Causal Association Between Major Depressive Disorder and Cortical Structure: A Bidirectional Mendelian Randomization...

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Observational studies suggest a link between major depressive disorder (MDD) and altered brain structure.
• The causal relationship between MDD and cortical thickness (CT) and surface area (SA) remains unclear.

Purpose of the Study:

• To investigate the bidirectional causal associations between MDD and CT/SA using Mendelian randomization.
• To explore MDD's effects on CT and SA across different brain regions.

Main Methods:

• Utilized summary-level data from two large genome-wide association studies (GWAS).
• One GWAS focused on MDD (n=135,458), the other on CT and SA (n=51,665).
• Employed Mendelian randomization (MR) to infer causality.

Main Results:

• MDD was associated with decreased CT in the medial orbitofrontal cortex and decreased SA in the paracentral region.
• MDD was linked to increased SA in the lateral occipital region.
• Reduced CT in the precentral cortex and reduced SA in orbitofrontal regions may increase MDD risk.

Conclusions:

• The study did not establish a definitive causal association between MDD and global cortical thickness or surface area.
• Findings suggest potential regional impacts, but overall bidirectional causality was not supported.