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Causal relationship and mediating role between depression and cognitive performance.
Xinyu Hao1, Fuyang Cao2, Ziyao Xu3
1Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, PR China.
The Journal of Prevention of Alzheimer'S Disease
|May 9, 2025
Summary
This study reveals a two-way causal link between depression and cognitive performance. Depression can worsen cognition, and cognitive decline may increase depression risk, with pain and frailty as key mediators.
Area of Science:
- Psychiatry
- Neuroscience
- Genetics
Background:
- Growing evidence links depression and cognitive function.
- Causality between depression and cognitive performance remains unclear.
- Mendelian randomization (MR) offers a method to investigate genetic links.
Purpose of the Study:
- To investigate the bidirectional causal relationship between depression and cognitive performance.
- To identify potential mediating factors in this relationship.
Main Methods:
- Two-sample bidirectional Mendelian randomization (MR) analyses were performed.
- Genome-wide association study (GWAS) data for depression and cognitive performance were utilized.
- Sensitivity analyses, including heterogeneity and pleiotropy assessments, ensured result reliability.
Main Results:
- A significant bidirectional causal association was found between depression and cognitive performance.
- Depression was associated with increased risk of deteriorating cognitive performance (IVW β = -0.11, P = 5.97E-04).
- Cognitive performance decline was linked to a predisposition to depression (OR = 0.85, P = 0.004).
Conclusions:
- A bidirectional causal relationship exists between depression and cognitive performance.
- Pain mediates the effect of depression on cognitive performance.
- Frailty mediates the effect of cognitive performance on depression.
Keywords:
BidirectionalCognitive performanceDepressionMediation effectMendelian randomizationTwo-sampleMore Related Videos
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