Ukuxinezeleka ngenye yezinto eziqhelekileyo zempilo yengqondo eMelika. Uphando lwangoku lubonisa ukuba ukudakumba kubangelwa kukudibanisa imfuza, i-biological, ecological, kunye nengqondo. Ukudandatheka kukuyiyona nkxalabo yeengqondo emhlabeni jikelele kunye noxinzelelo olukhulu kwezoqoqosho noluntu kwingqondo. Ngethamsanqa, ukuxinezeleka, kwimeko enzima kakhulu, kunokuphathwa. Ekuqaleni unyango luya kuqala, lusebenza ngakumbi.

Ngenxa yoko, nangona kunjalo, kunesidingo samagcobhozi azinzileyo eziya kunceda ekuphuculeni ukuxilongwa ukuze kuphuculwe inkqubo yokufumana iziyobisi kunye / okanye unyango ngamnye kwisifo. Ezi ziinjongo, izixhobo zomzimba zendawo apho ubukhona bungasetyenziselwa ukuqikelela ukuba kunokwenzeka ukuqala okanye ubukho bexinzelelo, ukucwangcisa ngokuhambelana nobuqhetseba okanye uphawu lweempawu, kubonise ukuqikelela kunye nokuxela okanye ukubeka esweni impendulo kwindlela yokungenelela. Injongo yale nqaku elandelayo kukubonisa ukuqonda kwangoku, iingxaki ezikhoyo kunye neengxaki ezizayo malunga nokufunyanwa kweentlobo ezahlukeneyo biomarkers ngenxa yokudandatheka kunye nokuba zinokukunceda njani ukuphucula ukuxilongwa kunye nonyango.

I-Biomarkers yoxinzelelo: IiNgcaciso zamva nje, iMingeni ekhoyo kunye neenjongo ezizayo

Abstract

I-plethora yophando iye yabandakanya amakhulu eminyaka yokubeka ingcinezelo, kodwa engakhange ecacise ngokucacileyo iimbopheleleko zabo kwizifo ezidandathekileyo okanye ezisungulwe okokungaqhelekanga kwizigulane kunye nendlela i-biologic ingasetyenziswa ngayo ukuphucula ukuxilongwa, unyango kunye nokuxela. Ukuntuleka kwenqubekela phambili kuyingxenye ngenxa yendalo kunye nokuxhatshazwa kwexinzelelo, ngokubambisana ne-methodological heterogeneity ngaphakathi kwincwadi yophando kunye neendidi ezininzi zezinto eziphilayo ezinokubakho, ukubonakaliswa kwezinto ezihlala zihluka ngokwezinto ezininzi. Sihlolisisa iincwadi ezikhoyo, ezibonisa ukuba abamakishi abandakanyekayo kwiinkqubo ezivuthayo, ezinokwenziwa kwe-neurotrophic and metabolic, kunye ne-neurotransmitter kunye ne-neuroendocrine system systems, zimela abaviwa abathembisayo. Ezi zingalinganiswa ngokuhlolwa kweemvelo kunye ne-epigenetic, i-transcriptomic kunye neproteomic, i-metabolomic ne-neuroimaging. Ukusetyenziswa kweendlela zamanqaku kunye neenkqubo zophando ngokucwangcisiweyo ngoku kuyafuneka ukuba zichonge ukuba ngaba, kunye naziphi na izinto eziphilayo ezingasetyenziselwa ukuxela impendulo kwonyango, ukucwangcisa izigulane kwizonyango ezithile kunye nokuphuhlisa iithagethi zongenelelo olutsha. Siphetha ukuba kukho isithembiso esincinci sokunciphisa umthwalo wokudakumba ngokuqhubeka nokuphuhlisa kunye neendlela zokuphanda.

Internet: ukuphazamiseka kwemizwelo, ingxaki enkulu yokudandatheka, ukuvuvukala, impendulo yonyango, ukucwangcisa, unyango oluthile

intshayelelo

Iingxaki kwiMpilo yengqondo kunye neengxaki zoMoya

Nangona i-psychiatry inomthwalo onxulumene nesifo ekulu kunanoma yiphi enye inqanaba lokuxilongwa kwezonyango, i-1 ukungafani nokuhlonipha kusekhona phakathi kwempilo yengqondo kunye neengqondo kwiindawo ezininzi ezibandakanya inkxaso-mali yophando2 kunye nokupapashwa.3 Phakathi kobunzima obubhekiselele kwimpilo yengqondo ukungabikho ukuvumelanisa, ukuxilongwa kunye nokunyanga okubangelwa ukungaqondi ngokupheleleyo kweenkqubo eziphambili kwezi ngxaki. Oku kubonakala kakhulu kwiinkathazo zengqondo, uluhlu olunomthwalo owodwa owona mkhulu kwimpilo yengqondo.3 Isifo esiphezulu sengqondo, ingxaki enkulu yokudakumba (MDD), isifo esiyinkimbinkimbi, esiyingozi apho i-60% yezigulane zinokufumana inqanaba elithile lokuxhatshazwa konyango olwandisa kwaye lugqithise izidumbu ze-episodes.4 Ukukhathazeka kwemizwelo, kunye nasentsimini ebanzi yempilo yengqondo, iziphumo zonyango ziya kuphuculwa ngokufunyanwa kwamagqabantshintshi anamandla, aphakathi kwazo (nakwezinye) iindidi zokuxilonga, apho unyango inokukhatyathwa. Ekuqapheliseni oku, iiprojekthi zomhlaba jikelele zokucacisa i-subtypes esebenzayo ngoku ziyaqhubeka, njenge-criteria search domain domain.5 Kuye kwafunyanwa ukuba abaphawuli be-biologic ngabaviwa abaphambili kwiinkcenkcesho zengqondo.6

Ukuphucula ukuphendula kwiZonyango zokudandatheka

Nangona kukho uluhlu oluninzi lwezonyango zokudakumba okukhulu, malunga nesithathu kwisigulane sezigulane ezine-MDD zifumana ukuxolelwa, nangona zifumana unyango oluchanekileyo ngokuchanekileyo kunye nokusebenzisa unyango olulinganiselwe, kunye nemilinganiselo yempatho yonyango ibonakala iphantsi kwonyango olutsha. .7 Ngaphezu koko, ukudandatheka kwengxaki yokungathinteli unyango (TRD) kudibaniswa nokukhubazeka okusebenzayo, ukufa, ukugula kunye nokuphindaphindiweyo okanye iziganeko ezingapheliyo kwixesha elide.8,9 Ngenxa yoko, ukufumana ukuphuculwa kwempendulo yonyango kunanaluphi na umgangatho wezonyango kuya kunika izibonelelo ezibanzi kwiziphumo ezipheleleyo ekucindezelekeni. Nangona umthwalo omkhulu obangelwa kwi-TRD, uphando kule ndawo luye lwaba lukhulu. Iinkcazo ze-TRD azange zilungelelaniswe, nangona zizame zangaphambili: I-4 ethile imfuno ifuna ityala elilodwa lonyango elingafezekisi ukunciphisa amanqaku e-50% (ukusuka kumlinganiselo oqinisekisiweyo wokubandezeleka kwengxaki), ngelixa ezinye zifuna ukungaphumeleli ukuxolelwa ngokupheleleyo okanye ngokungakhathaliseki ubuncinane ubuncinane amabini ahlukumezekileyo okwehlukileyo ahlukeneyo kwiiklasi ezahlukeneyo ngaphakathi kwinqanaba eliza kuthathwa njenge-TRD.4,10 Ngaphezulu, isiteji kunye nokubikezelwa kokuchaswa kwonyango kuphuculwe ngokufaka iinkalo eziphambili zekliniki zobunzima kunye nokuxhamla kwinani lezonyango ezingaphumeleli.9,11 Nangona kunjalo, ukungahambelani kwintetho kuguqulela uhlalutyo lweencwadi zophando kwi-TRD umsebenzi onzima ngakumbi.

Ukuze kuphuculwe impendulo kwonyango, kunceda ngokucacileyo ukuchonga iziganeko zobungozi bokungaboni. Ezinye iziganeko eziqhelekileyo ze-TRD ziye zaphawulwa, kubandakanya ukungabikho kokuxolelwa ngokupheleleyo emva kweengqungquthela zangaphambili, ukuxhalabisa, ukuzithiba nokuqala kokudakumba, kunye nobuntu (ngokukodwa ukutsalwa kwezinto eziphantsi, ukuxhomekeka komvuzo ophantsi kunye ne-neuroticism ephezulu) kunye ne-genetic factors.12 Ezi ziphumo zivunyelwene ngokuphonononga ukuhlanganisa ubungqina ngokwahlukileyo kwi-pharmacologic13 kunye nengqondo yengqondo14 unyango lokudandatheka. Iingxaki zokuxhatshazwa kunye neendlela zokuziphatha ezibonisa ukufana nokusebenza ngendlela efanayo, i-15 kodwa ngenxa yeendlela ezahlukileyo zokuthatha isenzo kunokulindelwa ukuba zibe neendlela ezahlukileyo zokuphendula. Ngexesha elide-ukuxhatshazwa kwexesha elidlulileyo kuye kwadibaniswa kunye neziphumo zonyango ezihlwempuzekileyo kunye nokunciphisa iimpendulo zonyango, izibonakaliso ze-16 zangaphambili zibonisa ukuba abantu abaneengxaki zobuntwaba bangaphendula kangcono kwizengqondo kunokwelashwa kwe-pharmacologic.17 Naphezu koku, ukungaqiniseki kubakho kwaye akukho Ukuqulunqwa kweyeza kufikelele kwiikliniki.18

Olu hlalutyo lugxininisa ubungqina obuxhasa ukusetyenziswa kwezinto eziphilayo njengamathuluzi ekliniki ancedo ukuphucula impatho yokunyanzeliswa.

Biomarkers: Iinkqubo kunye nemithombo

I-Biomarkers inikezela iinjongo ezijoliswe ekujoliseni iziganeko zokuphendula ngamanyathelo ahlukeneyo.19 Ubungqina obuya kumhla bubonisa ukuba amanqaku abonakalisa umsebenzi wokuvutha, i-neurotransmitter, i-neurotrophic, neurotocrine kunye neenkqubo zokuxilisa unokwazi ukuqikelela iziphumo zempilo yengqondo kunye nempilo kubantu abadandathekileyo ngoku , kodwa kukho ukungahambisani okukhulu phakathi kwezinto ezifunyenweyo.20 Kule ngongoma, sigxininisa kulezi zixhobo ezinhlanu ze-biologic.

