Post-traumatic stress disorder symptom severity, trauma load and sleeping difficulties in trauma-exposed, treatment-seeking adolescents

Introduction: Sleep disturbances are associated with various anxiety- and trauma-related disorders, and specifically with post-traumatic stress disorder (PTSD). Two of the core symptoms of PTSD are recurrent distressing dreams about the traumatic event and difficulty in falling or staying asleep (insomnia). Sleep is essential for functioning, with poor sleep compromising cognitive, emotional and behavioural regulations. Sleep is also of particular importance for brain development and information processing in children and adolescents. The aim of this study was to determine if PTSD symptom severity and trauma load is associated with nightmares and insomnia in a sample of trauma-exposed, treatment-seeking adolescents. Methods: A total of 358 South African adolescents, between 12 and 18 years of age, exposed to at least one DSM-5 qualifying traumatic event, were assessed for PTSD-related sleep difficulties using the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS). Childhood exposure to 10 common trauma types was also recorded using the KSADS trauma checklist. PTSD symptom severity was measured using the child PTSD checklist (CPC). Results: Adolescents reporting current trauma-related nightmares (F[268.2] = 0.68, t = -8.16, p = 0.000) and current insomnia (F[265.2] = 0.16, t = -9.03, p = 0.000) had significantly higher PTSD symptom severity scores compared to those without current nightmares and insomnia. Adolescents with current trauma-related nightmares (F[355.2] = 0.15, t = -3.30, p = 0.001) and insomnia (F[353.2] = 0.15, t = -2.51, p = 0.013) were also exposed to a significantly greater number of different trauma types compared to those without current nightmares and insomnia. Conclusion: Assessing and treating sleep difficulties related to PTSD in trauma-exposed adolescents, in an effort to reduce the developmental impact of trauma on the brain and general functioning, should not be overlooked. Longitudinal studies may contribute to a better understanding of the long-term effects of trauma-related insomnia and nightmares on mental and physical health outcomes

Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors

CITATION: Nothling, J., et al. 2021. Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors. Translational Psychiatry, 11:594, doi:10.1038/s41398-021-01608-z.The original publication is available at https://www.nature.comPublication of this article was funded by the Stellenbosch University Open Access FundENGLISH ABSTRACT: Rape is associated with a high risk for posttraumatic stress disorder (PTSD). DNA methylation changes may confer risk or protection for PTSD following rape by regulating the expression of genes implicated in pathways affected by PTSD. We aimed to: (1) identify epigenome-wide differences in methylation profiles between rape-exposed women with and without PTSD at 3-months post-rape, in a demographically and ethnically similar group, drawn from a low-income setting; (2) validate and replicate the findings of the epigenome-wide analysis in selected genes (BRSK2 and ADCYAP1); and (3) investigate baseline and longitudinal changes in BRSK2 and ADCYAP1 methylation over six months in relation to change in PTSD symptom scores over 6 months, in the combined discovery/validation and replication samples (n = 96). Rape-exposed women (n = 852) were recruited from rape clinics in the Rape Impact Cohort Evaluation (RICE) umbrella study. Epigenome-wide differentially methylated CpG sites between rape-exposed women with (n = 24) and without (n = 24) PTSD at 3-months post-rape were investigated using the Illumina EPIC BeadChip in a discovery cohort (n = 48). Validation (n = 47) and replication (n = 49) of BRSK2 and ADCYAP1 methylation findings were investigated using EpiTYPER technology. Longitudinal change in BRSK2 and ADCYAP1 was also investigated using EpiTYPER technology in the combined sample (n = 96). In the discovery sample, after adjustment for multiple comparisons, one differentially methylated CpG site (chr10: 61385771/ cg01700569, p = 0.049) and thirty-four differentially methylated regions were associated with PTSD status at 3-months post-rape. Decreased BRSK2 and ADCYAP1 methylation at 3-months and 6-months post-rape were associated with increased PTSD scores at the same time points, but these findings did not remain significant in adjusted models. In conclusion, decreased methylation of BRSK2 may result in abnormal neuronal polarization, synaptic development, vesicle formation, and disrupted neurotransmission in individuals with PTSD. PTSD symptoms may also be mediated by differential methylation of the ADCYAP1 gene which is involved in stress regulation. Replication of these findings is required to determine whether ADCYAP1 and BRSK2 are biomarkers of PTSD and potential therapeutic targets.https://www.nature.com/articles/s41398-021-01608-zPublisher's versio

