Canje-canje a daurin DodNUMX-receptor dopamine suna haɗuwa da raguwa ta nuna rashin lafiya idan sunyi kwaskwarima a yanayin rashin tausayi (2)

Kira: Magungunan asibiti (2012) 2, e120; Doi: 10.1038 / tp.2012.40

S Cervenka¹, E Hedman^1,2, Y Ikoma^1,3, D Radu Djurfeldt¹, C Rück¹, C Halldin¹ da N Lindefors¹

¹Ma'aikatar Clinical Neuroscience, Division of Psychiatry, Karolinska Cibiyar, Stockholm, Sweden
²Ma'aikatar Clinical Neuroscience, Cibiyar Nazarin Cibiyar Harkokin Kasuwanci da Harkokin Ilimin Kimiyya, Osher, Karolinska Institutet, Stockholm, Sweden
³Cibiyar Harkokin Harkokin Kwayoyin Halitta, Cibiyar Nazarin Harkokin Kimiyya ta Duniya, Chiba, Japan

Adadin: Dr S Cervenka, Ma'aikatar Clinical Neuroscience, Division of Psychiatry, Karolinska Cibiyar, Jami'ar Jami'ar Karolinska Solna, Ginin R5, 171 76 Stockholm, Sweden. E-mail: [email kariya]

An samu 19 Maris 2012; An karɓa 10 Afrilu 2012

Abstract

Anyi amfani da tsarin dopamin don taka rawar a cikin rikice-rikice na zamantakewa (SAD), wanda ya danganci nazarin ilimin kwayoyin halitta wanda ke nuna alamun ƙananan alamun alamu na kwayoyin cutar marasa lafiya idan aka kwatanta da kula da batutuwa. Duk da haka, tsarin nazarin dopamin ba a duba shi a gaba ba kuma yankuna masu kwakwalwa ne suka buƙaci su zama tsakiya a ilimin sad. A cikin binciken na yanzu, mun yi tsammanin matakin matakan dopamine D2-receptor (D2-R) wanda aka auna ta hanyar yin amfani da hoton kwaikwayo (PET) zai yi la'akari da ragowar bayyanar cututtuka bayan farfadowa na al'ada (CBT). Ma'aikatan SAD guda tara an yi nazarin su ta hanyar amfani da PET mai matukar mahimmanci da kuma haɗakarwar dan Adam D2-R radioligand [¹¹C]FLB 457, kafin da bayan 15 makonni na CBT. An kiyasta matakan da aka gwada ta hanyar amfani da nauyin damuwa na ragowar Balance Social Social (LSAS)_damuwa). A lokacin da aka yi bala'i, an samu raguwa da yawa na zamantakewar tashin hankali (P<0.005). Amfani da maimaita matakan bincike na canzawa, mahimman sakamako don lokaci da lokaci × LSAS_damuwa canji a kan D2-R-daura m (BP_ND) aka nuna (P<0.05). A cikin nazarin yanki-yanki na gaba, halayen haɓaka tsakanin canji a cikin D2-R BP_ND da LSAS_damuwa an sami canji ga magunguna na farko da na hippocampus (P<0.05). Wannan shine binciken farko don bayar da rahoton dangantaka ta kai tsaye tsakanin bayyanar cututtuka bayan nazarin zuciya da alamar kwakwalwa neurotransmission. Yin amfani da kwatancen mutum na kwatankwacin mutum, binciken yana taimakawa wajen tsarin dopamine a cikin yankuna masu kwakwalwa a cikin ƙwayoyin cuta na SAD.