Ukufumana ukuqonda okugcweleyo kweendlela zeemolekyuli kunye negalelo labo kwizifo zengqondo, ngoku kujongwa njengokubalulekile ukuvavanya i-vellevels ezininzi zebhayoloji, kwinto eyaziwa njengeyona ndlela omics . 21 Umzobo 1 unikezela ukubonakaliswa kweendlela ezahlukeneyo amanqanaba e-biologic apho kuvavanywa khona inkqubo nganye kwezi ezintlanu, kunye nemithombo enokubakho yokumakisha ekunokwenziwa kuyo olu vavanyo. Nangona kunjalo, qaphela ukuba ngelixa inkqubo nganye inokuhlolwa kwinqanaba ngalinye le-omics, eyona mithombo ilungileyo yemilinganiselo iyahluka ngokucacileyo kwinqanaba ngalinye. Umzekelo, i-neuroimaging ibonelela ngeqonga lovavanyo olungqalileyo lobume bengqondo okanye ukusebenza, ngelixa iimviwo zeprotheyini egazini zivavanya ngokuthe ngqo amanqaku. I-Transcriptomics22 kunye ne-metabolomics23 ziyanda ngokuthandwa, zinika uvavanyo lwenani elinokubaninzi labamakishi, kwaye iProjekthi yeMicrosoft Microbiome ngoku izama ukufumanisa zonke iintsholongwane kunye nokwakheka kwemfuza ngaphakathi ebantwini.24 Itekhnoloji yeNoveli iphucula amandla ethu okulinganisa ezi, kubandakanya neminye imithombo eyongezelelweyo. ; umzekelo, iihormone ezinje ngecortisol ngoku zinokuvavanywa kwizinwele okanye kwiinzipho (ukubonelela ngesalathiso esinganyangekiyo) okanye ukubila (ukubonelela ngomlinganiso oqhubekayo), 25 nasegazini, ulwelo lwe-cerebrospinal, umchamo kunye namathe.

Ngenxa yenani lemithombo yokubeka, amanqanaba kunye neenkqubo ezichaphazelekayo kuxinzelelo, ayothusi into yokuba isikali seebiomarkers ezinamandla okuguqulela zibanzi. Ngokukodwa, xa unxibelelwano phakathi kwamakishayo luqwalaselwa, mhlawumbi akunakulindeleka ukuba kuvavanywe ii-biomarkers ezizodwa zodwa kuya kunika iziphumo ezineziqhamo zokuphucula ukuziqhelanisa neklinikhi. Schmidt okqhubekayo 26 icebise ukusetyenziswa kweepaneli zebhayomarker kwaye, emva koko, uBrand et al27 ucacisile ipaneli yoyilo esekwe kubungqina bangaphambi kweklinikhi kunye nobuchwephesha be-MDD, echonga iithagethi ze-biomarker ezili-16, nganye kuzo enqabileyo ukuba ibe luphawu olunye. Zibandakanya ukunciphisa ivolumu yento engwevu (kwi-hippocampal, preortal cortex kunye nemimandla ye-basal ganglia), utshintsho lomjikelezo we-circadian, i-hypercortisolism kunye neminye imiboniso ye-axoth hyperactivation ye-hypothalamic, pituitary adrenal (HPA), ukungasebenzi kwe-thyroid, ukunciphisa i-dopamine, i-noradrenaline okanye i-5-hydroxyindoleacetic acid , ukunyuka kwe-glutamate, ukunyuka kwe-superoxide dismutase kunye ne-lipid peroxidation, i-cyclic adenosine 3?, 5? -monophosphate kunye ne-mitogen-activated protein kinase pathway, ukwanda kwee-cytokines ezinamandla, utshintsho kwi-tryptophan, kynurenine, insulin kunye ne-polymorphisms ethile yemfuza. Aba bamakishi akuvunyelwananga ngabo ngokuvumelana kwaye banokulinganiswa ngeendlela ezahlukeneyo; Kucacile ukuba umsebenzi ojolise kwinkqubo kufuneka ujongane nalo msebenzi mkhulu ukuze kungqinwe izibonelelo zabo zeklinikhi.

Iinjongo zale Mbuyekezo

Njengobuhlolo ngokubanzi ngokubanzi, eli nqaku lifuna ukucacisa iimfuno ezipheleleyo zophando lwe-biomarker ekudandathelweni kunye nendlela abenzi bezinto eziphilayo abazibandakanya ngayo ukuguqulela ngokwenene ukuphucula impendulo kwonyango. Siqala ngokuxoxa ngeziphumo ezibalulekileyo kunye nezikhuthazayo kule ntsi kwaye siqondise umfundi kumanqaku athile ngokubhekiselele kumakishi afanelekileyo kunye nokuthelekiswa. Sichaza imingeni ekhoyo ejongene nokukhanya kobungqina, ngokunxulumene neemfuno zokunciphisa umthwalo wokudakumba. Ekugqibeleni, sijonge phambili kwiindlela ezibalulekileyo zophando zokuhlangabezana nemingeni ekhoyo yangoku kunye neempembelelo zabo kwizonyango.

Ukuqonda kwangoku

Ukukhangela izilwanyana ezinobuncedo bezonyango kubantu abanexinzelelo kuye kwavelisa nophando olunzulu kwisithuba sokugqibela senkulungwane. Iindlela zonyango ezisetyenziswa ngokuqhelekileyo zithathwe kwi-monoamine theory of depression; emva koko, iingcinga ze-neuroendocrine zafumana ingqalelo enkulu. Kwiminyaka yakutshanje, uphando olunzulu luye lwajikeleza ingcamango evuzayo yokudandatheka. Nangona kunjalo, inani elikhulu lamanqaku okuhlaziywa afanelekileyo agxininise kuzo zonke iinkqubo ezihlanu; Jonga i-Table 1 kunye nezantsi ukuze uqokelele ulwazi olutshanje kwiinkqubo ze-biomarker. Nangona zilinganiswe kumaninzi amaninzi, iiprotheni ezithathwe ngegazi ziye zahlolisiswa kakhulu kwaye zinikezela umthombo we-biomarker onokulungelelanisa, onokubiza imali kwaye unokusondela kumandla okuguqulela ngaphandle kwemithombo; Ngako oko, iinkcukacha zinikezelwa kwiimveliso ezihamba ngegazi.

Kuphononongo olucwangcisiweyo lwamva nje, uJani et al20 yavavanya i-peripheral yegazi-based biomarkers yoxinzelelo ngokunxulumana neziphumo zonyango. Kwizifundo ezili-14 kuphela ezibandakanyiweyo (zakhangelwa kwada kwangoko ku-2013), ii-biomarkers ezingama-36 zafundwa apho i-12 yayingabalulekanga ababalulekileyo bokuphendula ngokwengqondo okanye ngokomzimba kuphando olunye. Abo bachongwe njengabamele umngcipheko wokungaphenduli kubandakanya iiprotein ezivuthayo: i-interleukin ephantsi (IL) -12p70, umlinganiselo we-lymphocyte ukuya kwi-monocyte count; Iimpawu ze-neuroendocrine (i-dexamethasone nonsuppression ye-cortisol, i-cortisol ejikelezayo ephezulu, inciphise i-hormone evuselela i-thyroid); Iimpawu ze-neurotransmitter (i-serotonin esezantsi kunye ne-noradrenaline); imetabolism (ephantsi koxinano oluphezulu lwe-lipoprotein cholesterol) kunye nezinto ze-neurotrophic (ukunciphisa iprotheyini ebophayo ye-S100 ye-calcium B). Ukongeza koku, olunye uphononongo luxele ngemibutho phakathi kweempawu ezongezelelweyo zebhayomarker kunye neziphumo zonyango.19,28-30 Inkcazo emfutshane yabamakishi bokubekwa kwinkqubo nganye ichaziwe kumacandelo alandelayo nakwiTheyibhile 2.

Iziphumo ezivuthayo ekudandathekeni

Ukusukela kwiphepha le-Smith's seminal elichaza i-macrophage hypothesis, i-31 olu ncwadi luye lwafumana amanqanaba anyukayo eempawu zokutshisa kwizigulana ezixinezelekileyo, eziye zaqwalaselwa ngokubanzi.32-37Iiproteni ezilishumi elinambini ezivuthayo ziye zavavanywa kwiimeta zohlalutyo ngokuthelekisa uxinzelelo kunye nempilo. ulawulo lwabantu. 38-43

