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Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women
Kapp, Lianna Kaycee. 2023. Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za...
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Stellenbosch : Stellenbosch University
2023
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| _version_ | 1867613932556910592 |
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| access_status_str | Open Access |
| author | Kapp, Lianna Kaycee |
| author2 | Hemmings, Sian M. J. |
| author_browse | Hemmings, Sian M. J. Kapp, Lianna Kaycee |
| author_facet | Hemmings, Sian M. J. Kapp, Lianna Kaycee |
| author_sort | Kapp, Lianna Kaycee |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Kapp, Lianna Kaycee. 2023. Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za/items/7e66290a-591e-4237-ac05-8d71e8197e29 |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/129374 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:43:59.926Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/129374 Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women Kapp, Lianna Kaycee Hemmings, Sian M. J. Nothling, Jani Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics. Post-traumatic stress disorder Rape victims -- Mental health Enzyme-linked immunosorbent assay Depression, Mental -- Pathophysiology Epigenetics UCTD Kapp, Lianna Kaycee. 2023. Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za/items/7e66290a-591e-4237-ac05-8d71e8197e29 Thesis (MSc)--Stellenbosch University, 2023. ENGLISH ABSTRACT: Background: Rape is associated with an increased risk of post-traumatic stress disorder (PTSD) and depression. One biological mechanism involved in the pathophysiology of these disorders is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The adenylate cyclase-activating polypeptide 1 gene (ADCYAP1) and its protein product, pituitary adenylate cyclase-activating polypeptide (PACAP), are master regulators of the HPA axis and, subsequently, the stress response. In a previous epigenome-wide analysis study conducted by our group, two CpG sites in ADCYAP1 (chr18:905177-905180) were found to be differentially methylated in relation to PTSD status in the Rape Impact Cohort Evaluation (RICE) study. As a separate study showed that PACAP plasma levels were positively associated with symptoms of PTSD and depression, particularly in women, we hypothesized that increased methylation of ADCYAP1 was likely to result in decreased expression of PACAP. As a second step, and to build on these results, we aimed to investigate longitudinal changes in PACAP concentration in relation to post-traumatic stress symptom (PTSS) and depression scores in a subset of the RICE cohort. Our secondary aim was to explore the role of ADCYAP1 methylation in relation to PACAP concentration and PTSS scores 3-months following rape. Methodology: PACAP plasma concentration was investigated using an enzyme-linked immunosorbent assay in a subset of 30 rape-exposed South African women. Self-reported PTSS scores were measured using the Davidson Trauma Scale (DTS) and self-reported depression symptoms were measured using the Center for Epidemiologic Studies Depression (CES-D) Scale. PACAP concentration and symptom scores were assessed at baseline (within 20 days post-rape), 3-, 6-, and 12-months post-rape. Joint modelling was used to investigate the relationship between PACAP concentration, ADCYAP1 methylation, and symptom scores over time. Results: PACAP plasma concentration was not found to be significantly correlated with methylation of CpG sites in ADCYAP1. However, the findings of this study indicated that PACAP concentration was positively associated with PTSS and depression symptom scores in an age and time-dependent manner. The expected value of square root PACAP concentration was found to be marginally predictive of square root PTSS scores (β = 0.48; 95% CI: -0.06, 1.03; p = .082) and significantly predictive of depression scores (β = 3.62; 95% CI: 0.80, 6.44; p = .012) over time. Conclusion: Few previous studies have investigated the trajectory of PTSS and depression scores following exposure to trauma such as rape. Our results support the hypothesis that increased PACAP concentration is associated with increased depression symptom scores and potentially with PTSS scores. The findings provide preliminary support for PACAP as a predictive biomarker of PTSS and depression pathogenesis and symptom severity in women. Furthermore, this study may contribute to understanding the role of PACAP as a regulatory factor in the trajectory of PTSS and depression scores in the 12-months following trauma exposure. However, replication of the findings in future larger-scale studies is needed to confirm these preliminary findings and better understand the mechanisms of PACAP contributing to PTSD and depression in