Gabatarwa

Tsarin dopamine yana cikin halin zamantakewa, koyo da kuma tsari na tunani, yana tsinkayar wani rawar a cikin ilimin cututtuka na rashin lafiyar zamantakewa (SAD). Masanan binciken nazarin kwayoyin halitta sun ba da tallafi na farko ga wannan tsinkaya, suna nuna matakan ƙananan alamun maganin maganin maganin maganin maganin maganin maganin maganin maganin maganin maganin ƙwayoyin cuta kafin su kasance marasa lafiya idan sun kwatanta da sarrafa batutuwa.^{1, 2, 3} Duk da haka, an samu sakamako mai ma'ana.⁴ Bayanan yiwuwar wannan rashin daidaituwa na iya zama cewa babu wani binciken da aka yi a yanzu ya bincika tsarin dopamine a cikin yankunan kwakwalwa na gaba ko na gaba, wanda ya nuna cewa yana cikin SAD bisa la'akari da karatun kwakwalwa (don dubawa, duba ref. 5). A wani ɓangare, wannan ya kasance saboda iyakokin ka'idoji, kamar yadda D2-receptor (D2-R) na farko suka gabatar da shi (PET) radioligands kamar su [¹¹C] raclopride ba su da ƙarancin daidaituwa ga ma'auni a cikin ƙananan ƙwararrun kwakwalwa.

Ilimi na PET sun nuna nuna bambanci tsakanin mutum daya a cikin matakan alamar lambobi a cikin maganganun lafiya.⁶ Wannan yana haifar dashi a nazarin inda aka kwatanta matakan marasa lafiya da masu kula da su, kamar yadda ake buƙatar girma masu girma don gane ƙananan bambance-bambance. Bugu da ƙari, rabuwar rukuni a cikin matakan mai ba da kariya ba zai haifar da haɗin kai ba zuwa ga cutar bayyanar cututtuka. Wani zane na gwaji inda aka lura da alamar nazarin halittu a matsayin aiki na canji a yanayin cututtuka ana iya la'akari da tsarin da ya fi karfi a cikin wadannan hanyoyi. A cikin ilimin ƙwaƙwalwar hankali, ci gaban ƙwayoyin mahimmanci na psychotherapy na ba da dama na musamman don inganta bayyanar cututtuka ba tare da tsangwama tare da kwakwalwar kwakwalwa ba. Ga SAD, farfadowa na halayyar kwakwalwa (CBT) zai haifar da ingantaccen asibiti har zuwa 75% na marasa lafiya.^{7, 8}

Kodayake yawancin nazarin sun binciki tasirin psychotherapy a kan kwakwalwar kwakwalwa kamar yadda aka yi amfani dashi ta amfani da PET da kuma yanayin hoton jiki na magnetic (MRI), rahotanni kan canje-canje a cikin neurotransmission basu da yawa. Ƙara haɗari ga mai ɗaukar serotonin a cikin tsakiyar tsakiya bayan bayan watanni 12 na farfadowa na kwakwalwa ya nuna a cikin wani rukuni na marasa lafiya da ciwon ciki. Babu wata canjin da aka nuna a cikin matakan shuke-shuke na dopamine.⁹ A cikin binciken na gaba da amfani da PET da [¹¹C] WAY-100635, 5HT_1a-Bacewar ɗaure da aka nuna ya karu a marasa lafiya tare da babban cututtukan zuciya bayan taƙaitaccen psychotherapy psychotherapy.¹⁰ Duk da haka, ba a cikin waɗannan nazarin ba za a iya nuna dangantaka tsakanin canje-canje a cikin matakan halitta da kuma cigaba da alamar alama. A ƙarshe, a cikin binciken da aka yi kwanan nan a cikin marasa lafiya da ciwon ciki, ba a nuna tasirin psycho psychological a dopamine D2-R a cikin striatum ba.¹¹ Har zuwa yau, babu wani nazari da aka bincika sakamakon CBT a kan alamomin kwakwalwa neurotransmission. Kamar yadda CBT ya kasance mai kulawa mai tsanani tare da karfafawa a kan abin da ya faru akai-akai don jin tsoron matsala don rage matakan damuwa (alal misali, duba ref. 12), wannan nau'i na psychotherapy zai iya kasancewa wuri mafi mahimmanci don gano kwayoyin halitta ba tare da alaƙa ga canzawar alama ba.

