title: Dopaminergic polymorphisms associated with time-on-task declines and fatigue in the Psychomotor Vigilance Test.
abstract: Prolonged demands on the attention system can cause a decay in performance over time known as the time-on-task effect. The inter-subject differences in the rate of this decline are large, and recent efforts have been made to understand the biological bases of these individual differences. In this study, we investigate the genetic correlates of the time-on-task effect, as well as its accompanying changes in subjective fatigue and mood. N = 332 subjects performed a 20-minute test of sustained attention (the Psychomotor Vigilance Test) and rated their subjective states before and after the test. We observed substantial time-on-task effects on average, and large inter-individual differences in the rate of these declines. The 10-repeat allele of the variable number of tandem repeats marker (VNTR) in the dopamine transporter gene and the Met allele of the catechol-o-methyl transferase (COMT) Val158Met polymorphism were associated with greater vulnerability to time-on-task. Separately, the exon III DRD4 48 bp VNTR of the dopamine receptor gene DRD4 was associated with subjective decreases in energy. No polymorphisms were associated with task-induced changes in mood. We posit that the dopamine transporter and COMT genes exert their effects by increasing dopaminergic tone, which may induce long-term changes in the prefrontal cortex, an important mediator of sustained attention. Thus, these alleles may affect performance particularly when sustained dopamine release is necessary.
authors.affiliation: Cognitive Science Lab, Temasek Laboratories, National University of Singapore, Singapore, Singapore. tsllzj@nus.edu.sg
authors.forename: Julian
authors.initials: J
authors.lastname: Lim
authors.forename: Richard
authors.initials: R
authors.lastname: Ebstein
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Tse
authors.forename: Mikhail
authors.initials: M
authors.lastname: Monakhov
authors.forename: Poh San
authors.initials: PS
authors.lastname: Lai
authors.forename: David F
authors.initials: DF
authors.lastname: Dinges
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kwok
mesh_terms: D000293:Adolescent; D000328:Adult; D001143:Arousal / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D005222:Mental Fatigue / Q000235:genetics* / Q000503:physiopathology; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011597:Psychomotor Performance / Q000502:physiology; D050638:Receptors, Dopamine D4 / Q000235:genetics* / Q000502:physiology; D013647:Task Performance and Analysis; D055815:Young Adult
chemical_list: D017931:DNA Primers; C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D002394:Catechol O-Methyltransferase