I-IL-6 (P <0.001 kulo lonke uhlalutyo lwe-meta; Izifundo ezingama-31 zibandakanyiwe) kunye ne-CRP (P <0.001; Izifundo ezingama-20) zivela rhoqo kwaye zithembekile ekuphakameni koxinzelelo.40 I-tumor necrosis factor alpha (TNF?) (P <0.001), 38 kodwa ubukhulu becala ukungafaniyo kunikezele ngokungangqinelaniyo xa kusenziwa uphando lophando lwamva nje (izifundo ze-31) .40 IL-1? ihambelana ngokungaphaya nokudakumba, kunye nohlalutyo lwe-meta olucebisa amanqanaba aphezulu kuxinzelelo (P = 0.03), amanqanaba aphezulu angama-41 kuphela kwizifundo zaseYurophu42 okanye akukho mahluko kulawulo. 40 Ngaphandle koku, inqaku lakutshanje licebise iimpembelelo ezithile zoguqulo kwi-IL- 1?, 44 ixhaswe sisiphumo esibaluleke kakhulu se-IL-1 ephezulu? i-ribonucleic acid eqikelela impendulo engeyiyo kwizidambisi zengqondo; ezinye iziphumo ezingaphezulu ezingama-45 zinxulumene nokujikeleza kwee-cytokines ezivela kwigazi. I-chemokine monocyte chemoattractant protein-1 ibonakalise ukuphakama kwabathathi-nxaxheba abadandathekileyo kuhlalutyo olunye lweemeta.39 I-Interleukins IL-2, IL-4, IL-8, IL-10 kunye ne-interferon gamma zazingahlukanga ncam phakathi kwezigulana ezixinezelekileyo kunye nolawulo kwi inqanaba le-meta-analytic, kodwa nangona kunjalo libonakalisile ukuba linokwenzeka ngokutshintsha kunyango: I-IL-8 ixeliwe iphakanyisiwe kwabo banexinzelelo olunamandla kwaye benqamleza ngokwamacandelo, iipateni ezingama-46 zotshintsho kwi-IL-10 kunye ne-interferon gamma ngexesha lonyango kwenzeke phakathi kwabaphenduli bokuqala ngokuchasene nabangaphenduliyo, i-47 ngelixa i-IL-4 kunye ne-IL-2 ziye zancipha ngokuhambelana nokuxolelwa kwempawu.48 Kuhlalutyo lwe-meta, ukuncipha okuncinci ecaleni kwonyango kubonisiwe kwi-IL-6, IL-1? IL- 10 kunye neCRP.43,49,50 Ukongeza, i-TNF? inokunciphisa kuphela unyango kubaphenduli, kwaye isalathiso semakethi esidityanisiweyo sinokubonisa ukwanda kokudumba kwizigulana ezingaphenduliyo kunyango. . Ke, ubuncinci utshintsho olwenziweyo ngexesha lonyango kunokwenzeka ukuba lubangelwe zizidambisi. Iziphumo ezichanekileyo zokuvuvukala kwezidambisi ezahlukeneyo azikasekwa, kodwa ubungqina obusebenzisa amanqanaba eCRP bacebisa ukuba abantu baphendule ngokwahlukileyo kunyango oluthile olusekwe kukudumba okuyisiseko: U-Harley et al43 uxele i-CRP yangaphambi kokunyanga kwangaphambili yokuxela impendulo engeyiyo kunyango lwengqondo. Unyango ngengqondo), kodwa impendulo elungileyo kwi-nortriptyline okanye kwi-fluoxetine; Uher okqhubekayo51 uyiphindaphindile le nto ifunyanisiweyo kwi-nortriptyline kwaye uchonge isiphumo esichaseneyo se-escitalopram. Ngokwahlukileyo, u-Chang et al52 ufumene i-CRP ephezulu kubantu abaphendula kwangoko kwi-fluoxetine okanye i-venlafaxine kunabo bangaphenduliyo. Ngapha koko, abaguli abane-TRD kunye ne-CRP ephezulu baphendule ngcono kwi-TNF? antagonist infliximab kunaleyo inamanqanaba kuluhlu oluqhelekileyo.53

Ngokubambisana, ubungqina bubonisa ukuba nangona ukulawula izinto ezinjenge-mass mass index (BMI) kunye nobudala, iimpendulo ezivuthayo zibonakala zingabonakalisi kwisigidi sesithathu sezigulane ezinexinzelelo.55,56 Inkqubo yokuvuvukala, nangona kunjalo, iyinkimbinkimbi kakhulu kwaye kukho ezininzi zezinto eziphilayo ezimele iinkalo ezahlukeneyo kule nkqubo. Kungekudala, i-cytokines kunye ne-chemokines eyongezelelweyo iye yafaka ubungqina bokungaqhelekanga ekudakaleni. Ezi ziquka: iprotheni ye-macrophage inhibitory 1a, i-IL-1a, i-IL-7, i-IL-12p70, i-IL-13, i-IL-15, i-eotaxin, i-granulocyte i-macrophage i-colony-stimulating factor, i-57 IL-5,58 IL-16,59 IL-17,60 i-monocyte i-protein ye-chemoattractant -4,61 thymus kunye chemokine lokuvula-ngokomthetho, 62 eotaxin-3, TNFb, 63 interferon wesigrike-eyabangelwa protein 10,64 serum amyloid A, 65 ezinyibilikayo adhesion intracellular molecule66 kunye enyibilikayo nemithambo cell adhesion molecule 1.67

I-Factor Factor Iziphumo kwiinkxalabo

Ngokubaluleka kokubaluleka kwezinto ezingenayo i-neurotrophic factors (njengalezo ezinxulumene ne-angiogenesis), sibhekisela kuma-neurogenic biomarkers phantsi kwengcaciso ebanzi yokukhula.

I-Brain-derived neurotrophic factor (BDNF) yeyona nto iphandwa rhoqo kwezi. Uhlalutyo lweemeta ezininzi lubonisa ukufunyanwa kweprotein ye-BDNF kwi-serum, ebonakala ngathi iyonyuka kunye nonyango lwe-anti-depressant.68-71 Olona hlaziyo lwakutshanje lubonisa ukuba olu fuduko lwe-BDNF luchazwa ngakumbi kwizigulana ezidandathekileyo, kodwa ezo zoxinzelelo zibonakala ngathi yonyusa amanqanaba ale protein nokuba kungabikho ukuxolelwa kweklinikhi. 70 proBDNF ifundwe kancinci kunohlobo oluvuthiweyo lwe-BDNF, kodwa ezi zimbini zibonakala zahlukile ngokusebenza (ngokwempembelelo yazo kwi-tyrosine receptor kinase B receptors) nakutshanje Ubungqina bucebisa ukuba ngelixa i-BDNF evuthiweyo inokuncitshiswa kuxinzelelo, iproBDNF inokuphinda igqitywe.72 Ukukhula kwamathambo kuvavanywa ngokungxolayo kuye kwanikwa ingxelo yokuba kuncinci kuxinzelelo kunolawulo kuhlalutyo lwe-meta, kodwa ayinakutshintshwa ngonyango lokudakumba noxinzelelo Uninzi lwezona ziguliweyo kwizigulana ezinokudakumba okukhulu.73 Iziphumo ezifanayo zixeliwe kuhlalutyo lwe-meta yeseli ye-glialumgca we-neurotrophic factor.74

Ukukhula kwe-Vascular endothelial factor (VEGF) kunendima ekukhuthazeni i-angiogenesis kunye neurogeneis kunye namanye amalungu osapho lwe-VEGF (umzekelo, i-VEGF-C, i-VEGF-D) kwaye ithembisa ngokudakumba. Kutshanje kubonisiwe ukuphakama kwe-VEGF egazini lezigulana ezixinezelekileyo xa kuthelekiswa nolawulo (kwizifundo ezili-75; P <16) .0.001 Nangona kunjalo, i-VEGF esezantsi ichongiwe kwi-TRD76,77 kwaye amanqanaba aphezulu aqikelele ukungaphenduli kunyango lwe-anti-depressant.78 Akuqondwa Kutheni amanqanaba eprotein ye-VEGF enokuphakanyiswa, kodwa ngokuyinxenye inokubangelwa kukuchaphazeleka komzimba kunye / okanye ukonyuka kokuthintela kwegazi brain kwizimo zoxinzelelo ezibangela ukuncitshiswa kwentetho kulwelo lwe-cerebrospinal. 79 Ubudlelwane phakathi kwe-VEGF kunye nempendulo yonyango akucaci. ; uphononongo lwakutsha nje alufumananga buhlobo phakathi kwe-serum VEGF okanye i-BDNF ngempendulo okanye ubunzima boxinzelelo, ngaphandle kokuncipha kunye nokunyanga okunyanga uxinzelelo. Iinkqubo ze-neurotrophic.80 Isiseko sokukhula kwe-fibroblast (okanye i-FGF-81) lilungu le-fibroblast yokukhula kosapho kwaye libonakala liphezulu kuxinzelelo kunamaqela olawulo.1 Nangona kunjalo, iingxelo azihambelani; Omnye wafumanisa ukuba le protein yayisezantsi kwi-MDD kunolawulo olusempilweni, kodwa yancitshiswa ngakumbi ecaleni kwonyango lokudakumba.82,83

imiba yokukhula Further ezingakhange iphicothwe ngokwaneleyo xa uxinezeleko ziquka tyrosine kinase 2 kunye enyibilikayo FMS-ezifana tyrosine kinase-1 (esikwabizwa ngokuba sVEGFR-1) apho enze isineji VEGF, kunye receptors tyrosine kinase (ebopha BDNF) ukuze okuncitshiswe kwixinzelelo.86 Inkalo yokukhula kwamaplahla iyindawo yentsapho ye-VEGF, kodwa ayizange ifundwe kwisampuli ecinezelekileyo kwindlela yethu yolwazi.

Iziphumo zeMetabolic Biomarker kwiNkxwaleko

Iimpawu eziphambili ezinxulumene nezifo eziguquka ziquka i-leptin, i-adiponectin, i-ghrelin, i-triglycerides, i-lipoprotein ephezulu (i-HDL), i-glucose, i-insulin kunye ne-albin.87 Imibutho phakathi kwezinto ezininzi kunye nokudandatheka kuye kwahlaziywa: i-leptin88 kunye ne-ghrelin89 ibonakala iphantsi kwixinzelelo ngaphezu kolawulo kwi-periphery kwaye inokunyuka kunye neyeza zokuxhatshazwayo okanye ukuxolelwa. Ukuxhatshazwa kwe-insulin kunokunyuswa kwixinzelelo, nangona ixabiso elincinci.Iziprofayili ze-90 Lipid, eziquka i-HDL-cholesterol, zibonakala ziguqulwe kwizigulane ezininzi ezinexinzelelo, kubandakanywa nabangenazo izifo ezikhuseleyo, nangona olu lwalamano luyinkimbinkimbi kwaye ludinga ukuhlengahlengiswa .91 Ukongeza, i-hyperglycemia92 kunye ne-hypoalbuminemia93 ekudakaleni kuye kwabikwa kwiingxelo.

