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The effect of dopamine related genetic variants on reward-related neuronal processing : a neuroimaging genetics study
Thesis (MSc)--Stellenbosch University, 2022.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867613827159293952 |
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| access_status_str | Open Access |
| author | Roomaney, Aqeedah Abbas |
| author2 | Hemmings, Sian Megan Joanna |
| author_browse | Hemmings, Sian Megan Joanna Roomaney, Aqeedah Abbas |
| author_facet | Hemmings, Sian Megan Joanna Roomaney, Aqeedah Abbas |
| author_sort | Roomaney, Aqeedah Abbas |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/125033 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:42:19.474Z |
| 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:10019.1/125033 The effect of dopamine related genetic variants on reward-related neuronal processing : a neuroimaging genetics study Roomaney, Aqeedah Abbas Hemmings, Sian Megan Joanna Womersley, Jacqueline Samantha Swart, Patricia Cathryn Du Plessis, Stefan Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics. Brain -- Imaging Cognitive neuroscience Dopaminergic neurons UCTD Thesis (MSc)--Stellenbosch University, 2022. ENGLISH SUMMARY: Dopaminergic signalling is influenced by dopamine synthesis, release, re-uptake and degradation, as well as receptor availability and binding capacity. Genetic variation in these components may mediate reward processing in the ventral striatal reward network. Though altered signalling in this network has been implicated in a range of mental disorders, it is not clear whether the observed changes in reward processing are influenced by underlying genetic risk. There is thus a need to first understand potential genetic influences on the reward system in a healthy population. This study generated a genetic-imaging dataset, identifying gene variants involved in endogenous dopamine signalling in 93 healthy participants with functional magnetic resonance imaging (fMRI) data. We selected variants in dopamine receptor genes (DRD) – DRD1 rs686 and DRDI rs4532; DRD2 rs1800497, DRD2 rs4274224 and DRD2 rs12364283; DRD3 rs6280 and the DRD4 variable number of tandem repeats (VNTR) region, as well as the catechol-O-methyltransferase (COMT rs4680), dopamine transporter (DAT VNTR) and brain-derived neurotrophic factor (BDNF rs6265) genes and determined the association of these variants with performance on a reward-based monetary incentive delay task (MID) task. The MID task was used to quantify the blood-oxygen-level dependent (BOLD) response in reward networks during reward anticipation and response. We used a repeated measures analysis of variance to investigate the relationship between the selected dopamine-related genetic variants and reward processing. In general, participants showed expected behavioural responses and functional brain activity when performing the task. Ten genetic variants were tested, and we observed a significant association between the ventral striatum BOLD response during reward anticipation and the BDNF rs6265 variant, with heterozygous (C/T) participants exhibiting significantly increased activity compared to participants in the homozygous C/C group (p = 0.048). In addition, participants homozygous for the DRD2 rs4274224 A allele exhibited increased activity during reward anticipation compared to heterozygous (G/A) participants (p = 0.009). During reward outcome, participants with the DRD3 rs6280 T/T genotype showed increased BOLD activity in the orbitofrontal cortex compared to participants with the C/T genotype (p = 0.035). We did not find any associations between reward-related neuronal activity and the other genetic variants of interest. The findings of this study demonstrate the potential genetic influences on the reward system, both during reward anticipation in the ventral striatum and reward outcome in the orbitofrontal cortex. This study thus highlights the need for future research on the genomic pathways associated with impaired reward processing and how this relates to mental disorders. AFRIKAANSE OPSOMMING: Dopaminerge aktiwiteit word deur verskeie faktore beinvloed, soos byvoorbeeld dopamien