{"id":2474,"date":"2022-10-26T10:30:27","date_gmt":"2022-10-26T08:30:27","guid":{"rendered":"https:\/\/www.newslab.sk\/metabolomika-potencialny-nastroj-individualneho-pristupu-k-depresivnym-ochoreniam\/"},"modified":"2022-10-26T10:32:54","modified_gmt":"2022-10-26T08:32:54","slug":"metabolomika-potencialny-nastroj-individualneho-pristupu-k-depresivnym-ochoreniam","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/metabolomika-potencialny-nastroj-individualneho-pristupu-k-depresivnym-ochoreniam\/","title":{"rendered":"Metabolomics: a potential tool for an individual approach to depressive diseases"},"content":{"rendered":"

*A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens<\/strong><\/span><\/p>\n

 <\/p>\n

Depresia<\/strong><\/p>\n

Depresia je z\u00e1va\u017en\u00e9, neuropsychiatrick\u00e9 ochorenie, ktor\u00e9 v s\u00fa\u010dasnosti postihuje a\u017e 350 mili\u00f3nov \u013eud\u00ed na celom svete. Depresia je jednou z najviac invalidizuj\u00facich chor\u00f4b a sp\u00f4sobuje zna\u010dn\u00fa z\u00e1\u0165a\u017e pre jednotlivca aj pre spolo\u010dnos\u0165(1). Po\u010das pandemickej kr\u00edzy COVID-19 sa celosvetovo zv\u00fd\u0161il v\u00fdskyt pr\u00edznakov \u00fazkosti, depresie, posttraumatick\u00e9ho stresu \u010di psychick\u00fdch \u0165a\u017ekost\u00ed, \u010do nazna\u010duje sedemn\u00e1sobn\u00e9 zv\u00fd\u0161enie prevalencie v porovnan\u00ed s rokom 2017(2). Medzi k\u013e\u00fa\u010dov\u00e9 pr\u00edznaky depresie patr\u00ed zl\u00e1 n\u00e1lada, strata z\u00e1ujmu a pote\u0161enia, deficit koncentr\u00e1cie, pocity bezcennosti, chudnutie a nespavos\u0165. Depresia m\u00f4\u017ee by\u0165 \u010dasto vyvolan\u00e1 psychick\u00fdm stresom a je spojen\u00e1 s dysfunkciou osi hypotalamus \u2013 hypof\u00fdza \u2013 nadobli\u010dky. Dysfunkcia tohto syst\u00e9mu je potom z\u00e1va\u017en\u00fdm rizikov\u00fdm faktorom vzniku a progresie kardiovaskul\u00e1rnych a in\u00fdch ochoren\u00ed. Okrem toho vykazuj\u00fa pacienti s v\u00fdraznou depresiou zv\u00fd\u0161enie s\u00e9rov\u00fdch hlad\u00edn proz\u00e1palov\u00fdch cytok\u00ednov(3).<\/p>\n

Je zn\u00e1me, \u017ee depresia je ve\u013emi heterog\u00e9nne ochorenie, ktor\u00e9ho pr\u00edznaky, stupe\u0148 \u0165a\u017ekosti aj odpove\u010f na lie\u010dbu s\u00fa ve\u013emi individu\u00e1lne, preto sa depresia st\u00e1va iba \u010diasto\u010dne predpovedate\u013enou klinick\u00fdmi profilmi pr\u00edznakov. \u00dasilie o lep\u0161ie analyzovanie tejto heterogenity zah\u0155\u0148a molekul\u00e1rne, fyziologick\u00e9, zobrazovacie a neuropsychologick\u00e9 opatrenia kombinovan\u00e9 s klinick\u00fdmi \u00fadajmi s cie\u013eom u\u013eah\u010di\u0165 personalizovan\u00fa starostlivos\u0165 o pacienta(4).<\/p>\n