Uphando lwamazwe onke e-metabolic aya esiba rhoqo ngokusebenzisa iipaneli zemetabolomics zeemolekyuli ezincinci ngethemba lokufumana utyikityo olunamandla lwe-biochemical yezifo zengqondo. Kuphononongo lwakutshanje kusetyenziswa imodeli yobukrelekrele bokuzenzela, iseti yeemetabolites ezibonisa ukwanda kwe-glucose lipid signaling yayixela kwangaphambili ukuxilongwa kwe-MDD, i-94 ixhasa izifundo zangaphambili.95

Iziphumo ze-Neurotransmitter in Depression

Ngelixa ingqalelo ihlawulwe kwii-monoamines kuxinzelelo ivelise unyango olunempumelelo, akukho zimakethi ze-neurotransmitter zichongiwe zonyusa unyango olusekwe kukhetho lweethagethi ze-monoamine ye-anti-depressants. Amanqaku okusebenza akutshanje kwi-serotonin (5-hydroxytryptamine) 1A receptor njengokubaluleka kokubini ukuxilongwa kunye nokuxela ukuxinezeleka, kulindeleke iindlela ezintsha zofuzo kunye nokucinga.96 Kukho iindlela ezintsha zonyango ezinokujolisa kwi-5-hydroxytryptamine; umzekelo, ukusebenzisa ulawulo lokukhupha kancinci lwe-5-hydroxytryptophan.97 Ukonyusa ukuhanjiswa kwedopamine kunxibelelana nezinye ii-neurotransmitters ukuphucula iziphumo zokuqonda ezinje ngokwenza izigqibo kunye nenkuthazo.98 Ngokufanayo, ii-neurotransmitters glutamate, noradrenaline, histamine kunye ne-serotonin inokusebenzisana kwaye isebenze njengenxalenye yempendulo yoxinzelelo enxulumene nokudakumba; oku kunganciphisa imveliso ye-5-hydroxytryptamine ngokusebenzisa i- flooding . Uphengululo lwamva nje lubeka le thiyori kwaye icebisa ukuba kwi-TRD, oku kungabuyiselwa umva (kunye ne-5-HT ibuyiselwe) ngonyango lweemodemodal ezijolise kwii-neurotransmitters ezininzi. , ii-metabolites ze-neurotransmitter ezinje nge-99-methoxy-100-hydroxyphenylglycol, ye-noradrenaline, okanye i-homovanillic acid, ye-dopamine, ziye zafunyanwa zanda kunye nokuncitshiswa koxinzelelo kunyango lwe-anti-depressant3 okanye amanqanaba asezantsi ezi metabolites axela impendulo engcono Unyango lwe-SSRI.4

Ukufunyaniswa kwe-Neuroendocrine kuXinzelelo

I-Cortisol yinto eqhelekileyo ye-HPA i-biomarker ukuba ifundwe ngokudandatheka. Ukuphononongwa okuninzi kuye kwagxila kwiimvavanyo ezahlukeneyo ze-HPA; ngokubanzi, ezi zibonisa ukuba ukuxinezeleka kuhambelana ne-hypercortisolemia kwaye i-cortisol ivuselela impendulo iyancitshiswa .104,105 Oku kuxhaswa ngokuphononongwa kwangoku kwama-cortisol angapheliyo ezinweleni, exhasa uxolo lwe-cortisol lokungabikho kokuxinezeleka kodwa ukunyaniseka kwezinye izifo ezinjalo njengengxaki yesifo .106 Ngaphezulu, ngokukodwa, amanqanaba e-cortisol aphakanyisiwe angachaza impendulo embi kwi-psychological107 kunye ne-antidepressant108 unyango. Ngokomlando, ummakishi othembisekileyo we-neuroendocrine wempendulo yokwelapha kuye kwaba yi-test de dexamethasone yokunyanzeliswa, apho ukuphathwa kakubi kwe-cortisol emva kokulawulwa kwe-dexamethasone kudibaniswa nokunciphisa ubuncinane bokuxolelwa okulandelayo. Nangona kunjalo, le nto ayifumanekanga njengento elungeleyo kwisicelo seklinikhi. Iimpawu ezinxulumene ne-corticotrophin-ukukhulula i-hormone kunye ne-adrenocorticotropin hormone kunye ne-vasopressin zifunyaniswa ngokungahambelani ukuba zenzeke ngaphezu kokudakumba kwaye i-dehydroepiandrosterone ifumaneka ingqalelo; umlinganiselo we-cortisol ukuya kwi-dehydroepiandrosterone inokuphakanyiswa njengomakishi ozinzileyo kwi-TRD, ukuphikelela emva kokuxolelwa. I-109 i-hormone ye-hormone i-dysfunctions iye yadibana nexinzelelo, kwaye i-hypothyroidism inokudlala indima ebangela ingcinezelo .110 Ngaphezu koko, iimpendulo ze-thyroid ukuqhelanisa nokuphumelela unyango lokudandatheka.111

Ngaphakathi kokungentla, kubalulekile ukuba uqwalasele umqondiso weendlela kwiinkqubo, ezinje nge-glycogen synthase kinase-3, mitogen-activated protein kinase kunye ne-cyclic adenosine 3?, 5? -Monophosphate, ebandakanyeka kwi-synaptic plasticity112 kwaye yaguqulwa ngoxinzelelo. Abagqatswa be-biomarker abanokuthi bathathe iinkqubo ze-biologic ngokukodwa balinganiswa kusetyenziswa i-neuroimaging okanye i-genetics. Ukuphendula kukungabikho kokungafani okunamandla kunye nentsingiselo ye-genomic phakathi kwabantu abadandathekileyo nabangaxinzekanga, iindlela zohlobo lwe-113 zenoveli ezinje ngamanqaku e-polygenic114 okanye ubude be-telomere115 zinokuba luncedo ngakumbi. Amanqaku e-biomarkers ongezelelweyo afumana ukuthandwa avavanya imijikelezo ye-circadian okanye i-chronobiologic biomarkers esebenzisa imithombo eyahlukeneyo. I-Actigraphy inokubonelela ngovavanyo lokujongwa kokulala kunye nokuvuka komsebenzi kwaye uphumle ngesantya, kwaye izixhobo ze-actigraphic zinokulinganisa ngakumbi izinto ezongeziweyo njengokukhanya kokukhanya. Oku kunokuba luncedo ngakumbi ekufumanekeni kuneengxelo eziqhelekileyo ezisetyenziswayo zezigulana kwaye zinokubonelela ngengqikelelo yenoveli yempendulo yonyango.116,117 Umbuzo wokuba zeziphi i-biomarkers zezona zithembisayo kusetyenziso loguqulo zinzima, ezandiswe ngezantsi.

Iingxaki ezikhoyo

Kuzo zonke iinkqubo ezinhlanu ze-neurobiological zihlaziywe, ubu bungqina bulandela inqaku elifanayo: kukho ezininzi ze-biomarker ezikhoyo ezidibeneyo kwezinye iimeko kunye nokudandatheka. La manqaku ahlala edibeneyo kwindlela edibanisa, eyinkimbinkimbi-yohlobo. Ubungqina bungahambelani, kwaye mhlawumbi ezinye ziyi-epiphenomena yezinye iimeko kunye nezinye zibalulekile kwi-subset kuphela yezigulane. I-Biomarkers inokubaluleka ngeendlela ezahlukeneyo (umz., Abo baqikelela ukuphendula ngokulandelelweyo kunyango, ezo zibonisa unyango oluthile olunokuba luncedo okanye ezo ziguqulwa ngamanyathelo ngaphandle kokuphuculwa kwekliniki). Izindlela zeNveli zifunekayo ukwenzela ukwandisa ukuhambelana nokusebenza kweklinikhi yokuvavanya i-biologic kwiingqondo zengqondo.

Biomarker Variability

Ukutshintshwa kwezinto eziphathekayo kwixesha kunye neemeko zibhekiselele kwezinye iindidi (umzekelo, iproteomics) kunezinye (i-genomics). Iimiselo eziqhelekileyo ezininzi azikho okanye azizange zamkelwe ngokupheleleyo. Enyanisweni, impembelelo yeemeko zokusingqongileyo kwimakishi ixhomekeke kwizinto eziphilayo kunye nokunye ukuhlukelelana kwezinto eziphilayo phakathi kwabantu abangenakwenzeka. Oku kwenza uvavanyo lomsebenzi we-biomarker, kunye nokuchonga okungaqhelekanga kwezinto eziphilayo, kunzima ukutolika. Ngenxa yenani labaninzi bezinto ezibonakalayo, amaninzi awazange alinganiswe ngokubanzi okanye kwipaneli epheleleyo kunye namanye amanqaku afanelekileyo.

Zininzi izinto eziye zaxelwa ukuba zitshintshe amanqanaba eeprotheni kwiinkqubo ze-biologic kwizigulane ezineengxaki zokuphazamiseka. Ngokwezinto ezinxulumene nophando ezifana nobude kunye nemeko yokugcinwa (oku kungabangela ukuthotywa kweminye imichiza), oku kubandakanya ixesha lokulinganisa, ubuhlanga, ukusetyenziswa, i-119 yokutya (umzekelo, umsebenzi we-microbiome, ngokukodwa ukubonelelwa ukuba izifundo ezininzi ze-biomarker zegazi ayifuni isampula yokuzila ukudla), ukubhema kwe-120 kunye nokusetyenziswa kweziyobisi, i-121 kunye nempilo yezinto (ezifana ne-comorbid inflammatory, cardiovascular or other illnesses). Ngokomzekelo, nangona ukuvuvukala okugqithisiweyo kubonakala kuxinzelelekileyo kodwa abantu abanempilo xa kuthelekiswa namaqela angadliyo, abantu abadandathekileyo abanesimo esichaphazelekayo ngokumalunga ne-immune, banamazinga aphakamileyo ama-cytokines kunabanye abangenawo uxinzelelo okanye ukugula.122 Ezinye izinto ezivelele Ukubandakanyeka okunokwenzeka kwintsebenziswano phakathi kwama-biomarkers, ukuxinezeleka nokuphendula ngonyango zichazwe ngezantsi.

