Rashin hanzari tsakanin magungunan ƙwayoyin cuta da damuwa a cikin ma'aikatan 'yan sa kai na lafiya (2016)

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Gabatarwa

Ƙwarewa wani mahimmanci ne da ke ba da gudummawa wajen bunkasawa da haɓakawa da rashin lafiyar nakasa ta nakasassu na nakasassu, ciki har da ƙwaƙwalwa da kuma rashin tausayi. Ɗaya daga cikin hanyoyin da ake ciki shine 'farfadowa'; wannan shine, bin magungunan da aka yi wa magunguna da magungunan ƙwayoyin cuta, wasu illa zasu iya ci gaba sosai.^{1, 2, 3} A cikin mutanen da suka kamu da cutar, an ba da shawarar da aka inganta don magance rashin lafiya da kuma sake dawowa. ^{4, 5, 6, 7}

A cikin dabbobi, 'hankalta' ga psychostimulants shine batun daidaitawa tare da danniya.^{8, 9} Alal misali, a cikin rodents, sake bayyanawa ga likitoci na jiki yana ƙaruwa da damuwa don motsawa motar motsa jiki, tsoma baki da kuma dopamine (DA) saki.^{10, 11} Sabanin haka, ƙaddamarwa ga gwaji na gwaji zai iya ƙara haɓaka halin da DA zuwa psychostimulants.^{3, 12, 13, 14} Kodayake ba a fahimci kwayoyin halitta na kwayoyin halitta ba tare da cikakken fahimta ba, akwai shaidar cewa ya haɗa da haɗuwa tsakanin maɓallin hypothalamic-pituitary-adrenal axis da kuma DA, musamman wadanda suka taso daga mesencephalon.¹⁵ Yawan binciken da aka nuna sun nuna cewa duka damuwa da d-amphetamine za su kunna magungunan hypothalamic-pituitary-adrenal axis, wanda ya haifar da ƙara yawan matakan cortisol.¹⁶ Glucocorticoids, a biyun, na iya sauƙaƙe DA saki ta hanyoyi daban-daban, ciki har da maganin tyrosine hydroxylase, monoamine oxidase-A da DA reuptake.¹⁶ Tabbas, wannan zai iya haifar da ƙarin amsawar DA game da yaduwar wahala. Lalle ne, cirewar babban magunguna na glucocorticoids, ta hanyar tiyata ko kuma kariya daga kwayoyin halitta (metyrapone), ya rage cigaba da ci gaban kwayar cutar DA.¹⁷

Mun riga mun ruwaito yawan cigaba da aka ba da DA a kan tayar da hankali ga mutanen da ke lafiya wadanda suka shafe tsari na 1 wanda aka gwada a kalla 2 makonni bayan bayanan karshe, wanda aka fassara a kallo a matsayin shaida na haɓaka neurochemical.¹⁸ Nazarin na yanzu yana biyo bayan wannan kalma na farko¹⁸ don gwada zaton cewa irin wannan tsarin amphetamine din zai haifar da ƙarin amsawar DA zuwa wani danniya na psychosocial da aka gudanar da 2 makonni bayan biyo baya na karshe; wato, hujjoji na karuwa.

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kaya da matakai

Wanda su ka Halarta

Mazauna lafiyayyu sun samo asali ta hanyar tallace-tallace kan layi a cibiyar sadarwa da jaridu na gida. Bayan ganawar tarho don tantance albashi na farko, mahalarta sunyi cikakken bayani a ciki kamar: (1) wani tambayoyin mahimmanci na asibiti (Interview Clinical Interview for DSM-IV: Patient Edition, SCID-NP),¹⁹ (2) cikakken nazari na jiki wanda ya haɗa da gwaje-gwajen gwaje-gwajen da na'urar lantarki da kuma (3) matakai na girman kansu da kuma yanayin damuwa, ciki har da tambayoyin kwarewa da iko,²⁰ da Rosenberg kai girma sikelin²¹ da kuma Kasuwancin Raguwa ta Jihar-Trait.²² Abubuwan kulawa mafi mahimmanci sun haɗa da: (1) babban likita / rashin lafiya na jiki ko kuma yin amfani da magani zai iya tasiri ga aikin kwakwalwa ko kuma rikita batun sakamako na tasiri (PET); (2) na sirri ko tarihin iyali na rashin lafiya Axis I; (3) amfani da miyagun ƙwayoyi na yau da kullum ko magunguna (wato, ɗaukar hotuna ga magungunan ƙwayoyi ko na hallucinogens / sedatives a cikin watanni 12 na baya); (4) yin amfani da abubuwan da ke da mahimmanci, da magunguna ko hallucinogens da ke nuna faɗinta hudu; (5) yawan amfani da taba (5 cigarettes a kowace rana); (6) yawan amfani da cannabis (mafi girma fiye da amfani biyu a kowane mako); (7) gwajin gwaji a kan maganin maganin maganin ƙwayar maganin furotin don maganin miyagun ƙwayoyi ba bisa ka'ida ba a kwanakin bincike (Triage-TM); da (8) sun haɗu da wasu ka'idoji mara izinin PET / Magnetic Resonance (MRI) (duba Ƙarin Bayani). Cibiyar ta yarda da wannan binciken ta Cibiyar Nazarin Harkokin Kasuwancin Neurological Cibiyar Nazarin Neuro. Duk masu halartar sun ba da izinin sanar da izini.

