Cited by 67Circadian rhythm and melatoninAttention Deficit Hyperactivity DisorderSleep and related disorders

Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders: The melatonin pathway in ADHD

Chaste, Pauline, Clement, Nathalie, Botros, Hany Goubran, Guillaume, Jean-Luc, Konyukh, Marina, Pagan, Cécile, Scheid, Isabelle, Nygren, Gudrun +19 more·2011·Journal of Pineal Research

Abstract

Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) - detected exclusively in patients with ADHD - for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.

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Crossref · 10.1111/j.1600-079x.2011.00902.x

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Authors
Chaste, P., Clement, N., Botros, H. G., Guillaume, J.-L., Konyukh, M., Pagan, C., Scheid, I., Nygren, G., Anckarsäter, H., Rastam, M., Ståhlberg, O., Gillberg, I. C., Melke, J., Delorme, R., Leblond, C., Toro, R., Huguet, G., Fauchereau, F., Durand, C., Boudarene, L., Serrano, E., Lemière, N., Launay, J. M., Leboyer, M., Jockers, R., Gillberg, C., & Bourgeron, T.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • University of Gothenburg (SE)
  • Lund University (SE)
  • Institut Pasteur (FR)
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Inserm (FR)
  • St George's Hospital (GB)
Corresponding author
Bourgeron, Thomas
Venue
Journal of Pineal Research
Publisher
Wiley
Published
2011-05-26
Volume
51
Issue
4
Pages
394-399
ISSN
0742-3098 (ISSN-L)
OpenAlex
W2170669107
Cited by
67
References
34
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 10 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 6 · 2014: 13 · 2013: 7 · 2012: 8
FWCI
4.15
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Pineal Research (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords
attention deficit hyperactivity disorder, genetic variation, ASMT, MTNR1A, MTNR1B, GPR50, splice site mutation
MeSH terms
Acetylserotonin O-Methyltransferase, Attention Deficit Disorder with Hyperactivity, Female, Humans, Male, Melatonin, Nerve Tissue Proteins, Genetic Variation, Receptors, G-Protein-Coupled, Receptor, Melatonin, MT1, Arylalkylamine N-Acetyltransferase

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