Kushungurudzika ndechimwe chezvinhu zvakajairika zvehutano mupfungwa muUnited States. Tsvakurudzo yemazuva ano inoratidza kuti kuora mwoyo kunoguma nekubatanidzwa kwezvisikwa, zvezvisikwa, zvezvisikwa, uye zvepfungwa. Kushungurudzika ndechirwere chikuru chepfungwa chepasi rose nehuwandu hwehupfumi uye hwepfungwa munharaunda. Nenzira yakanaka, kuora mwoyo, kunyange nematambudziko akaoma, inogona kurapwa. Yekare iyo mushonga unogona kutanga, unonyanya kuitika.

Somugumisiro, zvisinei, pane chido chezvikwata zvinokonzera mazai izvo zvichabatsira mukuvandudza kufungidzirwa kuitira kuti kuwedzeredza mishonga uye / kana mishonga yekuwanikwa kwemishonga kune mumwe murwere ane chirwere. Izvi ndizvo zvinangwa, zvinoputika zvepanyama zviratidzo zvinogona kushandiswa kufanotaura kuti zvinogona kutanga kana kuvapo kwekuora mwoyo, zvakananga maererano nekuoma kana zviratidzo, kuratidzira kufanotaura uye kufungidzira kana kutarisa zvinopindira pakugadzirisa kurapa. Chinangwa chehurukuro inotevera ndechekuratidza manzwisisiro emangwana, zvinetso zvemazuva ano uye tarisiro yeramangwana pamusoro pekuwanikwa kwezvinhu zvakasiyana biomarkers nokuda kwokuora mwoyo uye kuti izvi zvinogona kubatsira sei kuwedzera kuongororwa uye kurapwa.

Biomarkers for Depression: Recent Insights, Current Challenges and Future Future Expectations

ngovepo

Chirongwa chekutsvakurudza chakaita kuti mazana evanhu vaite biomarkers ekuisa dambudziko, asi vasati vajekesa zvizere mabasa avo muhutano hwekuora mwoyo kana kuti kusimbisa izvo zvisingawanzogadziriswa nevarwere uye kuti ruzivo rwezve biologic rinogona kushandiswa sei kusimbisa kuongororwa, kurapwa uye kufungidzira. Kushayikwa kwekufambira mberi kunokonzerwa nehutano uye hutano hwekuora mwoyo, pamwe chete nehutano hwehutano hwakanaka mukati mezvinyorwa zvekutsvakurudza uye huwandu hwakawanda hwezvinyorwa zvinogona kuita, izvo zvinowanzosiyana-siyana maererano nezvimwe zvinhu. Tinoongorora mabhuku anowanikwa, anoratidza kuti zviratidzo zvinobatanidzwa mukuvhiringidza, neurotrophic nekugadzirisa zvirongwa, pamwe neurotransmitter uye neuroendocrine system components, zvinomiririra vanhu vanovimbisa. Izvo zvinogona kuyerwa kuburikidza nemagetsi uye epigenetic, transcriptomic uye proteomic, metabolomic uye neuroimaging. Kushandiswa kwevanoverengeka uye nzira dzekutsvakurudza dzakagadziriswa zvino zvinodiwa kuongorora kana, uye izvo, zvigadziriswa zvinogona kushandiswa kufanotaura kusarudzwa kwehutano, kuronga varwere kune zvimwe zvirwere uye kugadzira zvinangwa zvekugadzirisa matsva. Tinopedzisa kuti kune chivimbiso chikuru chekuderedza mutoro wekuora mwoyo kuburikidza nekuwedzera kuwedzera uye kuwedza idzi zvingororo.

Keywords: kushungurudzika kwepfungwa, kuora mwoyo kukuru, kurwisana, kupindura kurapa, stratification, mishonga yemunhu

ziviso

Matambudziko muMental Health uye Matambudziko eMafungiro

Kunyange zvazvo mishonga yepfungwa ine mutoro unorwara nehutano mukuru kudarika chero imwe yerumwe rutivi rwehutano hwehutano, 1 kusakosha kwekuremekedza kuchiri kuoneka pakati pehutano hwehutano uye hwepfungwa munzvimbo dzakawanda dzinosanganisira kushandiswa kwekubhadhara mari2 nekudhindwa.3 Pakati penhamo iyo hutano hwepfungwa hunotarisana nokushaiwa yekubvumirana kwakasiyana-siyana, kuongororwa uye kurapwa kunobva mukusanzwisisa kusakwana kwematambudziko anokonzera matambudziko aya. Izvi zvinonyatsooneka mumatambudziko emafungiro evanhu, boka rinosanganisira mutoro mumwe chete mukuru mune utano hwepfungwa.3 Chirwere chinowanzoitika kare, chirwere chikuru chekuora mwoyo (MDD), chirwere chakakomba, chinopesana uye umo kusvika ku60% yevarwere vanogona kuitika imwe yero yekurapa kwekurapa iyo inowedzera uye inotambudza zviitiko zvepfungwa.4 Nokusawirirana kwepfungwa, uye munharaunda yakawanda yehutano hwepfungwa, kuwanikwa kwehutano kunogona kuvandudzwa nekuwanikwa kwemasimba akaoma, akaenzana mukati me (uye nepamusoro) kuongororwa maitiro, nekurapa inogona kukonzerwa. Mukuziva kweizvi, maitiro epasi rose ekuderedza mabasa anoshanda pasi zvino ari kuenderera mberi, akadai sekutsvakurudza nzvimbo yekutsvakurudza.5 Zvakave zvichitarisirwa kuti biologic markers ndivo vanonyanya kutsvaga kwekutengesa pfungwa dzepfungwa.6

Kuvandudza Kupindura Kurapa Kwekuora Mwoyo

Pasinei nehuwandu hwehutano hwehutano hwekuderedza kukuru, asi chete chikamu chetatu chevarwere vane MDD vanobvuma kuregererwa kunyange kana vakagamuchira zvakakwana antidipressant kurapa maererano nekubatana kwemazano uye kushandisa kushandiswa-kutarisirwa, uye mitero yekurapa mishonga inoonekwa seinowa nehutano hutsva hupi .7 Uyezve, kurapa kusinganzwisisiki (TRD) kunobatanidza nekuwedzera kwehutachiona hwehutano, kufa, kushaya muviri uye kuitika kwenguva refu kana zviitiko zvisingagumi kwenguva refu.8,9 Nokudaro, kuwana kuvandudzwa kwehutano hwekurapa pane chero chikwata chechipatara kunogona kubatsira zvakakwana pamigumisiro yese mukuora mwoyo. Pasinei nemutoro mukuru wakabatwa neTrD, kutsvakurudza munharaunda iyi kwave kwakanyanya. Tsanangudzo dzeTDD hadzina kuenzaniswa, pasinei nekuedza kwekare: 4 imwe nzira inoda chirwere chimwe chete chekurapa chinokundikana kuwana 50% zviratidzo zvishoma kuderedza (kubva pane chirevo chakavhiringidzika chekuora mwoyo zvakanyanya), apo vamwe vanoda kushaikwa kwekuregererwa kwakakwana kana kusaremekedza kune zviviri zvakakwana zvinokonzerwa nevanorambidzana nehutachiona hwezvikwata zvakasiyana mukati mechiitiko chinofanirwa kuonekwa se TRD.4,10 Uyezve, kuenzanisa uye kufanotaura kwekushorwa kwekurapa kunovandudzwa nekuwedzera kemikirini inokosha yehutano hwakanyanya uye huwandu hwehuwandu hwehutano hwakakundikana.9,11 Kunyange zvakadaro, kusawirirana mune tsanangudzo kunoshandura kutsanangura mabhuku ekutsvakurudza paTDD basa rakaoma zvikuru.

Kuti uwedzere kugadzirisa mhinduro kumarapirwo, zviri pachena kuti zvinobatsira kutsvaga hunhu hunotyisa hunokonzerwa nekusaremekedza. Zvimwe zvirevo zvekare zveTDD zvakave zvichiratidzwa, kusanganisira kusava nekuregererwa kwakakwana mushure mezviitiko zvekare, kunyanya kuzvidya mwoyo, kuzviuraya uye kutanga kwekuora mwoyo, pamwe nehuunhu (kunyanya kudengenyeka kwakaderera, kupiwa mubayiro kwakaderera uye kuwedzerwa kwehutano nehutachiona huzhinji.12 Izvi zvakawanikwa zvinotsigirwa nekuongororwa kushandiswa kwehupupuriro humwechete kune pharmacologic13 uye mupfungwa_14 kurapa kwekuora mwoyo. Kuora mwoyo uye kugona-maitiro ekurapa kunoratidza zvakaenzana nekubudirira, 15 asi nekuda kwekusiyana kwezviito zvekuita zvinogona kutarisirwa kuti zvive nehutano hwakasiyana hwekupindura. Nekutanga-kushungurudzika kwehupenyu kwenguva refu kwave kuchibatanidza nehurombo hwezvipatara zvekugadzirisa uye kuderedza mhinduro dzekurapa, zviratidzo zve 16 kare zvinoratidza kuti vanhu vane nhoroondo yekushungurudzika kwevana vanogona kupindura zviri nani kune zvepfungwa pane zvemapirmacologic therapies.17 Pasinei neizvi, kusava nechokwadi kunowanikwa uye kuduku kwevanhu kana stratification yekurapa yasvika kuchipatara tsika.18

Kuongorora uku kunonyanya kuratidza huchapupu hunotsigira kushandiswa kwezvinhu zvinoshandiswa nehutachiona sezvinogona kubatsira zvipatara zvishandiso kusimudzira kurapwa kwehutano hwekuora mwoyo.

