Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time

Abstract

Intra-individual variability in response time has been proposed as an important endophenotype for attention deficit hyperactivity disorder (ADHD). Here we asked whether intra-individual variability is predicted by common variation in catecholamine genes and whether it mediates the relationship between these gene variants and self-reported ADHD symptoms. A total of 402 non-clinical Australian adults of European descent completed a battery of five cognitive tasks and the Conners' Adult ADHD Rating Scale. Exclusion criteria included the presence of major psychiatric or neurologic illnesses and substance dependency. A total of 21 subjects were excluded due to incomplete data or poor quality cognitive or genotyping data. The final sample comprised 381 subjects (201 males; mean age=21.2 years, s.d.=5.1 years). Principal components analysis on variability measures yielded two factors (response selection variability vs selective attention variability). Association of these factors with catecholamine gene variants was tested using single-step linear regressions, with multiple comparisons controlled using permutation analysis. The response selection variability factor was associated with two ADRA2A single-nucleotide polymorphisms (SNPs) (rs1800544, rs602618), p corrected=0.004, 0.012, respectively, whereas the selective attention variability factor was associated with a TH SNP (rs3842727), p corrected=0.024. A bootstrapping analysis indicated that the response selection variability factor mediated the relationship between the ADRA2A SNP rs1800544 and self-reported ADHD symptoms. Thus this study finds evidence that DNA variation in the ADRA2A gene may be causally related to ADHD-like behaviors, in part through its influence on intra-individual variability. Evidence was also found for a novel association between a TH gene variant and intra-individual variability.

Perception of emotion in facial stimuli: The interaction of ADRA2A and COMT genotypes, and sex

“…The G-allele of that genetic variant has been associated with inattention (Roman et al, 2006;Williams et al, 2010;Domschke et al, 2008), impulsive personality traits (Mäestu et al, 2008;Comings et al, 2000), and with ADHD (Kiive et al, 2010;Cummins et al, 2014;Roman et al, 2006). Thus, in this study we expected G-allele to predict slower response times in emotion detection (due to inattention during the task), and also affect emotion perception in interaction with COMT…”

Resting cardiac vagal tone predicts intraindividual reaction time variability during an attention task in a sample of young and healthy adults

“…The task was administered via E-Prime 1.0 software (Psychology Software Tools, Inc., Sharpsburg, PA). Similar attentional variants of the flanker (and Posner cueing) tasks have been previously used to index IIV (e.g., Cummins et al, 2014;Hultsch et al, 2002;Lu, Fung, Chan, & Lam, 2016;Tamnes, Fjell, Westlye, Østby, & Walhovd, 2012).…”

α2A‐Adrenergic receptor polymorphisms and mRNA expression levels are associated with delay discounting in cocaine users

“…In addition, another study presenting an association of rs1800544 with intra‐individual variability in response time suggested that ADRA2A SNPs are rather associated with objectively measureable endophenotypes of ADHD (such as intra‐individual variability in response time) than with the complete clinical phenotype of ADHD itself (Cummins et al . ). In line with these two studies, we provide evidence for an interaction between ADRA2A SNPs and cocaine use regarding DD, which has been proposed as an addiction endophenotype (MacKillop ).…”