A cikin binciken na yanzu, ainihin manufar shine bincika tasirin tsarin kwayoyin halitta a SAD ta hanyar amfani da kwatancin juna, ta hanyar nazarin dangantaka tsakanin canji a cikin matakan bayyanar bayan CBT kuma canzawa a cikin DAMNUMX-R. Mun annabta cewa karamin mikiyar karfi (BP_ND) za a danganta ta musamman tare da rage matakan damuwa a yanayin zamantakewa. An gudanar da binciken ne ta hanyar yin amfani da DLNNUMX-R mai zaman kansa mai suna radioligand [¹¹C] FLB 457,¹³ wanda ke ba da ma'auni a yankuna masu kwakwalwa na musamman wanda ke da sha'awa ga SAD, kuma an gudanar da nazari a kan tsarin PET da aka yi amfani da shi na bincike mai zurfi don ingantaccen ƙaddarar mutum.¹⁴

Ka tafi zuwa ga:

kaya da matakai

batutuwa

Ma'aikata guda tara da SAD sun karu daga binciken da aka kwatanta da CBT wanda aka gudanar ta hanyar Intanet tare da farfadowa na rukunin, wanda aka fitar da sakamakon a wasu wurare.¹⁵ A wani bangare na nazarin binciken, dukkanin batutuwa sunyi hira da wani babban jami'in ilmin likita kuma an sami su cika ka'idojin DSM IV don SAD¹⁶ ta yin amfani da tambayoyin Harkokin Gudanar da Harkokin Gudanar da Harkokin Gudanar da Harkokin Harkokin Harkokin Na'urar DSM-IV. Har ila yau, an yi amfani da maganin, ciki har da ƙwarewar miyagun ƙwayoyi da zalunci, ta yin amfani da Interview Neuropsychiatric Mini-International.¹⁷ Bayan an shiga cikin binciken na PET, marasa lafiya sun kasance marasa lafiya a cikin hanyar tsarawa ko magani ta Intanet. Abubuwan da suka shafi sun kasance lafiya kamar yadda ƙaddara ta jiki da gwaje-gwaje na jini na yau da kullum da kuma jarrabawar MRI ta kwakwalwa. Abubuwa uku da aka magance su a baya sun kasance tare da serotonin ko serotonin kuma wadanda suka hana masu maganin noradrenaline, amma babu wanda ya karbi magani na SAD a cikin watanni 2 kafin binciken. Babu masu amfani da nicotine. Ɗaya daga cikin haƙuri ya cika sharudda don matsalar rikici da ake ciki tare da agoraphobia, in ba haka ba babu wani abin da ya faru. Don ƙarin siffofi, duba Table 1. Wannan binciken ya amince da shi da kwamitin nazari na yanki na yanki da kuma kwamitin tsaro na tsaro a Karolinska Hospital, Stockholm. Abubuwan da aka ƙunshi sun haɗa ne kawai bayan bada izinin izini a rubuce.

Table 1

Masu haƙuri masu haƙuri

Alamar fasali

Bayan hadawa a binciken nazari da kuma bayan jiyya, an yi nazarin marasa lafiya tare da Sashen Lalɗar Soyayya ta Laybowitz Social Clinic (LSAS).¹⁸ Siffar kamfani na wannan sikelin (LSAS-SR)¹⁹ an kammala ta Intanit kai tsaye kafin kuma bayan jiyya. LSAS ya ƙunshi nau'i biyu, wanda yayi la'akari da juyayi a yanayi daban-daban (LSAS_damuwa), da sauran ƙididdigar mataki na kaucewa a cikin yanayi guda (LSAS_{kauce wa}). Yayin da muka tsammanin cewa D2-R bindiga za a danganta da farko zuwa matakan damuwa, LSAS_damuwa shi ne sakamako mai yawa na babban sha'awa. A lokuta da dama, lokaci ya kasance a tsakanin gwaji da gwajin PET har zuwa watanni da dama, kuma a wasu lokuta an nuna bambancin ra'ayoyin da magunguna daban-daban suka yi kafin kuma bayan jiyya. Saboda haka, kawai LSAS-SR ne aka haɗa a cikin bincike. An yi PET1 akan matsanancin 13 ± 14 (yana nufin ± sd) kwanakin kafin alamun magancewa, kuma lokaci tsakanin lissafin ƙaddamarwa da PET 2 shine 17 ± 15 kwanakin.

