Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT1B receptor gene in 273 nuclear families from a multi-centre sample
Abstract
Attention deficit hyperactivity disorder (ADHD) is a highly heritable and heterogeneous disorder, which usually becomes apparent during the first few years of childhood. Imbalance in dopamine neurotransmission has been suggested as a factor predisposing to ADHD. However, evidence has suggested an interaction between dopamine and serotonin systems in the pathophysiology of the disorder. Studies using selective agonists of the different 5-HT receptors microinjected into selected brain structures have shown a positive modulating effect on the functional activities of the mesotelencephalic dopaminergic system. This suggests that some of the genetic predisposition to ADHD might be due to DNA variation at serotonin system genes. In this study, we investigated polymorphisms in HTR(1B) and HTR(2A) (which encode the serotonin receptors 5-HT(1B) and 5-HT(2A) respectively) in a European ADHD sample. Using haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) analyses, we observed significant preferential transmission of the allele 861G of the HTR(1B) in the total sample (for HHRR; chi(2) = 7.4, P = 0.0065 and TDT; (chi(2) = 6.4, P = 0.014). Analysis of HTR(2A) failed to reveal evidence of association or linkage between the His452Tyr polymorphism and ADHD in the total sample. However, a significantly increased transmission of the allele 452His was observed in the Irish sample alone (chi(2) = 4.9, P = 0.026). These preliminary data suggest an important…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The imbalance of excitatory serotonin function has also been related to ADHD development.
“The imbalance of excitatory serotonin function has also been related to ADHD development [89, 90].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [90]
Serotonin regulates DA activity through its receptors 5-HTR1B or 5-HTR2A; dysfunction of these receptors can lead to problems of serotonin-DA dynamics, resulting in ADHD symptoms.
“Moreover, serotonin regulates DA activity through its receptors 5-hydroxytryptamine receptor 1B (5-HTR1B) or 5-hydroxytryptamine receptor 2A (5-HTR2A). The dysfunction of these receptors can lead to problems of serotonin–DA dynamics, resulting in ADHD symptoms [89, 90].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [90]
Other proteins related to 5-HT metabolism, such as TPH2 and NOS-1, which reduces SERT cell surface localization increasing the levels of extracellular serotonin, might be involved in the pathophysiology of ADHD.
“In addition, other proteins related to 5-HT metabolism, such as tryptophan 5-hydroxylase 2 (TPH2) and nitrous oxide synthase 1 (NOS-1), which reduces the serotonin transporter (SERT or SLC6A4) cell surface localization increasing the levels of extracellular serotonin, might be involved in the pathophysiology of ADHD [90, 92].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [90]
Cited by
Sorted by citations
Molecular genetics of attention-deficit/hyperactivity disorder
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., & Sklar, P. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.024 · Cited by 2,357 · see citing works
Genetics of attention deficit hyperactivity disorder
Faraone, S. V., & Larsson, H. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0070-0 · Cited by 1,338 · see citing works
Candidate gene studies of ADHD: a meta-analytic review
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009) · Human Genetics · doi:10.1007/s00439-009-0694-x · Cited by 1,020 · see citing works
Molecular biology of 5-HT receptors
Hannon, J., & Hoyer, D. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.03.020 · Cited by 815 · see citing works
Brookes, K., Xu, X., Chen, W., Zhou, K., Neale, B., Lowe, N., Aneey, R., Franke, B., Gill, M., Ebstein, R., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001869 · Cited by 533 · see citing works
Self-citationMolecular Genetics of Attention Deficit Hyperactivity Disorder
Faraone, S. V., & Mick, E. (2010) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2009.12.004 · Cited by 411 · see citing works
“A coding polymorphism in the HTR2A receptor gene (His452Tyr) was associated with ADHD in,(118,122) but not in.(113,116) Li and colleagues(124) found significant over-transmission of the C-759T/G-697C haplotype within the HTR2C gene, but no association was observed in Bobb and colleagues(111) or in the IMAGE project.”