Biomarkers: Maitiro uye Sources

Biomarkers inopa chinangwa chekujekesa kufanirwa kwekupindura kune zvakasiyana-siyana.19 Uchapupu huripo hunoratidza kuti zviratidzo zvinoratidzira basa rekuvhiringidza, neurotransmitter, neurotrophic, neuroendocrine uye masvomeri matsuro anogona kukwanisa kufanotaura nezvehutano hwepfungwa nehutano mumunhu iye zvino akaora mwoyo , asi kune zvakawanda zvisingabvumirano pakati pekuwana.20 Mukugadziriswa uku, tinoisa pfungwa pazvinhu izvi zvishanu zvebiologic.

Kuti uwane kunzwisiswa kwakazara kwema molecular nzira uye mupiro wavo mumatambudziko epfungwa, izvozvi zvinoonekwa sezvakakosha kuyera akawanda biologic levels , mune izvo zvinowanzozivikanwa kunzi nzira ye omics .21 Mufananidzo 1 inopa kuratidzwa kweakasiyana biologic mazinga apo imwe neimwe yemaitiro mashanu anogona kuongororwa, uye izvo zvingangove zvitubu zvemamaki panogona kuitwa ongororo idzi. Nekudaro, cherekedza kuti nepo sisitimu yega yega ichiongororwa padanho rega rega, iwo masosi akakwana ekuyera anonyatsosiyana padanho rega rega. Semuenzaniso, neuroimaging inopa chikuva chekutarisa zvisina kunangana kwehurongwa hwehuropi kana mashandiro, nepo bvunzo dzeprotein muropa dzinoongorora mamaki. Transcriptomics22 uye metabolomics23 iri kuramba ichizivikanwa, ichipa kuongororwa kweanogona kunge ari makuru mamaki, uye iyo Human Microbiome Project yave kuyedza kuona tupukanana tese nemaumbirwo aro mukati mevanhu. ; semuenzaniso, mahormone akadai secortisol anogona kuyedzwa muhudzi kana nzara (zvichipa chiratidzo chisingaperi) kana ziya (kupa chiyero chinoramba chichienderera), 24 pamwe neropa, cerebrospinal fluid, weti nemate.

Tichifunga huwandu hwekuisa masosi, mazinga uye masisitimu anobatanidzwa mukushushikana, hazvishamise kuti chiyero chema biomarkers ane simba rekushandura rakakura. Kunyanya, kana kufambidzana pakati pezviratidzo kuchitariswa, zvingangodaro zvisingaite kuti kuongorora mabiomarker ega uri wega kunounza zviwanikwa zvine michero yekuvandudza kiriniki maitiro. Schmidt et al26 vakakurudzira kushandiswa kwe biomarker mapaneru uye, zvichidaro, Brand et al27 yakadonhedza dhizaini pane inoenderana neamberi kliniki uye humbowo hwepamberi hwe MDD, ichiratidza 16 strong biomarker zvinangwa, chimwe nechimwe chacho chisingawanzo kuve chiratidzo chimwe chete. Dzinosanganisira yakaderedzwa grey nyaya vhoriyamu (mune hippocampal, prefrontal cortex uye basal ganglia matunhu), circadian kutenderera shanduko, hypercortisolism uye zvimwe zvinomiririra hypothalamic pituitary adrenal (HPA) axis hyperactivation, thyroid dysfunction, yakadzora dopamine, noradrenaline kana 5-hydroxyindoleacetic acid , yakawedzera glutamate, yakawedzera superoxide dismutase uye lipid peroxidation, yakagadziriswa cyclic adenosine 3?, 5? -monophosphate uye mitogen-activated protein kinase nzira nzira, yakawedzera proinfigueatory cytokines, shanduko ku tryptophan, kynurenine, insulin uye chaiwo magene polymorphisms. Aya mamaki haana kubvumiranwa nekubvumirana uye anogona kuyerwa nenzira dzakasiyana; zviri pachena kuti rakanangidzirwa uye rakarongeka basa rinofanira kugadzirisa iri rakakura basa kuratidza kwavo kiriniki kubatsirwa

Zvimwe zveNyaya iyi

Sekuongorora kukuru nemaune, nyaya ino inotsvaga kutsvaga zvidikanwi zvidikanwi zvekutsvakurudza kwezvinyorwa mukudengenyeka uye kuti zviyero zvakadini zvinoshandiswa pakugadzirisa zvinyorwa zvekuvandudza kupindura mishonga. Tinotanga nekukurukurirana zvinhu zvakakosha uye zvinonakidza mumunda uno uye tinotaurira muverengi kune mamwe maongorori akajeka ane chokuita neakakosha uye kuenzanisa. Tinotarisa matambudziko aripo iye zvino anotarisana nechiedza cheuchapupu, pamwe chete nezvido zvekuderedza mutoro wekuora mwoyo. Pakupedzisira, tinotarisana mberi nenzira dzinokosha dzekutsvakurudza nzira dzekusangana nematambudziko anowano uye zvazvinoreva pakugadzirisa kliniki.

Recent Insights

Kutsvaga kwezvinhu zvinogadziriswa kuchipatara kune vanhu vane kuora mwoyo kwakaita kuti pave nekutsvakurudza kwakawanda pamusoro pehafu yekupedzisira yezana remakore. Mishonga inowanzoshandiswa yakakonzerwa kubva mu monoamine nheyo yekuora mwoyo; mushure mezvo, neuroendocrine hypotheses yakawana kunyanya kukuru. Mumakore achangobva kupfuura, tsvakurudzo yakawanda kwazvo yakapoteredza kuvhiringidzika kwepfungwa yekuora mwoyo. Zvisinei, nhamba huru yezvinyorwa zvidzidzo zvakakosha zvakatarira kune dzimwe nhanho shanu; ona Tafura 1 nechezasi kuti uwane zvinyorwa zvenguva ichangopfuura pane zvigadzirwa zvebiomarker. Kunyange zvazvo ichienzaniswa pamakwikwi mazhinji, mapuroteni akawanikwa neropa akaongororwa zvakanyanya uye anopa chitubu chezvinyorwa zvinoshandiswa zvakanaka, zvinodhura uye zvinogona kunge zviri pedyo nekukwanisa kushandura kune mamwe mabviro; nokudaro, mamwe mashoko anopiwa kune zvisikwa zvinopararira muropa.

Mune ongororo yakarongeka yazvino, Jani et al20 akaongorora mhedzisiro yeropa-based biomarkers yekushungurudzika mukubatana nemhedzisiro yekurapa. Yezvidzidzo gumi nezvina chete zvaisanganisira (yakatsvaga kusvika kutanga kwa14), makumi matatu nematanhatu emagetsi akadzidziswa ayo gumi nemaviri aive akakosha kufungidzira kweanopindura kana epanyama mhinduro indices mune imwe ongororo. Izvo zvinoonekwa sezvingangomiririra njodzi dzekusavimbika dzaisanganisira mapuroteni ekuzvimba: low interleukin (IL) -2013p36, chiyero che lymphocyte kusvika monocyte kuverenga; neuroendocrine mamaki (dexamethasone kusadzora kwecortisol, yakakwira kutenderera cortisol, yakadzora thyroid-inokurudzira mahormone); zviratidzo zveeurotransmitter (yakaderera serotonin uye noradrenaline); metabolic (yakaderera yakakwira-density lipoprotein cholesterol) uye neurotrophic zvinhu (yakaderedzwa S12 calcium-inosunga protein B). Kupfuurirazve kune izvi, kumwe kuongorora kwakamhan'arira pamusoro pemasangano ari pakati pezvakawedzera biomarker uye mhedzisiro yekurapa.12-70 Tsananguro pfupi yemaputi ekuisa muhurongwa hwese yakatsanangurwa muzvikamu zvinotevera uye muTafura 100.

Kutsvaira Kunotsvaga Mukudengenyeka

Sezvo bepa raSmith's seminal rinotsanangura macrophage hypothesis, 31 iri rakasimbiswa mabhuku rakawana kuwanda kwematanho eproinfigueatory mamaki mune vakaora mwoyo varwere, ayo akaongororwa zvakawandisa.32-37 Mapuroteni gumi nemaviri ekuzvimba akaongororwa mune meta-ongororo achienzanisa akaora mwoyo uye ane hutano kudzora vanhu. 38-43

