Lofalitsidwa mu mawonekedwe omaliza omaliza monga:
- Biol Psychiatry. 2013 May 1; 73 (9): 827-835.
- Idasindikizidwa pa intaneti 2013 Mar 26. do: 10.1016 / j.biopsych.2013.01.032
PMCID: PMC3658316
NIHMSID: NIHMS461257
Rajita SinhaPhD
1,2,3 ndi Ania M. Jastreboff, MD, PhD
4,5
Mtundu womaliza wa chosindikiza wa nkhaniyi ukupezeka pa Biol Psychiatry
Onani zina mwa PMC zomwe anatchulapo nkhani yosindikizidwa.
Kudalirika
Kupsinjika maganizo kumayenderana ndi kunenepa kwambiri ndipo matenda a neurobiology opsinjika maganizo amakwera kwambiri ndi chilakolako cha kudya ndi mphamvu. Phunziroli lidzakambilana za nkhawa, allostasis, neurobiology ya kupsinjika maganizo ndipo imakhala ndi nthenda yokhudzana ndi njala ndi mphamvu zamagetsi. Kupsinjika maganizo ndi chinthu chofunikira kwambiri pachiopsezo chakumwa mowa ndi kusokoneza bongo. Mavuto apamwamba amasintha kudya zakudya ndipo amagwiritsa ntchito zakudya zopatsa mphamvu kwambiri (HP), zomwe zimapangitsa kuti chakudya cha HP chilimbikitse komanso chakudya cha allostatic. Njira zokhudzana ndi matenda a ubongo zomwe zimachititsa kuti munthu azivutika maganizo zimapindula ndi njira zowonjezerapo zomwe zimachititsa kuti HP zakudya komanso mankhwala osokoneza bongo adziwe. Chifukwa cholimbikitsana kwambiri zakudya za HP komanso zakudya zamagetsi, zimakhala zovuta kwambiri komanso zowonjezera mphotho zomwe zimalimbikitsa zokhudzana ndi nkhawa komanso zokhudzana ndi zakudya zokhudzana ndi zakudya za HP kuphatikizapo kusintha kwa kayendedwe kabwino ka madzi, kuphatikizapo kusinthika kwa shuga, shuga ya insulini, ndi mahomoni ena okhudzana ndi mphamvu homeostatsis. Kusintha kwa kagayidwe kake kameneka kumakhudzanso ntchito ya dopaminergic kuti iwonetsere chakudya komanso zakudya za HP. Kuphatikizapo njira yowonongeka yophatikizapo kumaphatikizidwa kuti mobwerezabwereza kupsinjika kwakukulu kumapangitsa kusintha kwachisokonezo ndi chilakolako cha mphamvu / mphamvu zamagetsi, ndipo zonsezi zimakhudza njira zokhudzana ndi njira za neural zomwe zimapangitsa kuti anthu azivutika maganizo ndi zakudya zomwe zimawathandiza kudya zakudya za HP komanso kudya nawo zakudya zotere kuonjezera chiopsezo cha kulemera ndi kunenepa kwambiri. Zotsatira zamtsogolo za kafufuzidwe zimadziwika kuti ziwathandize kumvetsetsa njira zomwe nkhawa ingapangitse ngozi ya kulemera ndi kunenepa kwambiri.
Kunenepa kwambiri ndi kuledzeretsa: udindo waukulu wa nkhawa
Kuledzeretsa kwa mowa ndi mankhwala osokoneza bongo kumakhalabe vuto lalikulu la thanzi la anthu ndi zotsatira zoopsa zachipatala, chikhalidwe ndi chikhalidwe cha anthu (1). Kupsinjika maganizo ndi chinthu choopsa kwambiri chomwe chimakhudza zonse zomwe zimayambitsa matenda osokoneza bongo komanso kubwerera ku zizoloŵezi zoledzera, motero kuopseza maphunziro ndi kuchiza matendawa (2Kunenepa kwambiri ndi mliri wapadziko lonse lapansi, ndipo United States ili patsogolo pa mliriwu ndi magawo awiri mwa atatu mwa anthu omwe amadziwika kuti ndi onenepa kwambiri kapena onenepa kwambiri (BMI> 25kg / m)2) (3). Kukula kwa kunenepa kwambiri ndi kuledzera kumakhudza maonekedwe a zamoyo, zachilengedwe ndi moyo wa munthu omwe onse amachititsa mliriwu (4); (5). Ngakhale ndemanga zam'mbuyomu zikuyang'ana pazifukwa izi, pepala ili likuwunika udindo wa nkhawa, chakudya komanso zakudya zomwe zimathandiza kuti mudye kwambiri.