BackgroundNeuroinflammation as a risk factor for attention deficit hyperactivity disorder
Dunn, G. A., Nigg, J. T., & Sullivan, E. L. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.05.005 · Cited by 299 · see citing works
Molecular genetics of attention-deficit/hyperactivity disorder: an overview
Banaschewski, T., Becker, K., Scherag, S., Franke, B., & Coghill, D. (2010) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-010-0090-z · Cited by 252 · see citing works
Walitza, S., Renner, T. J., Dempfle, A., Konrad, K., Wewetzer, C., Halbach, A., Herpertz-Dahlmann, B., Remschmidt, H., Smidt, J., Linder, M., et al. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001734 · Cited by 158 · see citing works
Retz, W., Freitag, C. M., Retz-Junginger, P., Wenzler, D., Schneider, M., Kissling, C., Thome, J., & Rösler, M. (2008) · Psychiatry Research · doi:10.1016/j.psychres.2007.05.004 · Cited by 142 · see citing works
Toward developmental models of psychiatric disorders in zebrafish
Norton, W. H. J. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00079 · Cited by 127 · see citing works
Burt, S. A., & Mikolajewski, A. J. (2008) · Aggressive Behavior · doi:10.1002/ab.20251 · Cited by 98 · see citing works
Review: Genetics of Attention Deficit/Hyperactivity Disorder
Wallis, D., Russell, H. F., & Muenke, M. (2008) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsn049 · Cited by 86 · see citing works
Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“In addition, other proteins related to 5-HT metabolism, such as tryptophan 5-hydroxylase 2 (TPH2) and nitrous oxide synthase 1 (NOS-1), which reduces the serotonin transporter (SERT or SLC6A4) cell surface localization increasing the levels of extracellular serotonin, might be involved in the pathophysiology of ADHD […”
BackgroundStoltenberg, S. F., Glass, J. M., Chermack, S. T., Flynn, H. A., Li, S., Weston, M. E., & Burmeister, M. (2006) · Psychiatric Genetics · doi:10.1097/01.ypg.0000176528.30362.34 · Cited by 62 · see citing works
Quantitative and Molecular Genetics of ADHD
Asherson, P., & Gurling, H. (2011) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2011_155 · Cited by 43 · see citing works
Self-citationFrom neurons to brain networks, pharmacodynamics of stimulant medication for ADHD
Parlatini, V., Bellato, A., Murphy, D., & Cortese, S. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105841 · Cited by 26 · see citing works
Hiraide, S., Ueno, K.-I., Yamaguchi, T., Matsumoto, M., Yanagawa, Y., Yoshioka, M., & Togashi, H. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.01.009 · Cited by 24 · see citing works
- Authors
- Hawi, Z., Dring, M., Kirley, A., Foley, D., Kent, L., Craddock, N., Asherson, P., Curran, S., Gould, A., Richards, S., Lawson, D., Pay, H., Turic, D., Langley, K., Owen, M., O'Donovan, M., Thapar, A., Fitzgerald, M., & Gill, M.
- Affiliations
- Trinity College Dublin (IE)
- University of Birmingham (GB)
- Cardiff University (GB)
- Corresponding author
- Hawi, Z
- Venue
- Molecular Psychiatry
- Published
- 2002-08-01
- Volume
- 7
- Issue
- 7
- Pages
- 718-725
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2096311792
- Cited by
- 175
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 3 · 2015: 7 · 2014: 4 · 2013: 7 · 2012: 10
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- attention deficit hyperactivity disorder, serotonergic system, 5-HT1B receptor, 5-HT2A receptor, HTR2A, genetic susceptibility, single nucleotide polymorphisms, haplotype relative risk, transmission disequilibrium test, serotonin-dopamine interaction, nuclear family, Irish population
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Child, Family Health, United Kingdom, Haplotypes, Humans, Ireland, Receptors, Serotonin, Risk Factors, Linkage Disequilibrium, Genetic Predisposition to Disease, Receptor, Serotonin, 5-HT1B, Receptor, Serotonin, 5-HT2A
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
