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Norepinephrine transporter and catecholamine-O-methyltransferase gene variants and attention-deficit/hyperactivity disorder symptoms in adults

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Summary.

Attention deficit/hyperactivity disorder (ADHD) is a complex, highly heritable psychiatric condition. Neuropsychological and pharmacological studies suggest a dysregulation of central noradrenergic neurotransmission in addition to dopaminergic and serotonergic mechanisms. Only a few studies have focused on the association of noradrenergic susceptibility genes with ADHD.

In this study, we investigated the association of several ADHD symptom scores (German short form of the Wender Utah Rating Scale, WURS-k; ADHD self report, ADHD-SB, and the German validated version of the WRAADDS, WRI) with haplotypes of the catechol-O-methyltransferase (COMT) and the norepinephrine transporter (SLC6A2) genes. Subjects were genotyped for three SLC6A2 (rs5569, rs998424, rs2242447) and two COMT single nucleotide polymorphisms (rs4680, rs4818). In addition, psychosocial adversity in childhood was assessed in order to evaluate putative gene-environment interactions.

We did not find main effects of the COMT and SLC6A2 NET1 gene haplotypes on any ADHD symptom severity score. Childhood psychosocial adversity was strongly associated with number of ADHD symptoms. No gene-environment interaction was found. A specific combination of two COMT and SLC6A2 gene haplotypes, containing the low functioning COMT variant was nominally associated with low ADHD scores in all scales. Results do not support the hypothesis that common variants in the SLC6A2 and COMT genes in particular are associated with ADHD, but might give some evidence for interactive effects between these gene variants on ADHD severity.

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Authors and Affiliations

  1. Institute for Forensic Psychology and Psychiatry, Saarland University Hospital, Homburg, Germany

    W. Retz & M. Rösler

  2. Department of Neuroscience and Molecular Psychiatry, Institute of Life Science, The School of Medicine, Swansea University, UK

    C. Kissling, R. Hünnerkopf, A. Coogan & J. Thome

  3. German Cancer Research Centre, Division of Molecular Genome Analysis, Heidelberg, Germany

    S. Wiemann

  4. Department for Child and Adolescent Psychiatry, Saarland University Hospital, Homburg, Germany

    C. Freitag

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  1. W. Retz
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  2. M. Rösler
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  3. C. Kissling
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  4. S. Wiemann
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  5. R. Hünnerkopf
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  6. A. Coogan
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  7. J. Thome
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Correspondence to W. Retz.

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Correspondence: Wolfgang Retz, Institute for Forensic Psychology and Psychiatry, Saarland University Hospital, 66421 Homburg/Saar, Germany

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Retz, W., Rösler, M., Kissling, C. et al. Norepinephrine transporter and catecholamine-O-methyltransferase gene variants and attention-deficit/hyperactivity disorder symptoms in adults. J Neural Transm 115, 323–329 (2008). https://doi.org/10.1007/s00702-007-0822-5

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