title: Can bipolar disorder be viewed as a multi-system inflammatory disease?
abstract: BACKGROUND
  Patients with bipolar disorder are known to be at high risk of premature death. Comorbid cardio-vascular diseases are a leading cause of excess mortality, well above the risk associated with suicide. In this review, we explore comorbid medical disorders, highlighting evidence that bipolar disorder can be effectively conceptualized as a multi-systemic inflammatory disease.
  
  
  METHODS
  We conducted a systematic PubMed search of all English-language articles recently published with bipolar disorder cross-referenced with the following terms: mortality and morbidity, cardio-vascular, diabetes, obesity, metabolic syndrome, inflammation, auto-antibody, retro-virus, stress, sleep and circadian rhythm.
  
  
  RESULTS
  Evidence gathered so far suggests that the multi-system involvement is present from the early stages, and therefore requires proactive screening and diagnostic procedures, as well as comprehensive treatment to reduce progression and premature mortality. Exploring the biological pathways that could account for the observed link show that dysregulated inflammatory background could be a common factor underlying cardio-vascular and bipolar disorders. Viewing bipolar disorder as a multi-system disorder should help us to re-conceptualize disorders of the mind as "disorders of the brain and the body".
  
  
  CONCLUSIONS
  The current literature substantially lacks longitudinal and mechanistic studies, as well as comparison studies to explore the magnitude of the medical burden in bipolar disorder compared to major mood disorders as well as psychotic disorders. It is also necessary to look for subgroups of bipolar disorder based on their rates of comorbid disorders.
  
  
  CONCLUSIONS
  Comorbid medical illnesses in bipolar disorder might be viewed not only as the consequence of health behaviors and of psychotropic medications, but rather as an early manifestation of a multi-systemic disorder. Medical monitoring is thus a critical component of case assessment. Exploring common biological pathways of inflammation should help biomarkers discovery, ultimately leading to innovative diagnostic tools, new methods of prevention and personalized treatments.
authors.affiliation: INSERM U955, University Paris-Est, FondaMental Fondation, Fondation de Coopération Scientifique, AP-HP, Groupe Hospitalier Mondor, 40, Rue de Mesly, Creteil, F-94000, France. Marion.leboyer@inserm.fr
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.forename: Isabella
authors.initials: I
authors.lastname: Soreca
authors.forename: Jan
authors.initials: J
authors.lastname: Scott
authors.forename: Mark
authors.initials: M
authors.lastname: Frye
authors.forename: Chantal
authors.initials: C
authors.lastname: Henry
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.forename: David J
authors.initials: DJ
authors.lastname: Kupfer
mesh_terms: D001714:Bipolar Disorder / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D015897:Comorbidity; D006801:Humans; D024821:Metabolic Syndrome / Q000453:epidemiology; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology / Q000503:physiopathology*