Epigenomic analysis of posttraumatic stress disorder in female rape survivors in South Africa

Thesis (PhD)--Stellenbosch University, 2021.ENGLISH SUMMARY : Compared to other trauma types, rape is associated with a high risk of developing posttraumatic stress disorder (PTSD). Women are at increased risk of developing PTSD compared to men and are also more frequently victims of sexual assault. PTSD is a complex, multifactorial disorder and an array of demographic, trauma-related, psychological and genetic putative risk and protective factors mediate or contribute to the development and course of the disorder. Few studies have comprehensively investigated demographic and psychological risk and protective factors for PTSD in a longitudinal prospective design, especially beyond the 3-month post-rape period and in low- to medium-income countries. There are currently no known epigenome-wide association studies (EWASs) investigating differential methylation in relation to PTSD in (1) an African population and (2) a sample of rape-exposed women exclusively. There are also no known studies investigating longitudinal change in the hypothalamic-pituitary-adrenal (HPA) axis associated candidate gene FK506 binding protein (FKBP5) in relation to PTSD in a sample of rape-exposed women exclusively. In this study we investigated the demographic, rape/assault-related, psychological, genetic (FKBP5) and epigenetic (epigenome-wide differential methylation) risk and protective factors associated with the development and course of PTSD symptoms over six months. Self-report measures and specimen collection was completed at baseline (within 20 day after the rape), 3-months and 6-months post-rape as part of the Rape Impact Cohort Evaluation (RICE) study. The RICE sample consisted of 852 Black African rape-exposed women, between the ages of 16 and 40 years and from a low socio-economic background. We found that baseline demographic, rape/assault-related and psychological protective factors were not significant predictors of PTSD symptoms over time. Baseline depression and rape stigma were significant psychological risk factors for the development and course of PTSD post-rape. We also identified one intergenic CpG site (cg01700569) that was differentially methylated in relation to PTSD status at 3-months post-rape on a genome-wide level. Thirty-four differentially methylated regions were identified and included a region in the HPA-axis-associated adenylate cyclase activating polypeptide 1 (ADCYAP1) gene and the neuroendocrine-associated brain-specific serine/threonine-protein kinase 2 (BRSK2) gene. Decreased BRSK2 and ADCYAP1 methylation at 3-months and 6-months post-rape was associated with increased PTSD symptom scores at the same time-points. Decreased FKBP5 methylation was a predictor of increased PTSD symptom scores at 3-months and 6-months post-rape. High childhood trauma and the CC genotype of FKBP5 rs1360780 resulted in decreased FKBP5 methylation and increased PTSD scores at baseline. The study builds on existing literature, highlighting the psychological risk factors for the development and course of PTSD in rape-exposed women. Methylation findings also build on the existing literature regarding the role of epigenetics in PTSD, although the genome-wide finding implicating differential methylation of BRSK2 in the development of PTSD is a novel finding in human studies. The study provides evidence that both psychological and biological factors have an impact on the symptom trajectory of PTSD and that both should be considered when designing and implementing interventions for the treatment of PTSD post-rape.AFRIKAANSE OPSOMMING : Verkragting word geassosieer met ‘n hoë risiko vir die ontwikkeling van posttraumatiese stresversteuring (PTSV) in