Ketsahalo ea khatiso ea maikutlo e sebelisoang ka tlas'a hau le bo-reboxetine: thuto ea fMRI e laoloang ke sebaka ka lipuo tse phetseng hantle (2014)

Int J Neuropsychopharmacol. 2014 Oct 31;18 (2). pii: pyu004. doi: 10.1093 / ijnp / pyu004.

Graf H¹, Likoloi tsa Wiegers M.², CD ea Metzger², Walter M², Grön G², Abele B².

inahaneloang

LITLHAHISO:

Ts'ebetso e mpe ea thobalano e ntse e tsejoa e le litlamorao tsa kalafo ea psychopharmacological. Leha ho le joalo, ho ntse ho lokela ho hlahlojoa methati ea ts'ebetso ea litlhare tse fapaneng ts'ebetsong ea thobalano. Re sebelisa litšoantšo tse sebetsang ka matla a khoheli, re kile ra etsa lipatlisiso tsa litlamorao tsa serotonergic (paroxetine) le dopaminergic (bupropion) antidepressants mabapi le ts'ebetso ea thobalano (Abler et al., 2011). Mona, re ithutile ka litlamorao tsa meriana ea noradrenergic le antidopaminergic ho li-neural correlates tsa tšusumetso ea thobalano ka mohlala o mocha oa lithuto.

LITLHAHISO:

Banna ba leshome le metso e robong ba phetseng hantle ba bong bo fapaneng (lilemo tse bolelele ba lilemo tse 24, SD 3.1) tlasa ho noa ka mokhoa o fetisisang (matsatsi a 7) a noradrenergic agent reboxetine (4 mg / d), antidopaminergic agent amisulpride (200mg / d), le placebo e kenyelelitsoe mme e ithutiloe ka ts'ebetso e sebetsang ho nahana ka matla a khoheli ka har'a moralo o hlophisitsoeng, o foufetseng habeli, o laoloang ka "placebo", kahare ho lihlooho tsa lithuto nakong ea mosebetsi o qapiloeng oa litšoantšo tse tsosang takatso. Ts'ebetso e ikhethileng ea thobalano e ile ea hlahlojoa ho sebelisoa lipotso tsa Massachusetts General Hospital-Sexual Functioning Questionnaire.

LIKOTSO:

Ha e bapisoa le placebo, ts'ebetso ea thobalano e ikhethileng e ile ea fokotsoa tlasa reboxetine hammoho le ts'ebetso e fokotsehileng ea methapo ea kutlo kahare ho mokokotlo oa caudate. Liphetoho tse fetotsoeng tsa li-neural tse amanang le lithahasello tse fokotsehileng tsa thobalano. Tlas'a li-amisulpride, ts'ebetso ea methapo le ts'ebetso ea thobalano e ikemetseng ha ea ka ea fetoha.

CONCLUSIONS:

Tumellanong le litlhaloso tsa pejana tsa karolo ea mokokotlo oa caudate maemong a ts'ebetso ea mantlha ea moputso, ts'ebetso e fokotsoang ea caudate e kanna ea hlahisa litlamorao tse mpe lintlheng tsa ts'usumetso ea ts'ebetso ea ts'usumetso e mpe ea maikutlo tlasa mahlahana a noradrenergic.

LINKOTSO:

boikakaso; ts'ebetso e tsosang takatso; fMRI; ts'ebetso ea thobalano; reboxetine

Selelekela

Ts'ebetso e mpe ea thobalano e ntse e nkuoa e le litlamorao tsa kalafo ea psychopharmacological e amang boleng ba bophelo le ho latela melao ea kalafo (Taylor le al., 2005; Park et al., 2012; Baldwin et al., 2013; La Torre et al., 2013) ka thahasello e holang mekhoeng ea motheo. Kaha ho se sebetse ka thobalano hape ke sesupo se tloaelehileng sa mafu a kelello, joalo ka khatello ea maikutlo e kholo, ka boeona, litlamorao tse amanang le kalafo li thata ho batlisisoa ho bakuli ba anngoeng ke (Baldwin le Mayers, 2003), Ho hloka hore ho etsoe lipatlisiso tsa litlamorao tsa kalafo taolong e phetseng hantle (Graf et al., 2014).

Ts'ebetso e phethahetseng ea thobalano e ipapisitse le tšebelisano e rarahaneng ea masapo le masapo a mokokotlo hammoho le ts'ebetso ea lihormone, pheriferale le boits'oaro. Tšusumetso ea li-neurotransmitters tse fapaneng le melao-motheo ea litlhare litšebelisanong tsena e ntse e sa hlaka hantle. Re se re ntse re batlisitse li-neural correlates tsa ho tsosa takatso ea thobalano lithutong tse phetseng hantle ho sebelisa litšoantšo tsa magnetic resonance imaging (fMRI) tlasa kalafo e fetisisang (matsatsi a 7) ka serotonin reuptake inhibitor (SSRI), paroxetine, le bupropion, dopamine e khethiloeng le noradrenaline ( NA) reuptake-inhibitor. Re bonts'itse hore ts'ebetsong ea thobalano e holofetseng tlasa SSRI e ne e tsamaea le ho fokotseha hoa ts'ebetso ea methapo ea kutlo kahare ho likarolo tsa boko le maoto le matsoho (Abler et al., 2011), E kanna ea amana le ho eketseha ha litšebelisano lipakeng tsa orbitofrontal cortex le ventral striatum (Abler et al., 2012). Joalokaha ho lebelletsoe ho tsoa tlhokomelong ea bongaka (Coleman et al., 2001; Taylor le al., 2013), Ts'ebetso e mpe ea thobalano e ne e sa bonahale tlasa bupropion, e lebisitseng le ho eketsa ts'ebetso ea methapo libakeng tsa boko tse amanang le ts'ebetso e matla le ea maikutlo (ke hore, amygdala e atolositsoeng). Le ha litlamorao tsena tsa SSRI le dopamine le NA reuptake-inhibitor kalafo li bonts'itsoe bakeng sa ts'usumetso e otlolohileng, ho fokotseha hoa ts'ebetso ka har'a marang-rang a tlhokomelo ea fronto-parietal le cingulo-opercular ho ne ho bonahala ho bupropion le paroxetine nakong ea tebello ea nako e tlang pele ho maikutlo a litšoantšo tse tsosang takatso (Graf et al., 2013). Kahoo, meriana ea serotonergic le noradrenergic / dopaminergic e bonts'itse litlamorao tse fapaneng le tse lumellanang ho latela likarolo tsa ts'ebetso ea ts'usumetso e tsosang takatso. Tumellanong le likhopolo-taba tse fetileng (Pessiglione et al., 2006), karolo ea dopaminergic ea bupropion e ile ea ts'oaroa e ikarabella bakeng sa ts'ebetso e ntseng e eketseha holima ts'usumetso e totobetseng ea bootsoa (Abler et al., 2011), Mme karolo ea noradrenergic e ile ea hlalosoa e le ho sebetsana le litlamorao tebellong ea ts'usumetso ea maikutlo.Graf et al., 2013). Ho tlatselletsa lipatlisiso tsa rona tsa pejana ka sampole e ncha ea lithuto, re ne re ikemiselitse ho tsoela pele ho hlakola litlamorao tsa meriana ea monoaminergic, eo joale re sebelisang kalafo ea noradrenergic le antidopaminergic.

