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Metabolic syndrome risk factor associations with clinical, functional and cognitive outcomes during the first year of treatment in schizophrenia spectrum disorders

dc.contributor.advisorEmsley, Robinen_ZA
dc.contributor.advisorDu Plessis, Stefan S.en_ZA
dc.contributor.advisorKilian, Sanjaen_ZA
dc.contributor.authorLuckhoff, Hilmar Klausen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.en_ZA
dc.date.accessioned2021-01-18T12:32:12Z
dc.date.accessioned2021-04-21T14:29:00Z
dc.date.available2021-01-18T12:32:12Z
dc.date.available2021-04-21T14:29:00Z
dc.date.issued2021-03
dc.identifier.urihttp://hdl.handle.net/10019.1/109854
dc.descriptionThesis (PhD)--Stellenbosch University, 2021.en_ZA
dc.description.abstractENGLISH SUMMARY : Treatment-emergent metabolic syndrome is an established risk factor for cardiovascular disease known to be associated with cognitive impairment, poor functioning and decreased quality of life in schizophrenia spectrum disorders. However, weight gain and increased lipids have also been correlated with clinical improvement in chronic schizophrenia patients. While most studies investigating the relationships between body mass and treatment outcome were conducted in patients treated with clozapine and olanzapine, it remains unclear to what extent the role of weight gain as a predictor of favourable clinical outcomes extends to include illness-specific symptom domains in first-episode patients treated with other antipsychotics with a lower obesogenic potential. The effects of other clinical (e.g. sex, substance use, baseline body mass) and treatment-related (e.g. antipsychotic dose, medication adherence) confounders on the above relationships is also unclear. In response to these knowledge gaps, the overarching aim of our doctoral studies was to explore the temporal evolution of metabolic syndrome risk factors and their effects on clinical outcome over 12 months of treatment in first-episode schizophrenia spectrum disorder patients. We found that an increase in body mass correlates with global psychopathology improvement as well as the disorganized symptoms domain of schizophrenia in first-episode patients (n=106) over 12 months of treatment, independent of the degree of antipsychotic exposure (sub-study I). The association between weight gain and clinical improvement extended to include better overall end-point cognition after 12 months of treatment in our first-episode patient cohort (n=72) (sub-study II). A differential effect for lower baseline body mass index as a predictor of end-point working memory performance was evident in substance users (unfavourable) compared to their non-using counterparts (favourable). The adverse role of low body mass index as an unfavourable prognostic marker was further substantiated by its associations with an earlier age of psychosis onset and more severe negative symptoms in first-episode patients (n=69) (sub-study III). The inclusion of a diffusion tensor imaging component to our research also revealed a similar differential association of body mass index with fronto-limbic white matter fractional anisotropy (FA) in first-episode patients (low body mass index, low FA) versus healthy controls (high body mass index, low FA) adjusting for age and sex (sub-study III). Extension of our structural neuroimaging research to include brain structures involved in the physiological, hedonic and cognitive control as part of a “core eating network” further identified smaller anterior hippocampal volumes as a sex-specific predictor of weight gain in first-episode patients (n=90) (sub-study IV). Our research supports the role of weight gain as a predictor of favourable clinical outcomes in first-episode schizophrenia patients for whom treatment adherence is assured. In contrast, low body mass and by extension failure to gain weight could represent an unfavourable prognostic marker in first-episode patients, particularly those who use substance users. Future studies would do well to combine clinical, biological and neuroimaging data in order to characterize intrinsic metabolic profiles in relation to long-term treatment outcomes in firstepisode schizophrenia.