Ho qeta leqheka la ho itšoara ka mokhoa o itšoereng ka mokhoa oa boitšoaro: Mokhoa oa ho rarolla bothata ba moputso e le mosebetsi oa dopaminergic neurogenetics le ho kopanya ha boko bo sebetsang ho amanang le lithethefatsi tsohle tlas'a rubano e tloaelehileng (2014)

KENNETH BLUM,1,3,7,* MARCELO FEBO,1 TS'ELISO MCLAUGHLIN,2 MAFAPA J. CRONJÉ,8 DAVIDA HANANE,9 'me S. MARK KHAUTA1,3

Eya ho:

inahaneloang

Background: Kamora kopano ea pele lipakeng tsa dopamine D2 receptor gene polymorphism le joala bo matla, ho bile le ho phatloha ha litlaleho tsa lipatlisiso libukeng tsa mafu a kelello le boits'oaro le neurogenetics. Ka tsebo ena e eketsehileng, tšimo e ntse e tletse likhang. Ntle le moo, ka ho fihla ha Whole Genome-Wide Study (GWAS) le Whole Exome Sequicing (WES), hammoho le Functional Genome Convergence, mokhoa oa liphatsa tsa lefutso o nang le likhetho tse ngata o ntse o tšoaneleha mme o nkuoa ke ba bangata e le mokhoa o bohlale ka ho fetisisa. Leha ho le joalo, ke kopanyo ea mekhoa ena e 'meli e tla qetella e hlalositse likamano tsa' nete, tsa lefutso, ho ipapisitse le kotsi le etiology. Ho tloha 1996, laboratori ea rona e qapile poleloana ea sekhele Reward Deficiency Syndrome (RDS) ho hlalosa mekhoa e tloaelehileng ea methapo ea methapo le liphatsa tsa lefutso tse amehang mokhoeng oa boitšoaro le o seng oa lithethefatsi. Mekhoa: Ena ke tlhahlobo e khethiloeng ea lipampiri tse hlahlojoang ke lithaka tse thathamisitsoeng ho Pubmed le Medline. Results: Tlhahlobo ea bopaki bo fumanehang e bonts'a bohlokoa ba litsela tsa dopaminergic le boemo ba phomolo, khokahano e sebetsang ea lipotoloho tsa moputso oa boko. Puisano: Habohlokoa, tlhahiso ke hore 'nete ea phenotype ke RDS le ho senyeha ha moputso oa bokong, ebang ke liphatsa tsa lefutso kapa tikoloho (epigenetically) e susumetsoang, e susumetsa lintho tse mpe le tse seng tsa lithethefatsi, boits'oaro bo lemalloang. Ho utloisisa mekhoa e tloaelehileng e kopanetsoeng ho tla qetella ho lebisitse ho fumanoeng hantle, kalafo le thibelo ea ho khutlela morao. Le hajoale, boemong bona, ha re so ka ra bolela hore "re qhotsitse lehe la boitšoaro bo hlephileng", re qala ho botsa lipotso tse nepahetseng mme ka boiteko bo matla ba lefats'e ka ts'epo re tla fumana mokhoa oa ho "lopolla thabo" le ho lumella homo sapiens phela bophelo, o lokolohile bokhobeng kapa bohlokong.

Keywords: neurogenetics, epigenetics, dopaminergic, Reward Defence Syndrome, dopamine agonist kalafo

Selelekela

Blum et al. ba se ba phatlalalitse lingoloa tse mabapi le neurogenetics ea Reward Deficiency Syndrome (RDS) ho latela boits'oaro bo amanang le lithethefatsi le tse seng amanang le lithethefatsi (Blum, Oscar-Berman, Badgaiyan, Palomo le Khauta, 2014). Le ha ho na le lipatlisiso tse batsi tsa neurogenetic mabapi le boits'oaro ba ho batla lithethefatsi, ha ho joalo ka litlamorao tse sa amaneng le lithethefatsi le boits'oaro leha mosebetsi sebakeng sena se secha o hola ka potlako (Demetrovics & Griffiths, 2012).

