title: Leptin in bipolar disorder: A systematic review and meta-analysis.
abstract: Bipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD.
  
  
  
  This study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges' adjusted g using random effects.
  
  
  
  Eleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g=-0.99, 95% CI -2.43 to 0.43, P=0.171), in depression (g=0.17, 95% CI -0.45 to 0.79, P=0.584), or in euthymia (g=0.03, 95% CI -0.39 to 0.46, P=0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls.
  
  
  
  Our meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia; Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: brisasf@gmail.com.
authors.forename: B S
authors.initials: BS
authors.lastname: Fernandes
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Dash
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Jacka
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia; Department of Psychiatry, University of Melbourne, Parkville, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Dodd
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: A F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Köhler
authors.affiliation: Department of Psychiatry, University of Magdeburg, Magdeburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Steiner
authors.affiliation: Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: da Graça Cantarelli
authors.affiliation: Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Nardin
authors.affiliation: Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: C-A
authors.initials: CA
authors.lastname: Gonçalves
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia; Florey Institute for Neuroscience and Mental Health, Department of Psychiatry and Orygen, The National Centre of Excellence in Youth Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Berk
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000097:blood*; D003527:Cyclothymic Disorder / Q000097:blood; D003863:Depression / Q000097:blood; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male
chemical_list: D020738:Leptin
keywords: Biomarker; Bipolar disorder; Depression; Leptin; Mania; Meta-analysis