I-New Biomarker ye-Hedonic Eating? Uphando oluPhambili lweCortisol kunye neempendulo ze-Nausea kwi-Opioid Blockade (2014).

. Umbhalo obhaliweyo ifumaneka kwi-PMC 2015 Mar 1.

Ishicilelwe kwifomu yokugqibela ehleliweyo njenge:

Umdla wokutya. 2014 Mar; 74: 92–100.

Ipapashwe kwi-intanethi ye-2013 u-Novemba 27. doi:  I-10.1016 / j.appet.2013.11.014

PMCID: PMC4125886

I-NIHMSID: I-NIHMS552807

Abstract

Abantu abatyebe kakhulu nabatyebe kakhulu bayahluka kwiqondo labo lokutya i-hedonic. Oku kunokubonakalisa uhlengahlengiso kwiisekethe ze-neural ezinxulumene nomvuzo, ezilawulwa ngokuyinxenye ngumsebenzi we-opioidergic. Sivavanye umlinganiselo ongathanga ngqo, osebenzayo womsebenzi we-opioidergic ephakathi ngokuvavanya i-cortisol kunye neempendulo ze-nausea kwi-blockade ye-opioid ebukhali kusetyenziswa i-opioid antagonist naltrexone kubafazi abakhulu kakhulu / abatyebileyo (ithetha i-BMI = 31.1 ± 4.8) ngaphambi kokuba uqale ukungenelela kokutya okunenkathalo ukunciphisa ukutya koxinzelelo. Ukongezelela, siye savavanya i-indices yokutya okuhlobene ne-hedonic, kubandakanywa nokuziphatha kokutya (ukutya ngokutya, ukutya ngokweemvakalelo, ukutya kwangaphandle, ukuzibamba) kunye nokuthatha iilekese / i-dessert kunye ne-carbohydrates (Block Food Frequency); ulwazi lwe-interoceptive (olunxulunyaniswa nokuziphatha ngendlela engafanelekanga yokutya); kunye nenqanaba le-adiposity kwisiseko. Ukunyuka okubangelwa yi-Naltrexone kwi-cortisol kwayanyaniswa nokutya okukhulu kweemvakalelo kunye nokuthintela kunye nokuqonda okuphantsi kokuqonda. Isicaphucaphu esibangelwa yiNaltrexone yayanyaniswa nokutya kakhulu kunye nokutyeba okuphezulu. Ngaphaya koko, kuhlalutyo oluncinci lokuphonononga, isicaphucaphu esibangelwa yi-naltrexone yaxela kwangaphambili impendulo yonyango kungenelelo lokutya ngokucokisekileyo, njengoko abathathi-nxaxheba abanesicaphucaphu esiqatha kwinqanaba lokuqala bagcina ubunzima ngelixa abo bangenazo iimpendulo zesicaphucaphu bathande ukufumana ubunzima. Ezi datha zangaphambili zibonisa ukuba ukukhutshwa kwe-cortisol eyenziwe yi-naltrexone kunye nesicaphucaphu kunokunceda ekuchongeni abantu abanokuxhomekeka okukhulu kokutya okuxhomekeke kumvuzo, okukhokelela kukutya okugqithisileyo. Uphando lwexesha elizayo luyafuneka ukuqinisekisa oku kufunyanisiweyo kunye nokuvavanya ukuba ngaba aba bamakishi bethoni ye-opioidergic banokunceda ukuqikelela impumelelo kwiintlobo ezithile zeenkqubo zokulawula ubunzima.

Internet: Naltrexone, ukutya i-hedonic, ukuba likhoboka lokutya, i-cortisol, isicaphucaphu, ukutyeba ngokugqithiseleyo

Ngokufika kwesifo sokutyeba kunye nobuninzi bokutya okunencasa kwindawo yokutya yangoku, ingcamango yokutya kwe-hedonic iye yavela. Ukutya i-Hedonic kubhekiselele ekutyeni ukutya okumnandi, okunemivuzo, ngokuchaseneyo nokutya okune-homeostatic, okubhekisa ekutyeni imfuno yekhalori.). Ukutya kwe-Hedonic kuye kwabandakanyeka kumbono "wokutya," ubukho babo buxoxwa ngokushushu kwiintetho zesayensi kunye noluntu (; ). Iithiyori zicebisa ukuba ukutya okuqhutywa yi-hedonic kunokubangela ukuba abantu babe likhoboka lokutya okanye izinto ezithile ngendlela efana neziyobisi.; ). Ngapha koko, ezi ndlela zokuziphatha zokutya zinokukhokelela ekufumaneni ubunzima kunye nokutyeba kwiseti yabantu.

Ubungqina obunxibeleleneyo obuxhasa umbono wokulutha kokutya buyanda njengoko izifundo ze-neuroimaging zityhila ukuba bobabini abantu abatyebe kakhulu nabangamakhoboka eziyobisi banotshintsho kwimimandla yobuchopho ehambelana nobuntununtunu bomvuzo, inkuthazo yenkuthazo, inkumbulo nokufunda, ulawulo lwempembelelo, ukuphinda uqalise ukusebenza ngoxinzelelo, kunye nokuqonda (kwi-interoceptive awareness). jonga kwakhona, yabona ). Kwizifundo zezilwanyana, ubungqina obukhulayo bubonisa ukuba ukutya okunencasa okuxhaphakileyo ekuboneleleni kwethu kokutya (ngakumbi, oko kunamanqanaba aphezulu eswekile kunye namafutha) kuneempawu zokukhobokisa. Iimpuku ezinikwe ufikelelo ekutyeni okunencasa kakhulu zibonisa iimpawu zakudala zokulutha, kubandakanya ukuzinkcinkca, ukurhoxa, ukunqwenela, kunye nokwazisana njengoko kufunyenwe ukuphendula kwiziyobisi zokuxhatshazwa ().

Inkqubo ye-opioid ngokuyinxenye iqulethwe kwisekethe ye-neural ebalulekileyo ebandakanyeka kusetyenziso lweziyobisi kunye nomvuzo wokutya. Ukusetyenziswa ngokungxamisekileyo kokutya okunencasa kukhuthaza ukukhululwa kwe-opioids engapheliyo, elamla iimvakalelo zolonwabo (). Nangona kunjalo, ukuvuselela okuphindaphindiweyo kwe-post-synaptic opioid receptors ngenxa yokutya okungapheliyo kokutya okunencasa kunokubangela utshintsho lwexesha elide kumsebenzi we-receptor okanye iindlela zokudlulisa ezithi emva koko zilawule isenzo se-opioid (). Umzekelo, iimpuku zinikwe ukufikelela rhoqo kwitshokholethi okanye i-sucrose ebangela ukuba umntu atye kakhulu abonakalise ukubonakaliswa kwe-enkephalins (i-opioid engapheliyo) kwi-ventral striatum, ingingqi yengqondo ebandakanyekayo kumvuzo.; ). Imeko ye-opioidergic enesiphumo inokubangela ukuba umntu arhoxe. Iigundane zinikwe ukufikelela okungapheliyo kwisidlo esine-sucrose ephezulu kwaye emva koko isuswe ngequbuliso okanye iphathwe nomchasi we-opioid ibonisa ukuziphatha okuhambelana nokurhoxiswa kwe-opiate (). Isimo sokurhoxa, sinokonyusa inkuthazo yeswekile, njengoko ifumaneka ekusebenziseni kakubi utywala (). "Ukufuna" komvuzo wokutya kulamlwa ngokusayinwa kwe-μ-opioid kwi-nucleus accumbens (). Ezi zifundo zezilwanyana zahlukeneyo zibonisa ukuba umsebenzi we-opioid osembindini ubandakanyeka kwiinkqubo zokukhobokisa ezingundoqo ezinxulumene nokutya okunencasa, ngakumbi, ukuzintyintya, ukurhoxa, kunye nokunqwenela.