vergelyking met ander tipes trauma. Vroue loop ‘n verhoogde risiko om PTSV te ontwikkel in vergelyking met mans en is ook meer gereeld slagoffers van seksuele aanranding in vergelyking met mans. PTSV is ‘n komplekse, multifaktoriese versteuring en ‘n verskeidenheid demografiese, trauma-verwante, sielkundige en genetiese vermeende risiko en beskermende faktore bemiddel of dra by tot die ontwikkeling en verloop van die versteuring. Min studies ondersoek die demografiese en sielkundige risiko en beskermingsfaktore vir PTSV op ‘n omvattende manier deur gebruik te maak van ‘n voornemende longitudinale ontwerp, veral buite die periode van 3 maande na die verkragting en in lae- to middel-inkomste lande. Daar is huidig geen epigenoom-wye assosiasie studies (EWAS’s) wat die verhouding tussen PTSV en differensiële metilering ondersoek in (1) ‘n Afrika-bevolking en (2) uitsluitlik vroue wat aan verkragting blootgesel was nie. Daar is ook huidig geen studies wat die longitudinale veranderinge in die hipotalamus-pituïtêre-adrenale (HPA) as geassosieerde kandidaat geen FK506-bindingsproteïen (FKBP5) in verhouding met PTSV in ‘n steekproef van vroue wat uitsluitlik aan verkragting blootgestel was, bestudeer nie. In hierdie studie het ons die demografiese, verkragtings-/aanrandingsverwante, sielkundige, genetiese (FKBP5) en epigenetiese (epigenoom-wye differensiële metilering) risiko en beskermende faktore in verwant met die ontwikkeling en verloop van PTSV-simptome oor ses maande bestudeer. Selfrapporteringskale en versameling van monsters was by basislyn (binne 20 dae na die verkragting), 3 maande en 6 maande na die verkragting voltooi, as deel van die verkragtingsimpak kohort evaluering (VIKE) studie. Die VIKE steekproef het bestaan uit 852 Swart vroue wat aan verkragting blootgestel was, wat tussen die ouderdom van 16 en 40 jaar was en wat vanuit ‘n lae sosio-ekonomiese agtergrond gekom. het Ons het gevind dat demografiese, verkragtings/aanrandingsverwante en sielkundige beskermende faktore op basislyn nie PTSV-simptome beduidend voorspel het nie. Depressie en verkragtingsstigma op basislyn was wel beduidende sielkundige risikofaktore vir die ontwikkeling en verloop van PTSV na verkragting. Een CpG (cg01700569) wat op ‘n genoomwye vlak differensieel gemetileer was in verhouding met PTSV-status 3 maande na die verkragting was ook geïdentifiseer. Vier en dertig differensieel gemetileerde streke was geïdentifiseer en het ‘n streek in die HPA-as geassosieerde adenilaat-siklase-aktiveerende-polipeptied (ADCYAP1) geen en ‘n streek in die neuro-edokriene geassosieerde berinspesifieke-serine-drieonien-proteïen-kinase 2 (BRSK2) geen ingesluit. ‘n Afname in BRSK2 en ADCYAP1 metilering by 3 maande en 6 maande na die verkragting was geassosieer met ‘n toename in PTSV-simptoomtelling by dieselfde tydpunte. ‘n Afname in FKBP5 metilering het ‘n toename in PTSV-simptoomtelling 3 maande en 6 maande na verkragting voorspel. Hoë kindertrauma en die CC genotipe van rs1360780 het gelei tot ‘n afname in FKBP5 metilering en ‘n toename in PTSV-simptoomtelling by basislyn. Die studie bou voort op die bestaande literatuur en beklemtoon die risikofaktore vir PTSV in vroue wat aan verkragting blootgestel is. Die metilering bevindinge bou ook voort op die bestaande literatuur, alhoewel die genoomwye bevinding dat differensiële metilering van BRSK2 verband hou met die ontwikkeling van PTSV ‘n nuwe bevinding in menslike studies is. Die studie bewys dat sielkundige en biologiese faktore ‘n impak het op die verloop van PTSV-simptome en dat beide oorweeg moet word wanneer intervensies vir die behandeling van PTSV na verkragting ontwerp en geïmplimenteer word.Doctora

Aanvaarding van roetine MIV berading en toetsing in die konteks van die gesondheidsoortuigingsmodel

