Profile of acylcarnitines, inflammation and oxidative stress in first-episode psychosis before and after antipsychotic treatment
Date
2018-10-26
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Abstract
Vaimuhaigused on pikka aega olnud osa inimkonna ajaloost, kuigi skisofreenia termin võeti kasutusele alles pisut üle 100 aasta tagasi. Skisofreenia all kannatab ligi 1% rahvastikust ja ning see kuulub 15 juhtiva töövõimetuse põhjuse hulka. Skisofreeniahaigete eluiga on keskmisest populatsioonist 15-20 aastat oodatust lühem. Skisofreeniaspektrihäired avalduvad esmase psühhootilise episoodiga enamasti noores täiskasvanueas ja psühhoosi puhul võivad kliinilises pildis ilmneda erinevad sümptomid, mis on iseloomulikud ka skisofreeniale, nagu näiteks taju-, mõtlemis-, tunde- ja tahteelu häired. Diagnoosimise muudavad subjektiivseks ja keerukaks erinevate psühhootiliste häirete sümptomite suhteline sarnasus ning diagnostiliste biomarkerite pakettide puudumine erinevate psühhootiliste haiguste eristamiseks.
Psühhoosile eelnevad tavaliselt muutused organismi ainevahetusprotsessides, näiteks süsivesikute ja lipiidide ainevahetuses, oksüdatiivse stressi või põletikumarkerite tasemetes (s.o metaboolne düsregulatsioon). Samas puudub ühtne seisukoht, et kuivõrd metaboolne düsregulatsioon krooniliste psühhootiliste häirete puhul on omistatav haigusele enesele või antipsühhootilise ravi kõrvalmõjudele. Antud küsimusele võimaldab vastuseid pakkuda esmase psühhoosiepisoodiga patsientide vereseerumi metaboolsete biomarkerite taseme uurimine enne antipsühhootilise ravi alustamist ja ravi kohaldamise järgselt.
Tartu Ülikooli Kliinikumi Psühhiaatriakliiniku esmase psühhootilise episoodiga patsientide uurimine ja tulemuste analüüsimine ning võrdlemine tervete vabatahtlikega võimaldas leida ja järeldada, et esmane psühhoosiepisood on seotud madalatasemelise kroonilise põletikulise seisundiga, millega kaasnevad muutused lipidoomikas (atsüülkarnitiinide spektris), kuid samal ajal ei esine sisulist erinevust oksüdatiivse stressi tasemes võrreldes kontrollgrupiga. Seitsmekuulise antipsühhootilise ravi tulemusena alaneb põletiku ja oksüdatiivse stressi tase ning atsüülkarnitiinide muutused normaliseeruvad kontrollgrupi tasemele.
Mental disorders have long been a part of human history, but as a discrete mental illness schizophrenia was first described slightly over 100 years ago. Schizophrenia is affecting about 1% of the population and is considered one of the top 15 leading causes of disability worldwide. Persons with schizophrenia have an exceptionally short life expectancy, resulting in approximately 15-20 years below that of the general population. Schizophrenia spectrum disorders tend to start with first-episode psychosis at an early adult age. Psychosis is a complex of symptoms accompanying schizophrenia like perceptual disturbances of reality, hallucinations, thought and executive function disorders. The diagnostic obstacles so far have been the relatively subjective diagnostic modality that may result in errors due to the complex spectrum of symptoms, their similarities to several mental disorders and the absence of specific set of diagnostic biomarkers. Psychosis is usually preceded by changes in metabolic processes including carbohydrate and lipid metabolism and shifts in oxidative stress or inflammatory biomarker levels (i.e. metabolic dysregulation). At the same time there is no final consensus of the greatest contributor to the metabolic dysregulation: whether it is the disease or the side-effects of antipsychotic treatment. Studying the status of metabolomic biomarkers in FEP patients before and after antipsychotic treatment may shed some light in this topic. Studying the first-episode psychosis patients of the Psychiatric Clinic of Tartu University Hospital and analysing and comparing the results with carefully selected control group enabled to draw the following conclusions: FEP is associated with low-grade inflammation with a remarkable change in lipidomics (the referred acylcarnitines) but without any considerable difference in OxS levels. Seven-month antipsychotic treatment of FEP is capable of reversing these changes in acylcarnitine levels and reduce oxidative stress and inflammation to the values seen in control group.
Mental disorders have long been a part of human history, but as a discrete mental illness schizophrenia was first described slightly over 100 years ago. Schizophrenia is affecting about 1% of the population and is considered one of the top 15 leading causes of disability worldwide. Persons with schizophrenia have an exceptionally short life expectancy, resulting in approximately 15-20 years below that of the general population. Schizophrenia spectrum disorders tend to start with first-episode psychosis at an early adult age. Psychosis is a complex of symptoms accompanying schizophrenia like perceptual disturbances of reality, hallucinations, thought and executive function disorders. The diagnostic obstacles so far have been the relatively subjective diagnostic modality that may result in errors due to the complex spectrum of symptoms, their similarities to several mental disorders and the absence of specific set of diagnostic biomarkers. Psychosis is usually preceded by changes in metabolic processes including carbohydrate and lipid metabolism and shifts in oxidative stress or inflammatory biomarker levels (i.e. metabolic dysregulation). At the same time there is no final consensus of the greatest contributor to the metabolic dysregulation: whether it is the disease or the side-effects of antipsychotic treatment. Studying the status of metabolomic biomarkers in FEP patients before and after antipsychotic treatment may shed some light in this topic. Studying the first-episode psychosis patients of the Psychiatric Clinic of Tartu University Hospital and analysing and comparing the results with carefully selected control group enabled to draw the following conclusions: FEP is associated with low-grade inflammation with a remarkable change in lipidomics (the referred acylcarnitines) but without any considerable difference in OxS levels. Seven-month antipsychotic treatment of FEP is capable of reversing these changes in acylcarnitine levels and reduce oxidative stress and inflammation to the values seen in control group.
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Keywords
psychoses, inflammation, biomarkers, treatment