Jiyya

Magunguna uku sun sami magungunan halayen halayen halayen halayyar halayyar halayyar¹² da kuma CBT guda shida marasa lafiya.²⁰ Tsawancin magani shine 15 makonni a cikin waɗannan yanayi. Gwargwadon da aka yi amfani da shi a cikin binciken, a cikin duka samfurori, ya bi tsarin samfurin CBT wanda ya karfafa muhimmancin kaucewa da halayyar aminci da kuma kuskuren abubuwan da suka shafi zamantakewa da kuma mayar da hankali a ciki kamar abubuwan SAD.^{21, 22} Bayanan da aka tsara da kuma hanyoyin da aka samar da su sun kasance daidai da kuma babban binciken da aka samu daga nazarin binciken, wanda aka samo samfurin na yanzu, shine CBT da kuma kungiyar CBT sune daidai da sakamakon maganin.¹⁵ Ƙididdigar ƙididdigar ɗakunan da aka kammala ko fasali ga duka samfurori sune 13 na 15 (ma'ana = 11.5; sd = 3.5). Dukkan mahalarta sun kasance sun nuna ainihin sifofin maganin.

Nazarin MR

A matsayin wani ɓangare na tsari, dukkan marasa lafiya sunyi jarrabawar MRI ta T1- da T2 ta amfani da 1.5T GE Signa Scanner (Milwaukee, WI, Amurka). An bincika hoton T2 don ilimin lissafi na macroscopic, kuma an yi amfani da hoton T1 don nazarin hoto na gaba.

Radiochemistry

Radioligand [¹¹C] FLB457 ne mai maye gurbin benzamide tare da dangantaka da 0.02nmoll^-1 don D2 da D3 dopamine receptors in vitro wanda yake da muhimmanci fiye da na [¹¹C] raclopride (1-2nmoll^-1).¹³ Wannan halayyar yana ba da izini don bincika yankunan ƙwaƙwalwar ƙananan ƙananan yankunan da D2-R ba su da yawa. [¹¹C] FLB457 an hada kamar yadda aka bayyana a baya.²³ Kashi na asibiti na PET1 da PET2 sune 468 ± 16 da 465 ± 19MBq, bi da bi. Don dalilai na fasaha, bayani game da takamaiman aiki da jimlar allurar da aka ƙwace ya ɓace saboda PET1 da PET2 guda ɗaya. Don sauran gwaje-gwajen, aikin musamman na musamman shine 1436 ± 2348 da 658 ± 583GBqμmol^-1 don PET1 da PET2, da kuma nau'in inji FLB 457 shine 0.41 ± 0.3 da 0.58 ± 0.6μg, bi da bi. Ƙaƙidar da aka yi masa, takamaiman aiki da taro ba su bambanta tsakanin layin da aka yi ba.P> 0.5, an haɗa su t-test), kuma mahimmanci, babu dangantaka tsakanin masallatai da aka ƙwace ko dai BP_ND ko canjin yanayi.

Gwajin PET

An yi nazarin PET a kan tsarin bincike mai zurfi na bincike (Siemens Molecular Imaging, Knoxville, TN, USA). Kafin gwajin farko na PET, an yi wa kwalkwali na gyaran kafa don kowane nau'i daya don rage motsin kai a lokacin ma'auni. Lokacin tsakanin PET1 da PET2 sune kwanaki 146 ± 23. Lokaci na lokaci don allura shi ne 12: 24 don PET 1 da 11: 53 don PET2. Kafin fitarwa, an yi amfani da lasisin 5-min don daidaitawa don haɓakawa da watsa. [¹¹C] FLB 457 an yi masa inject a cikin kwayar antecubital a matsayin ɓangaren hanyoyi kuma an ƙaddamar da radiyo don 87min. Ga batutuwa guda biyu, an kaddamar da binciken na biyu tsakanin 910 da 1416s da 3361 da 3623s, bi da bi. Wadannan lokaci ba a cire su daga nazarin maganin motsa jiki ba. An sake sake gina hotunan ta hanyar amfani da mahimmanci da yawa da ake amfani da su a cikin Poisson tare da ma'anar yaduwar aikin algorithm, yana samar da wani tsari na 1.5.mm a rabin iyakar a tsakiyar filin-of-view.¹⁴

