Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort
Thesis (MSc)--Stellenbosch University, 2022.
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | en_ZA |
| Published: |
Stellenbosch : Stellenbosch University
2022
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613805951844352 |
|---|---|
| access_status_str | Open Access |
| author | Rust, Thomas Martin |
| author2 | Womersley, Jacqueline |
| author_browse | Rust, Thomas Martin Womersley, Jacqueline |
| author_facet | Womersley, Jacqueline Rust, Thomas Martin |
| author_sort | Rust, Thomas Martin |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/126339 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:41:59.323Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/126339 The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort Rust, Thomas Martin Womersley, Jacqueline Hemmings, Sian Seedat, Soraya Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics. Anxiety in adolescence Epigenetics -- Variation Childhood trauma Structural neuroimaging UCTD Thesis (MSc)--Stellenbosch University, 2022. ENGLISH ABSTRACT: Anxiety disorders are a complex, multifactorial class of psychiatric disorders characterised by excessive fear or anxiety in the absence of anxiety-provoking stimuli. The aetiology of anxiety disorders is influenced by genetic and environmental factors, with childhood and adolescence being periods of increased sensitivity to environmental effects. Anxiety proneness (AP) is a risk factor for anxiety disorder development and is an endophenotype for anxiety disorders. Previous studies have implicated childhood trauma (CT), the neuropeptide oxytocin, and the gene encoding for the oxytocin receptor (OXTR) in anxiety pathology and brain morphology. Epigenetics provides a way to study gene-environment interactions, and DNA methylation is an epigenetic mechanism with the ability to influence gene expression. This study investigated the role that CT and OXTR single nucleotide polymorphisms (SNPs) and alterations in DNA methylation play in the development of AP and structural brain differences in a two-tier study consisting of Xhosa and South African Coloured (SAC) adolescents. Tier 1 (n = 951) investigated the effects of rs53576 and rs2254298 on AP, alone and in combination with CT. Tier 2 (n = 90) assessed methylation of a 413 bp region in OXTR exon 1 using EpiTYPER MassARRAY technology in a subset of participants grouped according to AP and CT severity. The contributions of OXTR SNPs and methylation on structural magnetic resonance imaging (sMRI) data for six bilateral brain regions were assessed in tier 2. In SAC males, the rs53576 A allele was associated with increased AP (p = 0.006, 95% CI = [G/A: -0.814 – 9.284] [A/A: 5.223 – 21.803]). Increased CT was associated with decreased AP in SAC females (p = 0.017, 95% CI = [G/A: -0.600 - 0.059] [A/A: -0.747 - 0.007]) and increased AP in SAC males (p = 0.032, 95% CI = [G/A: 0.032 – 0.670 [A/A: -4.169 – 0.869]) in rs2254298 GA carriers. The interaction of higher CT and the rs53576 A allele was associated with increased methylation at two cytosine-guanine dinucleotide (CpG) units, CpG 28.29 (p = 0.025, 95% CI = [G/A: -0.0014 – 0.0018] [A/A: -0.0001 – 0.0025]) and CpG 34.35 (p = 0.002, 95% CI = [G/A: -0.0001 – 0.0044] [A/A: -0.0001 – 0.0036]). High CT interacted with AP to result in increased methylation at CpG 3.4 in the high AP group and decreased methylation at CpG 3.4 in the low AP group (p = 0.017, 95% CI = 0.003 – 0.030). Increased left amygdala volume was reported in rs2254298 GG carriers (p = 0.009, 95% CI = -264 – -43.1). Increased left amygdala (p = 0.014, 95% CI = -255.2 – -33.66]), hippocampal (p = 0.043, 95% CI = -421.5 – -13.794) and thalamic (p = 0.008, 95% CI = -725.4 – -129.02]) volumes were reported in rs53576 GG carriers. Decreased CpG 27 methylation was associated with decreased left thalamus (p = 0.025, 95% CI = 1.403e+03 – 2.049e+04) and anterior cingulate cortex (ACC) volumes (p = 0.051, 95% CI = -4.204e+01 – 2.166e+04), and increased methylation was associated with decreased right amygdala (CpG3.4) (p = 0.022, 95% CI = -5.837e+03 – -4.731e+02), thalamus (CpG 13.14) (p = 0.025, 95% CI = -2.859e+04 – - 1.552e+03) and ACC (CpG 28.29) (p = 0.039, 95% CI = -1.911e+04 – -9.735e+02) volumes prior to correction for multiple testing. In conclusion, the present study suggests a role for CT and (epi)genetic variation of OXTR in AP and brain structure in South African adolescents. Angsversteurings is ‘n ingewikkelde veelfaktoriese klas van psigiatriese versteurings gekenmerk deur oormatige vrees of angs in die afwesigheid van angswekkende stimuli. Die etiologie van angsversteurings word deur genetiese