COMT Val158Met genotype is associated with fluctuations in working memory performance: converging evidence from behavioural and single-trial P3b measures

• Published in: NeuroImage (Orlando, Fla.) Vol. 100; pp. 489 - 497
• Main Authors: Saville, C.W.N., Lancaster, T.M., Stefanou, M.E., Salunkhe, G., Lourmpa, I., Nadkarni, A., Boehm, S.G., Bender, S., Smyrnis, N., Ettinger, U., Feige, B., Biscaldi, M., Mantripragada, K.K., Linden, D.E.J., Klein, C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2014
• Subjects: Adult; Catechol O-Methyltransferase - genetics; Electroencephalography; Endophenotype; Event-Related Potentials, P300 - physiology; Female; Genetic Pleiotropy - genetics; Genetic Pleiotropy - physiology; Humans; Individuality; Intra-subject variability; Male; Memory, Short-Term - physiology; Mental chronometry; P300; Psychomotor Performance - physiology; Reaction time variability; rs4680; Young Adult; RT; Intra-subject variability; Mental chronometry; P300; Reaction time variability; COMT; ISV; rs4680; Endophenotype
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2014.06.006

Intra-subject variability in reaction times (ISV) is a promising endophenotype for several psychiatric conditions, but its neural underpinnings are not yet established. Converging evidence from neuroimaging, molecular genetics, and psychopharmacology suggests that ISV could index catecholaminergically-mediated neural noise. The fine-grained temporal resolution of electroencephalography is ideal for investigating ISV, but only if potential neural correlates of ISV can be assessed in single trials. Based on evidence that ISV is associated with dopaminergic functioning, we apply a recently developed method of single-trial P3b analysis to investigate the association of COMT Val158Met genotype with measures of ISV on the behavioural and neural levels at different working memory loads. Greater number of Met alleles was associated with poorer and more intra-individually variable performance on the tasks, and greater latency jitter in single-trial P3bs. These converging results at the behavioural and neurophysiological levels confirm previous observations that prefrontal dopamine availability is associated with stability and accuracy of cognitive performance. Together with previous studies, these data imply pleiotropic cognitive effects of COMT genotype. •Val-carriers more accurate on n-back tasks than Met/Met carriers.•Val/Val carriers have less variable reaction times than Met carriers.•Val/Val carriers have less variable single trial P3b latencies than Met carriers.