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Background  The relationship between obesity and depression is complex. This study assessed the impact of body mass index (BMI) on the link between BMI, inflammation, oxidative stress, sleep quality and self-reported depressive symptoms.    Methods  We used data from the U.S. National Health and Nutritional Examination Survey 2005–2008 cycles ( n  = 9133; ≥20y). Depressive symptoms and sleep quality were determined from questionnaires. C-reactive Protein (CRP) was used as a biomarker of inflammation and γ-glutamyltransferase was used to assess oxidative stress. The relationship between depressive symptoms, sleep quality, and biomarkers were assessed with regression models. The moderating effects of BMI and sex were tested.    Results  BMI was a significant moderator of the relationship between γ-glutamyltransferase and depressive symptoms ( p  = 0.02), but not CRP or sleep quality. Higher BMI increased odds of depressive symptoms in women (OR (95% CI): 3.92 (1.85–8.30) for BMI ≥25 to < 30 kg/m 2 ; 3.17 (1.53–6.58) for BMI ≥30 to < 35 kg/m 2 ; and 7.38 (2.11–25.76) for BMI ≥35 kg/m 2 ). BMI was also a significant moderator of γ-glutamyltransferase levels in those with vs without depressive symptoms. Those with depressive symptoms had 24% poorer sleep quality compared to those without depressive symptoms after adjusting for inflammation, oxidative stress and other confounders.    Conclusions  The link between oxidative stress and depressive symptoms may be particularly relevant for females and people living with obesity. People with depressive symptoms also have a substantial reduction in sleep quality. Thus, research should examine these relationships prospectively to inform and improve the mental health of the adult population in developed countries.

Obesity moderates the complex relationships between inflammation, oxidative stress, sleep quality and depressive symptoms