Bohu\u017eia\u013e, s\u00fa\u010dasn\u00fd stav pochopenia depresie je do ve\u013ekej miery obmedzen\u00fd(5). Vzh\u013eadom na jej vysok\u00fa prevalenciu je znepokojuj\u00face, \u017ee antidepres\u00edva vykazuj\u00fa iba miernu \u00fa\u010dinnos\u0165 pri jej lie\u010dbe(6). Rovnako nem\u00f4\u017eeme predpoveda\u0165, ako m\u00f4\u017ee individu\u00e1lny pacient reagova\u0165 na zvolen\u00fa terapiu(5). Mimoriadne vysok\u00e1 osobn\u00e1 a spolo\u010densk\u00e1 z\u00e1\u0165a\u017e zd\u00f4raz\u0148uje potrebu overen\u00fdch biomarkerov, ktor\u00e9 by pomohli zodpovedne ur\u010di\u0165 diagn\u00f3zu, usmerni\u0165 v\u00fdber liekov a spo\u013eahlivo predpoveda\u0165 odpove\u010f na lie\u010dbu. Existuj\u00fa v\u0161ak molekul\u00e1rne mechanizmy, ktor\u00e9 m\u00f4\u017eu pom\u00f4c\u0165 odhali\u0165 patol\u00f3giu depresie, a tak prispie\u0165 k jej diagnostike a lie\u010dbe s oh\u013eadom na individualitu pacienta(7).<\/p>\n

 <\/p>\n

Metabolomika<\/h2>\n

V\u00fdvoj a valid\u00e1cia genetick\u00fdch, proteomick\u00fdch a metabolomick\u00fdch metod\u00edk m\u00f4\u017ee by\u0165 nevyhnutn\u00e1 pri identifik\u00e1cii patofyziol\u00f3gie, expresie, ako aj medikament\u00f3znej lie\u010dby. Metabolomika sa v s\u00fa\u010dasnosti objavila ako obzvl\u00e1\u0161\u0165 hodnotn\u00e1 oblas\u0165 v\u00fdskumu v psychiatrii, preto\u017ee na rozdiel od genomiky zachyt\u00e1va dynamick\u00fd charakter choroby a na rozdiel od proteomiky meria kone\u010dn\u00e9 produkty komplexn\u00fdch interakci\u00ed medzi mnoh\u00fdmi prote\u00ednmi, signaliza\u010dn\u00fdmi kask\u00e1dami a bunkov\u00fdm prostred\u00edm(8).<\/p>\n

Metabolomika je vhodn\u00fd prostriedok na pochopenie biologick\u00fdch syst\u00e9mov chor\u00f4b identifik\u00e1ciou metabolick\u00fdch substr\u00e1tov a produktov biochemick\u00e9ho syst\u00e9mu. Umo\u017e\u0148uje odhali\u0165 stav dan\u00fdch buniek, tkan\u00edv a organizmov(9). Je to najnov\u0161\u00ed sp\u00f4sob pr\u00edstupu \u201eomics\u201c, ktor\u00fd sl\u00fa\u017ei na definovanie por\u00fach metabolick\u00fdch dr\u00e1h a siet\u00ed po\u010das choroby. Okrem toho prispieva k objavu a v\u00fdvoju lie\u010div t\u00fdm, \u017ee poskytuje podrobn\u00e9 biochemick\u00e9 \u00fadaje o liekoch, ich mechanizme \u00fa\u010dinku, terapeutickom potenci\u00e1li a ved\u013eaj\u0161\u00edch \u00fa\u010dinkoch(9).<\/p>\n

Je zn\u00e1me, \u017ee po\u010das depresie doch\u00e1dza k poruch\u00e1m energetick\u00e9ho metabolizmu, ako aj k v\u00fdznamn\u00fdm zmen\u00e1m v metabolizme aminokysel\u00edn a lipidov(10). Depresia je jednou z najz\u00e1va\u017enej\u0161\u00edch chor\u00f4b, preto\u017ee sp\u00f4sobuje ve\u013ek\u00e9 bremeno pre jednotlivca i pre cel\u00fa spolo\u010dnos\u0165. Okrem toho v\u00fdskyt depresie je z\u00e1sadn\u00fdm sp\u00f4sobom spojen\u00fd s v\u00fdskytom in\u00fdch chor\u00f4b(1). Pr\u00edtomnos\u0165, pr\u00edznaky aj trvanie depres\u00edvnej f\u00e1zy sa medzi jednotlivcami l\u00ed\u0161ia. Presn\u00e1 identifik\u00e1cia depresie je nevyhnutn\u00fdm prv\u00fdm krokom v lie\u010dbe a starostlivosti o \u013eud\u00ed trpiacich t\u00fdmto ochoren\u00edm a je obzvl\u00e1\u0161\u0165 d\u00f4le\u017eit\u00e1 pre \u013eud\u00ed s chronick\u00fdmi zdravotn\u00fdmi probl\u00e9mami, u ktor\u00fdch sa zd\u00e1, \u017ee maj\u00fa vy\u0161\u0161iu prevalenciu depresie ako be\u017en\u00e1 popul\u00e1cia(11). Metabolity priamo reprezentuj\u00fa stav buniek, ktor\u00fd odr\u00e1\u017ea celkov\u00fd fyziologick\u00fd fenotyp. Zmeny metabolickej aktivity \u00fazko s\u00favisia s mnoh\u00fdmi chorobami vr\u00e1tane depresie. Preto metabolick\u00fd fenotyping pom\u00e1ha pri v\u010dasnej diagnostike, \u0161t\u00fadiu, a subtypovan\u00ed chor\u00f4b na molekul\u00e1rnej \u00farovni. Na kvantifik\u00e1ciu \u0161irok\u00e9ho spektra metabolitov v komplexn\u00fdch biologick\u00fdch vzork\u00e1ch sa hmotnostn\u00e1 spektrometria st\u00e1va jednou z met\u00f3d efekt\u00edvnej vo\u013eby. Be\u017en\u00fdm diagnostick\u00fdm met\u00f3dam ch\u00fdba citlivos\u0165 a \u0161pecifickos\u0165(8).<\/p>\n