Kupanikizika ndi allostasis
Zambiri, kupanikizika ndi njira yomwe iliyonse yovuta, yosasinthika komanso yowopsya yamalingaliro kapena zochitika za thupi kapena zochitika zina zimayambitsa njira zowonongeka kapena zowonongeka zofunikira kuti abwererenso homeostasis ndi / kapena kukhazikika (6), (2). Zitsanzo za kupsinjika maganizo kumaphatikizapo mkangano wosagwirizana, kusokonezeka kwa ubale, kusowa ntchito, imfa ya wachibale, kapena kutaya mwana. Zina zomwe zimagwirizanitsa thupi ndi njala kapena kusowa chakudya, kusowa tulo kapena kuwonongeka kwa kugona, matenda oopsa, hyperthermia kapena hypothermia, psychoactive mankhwala zotsatira ndi mankhwala kuchotsa mankhwala. Kusinthasintha kokhudzana ndi nkhawa kumaphatikizapo lingaliro la allostasis, omwe amatha kukwaniritsa kukhazikika kwa thupi mwa kusintha kwa mkati mwawo ndikukhalabe wosasunthika pa malo atsopano okhudza thupi (6); (7)). Malingana ndi McEwen ndi anzake, pali kusintha kosinthika kwa zinthu zakuthupi, ndi kusintha kwa thupi, maganizo, ndi ntchito monga munthu aliyense amayankha ndikugwirizana ndi zofunikira za chilengedwe (7). Kupanikizika kochulukira ku chamoyo, chomwe chimatchedwa kuchuluka katundu wothandizira, zimabweretsa "kusweka ndi kugwedeza" mwa njira zowonongeka zomwe zimapangitsa kusintha kwa zinthu zomwe zimafooketsa ndondomeko zomwe zimapangitsa kuti thupi likhale lopanda mphamvu komanso kukulitsa matenda omwe angayambitse matendawa (7). Choncho, kuchuluka kwa mavuto osasinthasintha ndi zochitika zomwe zimabwereza mobwerezabwereza ndi zosautsa zimapangitsa kuti pakhale mavuto osokoneza bongo omwe amachititsa kuti mitsempha yowonjezereka, yowonongeka komanso yowonongeka imapangitsa kuti azikhala ndi makhalidwe osokoneza bongo kunja kwa homeostatic range {McEwen, 2007 #4}.
Kusokonezeka maganizo, mavuto aakulu, ndi kuwonjezeka kwa chiopsezo cha kunenepa kwambiri
Mofananamo ndi zotsatira za kuwonjezeka ndi kupsinjika maganizo pa kukula kwa chizoloŵezi chovuta (2), umboni wochuluka wochokera m'mabungwe a anthu komanso maphunziro owonetsa zachipatala umasonyeza kuwonetsetsa kwakukulu komanso kokondweretsa zochitika zosasinthasintha zosalephereka komanso zovuta zapadera zomwe zimati ndizovuta, BMI ndi phindu lolemera (8), (9), (10), (11). Ubalewu umakhalanso wolimba kwambiri pakati pa anthu omwe ali olemera kwambiri komanso omwe amadya (8), (9), (12). Pogwiritsa ntchito ndondomeko yowonjezera yowonjezereka komanso yowonjezera kupanikizika mu chitsanzo cha anthu akuluakulu odwala (n = 588), tapeza kuti kuchuluka kwa zochitika zosautsa ndi zovuta zedi (onani Gulu 1) pa nthawi yonse ya moyo anali kugwiriridwa ndi kumwa mowa mopitirira muyeso, kukhala wosuta komanso BMI wapamwamba, atagonjetsa zaka, mtundu, chikhalidwe ndi chikhalidwe cha anthu (onani Chithunzi 1).
Pamene kupweteka kumayambitsa kulemera kwambiri ndi BMI, tinayesanso zotsatira zake pa shuga, insulini ndi insulini. Kuwonetseredwa kwa m'mawa kwa kusala kwa m'magazi a m'magazi (FPG) ndi insulini inayesedwa m'gulu lalikulu la anthu odzipereka mderalo komanso ma poloostasis (HOMA-IR) anawerengedwa ngati ndondomeko ya insulini kukana. Tapeza kuti vutoli limagwirizanitsidwa ndi kusintha kwa BMI m'magazi apamwamba a shuga, insulini ndi HOMA-IR (Chithunzi 2). Deta iyi imasonyeza mayanjano amphamvu pakati pa kuchepetsa nkhawa ndi kuchepa kwa kagayidwe pakati pa anthu omwe ali apamwamba poyerekeza ndi magulu apansi a BMI. Zotsatirazi zikufanana ndi kafukufuku wammbuyo zomwe zikuwonetsa zotsatira zowonjezera za kupsinjika kwa kuchuluka kwa mankhwala ogwiritsidwa ntchito mwa anthu omwe nthawi zonse amalemetsa poyerekeza ndi anthu osangalala kapena osangalatsa (2). Zonsezi, zotsatiridwazi zikusonyeza kuti kupanikizika ndi kupanikizika kumabweretsa chiopsezo cha kunenepa kwambiri komanso kuti anthu omwe ali ndi BMI apamwamba akhoza kukhala ovuta kuwonongera zakudya zomwe zimagwiritsidwa ntchito pazinthu zomwe zimagwiritsidwa ntchito pazomwe zimakhudza nkhawa.
Kusokonezeka maganizo ndi khalidwe la kudya
Kupanikizika kovuta kwambiri kumasintha kudya (13); (10); (9). Ngakhale kuti kafukufuku wina akuwonetsa kuchepa kwa chakudya chokhala ndi nkhawa, vutoli likhoza kuchepetsa kudya, makamaka pamene HP, zakudya zowonjezera zowonjezera zilipo (9, 13), (14), (15), (16). Mwachitsanzo, mwadzidzidzi okha, a 42% a ophunzira adanena kuti akuwonjezera chakudya chokwanira ndi nkhawa, ndipo 73% ya ophunzirawo akuwonjezera kuwonjezereka kwakumwa nthawi yachisoni (17). Gawo limodzi la magawo atatu pa theka la maphunziro a zinyama kapena anthu omwe amachititsa ma laboratory amasonyeza kuwonjezeka kwa kudya zakudya panthawi yovuta, pamene ena sasonyeza kusintha kapena kuchepetsa kudya (18), (11). Choncho, ngakhale kuti chakudya chowonjezeka chowonjezeka ndi nkhawa yaikulu sizimachitika kwa aliyense, ndithudi chimakhudza anthu ambiri. Kuonjezerapo, ndikofunika kuzindikira kuti zingapo zomwe zimayesayesa zingapangitse kufufuza za kusiyana kumeneku pa kudya kosautsa (19), (20), (12). Zinthu izi zimaphatikizapo mtundu wachisokonezo umene umagwiritsidwa ntchito poyendetsa, kutalika kwa kupanikizika, kutalika kwa nthawi yopatsidwa chakudya komanso kuchuluka kwa zakudya zomwe zimaperekedwa poyesera, komanso chiwerengero cha njala ndi njala kumayambiriro kwa kafukufuku. Izi zikhoza kuchititsa kusintha kwa zotsatira za kafukufuku wa labotale zomwe zimayambitsa vuto pa kudya.