Ukuxinezeleka. Zombili izimpendulo ze-endocrine kunye ne-immune ziyaziwayo ngokuphendula uxinzelelo (physiological or psychological), kunye nokuxinezeleka kwangethuba ngexesha lokuqokelela i-biologic yezinto eziqhelekileyo akunakulinganiswa kwizifundo zophando nangona ukuhluka kwale ngxaki phakathi kwabantu abathile abangabandakanywa iimpawu ezixinezelekileyo. Ukubandezeleka kwengqondo kunye neengxaki ezingapheliyo zengqondo zisebenza njengomngeni wokuzivikela komzimba, ukugxininisa iimpendulo ezivuthayo kwixesha elifutshane kunye nexesha elide.123,124 Oku kufunyanwe kufikelela kumava obomi bokuqala, obunxulumene nokuphakanyiswa kwabantu abadala abazimeleyo koxinzelelo olunzima umntu omdala.125,126 Ngethuba lobunzima babantwana, ukuvuvukala okukhulu kuye kwaxelwa kuphela kulabo bantwana abadandathekile ngoku .127 Ngokuchaseneyo, abantu abanexinzelelo kunye nembali yoxinzelelo lwabantwana banokuba baxhamle iimpendulo ze-cortisol ukuxinezeleka, xa kuthelekiswa nalabo abanexinzelelo akukho ekuqaleni-ubomi trauma.128 Stress-eyabangelwa HPA utshintsho axis abavelayo zihlobene nge function kwengqondo, 129 kwakunye depression uhlobo olunganeno okanye Umahluko ezinxulumene-HPA genes.130 Ntshikilelo une elifutshane ixesha elide oko kwenzakalise iziphumo neurogenesis131 nezinye kwenethiwekhi iinkqubo.132 Akucaci kakuhle indlela ukukhathazeka kwabantwana kuthintela ngayo abakhweli be-biologic ekucindezelekeni abantu abadala, kodwa kunokwenzeka ukuba uxinzelelo lobomi bexesha elidala lubangela abantu abathile ukuba babe nokunyamezela ukunyamezeleka kwengqondo xa bekhulile abakhuliswa ngokwengqondo nangokwenyama.

Ukusebenza kwengqondo. dysfunctions Neurocognitive kwenzeka rhoqo kubantu nokuphazamiseka ngokwenene, nkqu unmedicated ntsilelo MDD.133 Cognitive abonakale ezongezelelekayo ecaleni unyango resistance.134 Neurobiologically, i HPA axis129 kunye neurotrophic systems135 kusenokwenzeka ukuba adlale indima ephambili kule relationship. I-neurotransmitters noradrenaline kunye ne-dopamine kubalulekile ukuba kwenziwe iinkqubo ezinokwenziwa kwengqondo ezifana nokufunda kunye nenkumbulo. I-136 Impendulo ephakamileyo yokuvuvukala inxulumene nokuncipha kwengqondo, kwaye mhlawumbi inokuchaphazela ukusebenza kwengqondo kwiintlobo zexinzelelo, i-137 kunye nokuxoxwa, ngokusebenzisa iindlela ezahlukeneyo.138 Ewe, I-Krogh ne-al139 icetywe ukuba i-CRP ihambelana kakhulu nokusebenza kwengqiqo kunempawu eziphambili zokudakumba.

Ubudala, isini kunye ne-BMI. Ukungabikho okanye ubukho, kwaye ukhokelo lweengxaki zezinto ze-biologic phakathi kwamadoda nabasetyhini luye lwahluke ngokukodwa kubungqina obuza kube yimini. I-neuroendocrine i-hormone ukuhluka phakathi kwamadoda nabasetyhini abachaphazelekayo nokuxinzezeleka kwengqondo.140 Ukuphononongwa kweengxelo zokuvuvukala kwabambileyo kuthi ukulawula ukudala nobulili akuchasene nokungafani kokulawula isigulane kwii-cytokines ezivuthayo (nangona umbutho phakathi kwe-IL-6 kunye nokudandatheka okunciphise njengeminyaka yobudala, ehambelana nemibono yokuba ukuvuvukala ngokubanzi kuphakama ngobudala) .Iihluko ze-41,141 ze-VEGF phakathi kwezigulane kunye nokulawula zikhulu kwizifundo ekuvavanyeni iisampuli ezincinci, ngelixa i-sex, i-BMI kunye neenkalo zeklinikhi azichaphazeli ezi matshantshi kumgangatho we-meta-analysis .77 Nangona kunjalo, Ukungabikho kohlengahlengiso lwe-BMI kwiimviwo zangaphambili zokuvutha nokudakumba kubonakala kuphazamisa ukungafani okuphawulekayo phakathi kwala maqela. IXXUMUMX Yandisa i-adipose tissue ibonakaliswe ngokucacileyo ekuvuseleleni ukuveliswa kwe-cytokine kunye nokudibaniswa ngokuthe ngqo kunye nabakishi be-metabolic.41 Ngenxa yokuba imithi yengqondo ye-psychotropic no ku nxu lumana ufumane ubuncwane obunzima kunye ne-BMI ephezulu, kwaye ezi zidibene nokuxhatshazwa konyango ekudakaleni, oku kuyindawo ebalulekileyo yokuhlola.

Amayeza. Uninzi lwezifundo ze-biomarker kuxinzelelo (zombini ezinqamlezayo kunye nobude obude) ziqokelele iisampulu ezisisiseko kubathathi-nxaxheba abangafundanga ukunciphisa ukungafani. Nangona kunjalo, uninzi lolu vavanyo luthathwa emva kwexesha lokuhlanjwa elivela kumayeza, eshiya into enokubangela ukuphazamiseka okunokubakho kotshintsho olushiyekileyo kwi-physiology, olwenziwe luluhlu olubanzi lonyango olufumanekayo olunokuba neziphumo ezahlukeneyo kukudumba. Olunye uphononongo alukhuphelanga ngaphandle i-psychotropic, kodwa ayilulo olunye usetyenziso lwamayeza: ngakumbi, ipilisi yokuthintela ukukhulelwa yomlomo ihlala ivunyelwe kubathathi-nxaxheba kuphando kwaye ingalawulwa kuhlalutyo, oluye lwabonakaliswa kutshanje ukunyusa amanqanaba ehomoni kunye necytokine.143,144 Izifundo ezininzi zibonisa ukuba uxinzelelo amayeza aneziphumo kwimpendulo yokuvuvukala, i-34,43,49,145-147HPA-axis, i-108 neurotransmitter, i-148 kunye nomsebenzi we-neurotrophic149. Nangona kunjalo, uninzi lonyango olunokubakho kuxinzelelo lunezinto ezahlukileyo nezintsonkothileyo ze-pharmacologic, ukucebisa ukuba kunokubakho neziphumo zebhayoloji zeendlela ezahlukeneyo zonyango, ezixhaswa yidatha yangoku. Kuye kwafundwa ukuba ukongeza kwimiphumo ye-monoamine, amayeza athile okujolisa kwi-serotonin (okt, ii-SSRIs) anokujolisa kwi-Th2 shifts in inflammation, kunye ne-noradrenergic antidepressants (umz. ukumisela iziphumo zomntu ngamnye okanye indibaniselwano yamayeza kwii-biomarkers. Oku kunokwenzeka ukuba kulamle phakathi kwezinye izinto kubandakanya ubude bonyango (zimbalwa izilingo ezivavanya ukusetyenziswa kwamayeza exesha elide), isampulu ye-heterogeneity kwaye ingabacinezeli abathathi-nxaxheba ngokuphendula kunyango.

Heterogeneity

Indlela yokwenza. Njengoko kubhekiswe ngasentla, ukungafani (phakathi kwezifundo ngaphakathi) ngaphakathi kwimiqathango yonyango (kunye nokudibanisa) abathathi-nxaxheba abathabathayo kwaye bathathe kwangaphambili kufuneka bavelise ukuchithwa kwamanani kwiziphumo zophando, ingakumbi kwi-biomarker yophando. Ukongezelela oku, ezinye iimpawu kunye neesampuli iimpawu ziyahlukahluka kuzo zonke izifundo, oko kukunyusa ubunzima ngokutolika nokuchaza iziphumo. Ezi ziquka iiparameters zokulinganisa i-biomarker (umz., Iikiti zeesayiti) kunye neendlela zokuqokelela, ukugcina, ukucwangcisa nokuhlaziya amanqaku ekudakaleni. I-Hiles ne-al141 ihlolisise imithombo ethile yokungahambelani kwiincwadi ngokuvuvukala kwaye ifumene ukuba ukuchaneka kokuxilongwa kweengxaki, i-BMI kunye nezigulane ezidityanisiweyo zibaluleke kakhulu ukuba ziphendule ekuhloleni ukuvuvukala komzimba phakathi kwamaqela acinezelekileyo kunye namaqela angenanto.

I klinikhi. Ubuninzi be-heterogeneity yoluntu oluxinekekileyo lubhalwe kakuhle kwi151 kwaye luyinxaxheba ebalulekileyo ekufumaneni iziphumo ngaphakathi kwincwadi yophando. Kucingeka ukuba nakwii-diagnostic, iiprofayili ze-biologic ezingavamile zigcinwe kumagqabantshintshi abantu abangenako ukuzinza ngokuhamba kwesikhathi. Amacandelwana ahlangeneyo abantu abanengxaki yokudakumba bangabonakala ngokudibanisa kwezinto zengqondo kunye neengcali. Ngezantsi, sichaza amandla okuhlolisisa iinqunjana ekuhlangabezaneni nemingeni eyenza ukuhlukahluka kwezinto eziphilayo kunye ne-heterogeneity.

Iincinci zingaphantsi koxinzelelo

Ukuza kuthi ga ngoku, akukho maqela amancinci phakathi koxinzelelo lweziqendu okanye ukuphazamiseka okwenze ngokuthembekileyo ukukwazi ukwahlula phakathi kwezigulana ezisekwe kulwaziso lwempawu okanye ukuphendula ngonyango.152 Ubukho beqelana apho ukubonakaliswa kwe-biologic kuchazwe ngakumbi kuya kunceda ukucacisa ukungafani phakathi kwezifundo zangaphambili kunye inokuguqula indlela eya kunyango oluhleliweyo. UKunugi okqhubekayo153 bacebise ukuba kusetyenziswe iisuntswana ezine ezinokubakho ngokusekwe kwindima yeenkqubo ezahlukeneyo ze-neurobiological ezibonisa iiklinikhi ezifanelekileyo ezichaphazelekayo kuxinzelelo: abo bane-hypercortisolism ebonisa uxinzelelo lwe-melancholic, okanye i-hypocortisolism ebonisa i-atypical subtype, i-subset enxulumene ne-dopamine yezigulana ezinokuthi ibonakalise ngokubalaseleyo nge-anhedonia (kwaye ingaphendula kakuhle, umzekelo, aripiprazole) kunye ne-subtype yokuvuvukala ebonakaliswa kukudumba okuphezulu. Amanqaku amaninzi agxile kukudumba achaze imeko yobukho be- inflammatory subtype ngaphakathi koxinzelelo.55,56,154,155Ukulungelelaniswa kweeklinikhi kokudumba okuphezulu akukamiselwa kwaye zimbalwa iinzame ezithe ngqo ezenziweyo zokufumanisa ukuba ngabaphi abathathi-nxaxheba abanokubakho eli qela. Kucetyisiwe ukuba abantu abanexinzelelo lwe-atypical banokuba namanqanaba aphezulu okuvuvukala kune-melancholic subtype, 156 ekunokwenzeka ukuba ayihambelani neziphumo ngokubhekisele kwi-axis ye-HPA kwi-melancholic kunye ne-atypical subtypes yoxinzelelo. I-TRD37 okanye uxinzelelo olunempawu ezibonakalayo ze-somatic157 ikwachazwe njenge-subtype enokubangela ukudumba, kodwa i-neurovegetative (ukulala, ukuthanda ukutya, ukulahleka kwe-libido), imeko (kubandakanya imeko ephantsi, ukuzibulala kunye nokungakhathali) kunye neempawu zokuqonda (kubandakanya ukuthanda icala kunye netyala) 158 zonke zibonakala zihambelana neeprofayili zebhayoloji. Abanye abagqatswa abanokubakho kwi-subtype yokuvuvukala kubandakanya amava okuziphatha-njengeempawu 159,160 okanye isifo se-metabolic syndrome.158