Khethollo ea noradrenalin reuptake inhibitor (SNRI), reboxetine, e imeloa kelellong e nang le khetho e phahameng ho ea ho morekisi oa noradrenalin le kamano e batlang e le tlase bakeng sa morekisi oa serotonin, monoamine, histamine le acetylcholine receptors (Hajos et al., 2004). Ka hona, e fana ka koloi e loketseng hantle ho fuputsa litlamorao tsa NA ho li-neural correlates tsa ts'usumetso ea thobalano. Liphello tsa reboxetine likarolong tse ling tsa ts'ebetso ea thobalano li se li tlalehiloe ho bakuli (Clayton et al., 2003b), e nang le litlamorao tse mpe ha li bapisoa le li-SSRI (Whisky le Taylor, 2013), haholoholo mabapi le khotsofalo ea thobalano, bokhoni ba ho hlasimoloha ka thobalano (Baldwin et al., 2006), le ho fihlela mokokotlo (Langworth et al., 2006). Leha ho le joalo, ho latela litlaleho tsa linyeoe (O'Flynn le Michael, 2000; Haberfellner, 2002; Sivrioglu et al., 2007Tlhahisoleseling ea sehlahisoa sa sehlahisoa e tlaleha kotsi e atisang ho eketseha ea ho ba le litlamorao tsa thobalano mabapi le ho se sebetse hantle ha erectile le ho emisoa ka nako e telele / ho lieha le ho utloa bohloko ho isa ho 10% ea linyeoe tse alafiloeng, ka sekhahla se eketsehang sa litla-morao tse joalo tlasa litekanyetso tse phahameng tsa khatello ea maikutlo. bakuli (Tanum, 2000).

Amisulpride ea lithethefatsi ea antipsychotic e na le kamano e phahameng le e khethollang ho postsynaptic D₂ le D₃ receptors (Perrault et al., 1997; Castelli et al., 2001; Hartter et al., 2003). Khopolo-taba e tloaelehileng ho fetisisa ea ho hlalosa ho se sebetse ka thobalano tlasa li-antipsychotic (bona La Torre et al., 2013 bakeng sa tlhahlobo) ke thibelo ea dopamine D.₂ receptors (Haddad le Sharma, 2007) tseleng ea tuberoinfundibular, ka keketseho ea bobeli ea maemo a prolactin (Park et al., 2012). Ka hona, re ne re lebelletse hore ts'ebetso e tla fokotseha ea dopaminergic neural correlates ea ts'usumetso ea thobalano haholoholo tlasa sethethefatsi sena se khethehileng.

Ho etsa lipatlisiso tsa li-neural correlates tsa ts'ebetso ea thobalano tlasa noradrenergic (reboxetine) le meriana ea antidopaminergic (amisulpride) lihloohong tse phetseng hantle, re ne re ikemiselitse ho tlatsa litholoana tsa lipatlisiso tsa rona tsa pejana mabapi le tšusumetso ea methapo ea serotonergic le melao ea dopaminergic ts'ebetsong ea thobalano (Abler et al., 2011) le ho tsoela pele ho khetholla mekhoa ea monoaminergic mabapi le ts'ebetso ea thobalano le ts'ebetso ea ts'usumetso ho sampuli e ncha ea banna ba phetseng hantle.

Lisebelisoa le mekhoa

barupeluoa ba

Re batlisitse lithuto tse 20 tse phetseng hantle, tse fapaneng le tsa banna, tsa banna, tsa letsoho le letona tlasa litlhare tse sa foleng tse nang le amisulpride (AMS), reboxetine (REB), le placebo (PLA) ka tatellano e sa lekanyetsoang. Ho qheleloa ka thoko taba e le ngoe ho tsoa tlhahlobisong e tsoelang pele ka lebaka la lefu la bokong (liso tsa gliotic) ho lebisa ho sampole ea ho qetela ea bankakarolo ba 1 (lilemo tse bolelang lilemo tse 19, SD 24.0; moeli oa 3.1-20). Barupeluoa ba ile ba hiroa ke puisano ka seqo kapa lipapatso tse ngotsoeng khamphaseng ea Ulm University. Pele ho thuto, morupeluoa e mong le e mong o ile a fumana tlhahlobo e felletseng ea bongaka, ho kenyeletsoa nalane ea bongaka, tlhahlobo ea 'mele, le Puisano e hlophisitsoeng ea Kliniki bakeng sa DSM-IV Axis I Psychiatric Disorders. Barupeluoa ba nang le bothata leha e le bofe ba hona joale kapa ba nakong e fetileng ba kelello bo fumanoeng patlisisong ea mafu a kelello ka lipotso tse bulehileng ke e mong oa lingaka tsa boithuto (HG kapa BA) kapa ba nang le matšoao a ngotsoeng e le "hona joale" kapa "karoloana" ho efe kapa efe ea li-module tsa DSM-IV Axis I Psychiatric Disorders. e ka be e sa nkuoa thutong. Liteko tsa mali tsa laboratori le li-electrocardiograms li ile tsa etsoa ho khetholla maloetse a renal, a hepatic kapa a pelo. Mekhoa e meng ea ho khetholla e ne e le boemo bofe kapa bofe bo tebileng ba bongaka, bokuli ba hajoale kapa bo fetileng ba methapo, ts'oaetso ea mantlha ea thobalano kapa mathata a thobalano, ts'ebeliso ea lithethefatsi tse seng molaong, le ts'ebeliso e fetelletseng ea caffeine kapa joala. Ha ho hiroa, matšoao a mantlha a khatello ea maikutlo a ile a hlahlojoa ke mofuta oa Sejeremane (Hautzinger le Bailer, 1993) ea Setsi sa Epidemiologic Study Depression Scale (Radloff, 1977). Potso ea lipotso tse mabapi le thobalano ea Massachusetts General Hospital (MGH-SFQ; Labbate le Lare, 2001) e ne e fanoa ho lekola lithahasello tsa mantlha tsa thobalano, ho tsosa takatso ea thobalano, bokhoni ba ho fihlela sekhahla, bokhoni ba ho fihlela le ho boloka erection, le khotsofalo e akaretsang ea thobalano pele ho thuto. Ho ea ka protocol ea boithuto, lenane la lipotso le fetotsoe ho lekola liphetoho tsa ts'ebetso ea thobalano bekeng e fetileng ea meriana (Abler et al., 2011). Ha li kenyellelitsoe, lihlooho tse hlahisitsoeng ka kakaretso ea lipotso tsena tse mabapi le 10 (e bolelang 10.7; SD 1.7), e bonts'a ts'ebetso ea thobalano e sa sebetseng.

