Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder.

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.
Competing Interests: Declaration of competing interest Kassandra A. Zachos: none Jaehyoung Choi: none Ophelia Godin: none Timofei Chernega: none Haejin Angela Kwak: none Jae H. Jung: none Bruno Aouizerate: none Valérie Aubin: none Frank Bellivier: none Raoul Belzeaux R: none Philippe Courtet: none Caroline Dubertret: none Bruno Etain: none Emmanuel Haffen: none Antoine Lefrere A: none Pierre-Michel Llorca: none Emilie Olié: none Mircea Polosan: none Ludovic Samalin: none Raymund Schwan: none Paul Roux: none Caroline Barau: none Jean Romain Richard: none Ryad Tamouza: none Ana C. Andreazza: none Marion Leboyer: none
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