期刊
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
卷 17, 期 1, 页码 174-180出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1355617710001402
关键词
Cognition; Neuropsychological tests; Executive control; Catechol-O-methyltransferase; Polymorphism; Epistasis
资金
- National Institute of Neurological Disorders and Stroke [K23NS045830, R03NS056228, R01NS40472]
- National Multiple Sclerosis Society [RG3248, PP1214]
- Hitchcock Foundation
- National Institute on Aging [R01AG019771]
- National Institute on Disability and Rehabilitation Research [H133670031, H133G000136]
- National Institute of Child Health and Development [R01HD048176]
- Ira DeCamp Foundation
- NATIONAL CANCER INSTITUTE [R01CA101318] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS040472, K23NS045830, R03NS056228] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG019771] Funding Source: NIH RePORTER
The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene may be related to individual differences in cognition, likely via modulation of prefrontal dopamine catabolism. However, the available studies have yielded mixed results, possibly in part because they do not consistently account for other genes that affect cognition. We hypothesized that COMT Met allele homozygosity, which is associated with higher levels of prefrontal dopamine, would predict better executive function as measured using standard neuropsychological testing, and that other candidate genes might interact with COMT to modulate this effect. Participants were 95 healthy, right-handed adults who underwent genotyping and cognitive testing. COMT genotype predicted executive ability as measured by the Trail-Making Test, even after covarying for demographics and Apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), and ankyrin repeat and kinase domain containing 1 (ANKK 1) genotype. There was a COMT-ANKK 1 interaction in which individuals having both the COMT Val allele and the ANKK 1 T allele showed the poorest performance. This study suggests the heterogeneity in COMT effects reported in the literature may be due in part to gene gene interactions that influence central dopaminergic systems. (JINS, 2011, 17, 174-180)
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