Thesis (MA)--Stellenbosch University, 2011.ENGLISH ABSTRACT: South Africa is one of the countries with the highest HIV prevalence rates worldwide and younger age groups are often disproportionately affected. Knowledge of HIV status is regarded as an important prevention strategy for reducing HIV transmission and infection and it is viewed as a means to access antiretroviral therapy. Routine HIV Counseling and Testing (RCT) can significantly increase knowledge of HIV status, but it is unclear whether RCT will be accepted if offered. The aim of this study was to determine whether the main dimensions of the Health Belief Model (HBM) namely, perceived susceptibility, perceived severity, perceived benefits and perceived barriers can predict acceptance of RCT. A second objective of the study was to determine if the variable of the HBM, namely cue’s to action could significantly contribute to predicting acceptability of RCT. A sample of 1113 students at the University of Stellenbosch in the Western Cape Province of South Africa completed a structured questionnaire, measuring the acceptability of RCT. Multiple regression analysis was used to analyze the data and it was found that the main dimensions of the HBM could explain 25.1% of the variance in acceptance of RCT. It was however found that the variable perceived severity did not make a significant individual contribution to predicting acceptability of RCT. The addition of the variable cues to action also did not make a significant individual contribution to the prediction of RCT. It was therefore found that the HBM could partially, but not in its entirety, predict acceptability of RCT among the student population. Interventions should therefore aim to increase perceived benefits of RCT, reduce perceived barriers to RCT and facilitate correct personal risk assessment in order to increase perceived susceptibility.AFRIKAANSE OPSOMMING: Suid-Afrika is een van die lande met die hoogste MIV voorkomsyfers wêreldwyd en jonger ouderdomsgroepe word dikwels disproporsioneel geaffekteer. Kennis van MIV status word beskou as ’n belangrike voorkomingstrategie vir die vermindering van MIV oordrag en infektering en dit baan verder ook die weg tot antiretrovirale terapie. Roetine MIV Berading en Toetsing (RBT) kan daarin slaag om kennis van MIV status aansienlik te verhoog, maar dit is egter onduidelik of RBT aanvaar sal word, indien dit aangebied word. Die hoofdoel van hierdie studie was om te bepaal of die hoofdimensies van die Gesondheidsoortuigingsmodel (GOM), naamlik waargenome vatbaarheid, waargenome erns, waargenome voordele en waargenome hindernisse, aanvaarding van RBT sal kan voorspel. ’n Verdere oogmerk van die studie was om te bepaal of die veranderlike van die GOM, naamlik aanwysings tot aksie, ’n beduidende bydrae tot die voorspelling van aanvaarding van RBT kon lewer. ’n Steekproef van 1113 studente aan die Universiteit van Stellenbosch in die Weskaap Provinsie van Suid-Afrika het ’n gestruktureerde vraelys, vir die meting van aanvaarding van RBT, voltooi. Veelvuldige regressie-analise was gebruik om die data te analiseer en daar was bevind dat die hoofdimensies van die GOM 25.1% van die variansie in aanvaarding van RBT kon voorspel. Die veranderlike waargenome erns het egter nie ’n beduidende individuele bydra tot die voorspelling van RBT gelewer nie. Die byvoeging van die veranderlike aanwysings tot aksie het verder ook nie ’n beduidende individuele bydrae tot die voorspelling van RBT gelewer nie. Daar is dus bevind dat die GOM gedeeltelik, maar nie as geheel nie, aanvaarding van RBT onder die studentepopulasie kan voorspel. Intervensies behoort daarom te fokus op die vermeerdering van waargenome voordele verbonde aan RBT, die vermindering van waargenome hindernisse tot RBT en korrekte persoonlike risiko-evaluering vir die verhoging van waargenome vatbaarheid vir MIV

The perspectives of users of antiretroviral therapy on structural barriers to antiretroviral therapy adherence in South Africa

