Examining the potential role of adiponectin in the development of posttraumatic stress disorder in female rape survivors in South Africa

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dc.contributor.advisorSeedat, Soraya, 1966-en_ZA
dc.contributor.advisorAbrahams, Naeemahen_ZA
dc.contributor.advisorHemmings, Sian Meganen_ZA
dc.contributor.advisorPeer, Nasheetaen_ZA
dc.contributor.authorVuong, Eileenen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.en_ZA
dc.date.accessioned2022-10-08T02:43:32Z
dc.date.accessioned2023-01-23T06:50:05Z
dc.date.available2023-04-08T03:00:11Z
dc.date.issued2022-12
dc.descriptionThesis (PhD)--Stellenbosch University, 2022. en_ZA
dc.description.abstractENGLISH SUMMARY: Background: Sexual violence, including rape, is associated with adverse mental and physical health outcomes, including post-traumatic stress disorder (PTSD) and cardiometabolic diseases (CMDs). CMDs are prevalent in individuals with PTSD and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in both these disorders. A blood-based biomarker of future susceptibility to PTSD and CMDs following rape, could allow for the early identification of at-risk individuals when disease trajectories may still be reversible. Adiponectin is an anti-inflammatory, insulin-sensitizing, adipose-secreted cytokine that has reciprocal relationships with the HPA axis and cortisol secretion. Higher adiponectin levels have been associated with a lower risk of metabolic syndrome (MetS), a clustering of multiple cardiometabolic risk factors whose pathologic origins arise from insulin resistance and adiposopathy. Although cross-sectional associations between adiponectin and PTSD have been described, no prospective studies of adiponectin in PTSD exist. Aims: In this dissertation, adiponectin is investigated as a candidate biomarker for new-onset PTSD and MetS following rape. Study objectives were completed utilising (1) serum adiponectin levels (s-ADP), (2) adiponectin gene (ADIPOQ) polymorphisms and (3) hair cortisol concentrations (HCC), a HPA axis measure that reflects long-term cortisol production. Methods: This study is nested within the Rape Impact Cohort Evaluation (RICE) study, which enrolled 1 799 black African female participants (N = 852 rape-exposed [RE] and N = 947 rape-unexposed [RUE]) between the ages of 16 and 40 years from KwaZulu-Natal Province. Data collected at baseline and at 3-, 6- and 12-month follow-up visits were utilised in this study to determine prevalent and incident outcomes. This included history (sociodemographic, medical history, mental health), physical examination (anthropometry, blood pressure), and biochemical investigations. Results: A systematic review and meta-analyses of the existing literature demonstrated an inverse association between circulating adiponectin levels and PTSD. In the RICE cohort, higher s- ADP was associated with a reduced risk of PTSD at three and six-month follow-up. However, the interaction of rape x s-ADP on PTSD was not significant. No ADIPOQ variant was shown to be associated with PTSD symptom severity. Serum adiponectin was shown to be significantly associated with MetS prevalence at baseline. However, no associations with new onset MetS incidence were shown at the 12-month follow-up. In the RE, the rs2241766TT genotype was shown to influence s-ADP levels and significantly reduce the risk of MetS incidence at 12 months. Lastly, no evidence of an interactive effect for s-ADP and HCC in predicting PTSD over time was found. Conclusion: This study supports the hypothesis that adiponectin is a potential candidate risk biomarker for PTSD and MetS. Whether adiponectin is a candidate biomarker of risk for PTSD following rape has yet to be established. The lack of prospective association between s-ADP and MetS may be explained by the relatively young study cohort and short period of follow-up and requires further long-term investigation. Future research directions stemming from this PhD include examination for associations of s-ADP and ADIPOQ variants with traumas other than rape, cumulative trauma exposure over time and Mendelian Randomization studies.