Domestic water mineral exposure increases affective disorders vulnerability by impairing brain structural resilience

Abstract The neural mechanisms linking environmental mineral exposure to affective disorders remain poorly understood. Here, leveraging the large-scale UK Biobank cohort ( n = 389,984), we investigate the impact of domestic water mineral exposure on mental health. Beyond identifying population association of individual water mineral calcium (Ca) and magnesium (Mg) exposure, we developed a water mineral mixture exposure index (WMEx) to model mixture effect of Ca and Mg exposure on affective symptoms and disorders. We found that each unit increase in domestic water minerals exposure was associated with up to 0.24 standard deviation increase in elevated depressive symptoms (Ca: β = 0.24, P = 3.12 × 10 − 126 ; Mg: β = 0.07, P = 1.23×10 − 24 ; WMEx: β = 0.23, P = 1.55× 10 − 249 ), as well as an increased prospective risk of affective disorder incidence during 15.3 years follow-up (full model HR = 1.66, 95% CI: 1.40–1.96), which were all well replicated. Neuroimaging analyses uncovered the underlying neural substrates, revealing that mineral exposure was linked to impaired brain structural resilience, quantified by a novel brain structural resilience index (BSRI) representing the coupling between gray and white matter structures. Critically, causal mediation analyses demonstrated that the compromised brain structural resilience within visual-emotional circuits significantly mediated the pathway from mineral exposure to affective disorders. These neuromediating pathways were disproportionately stronger in females and individuals living in lower socioeconomic regions. Our findings reveal a crucial environmental-neurobiological axis, positioning domestic water minerals as a key determinant of mental health and highlighting how compromised brain structural resilience serves as a core neural mechanism of affective vulnerability.