Pali umboni wowonjezera womwe umasonyeza kuti zingakhale zovulaza za kudya zakudya (mwachitsanzo, kudya chakudya, kuletsa kudya, kubisala) ndi zakudya zokonda (10). Kupsinjika maganizo kungawonjezere chakudya chachangu (21), zopsereza (22), Zakudya zokhudzana ndi calorie komanso zowoneka bwino (23), komanso nkhawa zakhala zikugwirizana ndi kudya kwambiri kudya12). Zotsatira za kupanikizika zikhoza kukhala zosiyana ndi zowona poyerekezera ndi anthu olemera kwambiri (8, 24-26). Amayi olemera kwambiri amayamba kudya zakudya zopanikizika maganizo koma kudya zakudya zolimbitsa thupi kumawoneka kuti sagwirizana kwambiri ndi zakudya zomwe anthu amadya (24). Kuwonjezera apo, kusintha kwa kudya kumagwirizanitsa ndi kapangidwe kabakiteriya kake ndi insulini yokhudzidwa (27). Azimayi odwala, kudya mowa kwambiri kumawonjezera kudya kwa shuga, kuyankha kwa insulini, komanso kumasintha katemera wa leptin (28). Mafupipafupi afupipafupi adapezeka kuti akuwonjezera insulini poyesa chakudya choyesa pambuyo pa nthawi ya kudya moyenera (27). Kuphatikizidwa pamodzi, kafukufukuyu akusonyeza kuti kupanikizika kungalimbikitse zakudya zopanda phindu ndikusintha zakudya zokonda zakudya komanso kuti anthu olemera kwambiri ndi olemera kwambiri akhoza kukhala otetezeka ku zotsatirapo zoterozo, mwinanso kupangidwira kulemera kwa magetsi ndi ma homeostasis.
Kuthamanga kwa ubongo wochuluka wa nkhawa ndi mphamvu ya homeostasis
Zomwe thupi limayankha pa vuto lalikulu zimayambitsidwa kudzera m'maganizo awiri omwe akugwedezeka. Yoyamba ndi a hypothalamic-pituitary-adrenal (HPA) axis, yomwe khungu la corticotropin-release (CRF) imatulutsidwa kuchokera ku khungu (PVN) la pepala la hypothalamus, lomwe limatulutsa mphamvu ya adrenocorticotrophin hormone (ACTH) kuchokera ku anterior pituitary, yomwe kenako amachititsa kuti chisamaliro cha glucocorticoids (GC) (cortisol kapena corticosterone) chichoke ku adrenal glands. Chachiwiri ndi dongosolo lodzidzimitsa, lomwe limagwirizanitsidwa ndi symathoadrenal medullary (SAM) ndi machitidwe a parasympathetic. Zonse ziwiri zikuluzikulu za njira zopanikizikazi zimakhudzanso kutupa kwa cytokines ndi chitetezo cha mthupi (2); (6).
Kutulutsidwa kwa CRF ndi ACTH kuchokera ku hypothalamus ndi anterior pituitary panthawi yachisokonezo zimatulutsa GC kuchoka ku adrenal cortex, yomwe imathandizira mphamvu yolimbikitsa mphamvu ndi gluconeogenesis. Kuwukakamiza kumagwirizana ndi kupanikizika kumawonjezera kuthamanga kwa magazi ndi kupotoza kwa magazi kuchokera m'matumbo a m'mimba mpaka minofu ya ubongo ndi ubongo. Zomwe zimayambitsa mavuto a CRF ndi ACTH zimathetsedwa ndi mayankho oipa a GC, zothandizira kubwerera kunyumba, komanso pazipsinjo zovuta kwambiri, pali umboni wosonyeza kuti kuchepa, osati kuwonjezeka, kumadya (19), (9). The hypothalamus ndikumvetsera kwa GCs kudzera mu zolakwika, komanso insulin, atsekedwa ku zikondamoyo komanso okhudzana ndi shuga kusakaniza kagetsi ndi mphamvu yosungirako (29), (9), ndi ma hormone ena, monga leptin omwe amaletsa chilakolako chofuna kudya, ndi ghrelin yomwe imalimbikitsa chilakolako (5); (9); Currie, 2005). Glucocorticoids imapanga plasma leptin ndi ghrelin levels, ndipo ghrelin imakula ndi nkhawa ndipo imathandizira kuthetsa nkhawa ndi maganizo (30). Kuwonjezera apo, nthenda zambiri za hypothalamic neuropeptides, monga CRF, propriomelanocortin (POMC), Y (NPY) ya orexigenic netipeptide, ndi peptide yokhudzana ndi agroti (AgRP), komanso ovomerezeka a melanocortin ogwira ntchito yothetsera nkhawa, amachitanso kuthandizira kudyetsa (31). Glucocorticoids amasintha malingaliro a mapiritsi a neuropeptides omwe amachititsa kuti mphamvu zowonjezera mphamvu zisawonongeke (32), (31). Mwachitsanzo, adrenalecomy yapakati pafupipafupi imachepetsa chakudya, ndipo GC kayendetsedwe ka chakudya chimapangitsa kuti anthu azidya zakudya zowonjezera potulutsa ufulu wa NPY komanso kuteteza ufulu wa CRF (31). Kuwonjezera apo, kuletsedwa kwa zakudya ndi zakudya zapamwamba zimapangitsa HPAaxis mayankho kupsinjika ndi GC gene kufotokozera m'madera ambiri a ubongo omwe amagwiritsa ntchito energyostostisis ndi nkhawa (33), (20), (18), (34), (35). Choncho, hypothalamus ndi dera lovuta kwambiri mu dera lopanikizika komanso pakukhazikitsa chakudya ndi mphamvu.