Ngaphandle kokunyanzeliswa kweemodeli ze-neurobiological zokulutha kwizilwanyana, kukho ukunqongophala kobungqina obuthe ngqo bokuqinisekisa umbono wokutya okuqhutywa yi-hedonic okanye umlutha wokutya ebantwini (). Akukho ziphawuli ezisebenzayo eziqinisekisiweyo zomsebenzi ophakathi we-opioidergic ebantwini, okufutshane kwi-positron-emission tomography (PET) scans ukuvavanya amandla okubopha i-opioid receptor. Nangona kunjalo, njengomlinganiselo osebenzayo ongathanga ngqo, iziphumo zabachasi be-opioid kwi-hypothalamic-pituitary-adrenal axis (HPA) ziye zafundiswa ukuvavanya indima ye-opioidergic engapheliyo kutywala kunye ne-nicotine. ; ; ; ). I-opioids engapheliyo inqanda i-axis ye-HPA ngeendlela ezimbini. Okokuqala, i-neurons kwi-nucleus ye-arcuate equkethe i-β endorphin kunye ne-enkephalin isebenze i-μ receptors ye-opioid kwi-nucleus ye-paraventricular ukuvimbela ukukhululwa kwe-corticotropin-releasing-hormone (CRH)). I-opioids iphinda ithintele umsebenzi we-norephinephrine-containing neurons kwi-locus coeruleus, eyenza i-hypothalamic CRH neurons.). I-Phamacologic blockade ye-opioid receptors ikhupha i-opioidergic inhibitory input kwi-CRH neurons, ivuselela ihomoni ye-pituitary adrenocorticotropic (ACTH), kwaye ekugqibeleni i-cortisol evela kwi-adrenal gland. Ngenxa yoko, ukungafani komntu ngamnye kumsebenzi ophakathi kwe-opioidergic kunokubonwa ngempendulo ye-cortisol kwi-opioid antagonism. Ukonyuka okukhulu kokukhululwa kwe-cortisol kumchasi we-opioid kunokubonisa ithoni ye-opioid ebuthathaka ngenxa ye-opioid engapheliyo ekhoyo ekhoyo ukukhuphisana neziza ezibophelelayo, okanye ukuncipha kwe-opioid receptor density ekhokelela ekugqityweni okupheleleyo kwamagalelo e-inhibitory kwi-hypothalamus (; ). Ukuza kuthi ga ngoku, uphando oluthile lufumene ukuba izigulane ezine-bulimia zinezinga eliphezulu le-cortisol ekuphenduleni i-naloxone (i-opioid antogonist) xa kuthelekiswa nolawulo ().

Ngelixa iindlela ezichanekileyo eziphantsi kobudlelwane phakathi kweempendulo ze-cortisol, umsebenzi ophakathi we-opioidergic, kunye nabachasi be-opioid zingaziwa, siye sathi ukutyiwa okungapheliyo kokutya okunencasa kakhulu kunciphisa ukuveliswa kwe-opioid ye-opioid engapheliyo okanye ubuninzi be-receptor, obunokuthi bubonakaliswe ngokunyuka kwe-cortisol ekuphenduleni umchasi we-opioid. Siphinde sachaza ukuba iimpendulo zesicaphucaphu kwi-opioid antagonism inokuba sisalathisi sesibini somsebenzi we-opioid ephakathi, njengoko abo banethoni ye-opioidergic ephantsi banokuziva benesicaphucaphu ngakumbi emva kokuvalwa kwe-opioid ebukhali. Unyango lwe-Naltrexone (ikakhulukazi i-μ opioid antagonist) ngokudibanisa ne-bupropion iphumela ekulahlekeni kobunzima obubalulekileyo ngokwekliniki () ukuxhasa indima yenkqubo ye-opioid ekuziphatheni kokutya kunye nokuzuza ubunzima. Nangona kunjalo isicaphucaphu sisiphumo esixhaphakileyo se-naltrexone, kwaye ukuphononongwa komgangatho kucebisa ukuba kunokunyuswa kubantu abatyebe kakhulu (). Kwizilingo ezimbini ezinkulu zekliniki ezilawula i-naltrexone kubantu abatyebe kakhulu, i-30-34% ichaze isicaphucaphu kwimeko yonyango xa kuthelekiswa ne-5-11% kwiqela le-placebo.). Ukuza kuthi ga ngoku, ubudlelwane phakathi kwesicaphucaphu esibangelwa yi-naltrexone kunye nokutya okunxulumene ne-hedonic kuhlala kungajongwa.

Kuphononongo lwangoku, sivavanye i-cortisol kunye neempendulo zesicaphucaphu kumceli mngeni osemgangathweni we-naltrexone phakathi kwabasetyhini abatyebileyo nabatyebe kakhulu. Ekuhlalutyweni kwamacandelo, sivavanye ukuba ezi mpendulo zihambelana nokuziphatha okunxulumene ne-hedonic, kubandakanywa ukutya, ukuvakalelwa, kunye nokutya okusekelwe ngaphandle. Siphinde sabandakanya ukuthintela ukutya ngenxa yokuba, nangona ingalinganisi ngokucacileyo ukutya kwe-hedonic, abantu abaphezulu ekuthinteleni ukutya ngokugqithisileyo xa bejongene noxinzelelo okanye umthwalo wokuqonda (). Ukuthintela ukutya kuye kwaphinda kucingelwa kwakhona njengokubonisa i-hedonic yokutya efihliweyo, enabantu abathinteleyo kakhulu batya kancinci kunokuba bafuna, kunokuba bancinci kunokuba bafuna.). Siphinde savavanya ubudlelwane phakathi kwe-cortisol kunye neempendulo zesicaphucaphu kwi-naltrexone kunye nokutya okutyiwayo kunye ne-adiposity. Xa benikwa i-naltrexone, abasetyhini abaxela amanqanaba aphezulu okuziphatha okunxulumene ne-hedonic banokubonisa imeko yokurhoxa efana ne-opiate, efana nemodeli yegundane yeswekile ephezulu.). Ke ngoko, saqikelela ukuba isicaphucaphu esikhulu kunye neempendulo ze-cortisol kwi-naltrexone, ebonisa ukuba umsebenzi we-opioidergic ubuthathaka, unokunxulunyaniswa namanqanaba aphezulu okuziphatha okunxulumene ne-hedonic, ukutya okuninzi okunencasa, kunye nokudityaniswa okugqithisileyo.

Siphinde saphonononga unxulumano lweempendulo ze-naltrexone kunye nokwazisa nge-interoceptive, imbono yeemvakalelo ezivela ngaphakathi emzimbeni. Ngokweethiyori zamva nje, ukwazisa nge-interoceptive kubalulekile ekulawuleni i-homeostasis kwaye kunokutshintshwa ngenxa yokulutha.; ; ). Ngenxa yokuba abantu abakhotyokisiweyo behlala behlelwa ziimeko zomzimba eziguqukayo nokuba zibangelwa ziimpawu zokurhoxa okanye ukuxinezeleka ngokweemvakalelo, banokusabela ngokungxama ngakumbi kwiimvakalelo zokunqwenela okanye ukurhoxa nokuba banelise iminqweno okanye ukunciphisa imeko egwenxa (). Njengenyathelo lokuqala ekuqondeni unxulumano olunokubakho phakathi kweenkqubo zokulutha ukutya kwe-opioid kunye nokuqonda, siye savavanya ukuba ingaba imiba eyazixelayo yokwazisa nge-interoceptive inxulumene neempendulo ze-naltrexone.

Okokugqibela, iimpendulo kwi-acute opioid blockade zinokuba luncedo lweklinikhi ngokuxela kwangaphambili umahluko ngamnye kwimpendulo yonyango kungenelelo lwabantu abatyebileyo nabatyebe kakhulu. Sihlolisise ukuba ngaba iimpendulo ze-naltrexone kwisiseko esiqikelelweyo sokutshintsha ubunzima phakathi kwabasetyhini ababhalise kwi-randomized waitlist-control pilot study yeprogram esekelwe engqondweni yokutya uxinzelelo ().

tindlela

nxaxheba

Eli phepha linika ingxelo ngesiseko sedatha eqokelelwe kwi-subset yabasetyhini (N = 33) abanyule ukuba bathathe inxaxheba kwi-substudy yovavanyo lwe-randomized waitlist control pilot test of a mindful intervention for overeating and stress (N = 47), echazwe ngaphambili (). Iimpawu zesampulu zixelwe kwi 1 Table. Ukubunjwa kohlanga lwesampulu yayiyi-64% eMhlophe, i-18% yase-Asia-yaseMelika, i-15% ye-Hispanic / Latina, kunye ne-3% ichongiwe njengolunye uhlanga. Abahlanu abathathi-nxaxheba bebekwiyeza elizinzileyo lokulwa nokudakumba.

