʻiga faʻatonutonu e lua e aofia ai mataupu faʻapitoa i taaloga faitupe.Fong 'ua al, 2008; McElroy 'ua al, 2008), ma le isi D2-pei o le antagonist, haloperidol, ua maua e faʻateleina ai faʻaosofiaga ma amioga e fesoʻotaʻi ma taaloga faitupe i tagata taʻitoʻatasi o loʻo maua i taaloga fai tupe (Zack ma Poulos, 2007). Ole su'esu'ega a le Radioligand e taua tele e fa'amanino ai galuega fa'atino mo D3 ma D2 fa'afofoga i le pathophysiology o pathological gambling, ma o ia su'esu'ega e fa'alavelaveina e nei tali fa'asoa feso'ota'iga mo radioligands o iai.

I le amanaia o nei suʻesuʻega, e manaʻomia nisi suʻesuʻega e malamalama atili ai i le va o le impulsivity, compulsivity, ma le galuega a le DA pe a latou fesoʻotaʻi ma faʻafitauli faʻapitoa o le mafaufau e pei o le pathological gambling. O faʻafitauli faʻalavelave poʻo faʻalavelave faʻalavelave e ono mafua mai i le mesolimbic DA deficiency. Peita'i, ua fa'aalia e tagata fa'afeagai fa'apei o le D2 se fa'amanuiaga fa'afoma'i i nisi (OCD), ae le o isi fa'alavelave fa'aletonu (pathological gambling) o lo'o fa'aalia e uiga fa'amalosi ma/po'o fa'amalosi. O le su'esu'eina o le ventral ma le dorsal striatal circuitry i mataupu a le tagata ma faʻalavelave faʻalavelave ma faʻalavelave faʻapitoa e faʻaaoga ai serotonergic ma dopaminergic ligands faʻapitoa o le a avea ma laasaga taua i le malamalama i nei tulaga. Atonu e taua tele le suʻesuʻeina o aʻafiaga o le 5-HT2A ma le 2C antagonists ile faʻasalalauga a le DA i lenei matagaluega. O nei suʻesuʻega e mafai ona tuʻuina atu ai faʻamatalaga faaopoopo i itu e pei o le faʻaitiitia o le ventral striatal ma le faʻamalosia o le VMPFC o loʻo vaʻaia i suʻesuʻega e aʻafia ai faʻafitauli e faʻasoa ai uiga faʻamalosi ma faʻamalosi, e pei o le pathological gambling ma SAs (Reuter 'ua al, 2005; Potenza, 2007a).

O la tatou fa'amatalaga muamua o le fa'amalosia (o le fa'atupuina o gaioiga fa'asolosolo i se faiga masani/fa'ata'ita'iga e taumafai ai e puipuia a'afiaga leaga) ma le fa'amatalaga o lo'o i ai nei (le fa'aitiitia o se fa'alavelave fa'afuase'i e pei o le fa'amavae) e feso'ota'i fa'atatau. Mo se fa'ata'ita'iga, o le tali atu masani i fa'ailoga o fualaau fa'asaina e mafai ona faauigaina o se faiga e otometi ai ona va'ai i se ma'i fa'ate'a fa'ate'a ma fa'ate'a ae le'i tupu moni. O fa'amaumauga e feso'ota'i ai nei faiga masani a'oa'oga (po'o le fa'amalosi) i vaega o le pito i tua (le caudate mo se fa'ata'ita'iga), e pei ona toe iloiloina muamua. O fa'amatalaga lata mai nei o lo'o feso'ota'i ai le pito i tua (lona pito i tua) i le a'oa'oina fa'aosofia fa'amalosi (Seymour 'ua al, 2007). O lea la, mai se va'aiga neural, o fa'amaoniga e lagolagoina ai se fa'asagaga i le va o nei manatu e lua o le fa'amalosi.

