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Background <p>This study employs bidirectional Mendelian randomization (MR) analysis to explore the causal relationship between frailty and common psychiatric disorders.</p> Methods <p>Depression, anxiety disorder, bipolar disorder, schizophrenia, sleep disorders, and eating disorders were considered as outcomes, with frailty index as the exposure variable. The main method employed was inverse variance weighting. Two-step MR was used to evaluate the mediation proportions of body mass index (BMI) between frailty and psychiatric disorders. Additionally, reverse MR analysis was conducted using the same testing methods.</p> Results <p>Frailty index was positively associated with depression, anxiety disorder, bipolar disorder, sleep disorders, and eating disorders. Schizophrenia indicated no significant causal association. The effect of frailty index on the risk of sleep disorders, eating disorders, depression were all partially mediated by BMI, with mediation proportion of 24.40%, 14.23% and 5.22%. Reverse MR analysis revealed that depression increased the risk of frailty.</p> Conclusion <p>This study has supported the causal association of frailty with depression, anxiety disorder, bipolar disorder, sleep disorders, and eating disorders. Additionally, individuals diagnosed with depression exhibit a heightened susceptibility to frailty. This sheds new light on the causal relationship between frailty and psychiatric disorders.</p>

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Bidirectional causal association between frailty and six psychiatric disorders

  • 期刊论文

  • 发表日期：

    2025年9月19日

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  • Fangfang Qian,
  • Guoqiang Zheng,
  • Zhuoming Chen

摘要

Background

This study employs bidirectional Mendelian randomization (MR) analysis to explore the causal relationship between frailty and common psychiatric disorders.

Methods

Depression, anxiety disorder, bipolar disorder, schizophrenia, sleep disorders, and eating disorders were considered as outcomes, with frailty index as the exposure variable. The main method employed was inverse variance weighting. Two-step MR was used to evaluate the mediation proportions of body mass index (BMI) between frailty and psychiatric disorders. Additionally, reverse MR analysis was conducted using the same testing methods.

Results

Frailty index was positively associated with depression, anxiety disorder, bipolar disorder, sleep disorders, and eating disorders. Schizophrenia indicated no significant causal association. The effect of frailty index on the risk of sleep disorders, eating disorders, depression were all partially mediated by BMI, with mediation proportion of 24.40%, 14.23% and 5.22%. Reverse MR analysis revealed that depression increased the risk of frailty.

Conclusion

This study has supported the causal association of frailty with depression, anxiety disorder, bipolar disorder, sleep disorders, and eating disorders. Additionally, individuals diagnosed with depression exhibit a heightened susceptibility to frailty. This sheds new light on the causal relationship between frailty and psychiatric disorders.