CHRNA7 Deletions are Enriched in Risperidone-Treated Children and Adolescents.

TitleCHRNA7 Deletions are Enriched in Risperidone-Treated Children and Adolescents.
Publication TypeJournal Article
Year of Publication2017
AuthorsGillentine, MA, White, JJ, Grochowski, CM, Lupski, JR, Schaaf, CP, Calarge, CA
JournalJ Child Adolesc Psychopharmacol
Date Published2017 Dec
KeywordsAdolescent, alpha7 Nicotinic Acetylcholine Receptor, Antipsychotic Agents, Child, Cohort Studies, Female, Gene Deletion, Humans, Male, Neurodevelopmental Disorders, Prospective Studies, Risperidone, Treatment Outcome

OBJECTIVE: Aggression is among the most common indications for referral to child and adolescent mental health services and is often challenging to treat. Understanding the biological underpinnings of aggression could help optimize treatment efficacy. Neuronal nicotinic acetylcholine receptors (nAChRs), specifically the α7 nAChR, encoded by the gene CHRNA7, have been implicated in aggressive behaviors in animal models as well as humans. Copy number variants (CNVs) of CHRNA7 are found in individuals with neuropsychiatric disorders, often with comorbid aggression. In this study, we aimed to determine the prevalence of CHRNA7 CNVs among individuals treated with risperidone, predominantly for irritability and aggression.METHODS: Risperidone-treated children and adolescents were assessed for CHRNA7 copy number state using droplet digital PCR and genomic quantitative PCR. Demographic, anthropometric, and clinical data, including the Child Behavior Checklist (CBCL), were collected and compared across individuals with and without the CHRNA7 deletion.RESULTS: Of 218 individuals (90% males, mean age: 12.3 ± 2.3 years), 7 (3.2%) were found to carry a CHRNA7 deletion and one proband carried a CHRNA7 duplication (0.46%). T-scores for rule breaking, aggression, and externalizing behavior factors of the CBCL were higher in the deletion group, despite taking 58% higher dose of risperidone.CONCLUSIONS: CHRNA7 loss may contribute to a phenotype of severe aggression. Given the high prevalence of the deletion among risperidone-treated youth, future studies should examine the therapeutic potential of α7 nAChR-targeting drugs to target aggression associated with CHRNA7 deletions.

Alternate JournalJ Child Adolesc Psychopharmacol
PubMed ID28817303
PubMed Central IDPMC5725633
Grant ListT32 GM008307 / GM / NIGMS NIH HHS / United States

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