CITATION: Kagee, A., Nothling, J. & Coetzee, B. 2012. The perspectives of users of antiretroviral therapy on structural barriers to antiretroviral therapy adherence in South Africa. South African Family Practice, 54(6)540-544.The original publication is available at http://www.safpj.co.zaBackground: The effectiveness of antiretroviral therapy (ART) and the importance of adherence to treatment regimens are widely known. Yet, suboptimal adherence to ART and retention in care of patients still persists and, by many accounts, is fairly widespread. The aim of this study was to identify the structural barriers that influenced adherence among patients who were enrolled in the national ART programme in South Africa. Method: In this qualitative study, semi-structured interviews were conducted with a sample of 10 patients receiving ART at a public hospital in South Africa. Results: The results of the interviews were categorised according to poverty-related, institution-related and social barriers to clinic attendance and pill-taking, which collectively formed the structural barriers to adherence. The chief structural barriers to clinic attendance were time away from work, transport expenses, long waiting times and negative experiences with clinic staff. The chief barriers to pill-taking were food insecurity, stigma and discrimination. Conclusion: The barriers to adherence are discussed. Attention is called to the extraindividual factors that influenced ART adherence. We conclude that contextual factors, such as a healthcare-enabling environment, might play an important role in influencing healthcare-promoting behaviour among patients.http://www.safpj.co.za/index.php/safpj/article/view/2268Publisher's versio

Traumatic dissociation as a predictor of posttraumatic stress disorder in South African female rape survivors

Publication of this article was funded by the Stellenbosch University Open Access Fund.Background: HIV-related stigmatisation and discrimination by young children towards their peers have important consequences at the individual level and for our response to the epidemic, yet research on this area is limited. Methods: We used nationally representative data to examine discrimination of HIV-positive children by grade six students (n = 39,664) across nine countries in Southern Africa: Botswana, Lesotho, Malawi, Mozambique, Namibia, South Africa, Swaziland, Zambia and Zimbabwe. Descriptive statistics are used to compare discrimination by country, gender, geographic location and socioeconomic status. Multivariate logistic regression is employed to assess potential determinants of discrimination. Results: The levels and determinants of discrimination varied significantly between the nine countries. While one in ten students in Botswana, Malawi, South Africa and Swaziland would ‘‘avoid or shun’’ an HIV positive friend, the proportions in Lesotho, Mozambique, Zambia and Zimbabwe were twice as high (approximately 20%). A large proportion of students believed that HIV positive children should not be allowed to continue to attend school, particularly in Zambia (33%), Lesotho (37%) and Zimbabwe (42%). The corresponding figures for Malawi and Swaziland were significantly lower at 13% and 12% respectively. Small differences were found by gender. Children from rural areas and poorer schools were much more likely to discriminate than those from urban areas and wealthier schools. Importantly, we identified factors consistently associated with discrimination across the region: students with greater exposure to HIV information, better general HIV knowledge and fewer misconceptions about transmission of HIV via casual contact were less likely to report discrimination. Conclusions: Our study points toward the need for early interventions (grade six or before) to reduce stigma and discrimination among children, especially in schools situated in rural areas and poorer communities. In particular, interventions should focus on correcting misconceptions that HIV can be transmitted via casual contact.www.md-journal.comPublishers' Versio

Trauma exposure, posttraumatic stress disorder and the effect of explanatory variables in paramedic trainees