Sanya bayyani

Wa] anda suka halarci za ~ en sun samu ko dai ammonitamine (0.3 MG kg^-1, ta bakin) ko placebo a kan kwana uku, a kowace 48 h, a cikin wannan yanayi (a kan PET gantry), bin hanyoyin da aka gudanar da gwaje-gwajen kamar yadda muke cikin nazarinmu na farko.¹⁸ Dukan mahalarta sunyi amfani da PET 60-minti guda uku [¹¹C] raclopride scan (~ 7 mCi) zaman, a lokacin da aka gabatar da su zuwa ga Tasirin Taskar Tasirin Cikin Hotuna (MIST; Figure 1). Daya PET [¹¹C] raclopride scan aka gudanar tare da aikin kula (Control MIST), yayin da biyu PET [¹¹C] raclopride scans aka samu tare da aikin MIST tashar don tantance DA martani ga danniya kafin (MIST 1) da kuma 14 kwana bayan magani na karshe (amphetamine ko placebo) (MIST 2). Dukan masu halartar sunyi amfani da MRI mai kulawa da ƙananan ƙwararru na T1 mai ƙyama don manufar PET rajista. Don rage girman tasirin da ake ciki zuwa MIST, masu halartar sunyi aiki na MIST (kafin MIST) sau ɗaya kafin lokutan farko na PET, kamar yadda al'amuran maganganu suka fi karfi a tsakanin bayyanar farko da na biyu zuwa wannan aiki na damuwa.^{23, 24} An tambayi masu halartar su azumi kuma su guje wa maganin kafeyin da taba saboda mafi ƙarancin 4 h kafin kowace zaman. Dukan lokuta bakwai sun faru ne a lokacin kwanakin 21, kamar yadda aka bayyana a Figure 1 (duba Ƙarin Bayani). An umurce su kada su yi amfani da kwayoyi a duk tsawon lokacin nazarin. An tabbatar da hakan ta hanyar jarabawar kwayar cutar fitsari a farkon kowace zaman.

 

Gwajin gwaji

MIST yana aiki ne mai wuyar ganewa wanda ya dogara da Ayyukan Kwarar Mutuwar Kwara²⁵ kuma an daidaita shi don amfani a cikin yanayin yanayi.²⁶ Mun yi amfani da ƙananan 12-min guda uku, kowanne tare da sassan 3-min na hudu. A lokacin aikin, ana gabatar da ɗakunan lissafi a cikin na'urar daukar hoto ta hanyar allon kwamfuta. Masu amsa sun amsa ta amfani da linzamin kwamfuta. Matsalar aiki da ƙuntata lokaci don kowace lissafi ana gyara ta atomatik ta hanyar algorithm kwamfutarka a ainihin lokacin da ya dogara da aikin ɗan takara, don haka ya zama dan kadan fiye da damar kowane mutum. Bayan kowace gwaji, allon kwamfutar yana nuna bayani game da aikin ɗan takara (daidai, kuskure, lokaci-lokaci); bin kowane sashi, an ba da amsa mai mahimmanci a hanyoyi guda biyu: ta hanyar shirin da kuma ƙwararrun. Yawancin masu halartar su sunyi imanin cewa ayyukansu sun kasance a ƙasa da tsammanin, kuma ana tambayar su don kara yawan aiki don cika bukatun.