Phuputso e ile ea amoheloa ke komiti ea boitšoaro ea lehae ea Univesithi ea Ulm, mme bankakarolo bohle ba fana ka tumello e ngotsoeng e nang le tsebo e lumellanang le Phatlalatso ea Helsinki.

Moralo oa Boithuto le Mekhoa

Ka har'a moralo o hlophisitsoeng, o habeli o foufetseng, o laoloang ke placebo, kahare ho sehlooho, lithuto li amohetse 200mg AMS (100mg habeli ka letsatsi), 4mg REB (2mg habeli ka letsatsi), le PLA (habeli ka letsatsi) matsatsi a 7 ka 'ngoe, e arotsoe ke karolo ea ho hlatsoa bonyane libeke tse 2. Joalo ka leano la rona la pele la thuto (Abler et al., 2011), sampole ena e ncha ea lithuto e ile ea batlisisoa ka makhetlo a fapaneng a 3, mme litlhahlobo tsa fMRI li etsahetse ka letsatsi la bosupa la meriana, lihora tsa 2 kamora ho noa capsule ea ho qetela. Bafo ba ile ba botsoa hore ba tlohele joala bo ts'oanang le meriana ea boithuto mme haholo bakeng sa matsatsi a 3 pele ho fMRI. Ba ile ba kopuoa hape ho tlohela kofi ka letsatsi la lisene. Ho fana ka tumello ea ho pepesetsoa lithethefatsi le ho e latela, lisampole tsa mali li fumanoe kamora ho lekola ka seng (hoo e ka bang lihora tse 3 kamora ho noa lithethefatsi) le ho hlahlojoa kamora ho phethela thuto eohle. Tekanyo ea karolelano ea plasma amisulpride e ne e le 137.7ng / mL (SD 54.8), mme boemo bo bolelang ba reboxetine e ne e le 75.7ng / mL (SD 28.9). Maemo a mali kahare ho sebaka se lebelletsoeng a fumanoe ho e 'ngoe le e' ngoe ea lithuto tsa 19 bakeng sa lithethefatsi ka bobeli, ho bonts'a hore ho latela tšebeliso ea lithethefatsi ho ne ho ts'oana le lithuto tsohle.

Lipotso tsa lipotso tse ling

Ts'ebetso ea thobalano bekeng e fetileng ka tšebeliso ea lithethefatsi kapa placebo e ile ea hlahlojoa ho sebelisoa MGH-SFQ kamora ho skena ka seng. MGH-SFQ e na le lipotso tse 5 tse nang le lintlha tse tsoang ho 1 ho isa ho tse 6. Lintlha tse kenyelletsoang li tloha ho 5 (boleng bo fokolang: ntlafatso ea ts'ebetso ea thobalano) ho feta 10 (thobalano e sa fetohe ha e bapisoa le e tloaelehileng) ho 30 (boleng bo phahameng: ts'ebetso ea thobalano e senyehile haholo ha e bapisoa le tloaelehileng). Lintlha tsa <2 bakeng sa lipotso tse le 'ngoe kapa lintlha tse bokellaneng> 10 li bonts'a ts'oaetso e sa sebetseng ea thobalano (bakeng sa lintlha, bona Labbate et al., 2001; Abler et al., 2011). Litla-morao tsa meriana li ile tsa hlahlojoa ke e mong oa lingaka tsa thuto (HG kapa BA) nakong ea tlhahlobo ea bongaka ka lipotso tse bulehileng le karolo e hlophisitsoeng (sekhahla sa litlamorao tsa UKU, Lingjaerde et al., 1987) lenaneong ka leng. Litlamorao tsa meriana li ile tsa hlahlojoa le Stanford Sleepiness Scale (SSS; Hodes et al., 1973). Mehato e phetoang ea tlhahlobo ea phapang (ANOVA) le liteko tsa post-hoc tsa Newman Keuls li ile tsa ngolisoa ho sekaseka sephetho sa lipotso.

Khothatso ea fMRI

Ho ile ha sebelisoa livideo tse tsosang takatso le tse sa nke lehlakore bakeng sa ho susumetsa pono ka nako e telele ka har'a moralo o tloaelehileng joalo ka ha re ne re etsa teko ea peleAbler et al., 2011). Likoto tsa video tse tsosang takatso li ile tsa nkuoa lifiliming tsa batho ba baholo tsa khoebo 'me tsa bonts'a thobalano (ho pholla litho tsa botona kapa botšehali, ho etsa thobalano ka molomo, thobalano) pakeng tsa monna a le mong le mosali a le mong kapa ba babeli. Livideo tsa ho se nke lehlakore li bontšitse banna le basali likamanong tse sa jeleng paate le maikutlong. Lintho tse khahlisang le tse sa nke lehlakore li ne li lekana le 'mala, palo le bong ba lithuto tse sebelisanang, bolelele ba tšebelisano, le hore na lihlooho tse bontšitsoeng li apere kapa li hlobotse. Likoto tsa video tse robong tsa se seng le se seng sa maemo a 1 li hlahisitsoe bakeng sa metsotsoana e 1 ka 'ngoe, li arotsoe ke nako ea ho lokisa metsotsoana e 2, e hlahisang bolelele ba paradigm ea metsotsoana e 2. Likoto tsa video li hlahisitsoe ke li-goggles tsa video tse lumellanang le matla a khoheli ka tatellano ea maiketsetso e nang le likoto tse 20 tse latellanang tsa boemo bo tšoanang. Tlhophiso ea likarolo tse tšoanang tsa video e ne e sa lekana ho latela lithuto le meriana.