Morero oa mantlha oa tlhahlobo ena ke ho bonts'a likhang tse fapaneng eseng feela, empa hape le ho bonts'a likhokahano tse teng lipakeng tsa lithethefatsi le tseo e seng tsa lithethefatsi, boitšoaro bo lemalloang. Tšepo ea rona ke ho fana ka moralo o tšoanang bakeng sa mefuta e 'meli ea boits'oaro, joalo ka ha e bile sepheo sa bangoli ka lilemo tse ka bang mashome a mabeli (Blum et al., 1996). Taba ena ea hajoale ha ea lokela ho nkuoa e le tlhahlobo e felletseng empa e le tsoelo-pele ea sehokela sa bohlokoa ho li-genomics le li-connectomics molemong oa bokamoso, tharollo e bohlale ea tahi.

Ho latela mosebetsi oa mantlha oa Blum et al. (1990), e amanang le Taq-A1 boemo ba mokelikeli oa dopamine D2 o nang le tahi e matla, bafuputsi ba bang ba tlalehile sephetho se nang le likhang kapa tse sa lumellaneng, tse ling tsa tsona li ka bakoang ke ho se hlahlojoe hantle ha taolo. Mohlala oa tlhahlobo e mpe e ka bonoa mosebetsing oa Creemers et al. (2011), ea ileng a tlaleha liphuputso tse mpe tse amanang le karolo ea li-polymorphisms tsa lefutso la dopaminergic ka boits'oaro ba ho batla moputso ho batho ba maDutch ka kakaretso. Leha a hlokomelisitsoe hore ho kenyelletsoa ha boitšoaro bo poteletseng ba Reward Deficiency Syndrome (RDS) sehlopheng sa taolo ho ka lebisa liphellong tse fosahetseng, leha ho le joalo bothata bo ntse bo le teng le kajeno.

Ho tloha 1990, ha ho so ka ho ba ka tlase ho 3738 (PubMed-6-23-14) lingoloa tse hlahlojoang ke lithaka ka boits'oaro bo fapaneng le boits'oaro ba methapo ea methapo (CNS) le lits'ebetso tsa mmele (tse amanang le lithethefatsi) ho mofuta oa DRD2 feela. Ka ho utloahalang, bokhoba ba tahi kapa esita le lentsoe le pharaletseng, RDS, le kenyelletsa tšebelisano e rarahaneng haholo ea lefutso le tikoloho. Kahoo, motho a ke ke a lebella hore lefutso le le leng le kang la DRD2 le be le tšusumetso e ikhethang. Leha ho le joalo, leha ho na le liphuputso tse 'maloa tse mpe, ho ntse ho na le bopaki bo bongata bo hokahanyang hantle liphatsa tsa lefutso tsa liphatsa tsa lefutso tsa DRD2 le boits'oaro ba ho lemalla moputso le ho se lemalle, ho kenyeletsoa le tse thathamisitsoeng ho Lethathamo 1.

Ho 'nile ha boleloa hore bohlokoa ba Taba ea 1A polymorphism e lutse phokotsong e amanang le ts'oaetso ea methapo ea pelo bokong bo bokelletseng moputso. Le ha ho tlalehiloe maemo a tlase a li-receptor tsa DAD2 tse hlahang lithutong tsa litšoantšo tsa lihlooho tse nang le Taba ea 1A polymorphism, bohlokoa ba liphuputso tsena ha bo hlake. Lithuto tsa PET tsa lithuto tse nang le Taba ea 1A polymorphism e tlalehile keketseho e kholo ea ho nkuoa ha striatal ea 18F-6FDOPA, e tsamaellanang le ts'ebetso e eketsehileng ea DA. Leha ho le joalo, haeba ho na le ts'ebetso e eketsehileng ea DA le ho lokolloa, sena se ka tsamaellana le ho fokotseha ha li-receptor tsa DAD2 ho arabela maemo a eketsehileng a kantle ho lisele tsa DA (ke hore, ka lebaka la phokotso ea li-auto-receptors tsa D2 tse bolaeang). Haeba khopolo ena e nepahetse, e tla hanana le khopolo ea leshano ea ho itšetleha ka lithethefatsi. Ho joalo, likhopolo tsa ho qhekelloa li atolositsoe ho hlalosa keketseho ea tlhekefetso ea koae, ho tseka hore tlhekefetso e eketsehang e bakoa ke keketseho ea ts'ebetso ea dopaminergic ho li-nucleus accumbens. Leha ho le joalo, bopaki ba haufinyane (Willuhn, Burgeno, Groblewski le Phillips, 2014) o pheha khang khahlanong le tlhaloso ena. Ebile, bangoli bana ba pheha khang ea hore keketseho ea tlhekefetso ea koae e bakoa ke ts'ebetso e tlase ea dopaminergic. Ka hona, ba sebelisa litlhahlobo tse tsoetseng pele, ba pheha khang molemong oa boits'oaro bo matla ho fapana le ho kenella ho hanyetsanang, bakeng sa ho phekola bokhoba.

