Obesity is associated with a greater prevalence of neuropsychiatric disorders, including depression. Recent data support the notion that adiposity-driven inflammation contributes to this effect, given the notorious role of inflammatory processes in the pathophysiology of depressive symptoms. Moreover, it has been recently suggested that this effect may be potentiated by metabolic abnormalities associated with obesity. The objective of the present study was to determine the relative contribution of systemic inflammation and metabolic abnormalities to depressive symptomatology in subjects afflicted with severe obesity. The study was conducted in a large sample of severely or morbidly obese patients eligible for bariatric surgery and recruited from the units of digestive and bariatric surgery at the Tivoli (Bordeaux, France) and Jean Villar (Bruges, France) clinics. A group of age- and gender-matched lean healthy subjects were included as control participants. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) during a semi-structured clinical interview with a trained rater. Metabolic data, including high density lipoprotein cholesterol, triglycerides, fasting glucose and blood pressure, were collected from the patients' clinical charts. Information on the use of antihypertensive and antidiabetic medication was also obtained. Fasting blood samples were collected in all subjects for the measurement of serum concentrations of inflammatory markers by ELISA. These markers included the acute phase protein, high sensitive C-reactive protein (hs-CRP), the pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) and the adipokine, leptin. Results indicate higher levels of circulating inflammatory markers, especially hs-CRP, and greater MADRS scores in obese subjects compared to lean controls. Furthermore, multiple linear regression analyses adjusted for age and gender revealed that hs-CRP contributed significantly to the relationship between obesity and depressive symptoms. Interestingly, this relationship was not modulated by metabolic abnormalities, which did not explain depressive symptoms. Taken together these data support the hypothesis that chronic low-grade inflammation is a key determinant of depressive symptoms in obesity and that this effect does not rely on metabolic abnormalities.< Réduire