An nuna wannan aikin don nuna halayyar hali da halayen hormonal ga danniya kuma an haɗa shi da saki DA DAGA a cikin masu aikin sa kai lafiya, ciki har da cikin ɓangarorin da suka fi dacewa.^{26, 27} A lokacin yanayin kula da na'urar saninsa (MIST control), mahalarta sunyi rubutu na musamman don 36 min, kamar yadda aka bayyana a sama, ba tare da matsalolin lokaci ba, alamu na cigaba da aka gani, sauti ko koyo. An gabatar da masu halartar a karshen ƙarshen zaman na PET na karshe, kuma an gaya musu cewa an tsara aikin ne don su kasance waje da ƙwarewarsu ta hanyar tunani kuma ba a auna su ba.

An canza canje-canje na hali mai kyau tare da Bayanan halin Amurka²⁸ da kuma Jakadanci na Jihar-Trait Inventory,²² kafin da kuma nan da nan bayan ƙarshen kowace tasirin MIST; da kuma a ƙarshen zaman gwajin lokacin waje a na'urar daukar hoto (bayanan ba a nuna ba). Ana samo samfurori na jini don cortisol da ƙananan zuciya (MP100-Biopac Systems) a kowane fanni da kowane 12 min a kowace zaman (Figure 1).

Taswirar fasali mai sauƙi na Voxel da t-statistics

An gyara hotunan PET don haɓaka kayan aiki na tsakiya²⁹ da kuma rajista tare da MRI na kowane mutum. Hotuna na MRI da PET sun canza cikin wuri ta hanyar amfani da Cibiyar Neurological na Nano-305.³⁰ [¹¹C] Raclopride wanda ba'a iya ɗaukar nauyin (BP_ND=f_NDB_wadata/K_D) an kiyasta a kowace ƙananan, ta hanyar amfani da hanyar ƙwayar maƙalar sauƙi, tare da ƙwayar magunguna, ban da vermis, a matsayin yankin bincike.^{31, 32} Voxel-hikima t-maps kwatanta BP_ND a lokacin MND 1 dangane da MIST 2 an yi amfani da su ta hanyar amfani da haɗin t-iyyai da ƙofa t= 3.76 daidai da P= 0.05 don ƙididdigar ƙwaƙwalwar ƙwaƙwalwa ta kowane fanni bisa ka'idar ka'idar bazuwar.³³ Manufar wannan hanyar ita ce gano canje-canje a BP_ND a matakin voxel ba tare da ba a priori anatomical hypothesis, sabili da haka sunyi wasu daga cikin iyaka na girma na sha'awa (VOI) jeri.²⁷ Don Allah ga Ƙarin Bayani don cikakkun bayanai game da yadda aka samo girman ƙididdigar ƙwaƙwalwa da ƙididdigar ƙididdiga mai ƙididdigar ƙira.

Sakamakon VOI

An zabi nau'o'i uku masu zazzabi a kan MRI na kowane mutum, ciki har da straltum ventral stringe, abokiyar haɗin gwaninta (ƙaddarar ƙaddarar rigakafi, daddarar kwari da kwatsam) da sensorimotor striatum. Sakamakon zanewa cikin babban tsarin kwakwalwa ta jiki wanda aka samo ta farko ta hanyar amfani da hanyoyin sarrafawa ta atomatik zuwa ga MRI na al'ada.³⁴ Kowace ƙungiyar VOI ta ƙungiyar ta kasance ta tsabtace hannu.¹⁸ Don daidaita daidaitattun VOI a kan PET bayanai mai zurfi da kuma cire bangarori na ayyukan lokaci na zamani, kowane nauyin rediyo na rediyo na PET ya karu tare da lokacin girma da kuma rijista zuwa MRI.³⁵ Bayani na ƙimar BP_ND a cikin waɗannan ayoyin sun fito ne a cikin yanayin shafukan uku. Wani bincike mai mahimmanci game da bambancin da yanayin gwajin (MIST control, XISTAN XIST, MIST 1) a matsayin maɗamfan matakan dake ciki da kuma daya daga tsakanin batutuwa da ke haɓaka subgroup (placebo, d-amphetamine) an gudanar da su ga kowane VOI, don bincika bambance-bambance a BP_ND. An yi gyare-gyaren 'yanci ta hanyar yin amfani da gwajin Greenhouse-Geisser a cikin yanayin rashin kuskure, kamar yadda binciken Mauchly ya ƙaddara (duba ma Ƙarin Bayani).

