Sex-Specific Regional Brain Morphometric Correlates of Neighborhood Socioeconomic Disadvantage in Clinical Neuroimaging

<jats:p>BACKGROUND AND PURPOSE: Neighborhood-level socioeconomic disadvantage is associated with adverse brain morphometry, yet whether these associations differ by biological sex remain opaque. Here, we investigated sex-specific associations between the area deprivation index and brain morphometry derived from routine clinical MRI in a real-world clinical population. MATERIALS AND METHODS: Intracranial volume-normalized regional brain volumes were extracted from T1-weighted MRI examinations performed in 2,863 consecutive clinical patients (median age 54 years [IQR 38-68]; 61.2% female) at a single academic medical center and associated community partners using an automated atlas-based segmentation pipeline. Exploratory factor analysis was applied to 131 regional brain volumes to identify latent neuroanatomical morphometric networks. Sex-stratified linear regression models examined associations between area deprivation index national percentile rank and each factor score, adjusting for age, with correction for multiple comparisons. RESULTS: Factor analysis identified five neuroanatomical morphometric networks: cerebellar (ML1), frontal/executive (ML2), subcortical-ventricular (ML3), medial temporal/limbic (ML4), and posterior cortical/visual (ML5). In male patients (n = 1,112), linear regressions revealed that greater neighborhood-level socioeconomic disadvantage was significantly associated with lower factor scores on the cerebellar (β = -0.006, 95% CI [-0.009, -0.003], P &lt; .001), medial temporal/limbic (β = -0.004, 95% CI [-0.007, -0.001], P = .01), and frontal/executive (β = -0.004, 95% CI -0.007, -0.0004], P = .04) networks. No significant associations were observed in female patients (all Ps ≥ .61). CONCLUSIONS: In a real-world clinical population, neighborhood-level socioeconomic disadvantage was associated with lower regional brain volumes across cerebellar, frontal/executive, and medial temporal/limbic neuroanatomical morphometric networks in male but not female patients. These findings suggest that the neuroanatomical correlates of neighborhood disadvantage may be sex-specific, and that sex-stratified analyses may be necessary to fully characterize the relationship between the social exposome and brain morphometry in clinical neuroimaging research.</jats:p>