Theko ea fMRI

Litšoantšo tsa li-anatomical tsa T1 (li-voxels tsa 1x1x1-mm) le litšoantšo tse sebetsang tsa matla a khoheli li fumanoe ho sebelisoa sistimi ea imaging ea matla a khoheli a 3T feela (Siemens Magnetom Allegra, Erlangen, Jeremane). Ho fumanoe likarolo tse mashome a mabeli a metso e meraro tse nang le boholo ba setšoantšo sa pixels tsa 64 × 64 le lebala la pono la 192mm. Botenya ba selae e ne e le 3mm ka lekhalo la 0.75-mm, e leng se hlahisang boholo ba voxel ba 3x3x3.75mm.

Likarolo li ne li sekametse ho feta moleng oa bicommissural ka lehlakore la -15 ° lipakeng tsa lifofane tse parolang le tsa coronal ho fokotsa kotsi ea ho hlaseloa habonolo mehahong ea mantlha ea bokong ho kenyeletsoa libaka tse khahlisang (amygdala, basal ganglia le libaka tse tlase tse ka pele). Ka lebaka la palo e fokotsehileng ea lilae ka lebaka la nako e khutšoane ea ho pheta-pheta (TR) ea metsotsoana ea 1.5, ho ne ho se na tšireletso e felletseng ea boko. Litšoantšo tse sebetsang li tlalehiloe ho sebelisoa T2 * -sensitive gradient echo echo-planar imaging liphetoho lipakeng tsa BOLD. Kakaretso ea meqolo e 487 e fumanoe nakong ea ho shebella livideo ho TR ea li-millisecond tse 1500 (TE 35 milliseconds, flip angle 90 °). Litšoantšo tsa pele tsa 7 li fumanoe ho lumella litlamorao tsa T1 mme hamorao tsa lahloa. Litheko tse ling tse peli tse fumanoeng qalong ea tatellano ka 'ngoe' me li sa bolokoa disk e kentsoe nakong ea tekano ea T1 (metsotsoana e 3). Qetellong ea ho sekaseka, ho ile ha fumanoa setšoantšo sa sebopeho se phahameng sa T1 ka ho tsamaisa matla a khoheli a hlophisitseng tatellano e potlakileng ea ho fumana gradient echo (TR = 2300 milliseconds, TE = 3.93 milliseconds, inversion time = 1100 milliseconds, flip angle = 12 °, FoV = 256mm, boholo ba matrix: 256 x 256, voxel volume = 1mm³Tloaelo ea selae: sagittal; nako ea ho lekola = metsotsoana e 517).

fMRI Analysis

Ho etsa lits'oants'o tsa litšoantšo le lipalo-palo ho entsoe ho sebelisoa Statistical Parametric Mapping (Lefapha la Wellcome, London, UK) ka mokhoa o sa reroang oa litlhahlobo tsa sehlopha. Lintlha tse tsoang thutong ka 'ngoe li ile tsa etsoa esale pele ho kenyeletsoa nako ea nako, ho hlophisoa bocha le ho hlophisoa hore e be template e tloaelehileng (Montreal Neurological Institute) e nang le qeto ea sebaka sa 2x2x2mm³. Smoothing e ne e sebelisoa ka 8-mm FWHM isotropic Gaussian kernel. Li-autocorrelations tsa kahare li ile tsa tlalehoa ke AR (1), 'me marotholi a maqhubu a tlase a ile a tlosoa ka ho sefa sefahleho se phahameng.

E tšoana le ho Abler et al. (2011), litlhahlobo tsa boemo ba pele li ile tsa etsoa bakeng sa sehlooho ka seng. Ho latela mofuta o akaretsang oa linear, re hlalositse li-regress tsa 2 ho sekaseka e 'ngoe le e' ngoe ea mefuta ea 2 ea livideo tse tsosang takatso (tse tsosang takatso, tse sa amaneng le 'mele). Livideo tsa video li ile tsa etsisoa e le liketsahalo tse atolositsoeng ka nako ea metsotsoana e 20 mme tsa kholisoa ka ts'ebetso ea karabelo ea hemodynamic. Mefuta e 6 ea tokiso ea tokiso ea mohlala e setseng e kenyelelitsoe mefuteng e meng le e meng. Ha ho le lethathama la nako le neng le na le motsamao oa 1mm kapa ho feta ka tsela efe kapa efe kapa liphetolo tsa> 1 degree lipakeng tsa mefuta e latellanang. Litšoantšo tse fapaneng tsa maemo a litšila le a seng a tlhaho li ile tsa kenyelletsoa tlhahlobo ea sehlopha sa boemo ba bobeli ho sebelisoa mofuta oa ANOVA o nang le boemo (erotic / nonerotic) e le eona ntho ea pele. Kalafo (PLA / AMS / REB) e ekelitsoe e le ntho ea bobeli ka methati ea 3 ho lekola litlamorao tse kholo tsa ts'ebelisano kalafong ka phapang ea lits'oants'o tse mpe tsa maikutlo. Ntlha ea boraro e etsisitse phapang e amanang le taba.

Litlamorao tsa kalafo li ile tsa hlahlojoa ka ho sebelisana le likamano tse 1 tsa mohatla le kalafo ho ikarabella bakeng sa kompone e le 1 e sebetsang le boemo bo sebetsang ba 1 vs 1 placebo le boemo ba taolo ea 1 (erotic, nonerotic; placebo, verum). Ho nka lehlakore le le leng la t-phapang ho latela, litlamorao li nkuoa li le bohlokoa moeling oa lipalo P<0.0025, e sa nepahala boemong ba voxel le boholo ba sehlopha sa bonyane li-voxels tse makatsang tse 419 tse lumellanang le boemo ba P<0.05, phoso ea lelapa (FWE) e lokisitsoe sehlopheng.

