Attention deficit hyperactivity disorder (ADHD) and 5HT2C receptor

A slight increase in the transmission of Cys23 to ADHD cases

E. Nugent, Z. Hawi, N. Lowe, A. Kirley, Michael F Fitzgerald, M Gill

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Recent evidence suggests that interaction with and balance between serotonergic and dopaminergic neurotransmission is important in the mediation of hyperactive behaviour. Animal model studies have firmly implicated the genes of the serotonergic system in predisposing to ADHD. Serotonin exerts its effects via a heterogenous family of receptors of which there are at least 14 distinct subtypes. The non-specific serotonin receptor agonist (m-chlorophenylpiperazine) is known to suppress locomotion in normal mice. However, when administered to mice bearing a mutated 5-HTR2C gene, it induces hyperactivity in these animals (Lora et al., 2000). This effect was blocked by pretreatment with 5HT1B receptor antagonist, indicating that the behavioural consequences of the mCPP-induced 5HT1B receptor stimulation are unmasked in animals devoid of 5HT2C receptor function. A Cysteine to Serine substitution at amino acid 23 of the 5HT2C has been identified which may influence the receptor folding thereby hindering the formation of a normal hydrophobic pocket and subsequently the binding of bulky ligands. In a family based association study design, we analysed the Cys-Ser polymorphism at the 5HT2C receptor gene in 60 Irish ADHD trios using transmission disequilibrium test (TDT). We observed a slight increase in the transmission of the Cysteine allele to the affected ADHD cases (Chi-square = 1.8. P = 0.26). This may suggest the involvement of 5HT2C gene in predisposing to ADHD.

Original languageEnglish
Pages (from-to)637
Number of pages1
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume105
Issue number7
Publication statusPublished - 8 Oct 2001
Externally publishedYes

Cite this

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title = "Attention deficit hyperactivity disorder (ADHD) and 5HT2C receptor: A slight increase in the transmission of Cys23 to ADHD cases",
abstract = "Recent evidence suggests that interaction with and balance between serotonergic and dopaminergic neurotransmission is important in the mediation of hyperactive behaviour. Animal model studies have firmly implicated the genes of the serotonergic system in predisposing to ADHD. Serotonin exerts its effects via a heterogenous family of receptors of which there are at least 14 distinct subtypes. The non-specific serotonin receptor agonist (m-chlorophenylpiperazine) is known to suppress locomotion in normal mice. However, when administered to mice bearing a mutated 5-HTR2C gene, it induces hyperactivity in these animals (Lora et al., 2000). This effect was blocked by pretreatment with 5HT1B receptor antagonist, indicating that the behavioural consequences of the mCPP-induced 5HT1B receptor stimulation are unmasked in animals devoid of 5HT2C receptor function. A Cysteine to Serine substitution at amino acid 23 of the 5HT2C has been identified which may influence the receptor folding thereby hindering the formation of a normal hydrophobic pocket and subsequently the binding of bulky ligands. In a family based association study design, we analysed the Cys-Ser polymorphism at the 5HT2C receptor gene in 60 Irish ADHD trios using transmission disequilibrium test (TDT). We observed a slight increase in the transmission of the Cysteine allele to the affected ADHD cases (Chi-square = 1.8. P = 0.26). This may suggest the involvement of 5HT2C gene in predisposing to ADHD.",
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Attention deficit hyperactivity disorder (ADHD) and 5HT2C receptor : A slight increase in the transmission of Cys23 to ADHD cases. / Nugent, E.; Hawi, Z.; Lowe, N.; Kirley, A.; Fitzgerald, Michael F; Gill, M.

In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol. 105, No. 7, 08.10.2001, p. 637.

Research output: Contribution to journalArticleResearchpeer-review

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