Ukuxhomekeka kwi-hypo (mania) iyakwazi ukwahlula i-biologically phakathi kwezigulane ezinexinzelelo. Ubu bungqina bubonisa ukuba izifo ezibangelwa yi-bipolar ziyiqela elininzi leemvakalelo zengqondo, kunye neengxaki zentsholongwane ye-bipolar i-subsyndromal disorder ifunyenwe ngokubanzi kunokuba yayiye yaqaphela ngaphambili.161 Ukungafumani kakuhle okanye / okanye ukulibaziseka kwe-bipolar disorder kusandul 'ukugqitywa njengengxaki enkulu kwizonyango zengqondo, ixesha eliqhelekileyo ukulungisa ukuxilongwa rhoqo kwixesha elidlulileyo elishumi kwiXXUMUMX kunye nokulibaziseka okubangela ukonakala okukhulu kunye neendleko zesifo sonke .162 Uninzi lwezigulane ezineengxaki ze-bipolar eziboniswa ekuqaleni kunye nezinye iipasiti ezidandathekileyo kunye nokudakumba kwe-unipolar kuba yiyona ndlela ihamba phambili, izinto ezinokuba umahluko phakathi kokudakumba unipolar kunye vuvabyi iye kakhulu implications.163 Bipolar spectrum disorders mhlawumbi ziye ababanjwa kwezinye uphando ezidlulileyo biomarker MDD, kunye smatterings ubungqina zibonise umahluko of HPA axis activity164 okanye inflammation109 phakathi disorder unipo ukuxinezeleka. Nangona kunjalo, oku kuthelekiswayo kunqongophe, kuba neesampula ezincinci ezincinci, iziphumo ezingabonakaliyo zempembelelo okanye abantu abaqashiweyo abangabonakali kakuhle ngokuxilongwa. Olu phando aluhlolisanga indima yempendulo yokwenza unyango kula malamano.

Ukubandezeleka kwe-bipolar167 kunye nokuxhatshazwa kwonyango168 ayinanto yokwakha kwaye ilala ngokuqhubekayo, okwandisa umngeni we-subtype identification. Ngaphandle kokubambisana, kubalulekile ukuba kuqaphele ukuba ezininzi izinto ezingekho phantsi kwezinto eziphilayo ezibonwe ekudakaleni zifumaneka kwizigulane ezinezinye izifo. Ngako oko, iimviwo ze-transdiagnostic nazo zibalulekile.

Iingxaki zeBeomarker Measurement

Ukhetho lwe Biomarker. Inani elikhulu lama-biomarker anokuba luncedo luzisa umceli mngeni kwizifundo zengqondo ekumiseleni ukuba ngabaphi abamakishi abachaphazelekayo. Ukonyusa umceli mngeni, bambalwa kwezi biomarker ziphantsi kophando olwaneleyo kuxinzelelo, kwaye uninzi lwazo, iindima zazo ezichanekileyo kubantu abasempilweni nakwiklinikhi aziqondwa kakuhle. Ngaphandle koku, kwenziwe iinzame zokucebisa iipaneli zebhayomarker ethembisayo. Ukongeza kwiBrand et al's iiseti ze-16 zamakishi ezinokubakho okunamandla, i-27 Lopresti et al icacisa iseti ebanzi yabamakishi yoxinzelelo lwe-oxidative enokubakho ekuphuculeni impendulo yonyango. 28 Papakostas okqhubekayo ichaze i-priori iseti yamanqaku asithoba e-serum Iinkqubo ze-biologic (i-BDNF, i-cortisol, i-TNF enyibilikayo? uhlobo lwe-receptor II, i-alpha1 antitrypsin, i-apolipoprotein CIII, ukukhula kwe-epidermal factor, i-myeloperoxidase, i-prolactin kunye ne-resistin) kwiisampulu zokuqinisekisa nokuphindaphinda nge-MDD. Xa sele idityanisiwe, umlinganiso odityanisiweyo wala manqanaba wakwazi ukwahlula phakathi kwe-MDD kunye namaqela olawulo ngokuchaneka kwe-80% -90 %.169 Siphakamisa ukuba nazo ezi azibandakanyi bonke abanokubakho kule ndima; Jonga iTheyibhile 2 malunga nokuchazwa okungagungqiyo kwee-biomarkers ezinokubakho kuxinzelelo, eziqulathe zombini ezo zinobungqina kunye nabamakishi benoveli abathembisayo.

Te knoloji. Ngenxa yentuthuko yezobuchwepheshe, ngoku kuya kwenzeka (okunene, ekulungeleyo) ukulinganisa iindidi ezininzi zeemveliso zexabiso kunye neendleko eziphantsi kunye novelwano oluphezulu kunokuba bekunjalo ngaphambili. Okwangoku, oku kukwazi ukulinganisa iindidi ezininzi kunokuba sikwazi ukuhlalutya ngokuchanekileyo kunye nokutolika idatha, i-170 into eya kuqhubeka kunye nokunyuka kwamanqaku e-biomarker kunye namanqaku amasha afana ne-metabolomics. Oku kubangelwa ukungabikho kokuqonda malunga neendima ezichanekileyo kunye nokusebenzisana phakathi kwamanqaku, kunye nokuqonda okungapheliyo malunga nabamakishi abandakanyekayo kumanqanaba ahlukeneyo e-biologic (umz., I-genetic, i-transcription, iprotheni) ngaphakathi naphakathi kwabantu. Idatha enkulu usebenzisa iindlela ezintsha zokuhlalutya kunye nemigangatho iya kunceda ekujongeni oku, kwaye iindlela ezintsha zicetywayo; Omnye umzekelo ukuphuhliswa kwendlela yokubalwa kwemilinganiselo esekelwe kwisicatshulwa esisekelwe kwi-flux ukufumana amanqaku amatshini angabonakaliyo ngokubhekiselele ekusebenziseni kwabo phakathi kwamanethiwekhi kunye nokudibanisa imbonakalo yemfuza kunye needabolite data.Izixhobo zokufunda kumashishini sele zisetyenzisiweyo kwaye ziya kunceda ngeemodeli zisebenzisa i-biomarker idatha ukuxela iziphumo zonyango kwizifundo kunye nedatha enkulu.171

Ukuhlanganiswa kwezinto eziphilayo. Ukuphonononga uluhlu lwee-biomarkers ngaxeshanye yenye indlela yokuhlola amanqaku angabodwa anokubonelela ngombono ochanekileyo ngakumbi kwiwebhu entsonkothileyo yeenkqubo zebhayoloji okanye iinethiwekhi. kunye nokunxibelelana kuqondwa kakuhle), idatha ye-biomarker inokudityaniswa okanye ifakwe kwisalathiso. Umceli mngeni omnye kukuchonga eyona ndlela isebenzayo yokwenza oku, kwaye inokufuna ukuphuculwa kwitekhnoloji kunye / okanye ubuchule bokuhlalutya inoveli (jonga icandelo le- Big data ). Ngokwembali, umlinganiso phakathi kweebhayomarkers ezibini ezahlukileyo zivelise iziphumo ezinomdla.26 Zimbalwa iinzame ezenziweyo zokuhlanganisa idatha ye-biomarker kwizinga elikhulu, njengalezo zisebenzisa uhlalutyo lwecandelo leenethiwekhi ze-cytokine.109,173 kuhlalutyo lwe-meta, ii-cytokines ezinokubakho eguqulweyo yamanqaku esiphumo sophando olunye kwisifundo ngasinye, kwaye iyonke ibonakalise ukuvuvukala okuphezulu kakhulu ngaphambi konyango lwe-antidepressant, ukuqikelela ukungaphenduli okulandelayo kwizifundo zonyango. Iiphaneli ze-biomarker ezidityanisiweyo zombini zingumceli mngeni kunye nethuba lophando lwexesha elizayo lokuchonga iziphumo ezinokuthenjwa ezinokusetyenziselwa ukuphucula iziphumo zonyango.174 Uphononongo olwenziwe nguPapakostas et al luthathe enye indlela, kukhethwa ipaneli ye-serum biomarkers (ye-inflammatory, I-axPA ye-HPA kunye neenkqubo ze-metabolic) ezazibonisiwe ukuba zahlukile phakathi koxinzelelo kunye nolawulo lwabantu kwisifundo esingaphambili kwaye bazidibanisa baba ngamanqaku omngcipheko okwahluka kwiisampulu ezimbini ezizimeleyo kunye neqela lolawulo eline> 43% yemvakalelo kunye nokucaciswa.80

