A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia.
A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia.
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强力霉素使用与精神分裂症发展之间的性别依赖性关联。
DOI：
10.1093/schbul/sbad008
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发表时间：
2023
影响因子：
6.6
通讯作者：
Bergink,Veerle
中科院分区：
文献类型：
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作者：
deWitte,LotD;MunkLaursen,Thomas;Corcoran,CherylM;Kahn,RenéS;Birnbaum,Rebecca;Munk-Olsen,Trine;Bergink,Veerle
背景多西环素和米诺环素是具有脑渗透性的四环素类抗生素，因其具有免疫调节和神经保护作用而受到关注。观察性研究表明，接触这些药物可能会降低患精神分裂症的风险，但结果不一致。本研究的目的是调查之间的潜在关联使用强力霉素和后来发病的schizophrenia.DesignWe使用的数据从1980年至2006年之间出生的1 647 298人通过丹麦人口登记。这些人中有79078人暴露于多西环素，定义为至少1个处方的赎回。生存分析模型分层性别随时间变化的协变量，以评估发病率比（IRR）为精神分裂症（ICD-10代码F20. XX），调整年龄，日历年，父母的精神状态，和教育level.ResultsIn非分层分析，有没有多西环素暴露和精神分裂症的风险之间的关联。然而，与未使用强力霉素的男性相比，使用强力霉素的男性精神分裂症发病率显著降低（IRR 0.70; 95%CI 0.57-0.86）。相比之下，与未使用强力霉素处方的女性相比，女性精神分裂症发病率显著更高（IRR 1.23; 95%CI 1.08，1.40）。未发现其他四环素类抗生素的影响（IRR 1.00; 95%CI 0.91，1.09）。下一步是在独立的特征良好的人群队列中复制结果，以及临床前研究，以调查多西环素对精神分裂症相关生物学机制的性别特异性影响。
BackgroundDoxycycline and minocycline are brain-penetrant tetracycline antibiotics, which recently gained interest because of their immunomodulatory and neuroprotective properties. Observational studies have suggested that exposure to these drugs may decrease the risk to develop schizophrenia, but results are inconsistent. The aim of this study was to investigate the potential association between doxycycline use and later onset of schizophrenia.DesignWe used data from 1 647 298 individuals born between 1980 and 2006 available through Danish population registers. 79 078 of those individuals were exposed to doxycycline, defined as redemption of at least 1 prescription. Survival analysis models stratified for sex with time-varying covariates were constructed to assess incidence rate ratios (IRRs) for schizophrenia (ICD-10 code F20.xx), with adjustment for age, calendar year, parental psychiatric status, and educational level.ResultsIn the non-stratified analysis, there was no association between doxycycline exposure and schizophrenia risk. However, men who redeemed doxycycline had a significantlylowerincidence rate for schizophrenia onset compared to men that did not (IRR 0.70; 95% CI 0.57–0.86). By contrast, women had a significantlyhigherincidence rate for schizophrenia onset, compared to women that did not redeem doxycycline prescriptions (IRR 1.23; 95% CI 1.08, 1.40). The effects were not found for other tetracycline antibiotics (IRR 1.00; 95% CI 0.91, 1.09).ConclusionsDoxycycline exposure is associated with a sex-dependent effect on schizophrenia risk. The next steps are replication of the results in independent well-characterized population cohorts, as well as preclinical studies to investigate sex-specific effects of doxycycline on biological mechanisms implicated in schizophrenia.