Genetic evidence of increased schizophrenia risk due to antidepressant use in European and East Asian populations

IF 1.5 4区医学 Q2 PSYCHIATRY

European Journal of Psychiatry Pub Date : 2025-03-01 DOI:10.1016/j.ejpsy.2025.100302

Zhiqiang Du , Xiangjun Zhou , Qin Zhou, Rongrong Lu, Ying Jiang, Haohao Zhu

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引用次数: 0

Abstract

Background and objectives

Understanding the relationship between antipsychotic drugs (ATDs) use and schizophrenia (SCZ) is crucial. Thus, the objective is to explore the bidirectional causal relationship between ATDs use and SCZ via Two-Sample Mendelian Randomization (TSMR) analysis, aiming to offer new insights for the clinical treatment of SCZ.

Methods

We employed data from Genome-Wide Association Studies (GWAS) and conducted TSMR analysis using the Inverse Variance Weighted (IVW) method. The results were evaluated using P-values, OR values, and 95% Confidence Intervals (95% CI) to assess the bidirectional causal relationship.

Results

At the genetic level, we found a bidirectional positive correlation between European ATDs use and SCZ [OR: 1.283, 95% CI: 1.136–1.449; P = 5.73E-05] and [OR: 1.130, 95% CI: 1.082–1.180; P = 4.27E-08]. East Asian ATDs use and SCZ also showed a positive correlation [OR: 1.174, 95% CI: 1.038–1.328; P = 0.011], while no significant causal relationship was found between East Asian SCZ and ATDs use [OR: 1.004, 95% CI: 0.999–1.009; P = 0.161]. Sensitivity analysis further supported the robustness and reliability of these findings.

Conclusion

At the genetic level, we found that European and East Asian ATDs use may increase the risk of developing SCZ. This can help in formulating clinical medication strategies, where more caution may be needed in deciding whether to prescribe ATDs to SCZ patients. Additionally, we discovered that European SCZ might increase ATDs use, whereas no such risk was found in East Asians.

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欧洲和东亚人群使用抗抑郁药导致精神分裂症风险增加的遗传证据

背景与目的了解抗精神病药物（ATDs）使用与精神分裂症（SCZ）之间的关系至关重要。因此，我们的目的是通过双样本孟德尔随机化（TSMR）分析，探讨ATDs使用与SCZ之间的双向因果关系，旨在为SCZ的临床治疗提供新的见解。方法采用全基因组关联研究（GWAS）数据，采用逆方差加权（IVW）方法进行TSMR分析。使用p值、OR值和95%置信区间（95% CI）对结果进行评估，以评估双向因果关系。结果在遗传水平上，我们发现欧洲人使用ATDs与SCZ呈双向正相关[OR: 1.283, 95% CI: 1.136-1.449；P = 5.73E-05]和[OR: 1.130, 95% CI: 1.082-1.180；P = 4.27e-08]。东亚地区ATDs使用与SCZ也呈正相关[OR: 1.174, 95% CI: 1.038 ~ 1.328；P = 0.011]，而东亚SCZ与ATDs使用无显著因果关系[OR: 1.004, 95% CI: 0.999-1.009；P = 0.161]。敏感性分析进一步支持了这些发现的稳健性和可靠性。结论在遗传水平上，我们发现欧洲和东亚使用ATDs可能增加SCZ发生的风险。这有助于制定临床用药策略，在决定是否给SCZ患者开ATDs时可能需要更加谨慎。此外，我们发现欧洲SCZ可能会增加ATDs的使用，而东亚人没有发现这种风险。

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

European Journal of Psychiatry PSYCHIATRY-

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

43 days

期刊介绍： The European journal of psychiatry is a quarterly publication founded in 1986 and directed by Professor Seva until his death in 2004. It was originally intended to report “the scientific activity of European psychiatrists” and “to bring about a greater degree of communication” among them. However, “since scientific knowledge has no geographical or cultural boundaries, is open to contributions from all over the world”. These principles are maintained in the new stage of the journal, now expanded with the help of an American editor.