Bayanan hotuna

An gyara hotuna PET don motsi na motsi ta hanyar amfani da tsarin gyare-gyare na frame-by-frame,²⁴ tare da kowane ɓangaren siffar da ke aiki a matsayin abin nufi ga gaba. T1 MR hotuna sun kasance sun hada da sakonni na baya-bayan nan - haɗin jirgin sama na baya. Ƙungiyoyin sha'awa (ROIs) an haɗa su da hannu a kan MRI akan kowane batu na kowanne, ta amfani da ƙwararrun ɗan adam Atlas software²⁵ (Figure 1). Yankunan da aka zaba sune amygdala, hippocampus da kuma abubuwan da suka dace, bisa ga aikin da suke da shi a SAD,⁵ kuma an fassara Rukunin ta hanyar amfani da jagororin da aka buga a baya.^{26, 27} An rabu da man fetur na farko a cikin yankuna masu rarrafe, na tsakiya da kuma kobitofrontal.²⁷ Ƙananan yankuna ba a kimanta su ba, kamar yadda matsayi mai girma na [¹¹C] FLB 457 ba ya ƙyale ma'auni a cikin ƙwayar gwajin PET, saboda haka hana ƙayyadadden ma'anar radioligand.²⁸ An rarraba nau'in MRI zuwa cikin launin toka, nau'in fari da kuma ruwan sanyi, da kuma rubutun zuwa kowane nau'i na PET biyu ta amfani da SPM5. An yi amfani da sigogin canjin da aka samo don amfani da Hannuna a kan tasirin PET masu haɓaka don samar da ɗakunan aiki na lokaci (TACs). Ga yankunan da ke ƙarƙashin ƙasa, kawai siffofi na ɓangare na launin toka an haɗa su a cikin ROI. Har ila yau, ƙarfin gyare-tsaren tasirin girma ta amfani da hanyar Meltzer an yi amfani da wadannan yankuna don kaucewa sakamakon lalata daga CSF voxels.²⁹ An yi amfani da hotuna a kan SPM5 yana aiki a Matlab R2007b (MathWorks, Natick, MA, USA).

Figure 1

(a-c) Hotuna masu girman kai tare da yankuna masu sha'awar amygdala (red), hippocampus (rawaya), gurbin kafa na farko (cyan), ƙwayar cuta ta farko (blue) da kuma orbitofrontal cortex (kore). (d-f) Hoton hotuna na [¹¹C] FLB (Kara …)

BP_ND an lissafta daga TAC ta hanyar amfani da samfurin ƙwayoyin tunani mai sauƙi (SRTM), tare da cerebellum a matsayin tunani. A wannan mahallin, BP_ND wakiltar rabo ne a ma'auni na ɗaurin radioligand da aka ɗauka musamman zuwa na radioligand ba wanda zai iya ganewa a jikinsa.³⁰ An riga an inganta SRTM don [¹¹C] FLB 457.²⁸ Tun da ba mu da wata alama game da bambance-bambance na bambancin da ke tattare da maganin neurotransmission a cikin SAD, BP_ND domin an ƙidaya kowane yanki ta hanyar amfani da TAC masu girman kai don ƙananan hagu don haɓaka lissafin TAC.

Nazarin lissafi

Canje-canje a cikin LSAS scores da D2-R BP_ND an kiyasta ta yin amfani da juna t-test. Ƙungiyoyi tsakanin D2-R BP_ND da kuma LSAS ƙididdiga a asali aka lasafta ta yin amfani da haɗin haɗin kai, mai sarrafawa don shekaru. Mawuyacin dangantaka tsakanin canje-canje a ɗaukar D2-R na yankin kuma ya canza cikin LSAS_damuwa an kiyasta ƙididdigar ta hanyar yin amfani da matakan mahimmanci na nazarin haɗin kai, tare da lokaci da yankin kamar abubuwan da ke ciki da LSAS_damuwa canjin canji kamar yadda ya kamata. An yi nazari na biyu don LSAS_{kauce wa} da kuma biyan kuɗi biyu. Daga bisani, haɗin gwargwadon daidaito sun lasafta tsakanin canjin canji a D2 BP_ND da canjin canji a LSAS_damuwa ƙidaya. A cikin post-hoc bincike, mutane sun raba su zuwa masu amsa (50% rage yawan alamun) da masu ba da amsawa, da bambance-bambance a canji a BP_ND An bincika dabi'un da aka yi amfani da su ta hanyar yin amfani da hanyar yin musayar bambancin juna. Ga dukkan gwaje-gwajen, an yi la'akari da muhimmancin a P<0.05. An gudanar da nazarin ilimin lissafi ta amfani da PASW 18 (SPSS, Chicago, IL, Amurka).

