Abnormal melatonin synthesis in autism spectrum disorders

Research output: Contribution to journalArticle

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Abnormal melatonin synthesis in autism spectrum disorders. / Melke, Jonas; Goubran-Botros, Hany; Chaste, Pauline; Betancur, Catalina; Nygren, Guddrun; Anckarsäter, Henrik; Råstam, Maria; Ståhlberg, Ola; Gillberg, I Carina; D3elorme, Richard; Chabane, Nadia; Mouren-Simeoni, Marie-Christine; Fauchereau, Fabien; Durand, Christelle M; Chevalier, Fabien; Drouot, Xavier; Collet, Corinne; Launay, Jean-Marie; Leboyer, Marion; Gilblerg, Crhstopher; Bourgeron, Thomas; and, The Paris Study.

In: Molecular Psychiatry, Vol. 13, No. 1, 2008, p. 90-98.

Research output: Contribution to journalArticle

Harvard

Melke, J, Goubran-Botros, H, Chaste, P, Betancur, C, Nygren, G, Anckarsäter, H, Råstam, M, Ståhlberg, O, Gillberg, IC, D3elorme, R, Chabane, N, Mouren-Simeoni, M-C, Fauchereau, F, Durand, CM, Chevalier, F, Drouot, X, Collet, C, Launay, J-M, Leboyer, M, Gilblerg, C, Bourgeron, T & and, TPS 2008, 'Abnormal melatonin synthesis in autism spectrum disorders', Molecular Psychiatry, vol. 13, no. 1, pp. 90-98. https://doi.org/10.1038/sj.mp.4002016

APA

Melke, J., Goubran-Botros, H., Chaste, P., Betancur, C., Nygren, G., Anckarsäter, H., ... and, T. P. S. (2008). Abnormal melatonin synthesis in autism spectrum disorders. Molecular Psychiatry, 13(1), 90-98. https://doi.org/10.1038/sj.mp.4002016

CBE

Melke J, Goubran-Botros H, Chaste P, Betancur C, Nygren G, Anckarsäter H, Råstam M, Ståhlberg O, Gillberg IC, D3elorme R, Chabane N, Mouren-Simeoni M-C, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C, Launay J-M, Leboyer M, Gilblerg C, Bourgeron T, and TPS. 2008. Abnormal melatonin synthesis in autism spectrum disorders. Molecular Psychiatry. 13(1):90-98. https://doi.org/10.1038/sj.mp.4002016

MLA

Vancouver

Melke J, Goubran-Botros H, Chaste P, Betancur C, Nygren G, Anckarsäter H et al. Abnormal melatonin synthesis in autism spectrum disorders. Molecular Psychiatry. 2008;13(1):90-98. https://doi.org/10.1038/sj.mp.4002016

Author

Melke, Jonas ; Goubran-Botros, Hany ; Chaste, Pauline ; Betancur, Catalina ; Nygren, Guddrun ; Anckarsäter, Henrik ; Råstam, Maria ; Ståhlberg, Ola ; Gillberg, I Carina ; D3elorme, Richard ; Chabane, Nadia ; Mouren-Simeoni, Marie-Christine ; Fauchereau, Fabien ; Durand, Christelle M ; Chevalier, Fabien ; Drouot, Xavier ; Collet, Corinne ; Launay, Jean-Marie ; Leboyer, Marion ; Gilblerg, Crhstopher ; Bourgeron, Thomas ; and, The Paris Study. / Abnormal melatonin synthesis in autism spectrum disorders. In: Molecular Psychiatry. 2008 ; Vol. 13, No. 1. pp. 90-98.

RIS

TY - JOUR

T1 - Abnormal melatonin synthesis in autism spectrum disorders

AU - Melke, Jonas

AU - Goubran-Botros, Hany

AU - Chaste, Pauline

AU - Betancur, Catalina

AU - Nygren, Guddrun

AU - Anckarsäter, Henrik

AU - Råstam, Maria

AU - Ståhlberg, Ola

AU - Gillberg, I Carina

AU - D3elorme, Richard

AU - Chabane, Nadia

AU - Mouren-Simeoni, Marie-Christine

AU - Fauchereau, Fabien

AU - Durand, Christelle M

AU - Chevalier, Fabien

AU - Drouot, Xavier

AU - Collet, Corinne

AU - Launay, Jean-Marie

AU - Leboyer, Marion

AU - Gilblerg, Crhstopher

AU - Bourgeron, Thomas

AU - and, The Paris Study

PY - 2008

Y1 - 2008

N2 - Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level was reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2×10−10). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2×10−12) and melatonin level (P=3×10−11) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.

AB - Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level was reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2×10−10). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2×10−12) and melatonin level (P=3×10−11) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.

KW - melatonin

KW - autism

KW - circadian rhythm

KW - sleep

KW - HIOMT

KW - ASMT

U2 - 10.1038/sj.mp.4002016

DO - 10.1038/sj.mp.4002016

M3 - Article

VL - 13

SP - 90

EP - 98

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 1

ER -