Abstract Introduction: Prior studies indicate greater disease burden for obesity among rural compared with urban residents but no differences for mood disorder based on geographic location. Recent attention has focused on the need to examine regional rural–urban disparities in disease burden. We focused on mood disorders and obesity prevalence within three southeastern Minnesota counties served by the Mayo Clinic Center for Translational Science Award, in Rochester, Minnesota, as these were top priorities identified in community health needs assessments. Methods: Cross-sectional study to assess the association of rural–urban locality on 5-year (2009–2014) prevalence of mood disorder and obesity obtained using the Rochester Epidemiological Project medical records linkage system, among subjects residing in three mixed rural–urban counties on April 1, 2014. Multivariable analyses adjusted for demographics, socioeconomic status using an individual housing-based measure, and counties. Results: The study cohort (percent rural location) included 91,202 (15%) for Olmsted, 10,197 (51%) in Dodge, and 10,184 (57%) in Wabasha counties. On multivariate analysis, 5-year prevalence of mood disorders and obesity was significantly greater for urban compared with rural residents, after adjusting for confounders; odds ratios (95% confidence intervals): 1.21 (1.17–1.26), P < 0.001, and 1.05 (1.01–1.10), P = 0.016, respectively. Observed effects were not modified in additional models adjusted for health care utilization (HCU; ≥1 general medical examination visit and flu vaccination). Conclusions: Rural–urban health disparities for burden of mood disorders and obesity are independent of socioeconomic status and HCU in a Midwestern community. It is important to assess potential regional heterogeneity of rural–urban disparities on health outcomes.
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