Ho etsa lipatlisiso mabapi le likamano tse kholo lipakeng tsa litlamorao tsa kalafo ea fMRI le ts'ebetso ea motho ka mong ea thobalano, re ile ra bala tlhaiso-leseling e mengata e kenyelletsang e ngoe le e ngoe ea liphallelo tsa 5 MHG-SFQ ka har'a mask ea ts'ebelisano e bohlokoa ea kalafo. Mefuta e fapaneng e ne e le likhakanyo tse ikhethileng tsa tšebelisano-ka-kalafo ho tloha sebakeng se fapaneng khahlanong le reboxetine. Barekisi e ne e le phapang ea phapang pakeng tsa placebo le reboxetine bakeng sa li-subscales tse 5. Mehatla e le 'ngoe ea mohatla e ne e sebelisetsoa ho leka litlamorao tse kholo tsa khatello ea maikutlo. Liphello li ne li nkuoa li le bohlokoa boemong ba P<0.0025 boemong ba voxel le sehlopha sa bonyane li-voxels tse 16 tse ikhethang tse ikhethang, tse tsamaellanang le boemo ba P<0.05, FWE e lokisoa sehlopheng.

Results

Lipotso tsa lipotso

Karolelano ea Setsi sa Epidemiologic Study Depression Scale kakaretso ea 8.0 (SD 6.04) ha e bonts'a matšoao a sithabetsang ho bankakarolo.

Litla-morao tse hlahlobiloeng ke sekhahla sa litlamorao tsa UKU ha lia ka tsa hlaha bakeng sa mefuta e latelang: ho eketseha ha nako ea boroko, ts'ebetso e eketsehileng ea litoro, dystonia, ho tia, hypokinesia / akinesia, mohopolo oa hyperkinesia, ho thothomela, akathisia, ho oa ha sethoathoa, paraesthesias, salivation e eketsehileng, letšollo, pherekano ea micturition, polyuria / polydipsia, ho ba le botsoa, orthostatic, ho otloa ke pelo, tachycardia, ho eketsa ho fufuleloa, ho phatloha, pruritus, photosensitivity, ho eketsa pigmentation, boima ba 'mele, boima ba' mele, galactorrhoea le gynaecomastia. Bonyane ponts'o e le 'ngoe ea litlamorao tlasa moriana o fanoe bakeng sa lintho tse latelang, athe liphapang lipakeng tsa kalafo li ne li se bohlokoa: mathata a mahloriso (F (2,36) = 0.55; P= 0.582), asthenia / lassitude / eketseha ho felloa ke matla (F (2,36) = 2.15; P= 0.131), boroko / sedation (F (2,36) = 1.61; P= 0.214), memori e sa sebetseng (F (2,36) = 1.00; P= 0.378), khatello ea maikutlo (F (2,36) = 1.31; P= 0.283), ho se tsotelle hoa maikutlo (F (2,36) = 1.18; P= 0.320), litšitiso tsa bolulo (F (2,36) = 0.19; P= 0.827), ho nyekeloa ke pelo / ho hlatsa (F (2,36) = 0.24; P= 0.788), ho patoa (F2,36) = 0.08; P= 0.924), le (tsitsipano) hlooho e bohloko (F2,36) = 0.12; P= 0.888). Liphapang tsa bohlokoa lipakeng tsa kalafo li ile tsa bonoa bakeng sa litla-morao tsa 3: ho fokotsa mathe (F (2,36) = 4.58; P= 0.017), merusu ea ka hare (F (2,36) = 3.71; P= 0.034), le nako e fokotsehileng ea boroko (F (2,36) = 6.87; P= 0.003). Teko ea Post-hoc e bonts'itse mathe a fokotsehile tlasa reboxetine (REB) ha e bapisoa le placebo (P= 0.033) le amisulpride (P= 0.013), athe amisulpride (AMS) e ne e sa fapane le placebo (P> 0.05). Merusu ea kahare e ne e boetse e totobala tlasa REB ha e bapisoa le AMS (P= 0.032) empa e sa amane le placebo (P= 0.067); hape, AMS le placebo ha lia ka tsa fapana (P> 0.05). Nako ea boroko e fokotsehileng e tlalehiloe tlasa REB ha e bapisoa le placebo (P= 0.006) le AMS (P= 0.004), athe nako ea boroko e ne e sa fapana haholo tlasa AMS mabapi le placebo (P> 0.05). Hoa hlokomeleha moelelong ona hore ANOVA ea litekanyo tse phetoang ha ea ka ea bontša ts'oaetso ea bohlokoa ho sedation kapa boroko hang kamora ho skena ha fMRI (SSS; F (2,36) = 1.47; P= 0.244; bakeng sa lintlha tse qaqileng sheba Tafole S1)

Lipalo tse akaretsang tsa MHG-SFQ ha ho ngolisoa e ne e le 10.7 (SD 1.70) le 11.7 (SD 2.50) tlasa placebo. Ho lekoa ka bobeli ho bontšitse hore ha ho na phapang e kholo lipakeng tsa li-placebo le lintlha tsa ngoliso (t (18) = - 1.55; P= 0.138), le MGH-SFQ-data ha e ngolisoa ha ea ka ea nkuoa hape. Litlamorao tsa kalafo ho lintlha tse akaretsang ho MHG-SFQ li ne li le bohlokoa (F (2,36) = 8.10; P= 0.001). Liteko tsa Post-hoc (Newman Keuls) li netefalitse ts'oaetso e mpe ea thobalano tlasa SNRI reboxetine ha e bapisoa le li-placebo ka bobeli (P= 0.002) le amisulpride (P= 0.003). Ts'ebetso ea thobalano tlasa antidopaminergic drug amisulpride e ne e sa fapane le placebo (P= 0.850). Ha ho nahanoa ka liphallelo tse fapaneng (Lethathamo 1), reboxetine e bile le litlamorao tse mpe tse amanang le placebo kapa amisulpride bakeng sa ho tsosa takatso ea botona kapa botšehali, 'mele o moholo, le bokhoni ba ho fihlela / ho boloka erection. Phokotso ea khotsofalo ea thobalano le eona e bonoe tlasa reboxetine e amanang le amisulpride, empa eseng ha e bapisoa le placebo. Papiso lipakeng tsa amisulpride le placebo ha ea ka ea senola phapang e kholo ho efe kapa efe ea lihlapiso (Setšoantšo sa 1A-B).

