Investigating inflammation in neuropsychiatric disorders
Date
2021-03
Authors
Journal Title
Journal ISSN
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Publisher
Stellenbosch : Stellenbosch University
Abstract
ENGLISH ABSTRACT: Chronic systemic inflammation, characterised by the elevated production of pro-inflammatory cytokines, has been implicated in the pathophysiology and severity of neuropsychiatric disorders (NPDs), such as posttraumatic stress disorder (PTSD), Parkinson’s disease (PD) and schizophrenia (SCZ). However, the exact role pro-inflammatory cytokines play in NPDs has yet to be fully established, with several studies reporting inconsistent findings. The current study aimed to measure the association between levels of interferon gamma (IFN), interleukin one beta (IL-1), interleukin six (IL-6), tumour necrosis factor alpha (TNF) and C-reactive protein (CRP), and PTSD, PD and SCZ.
Serum samples were previously collected as part of a parent cohort study (SHARED ROOTS Flagship Project). Diagnoses of PTSD, PD and SCZ were made by clinicians and assessed according to the Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) for PTSD and PD. Severity of the disorders were evaluated using the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) for PTSD, the Unified Parkinson’s Disease Rating Scale (UPDRS) for PD and the Positive and Negative Syndrome Scale (PANSS) for SCZ. Pro-inflammatory cytokines, IFN, IL-1, IL-6, TNF and CRP were measured in serum samples of participants (PTSD cohort: 139 cases, 179 controls; PD cohort: 46 cases, 21 controls; 31 SCZ cohort: 18 first-episode cases, 13 chronic cases, 39 controls) using multiplex and immunoturbidimetric assays.
Statistically significant lower levels of IL-1 were found to be associated with PTSD status after controlling for age, smoking and metabolic syndrome (OR = 0.24; p = 0.0146), whilst PD status was associated with statistically significant elevated levels of IL-6 (OR = 34.97; p = 0.0254) and lower levels of CRP (OR = 0.57; p = 0.0401), after adjusting for sex. Increased levels of TNF were significantly associated with chronic SCZ diagnosis after controlling for metabolic syndrome (OR = 5.52; p = 0.0218). The findings observed in this study contributes to the evidence that immune processes are dysregulated in NPDs, however future studies are required to provide further insight into the relationship between pro-inflammatory markers and NPDs.
AFRIKAANSE OPSOMMING: Chroniese sistemiese inflammasie, gekenmerk deur die verhoogde produksie van pro- inflammatoriese sitokiene, is betrokke by die patofisiologie en die erns van neuropsigiatriese versteurings (NPVs), soos posttraumatiese stresversteuring (PTSV), Parkinson se siekte (PD) en skisofrenie (SKS). Die presiese rol wat pro-inflammatoriese sitokiene in NPVs speel, is egter nog nie ten volle vasgestel nie, met verskeie studies wat teenstrydige bevindinge rapporteer. Die doel van die huidige studie is om die assosiasie tussen vlakke van pro-inflammatoriese sitokiene, interferon gamma (IFN), interleukin een beta (IL-1), interleukin ses (IL-6), tumor-nekrose- faktor alfa (TNF) en C-reaktiewe proteïen (CRP), en PTSV, PD en SCZ te ondersoek. Serummonsters was vantevore ingesamel as deel van 'n ouerkohortstudie (‘SHARED ROOTS Flagship Project’). Diagnose van PTSV, PD en SKS is deur klinici gemaal en was geasseseer volgens die Diagnostiese en Statistiese Handleiding vir Geestesversteuring 5de uitgawe (DSH-5) vir PTSV en PD. Die erns van die versteurings was geëvalueer met behulp van die Klinikus geadministreerde PTSV-skaal (KGPS-5) vir PTSV, die Verenigde Parkinson se siekte- graderingskaal (VPSGS) vir PD en die Positiewe en Negatiewe Sindroomskaal (PENSS) vir SKS. Pro-inflammatoriese sitokiene, IFN, IL-1, IL-6, TNF en CRP was gemeet in serummonsters van deelnemers (PTSV-kohort: 139 pasiënte, 179 kontroles; PD-kohort: 46 pasiënte, 21 kontroles; 31 SKS-kohort: 18 eerste episodes pasiënte, 13 chroniese pasiënte, 39 kontroles) deur gebruik te maak van multipleks en immunoturbidimetriese toetse. Daar was bevind dat laer vlakke van IL-1 geassosieer was met PTSV-status nadat daar vir ouderdom, rook en metaboliese sindroom gekontroleer was (KV = 0,24; p = 0,0146) terwyl PD- status geassosieer was met verhoogde vlakke van IL-6 (KV = 34.97; p = 0,0254) en laer vlakke van CRP (KV = 0,57; p = 0,0401) nadat daar vir geslag aangepas was. Verhoogde vlakke van TNF was geassosieer met chroniese SKS-diagnose nadat daar vir metaboliese sindroom gekontroleer was (KV = 5.52; p = 0.0218). Die verkennende bevindinge wat in hierdie studie waargeneem was, dra by tot die bewyse dat immuunprosesse gedisreguleer is in NPVs, toekomstige studies is egter nodig om die verband tussen pro-inflammatoriese merkers en NPVs op die korrekte manier te ondersoek.
