Causal relationship between cortical structural changes and onset of anxiety disorder: evidence from Mendelian randomization

Abstract Previous studies have reported a correlation between anxiety disorders and changes in brain structure, yet the specific alterations in brain region volumes remain unclear. This study aimed to infer the causal relationship between anxiety disorders and changes in brain structure volume through Mendelian Randomization analysis. We selected 63 cortical structure volumes from the GWAS database as exposure data and anxiety disorder data from the FinnGen and UK Biobank databases as outcomes. We found a significant correlation between atrophy in the Left precentral volume area (Odds Ratio [OR] = 0.935, 95% Confidence intervals [CI]: 0.891–0.981, P value, P = 0.007) and an increased risk of anxiety disorders. Additionally, changes identified in specific brain regions, such as atrophy in the Right rostral anterior cingulate area (OR = 0.993, 95% CI: 0.987–0.999, P = 0.025) and increased volume in the Left superior parietal area (OR = 1.001, 95% CI: 1.000–1.001, P = 0.028), may correlate with an increased risk of anxiety disorders. Furthermore, both phenotypes demonstrated directional consistency in their respective and overall meta-analyzed OR values pre- and post-merger, enhancing the reliability of the results. This study elucidates the causal relationship between anxiety disorders and specific brain structures, providing new insights for further research into psychiatric disorders.