IL-6 (P <0.001 mune meta-ongororo dzese; 31 zvidzidzo zvinosanganisirwa) uye CRP (P <0.001; 20 zvidzidzo) zvinowoneka kazhinji uye zvakavimbika zvakasimudzwa mukushushikana. 40 Yakakwidzwa bundu necrosis factor alpha (TNF?) Yakaonekwa muzvidzidzo zvekutanga. (P <0.001), 38 asi hukuru hwakasiyana hwakapa izvi zvisingaenzanisike pakuverenga ongororo dzichangoburwa (31 zvidzidzo) .40 IL-1? inotonyanya kusanganisika nekushushikana, ine meta-ongororo inoratidza huwandu hwepamusoro mukushushikana (P = 0.03), 41 mazinga epamusoro chete muzvidzidzo zveEuropean42 kana pasina mutsauko kubva kumatongero. 40 Kunyangwe izvi, chinyorwa chazvino chakaratidza zvimwe zvinoreva kududzira kune IL- 1?, 44 inotsigirwa neakanyanya kukosha mhedzisiro yeiyo yakakwira IL-1? ribonucleic acid kufungidzira kusarongeka kupindura kune anodzvinyirira; makumi mashanu nezvimwe zvakawanikwa pamusoro zvine chekuita nekutenderera kweropa-cytokines. Iyo chemokine monocyte chemoattractant protein-45 yakaratidza kukwidziridzwa muvatori vechikamu vakaora mwoyo mune imwe meta-ongororo. 1 Interleukins IL-39, IL-2, IL-4, IL-8 uye interferon gamma yanga isina kunyanya kusiyana pakati pevarwere vane kushushikana nekutonga pane meta-analytic level, asi zvakadaro zvakadaro yakaratidza kugona maererano nekuchinja nekurapwa: IL-10 yakanzi yakakwidziridzwa kune avo vane kushushikana kwakanyanya tarisiro uye muchinjikwa-chikamu, 8 akasiyana maitiro ekuchinja muI IL-46 uye interferon gamma panguva yekurapa. zvakaitika pakati pevapinduri vekutanga vachipesana nevasina kupindura, 10 nepo IL-47 uye IL-4 zvadzikira maererano nechiratidzo kuregererwa.2 Mune meta-ongororo, kuderera kudiki pamwe chete nekurapwa kwakaratidzirwa IL-48, IL-6? IL- 1 uye CRP.10 Kuwedzera, TNF? zvinogona kungodzora nemushonga mune vanopindura, uye iyo inoumbwa nemaki index inogona kuratidza kuwedzera kuzvimba muvarwere vasingazopindure kurapwa.43,49,50 Zvinokosha, zvisinei, kuti ingangoita rese tsvagurudzo inoongorora kupisa mapuroteni uye mhinduro yekurapa inoshandisa pharmacologic kurapwa miedzo. . Nekudaro, angangoita kumwe kuchinjika kwekuchinja panguva yekurapa ingangoitika kunokonzerwa neanodzvinyirira. Izvo chaizvo zvinokonzeresa mhedzisiro yezvakasiyana antidepressants zvisati zvasimbiswa, asi humbowo hunoshandisa CRP mazinga hunoratidza vanhu vanopindura zvakasiyana kune chaiwo marapiro anoenderana nekutanga kuzvimba: Harley et al43 yakashuma kukwidziridzwa kwepamberi kweCRP kufanotaura kusanzwisisika kupindura kune kurapwa kwepfungwa (kuziva -kuzvibata kana kushamwaridzana psychotherapy), asi mhinduro yakanaka kune nortriptyline kana fluoxetine; Uher et al51 vakadzokorora kutsva uku kwe nortriptyline uye vakaratidza mhedzisiro inopesana neye escitalopram. Mukupesana, Chang et al52 vakawana yakakwira CRP mune vekutanga vanopindura fluoxetine kana venlafaxine kupfuura vasinga pindiri. Uyezve, varwere vane TRD uye yakakwira CRP vakapindura zvirinani kune iyo TNF? antagonist infliximab pane avo vane mazinga ari akajairwa renji.53

Pamwe chete, humwe uchapupu hunoratidza kuti kunyange kana kutarisa zvinhu zvakadai semuviri mass index (BMI) nezera, mhinduro dzinoputika dzinoita sokuti inenge inenge chikamu chetatu chevarwere vane dambudziko.55,56 Mamiriro ekuvhiringidza, zvisinei, akaoma zvikuru, uye kune dzakawanda zvinomirira zvikamu zvakasiyana-siyana zvegadziriro ino. Munguva pfupi yapfuura, mamwe mabhuku e cytokines uye chemokines ave achipa uchapupu hwekusava nehupenyu mukuora mwoyo. Izvi zvinosanganisira: macrophage inhibitory protein 1a, IL-1a, IL-7, IL-12p70, IL-13, IL-15, eotaxin, granulocyte macrophage colony-stimulating factor, 57 IL-5,58 IL-16,59 IL-17,60 monocyte chemoattractant protein -4,61 thymus uye kushandiswa-kutungamirirwa chemokine, 62 eotaxin-3, TNFb, 63 interferon-induced protein 10,64 serum amyloid A, 65 inogadziriswa inopellular adhesion molecules66 uye yakasanganiswa vascular cell adhesion molecule 1.67

Kukura Kwezvinhu Kuwana Mukuderera

Mukuona kwezvinokosha zvekuti kwete-neurotrophic kukura zvinhu (zvakadai sezvo zvine chokuita neangiogenesis), tinoreva neurogenic biomarkers pasi pechirevo chakazara chekukura kwezvinhu.

Brain-yakatorwa neurotrophic factor (BDNF) ndiyo inonyanya kudzidza nezve izvi. Meta-ongororo dzinoverengeka dzinoratidza kuderedzwa kweprotein yeBDNF muserum, inoita kunge ichiwedzera pamwe neanodzvinyirira kurapwa.68-71 Kwazvino kuongororwa uku kunoratidza kuti kudzikiswa kweBDNF kunonyanya kutaurwa muvarwere vakaora mwoyo zvakanyanya, asi kuti mishonga yekudzvinyirira inoita kunge wedzera mazinga eprotini aya kunyangwe mukusavapo kwekuregererwa kwekiriniki. 70 proBDNF yakadzidzwa zvishoma kupfuura fomu yakakura yeBDNF, asi iwo maviri anoita kunge akasiyana mushe (maererano nemhedzisiro yavo pa tyrosine receptor kinase B receptors) uye zvichangoburwa humbowo hunoratidza kuti nepo BDNF yakakura inogona kudzikiswa mukushushikana, proBDNF inogona kuburitswa.72 Tsinga yekukura chinhu chinoongororwa pariperi zvakare yakanzi yakaderera mukudzvinyirira pane mukutonga mune meta-ongororo, asi haigone kuchinjwa nemushonga unodzvinyirira kunyangwe iri kunyanya kuderedzwa kune varwere vane zvakanyanya kushushikana.73 Zvakafanana zvakawanikwa zvakataurwa mune meta-kuongororwa kweiyo glial cellmutsara-wakatorwa neurotrophic factor.74

Vascular endothelial grow factor (VEGF) ine basa mukusimudzira angiogenesis uye neurogenesis pamwe nedzimwe nhengo dzemhuri yeEGEGF (semuenzaniso, VEGF-C, VEGF-D) uye ine vimbiso yekushushikana .75 Zvisinei nehumwe humbowo husingaenderane, meta-ongororo mbiri munguva pfupi yapfuura yakaratidza kukwidziridzwa kweVEGF muropa revarwere vane kushushikana kana ichienzaniswa neanodzora (pane gumi nematanhatu zvidzidzo; P <16) .0.001 Zvisinei, yakaderera VEGF yakaonekwa muTRD76,77 uye nhanho dzakakwirira dzakafanotaura kusapindura kurapwa kwekudzvinyirira.78 Hazvinzwisisike nei huwandu hweVEGF protein hungakwidziridzwa, asi pamwe hunogona kukonzereswa nehutachiona uye / kana kuwedzera muropa brain chipingamupinyi kukwana mumatunhu akashungurudzika anokonzeresa kutaura mucerebrospinal fluid.79 Hukama huripo pakati peVEGF nemhinduro yekurapa hauna kujeka ; ongororo ichangoburwa haina kuwana hukama pakati peimwe serum VEGF kana BDNF ine mhinduro kana kushushikana kwekushushikana, kunyangwe ichiderera pamwe chete neanodzvinyirira kurapwa.80 Insulin-senge kukura chinhu-81 chimwe chinhu chinowedzera neurogenic mabasa anogona kuwedzerwa mukuora mwoyo, kuratidza kusaenzana mukati maitiro eurotrophic.1 Basic fibroblast grow factor (kana FGF-82,83) inhengo yeiyo fibroblast yekukura mhuri uye inoonekwa yakakwira mukuora mwoyo kupfuura mapoka ekudzora.2 Zvisinei, mishumo haina kuenderana; mumwe akawana kuti protein iyi yaive yakaderera mu MDD pane kudzoreredza zvine hutano, asi yakadzikira mberi pamwe neanodzvinyirira kurapwa.84

Zvimwe zvinokura izvo zvisina kuongororwa zvakakwana mukudzvinyirira zvinosanganisira tyrosine kinase 2 uye inogadziriswa fms-sa tyrosine kinase-1 (inonziwo sVEGFR-1) iyo inobatanidza neVEGF, uye tyrosine kinase receptors (iyo inosunga BDNF) inogona kuvharwa mune kuora mwoyo.86 Placental kukura chimwe chinhu chiriwo chikamu chemhuri yeVEGF, asi hachina kuongororwa mumasikirwo akaodzwa mwoyo ku ruzivo rwedu.

Metabolic Biomarker Zviwanikwa Mukuderera

Huru biomarkers chokuita metabolic chirwere zvinosanganisira leptin inoderedza, adiponectin, ghrelin, triglycerides, mukuru arambe achirema lipoprotein (HDL), shuga, jekiseni uye albumin.87 The ushamwari pakati dzakawanda izvi uye kuora mwoyo vave akaongororwa: leptin88 uye ghrelin89 kuoneka ezasi kuora mwoyo pane kutungamira munharaunda uye inogona kukura pamwe chete nehutachiona hwehutachiona kana kuregererwa. Insulin kurwisana kunogona kuwedzera mukudzvinyirira, kunyangwe nemari shomanana.ZIMNUMX Lipid zvinyorwa, zvinosanganisira HDL-cholesterol, zvinowanzochinjwa kune varwere vakawanda vane kushushikana, kusanganisira avo vasina chirwere chinorwara, kunyange zvazvo ukama uhwu huri hwakaoma uye hunoda kujekesa zvakare.90 Kuwedzera, hyperglycemia91 uye hypoalbuminemia92 mukuora mwoyo kwakave zvataurwa mukuongorora.

