The serotonin transporter gene polymorphism 5‐ HTTLPR moderates the effects of stress on attention‐deficit/hyperactivity disorder
Open accessAbstract
Introduction: The role of the serotonin transporter gene polymorphism 5‐ HTTLPR in attention‐deficit/hyperactivity disorder ( ADHD ) is unclear. Heterogeneity of findings may be explained by gene–environment interactions ( G x E ), as it has been suggested that S‐allele carriers are more reactive to psychosocial stress than L‐allele homozygotes. This study aimed to investigate whether 5‐ HTTLPR genotype moderates the effects of stress on ADHD in a multisite prospective ADHD cohort study. Methods: 5‐ HTTLPR genotype, as well as the number of stressful life events in the past 5 years and ongoing long‐term difficulties, was determined in 671 adolescents and young adults with ADHD , their siblings, and healthy controls (57.4% male, average age 17.3 years). Linear mixed models, accounting for family relatedness, were applied to investigate the effects of genotype, experienced stress, and their interaction on ADHD severity at time point T2, while controlling for ADHD severity at T1 (mean follow‐up time 5.9 years) and for comorbid internalizing problems at T2. Results: The interaction between genotype and stress significantly predicted ADHD severity at T2 ( p = .006), which was driven by the effect on hyperactivity–impulsivity ( p = .004). Probing of the interaction effect made clear that S‐allele carriers had a significantly more positive correlation between stress and ADHD severity than L‐allele homozygotes. Conclusion: The results show that the interaction between 5‐ HTTLPR and stress is a mechanism involved particularly in the hyperactivity/impulsivity dimension of ADHD , and that this is independent of comorbid internalizing problems. Further research into the neurobiological mechanisms underlying this interaction effect is warranted.
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A variant of 5-HTTLPR is involved in the hyperactivity and impulsivity dimensions of ADHD in interaction with stress.
“For example, a variant of 5-HTTLPR -a polymorphic region located in the promoter of SLC6A4 - is involved in the hyperactivity and impulsivity dimensions of ADHD in interaction with stress 60 .”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [60]
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Attention-deficit/hyperactivity disorder
Faraone, S. V., Asherson, P., Banaschewski, T., Biederman, J., Buitelaar, J. K., Ramos-Quiroga, J. A., Rohde, L. A., Sonuga-Barke, E. J. S., Tannock, R., & Franke, B. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.20 · Cited by 1,479 · see citing works
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- Authors
- van der Meer, D., Hartman, C. A., Richards, J., Bralten, J. B., Franke, B., Oosterlaan, J., Heslenfeld, D. J., Faraone, S. V., Buitelaar, J. K., & Hoekstra, P. J.
- Affiliations
- Department of Psychiatry University of Groningen University Medical Center Groningen Groningen the Netherlands
- University Medical Center Groningen (NL)
- Radboud University Nijmegen (NL)
- Vrije Universiteit Amsterdam (NL)
- SUNY Upstate Medical University (US)
- ORCID
- Venue
- Journal of Child Psychology and Psychiatry
- Publisher
- Wiley
- Published
- 2014-05-03
- Volume
- 55
- Issue
- 12
- Pages
- 1363-1371
- ISSN
- 0021-9630 (ISSN-L)
- 1469-7610
- PMC
- PMC4218913
- OpenAlex
- W2084372584
- Cited by
- 51
- References
- 43
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 9 · 2016: 11 · 2015: 9
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Child Psychology and Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- VU Research Portal (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- NIH (R01MH62873)
- NWO (1750102007010)
- Radboud University Medical Center
- University Medical Center Groningen and Accare
- VU University Amsterdam
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- 5-HTTLPR, serotonin transporter gene, attention deficit hyperactivity disorder, gene-environment interaction, psychosocial stress, life events, hyperactivity/impulsivity, ADHD symptom severity, adolescents and young adults, internalizing problems
- MeSH terms
- Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Female, Follow-Up Studies, Humans, Life Change Events, Male, Polymorphism, Genetic, Severity of Illness Index, Siblings, Serotonin Plasma Membrane Transport Proteins, Young Adult, Gene-Environment Interaction
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