Matenda osapitirira ndi apamwamba a nkhawa mobwerezabwereza ndi osasinthiratu amachititsa kuwonongeka kwa malo a HPA, ndi kusintha kwa GC gene expression (6), (36), zomwe zimakhudzanso mphamvu ya homeostasis ndi khalidwe lodyetsa. Kusintha kwa kanthawi kochepa kwa HPA kumadziwika kuti kusintha kagawo kamene kamayambitsa shuga ndikulimbikitsanso kusakanikirana, ndi kusintha kwa mahomoni ambiri (monga leptin, ghrelin) ndi kudyetsa neuropeptides (mwachitsanzo, NPY) (37), (38), (39), (40). Kupanikizika kosalekeza kumapitiriza kuwonjezera ma GC, ndipo kumalimbikitsa mafuta a m'mimba, omwe pakakhala insulini, amachepetsa ntchito ya HPA.9), (38) (33). Kafukufuku wa sayansi yeniyeni asonyeza kuti adrenal steroid imachulukitsa shuga ndi insulini komanso kusankha ndi kudya zakudya zamtundu wa caloric (13), (14), (15), (41). Matenda apamwamba a GCs ndi kuwonjezeka kwa insulini zimakhala ndi zotsatira zowonjezera pakuwonjezeka kwa HP chakudya chokwanira ndi mafuta a m'mimba (23), (9); (42). Makhalidwe apamwamba obwerezabwereza amachititsanso kuti munthu asamamve bwino, komanso kuwonjezereka maganizo pazowonjezereka kumayenderana ndi insulini komanso kuchepa kwa insulini achinyamata komanso akuluakulu (43).
Zotsatira za kupanikizika pa chakudya, mphotho ndi kudya
Maofesi a hypothalamic opanikizika ali pansi pa kayendedwe ka extrahypothalamic cortico-limbic njira zojambulidwa ndi CRF, NPY ndi noradrenergic njira. Kusokonezeka maganizo kumayambira kudzera mu amygdala ndi malamulo opsinjika maganizo amapezeka kudzera mu GC zowonongeka kwa hippocampus ndi zigawo zamkati zapopalal cortical (mPFC)6). Zizindikiro za CRF zimaphatikizapo mayankho ogonjera komanso okhudza khalidwe, pamene kumasulidwa kwa NPY pa nthawi yachisokonezo ndi kuwonjezeka kwa NPY mRNA mu phokoso la hypothalamus, amygdala ndi hippocampus, kumawonjezera kudyetsa, komanso kuchepetsa nkhawa ndi nkhawa (31). Kupanikizika ndi ma GC angathe kutenga mavitamini a dopaminergic ndi mphotho yopempha ndi kudya muzilombo zamatera (18), (13) (2). Kupanikizika kwakukulu kumapangitsa munthu kupeza chakudya chamtengo wapatali, kudya zakudya zamtengo wapatali (11), (16), ndi chakudya chofunafuna zakudya za HP (25), ndipo amalimbikitsa zizolowezi zowonjezera mphotho (44). Kupsinjika maganizo kumapangitsanso chidwi cha mchere, zakudya zopangira zakudya zokwanira komanso zakudya zina zapamwamba za HP zomwe zimadya anthu olemera kwambiri okhutira kwambiri okhudzana ndi oonda kwambiri (25).