Tsvagurudzo yehuwandu hwesimba metabolic nyika dziri kuramba dzichinyanya kushandisa metabolomics mapaneru emamorekuru madiki netariro yekuwana siginecha yakasimba yezvigadzirwa zvemagetsi yezvirwere zvepfungwa. Mune ongororo ichangoburwa ichishandisa yekuchenjera kwekunyepedzera modhi, seti yemetabolites inoratidza kuwedzera glucose lipid siginicha yainyanya kufungidzira nezve MDD kuongororwa, 94 inotsigira zvidzidzo zvekare .95

Neurotransmitter Zvitsva mukudengenyeka

Nepo kutariswa kwakabhadharwa kumonoamines mukushungurudzika kwakaunza kurapwa kwakabudirira, hapana makemikari akasimba eurotransmitter akawanikwa kuti awedzere kurapwa kunoenderana nesarudzo yemonamine zvinangwa zvekudzvinyirira. Razvino basa rinonongedzera kune iyo serotonin (5-hydroxytryptamine) 1A inogamuchira seinogona kukosha kune zvese kuongororwa uye kufungidzira kwekusuwa, kuchimirira maitiro matsva emageneti uye ekufungidzira.96 Kune matsva marapirwo angangoita anonongedza 5-hydroxytryptamine; semuenzaniso, kushandisa inononoka-kuburitsa manejimendi ye5-hydroxytryptophan.97 Kuwedzera kutapurirana kwedopamine kunofambidzana nemamwe maurotransmitter ekuvandudza mhedzisiro yekuziva sekuita sarudzo uye kukurudzira.98 Saizvozvowo, maurotransmitter glutamate, noradrenaline, histamine uye serotonin inogona kupindirana uye kuita sechikamu chekushushikana kwakanangana nekushushikana kwepfungwa; izvi zvinogona kudzikira 5-hydroxytryptamine kugadzirwa kuburikidza ne flooding . Ongororo ichangoburwa inoisa dzidziso iyi uye inoratidza kuti muTRD, izvi zvinogona kudzoserwa (uye 5-HT yakadzoreredzwa) kuburikidza nemultimodal kurapwa yakanangana nemaurotransmitter akawanda.99 Zvinofadza kuti, kuwedzera kweserotonin hakuwanzo kuitika pamwe chete nekurapa antidipressant mabhenefiti.100 Kunyangwe izvi , neurotransmitter metabolites senge 3-methoxy-4-hydroxyphenylglycol, yenoradrenaline, kana homovanillic acid, yedopamine, yakawanzo kuwanikwa ichiwedzera pamwe nekuderedzwa kwekushushikana nemushonga wekudzvinyirira101,102 kana iwo mashoma masosi emametabolites aya anofanotaura mhinduro iri nani SSRI kurapwa. 102,103

Neuroendocrine Zviwanikwa muDambudziko

Cortisol ndiyo inonyanya kufanana neHPA axis biomarker yave yakadzidzwa mukuora mwoyo. Kuongororwa kwakawanda kwakaratidza kuongororwa kwakasiyana-siyana kweHPA basa; kazhinji, izvi zvinoratidza kuti kuora mwoyo kunobatanidza ne hypercortisolemia uye kuti cortisol inomutsa mhinduro inowanzovharwa.104,105 Izvi zvinotsigirwa nekuongorora kwezvinoitika kwekugara kwenguva refu kwecortisol kuyerwa nemvere, kubatsirana pfungwa ye cortisol kusagadzikana mukudzvinyirira asi kusava nehumwe mune dzimwe zvirwere zvakadai sekutya chirwere.106 Uyezve, kunyanya, cortisol yakakwirira inogona kufanotaura kupindura kwevarombo kune pfungwa dzepfungwa107 uye antidepressant108 kurapwa. Nhoroondo, inonyanya kuvimbiswa neuroendocrine marker yevanotarisira kurapwa kwekurapa yave iyo dexamethasone kudzvinyirira kuedza, uko cortisol kusasununguka kutevera dexamethasone administration inobatanidza nehuwandu huri pasi hwekuregererwa kwekupedzisira. Zvisinei, ichi chiitiko hachina kutaridzirwa zvakaringana kugadziriswa kwekliniki. Zvimwe zviratidzo zvinokonzera corticotrophin-kurega hormone uye adrenocorticotropin hormone pamwe nevasopressin hazviwanikwi kuti zvinowedzera kuwedzererwa mukuora mwoyo uye dehydroepiandrosterone inowanikwa kuvharwa; chiyero che cortisol kusvika dehydroepiandrosterone chingave chakasimudzirwa sechimiro chakasimba muTDD, ichiramba chichiregererwa.109 Neuroendocrine hormone dysfunction yakagara ichibatanidzwa nekuora mwoyo, uye hypothyroidism inogonawo kuita basa rinokonzera kuora mwoyo.110 Zvakare, mhinduro dzehutori dzinogona kumira nekugadzirisa kurapa kudzvinyirira.111

Mukati mezviri pamusoro, zvakakosha zvakare kufunga nezvekusaina nzira munzira, senge glycogen synthase kinase-3, mitogen-activated protein kinase uye cyclic adenosine 3?, 5? -Monophosphate, inobatanidzwa mu synaptic plasticity112 uye yakagadziridzwa neanodzvinyirira. vanogona biomarker musarudzo dzinotora biologic masisitimu anonyanya kuyerwa uchishandisa neuroimaging kana genetics. Mukupindura kushayikwa kwemasimba akasimba uye anonzwisisika ejenomiki pakati pevanhu vakaora mwoyo nevasina kudzvinyirirwa, 113 novel mageneti nzira dzakadai sepolygenic scores114 kana telomere urefu115 inogona kuratidza kubatsira. Kuwedzera biomarkers kuwana mukurumbira kuri kuongorora macircadian cycles kana chronobiologic biomarkers vachishandisa akasiyana masosi. Actigraphy inogona kupa chinangwa chekuongorora kurara uye kumutsa chiitiko uye kuzorora kuburikidza neaccecometer, uye zvishandiso zveacigraphic zvinogona kuwedzera kuyera zvimwe zvinhu sekuburitswa kwechiedza. Izvi zvinogona kubatsira zvakanyanya kuti zvionekwe kupfuura zvinowanzo shandiswa kuzviitira zvevarwere uye zvinogona kupa fungidziro yenoverengeka yemhinduro yekurapa.116,117 Mubvunzo wekuti biomarkers ndiyo inonyanya kuvimbisa kushandiswa kweshanduro iri dambudziko, iro rakawedzerwa pazasi.

Mazvinetso Mazvino

Kune imwe neimwe yezvikamu zvishanu zvehutano hwehutano hunoongorora, humwe humwe hunotevera hunotevera nhoroondo yakafanana: kune dzakawanda zvinonzi biomarker zviriko zvinosanganiswa mune zvimwe zvikonzero nekuora mwoyo. Aya mavara anowanzobatanidza mumutambo wakaomeswa, wakaoma-wekufananidzira. Icho uchapupu hahukwanisi, uye zvichida kuti zvimwe zvikamu zvepiphenomena zvezvimwe zviitiko uye zvimwe zvakakosha mune chikamu chiduku chevarwere. Biomarkers inogona kubatsira kuburikidza nemigwagwa yakasiyana-siyana (semuenzaniso, iyo inofanotaura kuti inotevera kupindura kurapwa, iyo inoratidzira marapirwo akadai seanogona kunge akabudirira kana ayo anogadzirisa nekugadzirisa pasinei nekuvandudzwa kwechipatara). Nzira dzinoverengeka dzinodiwa kuti kuwedzere kusagadzikana uye kliniki yekushandiswa kwezvidzidzo zvehupenyu muhutano hwepfungwa.

Biomarker Variability

Kusiyana kwezvisikwa zvehupenyu munguva uye mumamiriro ezvinhu zvinoreva zvakawanda kune mamwe marudzi (semuenzaniso, proteomics) kupfuura mamwe (genomics). Mitemo yakagadziriswa yevakawanda haisiko kana kuti haina kubvumidzwa zvikuru. Zvechokwadi, simba rezvakatipoteredza pane zviratidzo zvinowanzoenderana nemasikirwo akasiyana-siyana uye mamwe maonero ehupenyu pakati pevanhu vasingagoni kuverengwa vose. Izvi zvinoita kuti kuongororwa kwebasa rekuita zvinhu, uye kujekesa zvisikwa zvebiologic, zvakaoma kududzira. Pamusana pehuwandu hwezvinhu zvinogona kuitika, vazhinji havana kuyerwa zvizere kana mupeji yakazara pamwe chete nemamwe mazita akakodzera.

Zvinhu zvakawanda zvakave zvichinzi zvinoshandura kuchinja mapuroteni kumaitiro ezvigadzirwa zvebiologic kune varwere vane zvinetso zvepfungwa. Pamwe pamwe nekutsvakurudza-zvakabatana zvakadai sehuwandu nemamiriro ekuchengetedza (izvo zvinogona kukonzera kukanganisa kwezvimwe zvinokonzerwa), izvi zvinosanganisira nguva yezuva yakayera, dzinza, maitiro, 119 kudya (semuenzaniso, basa re microbiome, kunyanya rakapiwa kuti zvidzidzo zveropa rega kwete chirongwa chekutsanya), 120 kusvuta uye kushandisa zvinodhaka, 121 pamwe nehutano hwezvinhu (zvakadai sekuvhiringidza, kuora mwoyo kana zvimwe zvirwere zvepanyama). Semuenzaniso, kunyange zvazvo kuputika kwakanyanya kuchionekwa mune mwoyo yakaora mwoyo asi vamwe vanhu vane utano vakaenzaniswa nemapoka asina kufara, vanhu vakaora mwoyo vanewo comorbid vane hukama hwehutachiona hunowanzova nehupamhi hwei cytokines kupfuura yeavo vasina kushungurudzika kana kurwara.122 Zvimwe zvinhu zvakakurumbira zvine zvichida kubatanidzwa muhukama pakati pezviomarkers, kuora mwoyo uye kupindura kurapwa kwakanyorwa pasi apa.