1 Table 

Iimpawu zeSampuli (N=33)

IBhodi yokuHlola yeziko yeYunivesithi yaseCalifornia, eSan Francisco (UCSF) ivume olu phononongo kwaye bonke abathathi-nxaxheba banikezela ngemvume enolwazi. Ngokufutshane, abathathi-nxaxheba basetyhini abadala baqeshwe ngamajelo eendaba kunye neendlela eziphambili zokufaneleka ngolu hlobo lulandelayo: i-index mass body (BMI) phakathi kwe-25 kunye ne-40; ngaphambi kokuya exesheni; akukho mlando wesifo sikashukela okanye isifo se-cardiovascular, okanye i-endocrinologic disorder esebenzayo; engakhulelwanga okanye engaphantsi konyaka omnye emva kokubeleka; akukho ukucamngca kwangaphambili okanye okwangoku okanye ukuziqhelanisa neyoga; hayi okwangoku kwisicwangciso sokutya okanye ukuthatha amayeza anokuchaphazela ubunzima; akukho ngxaki yangoku yokuzixelayo ngokutya okanye utywala okanye iziyobisi; ukungathathi amayeza eentlungu ze-opiate, i-steroids, okanye i-antipsychotic; kunye nabafundi besiNgesi. Abathathi-nxaxheba banikezela ngesampuli yomchamo ukuvavanya ubukho be-opioids okanye ezinye iziyobisi kunye nokukhulelwa. Zonke iimvavanyo zabonisa ukuba awunayo. Abathathi-nxaxheba abafanelekileyo nabanomdla bagqibe ukutyelelwa kabini kwi-UCSF Clinical Research Centre (ukufaneleka kunye ne-anthropometrics) kunye ne-intanethi ye-questionnaire ibhetri kwisiseko. Baye bavavanywa kwakhona ngotyelelo olufanayo kunye ne-questionnaire yebhetri emva kokungenelela.

Iimvavanyo ezisisiseko

Iimpendulo zeCortisol kunye neNausea kwiNaltrexone

Zonke iimvavanyo ezisisiseko zagqitywa ngaphambi kokwenziwa ngokungenamkhethe. Abathathi-nxaxheba bayalelwa ukuba bagqibezele iikiti zesampulu zamathe zasekhaya ukuvavanya amanqanaba e-cortisol ngeentsuku ezi-4. Iintsuku ezintathu zokuqala yayiziintsuku zokulawula ukuvavanya izingqisho ze-diurnal cortisol ekuvukeni, imizuzu engama-30 emva kokuvuka (ukubamba ukunyuka kwasekuseni), ngo-1pm, 2pm, 3pm, kunye ne-4pm. Abathathi-nxaxheba bayalelwa ukuba baqokelele isampuli yokuqala ngelixa belele, kwaye bangadli, bangaseli, baxube amazinyo okanye bahlanganyele kumsebenzi onamandla phakathi kweesampuli ezimbini zokuqala zentsasa okanye imizuzu engama-20 ngaphambi kwazo zonke ezinye iisampuli.

Ngosuku lwesine, abathathi-nxaxheba bathatha umthamo wekliniki we-naltrexone (50 mg) emva kwesampuli ye-saliva ye-1pm emva kwesidlo sasemini ukulawula iimpendulo ze-cortisol ekutyeni ukutya. I-dose ye-50 mg ikhethwe ngenxa yokuba yi-dose evunyiweyo ye-FDA yonyango lokuxhomekeka kotywala kunye ne-opioid kwaye isetyenziswe kwezinye izifundo.). Ixesha lokuqokelela amathe linqunywe ngokusekelwe kwizifundo ezibonisa ubungqina bezinga eliphezulu le-naltrexone kunye ne-cortisol yogxininiso kwiiyure ze-2-3 emva kokulawulwa kwe-naltrexone.). Abathathi-nxaxheba baxelelwa malunga neziphumo ebezingalindelekanga ezingalunganga ezinokubakho kubandakanya isicaphucaphu kwaye banikwe uluhlu lweMibuzo ebuzwa rhoqo malunga ne-naltrexone ukuya nayo ekhaya echaza iziphumo ebezingalindelekanga. Akukho meko ye-placebo iye yalawulwa. Isampulu nganye yaqokelelwa ngokuvuza kwi-straw kwiityhubhu ze-2 mL ze-SaliCaps (IBL Hamburg, eJamani). Uhlalutyo lweCortisol lwenziwa kwiDresden LabService kwiYunivesithi yaseDresden yeTekhnoloji (eJamani) isebenzisa i-chemiluminescence immunoassay yorhwebo (CLIA; IBL Hamburg, eJamani). Amaxabiso angaphezu kwe-100 nmol/L akabandakanywanga ngenxa yokuba awela ngaphandle koluhlu lovavanyo.

Ukuvavanya iimpawu ze-nausea, abathathi-nxaxheba bagqibe uluhlu lokutshekisha iimpawu ze-14, kubandakanywa isicathulo, usebenzisa i-4-point scale (0 = akukho, 1 = imnene, i-2 = imodareyitha, i-3 = inzima). Abathathi-nxaxheba bacelwa ukuba bagcwalise uluhlu lokukhangela kanye phambi kokulala. Abathathi-nxaxheba abangenalo uluhlu olupheleleyo lokukhangela babizwe ngabasebenzi bophando ukuba bagqibezele izinto ezingekhoyo.

Iiguquguquko ze-Anthropometric

I-stadiometer eqhelekileyo (i-Perspective Enterprises, i-Portage, i-MI) isetyenziswe ukulinganisa ubude ukuya kwi-intshi ye-1 / 8th ekufutshane. Isikali sedijithali (i-Wheelchair Scale 6002, Scale-Tronix, Carol Stream, IL) isetyenziswe ukulinganisa ubunzima kwi-0.1kg ekufutshane. Isalathisi sobunzima bomzimba sibaliwe (kg/m2). Ubunzima buphinde bavavanywa emva kokungenelela.

Amafutha Omzimba

Umzimba wonke wamandla amabini e-X-ray absorptiometry (DEXA) iskeni senziwe ukuvavanya ipesenti epheleleyo yamafutha omzimba. I-densitometer ye-DEXA (i-GE Healthcare Lunar Prodigy, Madison, WI, USA) yahlengahlengiswa kwimodi ye-fan beam kunye ne-EnCore software version 9.15 isetyenzisiwe. I-coefficient of variation ekuhloleni ubunzima bamanqatha kwi-UCSF General Clinical Research Centre densitometer yi-4%.

Ukutya ii-Behaviors

I-Questionnaire ye-Dutch Eating Behavior (DEBQ) (Van Strien, 1986) ivavanya ukutya okunqandayo, ukutya okuvakalelwa, kunye nokutya okusekelwe ngaphandle. I-Restrained Eating subscale ivavanya iinjongo kunye nokuziphatha ukukhawulela ukutya ngenxa yeenkxalabo malunga nobunzima. Okumangalisayo kukuba, ukutya okuthintelweyo kuxela kwangaphambili ukutya okunencasa ekuphenduleni imisebenzi yengqondo engenaxinzelelo, ebonisa ukuba abantu abatyayo banotyekelo olufihlakeleyo lokutya ukutya okunencasa.). I-Emotional Eating imilinganiselo ephantsi yokutya okubangelwa ziimvakalelo ezingalunganga, ezinjengomsindo, ukukruquka, ixhala, okanye uloyiko. I-External-based Eating subscale ihlola ukutya ngokuphendula kwizinto ezinxulumene nokutya, ezifana nevumba okanye incasa yokutya okanye ubukho bokutya kwindawo engqongileyo. Iimpendulo zenziwe kwisikali se-5-point ukusuka kwi-1 = ungalokothi ukuya kwi-5 = rhoqo kakhulu.

I-Binge Eating Scale (BES) yayisetyenziselwa ukuvavanya ubungakanani kunye nobukhulu bokunyanzeliswa kweepatheni zokutya, kubandakanywa utyekelo lokuziphatha (umzekelo, ukutya ukutya okuninzi) kunye neemvakalelo ezingalunganga kunye neengcinga ezinxulumene nokutya kakhulu okanye umzimba womntu.). Ingumlinganiselo oqhubekayo ovakalelwa kuluhlu olubanzi lweenkxalabo kunye neepatheni ngokutya kakhulu kunokuba kuxilongwe ukuphazamiseka kokutya.