 <\/p>\n

Te\u00f3rie vzniku depres\u00edvnych por\u00fach<\/h2>\n

Monoam\u00ednov\u00e1 te\u00f3ria vykres\u013euje verziu, \u017ee riziko rozvoja depresie je v \u00fazkej korel\u00e1cii so zn\u00ed\u017een\u00fdmi hladinami centr\u00e1lne dostupn\u00fdch monoam\u00ednov. Ide najm\u00e4 o katecholam\u00edny, a to noradrenal\u00edn, indoleam\u00edn a s\u00e9roton\u00edn(12). Neurog\u00e9nna alebo hipokamp\u00e1lna te\u00f3ria zasa hovor\u00ed o naru\u0161enej neurogen\u00e9ze u dospel\u00fdch jedincov po\u010das depresie, ke\u010f\u017ee v hipokampe sa u ka\u017ed\u00e9ho dospel\u00e9ho jedinca tvor\u00ed pribli\u017ene 700 nov\u00fdch granulovan\u00fdch buniek denne(13). Pacienti trpiaci depresiou maj\u00fa vo v\u0161eobecnosti men\u0161\u00ed hipokampus a vy\u0161\u0161ie hladiny glukokortikoidov, ktor\u00e9 m\u00f4\u017eu naru\u0161i\u0165 proces neurogen\u00e9zy a tak podpori\u0165 vznik depresie(13). Inflama\u010dnou te\u00f3riou vzniku depresie sa vedci zaoberali posledn\u00fdch 14 rokov. Pri\u0161li s n\u00e1zorom, \u017ee fyzick\u00fd, ale aj psychologick\u00fd (emocion\u00e1lny) stres zvy\u0161uje riziko rozvoja ment\u00e1lnych ochoren\u00ed v d\u00f4sledku sledu hormon\u00e1lnych, biochemick\u00fdch a epigenetick\u00fdch mechanizmov, ku ktor\u00fdm patr\u00ed kynuren\u00ednov\u00e1 dr\u00e1ha, inflama\u010dn\u00e9 enz\u00fdmy, oxida\u010dn\u00fd, nitroza\u010dn\u00fd stres, proinflama\u010dn\u00e9 a antiinflama\u010dn\u00e9 cytok\u00edny, hypotalamo-hypof\u00fdzov\u00e1 os alebo somatick\u00e9 komorbidity(14).<\/p>\n

