JCJC SVSE 1 - JCJC - SVSE 1 - Physiologie, physiopathologie, santé publique

Role of Inflammation in the Pathophysiology of Neuropsychiatric Co-Morbidity in Obesity – OBEPSY

Submission summary

The prevalence of obesity over the world is reaching pandemic proportions. Not only related to an increased risk of metabolic and cardiovascular diseases, obesity is also associated with a higher incidence 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. The pathophysiological mechanisms linking obesity to an increased vulnerability to neuropsychiatric symptoms remain unknown. Although psychological factors may contribute, recent data suggest the implication of immune processes. Obesity is characterized by low-grade chronic inflammation, with increased circulating levels of acute phase proteins and pro-inflammatory cytokines. Interestingly, weight loss induced by bariatric surgery was found to reduce levels of pro-inflammatory cytokines in obese subjects. Pro-inflammatory cytokines have been repeatedly linked to the development of neuropsychiatric symptoms. In addition, findings from our group in a clinical model of chronic inflammation suggest that alterations in hypothalamo-pituitary-adrenal (HPA) axis and disturbance in cognitive information processing may contribute to the neuropsychiatric effects of inflammation. The principal aim of this project is to investigate the role of chronic low-grade inflammation in the pathophysiology of neuropsychiatric symptoms in obese individuals. For this purpose, three aims, corresponding respectively to specific tasks, are proposed:

Aim 1: To characterize neuropsychiatric symptoms in 100 patients with severe or morbid obesity and to determine the relationship of these symptoms with systemic inflammation related to adiposity. To further investigate this relationship, the effects of weight loss induced by gastric bypass surgery on inflammation and related neuropsychiatric symptoms will be assessed. At baseline, and 3, 6 and 12 months post-surgery, neuropsychiatric evaluations assessing mood, cognitive and neurovegetative symptoms in a dimensional approach will be performed and blood draws will be collected for the measurement of inflammatory markers. The relationship of adiposity-related inflammation and neuropsychiatric symptoms will be assessed and the influence of surgery-induced weight loss on this relationship will be determined. Results will be contrasted to data obtained in 50 non-obese/non-overweight subjects undergoing parietal surgery for a non inflammatory condition (hernia) recruited as control participants.

Aim 2: To determine the involvement of alterations in HPA axis function related to inflammation in neuropsychiatric symptoms in obese patients. To address this aim, 15 patients with severe or morbid obesity and 15 non-obese/non-overweight subjects drawn from Aim 1 will be selected. HPA axis function will be assessed using a functional genomic approach. Relationships between functional genomic profiles and neuropsychiatric symptoms will be determined as well as the influence of surgery-induced weight on these profiles.

Aim 3: To assess the relationship between neuropsychiatric symptoms and altered cognitive information processing in obese subjects, using a functional magnetic resonance imaging (fMRI) paradigm. Fifteen subjects with severe or morbid obesity and 15 non-obese/non-overweight subjects drawn from Aim 1 will be recruited. Altered information processing will be assessed during a task of conflict processing recruiting the dorsal anterior cingulate cortex, and relationships with neuropsychiatric symptoms and inflammatory profiles will be determined.

This interdisciplinary project associating complementary approaches will provide important new information regarding the role of inflammation in the development of neuropsychiatric co-morbidity in obesity and will help to identify some pathophysiological mechanisms underlying these effects.

Project coordination

Lucile Capuron (INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE - CENTRE DE RECHERCHE DE BORDEAUX - AQUITAINE) – lucile.capuron@bordeaux.inra.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

INRA INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE - CENTRE DE RECHERCHE DE BORDEAUX - AQUITAINE

Help of the ANR 206,424 euros
Beginning and duration of the scientific project: December 2011 - 36 Months

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