Mathata le Phehisano - Dopaminergic Surfeit or Deficit?

Ho na le phehisano mabapi le mekhatlo lipakeng tsa mefuta e fapaneng ea liphatsa tsa lefutso tsa dopaminergic, joalo ka lefutso la dopamine transporter (DAT) le BMI. Chen le al. (2008) o ne a tlalehile kamano e kholo, e mpe lipakeng tsa BMI le maemo a striatal a DAT1, leha ho le joalo, van de Giessen et al. (2013) ha e netefatse mokhatlo ona. Phuputsong ena khetho ea seo ho thoeng ke, 'bophelo bo botle' ba ba nonneng e beha lipelaelo ts'ebetsong ea ho lekola taolo ea boits'oaro ba RDS. Ntle le moo, mokhatlo o joalo o seng oa mokhatlo o tlalehiloe ke Thomsen et al. (2013), ea sebelisitseng le seo ho thoeng ke lithuto tse phetseng hantle tse nonneng. Leha ho le joalo, ho na le litlaleho tse ling tse ngata tse tšehetsang kopano e mpe ea DAT1 le BMI (Fuemeler et al., 2008; Hloka, Ahmadi, Spector & Goldstein, 2006; Sikora et al., 2013; Valomon et al., 2014; Wang et al., 2011). Mokhatlo o mobe oa DAT1 le BMI o tšehelitsoe ke Danilovich, Mastrandrea, Cataldi le Quattrin (2014), ea bonts'itseng methamphetamine, e tsejoang ho thibela DAT1, e fokotsa ho ja le mafura a k'habohaedreite.

Khang e 'ngoe e mabapi le karolo ea' nete ea BMI joalo ka lets'oao la tlhaho ea botenya joalo ka Shah le Braverman (2012) e bontšitsoe ka ho hlaka - e bapisa hampe le liperesente tsa mafura a 'mele. Qeto ena e ile ea totobatsoa ke Chen et al. (2012), moo ba fumaneng kamano e kholo lipakeng tsa bajari ba DRD2 Taq-A1 le liphesente tse phahameng tsa 'mele ha li bapisoa le bajari ba DRD2 Taq-A2.

Qeto ea ho lemalla tsoekere e ka lebisa botenya (Hone-Blanchet & Fecteau, 2014) hape e na le likhang. Leha ho le joalo, bopaki bo bonahala bo rata tlamahano lipakeng tsa Mathata a Ts'ebeliso ea Ts'ebeliso ea Lithethefatsi, joalo ka ha li arotsoe ka bongaka ho DSM-5, le moputso oa lijo (Brownell, 2012; Khauta le Avena, 2013).

Blum le ba bang. (2011) o buile ka phetisetso ea bokhoba ba tahi e le bothata bo ka bang teng bo amanang le bariatric, le mosebetsi oa Dunn et al. (2010) e senotse phokotso ea phumaneho ea D2R (hypo-dopaminergic state) kamora ho buuoa ka bariatric, e fana ka maikutlo a tlhoko e eketsehang ea lithethefatsi tse itšebetsang kapa boits'oaro bo amanang le ts'ebetso ea dopaminergic. Ho khahlisang ke hore Steele et al. (2010) o fumane ho fumaneha ho tlase ha D2 R pele ho opereishene ea bariatric lihloohong tse hlano tse nonneng, ha ho bapisoa le ho buuoa kamora 'ho buuoa ho ekelitse maemo a D2R libeke tse tšeletseng kamora ho buuoa. Kamohelo e eketsehileng ea dopamine e kanna ea fana ka maikutlo a ho fokotsa lithethefatsi le / kapa boits'oaro bo lemalloang bo hokahantsoeng le ts'ebetso e ntlafalitsoeng ea dopaminergic. Leha ho le joalo, potso ha e rarolloe ka lebaka la se fumanoeng ke Dunn et al. (2010), e nkiloeng liphuputsong libeke tse supileng kamora ho buuoa, ha li bapisoa le libeke tse tšeletseng tsa Steele et al. (2010), e fumaneng mokhoa o theohelang o isang hape ts'ebetsong ea hypo-dopaminergic. Khopolo-taba e mabapi le phetisetso ea bokhoba ba tahi e bonahala e le ngata haholo, kamora nako e telele ho feta ea ho buuoa kamora 'bariatric.

