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

Previous observational studies have reported a possible association between major depressive disorder (MDD) and abnormal cortical structure. However, it is unclear whether MDD causes reductions in global cortical thickness (CT) and global area (SA).

We aimed to test the bidirectional causal relationship between MDD and CT and SA using a Mendelian randomization (MR) design and performed exploratory analyses of MDD on CT and SA in different brain regions.

Summary-level data were obtained from two GWAS meta-analysis studies: one screening for single nucleotide polymorphisms (SNPs) predicting the development of MDD (n = 135,458) and the other identifying SNPs predicting the magnitude of cortical thickness (CT) and surface area (SA) (n = 51,665).

The results showed that MDD caused a decrease in CT in the medial orbitofrontal region, a decrease in SA in the paracentral region, and an increase in SA in the lateral occipital region. C-reactive protein, tumor necrosis factor alpha (TNF-α), interleukin-1β, and interleukin-6 did not mediate the reduction. We also found that a reduction in CT in the precentral region and a reduction in SA in the orbitofrontal regions might be associated with a higher risk of MDD.

Our study did not suggest an association between MDD and cortical CT and SA.