Hair cortisol as a neuroendocrine biomarker to evaluate the impact of chronic stress on the interaction between neuropsychiatric disorders and metabolic syndrome

Van den Heuvel, Leigh Luella (2020-03)

Thesis (PhD)--Stellenbosch University, 2020.

Thesis

ENGLISH SUMMARY : Individuals with neuropsychiatric disorders (NPDs) demonstrate increased rates of cardiovascular disease (CVD) and metabolic syndrome (MetS). There is evidence of dysregulated hypothalamic pituitary adrenal (HPA) axis functioning in both NPDs and CVD and the HPA-axis may be a shared mechanistic pathway contributing to NPD-CVD comorbidity. Very few studies have, however, directly examined the association between NPDs, CVD risk and HPA-axis function. Hair cortisol concentrations (HCC), reflecting longerterm systemic cortisol levels, can provide insight into the role of HPA-axis dysregulation in the occurrence of CVD risk, as defined by MetS, in NPDs. This study was a neuroendocrine ancillary study to ‘Understanding the SHARED ROOTS (SR) of Neuropsychiatric Disorders and Modifiable Risk Factors for Cardiovascular Disease’. SR was a cross-sectional matched case-control study investigating the pathways contributing to the comorbidity of MetS in NPDs and included three NPD cohorts (posttraumatic stress disorder (PTSD), schizophrenia and Parkinson’s disease). This study investigated the role of HPA-axis dysfunction, as measured by HCC, in the three NPDs as compared to controls and in relation to NPD-MetS co-occurrence. We demonstrated that HPA-axis function was altered in the three NPDs, with higher HCC in PTSD patients than trauma exposed controls, lower HCC in patients with schizophrenia than controls and higher hair cortisone levels, but not HCC, in Parkinson’s disease patients than controls. MetS was not associated with HCC in any of the individual cohorts. The lack of significant findings related to MetS may have been due to limited statistical power to detect significant associations in the individual cohorts. Additionally, as this is one of the first studies investigating HCC in South Africa and the majority of studies have been conducted in developed regions, we sought to identify basic determinants of HCC in a South African mixed ancestry control sample. The main determinants associated with HCC were age, level of education, duration of sun exposure, hair product use, duration of sample storage and breastfeeding in women. We also demonstrated that resilience, but not self-perceived stress, was significantly inversely associated with HCC, underscoring the importance of identifying stress-resilience indicators of HCC in non-pathological samples. Finally we also found that poorer working memory performance was associated with higher HCC, suggesting an association between a neuroendocrine marker of chronic stress and working memory deficits. This is the first study to utilise a measure of longer-term HPA axis function to investigate the links between HPA-axis, NPDs and CVD risk. Considering the high burden of CVD in NPDs, this study provides a step towards better understanding the role played by chronic stress, as reflected by long-term HPA axis dysfunction, in the co-occurrence of CVD in NPDs. Furthermore, this study provides insights into the role of HPA-axis dysfunction in relation to clinical conditions and subjects of relevance to South Africa and contributes to broader geographic, cultural and ethnic representation in hair cortisol research.

AFRIKAANSE OPSOMMING : Individue met neuropsigiatriese versteurings (NPVs) demonstreer ‘n verhoogde voorkoms van kardiovaskulêre siekte (KVS) en metaboliese sindroom (MetS). Daar is bewyse dat die hipotalamus pituïtêre adrenale (HPA) as in beide NPVs en KVS wanfunksioneer en die HPAas is moontlik 'n gemeenskaplike meganistiese baan wat tot NPD-KVS komorbiditeit bydra. Baie min studies het egter al die verwantskap tussen NPVs, KVS risiko en HPA-as funksie direk ondersoek. Haar kortisol konsentrasies (HKK), wat langtermyn sistemiese kortisolvlakke weerspieël, kan insig aangaande die rol van HPA-as disregulasie in die voorkoms van KVS risiko, soos gedefinieer deur Mets, in NPVs bied. Hierdie studie was 'n neuro-endokriene aanvullende studie tot ‘Understanding the SHARED ROOTS (SR) of Neuropsychiatric Disorders and Modifiable Risk Factors for Cardiovascular Disease’. SR was 'n deursnit gepaarde gevallekontrolestudie wat die roetes wat tot die komorbiditeit van MetS in NPVs bydra in drie NPV kohorte (post-traumatiese stresversteuring (PTSV), skisofrenie en Parkinson se siekte) ondersoek het. Hierdie studie het die rol van HPA-as disfunksie, soos gemeet deur HKK, in die drie NPVs met kontroles vergelyk, asook in verhouding tot NPV-MetS mede-voorkoms ondersoek. Ons het getoon dat HPA-as funksie in die drie NPVs gewysig is, met hoër HKK in PTSV pasiënte as trauma blootgestelde kontroles, laer HKK in pasiënte met skisofrenie as kontroles en hoër hare kortisoon vlakke, maar nie HKK nie, in pasiënte met Parkinson se siekte as kontroles. MetS was nie geassosieer met HKK in enige van die individuele kohorte nie. Die gebrek aan betekenisvolle bevindinge met betrekking tot MetS is moontlik te wyte aan beperkte statistiese onderskeidingsvermoë om betekenisvolle assosiasies in die individuele kohorte te demonstreer. Aangesien hierdie een van die eerste studies is wat HKK in Suid-Afrika ondersoek en die meerderheid van die studies in ontwikkelde streke gedoen is, het ons beoog om die basiese bepalingsfaktore van HKK in 'n Suid-Afrikaanse gemengde afkoms kontrole steekproef te identifiseer. Die belangrikste bepalingsfaktore wat met HKK verband gehou het was ouderdom, opvoedingsvlak, duur van blootstelling aan die son, gebruik van haarprodukte, duur van monster berging en borsvoeding in vroue. Ons het ook getoon dat veerkragtigheid, maar nie self-waargenome stres nie, aansienlik omgekeerd met HKK geassosieer was, wat beklmetoon hoe belangrik dit is om stres-veerkragtigheid aanwysers van HKK in niepatologiese steekproewe te identifiseer. Laastens het ons ook bevind dat swakker werkende geheue prestasie, met hoër HKK geassosieer was, wat dui op ‘n assosiasie tussen 'n neuroendokriene merker van chroniese stres en werkende geheue terkorte. Hierdie is die eerste studie wat ‘n maatstaf van langtermyn-HPA-as funksie gebruik om die verband tussen HPA-as, NPVs en KVS risiko te ondersoek. In ag genome die hoë las van KVS in NPVs, bied hierdie studie 'n tree tot ‘n beter begrip van die rol wat kroniese stres, soos weerspieël deur lang termyn HPA-as disfunksie, in die mede-voorkoms van KVS in NPVs speel. Verder bied hierdie studie insigte aangaande die rol van HPA-as disfunksie in kliniese toestande en onderwerpe van belang vir Suid-Afrika en lewer ‘n bydrae tot breër geografiese, kulturele en etniese verteenwoordiging in haar kortisol navorsing.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/108451
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