sintese, vrystelling, heropname en afbraak, sowel as beskikbaarheid van reseptore en bindingsvermoe. Genetiese variasie in dopaminerge komponente kan beloningsverwerking in die ventrale-striatale beloningsnetwerk bemiddel. Alhoewel wisselende aktiwiteit in hierdie netwerk by 'n verskeidenheid geestesversteurings betrokke is, is dit nie duidelik of veranderinge in beloningverwerking beinvloed word deur onderliggende genetiese risiko nie. Daar is dus 'n behoefte om moontlike genetiese invloede op die beloningstelsel in 'n gesonde bevolking te verstaan. In hierdie studie was 'n genetiese-beeld datastel gebruik om geenvariante te identifiseer wat betrokke is by endogene dopamien aktiwiteit in 93 gesonde deelnemers met funksionele magnetiese resonansie beelding (fMRI) data. Ons het variante in die dopamienreseptor-gene (DRD1, DRD2, DRD3 en DRD4), sowel as die catechol-O-methyltransferase (COMT), dopamien transporter (DAT) en brein-afgeleide neurotrofiese faktor (BDNF) gene gekies. Assosiasies tussen hierdie variante met uitvoering op 'n beloninggebaseerde monetere aansporingsvertragingtaak (MID) bepaal. Die MID-taak is gebruik om die bloed-suurstofvlak-afhanklike (BOLD) reaksie in beloningsnetwerke te kwantifiseer tydens beloningafwagting en reaksie. Ons het 'n herhaalde metings-variansieanalise gebruik om die verband tussen die geselekteerde dopamienverwante genetiese variante by beloningverwerking te ondersoek. Oor die algemeen het deelnemers verwagte gedragsreaksies en funksionele aktiwiteit getoon tydens die uitvoering van die taak. Ons het egter 'n beduidende verband tussen die BOLD reaksie in die ventrale striatum tydens afwagting van beloning in die BDNF rs6265 -variant waargeneem, met deelnemers met die C/T -genotipe wat beduidend verhoogde aktiwiteit toon in vergelyking met deelnemers met die homosigotiese C/C -groep (p = 0,048). Deelnemers met die homosigotiese rs4274224 (DRD2) A/A genotipe het ook 'n relatiewe verhoog in aktiwiteit tydens beloningafwagting getoon in vergelyking met deelnemers in die G/A -groep (p = 0.009). Tydens die belonging/beloningsuitkoms, het deelnemers met die homosigotiese rs6280 (DRD3) T/T -genotipe verhoogde BOLD -aktiwiteit in die orbitofrontale korteks getoon in vergelyking met deelnemers met die C/T -genotipe (p = 0.035). Die bevindinge van hierdie studie demonstreer die potensiele genetiese invloed op die beloningstelsel, beide tydens beloningafwagting in die ventrale striatum en beloningsuitkoms in die orbitofrontale korteks. Hierdie studie ondersoek dopaminerge genetiese variasie onderliggend aan beloningsverwerkingsafwykings en beklemtoon die behoefte aan toekomstige navorsing oor die genomiese wee wat verband hou met verlaagde beloningverwerking en hoe dit verband hou met geestesversteurings. Masters 2022-02-17T10:23:26Z 2022-04-29T12:51:11Z 2022-08-17T03:00:09Z 2022-04 Thesis http://hdl.handle.net/10019.1/125033 en_ZA Stellenbosch University viii, 67 pages : illustrations, includes annexures application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Brain -- Imaging Cognitive neuroscience Dopaminergic neurons UCTD Roomaney, Aqeedah Abbas The effect of dopamine related genetic variants on reward-related neuronal processing : a neuroimaging genetics study |
| title | The effect of dopamine related genetic variants on reward-related neuronal processing : a neuroimaging genetics study |
| title_full | The effect of dopamine related genetic variants on reward-related neuronal processing : a neuroimaging genetics study |
| title_fullStr | The effect of dopamine related genetic variants on reward-related neuronal processing : a neuroimaging genetics study |
| title_full_unstemmed | The effect of dopamine related genetic variants on reward-related neuronal processing : a neuroimaging genetics study |
| title_short | The effect of dopamine related genetic variants on reward-related neuronal processing : a neuroimaging genetics study |
| title_sort | effect of dopamine related genetic variants on reward related neuronal processing a neuroimaging genetics study |
| topic | Brain -- Imaging Cognitive neuroscience Dopaminergic neurons UCTD |
| url | http://hdl.handle.net/10019.1/125033 |
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