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Title: Genetic dissection of neurocognitive phenotypes : implications for psychopathological susceptibility
Author: Lancaster, Thomas Matthew
Awarding Body: Prifysgol Bangor University
Current Institution: Bangor University
Date of Award: 2012
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This thesis aimed to uncover some of the more precise mechanisms by which genetic loci may influence neuropsychiatric susceptibility. I aim to identify genetic susceptibility for neuropsychiatric disorders using quantitative traits such as behaviour and neuroimaging parameters, which may help to index subclinical components present across several neuropsychiatric classifications. I probe specific neural networks/parameters of neurocognition; hypothesising to witness larger and more specific effects than assaying global parameters such as IQ and brain volume. I aim to uncover novel mechanisms by which some of the most intriguing genetic polymorphisms identified from recent genetic discoveries may modulate susceptibility. The first study provides evidence suggesting that a common genetic variant hypothesized to modulate dopamine levels (COMT), may account for individual differences in the brain's global valuation system, which may then mediate susceptibility to a host of neuropsychiatric illness characterised by deficits in reward processing. The second study provides evidence that genes identified by agnostic approaches (genome-wide association studies) may have a role in neurobiological pathways mechanistically linked to disorders such as schizophrenia/psychosis. I show a component of the working memory network for emotional 'faces is modulated by a variant on the ZNFB04A gene in a manner that mirrors the disruptions seen in patients with schizophrenia. The third study demonstrates that a variant on the CLU gene may modulate susceptibility to Alzheimer's disease in a similar functional manner to well-established genetic variants such as APOE.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available