biostudies-literatureZheng HSichuan Province Science and Technology Support ProgramSichuan Provincial Science and Technology Support ProgramNational Natural Science Foundation of Chinae70319https://www.ebi.ac.uk/biostudies/studies/S-EPMC11890974biostudies-literatureUnknown31(3)<h4>Background</h4>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).<h4>Objective</h4>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.<h4>Methods</h4>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 = 51,665CNS neuroscience & therapeuticsCausal Association Between Major Depressive Disorder and Cortical Structure: A Bidirectional Mendelian Randomization Study and Mediation Analysis.PMC118909742021JDTD00072022NSFSC150382274529Zheng HFeng SJChen MTang TCFang YJWang XYfalseCausal Association Between Major Depressive Disorder and Cortical Structure: A Bidirectional Mendelian Randomization Study and Mediation Analysis.<h4>Background</h4>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).<h4>Objective</h4>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.<h4>Methods</h4>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 = 51,6652025-01-01T00:00:00Z2025 Mar2026-06-01T20:12:23.195Z2025-04-07T07:49:31.372ZS-EPMC118909744005906810.1111/cns.70319