Le ha ho na le bopaki ba phokotso ea phumaneho ea D2R lithutong tse batenya haholo (Volkow et al., 2009), ho na le likhang tse phehang khang ea hore sena ke 'nete feela bakeng sa botenya bo matla (Eisenstein et al., 2013; Kessler, Zald, Ansari, Li & Cowan, 2014). Mefuta e ferekanyang e kenyelletsa lihlopha tsa taolo tseo mekhoa e meng ea RDS e sa qheleloang ka thoko, ts'ebeliso ea BMI joalo ka lebaka e kanna ea se tšoanelehe joalo ka phenotype mme botenya bo bobebe bo kanna ba se bontše lefu la 'nete. Ts'ebeliso ea "ho tiea" ho fana ka mofuta oa 'nete oa endophenotype joalo ka ha ho boletsoe ke bafuputsi ba' maloa (Blum et al., 1990; Connor, Young, Lawford, Ritchie le Noble, 2002) e hatisa taba e amanang le "linyeoe tse bonolo" joalo ka phenotype. Habohlokoa, sehlopha sa Volkow se se se phatlalalitse bonyane lipampiri tse 13 tse tšehetsang mohopolo oa bona oa mantlha, phumaneho e tlase ea D2R ho botenya (Tomasi le Volkow, 2013). Ka lehlakoreng le leng, ho theola ho fumaneha ha D2R ha hoa fumanoa ho amahanngoa le ho batla mokhoa o mocha oa botenya (Savage et al., 2014).

Ho na le bopaki bo tsoang sehlopheng sa Stice ba hore li-polymorphism tse kahare ho dopamine D2 le D4 li baka karabelo e fosahetseng lijong tse monate le ho nona kamora moo (Stice & Dagher, 2010; Stice, Davis, Miller & Marti, 2008; Stice, Spoor, Bohon le Nyane, 2008; Stice, Spoor, Bohon, Veldhuizen & Nyane, 2008; Stice, Yokum, Blum & Bohon, 2010; Stice, Yokum, Bohon, Marti & Smolen, 2010; Stice, Yokum, Burger, Epstein & Smolen, 2012; Stice, Yokum, Zald & Dagher, 2011). Pampiring ea bona ea morao-rao Stice et al. (2012) o sebelisitse fMRI ho bonts'a hore, bocheng, ho eketseha ha lefu la methapo ea methapo ea methapo, joalo ka ha e le phapang, le eona e ka ba sesosa sa kotsi sa botena. Ehlile sena se tšehetsa mohopolo oa maiketsetso oa dopamine o hlahisitsoeng ke Berridge le Robinson (2000) 'me ka nepo e totobatsa ho rarahana ha mathata a ho ja. Motho ea nang le tšusumetso e eketsehileng ea lijo a ka oela mekhahlelo e 'meli e tšehetsang khaello kapa likhopolo tse nyonyehang, mabapi le ts'ebetso ea dopaminergic. Leha ho le joalo, lipatlisiso tse ling tse ipapisitseng le liphatsa tsa lefutso le tikoloho (epigenetics) ka ho nahanisisa ka mefuta e meng e joalo ka bong, lilemo tsa ho qala, le ho latela "ho rata le ho batla" ho ka hlokahala ho utloisisa liphapang tsena (Blum, Gardner, Oscar-Berman & Khauta, 2012; Willuhn et al., 2014).

Na ho na le Tharollo ho RDS?

Mothating ona, ha ho na "pheko" e tsebahalang kapa pilisi ea boloi bakeng sa lintho tsohle le tse seng tsa lithethefatsi, boits'oaro ba RDS, haholo-holo, li-subtypes tsa boits'oaro (meriana e lumelletsoeng ke US FDA, meriana e thusitsoeng ke bongaka bakeng sa lithethefatsi tse amanang le lithethefatsi feela), ha e shebiloe ka phoso nyakallo e bakoang ke dopamine ke bahanyetsi ba kang Naltrexone le Acamprosate. Ho utloisisa bohlokoa ba ho sebelisa kalafo ea agonist ea dopamine ho phekola mekhoa eohle ea boitšoaro, ho fapana le ho thibela ts'ebetso ea tlhaho ea dopaminergic ho bonahala ho le bohlale le ho feta nakong e telele. Ka ts'ehetso ea ts'ebeliso ea dopaminergic, laboratori ena e hlahisitse agonist e thata, e behang dopamine agonist, KB220Z, e nang le litlamorao tse 'maloa tsa bohlokoa tse khahlano le lithethefatsi (Blum, Chen le al., 2012). Joalokaha ho tlalehiloe ho sengoloa se qaqileng sa tlhahlobo ea Chen et al. (2011), Mefuta e fapaneng ea KB220 e bonts'itsoe ho ntlafatsa maemo a enkephalin a litoeba, ho fokotsa boits'oaro ba ho batla joala ho litoeba tsa C57 / BL le pharmacogenetically fetola kamohelo ea ethanol ka ho khetha litoeba ho etsisa boitšoaro ba litoeba tse sa rateng, joalo ka DBA / 2J.