Halin yanayi da Psychophysiology

 

An gwada matakan da aka samo ta hanyar yin amfani da mahimmancin bincike game da bambancin. Ƙungiyoyi (placebo vs am amitatamine) shi ne tsakanin-batutuwa factor. Abubuwan da ke cikin batutuwa don yanayin halayen sune yanayin gwaji (Control MIST, MIST 1, MIST 2) da kuma lokaci (asali, bayan aiki). Don HR da cortisol, yanki a ƙarƙashin igiyoyi (aka lissafta su a cikin ref. 36) ga kowane yanayin gwaji shi ne abin da ke ciki.

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results

Maza maza goma sha takwas sun shiga cikin binciken (d-amphetamine n= 9; placebo n= 9). Ɗaya daga cikin mahalarta (d-amphetamine) ya nuna alamar canje-canjen a cikin BP_ND (a fadin yankuna) a yayin da ake nunawa ga MIST 1 (MIST 1 vs MIST iko) ƙayyadaddun ƙaura uku na sama da samfurin samfurin (kuma sau biyar mafi girma fiye da canje-canje da aka ruwaito a cikin 'martani' a cikin wani binciken da suka gabata ta amfani da MIST).²⁷ Wadannan mawuyacin BP_ND Ƙididdiga a wannan ɗan takara sun kasance kusan saboda kuskuren fasaha. An cire wannan dan takarar daga binciken. Mahalarta a cikin placebo vs d-amphetamine subgroups (Table 1) bai bambanta da bambanci ba game da tsarin dimokuradiyya ko ma'aunin mutum, ko a cikin kashi da injected [¹¹C] raclopride a cikin kowane taron PET guda uku (duba Table 1). Ko da yake injected adadin ya bayyana kadan bayan damuwa 2 dangane da damuwa 1, wannan tasiri ne mai zaman kanta daga irin magani (d-amphetamine ko placebo; P= 0.94).

 

Nazarin PET

Hikimar Voxel-hikima

 

Dama na bayyanar tashin hankali kafin maimaitawa d-amphetamine ko placebo (MIST 1 vs MIST iko). Hanyar damuwa a gaban tsarin tsarin amphetamine (MIST 1 vs MIST iko) wanda ya dace amma ya rage raguwa a BP_ND ƙididdiga, da farko a cikin saƙar. Girman canje-canje (% raguwa da girma) yana da kama da mahimmanci ga duka rukuni guda biyu (Table 2).

 

Sakamakon tasirin zafi yayin da aka ambata daga amphetamine ko placebo (MIST 2 vs MIST 1)

 

Kodayake yaduwar tashin hankali kafin tsarin amphetamine da aka ba da izinin yin amfani da ƙananan ƙwayoyi masu yawa na rage [¹¹C] raclopride BP_ND ƙididdiga (duba sama), ƙuntatawa-ƙaddamar da raguwa a BP_ND bin tsarin tsarin abin da ya fi dacewa ya fi girma (Figure 2; Table 2 da kuma Table 3). Wadannan gungu masu yawa na rage BP_ND bayan sake sakewa zuwa ga danniya ba a kiyaye bayan tsarin wuribo.

 

Sakamakon VOI

 

Sakamakon binciken na VOI ya nuna cewa kafin nunawa ga tsarin amfétamine din ya jagoranci mai yawa, amma rashin fahimta, canje-canje a [¹¹C] raclopride BP_ND, kuma ba akwai bambancin da ke tsakanin MIST 2 da MIST 1 a cikin rukunin wuri ba (Karin S1). Duk da haka, a cikin MIST 2 vs MIST iko, yanayin na biyu VOI ya nuna cewa, a cikin placebo kungiyar, ragu ragewa a BP_ND an lura da su a cikin haɗin gwiwar dama (F (2,16) = 4.44, P= 0.03), ƙananan ƙwararraƙi (F (2,16) = 4.11, P= 0.04) da dama (F (2,16) = 3.76, P= 0.05) da hagu (F (2,16) = 4.94, P= 0.02) sensorimotor striatum.

Aminci da kuma psychophysiology

Maganar yanayi

 

Abinda ke da alaka da kulawar MIST, ƙarfin zubar da hankali ta MIST 1 ya haifar da karuwar 'juyayi', kamar yadda aka auna ta hanyar Profile na yanayi na yanayi (yanayin gwaji / lokaci: F (2,30) = 4.31, P= 0.02; 1 MISTA tare da iko: (1,15) = 8.81; P= 0.01) da kuma Jakadanci na Jihar-Trait Inventory (yanayin gwaji / lokaci: F (2,30) = 4.12, P= 0.02; F (1,15) = 8.41; P= 0.01). Wadannan sakamako ba a lura da su ba a lokacin da aka sake nunawa MIST a kwanakin 21; kuma waɗannan cututtuka ba su bambanta tsakanin ƙungiyoyi (d-amphetamine ko placebo). Babu dangantaka mai mahimmanci tsakanin canje-canje a [¹¹C] raclopride BP_ND da kuma karfin haɓakar hali. Duba kuma Karin Ƙarin S1.