FA'A'AU'A'I MA FA'AFIO

Pathological gambling ma SA e faʻasoa le tele o foliga. O faʻafitauli e masani ona tupu faʻatasi ma faʻaalia mea tutusa e faʻatatau i faʻamatalaga faʻaalia, eseesega o itupa, tala faʻanatura, ma mea faʻapitoa i aiga (Grant ma Potenza, 2006). Pathological gambling ma SA o loʻo faʻaalia le maualuga o le le mautonu i luga o galuega faʻaitiitiga taui, lea e fetaui lelei ma le le lelei o le gaioiga (Bechara, 2003) ma le leaga o taunuuga o togafitiga (Krishnan-Sarin 'ua al, 2007) mo tagata taʻitoʻatasi o loʻo iai SA ma faʻapea e mafai ona i ai se aoga faʻapitoa mo taaloga faʻamaʻi ma isi ICDs. O faʻamaumauga a le Neurocognitive ma le fMRI o loʻo faʻaalia ai le faʻaogaina o taaloga faitupe ma SA e tutusa lelei le mediating neurocircuitry, lea, pe a faʻatusatusa i mataupu faʻatonutonu, faʻaitiitia le faʻagaoioia o le ventral striatum ma le VMPFC ua matauina i le gaosiga o taui ma isi faʻataʻitaʻiga (Potenza 'ua al, 2003a, 2003b). O le faʻaogaina o le fMRI e le masani ai o le ventral striatum i le taimi o le gaosiga o taui ua faʻaalia i totonu o aiga o tagata taʻitoʻatasi ma le SA ma e mafai ona fai ma sui o le endophenotype o loʻo galue mo faʻafitauli o mea ua fai ma vaisu, e ui lava o lenei manatu e manaʻomia ai suʻesuʻega tuusaʻo i aiga e leʻi aʻafia o faʻataʻitaʻiga tau tupe.

I le aluga o taimi, o le tali atu ma le le mautonu i taaloga faitupe ma le SA e mafai ona suia agai i se mamanu sili atu ona malosi o amioga, ma ua faʻapea o le faʻagasologa o le faʻafaigaluegaina o tuaoi vavalalata ma faʻateleina dorsal, cortico-striatal loops e tupu i se faiga faʻafefe (Brewer ma Potenza, 2008) fa'amanatuina le fa'atupuina o le ta'amilosaga striato-nigrostriatal circuitry fa'ailoa mai i primate (Lynd-Balta ma Haber, 1994) ma rodent (Belin 'ua al, 2008) fa'ata'ita'iga o amioga fa'aosofia le fa'afanua o faiga fa'asolo mai le ventral to dorsal striatum. O su'esu'ega fa'amoemoe, fa'aumiumi pe a uma nei suiga i totonu o tagata ta'ito'atasi i le aluga o taimi o le a fa'amatalaga ma talafeagai ile falema'i. Suʻesuʻega faʻamaonia mai le togafitia o tagata taʻitoʻatasi o loʻo maua i taaloga faʻapitoa faʻatasi ai ma tagata faʻalavelave opioid (Fale faʻatau 'ua al, 2008) e le gata o le fa'aituau o taaloga fai tupe mai le OCD, lea na fa'aalia ai le fa'aleagaina o le OCD e pei o le naloxone (Insel ma Pikar, 1983), ae faʻapea foʻi ona fautua mai se galuega faʻafomaʻi mo tagata faʻalavelave opioid i isi ICDs e fesoʻotaʻi (Grant 'ua al, 2007).