Ho batho, KB220Z e tlalehiloe e fokotsa matšoao a tlohelang lithethefatsi le joala a bontšitsoeng ke tlhoko e tlase ea benzodiazepines, matsatsi a fokotsehileng ka ho thothomela ha matla, bopaki ba palo e tlase ea BUD [e hahang ho noa] mme ho se khatello ea maikutlo e matla e fumanoeng ho Minnesota Multiphasic Personality Lethathamo la libuka (MMPI). Bakuli ba kalafo ea sehlopha ba ne ba fokolitse likarabo tsa khatello ea maikutlo, joalo ka ha e lekantsoe ke boemo ba letlalo la boits'oaro, mme ba ntlafalitse haholo lintlha tsa 'mele hammoho le lintlha tsa boits'oaro, maikutlo, sechaba le bomoea (BESS). Ho bile le phokotso e imenneng makhetlo a tšeletseng ea sekhahla sa Against Medical Advice (AMA) kamora ho tlosa 'mele, ha lihlopha tsa li-placebo li ne li bapisoa le mofuta o mong oa KB220. Baithaopi ba phetseng hantle ba bonts'itse ho tsepamisa maikutlo (p300 ba sebelisa EEG) kamora ho nka mofuta oa KB220 likhoeli tse tharo. Hape ho na le bopaki ba ho fokotsa takatso ea joala, heroin, cocaine le nicotine. Hape, ho fokotsoe boits'oaro bo sa lokelang ba thobalano le matšoao a fokotsang khatello ea maikutlo a sithabetsang (PTSD) joalo ka paraphilia a tlalehiloe (McLaughlin et al., 2013). Liphuputso tsa Quantitative electroencephalography (qEEG) bathong li fumane hore KB220Z e hlophisa matla a theta ho anterior cingulate cortex. Ho heroine e sa sebetseng e lemalla tekanyetso e le 'ngoe ea KB220Z ha e bapisoa le placebo thutong ea lifofane (Blum, Chen, Chen, Rhoades, Prihoda, Downs, Bagchi et al., 2008) e hlahisitse ts'ebetsong ea N. Ntle le moo, ts'ebetso e ntlafalitsoeng haholo ea KB220Z e fumanoe ho bakuli ba batenya haholo ba nang le DRD2 A1 e amanang le bajari ba thoriso e tloaelehileng ea li-receptor tsa DRD2 tse sebelisang khokahano ea Pearson (Blum, Chen, Chen, Rhoades, Prihoda, Downs, Bagchi et al., 2008) Ho fana ka maikutlo a hore ts'ebetso e tlase ea dopamine e lekana le sephetho se betere le kalafo ea KB220Z.

Mekhoa ea Genomic le Ts'ebetso ho RDS

Boiteko bo ntse bo tsoela pele ho holisa tsebo ka mokhoa oa mantlha oa methapo le lintho tseo e seng tsa lithethefatsi. Mosebetsi ona o ipapisitse le tlhokomeliso e ncha ea hore bokong ba mammalian ho na le ho rarahana marang-rang a genomic a sebelisanang haufi-ufi le li-network tsa neural tse sebetsang. Liphatsa tsa lefutso li tlas'a taolo ea taolo ea marang-rang a epigenetic a ka etsang 'khoutu' e bopehileng, mme e kanna ea hlalosa, likarolo tse sebetsang tsa marang-rang a neural (Colvis et al., 2005). Ho hloleha maemong a genomic le epigenomic, ka mekhoa ea lefa Likamano tsa mantlha tse koalang maemo ana a genomic le ts'ebetso li haelloa mme lia hlokahala ho thusa kalafo e sebetsang e lumellanang le mafu a itseng a bophelo bo botle ba kelello a motho ka mong.