Ukuqaphela i-Interioceptive

I-Questionnaire ye-Body Responsiveness (BRQ) sisikali sezinto ezi-7 ezisetyenziselwa ukuvavanya imiba yolwazi lwe-interoceptive (; ). Uhlalutyo lwamacandelo aphambili lubonisa izinto ezimbini kuphando oludlulileyo (i-Daubenmier, uhlalutyo olungashicilelwanga) kunye nakwisifundo sangoku. I-factor loadings yayinkulu kune-.40 echaza i-68% yokuhluka kwesikali. I-subscale yokuqala, "Ukubaluleka kokuQaphela koLwazi nge-Interoceptive," ivavanya ukubaluleka kokusebenzisa ulwazi lwe-interoceptive ukulawula ukuziphatha kunye nokuzazi (izinto zesampuli ziquka: "Kubalulekile kum ukwazi ukuba umzimba wam uziva njani imini yonke"; " Ndiqinisekile ukuba umzimba wam uya kundazisa oko kulungileyo kum”; “Ndiyakonwabela ukwazi ukuba umzimba wam uziva njani”). I-subscale yesibini, "Uqhawulo olubonwayo," lulinganisa ubungakanani boqhawulo phakathi kweemeko zengqondo nezomzimba (izinto zesampulu ziquka: "Ingqondo yam nomzimba wam usoloko ufuna ukwenza izinto ezahlukeneyo"; "Iminqweno yam yomzimba ikhokelela ekubeni ndenze izinto endiziphelisayo. ngokuzisola”). Iimpendulo zilinganiswe kwinqanaba le-7 ukusuka kwi-1 = ayikho yonke into eyinyaniso malunga nam ukuya kwi-7 = inyaniso kakhulu ngam.

Ukutya kokutya

I-Block 2005 Food Frequency Questionnaire, i-semi-quantitative food frequency questionnaire isetyenziselwe ukuvavanya ukusetyenziswa kokutya kwe-110 yokutya kulo nyaka uphelileyo (). Ipesenti yeekhalori ezisuka kwiicarbohydrates, amafutha, kunye neelekese/izimuncumuncu zibalwe ngokohlalutyo olwenziwa yiNutritionQuest. Nangona isetyenziswa kakhulu, ayikhathali ngandlel’ ithile ekutyeni ngokugqithisileyo okanye kwiipateni zokuzinkcinkca njengesona sixa sikhulu esinokuboniswa njengoko siqhele ukusetyenziswa silinganiselwe kwizinto ezininzi zokutya.

Amaqela angenelelo

Bonke abathathi-nxaxheba bahlelwe ngokungaqhelekanga kunyango okanye kwiqela lolawulo lokulinda kwi-1: umlinganiselo we-1 kunye ne-stratified yi-BMI yecandelo (ubunzima obuninzi: i-BMI 25 - 29.99 vs. Obese: 30 - 39.99), ubudala (≥ iminyaka eyi-40) kunye neyeza zangoku zokudakumba. sebenzisa (n=7), njengoko ezi zinto zinokuchaphazela ukutshintsha kobunzima. Kwi-substudy yangoku, i-16 yayingahleliwe kungenelelo kunye ne-17 kwiqela lolawulo.

Imeko yoNyango

Ungenelelo lwenoveli lwaphuhliswa ngokudibanisa amacandelo avela kwiiprogram ezintathu eziqinisekisiweyo, ukuNcitshiswa kweNxibelelo yokuNxibelela kwengqondo (MBSR)), iMindfulness-Based Cognitive Therapy for Depression, (), kunye noQeqesho oluSekelwe kwiMindfulness ngokuTyayo (MB-EAT) (; ). Ukucamngca ngengqondo kubandakanya uqeqesho olucwangcisiweyo lwemeko yokuqonda ngokuzimasa ngokuphindaphindiweyo iimvakalelo zokuphefumla, amanye amava eemvakalelo, iingcinga, kunye neemvakalelo, kunye nophuhliso lwesimo sengqondo sokungagwebeli. I-MB-EAT, ngokukodwa, ikhuthaza ulwazi lweempawu zomzimba ezinxulumene nendlala, ukuhlutha, kunye nokwaneliseka kwencasa kunye nezinto ezibangela iimvakalelo zokutya kakhulu. Kuphononongo lwangoku, inkqubo yongenelelo iqulethwe ziiklasi ezilithoba zeeyure ze-2.5 kunye neyure enye ye-7 yosuku oluthuleyo lokucamngca ngesikhokelo kwiveki yesithandathu yenkqubo. Abathathi-nxaxheba bakhuthazwa ukuba bathathe inxaxheba kwizabelo zasekhaya zemihla ngemihla ezibandakanya ukuya kwimizuzu engama-30 ngosuku lweendlela zokucamngca ngokusesikweni kunye nokuziqhelanisa nokutya okunengqondo ngexesha lokutya. Iinkcukacha ezithe vetshe malunga nongenelelo zichazwe kwenye indawo ().

Imeko yokulawula

Ukubonelela ngezikhokelo zokutya okunempilo kunye nokuzivocavoca ngexesha lokungenelela kunye nokulawula imiphumo yolwazi olunjalo kwiziphumo zokufunda, zombini amaqela athatha inxaxheba kwisondlo seyure ye-2 kunye neseshoni yolwazi olujoliswe ekulahlekeni kwesisindo esiphakathi phakathi kokungenelela, apho ukunyanzeliswa kwengqondo. akuzange kuxoxwe.

Uhlalutyo lweSatisati

Abathathi-nxaxheba abanosuku olunye lolawulo lwedatha ye-cortisol bafakwe kuhlalutyo. Iisampulu ezidityanisiweyo ze-t-mvavanyo zisebenzisa eyona ndlela incinci yokwahlukana kwezikwere zisetyenziselwe ukuthelekisa umahluko phakathi koxinzelelo lwe-cortisol ngo-1pm, 2pm, 3pm, kunye ne-4pm malunga neentsuku ezintathu zolawulo kunye nosuku lwenaltrexone, kunye nokuthelekisa umahluko phakathi kwamaxesha kulawulo. iintsuku kunye nosuku lwe-naltrexone. Sibale izikhombisi ezibini zempendulo ye-cortisol kwi-naltrexone ukuphonononga usetyenziso oluqikelelweyo lomlinganiselo ngamnye. Isalathisi sokuqala sibalwa ngokukhupha impendulo ye-cortisol ephezulu (nge-4pm) ukusuka kwinqanaba le-cortisol kwisampuli ye-1pm ngosuku lwe-naltrexone. Isalathisi sesibini sibalwa ngokususa utshintsho kwi-cortisol ukusuka kwi-4pm-1pm ngosuku lwe-naltrexone ukusuka kumlinganiselo ophakathi ukusuka kwi-4pm ukuya kwi-1pm kwiintsuku zokulawula ukuphonononga uvakalelo olongezelelweyo lomlinganiselo xa ugxininiso lwe-cortisol olusisiseko luthathelwa ingqalelo. Ngenxa yokusasazwa okugwenxa kwempendulo ye-cortisol, ulungelelwaniso lwenqanaba le-Spearman lusetyenziselwe ukuvavanya imibutho phakathi kweempendulo ze-cortisol kwi-naltrexone kunye namanye amanyathelo.