AFRIKAANSE OPSOMMING: Chroniese sistemiese inflammasie, gekenmerk deur die verhoogde produksie van pro- inflammatoriese sitokiene, is betrokke by die patofisiologie en die erns van neuropsigiatriese versteurings (NPVs), soos posttraumatiese stresversteuring (PTSV), Parkinson se siekte (PD) en skisofrenie (SKS). Die presiese rol wat pro-inflammatoriese sitokiene in NPVs speel, is egter nog nie ten volle vasgestel nie, met verskeie studies wat teenstrydige bevindinge rapporteer. Die doel van die huidige studie is om die assosiasie tussen vlakke van pro-inflammatoriese sitokiene, interferon gamma (IFN), interleukin een beta (IL-1), interleukin ses (IL-6), tumor-nekrose- faktor alfa (TNF) en C-reaktiewe proteïen (CRP), en PTSV, PD en SCZ te ondersoek. Serummonsters was vantevore ingesamel as deel van 'n ouerkohortstudie (‘SHARED ROOTS Flagship Project’). Diagnose van PTSV, PD en SKS is deur klinici gemaal en was geasseseer volgens die Diagnostiese en Statistiese Handleiding vir Geestesversteuring 5de uitgawe (DSH-5) vir PTSV en PD. Die erns van die versteurings was geëvalueer met behulp van die Klinikus geadministreerde PTSV-skaal (KGPS-5) vir PTSV, die Verenigde Parkinson se siekte- graderingskaal (VPSGS) vir PD en die Positiewe en Negatiewe Sindroomskaal (PENSS) vir SKS. Pro-inflammatoriese sitokiene, IFN, IL-1, IL-6, TNF en CRP was gemeet in serummonsters van deelnemers (PTSV-kohort: 139 pasiënte, 179 kontroles; PD-kohort: 46 pasiënte, 21 kontroles; 31 SKS-kohort: 18 eerste episodes pasiënte, 13 chroniese pasiënte, 39 kontroles) deur gebruik te maak van multipleks en immunoturbidimetriese toetse. Daar was bevind dat laer vlakke van IL-1 geassosieer was met PTSV-status nadat daar vir ouderdom, rook en metaboliese sindroom gekontroleer was (KV = 0,24; p = 0,0146) terwyl PD- status geassosieer was met verhoogde vlakke van IL-6 (KV = 34.97; p = 0,0254) en laer vlakke van CRP (KV = 0,57; p = 0,0401) nadat daar vir geslag aangepas was. Verhoogde vlakke van TNF was geassosieer met chroniese SKS-diagnose nadat daar vir metaboliese sindroom gekontroleer was (KV = 5.52; p = 0.0218). Die verkennende bevindinge wat in hierdie studie waargeneem was, dra by tot die bewyse dat immuunprosesse gedisreguleer is in NPVs, toekomstige studies is egter nodig om die verband tussen pro-inflammatoriese merkers en NPVs op die korrekte manier te ondersoek.
Description
Thesis (MScMedSc -)--Stellenbosch University, 2021.
Keywords
Proteins -- Structure, Nervous system -- Degeneration -- Pathophysiology, Neurobehavioral disorders -- Pathophysiology, Brain -- Pathophysiology -- Molecular aspects, Schizophrenia (SCZ), Parkinson’s disease (PD), Post-traumatic stress disorder (PTSD), UCTD