Liphetho tse tsoang ho ANOVA tse nang le "Phekolo" ea Ntlha (Reboxetine / Amisulpride / Placebo) ho Litekanyetso tsa Sehlopha-tse Akaretsang bakeng sa Tlatsetso ka 'ngoe ea MGH-SFQ.

Setšoantšo sa 1.

Setšoantšo sa 1.

A, Mean total scores (SD) ho Massachusetts General Hospital Functioning Questionnaire (MGH-SFQ). Ka kakaretso, ts'ebetso ea thobalano e ikemetseng e ne e le bohlokoa haholo (P<0.05) e holofetse tlasa reboxetine ha e bapisoa le placebo le amisulpride. Thobalano ...

Lipalo tsa fMRI

Liphello tse kholo

Ho pheta liphetho tse fetileng (Abler et al., 2011), Litholoana tsa mantlha tsa ts'usumetso ea pono e tsosang takatso tlasa placebo (livideo tsa thobalano tse sa amaneng le thobalano) sampoleng ea hajoale li bonts'a haholo (P<0.05 Lekala la sehlopha sa FWE le lokisitsoeng) le eketsehile ts'ebetso ea methapo ea kutlo ho gyrus ea maemo a holimo le e tlase, gyrus e bohareng ea occipital, parietal lobule e tlase, gyrus e ka tlase, precentral gyrus, insula, hippocampus, midbrain (e nang le likarolo tsa substantia nigra), putamen le mokokotlo oa caudate.

Liphello tsa Kalafo

Likamano tse matla tsa kalafo le kalafo li fumanoe bakeng sa lesihla le nang le khubu e nepahetseng ea caudate le likarolo tsa anterior putamen le mokokotlo oa lentiforme. Liteko tsa Post-hoc li netefalitse hore litlamorao tsena li amana le ts'ebetso ea methapo e fokolitsoeng tlasa reboxetine ha e bapisoa le placebo (bona Lethathamo 2; Setšoantšo sa 2A-B). Teko e khelositsoeng ea t-phapang mabapi le ts'ebetso e eketsehileng ea neural tlasa reboxetine khahlano le placebo ha ea ka ea senola litlamorao. Ho feta moo, ha ho liphetho tsa bohlokoa tse fumanoeng ha ho bapisoa sebaka sa "placebo" le "amisulpride" kapa "amisulpride" khahlanong le reboxetine, leha e le lipalo-palo tse bobebe tsa P<0.025 mme ntle le litokiso tsa sehlopha.

Tšebelisano ea Bohlokoa ea Phekolo ka Boemo Ha ho Fapanoa Phapang ea Placebo Minus Reboxetine bakeng sa Phapano ea Ts'usumetso e Ntle ea Ts'oaetso (ANOVA; P <0.0025, E sa nepisoe ho Voxel Level le Cluster Extent ea Bonyane 419 ka mokhoa o ts'oanang ...

Setšoantšo sa 2.

Setšoantšo sa 2.

Tšebelisano ea bohlokoa ea placebo-by-reboxetine kahare ho karolo e nepahetseng ea caudate e bonts'itsoeng ka lilae tsa sagittal le transversal tlhorong ea voxel (P<0.0025, e sa nepisoang boemong ba voxel le boholo ba sehlopha sa bonyane 419 e bohlokoa haholo ...

Tlhatlhobo

Tlhatlhobo e mengata ea khatello e ile ea etsoa tekong ea likamano tsa liphetoho tse ikhethileng mabapi le thobalano le ts'ebetso e fapaneng ea ts'ebetso ea fMRI tlasa SNRI reboxetine khahlano le placebo. Re senotse khokahano ea bohlokoa kahare ho karolo e bohareng ea karolo e nepahetseng ea caudate (e bolelang coefficient e lekanang ea khokahano r= 0.709, P = 0.05 FWE e lokisitsoe sehlopheng; Palo ea li-voxels: 22; tlhōrō ea boleng ba Z: 3.10; x, y, z = 10, 22, 4) le MGH-SFQ subscale "lithahasello tsa thobalano" e bonts'ang hore ho fokotseha ha ts'ebetso ea methapo e tsamaeang le lithahasello tsa thobalano (Setšoantšo sa 3). Ha ho le e 'ngoe ea lithuso tse ling tsa MGH-SFQ e amanang haholo le phapang ea ts'ebetso ea fMRI.

Setšoantšo sa 3.

Setšoantšo sa 3.

Liphetho tsa tlhahlobo ea makhetlo a mangata ea tlhaiso-leseling ea data ea fMRI le MGH-SFQ subscales joalo ka li-regressor ka har'a mask tse nang le li-voxels tse nang le tšebelisano e kholo ea placebo-by-reboxetine (boholo ba sehlotšoana sa sehlopha: 565). Tšebelisano ea bohlokoa (e bolela kamano e sa fellang ...

Puisano

Ho holisa lipatlisiso tsa rona tse fetileng (Abler et al., 2011) ho li-neural correlates tsa thobalano tlasa serotonergic le meriana ea dopaminergic, thutong ea hajoale re tsepamisitse maikutlo litlamorao tsa meriana ea noradrenergic le antidopaminergic ka har'a sampole e ncha ea lithuto. Ka har'a moralo oa blind-blind, o laoloang ke placebo, oa crossover, re ile ra fuputsa baithaopi ba banna ba 19 ba phetseng hantle ba sebelisa mosebetsi oa video o ts'oanelang ho ts'oaroa o ts'oanang le taolo ea lithethefatsi tsa noradrenergic reboxetine, antidopaminergic agent amisulpride le placebo. Reboxetine e fokotsa litekanyo tse ikemetseng tsa ts'ebetso ea thobalano ha e bapisoa le li-placebo le amisulpride, athe litekanyetso tsa ts'ebetso ea thobalano ha lia ka tsa fetoha tlasa amisulpride. Haholo-holo, ho tsosa takatso ea thobalano le bokhoni ba ho fihlela sekhahla le ho fihlela le ho boloka erection li ile tsa ameha tlasa reboxetine mabapi le placebo le amisulpride