TU'UINA FOU NEURAL

Ina ia malamalama atoatoa i le neurobiology o le impulsivity ma le faʻamalosi ma le gafatia mo le atinaʻeina o togafitiga fou, atonu e manaʻomia ona tatou suʻesuʻeina i tua atu o le neural circuitries o loʻo talanoaina i lenei tusiga e aofia ai isi fausaga neural, e pei o le insula. O fa'amaumauga o lo'o fa'ailoa mai e taua tele le insula i le fa'amaopoopoina o fa'atonuga 'malamalama'. O manu'a o le insula, mo se fa'ata'ita'iga ina ua uma le ta, ua feso'ota'i ma le fa'agata vave o le ulaula (Naqvi 'ua al, 2007). O le fa'aalia i fa'ailoga i le si'osi'omaga, po'o tulaga fa'anofonofo pei o le fa'amuta, fa'alavelave, po'o le popole, e ono fa'aoso ai fa'aaliga 'interoceptive' i totonu o le insula lea e fa'aliliuina i 'uuna'iga'. O le insula e faʻapitoa ma fesoʻotaʻi faʻatasi i le neural system ua taʻua i luga o loʻo aʻafia i le impulsivity, compulsivity, ma le taofiofia. E foliga mai, o le insula e fegalegaleai ma faiga o le impulsivity ma le faʻamalosia e ala i le tuʻuina atu o faailoilo (mai le siosiomaga poʻo le viscera) i le 5-HT 2C vs 5-HT 2A faʻafeiloaʻi i le pito i luma. O le mea lea, o faailoilo faʻafesoʻotaʻi faʻasalalau e ala i le insula e mafai, i le tasi itu, ona faʻalogoina le neural circuits e faʻaosoina ai le impulsivity poʻo le faʻamalosi. I le isi itu, o le gaioiga o le insula e mafai ona 'ave'esea' le faʻaogaina o le faʻaogaina o le pito i luma o le cortex ma faʻafefe ai le mafaufau, mafaufauga, fuafuaga, ma faiga faʻaiʻuga. ese mai le muai va'aia o a'afiaga leaga o se fa'atinoga, ma i fa'atulagaina o fuafuaga e saili ma maua ai fa'atupu fa'amalieina e pei o vaila'au (Naqvi 'ua al, 2007).

FAAIUGA

Toe foʻi mai la, i a tatou fesili faʻaosofia: (i) o le a le tele o le faʻamalosi ma le le mautonu e saofagā i nei faʻalavelave, (ii) o le a le tele latou te faʻalagolago i le fefaʻasoaaʻi poʻo le vavae ese o neural circuitry, (iii) o le a le mediating monoaminergic mechanisms, ( iv) pe i ai ni vaega fa'aoso fa'amalosi po'o le fa'atupu fa'amalosi e iai se fa'atatauga fa'atatau i togafitiga, ma (v) pe o iai se fa'ata'ita'iga fa'atasi e fetaui ma fa'amaumauga? E tusa ai ma faʻamaoniga o loʻo maua, impulsivity, ma le faʻamalosia, e foliga mai e tele vaega ma faʻavaeina a itiiti mai o nisi o faʻalavelave faʻalavelave ma faʻalavelave, e ui lava o faʻafitauli e faʻaalia ai le faʻapipiʻiina, ae faʻapitoa foi talaaga. O le mea lea, o le tele o faʻaletonu i totonu o le cortico-striatal neurocircuitry e faʻatonutonu vaega o le faʻatonuina o le pulea o loʻo matauina i suʻesuʻega o le mafaufau ma ata o faʻafitauli uma o loʻo iloiloina, e ui lava mo nisi faʻalavelave o faʻamaumauga e tumau pea le le atoatoa. Trichotillomania e mafai ona tu ese e pei o se faaletonu o le pulea o le afi ma le faaletonu i totonu o le RIF cortex ma ona cortico-subcortical connections, ae o le pathological gambling ua fesootaʻi ma le impulsivity e fesoʻotaʻi ma le le lelei o le faia o filifiliga ma le faaletonu o le ventral cortico-striatal circuitry, aemaise lava e aofia ai le VMPFC. ma le ventral striatum, e fa'ailoa atili ai ma SA. O maualuga maualuga o le faʻaogaina o taui e fesoʻotaʻi ma le le lelei o togafitiga mo SA ma e ono i ai le taua tele mo taaloga faʻapitoa ma isi ICDs. O amioga faʻamalosi e tupu ma autism e fesoʻotaʻi ma faʻalavelave tutusa i le vaʻaia o taui. O le OCD, i le isi itu, o loʻo faʻaalia ai le faʻaogaina o le afi ma le faʻamalosi, atonu e faʻasalalau e ala i le faʻalavelaveina o le OFC-caudate circuitry, faʻapea foʻi ma VLPFC, RIF cortex, cingulate, ma fesoʻotaʻiga parietal. Mo nei faʻafitauli, o fesoʻotaʻiga o le serotonin, DA, ma le noradrenaline e foliga mai o loʻo i ai ni galuega faʻaleleia taua, faʻapea foʻi ma isi faiga e leʻi atoatoa ona faʻaalia. I le aluga o taimi, e mafai ona tupu le impulsivity i le faʻamalosi ma le isi itu.