 <\/p>\n

Lipidov\u00fd metabolizmus pri depresii<\/h2>\n

S depresiou sa v\u00fdznamne sp\u00e1ja metabolizmus lipidov, preto\u017ee mozog je po tukovom tkanive druhou najv\u00e4\u010d\u0161ou z\u00e1sob\u00e1r\u0148ou tukov(15). Z toho d\u00f4vodu lipidomika, odvetvie metabolomiky zameran\u00e9 na sledovanie a objas\u0148ovanie lipidov\u00fdch dr\u00e1h, z\u00edskala v posledn\u00fdch rokoch v\u00fdznamn\u00fa pozornos\u0165 a pova\u017euje sa za nevyhnutn\u00fd n\u00e1stroj na sk\u00famanie mnoh\u00fdch neurodegenerat\u00edvnych chor\u00f4b, nielen depresie. Hypot\u00e9za polynenas\u00fdten\u00fdch mastn\u00fdch kysel\u00edn (PUFA) v poslednom \u010dase nazna\u010duje, \u017ee metabolizmus fosfo a sfingolipidov zah\u0155\u0148a potenci\u00e1lne dr\u00e1hy ochorenia(15). Posledn\u00fd v\u00fdskum zd\u00f4raznil potenci\u00e1lnu \u00falohu monitorovania perif\u00e9rnych PUFA a cholesterolu pri predikcii, stratifik\u00e1cii a riaden\u00ed depres\u00edvnych ochoren\u00ed. Najd\u00f4le\u017eitej\u0161ie v\u0161ak bude objasni\u0165, \u010di tak\u00e9 zmeny metabolizmu lipidov s\u00fa patofyziol\u00f3giou hnacej sily depresie alebo d\u00f4sledkom choroby(16). Klavins (2015) hl\u00e1sil aj zmeny hlad\u00edn fosfatidylchol\u00ednov (PC) a lyzofosfatidylchol\u00ednov (LysoPC) u stresovan\u00fdch \u013eud\u00ed(17). Zn\u00ed\u017een\u00e9 hladiny PC m\u00f4\u017eu by\u0165 spojen\u00e9 s aberantnou aktivitou fosfolip\u00e1zy A2 (PLA2). PLA2 s\u00fa enz\u00fdmy, ktor\u00e9 katalyzuj\u00fa \u0161tiepenie mastn\u00fdch kysel\u00edn z poz\u00edcie sn-2 a produkuj\u00fa vo\u013en\u00e9 mastn\u00e9 kyseliny a lysoPC(18). \u010eal\u0161ou, v\u00fdznamnou skupinou lipidov, ktor\u00e9 zohr\u00e1vaj\u00fa d\u00f4le\u017eit\u00fa \u00falohu v patofyziol\u00f3gii depresie, s\u00fa sfingomyel\u00edny. Sfingolipidy v membr\u00e1nach neur\u00f3nov hraj\u00fa d\u00f4le\u017eit\u00fa \u00falohu pri transdukcii sign\u00e1lu, bu\u010f modul\u00e1ciou lokaliz\u00e1cie a aktiv\u00e1cie membr\u00e1nov\u00fdch receptorov, alebo p\u00f4soben\u00edm ako prekurzory bioakt\u00edvnych lipidov\u00fdch medi\u00e1torov(19). Aktiv\u00e1cia receptorov cytok\u00ednov\u00fdch a neurotrofick\u00fdch faktorov viazan\u00fdch na sfingomyelin\u00e1zy vedie k tvorbe ceramidov a gangliozidov, ktor\u00e9 zasa modifikuj\u00fa \u0161truktur\u00e1lnu a funk\u010dn\u00fa plasticitu neur\u00f3nov. V starn\u00facich a neurodegenerat\u00edvnych podmienkach nast\u00e1va nadmern\u00e1 produkcia a akumul\u00e1cia ceramidov a zv\u00fd\u0161en\u00fd oxida\u010dn\u00fd stres spojen\u00fd s membr\u00e1nou, ktor\u00e9 n\u00e1sledne modifikuj\u00fa \u0161truktur\u00e1lnu a funk\u010dn\u00fa plasticitu neur\u00f3nov, \u010do n\u00e1sledne vy\u00fas\u0165uje do z\u00e1palov\u00fdch procesov, pri ktor\u00fdch doch\u00e1dza k degrad\u00e1cii neur\u00f3nov. \u0160t\u00fadie vzoriek mozgov\u00e9ho tkaniva \u013eud\u00ed a experiment\u00e1lnych zvierat nazna\u010duj\u00fa, \u017ee porucha metabolizmu sfingomyel\u00ednov je k\u013e\u00fa\u010dovou udalos\u0165ou pri dysfunkcii a degener\u00e1cii neur\u00f3nov, ku ktorej doch\u00e1dza pri depresii(10,20).<\/p>\n

Po\u010fakovanie<\/em><\/strong><\/p>\n

T\u00e1to<\/em> pr\u00e1ca<\/em> bola<\/em> podporen\u00e1<\/em> vedeckou<\/em> grantovou<\/em> agent\u00fa<\/em>rou VEGA (1\/0658\/20).<\/em><\/p>\n

