Doctoral Degrees (Psychiatry)

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Browsing Doctoral Degrees (Psychiatry) by Subject "Appetitive aggression"

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    Understanding and treating trauma and violence-related pathologies in South African townships : emergence and modifiability of epigenetic and neural memories of traumatic stressors and appetitive offending
    (Stellenbosch : Stellenbosch University, 2018-12) Xulu, Khethelo Richman; Hemmings, Sian M. J.; Seedat, Soraya; Malan-Muller, S.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
    ENGLISH SUMMARY : Prolonged exposure to traumatic stress results in sustained activation of biological responses, which affect shared similar pathways, leading to posttraumatic stress disorder (PTSD), a serious mental illness; and behavioural problems such as appetitive aggression. Appetitive aggression is the perpetration of violence that induces feelings of arousal and excitement. Chronic exposure to stress can modify mechanisms such as DNA methylation and telomere length, which are environmentally sensitive. DNA methylation and telomere length, including genetic variants have been implicated in the aetiology of both aggression and PTSD. Therefore, studying DNA methylation, telomeres, and genetic variation is essential to better understand appetitive aggression and PTSD. The overarching aim of this study was to investigate DNA methylation, telomere length and genetic variation in association with appetitive aggression and PTSD. The secondary aim was to investigate changes in DNA methylation and telomere length that may be involved in the effectiveness of psychotherapeutic interventions by identifying key biological markers related to appetitive aggression and PTSD symptom severity in Xhosa Black South African men. The third aim was to investigate the association between appetitive aggression and genetic variations of both the serotonin transporter in the promoter region (5-HTTLPR) and monoamine oxidase A (MAOA). Recruited participants with higher levels of appetitive aggression and higher PTSD symptom severity, as measured by the Appetitive Aggression Scale (AAS) and the PTSD Symptom Scale-Interview (PSS-1), respectively, were randomised to receive either Narrative Exposure Therapy for Forensic Offender Rehabilitation (FORNET), Cognitive Behavioural Therapy (CBT) and controls. Saliva collection occurred before the intervention (baseline) and at 8 and 16 months post-intervention, and genomic DNA was extracted at subsequent follow-up visits. The Human Mental Disorders EpiTect Methyl II Signature PCR Array was used to quantify DNA methylation. Telomere length was determined using quantitative polymerase chain reaction (qPCR). PCR was used for genotyping. The data were analysed using regression models, repeated measures of analysis of variance (ANOVA), mixed models and Fisher’s least significant difference (LSD). No significant changes in methylation were observed in the FORNET group. However, methylation in both autism susceptibility candidate 2 (AUTS2) (p=0.000) and reelin (RELN) (p=0.023) genes decreased significantly in the CBT group between first and second follow-up visits. In the catechol-o-methyltransferase (COMT) gene, methylation significantly decreased between baseline and first follow-up (p=0.007), while between first and second follow-up visits there was a significant increase (p=0.038). Methylation in the RELN (r=0.38, p=0.02) gene exhibited strong positive correlation with appetitive aggression, while methylation in the COMT gene correlated with PTSD symptom severity (r=0.35, p=0.01). No significant correlation between appetitive aggression and telomere length (r=0.09, p= 0.121) was observed; however, increased telomere length correlated with higher PTSD symptom severity (r=0.13, p=0.039). The STin2 VNTR 12-repeat homozygous genotype and L’-STin2.12/STin2.12 were associated with appetitive aggression (p=0.003 and p=8.00 x 10–8, respectively). This research provides insights into the biological mechanisms that may play a significant role in appetitive aggression and PTSD. DNA methylation and telomere length may be biological markers that are responsive to psychotherapeutic interventions. The STin2 VNTR 12-repeat may be a distinguishing marker of appetitive and reactive forms of aggression. These biological mechanisms provided preliminary insights into appetitive aggression and PTSD.