Ukuziphendulela kwe-nausea kwavavanywa ngokwahlula abathathi-nxaxheba kwiindawo eziphantsi (akukho nanye okanye zincinci) kunye namaqela eempawu eziphezulu (eziphakathi okanye ezinzima) kunye novavanyo oluzimeleyo lwe-t-mvavanyo lwenziwa ukuthelekisa ukungafani phakathi kwamaqela ekuziphatheni kokutya, ukuqaphela i-interoceptive, kunye namanyathelo omzimba womzimba. Uvavanyo lwe-Levene lokulinganisa ukulingana kweentlobo lusetyenziselwa ukuvavanya ukulingana kokungafani phakathi kwamaqela kunye needigri zenkululeko zahlengahlengiswa kwiimvavanyo zesampula ezizimeleyo ukuba uvavanyo lwalubalulekile (p <.05). Ukuhlolisisa i-nausea njenge-predictor yenguqu yesisindo ngaphakathi kweqela lonyango, i-2 × 2 i-ANCOVA yenziwa kunye neqela lonyango (unyango kunye neqela lokulawula uluhlu lokulinda) kunye neqela le-nausea (i-low vs. amayeza okudakumba asetyenziswa njenge covariates. Iinguqu eziqhubekayo zeempendulo ze-cortisol kwi-naltrexone zihlolwe njengezibikezelo zenguqu yesisindo ngeqela lonyango usebenzisa uhlalutyo oluninzi. Isiseko se-BMI, ukusetyenziswa kweyeza elichasayo, iqela lonyango, kunye nempendulo ye-cortisol yangeniswa kwinqanaba le-1 kunye nexesha lokusebenzisana (iqela lonyango × impendulo ye-cortisol) yangeniswa kwinqanaba le-2 ye-equation.

iziphumo

Abathathi-nxaxheba abanyule ukuthatha inxaxheba kwi-substudy babe nepesenti enkulu kakhulu ye-adiposity iyonke xa kuthelekiswa nabo banqabile (45.7 ± 5.0 vs. 42.5 ± 3.7, p = .047). Akukho mahluko omnye isiseko (kuquka ukuguquguquka kwentlalo yabantu okanye ngokwasengqondweni) ebebalulekile phakathi kwabo banyulileyo okanye abala ukuthatha inxaxheba kwisifundo. Abathathi-nxaxheba abathathu abazange banikeze iisampulu ze-saliva okanye bathathe i-naltrexone njengoko kuchaziwe, kwaye abazange bafakwe kuhlalutyo olufanelekileyo. Abathathi-nxaxheba abangamashumi amabini anesixhenxe (82%) babenedatha epheleleyo ye-cortisol kuzo zonke iintsuku ezintathu zokulawula kwaye abathathi-nxaxheba be-30 (91%) babenedatha epheleleyo ye-cortisol ngosuku lwe-naltrexone. Abathathi-nxaxheba abangamashumi amabini anesixhenxe (82%) babenedatha epheleleyo ye-cortisol ubuncinane bosuku olunye lolawulo kunye nosuku lwe-naltrexone. Abathathi-nxaxheba abathathu abakwazanga ukuphendula umbuzo wesicaphucaphu.

Cortisol kunye neempendulo zesicaphucaphu

I-Cortisol yehle ngo-3.6 ± 2.2 nmol / L phakathi kwe-1pm kunye ne-4pm kwiintsuku zokulawula (95% CI: 2.8 - 4.4; t (32) = 9.4, p <.001) kwaye yanda ngosuku lwe-naltrexone nge-8.0 ± 17.4 nmol / L (95% CI: 1.5 - 14.5; t (29) = 2.53, p = .02) phakathi kwe-1pm kunye ne-4pm (bona Umzobo 1). Ugxininiso lweCortisol aluzange luhluke kakhulu phakathi kweentsuku zokulawula ngokubhekiselele kwimini ye-naltrexone kwixesha lesiseko se-1pm [t (30) = 0.80; p = .43)]. Nge-2pm (iyure enye emva kokuthatha i-naltrexone) ixabiso le-cortisol laliyi-3.3 ± 8.1 nmol / L (95% CI: 0.2 - 6.4) ngaphezu komyinge weentsuku zokulawula kwi-2pm [t (28) = 2.2, p = .04]. Nge-3pm (iiyure ezimbini emva kokuthatha i-naltrexone) ixabiso le-cortisol laliyi-9.0 ± 12.5 nmol / L (95% CI: 4.4 - 13.6) ngaphezu komyinge weentsuku zokulawula kwi-2pm [t (30) = 4.0, p <.001]. Lo mahluko unyuke nge-4pm, kunye nemilinganiselo ye-cortisol ngosuku lwe-naltrexone eyayiyi-11.5 ± 17.9 nmol / L (95% CI: 5.1 - 18.0) ngaphezulu kwe-4 pm ngeentsuku zokulawula [t (31) = 3.6, p = . 001].

Umzobo 1 

Iimpendulo zeCortisol kwiiNtsuku zoLawulo kunye noSuku lweNaltrexone

Inqanaba eliphakathi lobunzima be-nausea laliyi-1.23 ± 1.3. Ngenxa yokusasazwa okugwenxa, abathathi-nxaxheba bahlulahlulwe baba ngamaqela aphantsi kunye namaqela aphezulu e-nausea, kunye ne-60% yabathathi-nxaxheba (n = 18) ababika ukuba akukho nanye kwi-nausea epholileyo kunye ne-40% ingxelo ephakathi ukuya kumanqanaba anzima (n = 12). Incopho yeempendulo ze-cortisol kwi-naltrexone (oko kukuthi, umahluko phakathi kwe-4pm - 1pm) ithande ukuba phezulu phakathi kwabathathi-nxaxheba ababika isicaphucaphu esibi kakhulu (13.4 ± 17.3 nmol/L) xa kuthelekiswa nezo zine-nausea ephantsi [2.0 ± 10.9 nmol/L; t (13.3 = -1.9, p = .08, bona Umzobo 2].

Umzobo 2 

Iimpendulo zeCortisol kwiNaltrexone ngamaQela eSicaphucaphu esiPhantsi kunye nesiPhezulu

Unxulumano phakathi kweempendulo ze-cortisol naltrexone kunye ne-adiposity, i-hedonic yokutya ukuziphatha, kunye nokuqonda okunzulu kuboniswa 2 Table. Iimpendulo eziphakamileyo ze-cortisol ngosuku lwe-naltrexone zazinxulunyaniswa kakhulu nokutya okuphakamileyo kunye nokunciphisa umzimba kunye nokubaluleka okuphantsi kolwazi lwe-interoceptive. Ukucacisa okufunyaniswe kuphezulu vs. abadli ngokweemvakalelo ukubona Umzobo 3. Incopho enkulu yeempendulo ze-cortisol kwi-naltrexone xa kuthelekiswa neentsuku zolawulo yayinxulumene kakhulu nokutya okuthintelweyo, amanqaku asezantsi ngokubaluleka kolwazi lokuqonda, ukuthathwa kwekhabhohayidrethi eninzi, kunye nomda onxulumene nokuthathwa okukhulu kweelekese kunye needessert.

Umzobo 3 

Iimpendulo zeCortisol Emva kweNaltrexone yiQela lokutya ngokweemvakalelo
2 Table 

Imibutho Phakathi kweempendulo zeCortisol kunye neNausea kwiNaltrexone kunye nezalathisi ze-Hedonic Eating kunye ne-Adiposity

Njengoko kuboniswe kuyo 3 Table, iqela eliphezulu le-nausea lalinamafutha amaninzi kakhulu epesenti yomzimba, lichaze iimpawu zokutya kakhulu, kwaye lithande ukuba ne-BMISs ephezulu, kwaye linike ingxelo yokutya okunovakalelo kunye nokubaluleka okuncinci kokuqonda kwengqondo xa kuthelekiswa neqela eliphantsi le-nausea, kunye nale miba mithathu yokugqibela yokwahlukana kwe-marginal. ukubaluleka kwamanani. Iindlela zeepesenteji zekhalori ezithatha kwiilekese kunye needessert bezikwicala eliqikelelweyo, kunye nokutya okuphezulu phakathi kweqela lesicaphucaphu, kodwa umahluko awufikelelanga kubaluleki bamanani.

3 Table 

Iindlela kunye nokuphambuka okuMgangatho we-Adiposity, i-Hedonic Eating, kunye noKwazisa nge-Interoceptive ngeQela lesicaphucaphu.

Uhlalutyo lokuhlola

Ngokubhekiselele kwimpendulo yonyango ekuphenduleni ukungenelela kwengqondo, iziphumo ze-ANCOVA zibonakalise iqela elibalulekileyo lonyango x ukusebenzisana kwesicaphucaphu ekutshintsheni ubunzima [F (1, 21) = 6.1, p = .02; bona Umzobo 4]. Ukulandelela i-ANCOVAs kubonise ukuba iqela elibi kakhulu le-nausea ligcine ubunzima kumyinge (-1.2 ± 2.9 kg) xa kuthelekiswa neqela eliphantsi le-nausea kwiqela lonyango elifumana ubunzima ngokomndilili (2.7 ± 1.7 kg) [F (1, 10) = 14.4, p = .004] kodwa akukho ntlukwano ebalulekileyo ngeqela le-nausea kwimeko yokulinda [F (1, 9) = 0.3, p = .58]. Ukuhlalutya okuphindaphindiweyo kuhlalutya ukuvavanya iimpendulo ze-cortisol kwi-naltrexone njenge-predictor yenguqu yesisindo ngeqela lonyango kunye namaqela onke ayengabalulekanga (p> .76).

