PDF(Pubmed)
Abstract：
Mental disorders are among the top causes of disease burden worldwide. Existing evidence regarding the repurposing of antihypertensives for mental disorders treatment is conflicting and cannot establish causation.
We used Mendelian randomization to assess the effects of angiotensin-converting-enzyme inhibitors (ACEIs), beta blockers (BBs), and calcium channel blockers (CCBs) on risk of bipolar disorder (BD), major depression disorder (MDD), and schizophrenia (SCZ). We used published genetic variants which are in antihypertensive drugs target genes and correspond to systolic blood pressure (SBP) in Europeans and East Asians, and applied them to summary statistics of BD (cases = 41,917; controls = 371,549 in Europeans), MDD (cases = 170,756; controls = 329,443 in Europeans and cases = 15,771; controls = 178,777 in East Asians), and SCZ (cases = 53,386; controls = 77,258 in Europeans and cases = 22,778; controls = 35,362 in East Asians) from the Psychiatric Genomics Consortium. We used inverse variance weighting with MR-Egger, weighted median, weighted mode, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. We performed gene-specific analysis and utilized various methods to address potential pleiotropy.
After multiple testing correction, genetically proxied ACEIs were associated with an increased risk of SCZ in Europeans (odds ratio (OR) per 5 mmHg lower in SBP 2.10, 95% CI 1.54 to 2.87) and East Asians (OR per 5 mmHg lower in SBP 2.51, 95% CI 1.38 to 4.58). Genetically proxied BBs were not associated with any mental disorders in both populations. Genetically proxied CCBs showed no benefits on mental disorders.
Antihypertensive drugs have no protection for mental disorders but potential harm. Their long-term use among hypertensive patients with, or with high susceptibility to, psychiatric illness needs careful evaluation.
We used Mendelian randomization to assess the effects of angiotensin-converting-enzyme inhibitors (ACEIs), beta blockers (BBs), and calcium channel blockers (CCBs) on risk of bipolar disorder (BD), major depression disorder (MDD), and schizophrenia (SCZ). We used published genetic variants which are in antihypertensive drugs target genes and correspond to systolic blood pressure (SBP) in Europeans and East Asians, and applied them to summary statistics of BD (cases = 41,917; controls = 371,549 in Europeans), MDD (cases = 170,756; controls = 329,443 in Europeans and cases = 15,771; controls = 178,777 in East Asians), and SCZ (cases = 53,386; controls = 77,258 in Europeans and cases = 22,778; controls = 35,362 in East Asians) from the Psychiatric Genomics Consortium. We used inverse variance weighting with MR-Egger, weighted median, weighted mode, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. We performed gene-specific analysis and utilized various methods to address potential pleiotropy.
After multiple testing correction, genetically proxied ACEIs were associated with an increased risk of SCZ in Europeans (odds ratio (OR) per 5 mmHg lower in SBP 2.10, 95% CI 1.54 to 2.87) and East Asians (OR per 5 mmHg lower in SBP 2.51, 95% CI 1.38 to 4.58). Genetically proxied BBs were not associated with any mental disorders in both populations. Genetically proxied CCBs showed no benefits on mental disorders.
Antihypertensive drugs have no protection for mental disorders but potential harm. Their long-term use among hypertensive patients with, or with high susceptibility to, psychiatric illness needs careful evaluation.
摘要：
背景：精神障碍是全球疾病负担的主要原因之一。关于将抗高血压药用于精神障碍治疗的现有证据相互矛盾，无法确定因果关系。
方法：我们使用孟德尔随机化来评估血管紧张素转换酶抑制剂（ACEI）的作用，β受体阻滞剂（BBs），和钙通道阻滞剂（CCB）对双相情感障碍（BD）的风险，重度抑郁症（MDD），精神分裂症（SCZ）。我们使用了已发表的遗传变异，这些变异在抗高血压药物的靶基因中，与欧洲人和东亚人的收缩压（SBP）相对应，并将其应用于BD的汇总统计（欧洲人的病例=41,917；对照组=371,549），MDD（病例=170,756；欧洲人控制=329,443，病例=15,771；东亚人控制=178,777），和SCZ（病例=53,386；欧洲人的对照组=77,258，病例=22,778；东亚人的对照组=35,362）来自精神病学基因组学联盟。我们使用MR-Egger的方差逆加权，加权中位数，加权模式，和孟德尔随机化多效性RESidualSum和离群值。我们进行了基因特异性分析，并利用各种方法来解决潜在的多效性。
结果：经过多次测试校正后，在欧洲人(SBP为2.10,比值比(OR)每5mmHg降低,95%CI1.54~2.87)和东亚人(SBP为2.51,95%CI1.38~4.58)中,遗传代理ACEI与SCZ风险增加相关.在这两个人群中，遗传代理的BB与任何精神障碍均无关联。遗传代理CCB对精神障碍没有任何益处。
结论：抗高血压药物对精神障碍没有保护作用，但有潜在的危害。它们在高血压患者中的长期使用，或者对，精神病需要仔细评估。
方法：我们使用孟德尔随机化来评估血管紧张素转换酶抑制剂（ACEI）的作用，β受体阻滞剂（BBs），和钙通道阻滞剂（CCB）对双相情感障碍（BD）的风险，重度抑郁症（MDD），精神分裂症（SCZ）。我们使用了已发表的遗传变异，这些变异在抗高血压药物的靶基因中，与欧洲人和东亚人的收缩压（SBP）相对应，并将其应用于BD的汇总统计（欧洲人的病例=41,917；对照组=371,549），MDD（病例=170,756；欧洲人控制=329,443，病例=15,771；东亚人控制=178,777），和SCZ（病例=53,386；欧洲人的对照组=77,258，病例=22,778；东亚人的对照组=35,362）来自精神病学基因组学联盟。我们使用MR-Egger的方差逆加权，加权中位数，加权模式，和孟德尔随机化多效性RESidualSum和离群值。我们进行了基因特异性分析，并利用各种方法来解决潜在的多效性。
结果：经过多次测试校正后，在欧洲人(SBP为2.10,比值比(OR)每5mmHg降低,95%CI1.54~2.87)和东亚人(SBP为2.51,95%CI1.38~4.58)中,遗传代理ACEI与SCZ风险增加相关.在这两个人群中，遗传代理的BB与任何精神障碍均无关联。遗传代理CCB对精神障碍没有任何益处。
结论：抗高血压药物对精神障碍没有保护作用，但有潜在的危害。它们在高血压患者中的长期使用，或者对，精神病需要仔细评估。
