Examining the influence of childhood trauma and epigenetic variation in brain-derived neurotrophic factor on anxiety sensitivity

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dc.contributor.advisorWomersley, Jacquelineen_ZA
dc.contributor.advisorHemmings, Sianen_ZA
dc.contributor.authorChifamba, Leahen_ZA
dc.contributor.authorMartin, Lindien_ZA
dc.contributor.authorSeedat, Sorayaen_ZA
dc.contributor.authorHemmings, Sianen_ZA
dc.contributor.authorWomersley, Jacquelineen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics.en_ZA
dc.date.accessioned2022-02-24T09:48:47Zen_ZA
dc.date.accessioned2022-04-29T12:51:19Zen_ZA
dc.date.available2022-08-24T03:00:10Zen_ZA
dc.date.issued2022-02en_ZA
dc.descriptionThesis (MEng)--Stellenbosch University, 2022.en_ZA
dc.description.abstractENGLISH ABSTRACT: Anxiety sensitivity (AS) is defined as the likelihood of interpreting anxiety-related bodily sensations as having potentially harmful effects on psychological and physical wellbeing. Anxiety sensitivity is a risk factor for the development of anxiety disorders. The aetiology of AS is linked to genetic and environmental interactions. One environmental factor that has been linked to AS is childhood trauma (CT). The gene encoding the brain-derived neurotrophic factor (BDNF) has been implicated in psychiatric disorders, as well as neuroplastic changes that can occur after CT exposure. These changes can occur via epigenetic mechanisms, chemical modifications of DNA that alter expression without altering DNA sequence. DNA methylation is one epigenetic mechanism. The aim was to determine the associative and interactive effects of CT and epigenetic variation in BDNF on AS in adolescents from South Africa. This study investigated BDNF single nucleotide polymorphisms (SNPs), and DNA methylation associated with AS and CT effects in 951 participants who self-identified as being Xhosa or South African Coloured (SAC). Six BDNF SNPs, rs11030099, rs6265, rs11030101, rs2049046, rs908867 and rs1491850 were genotyped in 951 participants. Methylation of BDNF promoter I CpG sites was assessed in a subset of participants (n = 90). Statistical analysis was performed using R programming. In Xhosa females, the rs11030101 TT genotype was associated with decreased AS (p = 0.032). Furthermore, rs2049046 AT genotype was associated with decreased AS (p = 0.009) in SAC females. The interaction of CT with the BDNF rs2049046 AA genotype was associated with lower AS (p = 0.029) in Xhosa females. No significant association was found between CT, AS and methylation, also no significant genetype interaction with CT on methylation was identified. Our results provide insight into the role of genetic variation in BDNF on AS in adolescents and emphasises the importance of examining the influence of gene x environment interactions on AS in differentiated ethnic and sex groups.en_ZA
dc.description.abstractAngs-sensitiwiteit (AS) word gedefinieer as die waarskynlikheid om angsverwante liggaamlike sensasies te interpreteer as moontlik skadelik vir sielkundige en fisiese welstand. Angs-sensitiwiteit is 'n risikofaktor vir die ontwikkeling van angsversteurings. Die etiologie van AS hou verband met genetiese en omgewingsinteraksies. Een omgewingsfaktor wat verwant is aan AS, is kinderjare trauma (KT). Die geen wat brein-afgeleide neurotrofiese faktor (BDNF) kodeer was al bevind om betrokke te wees in psigiatriese versteurings sowel as neuroplastiese veranderinge wat kan voorkom na KT-blootstelling. Hierdie veranderinge kan plaasvind via epigenetiese meganismes - chemiese modifikasies van DNA wat geen uitdrukking verander sonder om die DNA-volgorde te verander. DNA-metilering is een epigenetiese meganisme. Die doel was om die verwantskappe en interaktiewe effekte van KT en epigenetiese variasie in BDNF op AS te bepaal, in Suid-Afrikaanse adolessente. Hierdie studie het BDNF-variante en DNA-metilering wat met AS- en KT-effekte geassosieer word, ondersoek in 951 deelnemers wat hulself as Xhosa of Suid-Afrikaanse Kleurling (SAK) geïdentifiseer het. Ses BDNF enkelnukleotied polimorfismes (ENP's), rs11030099, rs6265, rs11030101, rs2049046, rs908867 en rs1491850 is in 951 deelnemers ondersoek. Metilering van BDNF-promotor I CfG-plekke was in ‘n subset van deelnemers (n = 90) ondersoek. Statistiese analise was uitgevoer met behulp van R-programmering. Die rs11030101 TT genotipe was geassosieer met verlaagde AS (p = 0.032) in Xhosa vrouens. Verder was rs2049046 AT genotipe geassosieer met verlaagde AS (p = 0.009) in SAK vrouens. Die interaksie tussen KT en die BDNF rs2049046 AA genotipe was geassosieer met laer AS (p = 0.029) in Xhosa vrouens. Geen beduidende assosiasies tussen metilering, AS en KT was geïdentifiseer, verder geen beduidende assosiasie tussen metilering en die interaksie van genotipe en KT was geïdentifiseer. Ons resultate gee insig in die rol wat genetiese variasie in BDNF op AS speel in adolessente en beklemtoon die belangrikheid om die invloed van gene x omgewing interaksies op AS in gedifferensieerde etniese en geslags groepe te ondersoek.af_ZA
dc.description.versionMastersen_ZA
dc.embargo.terms2022-08-24en_ZA
dc.format.extentxi, 85 pages : illustrationsen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/125036en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subject.lcshAnxiety sensitivity -- South Africaen_ZA
dc.subject.lcshPsychic trauma in children -- South Africaen_ZA
dc.subject.lcshNeurotrophic functions -- South Africaen_ZA
dc.subject.lcshEpigenetics -- South Africaen_ZA
dc.titleExamining the influence of childhood trauma and epigenetic variation in brain-derived neurotrophic factor on anxiety sensitivityen_ZA
dc.typeThesisen_ZA
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