Umzobo 4 

Ukutshintsha kobunzima kuNyango ngokuchasene namaQela oLawulo yiQela lesicaphucaphu

ingxoxo

Kulwazi lwethu, olu luphononongo lokuqala lokuphanda umlinganiselo ongathanga ngqo womsebenzi we-opioidergic ophakathi ngokunxulumene nokuziphatha okunxulumene ne-hedonic phakathi kobunzima obukhulu kunye nabadala. Okokuqala, safumanisa ukuba i-paradigm yeklinikhi yokuphendula kwi-naltrexone yayisebenza njengoko kulindelwe. Sivavanye iziphumo ezibukhali zedosi enye, yekliniki ye-opioid antagonist naltrexone kugxininiso lwe-cortisol kunye nobunzima besicaphucaphu. Ukugxilwa kweCortisol kunyuke nge-103% ngokomndilili ekuphenduleni i-naltrexone kwisithuba seyure ezi-3, ngelixa behle nge-48% kwi-avareji kwiintsuku ezintathu zolawulo ngaphandle kwe-naltrexone ngexesha elifanayo. Ezi ziphumo ziphindaphinda ezo zifundo zangaphambili ezibonisa ukunyuka okuthembekileyo okwenziwe yi-naltrexone kumsebenzi we-HPA (; ; ). Siphinde safumana uluhlu olubanzi lweenguqu zomntu ngamnye kubunzima be-nausea ekuphenduleni i-naltrexone, kunye ne-subgroup ye-40% ebonisa inqanaba elinentsingiselo (eliphakathi ukuya elibi) le-nausea. Siye savavanya ukuba ngaba ezi mpendulo zahlukileyo kwi-cortisol kunye nesicaphucaphu zibikezele ii-indices zokutya ezinxulumene ne-hedonic.

Ngokuhambelana neengqikelelo zethu, ukungafani komntu ngamnye kwi-cortisol eyenziwe yi-naltrexone kunye neempendulo zesicaphucaphu zayanyaniswa nokuziphatha okunxulumene nokutya okunxulumene ne-hedonic, ukuthathwa kwe-carbohydrates, i-adiposity, umkhwa wokunyuka kokutya okunencasa, kunye nokuqonda okuncinci kwe-interoceptive. Akucaci kolu phononongo olunqamlezileyo ukuba i-hedonic yokutya inegalelo kumsebenzi ophantsi we-opioid, okanye ingaba umsebenzi ophantsi okhoyo ngaphambili ukhokelela ekuqhubeni ukutya, okanye zombini. Uphononongo lwezilwanyana lucebisa ukuba ukuzinkcinkca ngokutya ukutya okunencasa kunciphisa umsebenzi we-opioidergic (; ), ngelixa umsebenzi ophantsi we-opioidergic oqhutywa ngokwemfuza unokubangela ukutya kakhulu kwe-hedonic njengendlela yokubuyisela amanqanaba asezantsi olonwabo ngokusekelwe kwizifundo ze-μ opioid receptor OPRMI genotype ().

Nangona i-causality ingacacanga, imibutho emihle yeempendulo ze-cortisol ezenziwe nge-naltrexone kunye nokutya okuvakalelwa kunye nokuthintela kuyahambelana neemodeli zamva nje zokutya koxinzelelo. Abantu abaphezulu ekutyeni okuzithinteleyo okanye ngokweemvakalelo badla ngokutya kakhulu ukutya okuswiti nokutyebileyo ekuphenduleni kuxinzelelo okanye kwimisebenzi enzima ngokwengqondo (). Ukusetyenziswa kokutya okunencasa ngenxa yokutya okunovakalelo okanye okungathintelekiyo okuvela kwisimo sengqondo esithintelweyo sokutya kunokuvelisa ukwanda komsebenzi we-opioidergic kwaye kusebenze ukunciphisa iimpendulo zoxinzelelo olubukhali. Inkxaso yale modeli ivela kwizifundo zezilwanyana ezibonisa ukuba iigundane ezitya ukutya okunamafutha amaninzi kunye neswekile ziye zanciphisa iimpendulo ze-HPA kuxinzelelo olunzima xa kuthelekiswa neempuku ezitya i-chow.). Ukuba ukutya okuneemvakalelo okanye okuthintelweyo kuba yinto engapheliyo, oku kunokunciphisa-ukulawula umsebenzi we-opioidergic kwaye kuya kufuna ukusetyenziswa ngakumbi kokutya okunencasa ukulawula iimvakalelo zoxinzelelo okanye nokugcina iimvakalelo zokuphila kakuhle, ukukhuthaza ukuxhomekeka kunye nokuziphatha okukhobokisayo. Ke, iimpendulo ezinkulu ze-cortisol ezenziwe yi-naltrexone, ezinokubonisa umsebenzi ophantsi we-opioid, ngokuyinxenye zinokubonisa ukusetyenziswa ngokugqithisileyo kokutya okunencasa ukuthoba iimpendulo zoxinzelelo lwe-HPA.

Enye ingcaciso kukuba iimpendulo ze-cortisol eziphezulu ze-naltrexone azibonakalisi ubuntununtunu be-opioid kodwa zibonisa nje ukungasebenzi kakuhle kwe-HPA. Ukuba bekunjalo, umntu unokulindela ukufumana ulungelelwaniso oluqinileyo phakathi kweempendulo ze-cortisol ngosuku lwe-naltrexone kunye neentsuku zokulawula xa kungekho chiza lilawulwa; nangona kunjalo oku kwakungenjalo (i-Spearman's rho = .22, p = .25) iphakamisa ukuba i-hypersensitivity ye-axis ye-HPA yodwa ayinayo ingxelo malunga neziphumo ezikhoyo. Nangona kunjalo, uvavanyo olongezelelweyo luya kuba kukufumanisa ukuba amanqanaba e-cortisol ekuphenduleni enye i-stressor encinci okanye umngeni (umzekelo, i-ACTH) i-akhawunti epheleleyo yeziphumo. Kubalulekile ukuqaphela ukuba umsebenzi ongapheliyo we-endogenous opioidergic ongapheliyo unokukhokelela ekusebenzeni okukhulu kwe-cortisol kwizixinzelelo ngenxa yegalelo le-opioidergic inhibitory kwi-hypothalamus.

Iimpendulo eziphezulu ze-cortisol kwi-naltrexone nazo zazinxulumene ngokufanelekileyo nokutya okukhulu kweekhabhohayidrethi kwaye, kancinci, ekutyeni kakhulu iilekese kunye needessert, kodwa azihambelani nokutyiwa kwamafutha. Ezi ziphumo zihambelana nezo zezifundo zezilwanyana ezicebisa ukuba ukutyiwa kweswekile kukhokelela ekwehliseni ukulawulwa kwenkqubo ye-opioid engapheliyo (), kodwa ukuzinkcinkca ngokutya okunamafutha akunaziphumo zokulutha, njengoko ukutya okunamafutha akuvelisi zimpawu zesomatic okanye ezixhalabileyo zokurhoxa njenge-opiate (). Enye inkcazo enokwenzeka yokungakwazi kwamafutha ukuguqula inkqubo ye-opioid ibandakanya i-neuropeptide galanin (GAL), ekhuthazwa kwiindawo zomvuzo ekuphenduleni ukutya okunamafutha aphezulu. I-GAL inokuthintela umvuzo we-opiate, njengenaliti ye-peripheral ye-galnon, i-agonist yokwenziwa kwe-GAL, ukunciphisa iimpawu zokurhoxiswa kwe-opiate kwiimpuku ezikhotyokiswe yi-morphine (njengoko kuhlaziywe ). Ke, ukuzinkcinkca ngokutya okunamafutha aphezulu kunokunciphisa umvuzo we-opioid ngenxa yokonyuka kwe-GAL. Iziphumo zethu ziyangqinelana nethiyori yokuba iswekile etyebileyo ngecarbohydrate endaweni yokutya okunamafutha kuneempawu eziluthayo ezilawulwa yinkqubo ye-opioid ().