Tsarin aikin jiki

 

MIST yayi ƙaruwa sosai a lokacin da aka fara nazarin MIST PET da sake sakewa a kwanakin 21 (sakamako mai mahimmancin yanayin gwaji: F (2,30) = 18.58, P<0.001; MIST 1 vs sarrafawa: F (1,15) = 19.66, P<0.001; MIST 2 vs sarrafawa: F (1,15) = 19.81; P<0.001), amma babu wata ma'amala tare da ƙaramin rukuni (amphetamine, placebo) ko bambance-bambance tsakanin MIST 1 vs MIST 2. Cortisol ya ƙara haɓaka a yayin bayyanar MIST 1 (F (1,15) = 2.93; P= 0.107) da kuma karuwa sosai a sake dawowa ta MIST (a ranar 21; F (1,15) = 18.88; P= 0.001). Halin yanayin ƴan ƙungiyar subgroup ya nuna wani tayi ga muhimmancin (F (2,30) = 3.15, P= 0.057), tare da amsa cortisol lokacin sake sakewa zuwa MIST mafi girma bayan tsarin d amphetamine (F (1,15) = 5.20; P= 0.038), dangane da placebo. Babu dangantaka mai mahimmanci tsakanin canje-canje a [¹¹C] raclopride BP_ND da kuma maganganun da suka shafi psychophysiological ko cortisol. Don Allah a duba Karin Ƙarin S2.

Matakan Amphetamine

 

Daidai da bincikenmu na baya,¹⁸ plasma amphetamine concentrations ya tabbatar da kasancewar da magani stimulant a cikin dukan uku zaman daidai (duba Ƙarin Bayani don ƙarin bayani).

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tattaunawa

Binciken da aka yi a yanzu ya binciko ko wani tsarin tsarin amfétamine da aka nuna a baya ya nuna dashi a cikin masu aikin sa kai na mutum zai haifar da gagarumin martani ga damuwa na psychosocial. Sakamakon binciken yanzu ya ba da hujja na farko da zai iya. Daidai da tsinkayyar, maganganun da aka sanya DA da hypothalamic-pituitary-adrenal axis sun kasance mafi girma fiye da kwanaki 14 bayan tsarin d amphetamine mai maimaitawa. Wadannan mahimmancin martani sun bayyana a cikin layi tare da rahotanni na haɗin giciye a cikin dabbobin gwaje-gwaje.^{8, 11, 37}

DA sanarwa a cikin mahaifa accumbens an rubuta shi sosai a cikin gwajin dabbobi bayan an bayyana shi ga abubuwan da ke damuwa, irin su turawar wutar lantarki, tsintsa wutsiya da haɗin jiki.^{38, 39, 40} A cikin mutane, ƙananan binciken sun bincika maganganun maganganu da suka shafi damuwa. Hanyoyin da ke amsawa ga halayen kwaskwarima suna da matukar sauya, kuma suna da iyakancewa ga mutane masu tasowa (misali, mutanen da ke da girman kai, tarihin rashin kula da iyayen mata ko waɗanda suke da haɗari ga rashin lafiyar jiki)^{26, 27, 41} Binciken na yanzu ya haifar da yiwuwar cewa waɗannan martani mai yiwuwa za su iya kwatanta, a wani ɓangare, abubuwan tarihin rayuwa na yau da kullum game da abubuwan da ke damuwa.

Daidai da mahimmancin ra'ayi a nan, an gano cewa, bin amphetamine na maimaitawa, sake sakewa zuwa danniya ya kara rage BP_ND dabi'u a cikin mahalarta masu kirki. Wadannan binciken suna tunawa da lura da canzawa [¹¹C] - (+) - PHNO (a D₂/D₃ agonist ligand) yana maida martani a cikin mutane tare da kwakwalwa, ta yin amfani da wannan dakin gwaje-gwaje.⁴² Binciken da aka samu a yanzu yana ƙarfafa ra'ayi wanda ya nuna maimaitawa ga kwayoyi, da kuma fiye da wasu matsalolin halayen (alal misali, kwayoyin halitta), zai iya haɓaka matsalolin su na musamman don sauya bayanan tashin hankali a yankunan da ke ciki, kuma, yiwuwar haɗarin matsalar DA.