Kuwonjezereka kwa mankhwala osokoneza bongo komanso kudya zakudya zamtengo wapatali kumapangitsa CRF, GC ndi ntchito ya noradrenergic kuti iwonjezere mphamvu za njira (kuphatikizapo ventral tegmental area [VTA], nucleus accumbens [NAc], dorsal striatum ndi madera a mPFC) omwe amachititsa kuti zinthu zowonongeka komanso Zakudya za HP ndikuwonjezera chilakolako cha mankhwala / chakudya ndi zakudya (45), (2), (46). Chofunika kwambiri, dera lolimbikitsana limeneli limayendayenda ndi ziwalo zam'mimba / m'maganizo (mwachitsanzo amygdala, hippocampus, ndi insula) zomwe zimawathandiza kukhala ndi maganizo ndi nkhawa, komanso pakuphunzira ndi kukumbukira zomwe zimayambitsa kukambirana za makhalidwe abwino komanso zokhudzana ndi zidziwitso zoyenera kusintha. homeostasis (2); (47). Mwachitsanzo, amygdala, hippocampus ndi insula zimakhala ndi mbali yofunikira pakulembera mphotho, maphunziro omwe amapezekanso ndi maphunzilo omwe amapeza chifukwa chokhala ndi maganizo komanso mphotho komanso zotsatira zowonjezereka komanso zopatsa mphoto.48), (49). Kumbali ina, zigawo zapakati ndi zotsatila za kampani yamakono (PFC) zimaphatikizapo ntchito zapamwamba zoganizira komanso zogwira ntchito komanso zowonongeka maganizo, zokhudzana ndi thupi, zikhumbo, zikhumbo ndi kukhumba (50). Kupanikizika kwakukulu ndi kobwerezabwereza kumapangitsa kuti zikhale zovuta komanso zogwira ntchito m'madera ena a ubongo, zomwe zimapangitsa kuti pakhale mavuto omwe amakhala nawo pamadera a cortico-limbic omwe amachititsa kuti anthu azikhala ndi chakudya komanso chilakolako cha zakudya (51); (52). Zofukufukuzi zikugwirizana ndi kafukufuku wamakhalidwe ndi zachipatala omwe amasonyeza kuti kupanikizika kapena kukhumudwitsa kumachepetsetsa kuchepetsa maganizo, maonekedwe ndi khalidwe,2) zomwe zimagwirizanitsa ndi chizolowezi choledzeretsa mowa, kusuta, ndi mankhwala ena osokoneza bongo komanso kuwonjezeka kwa zakudya za HP (23); (53); (54). Poganizira kwambiri za kuledzera kwa zakudya komanso momwe kukhumba maswiti ndi mafuta kungapangitse kunenepa kwambiri (55), zingakhale zofunikira kulingalira ngati chiopsezo cha kuledzera kwa zakudya chikuwonjezeredwanso ndi kupsinjika kwanthawi yaitali.
Chakudya cha chakudya, mphotho ya chakudya, chilimbikitso ndi kudya
Zakudya zabwino kwambiri zowonjezera zimapezeka m'madera omwe alipo tsopano. Kuwonetsetsa kwa zakudya za HP chakudyachi kungapangitse chakudya kudyetsa komanso kumapangitsa kuti phindu likhale lolemera (49). Zakudya zoterezi zimapindulitsa, zimapangitsa ubongo kupereka mphotho njira, ndipo, kudzera mu njira zophunzirira / kupangidwira, kuwonjezera mwayi wa chakudya cha HP chofuna ndi kumwa (56), (57), (58). Nyama ndi anthu amatha kukhala ndi zida zofuna kudya ndi kudya zakudya za HP izi, makamaka m'nkhani ya zakudya kapena 'cues' zomwe zimagwirizana ndi zakudya za HP m'deralo (55), (59), (57). Kuwonjezeka kotereku mu chikhalidwe cha zakudya ndi zowonjezera kumawonjezera kudya kwa zakudya za HP kumapangitsa kusintha kwa njira za mphotho / zolimbikitsa, zomwe zimachitika ndi kuwonjezeka kwa zakudya za HP izi, zomwe zimawathandiza kukhala ndi "kufuna" ndi kufunafuna zakudya za HP, zofanana ndi zolimbikitsa zomwe zimachitika poonjezera kumwa mowa ndi mankhwala osokoneza bongo (60). Kafukufuku wochuluka wa zinyama ndi kafukufuku wokhudzana ndi ubongo waumunthu tsopano ukuwonetsa kuti kulimbikitsidwa kwa mphotho za m'mipingo ndi kuonjezera kutumiza kwa dopaminergic ndi kuwonetsetsa kwa chakudya cha HP, ndi kuwonjezeka kwa chakudya chokhumba ndi zolimbikitsa (61), (62), (63), komanso kuwonjezeka kwa ubwino wa ubongo m'madera ndi chakudya cha anthu pakati pa BMI (64), (65), (66), (67).
Pogwiritsa ntchito zakudya za HP kwambiri, kusintha kwa mavitamini ndi mavitamini, kuchepetsa mphamvu ya insulini komanso mavitamini omwe amachititsa kuti mphamvu zapakhomo zikhale ndi mphamvu, zimakhudzanso mphotho zapadera zomwe zimaphatikizapo kuwonjezeka, kufuna ndi kudyetsa chakudya (68), (57), (69), (70), (71), (72), (73). Mwachitsanzo, munthu wathanzi wokhudzana ndi zakudya m'magazi a m'magazi amachititsa kuti magazi asapitirire kusungunuka, zomwe zimathandiza kuti tizilombo toyambitsa matenda tizilombo toyambitsa matenda tizilombo toyambitsa matenda; chokondweretsa chapakati chapakati cha insulini chawonetsedwa kuti choletsa kudya ndi kudya (74); (75); (76); (77); (78). Komabe, matenda aakulu omwe amatha kuwonongeka ndi insulini ndi insulini, monga momwe amachitira ndi anthu ambiri olemera kwambiri, akhoza kulimbikitsa chilakolako cha chakudya ndi kudya komanso kusintha ntchito ya dopaminergic mu mphoto monga VTA, NAc ndi dorsal striatum (78), (79), (80), (81). Mofananamo, leptin ndi ghrelin zimakhudza matenda opatsirana a dopaminergic mu ubongo mphoto zigawo ndi chakudya chofunafuna nyama, ndikuwongolera ubongo m'madera mwa anthu (69), (70), (71), (73). Kukaniza kwa insulin ndi T2DM kumagwirizananso ndi kusintha kwa ntchito ya maulendo a mphoto ya neural ndi yankho lawo ku chakudya chamagulu (82), (79), (80). Posachedwapa tawonetsa limbic yowonjezera komanso kugwiritsira ntchito mankhwala osokoneza bongo kupsinjika ndi zakudya zomwe zimakhala zowonjezereka zokhudzana ndi anthu oonda (81) (onani Chithunzi 3). Kuwonjezera pamenepo, ntchito yoposa ya insula ndi dorsal striatum zimagwirizanitsa ndi ma insulini apamwamba, insulini kukana ndi chilakolako cha chakudya pamene ophunzira akuwonekera pazochitika zomwe amakonda zokondweretsa (81). Zonsezi, zotsatiridwazi zimagwirizana ndi lingaliro lakuti pangakhale zofanana ndi zofanana zokhudzana ndi maulendo amatsitsimutso ndi neural olimbikitsana omwe amagwirizana kwambiri pofuna kulimbikitsa njala, kusankha zakudya ndi kusankha, zolimbikitsa zakudya za HP ndi kudya zakudya za HP.