fMRI nakong ea ts'usumetso ea boits'oaro e pheta ts'ebetso e kholo ea libaka tsa boko tse seng li tlalehiloe liphuputsong tse fetileng (Redoute et al., 2000; Park et al., 2001; Arnow et al., 2002; Walter et al., 2008; Metzger et al., 2010; Abler et al., 2011; Georgiadis le Kringelbach, 2012), ka hona ho ts'ehetsa ho ts'epahala ha phephetso ea ts'ebetso. Likamano tse matla tsa kalafo ka maemo li ne li amana feela le reboxetine (SNRI) mabapi le phokotso ea ts'ebetso ea khubung ea caudate e nepahetseng ha e bapisoa le placebo le amisulpride. Ho feta moo, liphetoho tse kenngoang kahare ho karolo e bohareng ea mokokotlo oa caudate li ne li tsamaellana le liphetoho tsa litekanyetso tse ikhethileng tsa lithahasello tsa thobalano. Hammoho le tlhaiso-leseling e sa fetoheng ea boits'oaro, ha ho na litlamorao tse kholo kalafong ea ts'ebetso ea neural ha ho ts'oaroa maikutlo a litšila ho bonoe bakeng sa AMS mabapi le PLA.

Fuoa karolo ea dopamine ho sebetsana le litakatso tsa thobalano (Abler et al., 2011; Oei et al., 2012) le thepa ea antidopaminergic (Castelli et al., 2001; Assem-Hilger le Kasper, 2005) ea amisulpride, ho ne ho lebelletsoe litlamorao tse fetang tse bonoang (Setšoantšo sa 2B). Ho ba sieo ha litlamorao tse kholo ho kanna ha amahanngoa le thepa e itšetlehileng ka tekanyetso ea litlhare tsa moriana (Andrade, 2013). Litla-morao tsa li-antipsychotic tsa amisulpride li tlalehiloe bakeng sa litekanyo tse phahameng ho tloha ho 400 ho isa ho 600mg / d, ho hlahisang D e tšepahalang₂ bolulo ba li-receptor (Perrault et al., 1997). Leha ho le joalo, litlaleho li bontšitse katleho ea ho imeloa kelellong ka litekanyo tse tlase tsa 50 ho isa ho 200mg / d (joalo ka ha e sebelisitsoe thutong ea rona) ka ho thibela presynaptic dopamine autoreceptors (Perrault et al., 1997; Smeraldi, 1998; Montgomery, 2002). Litlamorao tsena tse bobebe tsa prodopaminergic li ka baka lebaka la ho haelloa ke ts'ebetso ea thobalano sampoleng ea rona. E le tlhaloso e 'ngoe e ka bang teng, tekanyo ea hona joale ea amisulpride e kanna ea se ke ea eketsa litekanyetso tsa prolactin tsa mali ka ho lekana tse atisang ho amahanngoa le ho se sebetse hantle ka thobalano.Hartter et al., 2003) 'Me li ka hlahisa litlamorao tsa tsona ka pheriferale eseng litsela tse bohareng tsa dopaminergic.

Hobane moemeli oa noradrenergic reboxetine o tlalehiloe hantle mabapi le ho se sebetse ka thobalano ho amanang le moriana o loantšang khatello ea maikutlo (Clayton le Zajecka, 2003a; Baldwin et al., 2006), re ne re lebelletse litlamorao tse tlase tsa lithethefatsi tsena ho feta kamoo re li boneng. Leha ho le joalo, litlaleho tsa pejana tsa palesa e telele (Haberfellner, 2002), ho se sebetse ha erectile, le ejaculation e itlelang feela (O'Flynn et al., 2000; Sivrioglu et al., 2007hammoho le anorgasmia (Langworth et al., 2006Tlas'a reboxetine li tsamaellana le liphetho tsa hona joale. Ho nka kamano e sothehileng ea u-curve, keketseho ea noradrenergic neurotransmission ho feta boholo ba sistimi e seng e ntse e leka-lekane, e phetseng hantle ea NA e kanna ea amana le phokotso ea ts'ebetso ea thobalano, joalo ka liphetho tse fetileng moo NA e fetelletseng e ileng ea ama ts'ebetso ea kelello lithutong tse phetseng hantle (Graf et al., 2011).

Ts'ebetsong, litlamorao tse kholo tsa kalafo ts'ebetsong ea li-neural li ne li lekantsoe khubung ea caudate e nepahetseng e nang le li-activated neural activations tlasa SNRI reboxetine ha e bapisoa le placebo kapa amisulpride. Ts'ebetso ea mokokotlo oa caudate e kentse letsoho khafetsa likarolong tsa boits'oaro ba sechaba, lerato la maikutlo a lerato, le ts'ebetso e matlafatsang ea maikutlo.Redoute et al., 2000; Bartels le Zeki, 2004; Aron et al., 2005; Walter et al., 2008) ka lateralization ho le letona joalo ka ha re ithuta (Aron et al., 2005; Walter et al., 2008). Ntle le moo, lithutong tsa pejana, mehato ea ho eketseha ha mokokotlo oa penile le ho ts'oaroa e 'nile ea amahanngoa le ts'ebetso e phahameng ea methapo ea kutlo ea mokokotlo oa caudate (Park et al., 2001; Arnow et al., 2002). Nakong ea tšusumetso ea boits'oaro, ts'ebetso ea `` caudate nucleus '' e hokahantsoe le boits'oaro bo tataisoang ke sepheo le moputso (Arnow et al., 2002). Le ha ts'ebetso e kahare ho likarolo tsa ventral tsa striatum, haholoholo tse nang le li-nucleus accumbens, hangata li amahanngoa le tebello le kamohelo ea likhothaletso, lipatlisiso tsa morao-rao lithutong tse phetseng hantle (Miller et al., 2014E ka kopanya likarolo tse fapaneng tsa moputso le ts'ebetso ea ts'usumetso le phapang e ts'oanang le caudate. Ts'ebetso ea ts'ebetso ea ts'ebetso ea morao-rao e eketsehile ka tšusumetso ha ho ntse ho eketseha ts'ebetso ea likarolo tse ling tsa khubung ea nyutlelie e eketsehile ka moputso. Ka hona, ho fumana ha rona ho fokotseha ha ts'ebetso ea caudate tlasa reboxetine le khokahano ea phokotso ea ts'ebetso le lithahasello tse fokotsehileng tsa thobalano ho ka hlahisa likarolo tse kholo tsa ts'usumetso ea thobalano. Tumellanong le tlhaloso ena, phuputso ea morao-rao e mabapi le litlamorao tsa reboxetine litekong tse ts'oanang hape le lihloohong tse phetseng hantle e senotse tšebetso e sa ameheng ea ts'ebetso ea ts'ebetso ea ts'ebetso nakong ea ts'ebetso ea lijo tse hlabosang ()McCabe et al., 2010).