Canje-canje a BP_ND an kuma lura da su a matsayin tsarin tsarin wuri. Rahotanni da aka ruwaito a cikin d-amphetamine subgroup sun kasance na musamman a yanki, yana faruwa a cikin hagu na kwakwalwa na hagu da kuma bilatin a cikin ƙananan ƙwayar. Ƙwararriyar maimaitawa ta musamman an nuna shi don canza jujjuya-corticolimbic DA saki a cikin dabbobin dabba.⁴³ A cikin 'yan adam, an nuna alamar wahala a baya, musamman mawuyacin halin rayuwa, a matsayin muhimmiyar mahimmancin ci gaba da rashin lafiyar zuciya a baya a rayuwa.^{44, 45} Kodayake halin yanzu ba zai yiwu a kafa dangantaka ta hanyar kai tsaye ba, an nuna cewa damuwa na farkon lokaci yana haɗuwa da ƙarar ƙwararru mai ƙarfi DA saki zuwa matsanancin matsala²⁶ kazalika da zane-zane na psychostimulant daga baya a rayuwa.⁴⁶ Abubuwan da muka gano na rage BP_ND (a cikin rukuni na placebo) yana goyon bayan wallafe-wallafen da suka gabata, maimaita rikicewar rikicewa, zai iya jawo hankalin.³ Rashin sakewa ga danniya bayan ammonitamine (game da placebo) na iya haifar da tasiri daban-daban a cikin wasu yankuna masu sassaucin ra'ayi.¹⁸

Kodayake sakamakon yana cikin layi tare da binciken da ya nuna yawan ƙarfin hali ko amphetamine-jawowa DA amsawar da aka samu a cikin dabbobin gwaje-gwajen da aka nuna a amphetamine akai-akai,³ Sakamakon bambancin da shaidar da aka samu ba tare da amsawa ba a cikin marasa lafiya tare da maganin rashin amfani (dangane da sarrafawa) bayan babban kalubale tare da methylphenidate ko amphetamine^{47, 48, 49} ko yadawa zuwa dakin gwaje-gwaje.⁴¹ Dalilin da ya sa wannan bambancin ya kasance marar tabbacin, amma zai iya yin la'akari da dabi'un da suka rigaya ya riga ya kasance, da raguwa da sauri daga waɗanda ke da tarihin abubuwa masu magungunan abu ko kuma matsawa daga DA zuwa wasu maganganun da ke tattare da kwayoyin halitta wanda ya haɓaka halayyar halin halayen kalubale.^{50, 51, 52} Tare, wadannan binciken sun nuna muhimmancin buƙatar nazarin tsarin DA (giciye) da ke cikin ƙwayoyin asibiti tare da matakai daban-daban na ƙwayar magungunan ƙwayoyi na gaba don ƙarin fahimtar muhimmancin DA (gicciye) ƙaddamarwa a farawa da sake dawowa daga dogara da miyagun ƙwayoyi.

Ƙarfi da ƙuntatawa

Wannan binciken ya amfana daga zaɓar wani abu mai kyau wanda aka kula dashi don yin amfani da miyagun ƙwayoyi da kuma matsalolin danniya a duk lokacin gwajin gwagwarmayar 30, don haka ya rage girman mawuyacin hali. Zai zama sha'awa, duk da haka, don ƙayyade ko za a iya samun sakamako ga sauran samfurori, ciki har da mata, marasa lafiya ko bin ɗaukan hotuna zuwa matsalolin maimaitawa. Tsarin lokaci mai tsawo zai taimaka.

Ko da yake wannan nau'in samfurin ba ya bambanta da wanda aka bincika a binciken binciken da aka rigaya (ciki har da mu), bai yarda da bincike mai mahimmanci akan hulɗar da ke tsakanin mutumtaka, psychophysiology da amsa DA ba. Wani samfurin da ya fi girma zai ƙyale nazarin tasiri mai dacewa na takamaiman alamu / jinsin (alal misali, Ƙarfin ƙa'idar polymorphism na COMT Val (158), kamar su Hernaus et al.⁵³). Hakazalika, samfurinmu bazai bayar da isasshen ƙididdiga ba don gane muhimmancin fassarar tsakanin BP_ND da kuma halayen aikin halayyar jiki. Bugu da ƙari, nazarin VOI ya nuna cewa amsawar DA zuwa gawarwar sakewa bayan tsarin d amphetamine ya kasance mai sauƙi sosai. Wannan babban haɓakawa an sanya shi a asusun don gaskiyar abin da aka yi amfani da shi ta hanyar amfani da shi t-Manza ba za a iya tabbatar da su ta hanyar VOI ba. A madadin, haɓakawa a cikin t-maps ya bambanta da VOI iyakoki kuma haka bazai saukar da su ta VOI binciken ba. Lallai, ƙananan hukumomi waɗanda suka dogara da haɗuwa da haɗin kai a cikin mutane sun bayyana sun fi girma fiye da yadda aka ba da shawara ta hanyar samfurin tafiya.⁵⁴