Umboni wochulukirapo umasonyeza kuti mahomoni omwe amakhudzidwa ndi njala ndi mphamvu zamagetsi (monga leptin, ghrelin, insulini) akhoza kuthandizira kulakalaka, mphotho ndi kufunafuna mowa ndi mankhwala osokoneza bongo (49); (57); (58); (68); (69); (72); (71) Mabungwewa apanga chidwi chofufuza lingaliro la "kusokoneza bongo", kapena kulowetsa "chizoloŵezi" chimodzi, pakudya izi zakudya zina, monga zina monga mowa kapena zinthu zina (83). Mwachitsanzo, kafukufuku waposachedwa anapeza kuti kumwa mowa kunachulukira pakutsata mwamsanga, kutayika kwakukulu monga momwe akuwonera kwa odwala omwe akuchitidwa opaleshoni yokhala ndi ubongo (84). Choncho, kafukufuku wamtsogolo wokhudzana ndi kupititsa patsogolo chakudya ndi mankhwala osokoneza bongo omwe ali pachiopsezo akhoza kufotokozera njira zomwe zimayambitsa zovutazi.
Kulemera kwa thupi ndi zakudya zokhudzana ndi zakudya komanso kusokonezeka maganizo: zikhumbo zokhumba chakudya ndi kudya
Kuwonjezeka kwa kulemera kwalemera pamwamba pa miyendo yathanzi komanso kudya zakudya za HP, kumabweretsa kusintha kwa shuga, kuchepetsa mphamvu ya insulini komanso mahomoni, kuyambitsa kudya ndi mphamvu zowonjezera mphamvu zamagetsi (85), (57), (58). Monga momwe tawonera m'magulu apitayi, izi zokhudzana ndi kugwiritsira ntchito mankhwalawa zimangotengera zowonjezereka zowonongeka, koma zimakhudzanso maulendo a hypothalamic, ndikugwirizanitsa ndi kupanikizika kwapadera ndi magetsi oyendetsa magetsi. Choncho, n'zosadabwitsa kuti kuwonjezeka kwa thupi, kupatsirana kwa insulini komanso zakudya zamtundu wapamwamba zimayambitsidwa ndi mayankho a GC omwe amachititsa kuti anthu asamapanikizike komanso asinthe maganizo awo omwe amachititsa kuti azimayi azikhala ndi nkhawa.43), (20), (33) (34). Monga tanenera poyamba, kulemera kwakukulu kwa nkhawa ndi glucocorticoids kumayambitsa shuga ndi insulini komanso kumalimbikitsa insulini kukana. Mofananamo, matenda aakulu a insulini amasonyezedwa kuti asokoneze mayankho a HPA ndikuwonjezera mau omvera (43), (86), (42), (87). Kuwonjezera pamenepo, umboni umasonyeza kuti nkhawa imakhudza kuchuluka kwa shuga ndi kusiyana kwa odwala omwe ali ndi mtundu wa 1 ndi 2 shuga (88), (89), (90), pamene ghrelin, yomwe kupyolera mu kuwonetsa mphotho njira zimalimbikitsa chilakolako ndi kudya (71), akuphatikizidwanso mu mphotho yopezera chakudya komanso kufunafuna chakudya (30) (73). Motero, kusintha kwa kayendedwe kokhudzana ndi kulemera kwapadera kumapangitsa kuti chiwerengero chazitsulo chazitsulo chikhale chowonjezeka komanso chidziwitso chokhazikika chokhazikika ndi kusintha kwa ntchito ya HPA.18), (91), (40), (6).
Mogwirizana ndi ntchito yapitayi yomwe ikuwonetsa BMI ndi kupsinjika maganizo komwe kumakhudza chakudya ndi mphotho, tawonetsa posachedwapa kuti kupanikizika kwakukulu kumawonjezera ntchito ya amygdala komanso kuyanjana kwa orbito-frontal cortex yankho ku milkshake vs. masewera opanda pake, koma zotsatirazi zinayesedwa ndi makina akuluakulu a cortisol ndi ndi BMI yapamwamba (92). Pogwiritsira ntchito chifuwa cha hyperinsulinemic, tinasonyezanso kuti kuchepa kwa hypoglycemia kunayambitsa mphamvu za ubongo ndi zimbic (hypothalamus, striatum, amygdala, hippocampus ndi insula) zomwe zimakonda kwambiri zakudya za HP, zomwe zimagwirizana ndi kuchuluka kwa cortisol. kutsegulira, zotsatira zomwe zimagwirizanitsidwa ndi kuchepa kwa magawo a shuga (93). Monga hypoglycemia yofatsa ingatengedwe kukhala thupi laumphawi, zomwe timapeza zimasonyeza kuti kugwiritsira ntchito shuga kungakhale kosiyana mu ubongo ndi kuwonjezeka kwa nkhawa, ndi kuwalimbikitsa komanso kuwonetsa zizindikiro pamaso pa chakudya cues koma kuchepa kwachisokonezo muzodziletsa ndi zigawo zoyendera . Komanso, nyerereyi inali yovuta kwambiri kwa anthu olemera kwambiri omwe amasonyeza kuti kusintha kotereku kumachitika ndi kulemera kwake, mwinamwake kuyambitsa njira yokhudzana ndi kulemera kwa thupi, maukwati ndi zovuta zomwe zimakhudza kwambiri chakudya cha HP. Phunziroli pamodzi ndi umboni wotchulidwa kale limasonyeza kuti pali zinthu zambiri zomwe zimapangitsa kuti thupi likhale labwino, limagwirizanitsa thupi ndi zokhudzana ndi maganizo komanso zowonongeka, koma zimakhala zovuta kwambiri komanso zowonongeka m'madera amenewa. za machitidwewa akhoza "kutengedwa", motero kumalimbikitsa kuwonjezeka kwa chakudya cha HP komanso chakudya.