O le mea lea, o le ata e foliga mai e mamao ese mai se diathesis laina faigofie ma le impulsivity ma le faʻamalosia o loʻo nofoia faʻafeagai pou, ma o le 'faʻataʻitaʻiga' atonu e aofia ai se fegalegaleaiga faigata o le tele o diatheses e fesoʻotaʻi faʻatasi, e fesuisuiaʻi faʻaalia i nei taʻaloga ma faʻafitauli. O fa'alavelave fa'atopetope ma fa'alavelave fa'alavelave e va'aia fa'apitoa, fefa'asoaa'i vaega o le impulsivity ma le fa'amalosi, ma atili fa'alavelave ma faigata ai ona fa'amavaeina i le aluga o taimi. Mo se faʻataʻitaʻiga, mo faʻalavelave faʻalavelave ma fai ma vaisu, o le faapalepale i le taui e mafai ona tupu ma o amioga e mafai ona faʻaauau pea o se auala e faʻaitiitia ai le faʻavauvau (faʻapena e sili atu le faʻamalosi). Mo fa'alavelave fa'amalosi, e mafai ona fa'amalosia le fa'atinoina o amioga fai soo i le aluga o taimi, e ui lava i a'afiaga leaga mo se taimi umi (fa'ata'ita'iga ua fa'aoso fa'atopetope). O le fa'avasegaina o nei fa'afitauli i le fa'aaogaina o se maa ua malilie i ai o fa'ailoga endophenotypic sui tauva e mafai ona fa'amanino atili ai lo latou va ma le tasi ma le isi, ma e tatau ona fa'amalosia atina'e su'esu'e fa'atasi i le lumana'i i totonu o nofoaga fa'atasi ma tomai fa'atasi. Atonu e mana'omia ni faiga fou e su'esu'e lelei ai e ala i 'auala tafatolu' e pei o feso'ota'iga lavelave. I lenei itu, o auala mo le faʻamaoniaina o faiga faʻaogaina o le faiʻai i faʻamaumauga o le neuroimaging, e pei o le auala o sikuea pito sili ona itiiti (lea e mafai ai ona suʻesuʻeina le tele o amioga ma faʻataʻitaʻiga fesuiaiga), e ono i ai se tulaga taua tele e fai ma taualumaga mo le lumanaʻi i lenei matata. E mafai foi ona tatou alualu i luma atili i le faʻavasegaina o le faʻaogaina o auala e aʻafia ai i le puleaina o amioga faʻamalosi ma le faʻamalosi e ala i le faʻaaogaina o sauniuniga o isumu transgenic i galuega lava e tasi na fuafuaina e pei o isumu (faʻataʻitaʻiga 5-CSRTT ma le toe aʻoaʻoina) ma suʻesuʻega o le atoaga o le 5- HT faʻafeiloaʻi e faʻaaoga ai liga faʻafomaʻi fou.

