Insomnia-Driven Hippocampal Atrophy: Evidence From Bidirectional Mendelian Randomization

Area of Science:

• Neuroscience
• Genetics
• Public Health

Background:

• Observational studies suggest a link between insomnia and hippocampal atrophy.
• Causal inference is limited by confounding and reverse causality.
• Bidirectional causality between insomnia and hippocampal subfield volumes remains unaddressed.

Purpose of the Study:

• To investigate the bidirectional causal relationship between insomnia and hippocampal volumes using Mendelian randomization.
• To determine if genetic predisposition to insomnia affects hippocampal subfield volumes.
• To assess if hippocampal volumes influence the risk of insomnia.

Main Methods:

• Conducted a bidirectional two-sample Mendelian randomization (MR) study.
• Utilized genome-wide association study (GWAS) summary data for insomnia and eight hippocampal volume imaging-derived phenotypes (IDPs).
• Employed inverse-variance weighted regression and sensitivity analyses, controlling for multiple testing with Benjamini-Hochberg FDR.

Main Results:

• Forward MR showed genetically proxied insomnia was inversely associated with six of eight hippocampal phenotypes, indicating reduced volumes.
• Sensitivity analyses confirmed the robustness of these findings.
• Reverse MR found no evidence that hippocampal volumes causally affect insomnia.

Conclusions:

• Insomnia has a causal effect on reducing hippocampal volumes.
• Early intervention for insomnia, such as cognitive-behavioral therapy, may help preserve hippocampal health.
• Addressing insomnia is a public health priority, warranting further research into biological mechanisms and generalizability.