Exploring causal association between functional/structural connectivity and major depression disorder: A bidirectional Mendelian randomization study.

Objectives: Prior observational studies have suggested a correlation between major depressive disorder (MDD) and communication imbalances within the resting-state brain network (RSN), but the causal relationship remains unclear. This research uses Mendelian randomization (MR) analysis to explore the potential causal effects between functional connectivity (FC), structural connectivity (SC) and MDD.

Methods: Two-sample bidirectional MR analysis was employed in this study. Inverse variance weighted (IVW) was used to explore the causal relationship between the FC/SC and MDD, with various methods such as MR-Egger to conduct sensitivity analyses.

Results: The IVW analysis results showed that higher genetic predicted dorsal attention network FC, limbic network SC, and dorsal attention network SC were associated with an increased risk of MDD (β: 15.08, 95%CI: 5.89-24.27, p = 0.001; β: 3.79, 95%CI: -0.22-7.8, p = 0.034; β: 9.89, 95%CI: 0.88-18.90, p = 0.031). Reverse MR analysis demonstrated that a genetically predicted elevated risk of MDD was associated with reduced frontal parietal network FC (β: -0.00046, p = 0.041).

Conclusions: The study suggests a causal relationship between the FC and SC within specific RSNs and the risk of MDD. Abnormalities in the dorsal attention network FC/SC and the limbic network SC were risk factors for MDD. The FC abnormality of the frontal parietal network may be the downstream influence following the MDD onset. Further investigation is needed to determine the potential utility of these neuroimaging markers in the prevention of MDD or the evaluation of treatment efficacy.