Lilemong tse leshome tse fetileng, mekhoa ea maano a ho etsa litšoantšo tsa tlhaho ea matla a khoheli (fMRI) e hlahisitse litekanyo tsa ts'ebetso ea naha ea phomolo ea boko, e hlophisitsoeng e le lits'ebetso tse hokahaneng tse sebetsang tse bonts'ang tšebetso e tsamaeang butle (Biswal, van Kylen & Hyde, 1997). Phomolo ea khokahano ea ts'ebetso ea mmuso (rsFC) e fokotsehile ka ho lemalla lithethefatsi tse 'maloa le lithethefatsi tse seng molaong le mefuta e meng e fapaneng ea tahi (Lu & Stein, 2014). Keketseho ea rsFC meputsong ea boko le marang-rang a memori lithutong tse lemalloang tsa batho le mefuteng ea liphoofolo e bonts'itsoe ho sebelisoa KB220Z, mochini o matlafatsang oa tlhaho oa dopaminergic. Mohaho o rarahaneng o ntlafalitse ts'ebetso ea hypodopaminergic eo ho thoeng ke RDS e na le metsoako e etselitsoeng ho tlatselletsa mehato e ikhethileng ea lipakeng e amehang ts'ebetsong ea methapo ea kutlo kahare ho boko ba moputso oa tlhaho (...Blum, Oscar-Berman le al., 2012). Maemo ao marang-rang a mantlha a fetotsoeng mme a ka bang le tšusumetso e mpe bokong ba khokahano e kahare ho sistimi ea moputso e kanna ea hlahlojoa le ho fetoloa ka metsoako e rarahaneng e kang KB220Z.

Leano lena le matla le ka fuoa matla bakeng sa ts'ebeliso ea batho, kamora liteko tsa mantlha tsa mahlale tse sebelisang tharollo e phahameng ea sebaka-sa nakoana ea ts'ebetso ea ho nahana ka boko, le lisebelisoa tsa lipotso tsa lefutso. Le ha lilaboratori tse ngata ho pholletsa le US le kantle ho naha li qala ho sebelisa lisebelisoa tsa optogenetic ho lekola kamano lipakeng tsa batho ba itseng ba neuronal le boits'oaro ba mehlala ea mafu ho litoeba, ho na le khaello e kholo ea lithuto tsa optogenetic tse kopantsoeng le litšoantšo tse sa hlaseleng tse phahameng.

Ha re khone ka nako ena ho tiisa hore "re qhotsitse lehe le lemaletseng boits'oaro". Leha ho le joalo, re qala ho botsa lipotso tse nepahetseng 'me re khothatsoa ke takatso ena e nchafalitsoeng ea likarabo tsa lefats'e, e le hore batho ba libilione ba ts'oaroang ke boitšoaro bo hlephileng' me ka tsatsi le leng ba fumane mokhoa oa "ho lopolla thabo" le ho phela bophelo. o lokolohile bokhobeng le bohlokong.

Mehloli ea lichelete

Marcelo Febo ke moamoheli oa NIH DA019946 'me e tšehelitsoe ke McKnight Brain Institute Foundation. Kenneth Blum ke moamoheli-'moho oa thuso ho tsoa LifeExtension Foundation, Ft. Lauderdale ke Pat Foundation NY.

Menehelo ea bangoli

Morero oa pele oa sengoloa o entsoe ke KB, MF le MSG. TMcL, DH le FJC li fane ka liphetoho tsa bohlokoa tsa ho ngola le kenyelletso ea bongaka tlhahlobisong. Bangoli ba ananela liphetoho tsa litsebi tsa Margaret A. Madigan.

Khohlano ea thahasello

Kenneth Blum ka lik'hamphani tsa hae tsa Synaptamine Inc. le KenBer LLC e na le litokelo tse 'maloa tsa Amerika le tsa kantle ho naha tse fanoeng le tse emetsoeng, litekong tsa liphatsa tsa lefutso le tharollo ea RDS. Kenneth Blum, le David Han ka bobeli ba lekhotleng la boeletsi la saense la Dominion Diagnostics LLC mme ke baeletsi ba lefuoang. Kenneth Blum le Mark Gold ke baeletsi ba lefuoang ba tsoang Malibu Beach Recovery Center. Ha ho na likhohlano tse ling.

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