Verebi Camille, Lebrun Nicolas, Duriez Philibert, Adoux Lucie, Saint-Pierre Benjamin, Gorwood Philip, Ramoz Nicolas, Bienvenu Thierry
Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, « Genetic vulnerability to addictive and psychiatric disorders » team, 75014, Paris, France.
GHU-Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne, CMME, F-75014, Paris, France.
J Psychiatr Res. 2025 Feb;182:358-367. doi: 10.1016/j.jpsychires.2025.01.026. Epub 2025 Jan 16.
Anorexia nervosa (AN) is a psychiatric disorder with a high heritability (h∼70%). Despite extensive meta-analysis of genome-wide association studies, the molecular mechanisms underlying genetics of AN and its complications, particularly suicidal behavior, remain unclear. We performed mRNA sequencing on peripheral blood mononuclear cells from 15 patients with AN (5 with a lifetime history of suicide attempts and 10 without). After correcting for multiple testing, we identified dysregulation of several genes, and confirmed our findings in an independent cohort of 34 patients with AN. Our analysis revealed significant dysregulation of several genes, including SNORD3C, which is implicated in vitamin D metabolism. These genes were enriched in RNA metabolism and innate immune pathways. The presence of these dysregulated genes was associated with suicidal behavior in patients with AN. Our findings suggest that SNORD3C and other differentially expressed genes may serve as potential biomarkers for suicidal risk in AN. This study enhances our understanding of the biological pathways involved in the pathogenesis of suicidal behavior in AN, paving the way for future research and potential clinical applications.
神经性厌食症（AN）是一种具有高遗传性（h∼70%）的精神疾病。尽管对全基因组关联研究进行了广泛的荟萃分析，但AN及其并发症（尤其是自杀行为）的遗传学潜在分子机制仍不清楚。我们对15例AN患者（5例有自杀未遂史，10例无自杀未遂史）的外周血单核细胞进行了mRNA测序。在进行多重检验校正后，我们鉴定出几个基因的失调，并在34例AN患者的独立队列中证实了我们的发现。我们的分析揭示了包括SNORD3C在内的几个基因的显著失调，SNORD3C与维生素D代谢有关。这些基因在RNA代谢和固有免疫途径中富集。这些失调基因的存在与AN患者的自杀行为相关。我们的发现表明，SNORD3C和其他差异表达基因可能作为AN患者自杀风险的潜在生物标志物。这项研究增进了我们对AN患者自杀行为发病机制中涉及的生物学途径的理解，为未来的研究和潜在的临床应用铺平了道路。