Kushungurudzika. Vose endocrine uye mhinduro dzezvirwere zvezvirwere zvezvirwere zvinozivikanwa zvikuru pakupindura kudzvinyirira (physiologic kana mupfungwa), uye kushungurudzika kwenguva pfupi panguva ye biologic specimen collection hakuwanzo kuyerwa mumatsvakurudzo ekutsvakurudza pasinei nekusiyana kwechikonzero ichi pakati pevanhu vanogona kuwedzererwa nezvino kuora mwoyo zviratidzo. Zvose zvakaoma uye zvisingaperi zvinokonzera mupfungwa mupfungwa zvinoshanda sechirwere chekudzivirira zvirwere, kuchikurudzira kuputira mhinduro munguva shoma uye kwenguva refu. 123,124 Kuwana uku kunowedzera kune zvakaitika muupenyu hwepakutanga-hupenyu, izvo zvave zvichibatanidzwa nekukura kwevanhu vakuru vanoremekedzwa mupfungwa inowanikwa se munhu mukuru.125,126 Munguva yehutambudzi hwehutano hwehutano, kuputika kwekuwedzera kwakave kwakataurwawo chete kune avo vana vakanga vachiri kuora mwoyo.127 Inopesana, vanhu vane kuora mwoyo uye nhoroondo yekushungurudzika kwevana vanogona kunge vakaisa mhinduro dze cortisol kudzvinyirira, zvichienzaniswa nevaya vane kuora mwoyo uye hakuna hutano-hutambudza hupenyu.128 Kushungurudzwa kwepfungwa-induced HPA kushandiswa kwemasikisi kunoonekwa kunopesana nekugogodza basa, 129 pamwe nekuora mwoyo subtype kana kuchinja kwemajeni anokonzerwa neHPA.130 Dambudziko rinowedzera kukanganisa kwenguva refu uye kwenguva refu pane neurogenesis131 nezvimwe zvechirwere maitiro.132 Hainyatsozivikanwi kuti kushungurudzika kwevana kunobata sei biologic markers mukuora mwoyo vanhu vakuru, asi zvinokwanisika kuti kunyanya-kushungurudzika kwepfungwa kunoita kuti vamwe vanhu vatsungirire kushushikana mupfungwa mukukura izvo zvakasimbiswa mupfungwa uye / kana zvehupenyu.

Kuchenjerera kushanda. Dysfunction neurocogniti inowanzoitika kune vanhu vane zvirwere zvehutano, kunyange muDMD.133 Kukanganisa kunzwisisika kunokonzerwa nekugadzikana nekurapa.134 Neurobiologically, HPA axis129 neurotrophic systems135 inogona kuita basa rinokosha muhukama uhwu. Neurotransmitters noradrenaline uye dopamine zvinogona kunge zvakakosha pakugadzirisa njere dzakadai sekudzidza nekuyeuka.136 Kupindura kwakaputika kwepamusoro kwakave kwakabatana nekuderera kwekuziva, uye zvichida kunokanganisa kugadzirisa kushanda mumatambudziko epfungwa, 137 uye mukuregererwa, kuburikidza nenzira dzakasiyana-siyana.138 Zvechokwadi, Krogh et al139 vakarondedzera kuti CRP inonyanya kuwirirana nekunzwisisa kugadziriswa kupfuura zvepfungwa dzedambudziko rekuora mwoyo.

Age, gender and BMI. Kusavapo kana kuvapo, uye kutungamirirwa kwehupenyu hwevakadzi nevakadzi nevechikadzi zvakange zvakasiyana-siyana muhumwe uchapupu huripo. Neuroendocrine hormone kusiyana pakati pevarume nevakadzi vanobatana nekunetseka kwepfungwa.140 Kuongororwa kwezvidzidzo zvekuputika kwakaratidza kuti kudzora kwezera uye zvepabonde hazvina kukanganisa kurongedza-kutarisa maonero mumakotokine ekuvhiringidza (kunyange zvazvo sangano pakati peI-6 uye kuora mwoyo kunopera sezvo makore akakura, iyo inowirirana nedzidziso dzokuti kuvhiringidzika kunowanzozara nezera) .41,141 VEGF kusiyana pakati pevarwere uye kutonga kwakakura muzviongorori kuongorora zviduku zviduku, nepo zvepabonde, BMI uye zvipatara zvinokanganisa hazvina kukanganisa kuenzanisa uku pane meta-analytic level.77 Zvisinei, kushayikwa kwekugadziriswa kweBMI muongororo yapfuura yekuputika uye kuora mwoyo kunoratidzika kunokonzera kukanganisa kukuru kwakataurwa pakati pemapoka aya.41 Yakakurumbira adipose tissue yakanyatsoratidzwa kuratidza kushandiswa kwechitokine pamwe nekubatana zvakanyanya nemagadzirirwo emagetsi.142 Nokuti mishonga yepothytropic inogona kuva shamwari inowedzerwa nehupfumi uye BMI yakakwirira, uye izvi zvave zvichibatanidzwa nekurapa kurapwa mukuora mwoyo, iyi inzvimbo inokosha yekuongorora.

Mishonga. Zvakawanda biomarker zvidzidzo mukuora mwoyo (ese maviri echinjikwa-chikamu uye kureba) akaunganidza zviyero zvekutanga mune vasina kudzidziswa vatori vechikamu kuti vadzikise huterogeneity. Nekudaro, mazhinji eaya ongororo anotorwa mushure mekushambidzwa nguva kubva kumushonga, izvo zvinosiya zvingangoita zvinokatyamadza zvekusara kweshanduko mune physiology, inowedzerwa nehurefu hwakawanda hwekurapa hunowanikwa hungave hwakave nemhedzisiro mukuzvimba. Zvimwe zvidzidzo zvakabvisa psychotropic, asi kwete kumwe kushandiswa kwemushonga: kunyanya, yemuromo yekudzivirira kubata piritsi inowanzo bvumidzwa muvatsvagidzi vatori vechikamu uye isingadzorwe mukuongororwa, izvo zvichangobva kuratidzwa kuwedzera mahormone uye cytokine mazinga.143,144 Ongororo dzinoverengeka dzinoratidza kuti antidepressant mishonga ine mhedzisiro pamhinduro yekuzvimba, 34,43,49,145-147 HPA-axis, 108 neurotransmitter, 148 uye neurotrophic149 chiitiko. Nekudaro, iyo yakawanda inogona kurapwa yekurapa kushushikana ine yakasarudzika uye yakaoma pharmacologic zvivakwa, zvichiratidza kuti panogona kunge paine discrete biologic mhedzisiro yesarudzo dzakasiyana dzekurapa, inotsigirwa nedata razvino Izvo zvave zvichitarisirwa kuti pamusoro pe monoamine mhedzisiro, chaiyo serotonin-inotarisa mishonga (kureva, SSRIs) inogona kunongedza Th2 mashifts mukuzvimba, uye noradrenergic antidepressants (semuenzaniso, SNRIs) inoita Th1 kuchinja.150 Izvo hazvisati sarudza mhedzisiro yemunhu kana yemubatanidzwa mishonga pane biomarkers. Izvi zvinogona kunge zvichipindirana nezvimwe zvinhu zvinosanganisira kureba kwekurapwa (mashoma miedzo anoongorora mashandisiro emishonga kwenguva refu), sampuro heterogeneity uye kwete kudzora vatori vechikamu nekupindura kurapwa.

Heterogeneity

Methodological. Sezvakataurwa pamusoro apa, kusiyana (pakati nepakati pezvidzidzo) maererano nemishonga (pamwe nekubatanidza) vatori vechikamu vari kutora uye vatora kare vakafanirwa kuzivisa huterogeneity mune zvitsvakurudzo zvakawanikwa, kunyanya mukutsvakurudza kwebiomarker. Pamusoro peizvi, zvimwe zvakawanda zvakagadziriswa uye sampuli zvinoshandiswa pane zvidzidzo, zvichiwedzera kuoma nekududzira uye kugovera zvitsva. Izvi zvinosanganisira biomarker measurement parameters (semuenzaniso, zviyero zvezviyero) uye nzira dzekuunganidza, kuchengetedza, kushandura uye kuongorora zviratidzo mukuderera. Hiles et al141 vakaongorora mamwe magumisiro ekusawirirana mune mabhuku pamusoro pokuputika uye vakaona kuti kunyatsoona kwekuora mwoyo kuongororwa, BMI uye zvirwere zvinokonzerwa nekodhi zvaive zvakakosha kuverengera pakuongorora kupera kwemhirizhonga pakati pevanhu vakaora mwoyo uye vasina hanya nemapoka.

Clinical. Iyo yakawanda heterogeneity yevanhu vakaora mwoyo yakave yakanyatsoratidzwa151 uye inokosha inobatsira kutsanangurira zvakawanikwa mukati mezvinyorwa zvekutsvakurudza. Zvinonzwisisika kuti kunyange mukati mekuongororwa, maitiro asinganzwisisiki e biologic anongowanikwa kune zvikamu zvevanhu vanogona kunge vasina kugadzikana kwenguva yakareba. Nhengo dzakabatana dzevanhu vanotambura nekuora mwoyo dzinogona kuonekwa kuburikidza nekubatanidzwa kwepfungwa neyezvinhu zvipenyu. Pasi apa, tinotsanangura mikana yekutsvaga mapoka mashoma mukutarisana nematambudziko anowanzosiyana-siyana nehutano hwakasiyana.