Idatha enkulu. Ukusetyenziswa kwedatha enkulu kusenokwenzeka ukuba kuyafuneka ekujonganeni nemiceli mngeni echazwe ngokujikeleza kwe-heterogeneity, ukwahluka kwe-biomarker, ukuchonga abamakishi abalungileyo kunye nokuzisa intsimi kuguqulelo, kusetyenziswa uphando kuxinzelelo. Nangona kunjalo, njengoko kuchaziwe apha ngasentla, oku kuzisa imiceli mngeni kwezobuchwephesha nakwezesayensi.175 Inzululwazi yezempilo isandula ukuqalisa ukusebenzisa uhlalutyo olukhulu lwedatha, ishumi leminyaka okanye emva koko kunakwicandelo loshishino. Nangona kunjalo, izifundo ezinje nge-SPOT-D152 kunye ne-Consortia ezinje nge-Psychiatric Genetics Consortium176 ziyaqhubeka ngokuqonda kwethu kweendlela zebhayoloji kunyango lwengqondo. I-algorithms yokufunda ngomatshini iye, kwizifundo ezimbalwa kakhulu, yaqala ukuba isetyenziswe kwii-biomarkers zoxinzelelo: uphando lwamva nje oluhlanganisiweyo lwedatha ukusuka> kubathathi-nxaxheba abangama-5,000 250 be-21 biomarkers; emva kokufakwa kwedatha okuphindaphindiweyo, ukufundwa komatshini okwandisiweyo kwenziwa, kubonisa i-177 enokubakho kwi-biomarkers. Ukulandela okunye ukuhlalutya ukuhlaziywa, i-biomarkers ezintathu zikhethwe njengezihambelana kakhulu neempawu zokudandatheka (ubukhulu beeseli ezibomvu zeeseli ezibomvu, i-serum glucose kunye namazinga e-bilirubin). Ababhali bagqiba kwelokuba idatha enkulu inokusetyenziswa ngokufanelekileyo ekuveliseni ii-hypothes.XNUMX Iiprojekthi ezinkulu ze-biomarker phenotyping ngoku ziyaqhubeka kwaye ziya kunceda ukuqhubela phambili uhambo lwethu ukuya kwikamva le-neurobiology yoxinzelelo.

Ithemba Elizayo

Ukuchongwa kweGeumarker Panel

Iziphumo kuncwadi ukuza kuthi ga ngoku zifuna ukuphindwaphindwa kwizifundo ezikhulu. Oku kuyinyani ngokukodwa kwii-biomarkers zenoveli, ezinje nge-chemokine thymus kunye ne-activation elawulwa yi-chemokine kunye nokukhula kwe-tyrosine kinase 2 ethi, kulwazi lwethu, ingakhange iphandwe kwiisampulu zoxinzelelo kunye nolawulo olusempilweni. Izifundo ezikhulu zedatha kufuneka zivavanye iipaneli zebhayomarker ezibanzi kwaye zisebenzise iindlela zohlalutyo olunobunkunkqele ekuqinisekiseni ngokupheleleyo ubudlelwane phakathi kwabamakishi kunye nezo zinto zibatshintsha kwiklinikhi nakwizinto ezingezizo ezonyango. Ukongeza, iimpendulo ezinkulu zohlalutyo lwecandelo zinokuseka amaqela ahambelana kakhulu e-biomarkers kwaye zinokwazisa ngokusetyenziswa kwe-'composites 'kunyango lwe-biologic psychiatry, olunokuthi luphucule ukufana kweziphumo ezizayo.

Ukufunyaniswa kweeNgqungquthela eziHlanganayo

Ngokuphathelele ukhetho lwe-biomarker, iipaneli ezininzi zingafuneka kwiindlela ezahlukeneyo ezinokuthi uphando lubangele. Kuthathwe ndawonye, ​​ubungqina bokuba bubonisa ukuba iiprofayili ze-biomarker ziqinisekisiwe, kodwa ziguqulelwe ngokugqithiseleyo kubantu abaye baxinezeleka. Oku kungasungulwa ngaphakathi okanye kwiinkalo zokuxilonga, eziza kubakho ukungahambelani kweziphumo ezingabonwa kule ncwadi. Ukuqulunqwa kweqela le-biologic (okanye iinqunkwana) zinokuthi zenziwe ngempumelelo ngokubanzi ngokuhlalutya kwamagqabantshintshini e-biomarker network. Oku kuya kubonisa ukungafani koluntu ngaphakathi; Uhlalutyo lweklasi olulandelayo lungabonisa iimpawu zeclini ezicacileyo ezisekelwe kulo, umzekelo, ukuvuvukala.

Iimpembelelo eziPhezulu zeZonyango kwi-Inflammation and Response

Zonke izifo zonyango eziqhelekileyo kufuneka zihlolwe ngokucacileyo kwiimpembelelo ezithile ze-biologic, kunye nokuphendula ngokuphumelela kwezilingo zonyango. Oku kunokwenza ukuba izakhiwo ezinxulumene nezicwangciso zendalo kunye nezibonakaliso zezibonakaliso zikwazi ukulungisa iziphumo kwiinkalo ezahlukeneyo zonyango ezithandwa ngumntu, kwaye zinokuthi zenzeke kumxholo wesifo sengqondo sokungaxhamli kunye nokuphazamiseka kwengqondo. Oku kunokuba luncedo kumathambo amasha kunye nokunyango okwangoku kuboniswa.

Ukuzimisela kokuMelana nokuPhathwa kweNyango

Ukusetyenziswa kwezi ndlela zingentla kungabangela ukuphuculwa kwamandla okubonelela ngokuchasene nonyango. Eyona nto iyinyani kwaye iyaqhubeka (umz., Ixesha elide) amanyathelo okuphendula impatho anokufaka isandla kulo. Uvavanyo lweminye imilinganiselo esemthethweni yesigulane-ntle (njengomgangatho wobomi kunye nokusebenza kwansuku zonke) kunokubonelela ngokubanzi ukuhlolwa kwempembelelo yonyango enokuthi inxulumane ngokuthe ngqo kunye ne-biomarkers. Nangona umsebenzi wezinto eziphilayo kuphela ongenako ukwazi ukwahlula abaphenduli bezonyango kubantu abangafaniyo, ukulinganisa ngokufanayo kwezixhobo ze-biomarkers kunye nokuguquguquka kwemimandla kungabandakanywa nolwazi lwe-biomarker ekuphuhliseni imodeli yokulandelelana yokungaphelelanga kwempatho. Ukuba ithe imodeli ethembekileyo yenzelwe ukuxela impendulo (nokuba yindawo exinezelekileyo okanye i-subpopulation) kwaye iqinisekisiwe ngokuphindaphindiweyo, ukuyila ukuguqulela kungayifaka isicelo sayo kwisilingo esilawulwayo.

Ukujongana neZonyango ezintle

Okwangoku, abaguli abanexinzelelo abakajoliswanga ukuba bafumane inkqubo yokungenelela. Ukuba kungqinisisiwe, uyilo olulinganiselweyo lunokuqeshwa ukuvavanya imodeli yokuqikelela ukungaphenduli kunye / okanye ukumisela ukuba isigulana sifuna ukuvavanywa kwimodeli yokhathalelo. Oku kunokuba luncedo kuzo zombini izicwangciso zonyango kunye nezendalo, kwiindidi ezahlukeneyo zongenelelo. Ekugqibeleni, imodeli esebenzayo yeklinikhi inokuphuhliswa ukubonelela abantu ngonyango olufanelekileyo, ukuqaphela abo banokuthi baphuhlise ukudakumba okunganyangekiyo kunye nokubonelela ngononophelo oluphuculweyo kunye nokubeka esweni kwezi zigulana. Izigulana ezichongwe njengabasemngciphekweni wokuchasana nonyango zinokumiselwa unyango oluhambelana nonyango kunye nonyango lwe-pharmacologic okanye indibaniselwano ye-pharmacotherapy. Njengomzekelo oqikelelweyo, abathathi-nxaxheba abangenakho ukunyusa i-cytokine ephakanyisiweyo banokubonakaliswa ukuba bafumane unyango lwengqondo kunonyango lwe-pharmacologic, ngelixa iseti yezigulana ezinokukrala okukhulu inokufumana iarhente echasayo ekonyuseni kunyango oluqhelekileyo. Kuyafana nokubekwa ecaleni, iindlela ezikhethwe ngonyango ezikhethiweyo zinokwenzeka kwixesha elizayo. Umzekelo, umntu othile oxinezelekileyo unokuba ne-TNF ephezulu kakhulu? amanqanaba, kodwa akukho okunye ukungaqheleki kwezinto eziphilayo, kwaye ngaba unokuxhamla kunyango lwexesha elifutshane nge-TNF? Umchasi.54 Unyango olwenzelwe umntu lunokubandakanya ukubekwa esweni kwe-biomarker expression ngexesha lonyango ukwazisa utshintsho olunokwenzeka, ubude bonyango oluqhubekayo olufunekayo okanye ukufumanisa ukumakisha kwangoko kokuphinda ubuye.

Iithagethi zonyango lweNew

Kukho inani elikhulu lonyango olunokuthi lusebenze kuxinzelelo, olungakhange luhlolwe ngokwaneleyo, kubandakanya inoveli okanye ungenelelo oluphindaphindiweyo kwezinye iindlela zonyango. Ezinye zeethagethi ezaziwa kakhulu bezikumayeza achasene nokuvuvukala anje nge-celecoxib (kunye nezinye i-cyclooxygenase-2 inhibitors), i-TNF? abachasene ne-etanercept kunye ne-infliximab, minocycline okanye i-aspirin. Oku kubonakala kuthembisa.178 I-Antiglucocorticoid compounds, kubandakanya i-ketoconazole179 kunye ne-metyrapone, i-180 iphandwe ngoxinzelelo, kodwa bobabini banezinto ezisilelayo kwiprofayili yecala labo kunye nokubakho kweklinikhi ye-metyrapone akuqinisekanga. I-Mifepristone181 kunye ne-corticosteroids fludrocortisone kunye ne-spironolactone, i-182 kunye ne-dexamethasone kunye ne-hydrocortisone183 zinokusebenza ngokunyanga uxinzelelo kwixesha elifutshane. Ukujolisa ekujongeni i-glutamate N-methyl-d-aspartate receptor antagonists, kubandakanya ketamine, inokubonisa unyango olusebenzayo kuxinzelelo.184 Omega-3 polyunsaturated fatty acids impembelelo kwimisebenzi yokuvuvukala kunye ne-metabolic kwaye zibonakala zibonisa ukusebenza kokudakumba.185 Kungenzeka ukuba i-statins baneziphumo zokulwa noxinzelelo186 ngeendlela ezifanelekileyo ze-neurobiological.187

Ngale ndlela, iziphumo ze-biochemical ze-anti-depressants (jonga icandelo le- Medication ) zisetyenziselwe izibonelelo zeklinikhi kwezinye iindlela: ngakumbi i-gastroenterological, neurologic kunye neempawu ezingacacanga zokugula.188 Iziphumo ezichasayo ezichasayo zinokubonisa inxenye yendlela ezi zibonelelo. I-lithium ikwacetyisiwe ukuba inciphise ukuvuvukala, ngokunzulu ngokusebenzisa i-glycogen synthase kinase-3 pathways.189 Ukugxila kwezi ziphumo kunokungqina ukuba kunolwazi ngesiginitsha yoxinzelelo lwe-biomarker kwaye, emva koko, ii-biomarkers zinokumela abarhwebi abamiselweyo kuphuhliso lweziyobisi.