Ka tafi zuwa ga:

results

Canje-canje a cikin matakan rikice-rikice da D2-R BP_ND

Duk marasa lafiya sun inganta bayan jiyya, kuma canji a duka LSAS scores kazalika da juyayi da kuma kaucewa biyan kuɗi sune mahimmanci (Table 2). Babu bambanci a cikin LSAS ya canza tsakanin marasa lafiya da ke karɓar maganin marasa lafiya da marasa lafiya da aka bi ta intanit, ko dai don dukan sikelin ko don biyan kuɗi (P> 0.74). A lokacin kulawa, mahalarta huɗu (44%) ba su ƙara cika ka'idojin bincike na SAD ba. A matakin rukuni, bambancin D2-R-ɗaure kafin zuwa da kuma kulawa bayan fage bai kai ga ƙididdigar lissafi ga kowane yanki ba, kamar yadda aka kimanta ta amfani da haɗi t-test (Table 2). Duk da haka, jagorancin da mataki na canji ya nuna matakan bambancin ra'ayi, wanda ya ba da damar lissafin ma'anoni masu mahimmanci tare da sauyawar alama.

Table 2

D2-receptor-binding m da alama alama scores pre-da kuma jinkirin

Ƙungiyoyi tsakanin D2-R BP_ND canji da zamantakewar tashin hankali

A cikin matakan da aka yi mahimmanci game da daidaituwa, an nuna gagarumar tasiri ga LSAS_damuwa (F = 7.61, P= 0.028 da F = 7.77, P= 0.027). A cikin wani yanki na yanki-by-region, daidaitattun lahani tsakanin canji a D2-R BP_ND da LSAS_damuwa an nuna canje-canje ga matakan farko na gaba (r= -0.78, P= 0.013), haɗin gwal na farko na tsakiya (r= -0.82, P= 0.007) da kuma hippocampus (r= -0.81, P= 0.008; Figure 2). Harkokin da aka yi a cikin tsinkayyi na farko da kuma hippocampus ya tsira daga gyara na Bonferroni (gyara P-kima <0.01). A cikin waɗannan yankuna, masu ba da amsa sun nuna ƙaruwa a ɗaure (5.0% da 9.5%, bi da bi, n= 4), alhali kuwa wadanda ba masu amsawa a matsakaici sun nuna karuwar (-8.6% da -8.3%, n= 5). Duk da ƙananan mutane a kowane rukuni, wannan bambanci ya kasance muhimmi ga MFC (P= 0.003) da kuma gagarumar matsayi na hippocampus (P= 0.097). Babu wani sakamako mai mahimmanci na lokaci ko lokaci × alama ta canzawa a kan ɓangaren bazawar. Wannan bambanci na tasiri tsakanin alamomi kuma ya nuna cewa a yayin da hada ma'auni guda biyu kamar yadda ake amfani da shi, an yi la'akari da yanayin cigaba don lokaci (F = 3.93, P= 0.088) da kuma lokacin hulɗa don canza lokacin × (F = 3.74, P= 0.095).

Figure 2

Ma'aikata da ke nuna bambanci tsakanin canji a cikin Laybowitz Social Sense (LSAS) da kuma kwayoyin da suka shafi dopamine D2-receptor-binding (BP) a cikin magunguna na farko (DLPFC), magunguna na farko (MFC) da hippocampus (HIP). (Kara …)

Saitunan da aka yiwa juna a tsakanin D2-R BP_ND da kuma jin dadin jama'a

Babu dangantaka tsakanin D2-R BP_ND da LSAS_damuwa ko LSAS_{kauce wa} ƙididdigar da aka yi a baya ko jinkirtawa, bayan da yake kula da shekaru.

