Changes in resting-state functional connectivity of large-scale brain networks in bulimia nervosa: evidence from causal analysis

Bulimia nervosa (BN) has been observationally linked to the functional connectivity (FC) of large-scale brain networks, but the biological mechanisms remain unclear. This study used two-sample Mendelian randomization (MR) with genetic variations as instrumental variables (IVs) to explore potential causal relationships between FC and BN. Summary data from genome-wide association studies (GWAS) involving 2,564 individuals were analyzed to identify genetically predicted BN. Functional magnetic resonance imaging parameters and materials were sourced from the UK Biobank. The variables underwent independent component analysis processing by the database to generate the final GWAS dataset. Various methods, including MR Pleiotropy RESidual Sum and Outlier, MR Egger, and weighted median, were employed to detect heterogeneity and pleiotropy, with inverse variance weighting serving as the principal estimation method (P < 0.05). The FC imaging-derived phenotypes revealed that BN exerted a causal influence on the FC between large-scale networks, including the visual network, default mode network (DMN), frontoparietal network, somatosensory network (SSN), and ventral attention network. Additionally, BN had a causal impact on the within-network FC of both the DMN and SSN. The study provides evidence that BN leads to further changes in FC patterns within and between large-scale brain networks.