CNS neuroscience & therapeutics · 2025
Causal Association Between Major Depressive Disorder and Cortical Structure: A Bidirectional Mendelian Randomization Study and Mediation Analysis.
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Zheng Hui, Fang Yong-Jiang, Wang Xiao-Ying, Feng Si-Jia, Tang Tai-Chun, Chen Min
Аннотация
BACKGROUND: 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).
OBJECTIVE: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSION: Our study did not suggest an association between MDD and cortical CT and SA.
OBJECTIVE: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSION: Our study did not suggest an association between MDD and cortical CT and SA.