tautinoga

Dr Fineberg na fa'atalanoa mo Lundbeck, Glaxo-Smith Kline, Servier, ma Bristol Myers Squibb; ua maua le lagolago suʻesuʻe mai Lundbeck, Glaxo-SmithKline, Astra Zeneca, Wellcome; ua maua le mamalu ma le lagolago e lauga i fonotaga faasaienisi mai Janssen, Jazz, Lundbeck, Servier, Astra Zeneca, Wyeth. O Dr Potenza e fa'atalanoa ma fautua ia Boehringer Ingelheim; ua fa'atalanoaina mo ma ei ai mea tau tupe i Somaxon; ua maua le lagolago su'esu'e mai le National Institutes of Health, Veteran's Administration, Mohegan Sun Casino, le National Center for Responsible Gambling and the Institute for Research on Gambling Disorders, ma Glaxo-SmithKline, Forest Laboratories, Ortho-McNeil ma Oy-Control/Biotie vaila'au; ua auai i su'esu'ega, meli, po'o fa'atalanoaga i telefoni e feso'ota'i ma vaisu, ICDs po'o isi mataupu tau soifua maloloina; ua fa'atalanoaina ofisa loia ma le ofisa feterale mo le puipuiga lautele i mataupu e feso'ota'i ma ICDs ma vaisu; ua faia iloiloga fesoasoani mo le National Institutes of Health ma isi lala sooupu; na faia lauga fa'alea'oa'oga i ta'amilosaga tetele, fa'alavelave CME, ma isi nofoaga fa'apitoa po'o fa'asaienisi; o lo'o iai vaega fa'asalalau fa'asalalau fa'asalalau; ua gaosia tusi po'o mataupu tusi mo le au fa'asalalau o tusitusiga o le soifua maloloina o le mafaufau; ma tu'uina atu tausiga fa'afoma'i ile Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program. Dr Chamberlain faufautua mo Cambridge Cognition, Shire, ma P1Vital. Ua maua e Dr Menzies se taui tau tupe e mafua mai i le fesiitaiga o se tekinolosi e le fesootai ma le mataupu o lenei tusiga i le va o Cambridge Enterprise Limited, Iunivesite o Cambridge, Cambridge, UK, ma Cypress Bioscience, Inc, San Diego. Ua maua e Dr Bechara totogi mai le PAR, Inc. Dr Sahakian umia sea i le CeNeS; sa feutagai mo Cambridge Cognition, Novartis, Shire, GlaxoSmithKline, ma Lilly; ma ua maua le mamalu mo ta'amilosaga tetele i le psychiatry i Massachusetts General Hospital (CME credits) ma mo le lauga i le International Conference on Cognitive Dysfunction in Schizophrenia and Mood Disorders (2007). Dr Robbins faufautua mo Cambridge Cognition, E. Lilly, GlaxoSmithKline, ma Allon Therapeutics. O Dr Bullmore o se tagata faigaluega a GlaxoSmithKline (50%) ma le Iunivesite o Cambridge (50%) ma se tagata e umia sea i GlaxoSmithKline. Ua maua e Dr Bullmore se taui tau tupe e mafua mai i le fesiitaiga o se tekinolosi e le fesootai ma le mataupu autu o lenei tusiga i le va o Cambridge Enterprise Limited, Iunivesite o Cambridge, Cambridge, UK, ma Cypress Bioscience, Inc, San Diego. Na fa'atalanoa e Dr Hollander ia Somaxon, Neuropharm, Transcept, ma Nastech. Ua fa'atalanoaina e Dr Hollander ofisa loia ma molimau i le mataupu a le Mirapex Product Liability. Na ia mauaina le lagolago suʻesuʻe mai le National Institutes of Health, Orphan Products Division of the Food and Drug Administration, National Alliance for Research in Schizophrenia and Affective Disorders, Autism Speaks, le Seaver Foundation, ma Solvay, Oy Contral, ma Somaxon. O lenei galuega sa lagolagoina i se vaega e le Wellcome Trust Program Grant (076274/Z/04/Z) ia Dr Robbins, Dr Sahakian, BJ Everitt, ma AC Roberts. O le Amio ma le Falemai Neuroscience Institute e lagolagoina e se faʻailoga tuʻufaʻatasia mai le Medical Research Council (MRC) ma le Wellcome Trust (G001354). Lagolagoina e le National Alliance for Research on Schizophrenia and Depression (RG37920 Distinguished Investigator Award ia Dr Bullmore), le Harnett Fund ma James Baird Fund (University of Cambridge) ma le Iunivesite o Cambridge School of Clinical Medicine, (MB/PhD studentship to Dr. Menzies), ma le Fono Suesuega Faafomai (MB/PhD tamaiti aoga ia Dr Chamberlain). Dr Bechara maua fesoasoani fesoasoani mai le National Institutes on Health (NIDA R01 DA023051, DA11779, DA12487, ma DA1670), (NINDS P01 NS019632), ma le National Science Foundation (NSF IIS 04-42586). s DA019039, DA020908, DA015757, DA020709; R37 DA15969; RL1 AA017539; P50s DA09241, AA12870, AA015632), le VA (VISN1 MIRECC ma REAP), ma Suʻesuʻega Soifua Maloloina a Tamaitai i Yale. Dr Robbins faufautua mo pfizer, Dr Menzies ua maua le mamalu mo le tuuina atu i le 8th Annual conference on Research of psychopathology ma mo le galuega i le UK Government Foresight Project i luga o le mafaufau ma le soifua manuia.

Faamatalaga Faʻamatalaga

TALANOAGA

Fai mai tusitala e leai se feteenaʻiga tului.

mau faasino

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