Exploring the Causal Association Between Erectile Dysfunction and Brain Cortical Structure: Insight from a Bidirectional Mendelian Randomization Study and Cross-Sectional Neuroimaging Study.

Purpose: This study aims to investigate the bidirectional causal relationship between erectile dysfunction (ED) and cerebral cortical structure.

Materials and methods: This study employed bidirectional two-sample Mendelian randomization (MR) framework. Exposure and outcome data were derived from genome-wide association study (GWAS) datasets. The MR analysis incorporated inverse variance weighted regression as the primary method, supplemented by the weighted median method and MR-Egger regression, to evaluate causal relationships between ED and brain cortical structure metrics, including surface area (SA) and cortical thickness (TH). Cerebral cortical morphology in ED patients was assessed using 3D T1-weighted magnetic resonance imaging (MRI).

Results: Whole-brain analysis demonstrated no significant association between ED and global SA or TH. Regional analyses revealed that ED was associated with reduced SA of the caudal anterior cingulate gyrus, increased SA of the insula, operculum, pars triangularis, and supramarginal gyrus, as well as increased TH of the insula and decreased TH of the transverse temporal gyrus. Regarding the effects of cerebral cortical characteristics on incidence of ED, TH in the inferior parietal gyrus, medial orbitofrontal gyrus, posterior cingulate gyrus, precentral gyrus and SA of cuneus exhibited significant effects on elevated risk of ED. Furthermore, the structure of insula, pars opercularis and precentral gyrus was further confirmed by MRI as associated with ED symptoms.

Conclusions: ED has been identified to be associated with structural alterations in multiple brain regions, suggesting potential associations with impairments in cognitive function, regulation of language processing, and sensory integration. Moreover, alterations in cortical structures of specific brain regions may serve as a predictor of ED incidence, offering novel insights for future prevention and therapeutic interventions. Overall, our results indicate the existence of a potential bidirectional interaction between genital sensory pathways and central neurological processes.