Fjeldheim, C. B. et al. Trauma exposure, posttraumatic stress disorder and the effect of explanatory variables in paramedic trainees. BMC Emergency Medicine, 14(1):11, doi:10.1186/1471-227X-14-11.The original publication is available at http://www.biomedcentral.com/1471-227X/14/11Publication of this article was funded by the Stellenbosch University Open Access Fund.Abstract Background: Emergency healthcare workers, including trainees and individuals in related occupations are at heightened risk of developing posttraumatic stress disorder (PTSD) and depression owing to work-related stressors. We aimed to investigate the type, frequency, and severity of direct trauma exposure, posttraumatic stress symptoms and other psychopathology amongst paramedic trainees. In order to create a risk profile for individuals who are at higher occupational risk of developing PTSD, we examined risk and resilience factors that possibly contributed to the presence and severity of posttraumatic symptomatology. Methods: Paramedic trainees (n = 131) were recruited from a local university. A logistic regression analysis was conducted using the explanatory variables age, gender, population group, trauma exposure, depression, alcohol abuse, alcohol dependence, resilience and social support. Results: 94% of paramedic trainees had directly experienced trauma, with 16% meeting PTSD criteria. A high rate of depression (28%), alcohol abuse (23%) and chronic perceived stress (7%) and low levels of social support was found. The number of previous trauma exposures, depression, resilience and social support significantly predicted PTSD status and depression had a mediating effect. Conclusion: There is a need for efficient, ongoing screening of depressive and PTSD symptomatology in trauma exposed high risk groups so that early psychological supportive interventions can be offered. Background Emergency healthcare workers, including trainees and individuals in related occupations are at heightened risk of developing posttraumatic stress disorder (PTSD) and depression owing to work-related stressors. We aimed to investigate the type, frequency, and severity of direct trauma exposure, posttraumatic stress symptoms and other psychopathology amongst paramedic trainees. In order to create a risk profile for individuals who are at higher occupational risk of developing PTSD, we examined risk and resilience factors that possibly contributed to the presence and severity of posttraumatic symptomatology. Methods Paramedic trainees (n = 131) were recruited from a local university. A logistic regression analysis was conducted using the explanatory variables age, gender, population group, trauma exposure, depression, alcohol abuse, alcohol dependence, resilience and social support. Results 94% of paramedic trainees had directly experienced trauma, with 16% meeting PTSD criteria. A high rate of depression (28%), alcohol abuse (23%) and chronic perceived stress (7%) and low levels of social support was found. The number of previous trauma exposures, depression, resilience and social support significantly predicted PTSD status and depression had a mediating effect. Conclusion There is a need for efficient, ongoing screening of depressive and PTSD symptomatology in trauma exposed high risk groups so that early psychological supportive interventions can be offered.Publishers' Versio

A pilot randomized control study to investigate the effect of the South African Adolescence Group Sleep Intervention (SAASI) on adolescent sleep and PTSD.

Background: Trauma exposure prevalence and consequent post-traumatic stress disorder among South African adolescents are significant. Sleep disturbances are among the most frequently reported difficulties faced by those dealing with PTSD. The current study examined the feasibility and preliminary efficacy of the South African Adolescence Group Sleep Intervention on PTSD symptom severity and sleep disturbance when delivered to South African adolescents with PTSD.Method: Sixty-one adolescents with PTSD diagnoses and sleep disturbance were randomly assigned (1:1) to one individual and four group sessions of a sleep intervention (SAASI) or a control group. At baseline, post- and 1-month follow-up participants completed the Child PTSD symptom scale for DSM5 (CPSS-5) and the Pittsburgh Sleep Quality Index (PSQI) among other sleep and psychiatric measures. The trial was registered on the Pan African Trial Registry (PACTR202208559723690)Results: There was a significant but similar decrease in PSQI scores in both groups over time indicating no overall intervention effect (wald test = -2.18, p=0.029), mean slope = -0.2 (95%CI: -0.37 to -0.02) (p=0.583). On the CPSS-5, interaction between groups was also not significant (p=0.291). Despite this overall finding, the mean difference in CPSS-SR-5 scores increased over time, with the difference between groups post-treatment -9.10 (95%CI: -18.00 to -0.21), p=.045 and the 1-month follow-up contrast -11.22 (95%CI: -22.43 to -0.03), p=0.049 suggesting that PTSD symptom severity decreased more in the intervention group than the control group. The dropout rate was higher than expected for both the intervention (n=10; 32%) and control (n=8; 26,7%) groups. Reasons provided for dropout were mostly school commitments or travel related.Conclusions: Early findings suggest a trend towards dual improvement in sleep quality and PTSD symptom severity in adolescents with a sleep disturbance and PTSD receiving a group sleep intervention (SAASI). Further investigation in a properly powered RCT with detailed retention planning is indicated. <br/