Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients.
Clin Epigenetics
; 11(1): 198, 2019 12 26.
Article
em En
| MEDLINE
| ID: mdl-31878957
ABSTRACT
BACKGROUND:
Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples.RESULTS:
Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (≥ 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03).CONCLUSIONS:
These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psicotrópicos
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Fatores de Transcrição
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Aumento de Peso
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Metilação de DNA
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Polimorfismo de Nucleotídeo Único
/
Obesidade
Tipo de estudo:
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article