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Agtergrond: Seksuele geweld, insluitend verkragting, word geassosieer met ongunstige geestelike en fisiese gesondheidsuitkomste, insluitend posttraumatiese stresversteuring (PTSV) en kardiometaboliese siektes (KMS'e). KMS'e kom algemeen voor in individue met PTSV en disregulering van die hipotalamus-pituitere-bynier (HPA)-as, is by beide hierdie afwykings geimpliseer. 'n Bloed-gebaseerde biomerker van toekomstige vatbaarheid vir PTSV en KMS'e na verkragting, kan die vroee identifikasie van individue in gevaar moontlik maak wanneer siektetrajekte nog omkeerbaar kan wees. Adiponektien is 'n anti-inflammatoriese, insulien-sensibiliserende, vetafgeskeide sitokien wat wederkerige verhoudings met die HPA-as en kortisolafskeiding het. Hoer adiponektienvlakke is geassosieer met 'n laer risiko van metaboliese sindroom (MetS), 'n groepering van veelvuldige kardiometaboliese risikofaktore waarvan die patologiese oorsprong spruit uit insulienweerstandigheid en adiposopatie. Alhoewel deursnee-assosiasies tussen adiponektien en PTSV beskryf is, bestaan geen voornemende studies van adiponektien in PTSV nie. Doelwitte: In hierdie proefskrif word adiponektien ondersoek as 'n kandidaat biomerker vir nuwe aanvang PTSV en MetS na verkragting. Studiedoelwitte is voltooi deur gebruik te maak van (1) serum-adiponektienvlakke (s-ADP), (2) adiponektien-geen (ADIPOQ) polimorfismes en (3) haarkortisolkonsentrasies (HCC), 'n HPA-as maatstaf wat langtermyn kortisolproduksie weerspieel. Metode: Hierdie studie is ingesluit in die Verkragtingsimpak-kohortevaluering (RICE) studie, wat 1799 swart vroulike Afrika-deelnemers ingeskryf het (N = 852 verkragting-blootgestelde [RE] en N = 947 verkragting-onblootgestelde [RUE]) tussen die ouderdomme van 16 en 40 jaar uit 'n lae sosio-ekonomiese agtergrond in die KwaZulu-Natal Provinsie. Data wat by basislyn en by 3-, 6- en 12-maande opvolgbesoeke ingesamel is, is in hierdie studie gebruik om algemene en voorvaluitkomste te bepaal. Dit het geskiedenis (sosiodemografie, mediese geskiedenis, geestesgesondheid), fisiese inspeksie (antropometrie, bloeddruk) en biochemiese ondersoeke ingesluit. Resultate: 'n Sistematiese oorsig en meta-ontledings van die bestaande literatuur het 'n omgekeerde verband tussen sirkulerende adiponektienvlakke en PTSV getoon. In die RICE-kohort was hoer s-ADP geassosieer met 'n verminderde risiko van PTSV by drie en ses maande opvolg. Geen ADIPOQ variant was geassosieer met PTSV simptome by drie and ses maande opvolg nie. Die interaksie van verkragting x s-ADP op PTSV was egter nie betekenisvol nie. Daar is getoon dat serumadiponektien beduidend geassosieer word met MetS- voorkoms by basislyn. Geen assosiasies met nuwe aanvang MetS- voorkoms is egter tydens die 12-maande-opvolging getoon nie. In die RE is getoon dat die rs2241766TT genotipe s-ADP vlakke beinvloed en die risiko van MetS voorkoms op 12 maande aansienlik verminder. Laastens, geen bewyse van 'n interaktiewe effek vir s -ADP en HCC in die voorspelling van PTSV oor tyd is gevind nie. Slotsom: Hierdie studie ondersteun die hipotese dat adiponektien 'n potensiele kandidaat risiko biomerker vir PTSD en MetS is. Of adiponektien 'n kandidaat-biomerker van risiko vir PTSV na verkragting is, moet nog vasgestel word. Die gebrek aan voornemende assosiasie tussen s-ADP en MetS kan verklaar word deur die relatief jong studiekohort en kort tydperk van opvolg en vereis verdere langtermyn ondersoek. Toekomstige navorsingsrigtings wat uit hierdie PhD voortspruit, sluit ondersoek in vir assosiasies van s -ADP- en ADIPOQ - variante met traumas anders as verkragting, kumulatiewe traumablootstelling oor tyd en Mendeliese Randomisering-studies. af_ZA
dc.description.versionDoctorate
dc.embargo.terms2023-04-08
dc.format.extentxxi, 391 pages : illustrations
dc.identifier.urihttp://hdl.handle.net/10019.1/126278
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch University
dc.rights.holderStellenbosch University
dc.subject.lcshPost-traumatic stress disorder -- South Africaen_ZA
dc.subject.lcshRape victims -- South Africaen_ZA
dc.subject.lcshMetabolic syndrome -- South Africaen_ZA
dc.subject.lcshRape victims -- Mental health -- South Africaen_ZA
dc.subject.lcshRape -- Psychological aspects -- South Africaen_ZA
dc.subject.nameUCTD
dc.titleExamining the potential role of adiponectin in the development of posttraumatic stress disorder in female rape survivors in South Africaen_ZA
dc.typeThesisen_ZA
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