Background: Obesity is associated with a higher prevalence of neuropsychiatric symptoms, including emotional distress, mood alterations and cognitive dysfunction. These symptoms significantly affect the quality of life of obese individuals and contribute to their social and occupational dysfunction. While the pathophysiological mechanisms linking obesity to an increased vulnerability to neuropsychiatric symptoms remain to be determined, recent data suggest the involvement of immune/inflammatory processes. The aim of this study was to assess the role of chronic low grade inflammation in neuropsychiatric comorbidity in obesity. Methods: A group of patients with severe or morbid obesity (body mass index, BMI > 35–40 kg/m2), enrolled in a bariatric surgery program, were recruited. Neuropsychiatric assessments were performed before surgery and at regular intervals during the first year post-surgery. Assessments included measures of depressive, anxious, cognitive and neurovegetative symptoms. Blood draws were collected at the same time points for the measurement of inflammatory markers and immune-related processes. Results: Before surgery, adiposity correlated with inflammatory markers and neuropsychiatric symptoms. Interestingly, surgery-induced weight loss was associated with significant reductions in the level of inflammatory markers, together with improvements in the neuropsychiatric status of patients. Inflammation-induced alterations in monoamine metabolism correlated with the intensity of neuropsychiatric symptoms before surgery. Conclusions: These findings are consistent with the involvement of inflammatory processes in neuropsychiatric comorbidity in obesity.< Réduire