Kaha striatum e ho batho ha e kenngoe haholo ke noradrenergic neurons (Wallman et al., 2011), Ts'ebetso ea methapo e fokolitsoeng ka har'a caudate tlasa SNRI e kanna ea bonts'a phello e sa tobang ea maemo a eketsehileng a NA. Likamano tse kopanetsoeng lipakeng tsa dopamine le NA system (Guiard et al., 2008) le ts'ebetso ea thibelo ea NA ho li-neuron tsa dopaminergic (El Mansari et al., 2010) e ka fana ka tlhaloso mona.

sheba mefokolo ea

Thutong ea hajoale, ke lithuto tsa banna feela tse ileng tsa batlisisoa ho qoba sephetho sa leeme ka lebaka la phapang ea lihormone tse amanang le ho ilela khoeli ho basali (mohlala, Abler, et al., 2013). Ka hona, liphetho tsa hajoale li ke ke tsa fetisetsoa sampoleng ea basali, e ka hlokang thuto e eketsehileng e laolang ka ho hlaka boemo ba lihormone. Nako e fokotsehileng ea boroko tlasa reboxetine joalo ka litlamorao tse lebelletsoeng tsa moemeli oa noradrenergic e kanna ea ba sesosa sa ho sitisa ho fumana data tlasa phephetso e sebetsang. Leha ho le joalo, liphetho tse tsoang ho SSS hanghang tse fumanoeng kamora ho skena ha fMRI li ne li sa bontše hore boroko kapa sedation li ne li tla bapala karolo ea bohlokoa. Ha re bapisa le litlhahlobo tse ikhethileng ha re ingolisa, re bone keketseho e nyane le ha e le nyane ea lipalo tsa MGH-SFQ tse seng li ntse li le tlasa placebo, tse ka bonts'ang hore tlhaiso-leseling ka litla-morao tsa putative e ka be e bakile litlamorao tsa mofuta o mong le tlasa placebo. Litlamorao tse joalo tsa tebello li ka be li ile tsa susumetsa liphapang pakeng tsa verum le placebo, ha feela litlamorao li ka be li fokolitse lintlha tsa MGH-SFQ tlasa placebo e lebisang keketseho e leeme lipakeng tsa verum le placebo. Keketseho e nyane ea sekhahla sa MGH-SFQ e bua khahlano le monyetla ona.

Le ha tlhaiso-leseling ea lipotso e ka fana ka tsebo e mabapi le boiphihlelo bo ikhethileng mabapi le ts'ebetso ea thobalano, litekanyo tsa sepheo sa likarolo tsa karabelo ea thobalano, mohlala, penile turgidity, li lokela ho nkuoa hape ho eketsoa lithutong tse tlang ka sehlooho se le seng. Ka mokhoa o ts'oanang, tekanyo ea sepheo sa ho noa joala e ka ba thuso ho tlatselletsa litlaleho tsa mantsoe mabapi le ho latela melaoana ea boithuto haholo-holo phuputsong ea baithuti ba univesithi ba bacha le ba phetseng hantle. Kamora nako, lipatlisiso tse ling li kanna tsa nahana ka litekanyo tse fapaneng tsa sethethefatsi se le seng tekong e le 'ngoe ea ho batlisisa litlamorao tse itšetlehileng ka litekanyetso tse ka hlalosang ho ba sieo ha tšebelisano' moho tlasa lethal dose e tlase ea amisulpride.

fihlela qeto e

Ka har'a moralo o sa sebetseng, o laoloang ke placebo le crossover, re ile ra etsa lipatlisiso tsa li-neural correlates tsa maikutlo a ts'oanang le a ts'oaetso ea litaba tse phetseng hantle tlasa noradrenergic antidepressant reboxetine le dopamine antagonist amisulpride ho lekola litlamorao tsa lithethefatsi ntle le liphetoho tse ling tse amanang le bokuli ts'ebetsong ea thobalano tlasa meriana ena. Amisulpride ea tekanyetso e tlase ha ea ka ea fetola litekanyetso tsa boits'oaro ba thobalano, mme ka hona, ts'ebetso ea methapo e ile ea lula e sa amehe, e ka amanang le litlamorao tse ka bang teng tsa prodopaminergic tlasa litekanyo tse tlase tsa sethethefatsi sena. Bakeng sa reboxetine ea moemeli oa noradrenergic, re bone ho holofala hoa thobalano lithutong tse phetseng hantle tse tsamaeang le ts'ebetso ea methapo ea kutlo e kenelletseng kahare ho mokokotlo oa caudate o ka bonts'ang likarolo tse fokotsehileng tsa ts'usumetso e sebetsanang le ts'oaetso e tlase tlasa mahlahana a noradrenergic.

Boitsebiso bo Eketsehileng

Bakeng sa lisebelisoa tse tlatselletsang tse tsamaeang le pampiri ena, etela http://www.ijnp.oxfordjournals.org/

Tlhaloso ea Thahasello

Bangoli bohle ba phatlalatsa hore ha ho na lithahasello tsa lichelete kapa lichelete tse qothisanang lehlokoa le mosebetsi o hlalositsoeng. C. Metzger le M. Walter ba ne ba tšehelitsoe ke SFB-779.

lumela hore baa fokola

Re leboha Moprofesa Dr C. Hiemke le basebetsi ba hae Univesithing ea Mainz (Jeremane), Lefapha la Psychiatry le Psychotherapy, bakeng sa ho metha maemo a serum ea lithethefatsi.

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