Abstract
The catecholamines dopamine and noradrenaline have been implicated in spontaneous low-frequency fluctuations in reaction time, which are associated with attention deficit hyperactivity disorder (ADHD) and subclinical attentional problems. The molecular genetic substrates of these behavioral phenotypes, which reflect frequency ranges of intrinsic neuronal oscillations (Slow-4: 0.027-0.073 Hz; Slow-5: 0.010-0.027 Hz), have not yet been investigated. In this study, we performed regression analyses with an additive model to examine associations between low-frequency fluctuations in reaction time during a sustained attention task and genetic markers across 23 autosomal catecholamine genes in a large young adult population cohort (n = 964), which yielded greater than 80% power to detect a small effect size (f2 = 0.02) and 100% power to detect a small/medium effect size (f2 = 0.15). At significance levels corrected for multiple comparisons, none of the gene variants were associated with the magnitude of low-frequency fluctuations. Given the study’s strong statistical power and dense coverage of the catecholamine genes, this either indicates that associations between low-frequency fluctuation measures and catecholamine gene variants are absent or that they are of very small effect size. Nominally significant associations were observed between variations in the alpha-2A adrenergic receptor gene (ADRA2A) and the Slow-5 band. This is in line with previous reports of an association between ADRA2A gene variants and general reaction time variability during response selection tasks, but the specific association of these gene variants and low-frequency fluctuations requires further confirmation. Pharmacological challenge studies could in the future provide convergent evidence for the noradrenergic modulation of both general and time sensitive measures of intra-individual variability in reaction time.
Highlights
Intra-subject variability in reaction time (RT) contains specific temporal components of relevance for different forms of psychopathology [1]
We present results that are significant at the uncorrected significance level for our a priori candidates (COMT/val158met and ADRA2A gene variants), and note that we have 100% power to detect associations of small effect size at this level
single-nucleotide polymorphism (SNP) that were excluded from analyses were: rs11568324, rs3730287 and rs62388321 (SLC6A2, ADRA1A and DRD1 genes, respectively), as the former SNP had a MAF
Summary
Intra-subject variability in reaction time (RT) contains specific temporal components of relevance for different forms of psychopathology [1]. A greater magnitude of low-frequency fluctuations in RT (< 0.1 Hz) has been associated with ADHD and subclinical attentional problems [1,2,3,4,5,6]. This suggests that an inability to modulate low-frequency RT fluctuations may underlie behavioral symptoms such as difficulty sustaining attention [1,2]. The inability to modulate low-frequency RT fluctuations could be caused by a catecholamine deficiency [2]. The question arises: do alterations in the regulation of catecholamine signaling modulate the strength of low-frequency RT fluctuations?
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