Subtypes mukati Mokuora Mwoyo

Parizvino, hapana zvikwata zvakaomarara mukati mekushushikana kwezvikamu kana kusagadzikana zvakave nekugona kugona kusiyanisa pakati pevarwere zvichienderana nezviratidzo zviratidzo kana kurapwa kurapwa.152 Kuvapo kwechikamu chidiki mune izvo biologic aberrations zvinonyanya kutaurwa kwaizobatsira kutsanangura hupombwe pakati pezvidzidzo zvekare uye inogona kukurudzira nzira inoenda kurapwa kwakasarudzika. Kunugi et al153 vakurudzira seti yezvina zvingangoitika zvidiki zvichibva pabasa rehurongwa hwakasiyana-siyana hwehutachiona hunoratidza makiriniki akakodzera mune zvekuora mwoyo. iripo zvakanyanya ne anhedonia (uye inogona kupindura mushe kune, semuenzaniso, aripiprazole) uye inoputika subtype inozivikanwa nekukwirisa kwakakwira. Zvinyorwa zvakawanda zvinotarisana nekuzvimba zvakatsanangura nyaya yekuvapo kwe''infigueatory subtype mukati mekushushikana.55,56,154,155Makiriniki ehukama hwekuputira kwakakwira haasati afungidzirwa uye mashoma maitiro akaedzwa akaitwa kuti aone kuti ndevapi vatori vechikamu vanogona kuve neboka iri. Izvo zvave zvichiratidzwa kuti vanhu vane atypical kushushikana vanogona kuve nematanho epamusoro ekuzvimba kupfuura iyo melancholic subtype, 156 iyo ingangodaro isingaenderane nezvakawanikwa maererano neiyo HPA axis mune melancholic uye atypical subtypes yekuora mwoyo. TRD37 kana kushushikana nezvakakurumbira somatic zviratidzo157 yakave ichionekwa senge ingangoita yekutsvaira subtype, asi neurovegetative (kurara, kuda kudya, libido kurasikirwa), mafungiro (kusanganisira kuderera kwemoyo, kuzviuraya uye kusagadzikana) uye zviratidzo zvekuziva (kusanganisira kusasarura uye mhosva) 158 zvese inoonekwa ine hukama nemaprofayiri ehupenyu. Kuwedzera vamwe vanogona kukwikwidza kweinopisa subtype kunosanganisira chiitiko chehurwere hunhu-kunge zviratidzo159,160 kana metabolic syndrome.158

Izvo zvinokonzera (hypo) mania zvinogona kusiyanisa biologically pakati pevarwere vane dambudziko rekuora mwoyo. Uchapupu huripo hunoratidza kuti bipolar zvirwere ndeye boka revanhu vakawanda rezvirwere zvepfungwa, uye bipolar subsyndromal disorder yakawanikwa yakawanda kupfuura yakambozivikanwa kare. 161 Yakarurama uye / kana kunonoka kuonekwa kwehutano hwebipolar ichangobva kuratidzirwa sechinetso chakakura mumagariro echechi chepfungwa, muvhareji wenguva yekugadzirisa kuongororwa kunowanzopfuura makore gumi162 uye kunonoka uku kunokonzera kuoma kukuru uye mari yehutano huzhinji.163 Nehuwandu hwevarwere vane bipolar disorder inotanga nekutanga kana zvimwe zvinodzvinyirira zvirwere uye kushungurudzwa kwe unipolar ndiko kunonyanya kushandiswa, kusarudzwa kwe zvikonzero zvinogona kusiyanisa pakati pekupopora uye bipolar kudengenyeka kune zvakakosha. 164 Bipolar spectrum zvinetso zvingave zvisina kuonekwa mune mamwe matongerwo aMDC ainge apfuura, uye kuputika kwehupatidzo kwakaratidza kusiyana kweHPA axis activity109 kana kuvhiringidzika165,166 pakati pe bipolar uye unipo kushungurudzika kwemarara. Kunyange zvakadaro, kuenzanisa uku hakusipo, kune minda mikuru yezviyero zvakasarudzwa, zvakaonekwa zvisingaiti zvayo zvinokanganisa kana kuunganidza vanhu vasina kunyatsozivikaniswa nekuzivikanwa. Izvozvi tsvakurudzo hazviongorori basa rokutora kurapa mune hukama huno.

Zvose bipolar disorders167 uye kusagadzikana kwehutano168 haisi dichotomous constructs uye inoreva nhema pamusoro pekuenderera mberi, izvo zvinowedzera dambudziko rekutsanangurwa kwemashoko. Kunze kwekuisa pasi, zvakakosha kuziva kuti zvizhinji zvezvigadzirwa zvebiologic zvakaonekwa mukudengenyeka zvakafanana kune varwere vane zvimwe zvirwere. Nokudaro, matanho ekutsvaga marongerwo enyika anogonawo kukosha.

Biomarker Measurement Challenges

Biomarker yokusarudza. Huwandu hukuru hweanogona kuve anobatsira biomarkers anounza dambudziko kune psychobiology mukusarudza kuti ndeapi mamaki anoenderana nenzira ipi uye kunaani. Kuti kuwedzere chinetso, vashoma veava ma biomarker vanga vari pasi pekuferefetwa kwakakwana mukushushikana, uye kune vazhinji, mabasa avo chaiwo muhutano nevekiriniki vanhu havanyatsonzwisisika. Kunyangwe izvi, kuyedza kwakawanda kwakaitwa kupa mazano anovimbisa biomarker mapaneru. Pamusoro peBrand et als 16 maseti emamaki ane simba rakasimba, 27 Lopresti et al anongedzera yakawedzera yakakura seti yeiyo oxidative kusagadzikana mamaki ane mukana wekuvandudza kurapwa kurapwa.28 Papakostas et al yakatsanangura a priori seti yemapfumbamwe serum mamaki anotenderera biologic masisitimu (BDNF, cortisol, inogadziriswa TNF? receptor mhando II, alpha1 antitrypsin, apolipoprotein CIII, epidermal kukura chinhu, myeloperoxidase, prolactin uye resistin) mukusimbisa uye kudzokorora masampula ane MDD. Kamwe kabatanidzwa, chiyero chakasanganiswa chematanho aya chakakwanisa kusiyanisa pakati peMDC uye mapoka ekudzora aine 80% -90% kurongeka.169 Isu tinokurudzira kuti kunyangwe izvi hazvivhare vese vanogona kukwikwidza mundima iyi; ona Tafura 2 yekusarudzika kusarongeka kwema biomarker ane mukana wekushungurudzika, iine vese avo vane humbowo hwesimba uye anovimbisa enoveiki mamaki.

Technology. Nokuda kwekufambira mberi kwekambaniki, ikozvino zvinobvira (zvechokwadi, yakakodzera) kuyera mhando yakawanda yezvigadzirwa zvemazuva ano panguva imwe chete uye nekunzwa kwepfungwa kupfuura yakamboitika kare. Parizvino, iyi inokwanisa kuongorora mapiritsi akawanda ari mberi kwekukwanisa kwedu kunyatsoongorora nekududzira iyo data, 170 chimwe chinhu chicharamba chichiwedzera nekusimudzirwa kwezvinyorwa zvebiomarker uye matsva maitiro akadai semetabolomics. Izvi zvinonyanya kukonzerwa nokushaikwa kwekunzwisisa pamusoro pezvinonyanya kukoshesa uye kushamwaridzana pakati pezvikwangwani, uye kushaya kukwana kwokuti vanobatanidza sei zviratidzo vanoshamwaridzana nehutano hwakasiyana-siyana hwehupenyu (semuenzaniso, genetic, transcription, protein) mukati uye pakati pevanhu. Dhavhidha yakawanda kushandisa nzira itsva yekuongorora uye mitemo inobatsira nekugadzirisa izvi, uye nzira itsva dziri kuendeswa; Imwe muenzaniso ndeyekuvandudzwa kwenhamba inoshandiswa yakagadziriswa mumagetsi ekutsvaga kutsvaga kutsvaga zvitsva zvinogona kugadzirisa zviratidzo zvichienderana nekusangana kwavo pakati pemakwikwi uye kubatanidza mazwi ekugadzirisa ne metabolite data.171 Maitiro emakadzi ekudzidza ari kutoshandiswa uye achabatsira nemhando yekushandisa biomarker dheseti kufanotaura zviitiko zvekurapa mune zvidzidzo nemakuru makuru.172

Kuwirirana kwezvigadzirwa. Kuongorora huwandu hwema biomarkers panguva imwe chete imwe nzira yekuongorora mamaki ari ega anogona kupa maonero akajeka muwebhu yakaoma yehurongwa hwebiologic kana maratidziro.26 Zvakare, kubatsira nekusavhiringidza humbowo hwakapesana mune ino zvinyorwa kusvika zvino (kunyanya, uko biomarker network uye kudyidzana kunonzwisiswa), biomarker dhata inogona kuunganidzwa kana kunyorerwa. Rimwe dambudziko nderekuona nzira yakakwana yekuitisa izvi, uye zvingangoda zvinowedzera muhunyanzvi uye / kana hunyanzvi hwekuongorora nzira (ona iyo Big data chikamu). Nhoroondo, zviyero pakati pezviviri zvakasarudzika biomarkers zvakapa zvinonakidza zvitsva. inoshandurwa kuita imwechete-mhedzisiro saizi mamakisi pachidzidzo chega chega, uye zvakazara zvakaratidza kuzvimba kwakanyanya kusati kwasvika kurapwa kwekudzvinyirira, kufungidzira kusazoteerera kusingazopinduri muzvidzidzo zvekurapa. Zvinoumba biomarker mapaneru zvese zvinonetsa uye mukana wekutsvagurudza mune ramangwana kuti uwane zviwanikwa zvine musoro uye zvakavimbika zvinogona kushandiswa kuvandudza mhedzisiro yekurapa.109,173 Chidzidzo chakaitwa naPapakostas et al chakatora imwe nzira, kusarudza jira rezvinhu zvakasiyana serum biomarkers (yekuzvimba, HPA axis uye metabolic masystem) ayo akange aratidzwa kuti akasiyana pakati pevakaora mwoyo uye vanodzora vanhu muchidzidzo chakapfuura uye akaisa izvi muzvikamu zvengozi izvo zvaisiyana mumasampuli maviri akazvimirira neboka rinodzora riine> 174% senitivity uye yakanangana. 43

Big data. Iko kushandiswa kwedata hombe kungangodaro kuri madikanwa kugadzirisa matambudziko aripo anotsanangurwa akakomberedza heterogeneity, biomarker kusiyanisa, kuzivisa iwo akanakisa mamaki uye kuunza munda kune wekushandura, wakashandiswa kutsvagisa mukuora mwoyo. Nekudaro, sezvakatsanangurwa pamusoro, izvi zvinounza zvipingaidzo zveetekinoroji nesainzi. 175 Masainzi ezvehutano achangotanga kushandisa hombe data analytics, makore gumi kana kupfuura mushure mekambani yebhizinesi. Nekudaro, zvidzidzo zvakaita seIPOT-D152 uye Consortia yakadai sePsychiatric Genetics Consortium176 iri kufambira mberi nekunzwisisa kwedu kweiyo biologic nzira mune zvepfungwa. Machine-kudzidza algorithms ane, mune mashoma mashoma zvidzidzo, akatanga kushandiswa kune biomarkers ekuora mwoyo: ongororo ichangoburwa yakaunganidza data kubva> zviuru zvishanu zveva 5,000 biomarkers; mushure mekumanikidzwa kwakawanda kwedata, muchina-kudzidza wakasimudzira kudzokororwa kwakaitwa, zvichiratidza 250 dzinogona kuve biomarkers. Kutevera kumwe kuongorora kwekudzokorodza, matatu ma biomarkers akasarudzwa sekubatana zvakanyanya nezviratidzo zvekushushikana (yakanyanya kusiyanisa tsvuku yeropa maseru, serum glucose uye mazinga ebilirubin). Vanyori vanopedzisa kuti data hombe rinogona kushandiswa zvinobudirira kugadzira fungidziro.21 Makuru biomarker phenotyping mapurojekiti arikuenderera mberi uye zvinobatsira kufambisa rwendo rwedu mune ramangwana reiyo neurobiology yekuora mwoyo.