Ubunzima be-nausea babunxulunyaniswa ngokuqinisekileyo ne-adiposity epheleleyo. Oku kufunyaniswayo kuqinisekisa uqwalaselo olusemgangathweni kuncwadi oluxela ukwanda kwesicaphucaphu nge-BMI (). Ukongezelela, ubunzima be-nausea budibene namanqaku aphezulu kwi-Binge Eating Scale, isalathisi somzekelo jikelele wokunyanzeliswa kokuziphatha ngokugqithisileyo. Ubukhali besicaphucaphu nabo buthande ukunxulumana nokutya okukhulu ngokweemvakalelo. Ezi ziphumo zifana nezo zivela kuphononongo lwegundane, xa emva kokutya ukutya okune-sucrose ephezulu, iigundane zibonisa iimpawu ezinkulu zokurhoxisa emva kokulawulwa kwe-naltrexone xa kuthelekiswa namagundane okulawula (). Isicaphucaphu esiqatha kakhulu sinokuba luhlobo lweempawu zokurhoxa ngenxa yamanqanaba asezantsi omsebenzi we-opioidergic. Njengoko kucetyisiwe kwizifundo zezilwanyana, ukutya okungapheliyo okungapheliyo kokutya okunencasa kunokuthoba-ukulawula umsebenzi we-opioidergic. Ke, abantu abatya kakhulu banokuba nomsebenzi ophantsi we-opioidergic.

Umbuzo omnye obalaseleyo malunga neziphumo zizonke uphathelene neepateni ezahlukeneyo zonxulumano phakathi kwamanqaku amabini omsebenzi we-opioidergic. Apha sicinga ukuba zombini isicaphucaphu kunye nokunyuka kwe-cortisol kwibhlokhi ye-opioid kubonakalisa umsebenzi ophantsi we-opioidergic kwaye ke unokubonakaliswa njengeempawu zokurhoxa kwibhlokhi. Enyanisweni, iqela eliphakamileyo le-nausea lithande ukuba neempendulo eziphezulu ze-cortisol xa kuthelekiswa neqela eliphantsi le-nausea. Nangona kunjalo, impendulo ye-cortisol inxulunyaniswa ngakumbi nokutya ngokweemvakalelo kunye nokuthintela ukutya, ngelixa impendulo yesicaphucaphu inxulumene kakhulu nokutya ngokutya kunye ne-adiposity. Ukugxilwa kweCortisol kunyuka ngenxa yokuncipha kwegalelo le-opioidergic inhibitory kwi-axis ye-HPA, ngelixa iingxelo ezizimeleyo zesicaphucaphu zisisiphumo seziganeko ezintsonkothileyo ezibandakanya ukusetyenzwa kwe-peripheral kunye ne-peripheral processing, kunye nokuqonda kwangaphambili kunye nomgangatho ophezulu kunye neempendulo zeemvakalelo. Ngoko ke, akumangalisi ukuba i-cortisol reactivity kunye ne-subjective nausea ayizimpendulo ezilungelelanisiweyo (bonisa ukuzimela) kwaye usebenze ngokuhlukileyo. Ngapha koko, ukonyuka kwe-cortisol bekucacile kwimpendulo ye-naltrexone, ngelixa umlinganiso wethu wesicaphucaphu unokuba ngathi ufana nomkhwa, njengoko singakhange sivavanye utshintsho kwisicaphucaphu kwixesha lokuphendula le-naltrexone okanye ngeentsuku zolawulo. Kwizifundo ezilawulwa ngakumbi, umsebenzi wexesha elizayo uyafuneka ukuze uqonde indlela i-cortisol kunye neempendulo ze-nausea zinokuthi zibe phantsi kweendlela ezizodwa kunye neziqhelekileyo zeempendulo ze-naltrexone ezinxulumene neepatheni zokutya ezinxulumene ne-hedonic.

Ukuqonda okuphantsi kokuqonda kuye kwafunyaniswa ukuba kuqikelele indlela yokuziphatha yokutya kwe-hedonic kunye nokutya okungalungelelananga (; ). Kukwacingelwa ukuba ulwazi lwe-interoceptive ludityanisiwe kubukhoboka (; ; ). Sifumene ukuba ulwazi oluphantsi lwe-interoceptive, ngokukodwa, ukubeka ukubaluleka okuncinci ekuqapheliseni i-interoceptive ukulawula ukuzazi ngokuziqonda kunye nokwenza izigqibo, kwayanyaniswa neempendulo ezinkulu ze-cortisol. Isicaphucaphu esikhulu sithande ukunxulumana nokuqonda okuncinci. Ezi ziphumo zenoveli zibonelela ngenkxaso yokuqala kwithiyori yokuba ulwazi lwe-interoceptive njengendlela yokuzazi eyenza kube lula ukuqonda kunye nokuzibamba kuncitshiswe kumlutha (). Uphando oluthe kratya lufanelekile ukuqonda ukubandakanyeka kolwazi lwe-interoceptive kwi-syndrome yokutya okusekelwe kumvuzo.

Okokugqibela, sivavanye ukuba ngaba i-cortisol okanye iimpendulo ze-nausea zibikezele impendulo yonyango kubasetyhini ababhalise kungenelelo lokucinga ngokutya uxinzelelo. Uhlalutyo lwethu lwaluphonononga, lunikwe ubungakanani besampulu encinci kunye nokungabikho koqikelelo oluthile. Ngakolunye uhlangothi, abafazi ababonisa isibonakaliso esikhulu se-opioid-mediated hedonic yokutya banokunganyangeki ngakumbi kunyango xa kuthelekiswa nabasetyhini abanezibonakaliso ezincinci. Ngakolunye uhlangothi, uqeqesho lokuqonda lubonise isithembiso sokunyanga ukusetyenziswa kweziyobisi kunye nokuphazamiseka kokutya ngokutya kwaye kunokuba kulungele ngakumbi ukuphucula ukuzilawula kunye nokutya ngokuphendula kwiminqweno kunye neemvakalelo ezimbi (; ; ). Okubangela umdla kukuba, safumanisa ukuba abathathi-nxaxheba nge Kaninzi isicaphucaphu esiqatha kwisiseko, mhlawumbi esibonisa umsebenzi ophantsi we-opioidergic, ubenokugcinwa kobunzima obungcono kulandela ungenelelo lokuqonda xa kuthelekiswa nabathathi-nxaxheba abanesicaphucaphu esincinci abathe batyeba. Akukho mahluko ekugcinweni kobunzima phakathi kwabantu abaphantsi kunye nabaphezulu be-nausea kwiqela lokulinda. Isampula yethu yayincinci kwaye izigqibo kufuneka zibanjwe ngokukhawuleza. Nangona kunjalo, ngalo mda engqondweni, ezi ziphumo zibonisa ukuba ukucinga kunokuba lunyango olusebenzayo lokutyeba kakhulu kubantu abadala abatyebileyo abanamanqanaba aphezulu okutya kwe-hedonic okanye iimpawu zokukhotyokiswa kokutya.

Sihlolisise izikhombisi ezibini zeempendulo ze-cortisol: ukunyuka okuphezulu kwe-cortisol kwiiyure ezintathu emva kokulawulwa kwe-naltrexone kunye nokunyuka kwe-peak ngokubhekiselele kwinguqu yentsingiselo xa i-naltrexone ingalawulwa. Impendulo kwangolo suku lunye (engathelekiswanga nosuku lolawulo) yayiyingqikelelo eyomeleleyo yedrive yokutya, icebisa ukuba uvavanyo losuku olunye lunokuba yi-biomarker eyaneleyo yomsebenzi we-opioidergic, nangona oku kufunyaniswayo kufuna ukuphindaphinda.

