Cumulative Dopamine Genetic Score predicts behavioral and electrophysiological correlates of response inhibition via interactions with task demand

• Published in: Cognitive, affective, & behavioral neuroscience Vol. 20; no. 1; pp. 59 - 75
• Main Authors: Enge, Sören, Sach, Mareike, Reif, Andreas, Lesch, Klaus-Peter, Miller, Robert, Fleischhauer, Monika
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2020; Springer Nature B.V
• Subjects: Behavior; Behavioral Science and Psychology; Catechol; Catechol O-methyltransferase; Cognitive ability; Cognitive Psychology; Dopamine; Impulsivity; Mathematical models; Methyltransferase; Neural coding; Neurosciences; Phenotypes; Polymorphism; Psychology; Punishment; Single-nucleotide polymorphism; Statistical analysis; Response inhibition; ERP; Dopamine; Genetic score; NoGo-P3
• ISSN: 1530-7026; 1531-135X
• DOI: 10.3758/s13415-019-00752-w

Functional genetic polymorphisms in the brain dopamine (DA) system have been suggested to underlie individual differences in response inhibition, namely the suppression of a prepotent or inappropriate action. However, findings on associations between single DA polymorphisms and inhibitory control often are mixed, partly due to their small effect sizes. In the present study, a cumulative genetic score (CGS) was used: alleles previously associated with both impulsive behavior and lower baseline DA level, precisely the DRD4 Exon III 7-repeat, DAT1 VNTR 10-repeat and the COMT 158val allele, each added a point to the DA-CGS. Participants (N = 128) completed a Go/No-Go task varying in difficulty and EEG recordings were made with focus on the NoGo-P3, an ERP that reflects inhibitory response processes. We found a higher DA-CGS (lower basal/tonic DA level) to be associated with better performance (lower %FA and more adaptive responding) in the very demanding/rapid than in the less demanding/rapid condition, whereas the reverse pattern was true for individuals with a lower DA-CGS. A similar interaction pattern of DA-CGS and task condition was found for NoGo-P3 amplitude. In line with assumptions of distinct optimum DA levels for different cognitive demands, a DA-CGS-dependent variation of tonic DA levels could have modulated the balance between cognitive stability and flexibility, thereby affecting the optimal DA level required for the specific task condition. Moreover, a task demand-dependent phasic DA release might have added to the DA-CGS-related basal/tonic DA levels, thereby additionally affecting the balance between flexibility and stability, in turn influencing performance and NoGo-P3.