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING : Metaboliese sindroom sekondêr to behandeling is ’n belangrike risikofaktor vir kardiovaskulêre siekte wat verbind word met kognitiewe aantasting, swak funksionering en ’n afname in lewensgehalte by skisofrenie spektrum steurings. ’n Toename in gewig en lipiede is egter ook al verbind met kliniese verbetering in pasiënte met chroniese skisofrenie. Terwyl meeste studies wat die verhouding tussen liggaamsmassa en uitkoms ondersoek gedoen is met pasiënte wat met klosapien en olansapien behandel is, is dit onduidelik tot watter mate die rol van gewigstoename as ’n voorspeller van gunstige kliniese uitkomste verder strek om siekte-spesifieke simptoomdomeine in te sluit in eerste-episode pasiënte wat met ander antipsigotiese middels met ’n laer obesogeniese potensiaal behandel word. Die uitwerking van ander kliniese (bv. geslag, middelgebruik, basislyn liggaamsmassa) en behandelings-verwante (bv. die dosis van antipsigotiese middels, hoe getrou medikasie gebruik word) faktore op bogenoemde verband is ook onduidelik. In reaksie op hierdie leemtes in kennis was die oorkoepelende doel van die doktorale studie om die temporele ontwikkeling van risikofaktore vir metaboliese sindroom te ondersoek asook die uitwerking daarvan op kliniese uitkoms oor 12 maande van behandeling in pasiënte met ’n eersteepisode van skisofrenie spektrum steurnisse. Ons het gevind dat ’n toename in liggaamsmassa verband hou met algemene psigopatologiese verbetering sowel as die gedisorganiseerde simptoomdomein van skisofrenie in eerste-episode pasiënte (n=106) oor 12 maande van behandeling, onafhanklik van die graad van antipsigotiese blootstelling (substudie I). Die verband tussen gewigstoename en kliniese verbetering het ook beter algemene eindpunt kognisie na 12 maande van behandeling in ons groep eerste-episode pasiënte ingesluit (n=72) (substudie II). Daar was ook ‘n differensiële effek vir laer basislyn liggaamsmassaindeks as ’n voorspeller van eindpunt-werkgeheue prestasie in middelgebruikers (ongunstig) in vergelyking met nie-gebruikers (gunstig). Die nadelige rol van lae liggaamsmassaindeks as ’n ongunstige prognostiese merker was ook gestaaf deur die verbintenis daarvan met ’n vroeër ouderdom waarop psigose begin het en ernstiger negatiewe simptome in eerste-episode pasiënte (n=69) (substudie III). Die insluiting van ’n diffusie tensor beelding komponent by ons navorsing het ook ’n soortgelyke onderskeidende verbintenis onthul tussen liggaamsmassaindeks en fraksionele anisotropie (FA) van frontaal-limbiese witstof in eerste-episode pasiënte (lae liggaamsmassaindeks, lae FA) teenoor gesonde kontroles (hoë liggaamsmassaindeks, lae FA) met aanpassings vir ouderdom en geslag (substudie III). ’n Uitbreiding van ons navorsing oor strukturele neurobeelding om breinstrukture in te sluit wat betrokke is by fisiologiese, hedoniese en kognitiewe beheer as deel van ’n “kern-eetnetwerk” het kleiner volumes van die anterior hippokampus verder geïndentifiseer as ’n geslag-spesifieke voorspeller van gewigs toename in eerste-episode pasiënte (n=90) (substudie IV). Ons navorsing ondersteun die rol van gewigstoename as ’n voorspeller van gunstige kliniese uitkomstes in pasiënte met ’n eerste episode van skisofrenie wie se getroue volging van behandeling verseker word. In teenstelling hiermee kan ’n laer liggaamsmassa en by uitbreiding die versuim om gewig aan te sit ’n ongunstige prognose merker wees in eersteepisode pasiënte, veral in die wat middels gebruik. Dit sal goed wees as toekomstige studies kliniese, biologiese en neurobeeldings data kan kombineer met die oogmerk om intrinsieke metaboliese profiele te identifiseer met betrekking tot langtermyn uitkoms in eerste-episode skisofrenie.af_ZA
dc.format.extent[100] pages ; illustrations, includes annexures
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch University
dc.subjectSchizophrenia -- Treatmenten_ZA
dc.subjectMetabolic syndromeen_ZA
dc.subjectWeight gain -- Psychological aspectsen_ZA
dc.subjectCardiovascular system -- Diseasesen_ZA
dc.subjectUCTD
dc.titleMetabolic syndrome risk factor associations with clinical, functional and cognitive outcomes during the first year of treatment in schizophrenia spectrum disordersen_ZA
dc.typeThesisen_ZA
dc.description.versionDoctoral
dc.rights.holderStellenbosch University


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