Zvichaitika mune ramangwana

Biomarker Panel Kuziva

Izvo zvakawanikwa mumabhuku kusvika pari zvino zvinoda kudzokororwa muzvidzidzo zvakakura. Izvi zvinonyanya kuitika kune inova biomarkers, senge chemokine thymus uye activation-inodzorwa chemokine uye iyo yekukura factor tyrosine kinase 2 iyo, kune ruzivo rwedu, isina kuongororwa mukiriniki yakaora mwoyo uye ine hutano yekudzora sampuli. Dzidzo hombe yedhata inofanirwa kuyedza yakazara biomarker mapaneru uye kushandisa akaomesesa ekuongorora matekiniki kuti uwane zvizere hukama pakati pezvimakisi uye izvo zvinhu zvinozvishandura mukiriniki uye zvisingaite zvevanhu. Pamusoro pezvo, kudzokororwa kwakakura kwechikamu chikuru chekuongorora kunogona kumisikidza mapoka akabatana ezvigadzirwa zvemagetsi uye zvinogona zvakare kuudza mashandisirwo e'composites 'mune biologic psychiatry, iyo inogona kusimudzira hukama hwezvinowanikwa mune ramangwana.

Discovery of Homogenous Subtypes

Pamusoro pekusarudza biomarker, pane zvikamu zvakawanda zvinogona kudiwa nenzira dzakasiyana-siyana dzinogona kutsvakurudza. Zvakatorwa pamwechete, uchapupu huripo hunoratidza kuti nhoroondo dze biomarker ndeyechokwadi, asi zvisingashandurwi zvakashandurwa muhuwandu hwevanhu iye zvino vari kutambura nekuora mwoyo. Izvi zvingave zvakagadzirirwa mukati kana mhiri kwekuongororwa kwezvikamu, izvo zvingaverengera kusawirirana kwezviwanikwa zvinogona kuonekwa mumabhuku aya. Kuchengetedza biologic subgroup (kana subgroups) inogona kubudirira zvikuru kuburikidza nekuongorora kukuru kwemasumbu ejomarker network panels mune kuora mwoyo. Izvi zvingaratidza mukati-kuwanda kwehuwandu hwevanhu; zvinyorwa zvitsva zvinongororwa zvinogona kuratidza zvakajeka zvipatara zvinoshandiswa kubva, somuenzaniso, kupisa.

Kunyanya Kurapa Migumisiro yekuvhiringidza uye Kupindura

Zvose zvinowanzopiwa kurapwa nokuda kwekuora mwoyo kunofanira kuongororwa zvakanzwisiswa kune zvakananga zvinokonzera biologic, uyewo kugadzirisa nokuda kwekubudirira kwekuedzwa kwehutano. Izvi zvinogona kuita kuti zvivakwa zvinogadziriswa nezviratidzo uye zviratidzo zvinoratidzira kuti zvifananidze zviitiko kune zvakasiyana-siyana zvekurwisa zvinopesana nemanzwiro mune imwe fashoni yepamusoro, uye inogona kuitika mumamiriro ezvinhu ose ekunyongedzerwa kwe unipolar uye bipolar. Izvi zvinogona kunge zvichishanda kune zvitsva zvinogona kurapwa pamwe chete nezvirwere zvinoratidzwa zvino.

Zvinotarisirwa Kusarudza Kurapwa Kupindura

Kushandisa nzira idzi pamusoro apa kunogona kuguma nekugadzirisa kukwanisa kuraira kurapwa kwekurapa zvakananga. Zvimwe zvakatendeseka uye zvinopfuurira (semuenzaniso, kwenguva refu) zviyero zvekupindura mhinduro zvinogona kuita izvi. Kuongororwa kwezvimwe zviito zvinokosha zvehutano hwakanaka (zvakadai sehupenyu hwehupenyu nekushanda kwezuva nezuva) zvinogona kupa huwandu hwekuongorora kwehupuridzo hunoita kuti hubatanidze zvakanyanya pamwe nevakashambadzira. Kunyange zvazvo basa rebiologic roga roga raigona kusagona kusiyanisa vanopindura mishonga kubva kune vasiri vanyori, kuenzaniswa kwakakwana kwezvinhu zvinokonzerwa nehupenyu hwepfungwa kana huwandu hwevanhu hunogona kubatanidzwa nehuwandu hwemashoko mukukudziridza muenzaniso wekufananidzira wekushaya kukodzera kurapwa. Kana mufananidzo wakavimbika wakagadzirirwa kufanotaura kupindura (zvichida kune vakaora mwoyo vagari vemo kana kuti kuwedzera) uye yakagadziriswa retrospectively, kushandurirwa kwekushandura kunogona kugadzirisa kushanda kwaro mumuedzo mukuru unodzorwa.

Kutarisa Kurapa Kwakasimba

Parizvino, varwere vane kushushikana havana kurongedzwa nenzira kwayo kuti vagamuchire yakagadziriswa chirongwa chekupindira. Kana ikasimbiswa, dhizaini yakatarwa dhizaini inogona kushandiswa kuyedza modhi kufanofungidzira kusapindura uye / kana kuona kuti murwere anoda kupihwa muyero wekutarisira. Izvi zvinogona kubatsira mune zvese zvakaenzana uye zvakasikwa kurapwa marongero, pamhando dzakasiyana dzekupindira. Pakupedzisira, muenzaniso unoshanda wekiriniki unogona kugadzirirwa kupa vanhu kurapwa kwakakodzera kwazvo, kuti vazive avo vangangodaro vanogadzira kushungurudzika kwekushushikana uye nekupa kuchengetedzwa kwakanyanya uye kuongorora kune varwere ava. Varwere vanoonekwa sevari panjodzi yekuramba kurapwa vanogona kupihwa mushonga unogadzikana wepfungwa uye pharmacologic kurapa kana musanganiswa wemishonga. Semuenzaniso wekufungidzira, vatori vechikamu vasina proinfigueatory cytokine kukwidziridzwa kunogona kuratidzwa kuti vagamuchire zvepfungwa kwete kurapwa kwemishonga, nepo chikamu chevarwere vane kunyanya kwakanyanya kuzvimba vaigona kugamuchira inorwisa-kupisa mumiririri mukuwedzera kune akajairwa kurapwa. Zvakafanana ne stratification, zvakasarudzika kurapwa-sarudzo nzira dzinogona kuitika mune ramangwana. Semuenzaniso, mumwe munhu akaora mwoyo angave akanyanya kukwirisa TNF? nhanho, asi hapana zvimwe zvipenyu zvisina kujairika, uye zvinogona kubatsirwa nekurapwa kwenguva pfupi neTNF? antagonist.54 Kurapa kwakasarudzika kunogona zvakare kusanganisira kuongorora biomarker expression panguva yekurapa kuzivisa zvinogona kuitika shanduko, kureba kwekuenderera kwekurapa kunodiwa kana kuona mamaki ekutanga ekudzokazve.

Novel Treatment Targets

Kune huwandu hwakawanda hweanogona kurapwa angave anokwanisa kushushikana, ayo asina kuongororwa zvakaringana, kusanganisira inoverengeka kana kudzokororwazve kupindira kubva kune mamwe marapirwo ekurapa. Zvimwe zvezvinonyanya kuzivikanwa zvave zviri mumishonga inorwisa-kupisa seye celecoxib (uye imwe cyclooxygenase-2 inhibitors), TNF? vanopikisa etanercept uye infliximab, minocycline kana aspirin. Izvi zvinoita sekuvimbisa. 178 Antiglucocorticoid makomponi, anosanganisira ketoconazole179 uye metyrapone, 180 yakaferefetwa nekuda kwekuora mwoyo, asi ese ari maviri ane zvipingaidzo neawo maitiro emhedzisiro uye iyo kiriniki inogona metyrapone haina chokwadi. Mifepristone181 uye iyo corticosteroids fludrocortisone uye spironolactone, 182 uye dexamethasone uye hydrocortisone183 inogona zvakare kushanda mukurapa kushushikana munguva pfupi. Targeting glutamate N-methyl-d-aspartate receptor antagonists, kusanganisira ketamine, inogona kumiririra inoshanda kurapwa mukuora mwoyo.184 Omega-3 polyunsaturated fatty acids inokonzeresa kupisa uye metabolic chiitiko uye inoita kunge inoratidza kumwe kushanda kwekuora mwoyo.185 Zvinokwanisika kuti ma statins anogona vane antidipressant mhedzisiro186 kuburikidza inoenderana neurobiological nzira.187

Neiyi nzira, iyo biochemical mhedzisiro yeanodzvinyirira (ona iyo Medication chikamu) ave achishandiswa kuchipatara mabhenefiti mune mamwe maratidziro: kunyanya gastroenterological, neurologic uye nonspecific zviratidzo zvezvirwere.188 Anti-anogumbura mhedzisiro yeanodzvinyirira inogona kumiririra chikamu cheiyo nzira ye mabhenefiti aya. Lithium yakafungidzirwawo kudzikisa kuzvimba, zvakanyanya kuburikidza neglycogen synthase kinase-3 nzira.189 Kutarisisa pamhedzisiro iyi kunogona kuratidza kudzidzisa kwekusaina biomarker siginecha uye, futi, biomarkers inogona kumiririra mamaki ekurapa ekuvandudza zvinodhaka.

