Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs
Abstract
Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable psychiatric disorder in children and adults. Recent meta-analyses have indicated an association between genes involved in dopaminergic signaling and childhood ADHD, but little is known about their possible role in adult ADHD. In this study of adults with ADHD, we evaluated the three most commonly studied ADHD candidate genetic polymorphisms; the dopamine receptor D4 (DRD4) exon 3 VNTR repeat, a microsatellite repeat 18.5 kb upstream of the DRD5 locus and the 3'UTR dopamine transporter SLC6A3 (DAT 1) VNTR. We examined 358 clinically diagnosed adult Norwegian ADHD patients (51% males) and 340 ethnically matched controls. We found a nominally significant overall association with adult ADHD for the DRD5 microsatellite marker (P = 0.04), and a trend toward increased risk associated with the 148-bp allele consistent with recent meta-analyses. The strongest overall association (P = 0.02) and increased risk for the 148-bp allele [odds ratio (OR) = 1.27 (95% CI: 1.00-1.61)] were seen in the inattentive and combined inattentive/hyperactive group as previously reported for childhood ADHD. No association was found for the DRD4 or SLC6A3 polymorphisms in this patient sample. In conclusion, our results among adults with a clinical diagnosis of ADHD support an association between ADHD and the DRD5 locus, but not the DRD4 or SLC6A3 loci. It is possible that the latter polymorphisms are associated with a transient form of ADHD with better long-term clinical outcome.
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Evidence on the association of DRD4 and DAT1 polymorphisms with childhood ADHD is inconsistent, with some candidate-gene studies finding associations and a case-control study finding none.
“For example, multiple candidate-gene association studies have indicated that polymorphisms in DRD4 and DAT1 are associated with cADHD (Brookes K. et al., 2006; Gornick et al., 2007), while results from a case-control study did not find any association between these two genes and ADHD (Johansson et al., 2008).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Johansson et al., 2008
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- Authors
- Johansson, S., Halleland, H., Halmøy, A., Jacobsen, K. K., Landaas, E. T., Dramsdahl, M., Fasmer, O. B., Bergsholm, P., Lundervold, A. J., Gillberg, C., Hugdahl, K., Knappskog, P. M., & Haavik, J.
- Affiliations
- Haukeland University Hospital (NO)
- University of Bergen (NO)
- University of Gothenburg (SE)
- Corresponding author
- Haavik, J.
- ORCID
- Venue
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2007-12-14
- Volume
- 147B
- Issue
- 8
- Pages
- 1470-1475
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2125049636
- Cited by
- 91
- References
- 30
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 8 · 2015: 12 · 2014: 2 · 2013: 7 · 2012: 5
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- adult ADHD, dopamine D4 receptor, dopamine transporter, dopaminergic signaling, genetic association, inattentive type ADHD
- MeSH terms
- Adult, Alleles, Attention Deficit Disorder with Hyperactivity, Female, Gene Frequency, Genetic Markers, Humans, Male, Polymorphism, Genetic, Retrospective Studies, Case-Control Studies, Microsatellite Repeats, Dopamine Plasma Membrane Transport Proteins, Receptors, Dopamine D4, Receptors, Dopamine D5
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