Kodayake matsalolin farko sun bayyana abubuwan da ake tsammani a kan sassan HR da kuma mummunan yanayi,⁵⁵ sake sakewa ga danniya bayan gwamnatin amphetamine subchronic ba ta haifar da halin kirki ba. Ba za a iya bayyana rashin karuwar halin da ake ciki a kan yaduwar danniya ba, cewa gaskiyar cewa halayyar kirkira ga psychostimulants a cikin mutanen kirki za a iya bayyana su a matsayin halayen yanayi, haɓaka ko halayyar psychomotor¹⁸ gyare-gyare wanda zai iya kalubalantar maganganun da ba daidai ba ga damuwar halayyar kwakwalwa.

Ƙarancin amsa da aka samu na DA zuwa damuwa a cikin rukuni na d-amphetamine subchronic zai iya rinjayar da mahalarta gwagwarmaya a cikin yanayin da aka daidaita tare da miyagun ƙwayoyi. Alal misali, a cikin kwayoyin gwaje-gwajen, miyagun ƙwayoyi masu haɗin gwiwar zai iya sauƙaƙan bayanin da aka samu na DA da kuma ƙaddamar da kwanciyar hankali mai dorewa DA saki.^{56, 57} Ayyukanmu na baya sun gano hujjoji irin wannan tasiri a cikin mutane. Lokacin da aka gwada mahalarta a cikin yanayin PET da aka haɗa da miyagun ƙwayoyi, mun sami tabbaci na farfadowa ta hanyar DA¹⁸ da kuma kwaskwarimar DA saki.⁵⁸ Idan aka kwatanta, sake sakewa zuwa yanayin da aka haɗa da miyagun ƙwayoyi ba tare da sanadiyar magunguna ba (placebo capsule) ba su kai ga amsa DA ba. Kamar yadda a cikin binciken da aka yi a yanzu, an ba da gwagwarmayar gwagwarmaya ta karshe a cikin yanayin da aka haɗa da miyagun ƙwayoyi ba tare da wata matsala ta placebo ba, yana yiwuwa a kara yawan ci gaba ta hanyar maganin magungunan miyagun ƙwayoyi, yayin da yake nuna wani abu banda ƙarawa tare da kwaskwarima da danniya-induced DA martani.^{59, 60}

Kodayake ƙarfin binciken shine amfani da hanyar ingantacciyar hanya, [¹¹C] raclopride kawai yana damu da canje-canje a DA release a cikin striatum. Zai zama sha'awa don yin nazarin ko mahimmanci ko mahimmanci ga ƙarfafawa yana faruwa a wasu yankuna (misali, ta yin amfani da [¹⁸F] fallypride). Lalle ne, mun nuna a baya an nuna DA saki a cikin tsaka-tsakin dakararre na tsakiya wanda ke biyo bayan ƙananan ƙananan psychosocial stress.⁵⁵

Wani iyakancewa mai mahimmanci shine yanayin da za'a iya nunawa. Nazarin binciken na farko ya nuna bambanci tsakanin ƙananan takamaiman nau'o'i guda biyu na matukar damuwa a cikin ikon da zasu iya haifar da hankali: 'abubuwan sarrafawa' da 'abubuwan da ba a iya lura da shi ba.⁶¹ Mawuyacin rikicewa, rikicewar rikice-rikicen yana nuna alama ce mai mahimmanci na abubuwan da suka haifar da damuwa wanda ke haifar da canjin neurobiological da ke haifar da hangen nesa.^{62, 63} Don dalilai na dabi'a, an yarda da mahalarta su dakatar da gwajin a duk lokacin da za su zaɓa, wanda zai iya rage rashin kulawa da halin da ake ciki, ya ba da izinin "kulawa" wanda zai iya rinjayar matsalolin 'danniya', don haka 'haskakawa' don ƙarfafawa.