Chidule ndi njira yosankhidwa
Mipukutu yowonongeka yomwe ikuwonetsedwa imasonyeza kuti zowonongeka za HP chakudya komanso nkhawa zambiri zingasinthe khalidwe la kudya ndikukhudza njira za ubongo / zolimbikitsa zomwe zimafunidwa pakufuna ndi kufunafuna zakudya za HP. Mayendedwe oterewa angapititse patsogolo kusintha kwa kulemera ndi mafuta a thupi. Umboni wochulukirapo umathandizira kusintha kwa chikhalidwe cha mthupi mwa kugwiritsira ntchito njira zamagetsi, neuroendocrine ndi neural (cortico-limbic-striatal), kuti zikhale ndi chilakolako cha zakudya ndi kudya mu zakudya za HP ndi zina zomwe zimagwirizana ndi nkhawa. Momwemonso, njira yopangira zakudya za HP, zakudya zopezera chakudya komanso kusokonezeka maganizo zingasinthe njira zowonongeka, zopanikizika komanso zopatsa mphotho mu ubongo ndi thupi kulimbikitsa HP chakudya cholimbikitsa ndi kudya (onani Chithunzi 4). Monga momwe tafotokozera m'magulu apitalo, mahomoni oteteza maganizo (CRF, GCs) ndi zinthu zamadzimadzi (insulini, ghrelin, leptin) iliyonse imakhudza ubongo wa dopaminergic, komanso kusintha kwachilengedwe (zinthu zosasintha), izi zikhoza kulimbikitsa mapepala apamwamba a HP zofuna za zakudya ndi kudya, kupyolera mu mphamvu ya ubongo mphoto. Choncho, a Kulimbikitsa njira yopititsira patsogolo chakudya Zingatheke kuti mchitidwe wokhudzana ndi kulemera kwa maselo, neuroendocrine ndi cortico-limbic njira zolimbitsa thupi zimalimbikitsa HP chakudya cholimbikitsa ndi kudya kwa anthu omwe ali pachiopsezo. Kulimbikitsana kotereku kunachulukitsanso chidwi cha HP chakudya ndi kudya, komweko kudzalimbikitsanso kupindulitsa kwa m'tsogolo, motero kudzathetsa kusintha kwa zolemetsa zokhudzana ndi kulemera ndi njira zamagetsi, komanso kuwonjezereka kwa ubongo njira za HP chakudya cues kapena nkhawa, kulimbikitsa HP chakudya cholimbikitsa ndi kudya. Kuphatikiza kulemera ndi BMI, kusiyana kwa majini ndi maumwini omwe amatha kukhala olemera kwambiri, kudya zakudya, insulin kukana, kupanikizika kosalekeza, ndi zina zosiyana maganizo zimatha kupititsa patsogolo njirayi.
Zotsatira zamtsogolo
Ngakhale kuti pali chisamaliro chowonjezeka cha sayansi pa zovuta zogwirizana pakati pa kupanikizika, mphamvu yowonjezera, kayendedwe ka kudya, komanso chakudya chokwanira komanso zotsatira zake pa mliri wa kunenepa kwambiri, pali kusiyana kwakukulu mukumvetsetsa kwa ubale umenewu. Mafunso angapo ofunika sakuyankha. Mwachitsanzo, sizikudziwika kuti kusintha kwa matenda a neuroendocrine kusintha kwa cortisol, ghrelin, insulini ndi leptin, kumakhudza HP chakudya cholimbikitsa ndi kudya. Ngati kupsinjika kosalekeza kumatsutsana ndi mayankho a HPA, monga momwe tawonetsera m'mbuyomu kufufuza, kodi kusintha kumeneku kumakhudza bwanji chilakolako cha chakudya ndi kudya? Zingakhale zothandiza kufufuza ngati kusintha kolemetsa kupsinjika, neuroendocrine ndi mayankhidwe a kagayidwe kachakudya kusintha HP chakudya cholimbikitsa ndi kudya, ndipo ngati kusintha koteroko kulosera kulemera kwa m'tsogolo ndi kunenepa kwambiri. Kuzindikiritsa anthu omwe ali ndi zida zowonongeka komanso kupanga zida zowonongeka kuti aone momwe zinthu zimayendera pokhudzana ndi nkhawa ndi zakudya zowonjezera chakudya zingathandize kutsogolera chithandizo chabwino chachipatala komanso kulumikiza magulu ena omwe ali pachiopsezo. Kuwonjezera apo, umboni wokhudza kusintha kwa mavoti omwe amapezeka m'maganizo ndi m'maganizo okhudzana ndi zakudya zamakono, komanso kupanikizika kosalekeza, komanso momwe zimagwirizanirana ndi kudya ndi kulemera kwa thupi, kungakhale kovuta kumvetsetsa zomwe zimawopsyeza komanso kusintha kwa maselo mu zokondweretsa chakudya, kudya kwambiri ndi kulemera phindu.
