Abstract:
Cognitive abilities demonstrate considerable heritability and the mapping of the human genome has facilitated research into the specific genes that may underlie individual differences in performance. The genes coding for brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) are considered to be likely candidates for impacting on brain structure, function and plasticity, as well as various cognitive abilities. Research on their effects has yielded notoriously inconsistent results, however. Inconsistencies may be in part due to conflated outcome measures and the presence of moderating variables. The overarching aim of this thesis was to further understanding of the effects of genetic variation in the BDNF and COMT genes on cognitive outcomes. In the first study, the BDNF val66met (Rs6265) and COMT val158met (Rs4680) polymorphisms were examined in relation to recall and recognition performance in young adults. Recall and recognition were assessed using the Family Pictures and Faces subtests of the Wechsler Memory Scale – Third Edition (WMS-III), respectively. The BDNF polymorphism was demonstrated to affect performance on the hippocampal-dependent recall task while not affecting recognition performance. This indicates the importance of distinguishing between neurologically distinct forms of memory when investigating the effects of genes on memory ability. In the second study, sample size was increased in order to test for sex-specific effects of the COMT val158met polymorphism on face recognition. This study revealed an interaction between sex and COMT genotype on face recognition performance. COMT genotype affected face recognition ability in male participants only. Sex differences were observed for val homozygotes, with female val/val participants scoring significantly higher scores than males of this genotype. In the third study, the personality trait of Conscientiousness was shown to moderate the relationship between the BDNF val66met polymorphism and recall performance. The BDNF met allele was only associated with poorer recall performance in individuals low in self-reported Conscientiousness. Conscientiousness predicts a range of health-related behaviours that may bolster hippocampal function in BDNF met allele carriers. The fourth study analysed data from the longitudinal Auckland Birthweight Collaborative (ABC) study to examine how exposure to antenatal maternal stress affects the relationship between genetic variants in the COMT gene and IQ performance in children. A gene-environment interaction was found. Children exposed to high maternal antenatal stress were demonstrated to have significantly lower full-scale IQ scores at both 7 and 11 years of age than those exposed to low stress, only when they were carriers of the COMT Rs165599 G allele. The Rs165599 polymorphism may thus confer differential susceptibility to negative cognitive outcomes following exposure to an early stressor, highlighting the need to consider gene-environment interactions when investigating effects of antenatal stress on cognition. Gene-sex and geneenvironment interactions can be obscured in analyses that only allow for main effects of candidate genes on cognition, with implications for inconsistencies in the literature.