A ƙarshe, kodayake an yi nazarin mahalarta a hankali don amfani da kwayoyi a baya kuma an yi gwajin magungunan fitsari a farkon kowace zaman, wasu mahalarta sun yi amfani da taba ko cannabis a baya, kuma ba a tabbatar da lokaci na karshe na nicotine ba ta gwajin jini. Dangane da binciken, a cikin dabbobi, wannan maimaitawar nicotine ko kuma cannabis zai iya haifar da hankali,⁶⁴ ana iya jaddada cewa mahalarta da suka taba shan taba sun rigaya sun zama masu basira, saboda haka yiwuwar wata damuwa. Duk da haka, yawan adadin nicotine ko cannabis yana da rauni sosai. Bugu da ƙari, d-amphetamine da kuma placebo ba su da bambanci sosai kafin su yi amfani da su, kuma ana iya kiyaye tasirin damun amphetamine duk da tasirin da aka yi amfani dasu.

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Tsarin taƙaitawa da ƙarshe

Binciken na yanzu yana ba da shaida na farko a vivo cewa dabarun da aka samu ga psychostimulants na iya haifar da gajiya a cikin mutane. Ana ba da shawara akai-akai game da abubuwan mamaki kamar yadda aka saba da su don magance rikice-rikice a cikin jita-jita ko rashin hankali, wato, a cikin lalacewar da DA ya yi imani da cewa yana da muhimmiyar rawa.^{2, 65} Binciken da aka yi a yanzu ya gano alamun amphetamine wanda zai iya danganta shi da yadda ake nuna magungunan miyagun ƙwayoyi da sauri zai haifar da farawa ko sake dawowa, musamman ga cututtukan da ke tattare da DA, lokacin da wani ya fallasawa ga wasu matsalolin rayuwa.

Abin sha'awa, maimaita wahalar tashin hankali kawai shi ma ya haifar da wani saki na DA a cikin sakon. Duk da haka, ko da yake yana da tsinkaye, yana bada goyon baya ga ka'idar da ta maimaita matsaloli tare da ko ba tare da mai da hankali ba, na iya haifar da matsala na abubuwan neurobiological⁶⁶ wanda kuma zai iya rinjayar da farawa ko sake komawa zuwa wasu lambobin DA masu alaka. Musamman, ainihin ma'anar 'farfadowa' don sake maimaita 'danniya' an yi la'akari da shi, da alama da kuma tattauna.

Binciken da ya gabata ya haifar da yiwuwar fahimtar juna da kuma tsinkayar giciye na iya kasancewa dacewa don cigaba da kuma bayyana yanayin ilimin psychiatric a cikin mutane masu fama da rauni.^{4, 5, 6, 7, 67} Alal misali, a cikin binciken da masu amfani da cutar cocaine suke da su, wadanda suka samu maganin motsa jiki, 65% ya ruwaito cewa ya zama mai saukin kamuwa da wannan sakamako (wato, dabarar ya zama mafi tsanani ko kuma ya haifar da ƙananan allurai, alamar nuna halayyar halayya), kuma waɗannan mutane zasu iya komawa zuwa yin amfani da miyagun ƙwayoyi bayan bin gogewa, kamar yadda aka ƙididdige ta da yawancin asibiti.⁵ Tabbatar da mafi mahimmanci ko mahimmanci na DN ya kara karuwa ga waɗannan da sauran matsalolin zasu buƙaci halayen motsa jiki, bincike da ƙwarewar psychopharmacological. Bugu da ƙari, zai zama mahimmanci don ƙayyade mahimmanci na ganewa da kuma ƙididdigar giciye zuwa ƙaddamar da ƙyama ga ƙofar don bambancin alamu da alaƙa da wasu alamun cututtuka; misali, tsarin kulawa da tsarin kulawa da nakasassu, raguwa mai juyayi, ƙwaƙwalwar hankali na zuciya, halayyar manya ciki har da haɓaka ƙa'idodin cibiyoyin da aka tsara da sabuntawa da neman amfani da miyagun ƙwayoyi. Kodayake ra'ayin da ra'ayoyin da ake ciki yanzu na iya zama cikakke ga samfurori na ƙwararrun ƙwayoyin cuta yana da tilasta, a yanzu, wannan ya kasance a tabbatar.

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Rikici na sha'awa

Masu marubuta ba su da wani tasiri na sha'awa.

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