Lipid disturbances induced by psychotropic drugs: clinical and genetic predictors for early worsening of lipid levels and new-onset dyslipidaemia in Swiss psychiatric samples.

IF 3.9 3区医学 Q1 PSYCHIATRY BJPsych Open Pub Date : 2024-12-05 DOI:10.1192/bjo.2024.757

Aurélie Delacrétaz, Marie Sadler, Franziska Gamma, Martin Preisig, Hélène Richard-Lepouriel, Armin von Gunten, Philippe Conus, Kerstin Jessica Plessen, Zoltan Kutalik, Chin B Eap

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Abstract

Background: Early worsening of plasma lipid levels (EWL; ≥5% change after 1 month) induced by at-risk psychotropic treatments predicts considerable exacerbation of plasma lipid levels and/or dyslipidaemia development in the longer term.

Aims: We aimed to determine which clinical and genetic risk factors could predict EWL.

Method: Predictive values of baseline clinical characteristics and dyslipidaemia-associated single nucleotide polymorphisms (SNPs) on EWL were evaluated in a discovery sample (n = 177) and replicated in two samples from the same cohort (PsyMetab; n₁ = 176; n₂ = 86).

Results: Low baseline levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and high baseline levels of high-density lipoprotein cholesterol (HDL-C), were risk factors for early increase in total cholesterol (P = 0.002), LDL-C (P = 0.02) and triglycerides (P = 0.0006), and early decrease in HDL-C (P = 0.04). Adding genetic parameters (n = 17, 18, 19 and 16 SNPs for total cholesterol, LDL-C, HDL-C and triglycerides, respectively) improved areas under the curve for early worsening of total cholesterol (from 0.66 to 0.91), LDL-C (from 0.62 to 0.87), triglycerides (from 0.73 to 0.92) and HDL-C (from 0.69 to 0.89) (P ≤ 0.00003 in discovery sample). The additive value of genetics to predict early worsening of LDL-C levels was confirmed in two replication samples (P ≤ 0.004). In the combined sample (n ≥ 203), adding genetics improved the prediction of new-onset dyslipidaemia for total cholesterol, LDL-C and HDL-C (P ≤ 0.04).

Conclusions: Clinical and genetic factors contributed to the prediction of EWL and new-onset dyslipidaemia in three samples of patients who started at-risk psychotropic treatments. Future larger studies should be conducted to refine SNP estimates to be integrated into clinically applicable predictive models.

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精神药物引起的脂质紊乱：瑞士精神病学样本中脂质水平早期恶化和新发血脂异常的临床和遗传预测因子。

背景：早期血脂水平恶化(EWL；高危精神药物治疗引起的≥5%的变化（1个月后）预示着长期内血脂水平的显著恶化和/或血脂异常的发展。目的：我们旨在确定哪些临床和遗传危险因素可以预测EWL。方法：在一个发现样本（n = 177）中评估EWL基线临床特征和血脂异常相关单核苷酸多态性（snp）的预测价值，并在同一队列的两个样本(PsyMetab；N1 = 176；N2 = 86)。结果：基线水平低的总胆固醇、低密度脂蛋白胆固醇（LDL-C）和甘油三酯以及基线水平高的高密度脂蛋白胆固醇（HDL-C）是早期总胆固醇升高（P = 0.002）、低密度脂蛋白胆固醇（P = 0.02）和甘油三酯升高（P = 0.0006）和早期HDL-C降低（P = 0.04）的危险因素。添加遗传参数（总胆固醇、LDL-C、HDL-C和甘油三酯的n分别为17、18、19和16个SNPs）改善了总胆固醇（从0.66到0.91）、LDL-C（从0.62到0.87）、甘油三酯（从0.73到0.92）和HDL-C（从0.69到0.89）早期恶化的曲线下面积（在发现样本中P≤0.00003）。在两个复制样本中证实了遗传学预测LDL-C水平早期恶化的附加价值（P≤0.004）。在合并样本（n≥203）中，加入遗传因素可改善总胆固醇、LDL-C和HDL-C对新发血脂异常的预测（P≤0.04）。结论：临床和遗传因素有助于预测3例开始高危精神药物治疗的患者的EWL和新发血脂异常。未来应该进行更大规模的研究来完善SNP估计，以整合到临床应用的预测模型中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BJPsych Open Medicine-Psychiatry and Mental Health

CiteScore

6.30

自引率

3.70%

发文量

610

审稿时长

16 weeks

期刊介绍： Announcing the launch of BJPsych Open, an exciting new open access online journal for the publication of all methodologically sound research in all fields of psychiatry and disciplines related to mental health. BJPsych Open will maintain the highest scientific, peer review, and ethical standards of the BJPsych, ensure rapid publication for authors whilst sharing research with no cost to the reader in the spirit of maximising dissemination and public engagement. Cascade submission from BJPsych to BJPsych Open is a new option for authors whose first priority is rapid online publication with the prestigious BJPsych brand. Authors will also retain copyright to their works under a creative commons license.