title: Medical comorbidity in bipolar disorder: The link with metabolic-inflammatory systems.
abstract: Bipolar disorder (BD) is associated with chronic low-grade inflammation, several medical comorbidities and a decreased life expectancy. Metabolic-inflammatory changes have been postulated as one of the main links between BD and medical comorbidity, although there are few studies exploring possible mechanisms underlying this relationship. Therefore, the aims of the current narrative review were 1) synthesize the evidence for metabolic-inflammatory changes that may facilitate the link between medical comorbidity and BD and 2) discuss therapeutic and preventive implications of these pathways.
  
  
  
  The PubMed and Google Scholar databases were searched for relevant studies.
  
  
  
  Identified studies suggested that there is an increased risk of medical comorbidities, such as autoimmune disorders, obesity, diabetes and cardiovascular disease in patients with BD. The association between BD and general medical comorbidities seems to be bidirectional and potentially mediated by immune dysfunction. Targeting the metabolic-inflammatory-mood pathway may potential yield improved outcomes in BD; however, further study is needed to determine which specific interventions may be beneficial.
  
  
  
  The majority of identified studies had cross-sectional designs, small sample sizes and limited measurements of inflammation.
  
  
  
  Treatment and prevention of general medical comorbidities in mood disorders should include preferential prescribing of metabolically neutral agents and adjunctive lifestyle modifications including increased physical activity, improved diet and decreased substance abuse. In addition, the use of anti-inflammatory agents could be a relevant therapeutic target in future research.
authors.affiliation: University of São Paulo (USP), São Paulo, Brazil; Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Federal University of São Paulo (Unifesp), São Paulo, Brazil.
authors.forename: Ana
authors.initials: A
authors.lastname: SayuriYamagata
authors.affiliation: Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Federal University of São Paulo (Unifesp), São Paulo, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rosenblat
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada.
authors.forename: Ron
authors.initials: R
authors.lastname: Kakar
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada. Electronic address: roger.mcintyre@uhn.ca.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000150:complications*; D002318:Cardiovascular Diseases / Q000150:complications; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000150:complications; D009765:Obesity / Q000150:complications; D019966:Substance-Related Disorders / Q000150:complications
keywords: Comorbidities; Cytokines; Immunity; Inflammation; Metabolic syndrome; Mood disorders