 <\/p>\n

LITERAT\u00daRA<\/strong><\/p>\n

    \n
  1. Sobocki P, J\u00f6nsson B, Angst J, Rehnberg Cost of depression in Europe. The journal of mental health policy and economics. Jun 2006; 9(2): 87-98.<\/li>\n
  2. Bueno-Notivol J, Gracia-Garc\u00eda P, Olaya B, Lasheras I, L\u00f3pez-Ant\u00f3n R, Santab\u00e1rbara J. Prevalence of depression during the COVID-19 outbreak: A meta-analysis of community-based studies. International journal of clinical and health psychology : Jan-Apr 2021; 21(1): 100196.<\/li>\n
  3. Smith KJ, Au B, Ollis L, Schmitz The association between C-reactive protein, Interleukin-6 and depression among older adults in the community: A systematic review and meta-analysis. Experimental gerontology. Feb 2018; 102: 109-132.<\/li>\n
  4. Rush AJ, Ibrahim Speculations on the Future of Psychiatric Diagnosis. The Journal of nervous and mental disease. Jun 2018; 206(6): 481-487.<\/li>\n
  5. Weiden PJ, Buckley Reducing the burden of side effects during long-term antipsychotic therapy: the role of \u201cswitching\u201d medications. The Journal of clinical psychiatry. 2007; 68 Suppl 6: 14-23.<\/li>\n
  6. DiMatteo MR, Lepper HS, Croghan Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Archives of internal medicine. Jul 24 2000; 160(14): 2101-2107.<\/li>\n<\/ol>\n

     <\/p>\n","protected":false},"excerpt":{"rendered":"

    *A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens   Depresia Depresia je z\u00e1va\u017en\u00e9, neuropsychiatrick\u00e9 ochorenie, ktor\u00e9 v s\u00fa\u010dasnosti postihuje a\u017e 350 mili\u00f3nov \u013eud\u00ed na celom svete. Depresia je jednou z najviac invalidizuj\u00facich chor\u00f4b a sp\u00f4sobuje zna\u010dn\u00fa z\u00e1\u0165a\u017e pre jednotlivca aj pre spolo\u010dnos\u0165(1). Po\u010das<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[1904],"tags":[1905,1906,1907],"class_list":["post-2474","post","type-post","status-publish","format-standard","hentry","category-metabolomika-en","tag-depresia-en","tag-lipidovy-metabolizmus-en","tag-metabolomika-en","typ_clanku-review-article"],"acf":{"abstrakt":"

    Depresia ka\u017edoro\u010dne prispieva k celosvetovej z\u00e1\u0165a\u017ei chor\u00f4b. Po\u010das kr\u00edzy COVID-19 sa v\u00fdskyt por\u00fach n\u00e1lad \u010di dokonca depresie v\u00fdrazne zv\u00fd\u0161il. Napriek prib\u00fadaj\u00facim inform\u00e1ci\u00e1m presn\u00e9 z\u00e1kladn\u00e9 mechanizmy depres\u00edvnych por\u00fach nie s\u00fa st\u00e1le zn\u00e1me. Metabolomika je vhodn\u00fd a v\u00fdkonn\u00fd n\u00e1stroj na pochopenie skor\u00fdch mechanizmov spojen\u00fdch s patol\u00f3giou depres\u00edvnych stavov. Deteguje poruchy v metabolizme, ktor\u00e9 odr\u00e1\u017eaj\u00fa zmeny v biologickom organizme. Vyu\u017eitie metabolomiky by teda mohlo pom\u00f4c\u0165 pri identifik\u00e1cii biomarkerov, monitorovan\u00ed terapeutickej odpovede organizmu a odha\u013eovan\u00ed progresie ochorenia. V tejto pr\u00e1ci poskytujeme z\u00e1kladn\u00fd preh\u013ead o metabolick\u00fdch zmen\u00e1ch, ktor\u00e9 nast\u00e1vaj\u00fa pri depres\u00edvnych ochoreniach.<\/p>\n

    K\u013e\u00fa\u010dov\u00e9<\/strong> slov\u00e1:<\/strong> depresia, metabolomika, lipidov\u00fd metabolizmus<\/p>\n","casopis":[{"ID":2437,"post_author":"7","post_date":"2022-10-26 08:29:25","post_date_gmt":"2022-10-26 06:29:25","post_content":"newslab 1\/2022<\/strong>\r\n

      \r\n \t
    • Using immunohistochemistry to examine MMR protein expression in endometrial tumours is a suitable method for the primary selection of potential cases with Lynch syndrome<\/li>\r\n \t
    • Metabolomics: a\u00a0potential tool for an individual approach to depressive diseases<\/li>\r\n \t
    • The role of epigenetics in endometrial cancer<\/li>\r\n \t
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