Psychiatry research · 2026
From isolation to inflammation-behavioral mediation explains the social origins of depression in obesity: insights from NHANES 2005-2023.
СтатьяНазвание и аннотация: Перевод в очереди
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Sun Yuan, Hou Xiao, Zhu Wenfen, Fu Yixiao
Аннотация
BACKGROUND: Depression and obesity frequently co-occur and share overlapping biological and psychosocial mechanisms. Yet, how social, dietary, and systemic inflammatory processes jointly shape depression risk in obesity remains unclear.
METHODS: Using nationally representative data from the U.S. National Health and Nutrition Examination Survey (NHANES 2005-2023), we analyzed obese adults (n = 11,608). A multidimensional Social Isolation Index (SII) was developed to capture structural and socioeconomic isolation, alongside the Dietary Inflammatory Index (DII) and serum C-reactive protein (CRP) representing behavioral and biological inflammation. Depression was defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥10. Survey-weighted logistic regressions assessed independent and joint associations of SII, DII, and CRP with depression. Mediation analyses examined behavioral and inflammatory pathways, while factorial and stratified models evaluated the full four-way interaction (SII × DII × CRP × BMI) and heterogeneity of the SII-depression association across demographic and metabolic subgroups.
RESULTS: Higher SII was robustly associated with greater odds of depression (OR = 1.42, 95% CI 1.29-1.57, p < 0.001), independent of DII, CRP, and BMI. DII was also positively associated with depression, although with a smaller effect size (OR = 1.17, 95% CI 1.04-1.33, p = 0.010), whereas CRP was not significantly associated with depression. A modest but significant indirect effect was observed through DII (ACME OR = 1.04, 95% CI 1.01-1.07, p = 0.023), whereas no mediation through CRP or higher-order interactions among SII, DII, CRP, and BMI were detected.
CONCLUSIONS: Social isolation, captured by a multidimensional index, emerged as the strongest and most consistent correlate of depression in obesity, partly mediated by pro-inflammatory dietary behavior. These findings underscore the behavioral embedding of social adversity within psychoneuroimmunological models of depression.
METHODS: Using nationally representative data from the U.S. National Health and Nutrition Examination Survey (NHANES 2005-2023), we analyzed obese adults (n = 11,608). A multidimensional Social Isolation Index (SII) was developed to capture structural and socioeconomic isolation, alongside the Dietary Inflammatory Index (DII) and serum C-reactive protein (CRP) representing behavioral and biological inflammation. Depression was defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥10. Survey-weighted logistic regressions assessed independent and joint associations of SII, DII, and CRP with depression. Mediation analyses examined behavioral and inflammatory pathways, while factorial and stratified models evaluated the full four-way interaction (SII × DII × CRP × BMI) and heterogeneity of the SII-depression association across demographic and metabolic subgroups.
RESULTS: Higher SII was robustly associated with greater odds of depression (OR = 1.42, 95% CI 1.29-1.57, p < 0.001), independent of DII, CRP, and BMI. DII was also positively associated with depression, although with a smaller effect size (OR = 1.17, 95% CI 1.04-1.33, p = 0.010), whereas CRP was not significantly associated with depression. A modest but significant indirect effect was observed through DII (ACME OR = 1.04, 95% CI 1.01-1.07, p = 0.023), whereas no mediation through CRP or higher-order interactions among SII, DII, CRP, and BMI were detected.
CONCLUSIONS: Social isolation, captured by a multidimensional index, emerged as the strongest and most consistent correlate of depression in obesity, partly mediated by pro-inflammatory dietary behavior. These findings underscore the behavioral embedding of social adversity within psychoneuroimmunological models of depression.