Umda obalulekileyo wolu phononongo lwangoku kukungabikho kwemeko ye-placebo. Ukongezelela, abathathi-nxaxheba banikwa, kwangaphambili, uluhlu lweziphumo ezininzi ezinokwenzeka, apho i-nausea yayinye, kwaye iimpendulo ze-nausea zingabonisa ukungafani komntu ngamnye ekucingeni. Kwakhona, abanye abathathi-nxaxheba bakhumbula inqanaba labo lesicaphucaphu ngokuphindaphindiweyo kwifowuni. Nangona kunjalo, ipesenteji yabathathi-nxaxheba ababika ubuncinci be-nausea ephakathi kolu phononongo (40%) iyafana nepesenti yezigulane ezityebileyo ezibika isicaphucaphu kwizilingo zekliniki ezilawulwa yi-placebo ze-naltrexone (30-34%) (). Nangona iingxelo zomthathi-nxaxheba zesicaphucaphu zibandakanya ukucetyiswa kwinqanaba elithile, i-30% yabathathi-nxaxheba ichaze isicaphucaphu esibi (kunye nesihlanu esixeliweyo sokugabha), nto leyo engenakwenzeka ukuba ibe sisiphumo sokucetyiswa. Ukucebisa kunokuphembelela umlinganiso wesicaphucaphu ukusa kwinqanaba elithile, kodwa akunakuphinda kubangele i-adiposity enkulu kunye ne-hedonic eating drive. Ngamanye amazwi, akunakwenzeka ukuba ukucetyiswa kubangele zombini isicaphucaphu kunye nemiqondiso yokutya okungekho mthethweni, okanye kubangela ubudlelwane obubonwe phakathi kwezi zibini. Uphando lwexesha elizayo luya kufuna ukulungisa lo mda ngokubandakanya imeko ye-placebo eyimfama kabini. Omnye umda yisampulu encinci, kwaye kunokuxoxwa ukuba amanqanaba okutya okungekho mthethweni okubonwe kule sampuli ayephakathi. Nangona kunjalo, ukungafani phakathi kwesampulu kunentsingiselo ecacileyo malunga neenkqubo zokulawula i-neurophysiological. Okokugqibela, isifundo sethu sasiphelele kwabasetyhini. Abasetyhini babonakaliswe ukuba baneempendulo ezinamandla ze-cortisol kwi-naltrexone kunamadoda (). Umsebenzi wexesha elizayo uya kufuna ukuphinda olu phononongo emadodeni.

Okwangoku akukacaci ukuba yeyiphi i-cortisol eyandisiweyo yeempendulo kwi-acute opioid blockade ebonisa malunga nomsebenzi ophakathi we-opioidergic kumxholo wokutya i-hedonic okanye phakathi kwabantu abaneempawu zokukhotyokiswa kokutya. Ngokusekwe kumsebenzi wangaphambili wale probe kunye nezifundo zezilwanyana ezibonisa ukulawulwa kwenkqubo ye-opioid ekuphenduleni ukutya okunencasa (), siye sathi ukonyuka okukhulu kokukhutshwa kwe-cortisol kubonisa ukuba buthathaka kwe-opioidergic engapheliyo ngenxa ye-opioids ekhoyo ekhoyo yokukhuphisana kwindawo ebophelelayo kunye nomchasi we-opioid, okanye ukuncipha kokuxinana kwe-opioid receptor okukhokelela ekuthinteleni okupheleleyo kwamagalelo athintelayo. kwi-hypothalamus (; ). Uphononongo lwe-PET lubonisa ukuba iimpendulo ezinkulu ze-cortisol kwi-naloxone, i-opioid receptor antagonist engekhoyo, inxulumene ezantsi μ kunye ne-δ amandla okubopha i-opioid-receptor kwimimandla emininzi yobuchopho (kubandakanya i-hypothalamus) phakathi kolawulo olusempilweni, kodwa hayi phakathi kwabathathi-nxaxheba abaxhomekeke kakhulu etywaleni (; ). Ngelixa sinokulindela ukuba iimpendulo ze-cortisol ziya kuba ngokuqinisekileyo ehambelana ne-opioid receptor yokubopha amandla, akucaci ukuba zeziphi izifundo ze-PET ezibonisa amandla okubopha, njengoko amandla okubophelela aphantsi angabonakalisa ukukhutshwa kwe-opioid engapheliyo, ukulawulwa kwe-receptors, okanye ukulahlekelwa kwe-neurons kunye ne-opioid receptors (). Ipateni engaguqukiyo yokufunyaniswa kweempendulo ze-cortisol kwi-acute opioid blockade kumlutha wotywala ayizange ibonwe. Ngokukodwa, impendulo ye-cortisol kubachasi be-opioid iphezulu kwabo basengozini yokusela utywala ngokusekelwe kwimbali efanelekileyo yentsapho (; ; ; ), kodwa ayingabo bonke abalufumeneyo olu nxulumano (). Ngaphaya koko, phakathi kwabathathi-nxaxheba abaxhomekeke etywaleni umsebenzi we-HPA ubonakala unjalo buthuntu xa kuthelekiswa nolawulo (; ) nangona kungekho kuzo zonke izifundo (). Ke, ukubaluleka kwempendulo ye-cortisol kubachasi be-opioid ebonisa malunga nokusayinwa kwe-opioid ngaphakathi nangaphaya kokulutha akucaci.

Ukufumana ukuqonda okungcono kwezi ndlela, uphando lwexesha elizayo lunokuvavanya i-cortisol eyenziwe yi-naltrexone kunye neempendulo zesicaphucaphu ngokumalunga novavanyo lwe-PET lwe-opioid receptor enokubakhona kubantu abanamanqanaba aphezulu okutya kwe-hedonic okanye iimpawu zokukhotyokiswa kokutya kunye nolawulo. Ezi mpendulo zinokuvavanywa ngokunxulumene nokwahluka kwimizila yemfuza elawula ii-opioid receptors. Obunye ubungqina bubonisa ukuba i-opioid-receptor polymorphism A118G iqikelela iimpendulo ze-cortisol kwinaloxone.).

Isishwankathelo, abantu abanamanqanaba aphezulu okutya okunxulumene ne-hedonic, njengokutya ngokweemvakalelo kunye nokutya kakhulu, banokuba nenkqubo ye-opioidergic elawulwa phantsi. Iziphumo zophononongo lwangoku zibonisa ukuba ithoni ye-opioid inokulinganiswa ngendlela engabonakaliyo, ekhaya, kubantu abadala kunye nabakhulupheleyo. Nangona ezi ziphumo kufuneka ziphindaphindwe kwizifundo zexesha elizayo, olu phononongo lucebisa ukuba i-cortisol kunye neempendulo zesicaphucaphu kwibhlokhi ye-opioid ebukhali inokusebenza njengeempawu zebhayoloji zokutya okunxulumene ne-hedonic kunye nokuba likhoboka lokutya.

​ 

Iimbalasane

  1. Iimpendulo zeCortisol kunye nesicaphucaphu kwi-acute opioid blockade zavavanywa.
  2. Iimpendulo zazinxulumene neemvakalelo, ukuzinkcinkca, kunye nokutya okuzibambayo, kunye nokutyeba.
  3. I-nausea iqikelele ukugcinwa kobunzima ekungeneleleni kwengqondo ngokutya kakhulu.
  4. Iimpendulo zeCortisol kunye nesicaphucaphu zinokuchonga abantu abaxhomekeke kumvuzo wokutya.

Imibulelo

Olu phando luxhaswe yiMt Zion Health Fund; UWilliam Bowes, Omnci., Ingxowa-mali; iNgxowa-mali kaRobert Deidrick; kunye ne-NIH isibonelelo i-K01AT004199 enikezelwa kwi-JD evela kwiZiko leSizwe lezoNyango oluFanelekileyo kunye nolunye lweNyanga kunye neZiko leSizwe lezeMpilo / iZiko leSizwe loPhando lweZibonelelo ze-UCSF-CTSI Isibonelelo seNombolo. ULI RR024131. Umxholo kuphela uxanduva lwababhali kwaye akufuneki ukuba ibonise iimbono ezisemthethweni zeZiko leSizwe lezoNyango oluNxulumeneyo kunye nolunye unyango okanye amaZiko ezeMpilo eSizwe.

Imihlathi

 

Iphepha elichazayo ukuba awusenanto oyifunayo: Le fayili yeFayile yombhalo wesandla ongabhalwanga owamkelwe ukushicilelwa. Njengenkonzo kumakhasimende ethu sinika le ngcaciso yokuqala kwincwadi yesandla. Umbhalo wesandla uza kufumana ukukopishwa, ukufakela, nokuphonononga ubungqina obunokubakho ngaphambi kokuba kukhutshwe kwifomu yayo yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kweeprogram ezinokuthi zifumaneke ezinokuthi ziphazamise umxholo, kunye nazo zonke izisemthethweni ezichasayo ezisetyenziswa kwiphephancwadi.

 

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