en omgewingsfaktore beinvloed, waarvan laasgenoemde ‘n verhoogde rol tydens kinderjare en adolessensie speel. Angs geneigdheid (AP) is ‘n risikofaktor vir die ontwikkeling van angsversteuring en is ‘n endofenotipe vir angsversteurings. Vorige studies dui daarop dat kinderjare trauma (CT), die neuropeptide oksitosien, en die gene wat enkodeer vir die oksitosien reseptor (OXTR), ‘n rol in angspatologie en breinmorfologie speel. Epigenetika baan die weg vir ‘n ondersoek na gene-omgewing-wisselwerking, en DNS metielasie is ‘n epigenetiee meganisme met die vermoë om gene uitdrukking te beinvloed. Hierdie studie het die rol wat CT en OXTR enkel nukleotied polimorfismes (SNPs) en veranderinge in DNS metielase speel in die ontwikkeling van AP en strukturele breinverskille in ’n twee-vlak studie wat uit Xhosa en SuidAfrikaanse bruin (SAC) adolessente bestaan, ondersoek. Vlak 1 (n = 951) het die effek van rs53576 en rs2254298 op AP ondersoek, beide alleenstaande en in kombinasie met CT. Vlak 2 (n = 90) het metilasie van ‘n 413 bp streek in OXTR ekson 1 geassesseer deur EpiTYPER MassARRAY tegnologie in ‘n subset van deelnemers gegroepeer volgens die erns van AP en CT. Die bydraes van OXTR SNPs en metilasie op stukturele magnetiese resonans beeld data (sMRI) vir ses bilaterale breingebiede is in vlak 2 geassesseer. In SAC mans was die rs53576 A alleel geassosieer met verhoogde AP (p = 0.006, 95% CI = [G/A: -0.814 – 9.284] [A/A: 5.223 – 21.803]). Verhoogde CT is geassosieer met verminderde AP in SAC vroue (p = 0.017, 95% CI = [G/A: -0.600 -0.059] [A/A: -0.747 - 0.007]), en met verhoogde AP by SAC mans (p = 0.032, 95% CI = [G/A: 0.032 – 0.670] [A/A: -4.169 – 0.869]) in rs2254298 GA draers. Die interaksie tussen hoër waardes van CT en die rs53576 A allele is geassosieer met verhoogde metilasie by twee sitosien-guanien dinukleotide (CpG) eenhede (CpG 28.29 (p = 0.025, 95% CI = [G/A: -0.0014 – 0.0018] [A/A: -0.0001 – 0.0025]) en CpG 34.35 (p = 0.002, 95% CI = [G/A: - 0.0001 – 0.0044] [A/A: -0.0001 – 0.0036]). Hoë CT interaksie met AP lei tot verhoogde metilasie by CpG 3.4 in die hoë AP groep, en verminderde metilasie by CpG 3.4 in die lae AP groep (p = 0.017, 95% CI = 0.003 – 0.030). Verhoogde linker amigdala volume is gerapporteer in rs2254298 GG draers (p = 0.009, 95% CI = -264 – -43.1). Verhoogde volumes van die linker amigdala (p = 0.014, 95% CI = - 255.2 – -33.66), hippokampus (p = 0.043, 95% CI = -421.5 – -13.794) en talamus (p = 0.008, 95% CI = - 725.4 – -129.02) is gerapporteer in rs53576 GG draers. Verminderde CpG 27 metilasie kom is geassosieer met verminderde volumes van die linker talamus (p = 0.025, 95% CI = 1.403e+03 – 2.049e+04) en voorste singulate korteks (ACC) (p = 0.051, 95% CI = -4.204e+01 – 2.166e+04), en verhoogde metilasie is geassosieer met verminderde volumes van die regter amigdala (CpG 3.4) (p = 0.022, 95% CI = -5.837e+03 – -4.731e+02), talamus (CpG 13.14) (p = 0.025, 95% CI = -2.859e+04 – - 1.552e+03) en ACC (CpG 28.29) (p = 0.039, 95% CI = -1.911e+04 – -9.735e+02) voor regstelling weens veelvuldige toetsing. Ter afsluiting: die huidige studie dui op ‘n rol vir CT en (epi)genetiese wisseling van OXTR in AP en brein struktuur in Suid-Afrikaanse adolessente. Masters 2022-11-21T09:10:17Z 2023-01-23T06:52:59Z 2022-11-21T09:10:17Z 2022-11 Thesis http://hdl.handle.net/10019.1/126339 en_ZA Stellenbosch University xv, 109 pages : illustrations. application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Anxiety in adolescence Epigenetics -- Variation Childhood trauma Structural neuroimaging UCTD Rust, Thomas Martin The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort |
| title | The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort |
| title_full | The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort |
| title_fullStr | The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort |
| title_full_unstemmed | The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort |
| title_short | The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort |
| title_sort | influence of childhood trauma and epigenetic variation in oxtr on anxiety proneness and structural neuroimaging measures in a south african adolescent cohort |
| topic | Anxiety in adolescence Epigenetics -- Variation Childhood trauma Structural neuroimaging UCTD |
| url | http://hdl.handle.net/10019.1/126339 |
| work_keys_str_mv | AT rustthomasmartin theinfluenceofchildhoodtraumaandepigeneticvariationinoxtronanxietypronenessandstructuralneuroimagingmeasuresinasouthafricanadolescentcohort AT rustthomasmartin influenceofchildhoodtraumaandepigeneticvariationinoxtronanxietypronenessandstructuralneuroimagingmeasuresinasouthafricanadolescentcohort |