Dr. Alex Jimenez's Insight

Kuora mwoyo kune chirwere chehutano hwepfungwa chinoratidzwa zviratidzo zvakakomba zvinokanganisa mafungiro, kusanganisira kurasikirwa kwechido mumabasa. Zvidzidzo zvitsvakurudzo zvenguva ichangopfuura, zvisinei, zvakawana kuti zvinogona kuitika kufungidzira kuora mwoyo kushandisa zvinopfuura kungoita zviratidzo zvehutano hwemurwere. Maererano nevatsvakurudzi, kuziva zviwanikwa zvinowanikwa nyore nyore zvinogona kunyatsonyatsoongorora kushungurudzika zvinokosha pakuvandudza utano hwakakwana hwehutano uye hukama hwakanaka. Nenzira yekuti, zvipatara zvinowanikwa zvinoratidza kuti vanhu vane chirwere chikuru chekuora mwoyo, kana MDD, vane madiki mashoma e moleculecule acetyl-L-carnitine, kana BAC, muropa ravo kupfuura kutonga kwakanaka. Pakupedzisira, kugadzirisa zvinhu zvinokonzera kuora mwoyo kunogona kubatsira kubatsira kuti ndiani ari pangozi yekuvandudza chirwere pamwe nekubatsira vashandi vezvehutano vanoona nzira yakanakisisa yokurapa kune murwere ane kushushikana.

mhedziso

Zvinyorwa zvinoratidza kuti inenge zvikamu zviviri kubva muzvitatu zvevarwere vane kuora mwoyo hazvikwanise kugadziriswa kumushonga wokutanga uye kuti mukana wekusaremekedza unowedzera nehuwandu hwemishonga inoderedzwa. Kupa maitiro asingabatsiri kune migumisiro yakawanda kumunhu mumwe nomumwe uye mari yevanhu, kusanganisira kutambura kunoramba kuripo uye kushaya hutano hwakanaka, pangozi yekuzviuraya, kurasikirwa kwekubudirira uye kuparadzwa kwehutano huripo. Iko mabhuku makuru ekudengenyeka anoratidza nhamba yakawanda yezvigadzirwa zvepanyama zvinogona kuvandudza kurapwa kwevanhu vane kuora mwoyo. Kuwedzera kune neurotransmitter uye neuroendocrine marker iyo yakave ichienderana nekupararira kwemazana emakumi emakumi, masayendisiti achangobva kuitika anotsanangura kupopota kwemaitiro (uye maitiro ezvirwere zvezvirwere zvezvirwere zvinowanzoitika), kushandiswa kwemasikisi uye kukura kwezvinhu zvakakosha pakubatanidzwa mukuora mwoyo. Zvisinei, humwe hupupuriro hunopesana hunoratidza kuti kune matambudziko akawanda anoda kuiswa pamberi pekutsvakurudza kwezvinhu zvinogona kushandiswa kuitira kuvandudza kutarisira uye kutarisira kwevanhu vane kuora mwoyo. Pamusana pekuoma kwakaoma kwehurongwa hwehupenyu, kuongororwa kwemasikati pamwe chete kwezveruzhinji rwakakosha rwemashamba muzvidzidzo zvakakura kune ruzivo rwakanyanya pakuziva kusangana kwepakati pezvigadzirwa zvebiologic uye zvepfungwa kune vanhu vose. Kugadzirisa kuyerwa kweeurobiological parameters uye kliniki matanho ekuora mwoyo zvinogona kuita kuti kunzwisisa kunzwisise. Kuongorora uku kunoratidzawo kukosha kwekuongorora zvinhu zvingangochinja (zvakadai sekurwara, makore, cognition nemishonga) pakuunganidza zvaunonzwisisa kunzwisisa kwehupenyu hwekuora mwoyo uye nzira dzekudzivirira kurapa. Zvichida kuti zvimwe zviratidzo zvicharatidza kuvimbiswa kwekufanotaura kwehutano hwekurapa kana kurwisana nemishonga yakasiyana-siyana muboka revarwere, uye kuenzaniswa kwezviitiko zvebiologic uye zvepfungwa kunogona kusimbisa kukwanisa kutarisa avo vari pangozi yezviitiko zvisina kunaka zvekurapa. Kugadzira bhizimusi rinowedzera kuwedzera kukurudzira kuongorora uye kufungidzira, pamwe chete nehutachiona hwehutachiona hwepakutanga hutachiona hwechirwere chekuora mwoyo uye inovandudza zvirongwa zvekurapa zvinobudirira. Izvozvo zvinogona kunge zvingasungirirwa kune zvikamu zvevanorwara vanoora mwoyo. Nzira dzinoenda kune izvi zvingabatsiridza nzira dzekutsvaga dzekutsvaga dzinobatanidza kliniki syndromes zvakanyanya pedyo ne-core neurobiological substrates.6 Kunze nekuderedza kusagadzikana, izvi zvinogona kuita kuti kuchinja kune hukama hwekuremekedza hutano hwepanyama nehutano. Zviri pachena kuti kunyange zvazvo basa rakawanda richidikanwa, kusimbisa ukama pakati pezvinhu zvakakosha uye zvinokonzera kushungurudzika kune zvakakosha pakugadzirisa mutoro wekuora mwoyo kune mumwe munhu uye munzanga.

Kutenda

Chirevo ichi chinomiririra ongororo yakazvimiririra yakapihwa mari neNational Institute for Health Research (NIHR) Biomedical Research Center kuSouth London neMaudsley NHS Foundation Trust neKing s College London. Maonero akataurwa ndeevanyori uye kwete hazvo zveNHS, iyo NIHR kana iyo Dhipatimendi rehutano.

Mashoko Omuzasi

Kuzivisa. AHY ane makore ekupedzisira e-3 akagamuchira kukudzwa kwekutaura kubva kuna Astra Zeneca (AZ), Lundbeck, Eli Lilly, Sunovion; honaria for consulting from Allergan, Livanova naLundbeck, Sunovion, Janssen; uye kutsvakurudza rubatsiro kubva kuna Janssen uye UK masangano ekubhadhara mari (NIHR, MRC, Wellcome Trust). AJC ine makore ekupedzisira anonzi 3 yakagamuchirwa nekutaura kubva kuAspra Zeneca (AZ), kukudzwa kwekutaurirana kubva kuna Allergan, Livanova uye Lundbeck, uye ruzivo rwekutsvakurudza rubatsiro kubva kuLundbeck neUnited States mafashoni (NIHR, MRC, Wellcome Trust).

Vanyori vanorondedzera pasina dzimwe nharo dzekufarira mubasa iri.

Mukupedzisa,Zvichakadaro zvidzidzo zvakawanda zvekutsvagurudza zvakawana mazana ezvigadzirwa zvekushungurudzika, havasi vazhinji vakagadza basa ravo mukurwara kwekushushikana kana kuti ruzivo rwe biologic runogona sei kushandiswa kuwedzera hutachiona, kurapwa uye kufungidzira. Nekudaro, chinyorwa chiri pamusoro chiri kuongorora zvinyorwa zviripo pane biomarkers zvinobatanidzwa mukati meimwe nzira uye zvichifananidza zvakawanikwa pakiriniki kune izvo zvekuora mwoyo. Zvakare, zvitsva zvitsva pane biomarkers zvekuora mwoyo zvinogona kubatsira zvirinani kuongorora kushushikana kuitira kuti uteedzere nekurapwa kuri nani. Ruzivo rwunotsanangurwa kubva kuNational Center yeBiotechnology Ruzivo (NCBI) .Kureba kweruzivo rwedu kunogumira kuchiropractic pamwe nekukuvara kwepamuviri nemamiriro. Kuti ukurukure nyaya yacho, ndapota inzwa wakasununguka kubvunza Dr. Jimenez kana kuti tibate isu pa 915-850-0900 .

Yakarongedzwa naDkt Alex Jimenez

Zvimwe Zvinyorwa: Kubva Painini

Kutambudzika shure ndechimwe chezvikonzero zvakakosha zvikuru zvekuremara uye mazuva asina kukwana kubasa pasi rose. Sezvakangoitika, kurwadziwa kwekudzokera shure kwave kuchiitwa sechipiri chikonzero chikuru chechiremba chekushanyira, chakanyanya kupfurikidza nehutachiona hwepamusoro-kuporesa. Inenge 80 muzana yevanhu vanozoona rumwe rudzi rwemarwadzo emutsipa kamwechete kamwe chete muupenyu hwavo hwose. Iyo musana inorongwa yakaoma yakaumbwa nemapfupa, mafundo, magirasi nemasumbu, pakati pezvimwe zvinyoro zvishoma. Nemhaka yeizvi, kukuvadzwa uye / kana mamiriro ezvinhu akawandisa, akadai herniated discs, zvinogona kutungamirira kune zviratidzo zvekurwadziwa shure. Kukuvara kwemitambo kana kukuvara kwepamberi yemotokari kazhinji kunowanzokonzera kukonzera kurwadziwa, zvisinei, dzimwe nguva kufamba kwakanyanya kunogona kuva nemigumisiro inorwadza. Nenzira yakanaka, nzira dzakasiyana dzokurapa, dzakadai sechiropractic, dzinogona kubatsira kuderedza marwadzo shure kuburikidza nekushandurwa kwepelinha nekugadzirisa maitiro, pakupedzisira kunatsiridza marwadzo ekurwadziwa.

NHAURWA INOKOSHA INOKOSHA: Low Back Pain Management

DZIMWE NYAYA: DZIMWE DZIMWE DZIDZISO: ronicKusingaperi Kurwadziwa & Marapirwo