Palinso nkhanza za deta pa njira zomwe zimalepheretsa kulemera kwa thupi kapena kuchepetsa kudya zakudya za HP ndi kupweteka kwa thupi, komanso zomwe mankhwala ochepetsa kunenepa kwambiri ndi oyenerera pa gulu la anthu. Malo osokoneza bongo amachititsa chidwi pa njira zomwe zimayambitsa matenda ozunguza bongo komanso kuchepa kwa mankhwala. Kulephera kusunga kulemera kwa thupi kunakambidwa pa nkhani yowonjezera machitidwe osokoneza bongo (94, 95), nkotheka kuti njira zofananamo zingayambitsire kudyetsa kudya zakudya za HP ndi kulemera kwake, koma maphunziro enieni pa mutu umenewu ndi osowa. Palinso chidziwitso chokhudzana ndi kusintha kwa kayendedwe ka kagayidwe kake ndi zotsatira zake zokhudzana ndi mphotho ndi nkhawa za neurobiology zomwe zingachitike ndi zosiyanasiyana zolemetsa, kuphatikizapo kuchepa kwapang'onopang'ono, kuperewera kwa msinkhu kupyolera mwa "zakudya zowonongeka," kapena njira zosiyanasiyana zochitidwa opaleshoni . Kuwonjezera pamenepo, matenda ambiri okhudzidwa ndi nkhawa, monga matenda a maganizo ndi nkhawa, amapezeka ndi kunenepa kwambiri ndi T2DM, ndipo chidwi, mankhwala opatsiranawo amachititsa kuti pakhale kulemera, koma pali umboni wochepa wosatsimikizira njira zoyendetsera zozizwitsa izi. Pakuika kwa T2DM, kulamulira kolimba kwa glycemic ndi mankhwala owonjezera a insulin nthawi zambiri kumalimbikitsa kulemera. Monga hyperinsulinemia, insulin kukana, kapena zotsatira za nthawi yaitali ya insulini kukana zingayambitse-mphoto neural pathways ndi chilakolako cha chakudya mu owonjezera, insulin osagonjetsedwa, zingakhale zopindulitsa kufufuza njira zothandizira zomwe zingakhale zosakayikitsa HP chakudya kukhumba ndi kudya kuti achepetse kupindula kwakukulu mwa anthuwa.
Potsirizira pake, pali kusintha kwatsopano pa kayendetsedwe ka khalidwe ndi kapangidwe ka mankhwala kodetsa kunenepa komatu sichidziwika bwino momwe zimakhalira ndi zovuta zowonjezereka, zovuta zowonongeka ndi zopatsa mphoto kwa anthu omwe ali oopsya. Mwachitsanzo, umboni wam'mbuyo umasonyeza kuti kulemera kwa thupi kumakhala kosautsika kwambiri komanso kulimbitsa thanzi labwino (96); (97). Pamene kupanikizika kumalimbikitsa chilakolako cha zakudya ndi kudya mowa kwambiri, njira zochepetsera kupsinjika maganizo zingakhale zothandiza pa mapulogalamu othandizira kulemera, ndipo maphunziro ena ochepetsa kuchepetsa kupanikizika kwabwino pa kulemera kwambiri ndi T2DM akuwonetsa zotsatira zowonjezera kupanikizika, chilakolako cha zakudya ndi ntchito ya thupi (98, 99). Komabe, kufufuza koteroko kuli koyambira ndipo kumafuna chidwi chachikulu m'tsogolomu. Komanso, mankhwala omwe amachiza kugwiritsa ntchito mankhwala osokoneza bongo akuonedwa kuti ndi othandiza kuti athe kulemera (100). Zoonadi, kafukufuku wamtsogolo kuti tipitirize kumvetsetsa za njira zamagetsi zokhudzana ndi kupweteka kwa thupi, kusokoneza bongo ndi kunenepa kwambiri zingakhale zopindulitsa kwambiri popanga chithandizo chamankhwala kuti athe kuchepetsa zakudya za HP, chakudya ndi kulemera.
Kuvomereza
Ntchitoyi inathandizidwa ndi NIDDK / NIH, 1K12DK094714-01, ndi NIH Roadmap ya Medical Research Common Grants Grants UL1-DE019586, UL1-RR024139 (Yale CTSA), ndi PL1-DA024859.
Mawu a M'munsi
Chodzikanira cha Wosindikiza: Imeneyi ndi fayilo ya PDF ya zolembedwa zosavomerezeka zomwe zavomerezedwa kuti zifalitsidwe. Monga ntchito kwa makasitomala athu ife tikupereka malemba oyambirira a zolembedwazo. Mipukutuyi idzayambanso kujambula, kufotokozera, ndi kubwereza umboni umene umapezekapo musanatulutsidwe mawonekedwe ake omalizira. Chonde dziwani kuti panthawi yopanga zolakwika zingapezeke zomwe zingakhudze zomwe zili, komanso zotsutsana ndi malamulo zomwe zimagwiritsidwa ntchito pa magaziniyo.
Kulengeza zachuma: Dr. Sinha ali pa Scientific Advisory Board kwa Embera Neutotherapeutics. Ania Jastreboff akuthandiza ManPower amene amapereka makontrakitala ku Pfizer New Haven Clinic Research Unit.
Zothandizira