Ka tafi zuwa ga:

tattaunawa

A cikin wannan binciken, mun tantance muhimmancin tsarin tsarin kwayoyin halitta na SAD, ta hanyar nazarin canje-canje a cikin kwayar dopamine D2-R a matsayin aiki na canjin yanayi bayan CBT. Abin mahimmanci, manufar wannan binciken ba shine bincikar ilimin magani na D2-R a SAD ba, saboda wannan zai haifar da amfani da yanayin kulawa. Maimakon haka, an yi amfani da CBT a matsayin kayan aiki don canza yanayin rashin lafiya ba tare da magani ba. Sakamakon haka, ƙungiyar tsakanin sauyawa a cikin alamomi da kuma canje-canje a ɗaurin mai karɓa shi ne ainihin sakamako, maimakon canje-canjen da aka yi a cikin rukuni na rukuni. Saboda haka, yayin da bambanci tsakanin PET1 da PET2 sun kasance a cikin gwajin gwajin gwajin da aka nuna a baya don [¹¹C] FLB 457,³¹ bambancin da aka yi a cikin canji ya isa don nazarin gyare-gyare. Yin amfani da irin wannan zane, canje-canje a ɗaurin D1-receptor dauka kwanan nan ya nuna cewa yana da alaka da ingantaccen aiki a ƙwaƙwalwar ajiyar bayan ƙwaƙwalwar ƙwaƙwalwar ajiya,³² kuma yanzu a farkon lokaci muna nuna dangantaka ta kai tsaye tsakanin raguwa ta alamar motsa jiki bayan da aka canza tunanin mutum da kuma canzawa a alamar kwakwalwa neurotransmission.

An nuna muhimmancin tsarin tsarin dopamine a yanayin zamantakewa a duka bincike na dabba da nazarin ɗan adam. Bayanan nazarin kwayoyin halitta sun nuna alamar rashin daidaituwa tsakanin batuttukan DA da kuma alamomin halayen mutum da kuma matakai daban-daban na zamantakewar al'umma da kuma matsayi na zamantakewa.^{33, 34, 35, 36, 37, 38, 39} Kwanan nan, mun gabatar da wannan layi na bincike ta hanyar nuna dangantaka tsakanin zamantakewar zamantakewa da kuma D2-R dake ɗaukar nauyi a cikin tsinkayen lobe kamar yadda aka auna ta amfani da [¹¹C] FLB 457.⁴⁰ A cikin ƙungiyoyi masu hulɗar ra'ayi, waɗannan dabi'un dabi'a za a iya kallon su don nuna biyayya ga zamantakewa kamar yadda ya saba da rinjayar zamantakewa,⁴⁰ kuma sakamakon haka ya yi nazarin bincike game da rodents da wadanda ba na dan Adam ba ne inda aka danganta dopaminergic neurotransmission tare da girman girman hali.^{41, 42, 43, 44} Na musamman sha'awa shi ne binciken da Morgan et al.,⁴⁴ inda aka nuna D2-R a cikin birai a canza matsayin aiki na matsayin matsayi kamar yadda dabbobi suka motsa daga mutum zuwa gidan zamantakewa. Binciken dangantakar dake tsakanin canji a cikin D2-R da kuma alamomin rikice-rikice na zamantakewa sunyi dacewa da waɗannan layi na bincike kuma za'a iya ganin su a matsayin goyon baya ga hanyar da aka ba da shawara a tsakanin tsaka-tsantsar yanayin da ake ciki da SAD.⁴⁵ Rikicin bai da muhimmanci ga LSAS_{kauce wa}, wadda ma'anar bambancin dabi'a ta iya bayyanawa. Alal misali, rage kaucewa tare da kiyaye halayen halayen halayya bazai sa ran tsayar da damuwa ba.²¹

Binciken da aka yi a baya sun nuna rage dopamine D2-R a cikin striatum a cikin marasa lafiya na 10 tare da SAD, da kuma a cikin samfurin 7 tare da OCD comorbid kwatankwacin kula da batutuwa.^{1, 2} A kan gefen magunguna, ƙaddamar da ɗaukar motar dopamin a cikin 11 marasa lafiya.³ A cikin binciken da aka yi kwanan nan ta yin amfani da PET, ba a nuna bambanci a cikin D2-R kasancewa ba, ko dai a asali ko bayan ƙalubalen amphetamine, kuma babu wani bambanci da ke ɗaukar daukar kwayar cutar dopamine (n= 15, 12 da 12, bi da bi).⁴ Duk da haka, babu wani daga cikin waɗannan nazarin da aka tantance masu karɓa na dopamin a cikin jihohin kwakwalwa.

