Linking kidney impairment to amygdala volume changes and mental disorders: a Mendelian randomization study

Area of Science:

• Neuroscience
• Nephrology
• Psychiatry

Background:

• Mental disorders are common in chronic kidney disease (CKD) patients.
• The causal link between kidney dysfunction and brain changes/mental disorders is not well understood.
• CKD affects a significant global population, necessitating research into its systemic effects.

Purpose of the Study:

• To investigate the causal effect of kidney dysfunction on brain volume traits.
• To explore the causal relationship between kidney dysfunction and mental disorders.
• To elucidate the kidney-brain axis in the context of CKD.

Main Methods:

• Utilized two-sample Mendelian randomization (MR) with genetic instruments from large genome-wide association studies (GWAS) including UK Biobank (n=1,201,909).
• Employed inverse variance weighted (IVW) method for causal estimates.
• Validated findings using one-sample MR with individual-level data from UK Biobank.

Main Results:

• Causal associations found between estimated glomerular filtration rate and amygdala traits (ORs 0.559-0.723, p<0.05).
• CKD showed causal associations with amygdala volume traits (ORs 1.042-1.059, p<0.05).
• Kidney dysfunction linked to increased depression risk, with robust findings confirmed by sensitivity analyses.

Conclusions:

• Kidney dysfunction causally alters amygdala volume, heightening susceptibility to depression.
• Findings support a significant kidney-brain axis.
• Emphasizes integrating mental health care into CKD management.