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Mol Psychiatry. 2014 Sep;19(9):1031-6. doi: 10.1038/mp.2013.140. Epub 2013 Oct 29.

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

Author information

1
1] School of Psychology, Monash University, Melbourne, VIC, Australia [2] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
2
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
3
1] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia [2] Prince Charles Hospital, Brisbane, QLD, Australia.
4
1] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia [2] Department of Child and Adolescent Psychiatry, Seoul National University, Seoul, South Korea.
5
School of Psychology, Cardiff University, Cardiff, Wales, UK.
6
1] School of Psychology, Monash University, Melbourne, VIC, Australia [2] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia [3] School of Psychology, The University of Queensland, Brisbane, QLD, Australia.

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.

PMID:
24166412
DOI:
10.1038/mp.2013.140
[Indexed for MEDLINE]

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