Insight of Dr. Alex Jimenez

Ukudandatheka kukuphazamiseka kwempilo yengqondo ebonakaliswe yimpawu ezinzima ezichaphazela isimo sengqondo, kuquka ukulahlekelwa ngumdla kwimisebenzi. Uphando olutshanje, nangona kunjalo, lufumene ukuba kunokwenzeka ukuba uhlolisise ukudandatheka usebenzisa okungaphezulu nje kweempawu zokuziphatha zesigulane. Ngokwabaphandi, ukufumanisa i-biomarkers efumanekayo efumanekayo ekwazi ukuchonga ngokucacileyo ukuxinezeleka kuyisisiseko ekuphuculeni impilo nempilo yonke. Ngokomzekelo, iziphumo zeklinikhi zibonisa ukuba abantu abaneengxaki ezinkulu zokudakumba, okanye i-MDD, banamazinga aphantsi e-acetyl-L-carnitine, okanye i-LAC, egazini labo kunezilawuli eziphilileyo. Ekugqibeleni, ukusungula izixhobo zokudakumba kunokusinceda ukukhetha ukuba ngubani osemngciphekweni wokuphuhliswa kwengxaki kwakunye nokunceda abaqeqeshi bezempilo ukuba banqume ukhetho olungcono lwegulane kwisigulane esicinezelekileyo.

isiphelo

Uncwadi lubonisa ukuba malunga neyesibini kwisigidi sezigulane ezinexinzelelo azikwazi ukufumana ukuxolelwa kwonyango lokuqala kwaye ukuba amathuba okungahambisani nenyuka ayenyuka kunye nenani lonyango olwenziwe. Ukubonelela ngeempembelelo ezingenzi kakuhle kunemiphumo emihle kwiindleko zomntu ngamnye kunye nentlalo, kuquka ukucinezeleka okuqhubekayo kunye nentlalo embi, ingozi yokuzibulala, ukulahlekelwa kwemveliso kunye nokuchithwa kwemithombo yolondolozo lwempilo. Uninzi lweencwadi ekudandathelweyo lubonisa inani elininzi lezinto eziphilayo ezinokukwazi ukuphucula unyango kubantu abanexinzelelo. Ukongeza kwiimpawu ze-neurotransmitter ne-neuroendocrine eziye zaxhomekeke kwizifundo eziqhelekileyo kwiminyaka emininzi, ukuqonda kwangoku kubonakalisa impendulo evuthayo (kunye ne-immune system ngokubanzi ngokubanzi), imiba yokuxilonga kunye nokukhula njengoko kubandakanyekile ekudakaleni. Nangona kunjalo, ubungqina obugqithisileyo bubonisa ukuba kukho imingeni emingeni efunekayo yokujongana nayo ngaphambi kokuba uphando lwe-biomarker lusetyenziswe ukwenzela ukuphucula ulawulo kunye nokukhathalela abantu abanexinzelelo. Ngenxa yobunzima beenkqubo ze-biologic, iimviwo zangexesha elide zohlu lwabamakishi kwiisampuli ezinkulu zinenzuzo eninzi ekufumaneni ukusebenzisana phakathi kwamazwe e-biological and psychological people. Ukuphucula ukulinganisa kweempawu ze-neurobiological kunye nemilinganiselo yesikliniki yokudakumba kunokunceda ukuqonda ngakumbi. Olu hlalutyo lubalaselisa ukubaluleka kokuhlola izinto ezinokuthi ziguqulwe (ezifana nokugula, ubudala, ukuqonda kunye namayeza) ekukhothozeni ukuqonda okuhambelanayo ne-biology yokudandatheka kunye neendlela zokuchaswa ngonyango. Kungenzeka ukuba ezinye iimpawu ziza kubonisa isithembiso esithile sokuxela impendulo yonyango okanye ukuchaswa kwonyango oluthile kwicandelo lezigulane, kwaye ukulinganisa okufanayo ngokuchanekileyo kwedatha kunye neengqondo kunokwandisa ukukwazi ukubona abantu abasemngciphekweni kwiziphumo zonyango ezingalunganga. Ukuseka iphaneli ye-biomarker inefuthe ekuphuculeni ukuchaneka kokuxilonga kunye nokuhlaselwa, kunye nokunyangwa kwamanye amayeza kwindlela yokuqala yokuguquka nokugula nokuphuhlisa iithagethi zonyango. Ezi mpembelelo zingagcinwa kwiinqununu zezigulane ezidandathekileyo. Iindlela eziya kulezi zizathu zizalisekisa izicwangciso zophando zakutshanje zokudibanisa ama-syndromes ekliniki ngokuthe ngqo kwi-substrates ye-neurobiological.6 Ngaphandle kokunciphisa u-heterogeneity, oku kunokuncedisa ukutshintshela ekuhambelaneni kokuhlonipha phakathi kwempilo yengqondo nengqondo. Kucacile ukuba nangona kudingekile umsebenzi omkhulu, ukusekwa kobudlelwane phakathi kwezinto ezichaphazelekayo kunye neengxaki zokudandatheka kunempembelelo enkulu ekunciphiseni umthwalo wokudakumba kwinqanaba lomntu kunye noluntu.

Imibulelo

Le ngxelo imele uphando oluzimeleyo oluxhaswa liZiko leSizwe loPhando ngezeMpilo (i-NIHR) kwiZiko loPhando ngezoBomi eMzantsi London naseMaudsley NHS Foundation Trust naseKing s College yaseLondon. Iimbono ezichaziweyo zezababhali kwaye ayisiyiyo leyo ye-NHS, i-NIHR okanye iSebe lezeMpilo.

Imihlathi

Ukwazisa. I-AHY ineminyaka eyi-3 yokugqibela eyamkela ukuhlonipha ngokuthetha evela kwi-Astra Zeneca (AZ), uLundbeck, uEli Lilly, i-Sunovion; ukuhlonipha ukubonisana no-Allergan, uLivanova kunye noLundbeck, i-Sunovion, iJanssen; kunye nenkxaso yesibonelelo segranti evela kwiijensi zenkxaso-mali zeJanssen ne-UK (iNIHR, MRC, Wellcome Trust). I-AJC ineminyaka eyi-3 yokugqibela ifumene imbeko ngokuthetha esuka kwi-Astra Zeneca (AZ), i-honoraria yokubonisana no-Allergan, uLivananova kunye neLundbeck, kunye nenkxaso-mali yokuphanda evela kwi-Lundbeck nase-UK agcini-mali (NIHR, MRC, Wellcome Trust).

Ababhali babika akukho nanye imibango yomdla kulo msebenzi.

Ukuququmbela,Ngelixa izifundo ezininzi zophando zifumene amakhulu ezinto eziphilayo zokudakumba, azikho zininzi eziye zadlala indima yazo kwisifo sokudakumba okanye ukuba ulwazi lwebhayoloji lunokusetyenziswa njani ukuphucula isifo, unyango kunye nokuxela. Nangona kunjalo, inqaku elingentla liphonononge uncwadi olukhoyo kwii-biomarkers ezichaphazelekayo ngexesha lezinye iinkqubo kwaye zithelekisa iziphumo zeklinikhi kunye nezoxinzelelo. Ngapha koko, ukufumanisa okutsha kwii-biomarkers zoxinzelelo kunokunceda ekuchongeni ngcono uxinzelelo ukuze kulandelwe unyango olungcono. Ulwazi olukhankanyiweyo kwiZiko leSizwe loLwazi lweBiotechnology (NCBI) .Ububanzi bolwazi lwethu bunqunyelwe kwi-chiropractic kunye nakulimala komqolo kunye neemeko. Ukuxoxa ngomxholo, nceda ukhululeke ukubuza uGqirha Jimenez okanye unxibelelane nathi ku915-850-0900 .

Ikhutshwe nguDkt. Alex Jimenez

Imixholo eyongezelelweyo: Ubunzima bokubuyisela

Umqolo obuhlungu enye yezona zizathu ezibangeleko zokukhubazeka kunye neentsuku eziphosakeleyo emhlabeni wonke. Njengokuba kunjalo, iintlungu zenziwa emva kweyona sibini isizathu esivakalayo sokutyelela iofisi yee-dkt. Ngokumalunga neepesenti ze-80 zabemi ziya kuba nolunye uhlobo lweentlungu zentlungu ubuncinane kanye kanye ebomini babo. Umgudu uyisakhiwo esiyinkimbinkimbi esakhiwa ngamathambo, amajoyina, iigaments kunye nezihlunu, phakathi kwezinye iifomthi ezithambileyo. Ngenxa yoko, ukulimala kunye / okanye iimeko ezihlaziyiweyo, ezifana disni, ekugqibeleni unokukhokelela kwiimpawu zentlungu. Ukulimala kwezemidlalo okanye ukulimala kwengozi yeemoto ngokuqhelekileyo kubangelwa yintlungu yokubuhlungu, kodwa ngamanye amaxesha ukuhamba kwezinto ezilula kunokuba neziphumo ezibuhlungu. Ngethamsanqa, ezinye iindlela zokhathalela unyango, ezifana nokunyamekelwa kwe-chiropractic, kunokunceda ukubuyisela intlungu emva kokusetyenziswa kwemilenze kunye nokunyanzeliswa kwemigaqo, ekugqibeleni ukuphucula intlungu.

ISIHLOKO ESIBALULEKILEYO: Ulawulo oluPhantsi lwePain Pain

IINKCUKACHA NGOKUGQITHISILEYO: UKONGEZA KWEZINTLOKO: PainUbuhlungu obungapheliyo kunye nonyango