A cikin karatun kwakwalwar karatun, daya daga cikin mafi yawan rikodin bincike an kara ƙaruwa a amygdala a sakamakon maganganu masu jin tsoro na zamantakewa^{46, 47, 48} amma har ma, an gano maƙaryata binciken.^{49, 50} Sauran yankuna da ke nuna alamar kunnawa a cikin SAD sun hada da hippocampal da cortices.^{5, 46, 47, 51, 52, 53} Ga magungunan na farko na tsakiya, muhimmiyar rawa don saka idanu ga zaman lafiyar al'umma an nuna shi a cikin marasa lafiya SAD^{51, 52} kuma wannan yanki kuma yana cikin mummunar tsoro.^{54, 55} Dopaminergic watsawa a cikin hippocampus ya nuna kasancewa a cikin aikin ƙwaƙwalwar ajiya a binciken dabba da kuma a cikin kwayoyin karatu imaging.^{56, 57, 58, 59} A haɗuwa, binciken yanzu na dangantaka tsakanin aikin dopaminergic a hippocampus da yankuna na gabas na tsakiya na iya zama alaƙa da rawar waɗannan yankuna a koyon ilmantarwa da zamantakewar jama'a.

Babban mahimmancin wannan binciken shine ƙananan samfurin samfurin. Kodayake yawan marasa lafiya na 126 sun haɗa da su a cikin binciken nazarin,¹⁵ don binciken da muke ciki a yanzu muna amfani da ka'idojin haɓaka mafi tsayayya don guje wa lalacewa na D2-R, alal misali ta amfani da maganin maganin maganin maganin maganin maganin magani ko nicotine. Bugu da ƙari, wasu marasa lafiya sun rasa saboda damun lokaci. Na biyu, ba zamu iya sanin ko canje-canje a BP ba_ND su ne saboda canje-canje a cikin karɓar mai karɓa ko ƙauna na fili, kamar yadda waɗannan sigogi ba za a iya raba su ba bisa la'akari da PET daya.³⁰ Daga cikin dalilan da ke tasiri na dangantaka mai mahimmanci, matakan lamarin dopamine sun nuna sun shafi [¹¹C] FLB 457 dauri,^{60, 61, 62} Duk da haka, wasu nazarin sun kasance mummunan.^{63, 64} A cikin rodents, inda matakan neurotransmitter sun kasance mafi muni, ƙara DA release aka lura a mayar da martani ga stressful stimuli.^{65, 66} Ko da yake nazarin yana amfani da ƙwarewar PET da yawa tare da ayyukan musamman na [¹¹C] FLB 457 sun nuna cewa asusun ajiyar ƙwaƙwalwar ajiyar lissafi ga mafi yawan bambancin a cikin BP_ND,⁶⁷ ba za a iya cire cewa bambance-bambance a cikin matakan lamarin dopamine zai iya kasancewa lissafi ga ƙungiyoyi da aka lura, alal misali misali mafi girma DA amsawa a yayin aikin gwaji a marasa lafiya tare da karamin cigaba bayan magani.

A ƙarshe, sakamakon daga wannan binciken na farko ya nuna cewa filastik canji a cikin tsarin kwayoyin halitta zai iya rage yawan alamun rashin jin tsoro a cikin marasa lafiya SAD bayan magani tare da CBT. Nazarin yana taimaka wa tsarin tsarin dopamine a SAD, kuma ya nuna cewa kwatancen mutum daya zai iya kasancewa mai matukar muhimmanci a gano masu cin hanci da kwakwalwa na kwakwalwa don rashin lafiya.

Ka tafi zuwa ga:

Acknowledgments

Binciken ya taimaka wa Söderström Königska Stiftelsen, Hukumar Kula da Lafiya ta Duniya, da Ƙungiyar Ƙasa ta Stockholm da Psykiatrifonden. Manyan ma'aikata a Karolinska PET Center da kuma Intanet Asibitin Harkokin Ƙwararrun Ƙwararru a Jami'ar Karolinska Hospital Huddinge an nuna godiya gamsu.

Ka tafi zuwa ga:

Notes

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

Ka tafi zuwa ga:

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