females. AFRIKAANSE OPSOMMING: Verkragting word geassosieer met 'n verhoogde risiko van posttraumatiese stresversteuring (PTSV) en depressie. Een biologiese meganisme betrokke by die patofisiologie van hierdie afwykings is wanregulering van die hipotalamus-pituïtêre-adrenale (HPA)-as. Die adenilaat-siklase-aktiverende polipeptied 1-geen (ADCYAP1) en sy proteïenproduk, pituïtêre adenilaat-siklase-aktiverende polipeptied (PACAP), is meesterreguleerders van die HPA-as en, gevolglik, die stresreaksie. In 'n vorige epigenoomwye assosiasie-studie wat deur ons groep uitgevoer is, is gevind dat twee CpGplekke in ADCYAP1 (chr18:905177-905180) differensieel gemetileer is in verhouding tot PTSD-status in die Verkragting Impak Kohort Evaluering (RICE) studie. Dit stem ooreen met vorige bevindings waar PACAP-vlakke positief geassosieer was met simptome van PTSV en depressie, veral by vroue. As 'n tweede stap, en om op hierdie resultate voort te bou, het ons daarop gemik om longitudinale veranderinge in PACAP-konsentrasie en ADCYAP1-metilering te ondersoek in verhouding tot posttraumatiese stres simptoom (PTSS) tellings in 'n subset van RICE-deelnemers. Gegewe die hoë comorbiditeit tussen verkragting, PTSV en depressie, het ons ook daarop gemik om die longitudinale verband tussen PACAP-konsentrasie, ADCYAP1-metilering en depressie-simptomtellings te bepaal. Metodologie PACAP-plasmakonsentrasie is ondersoek met behulp van 'n ensiemgekoppelde immunosorbent-toets in 'n subset van 30 Suid-Afrikaanse vroue wat aan verkragting blootgestel is. Selfgerapporteerde PTSStellings is gemeet met behulp van die Davidson Trauma-skaal (DTS) en self-gerapporteerde depressiesimptome is gemeet met behulp van die Sentrum vir Epidemiologiese Studies Depressieskaal (CES-D). PACAP-konsentrasie- en simptoomtellings is by basislyn (binne 20 dae na verkragting), 3-, 6- en 12 maande na-verkragting geassesseer. Gesamentlike modellering is gebruik om die verband tussen PACAP-konsentrasie, ADCYAP1-metilering en simptoomtellings oor tyd te ondersoek. Resultate Daar is gevind dat PACAP-plasmakonsentrasie nie beduidend gekorreleer was met metilering van CpG-plekke in ADCYAP1 nie. Die bevindinge van hierdie studie het egter aangedui dat PACAP konsentrasie positief geassosieer was met PTSS en depressie tellings op 'n ouderdom en tyd afhanklike wyse. Die verwagte waarde van vierkantswortel PACAP konsentrasie was marginaal voorspellend van vierkantswortel PTSS tellings (β = 0.48; 95% CI: -0.06, 1.03; p = .082) en beduidend voorspellend van depressie telling (β = 3.62; 95 % CI: 0.80, 6.44; p = .012) oor tyd. Afsluiting Min vorige studies het die verloop van PTSS- en depressietellings na blootstelling aan 'n trauma soos verkragting ondersoek. Ons resultate ondersteun die hipotese dat verhoogde PACAP-konsentrasie geassosieer word met verhoogde depressietellings en moontlike met PTSS tellings. Die bevindings bied voorlopige ondersteuning vir PACAP as 'n voorspellende biomerker van PTSS en depressiepatogenese by vroue. Verder kan hierdie studie bydra tot die begrip van die rol van PACAP as 'n regulerende faktor in die verloop van PTSS en depressie simptome in die 12-maande na trauma blootstelling. Herhaling van die bevindinge in toekomstige grootskaalse studies is egter nodig om hierdie bevindinge te bevestig en die meganismes van PACAP wat bydra tot PTSV en depressie by vroue beter te verstaan. Masters 2023-11-16T08:16:21Z 2024-02-20T09:20:23Z 2023-11-16T08:16:21Z 2024-02-20T09:20:23Z 2023-11 Thesis https://scholar.sun.ac.za/handle/10019.1/129374 en Stellenbosch University 75 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Post-traumatic stress disorder Rape victims -- Mental health Enzyme-linked immunosorbent assay Depression, Mental -- Pathophysiology Epigenetics UCTD Kapp, Lianna Kaycee Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women |
| title | Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women |
| title_full | Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women |
| title_fullStr | Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women |
| title_full_unstemmed | Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women |
| title_short | Longitudinal associations between PACAP plasma concentration and symptoms of post-traumatic stress and depression in South African rape-exposed women |
| title_sort | longitudinal associations between pacap plasma concentration and symptoms of post traumatic stress and depression in south african rape exposed women |
| topic | Post-traumatic stress disorder Rape victims -- Mental health Enzyme-linked immunosorbent assay Depression, Mental -- Pathophysiology Epigenetics UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/129374 |
| work_keys_str_mv | AT kappliannakaycee longitudinalassociationsbetweenpacapplasmaconcentrationandsymptomsofposttraumaticstressanddepressioninsouthafricanrapeexposedwomen |