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Bidirectional causal association between frailty and six psychiatric disorders
Fangfang Qian1,2, Guoqiang Zheng2, Zhuoming Chen3
1Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, People's Republic of China.
European Archives of Psychiatry and Clinical Neuroscience
|September 19, 2025
Summary
This study found that frailty causally increases the risk for depression, anxiety, bipolar disorder, sleep, and eating disorders. Depression also increases frailty risk, highlighting a bidirectional relationship.
Area of Science:
- Gerontology
- Psychiatry
- Genetics
Background:
- Investigating the causal links between physical frailty and mental health is crucial for comprehensive patient care.
- Previous research suggests correlations, but causal pathways remain unclear.
Purpose of the Study:
- To determine the causal relationship between frailty and common psychiatric disorders using bidirectional Mendelian randomization.
- To explore the mediating role of Body Mass Index (BMI) in the association between frailty and psychiatric conditions.
Main Methods:
- Bidirectional Mendelian randomization (MR) analysis.
- Inverse variance weighting (IVW) and two-step MR for mediation analysis.
- Utilized large-scale genetic data for frailty index (exposure) and psychiatric disorders (outcomes).
Main Results:
- Frailty significantly increases the risk for depression, anxiety disorder, bipolar disorder, sleep disorders, and eating disorders.
- Body Mass Index (BMI) partially mediates the effects of frailty on sleep disorders (24.40%), eating disorders (14.23%), and depression (5.22%).
- Reverse MR analysis indicated that depression causally increases the risk of frailty.
Conclusions:
- Establishes a causal link between frailty and several psychiatric disorders, supporting a bidirectional relationship.
- Highlights BMI as a partial mediator in the frailty-psychiatric disorder pathway.
- Provides novel insights into the complex interplay between physical aging and mental health.
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