title: Metformin: repurposing opportunities for cognitive and mood dysfunction.
abstract: BACKGROUND
  Cognitive deficits differentially affect individuals with type 2 diabetes mellitus (T2DM) and mood disorders. Accumulating evidence implicates disturbances in metabolism as salient to cognitive function. Thus, the mitigation of metabolic disturbances may preserve or ameliorate cognitive function. This review aims to evaluate available evidence investigating the effects of metformin on cognitive function as well as summarize putative mechanistic properties related to these clinical effects.
  
  
  METHODS
  A PubMed search was conducted using the search words including, but not limited to: metformin, Major Depressive Disorder, type 2 diabetes mellitus, and cognitive dysfunction. All English language articles published from 1990 to July 2014 were reviewed.
  
  
  RESULTS
  Extant preclinical and clinical data have been mixed, wherein both cognitive disruption and pro-cognitive effects have been reported with the administration of metformin. Sound mechanistic evidence supports metformin as a treatment; however, the heterogeneity of study designs has contributed to an inability to arrive at an unequivocal conclusion regarding metformin effects upon cognition.
  
  
  CONCLUSIONS
  Available evidence does not provide a robust signal for improvement in cognition in either mood disorder or T2DM samples. Notwithstanding, it is premature to label metformin as a "no-go" agent for further testing and development for cognitive dysfunction. A well designed, proof-of-concept trial of metformin investigating its possible cognitive effects in mood disorders is therefore warranted.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Ying
authors.forename: Nadia
authors.initials: N
authors.lastname: Maruschak
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Mansur
authors.forename: Andre F
authors.initials: AF
authors.lastname: Carvalho
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Cha
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, Toronto, Ontario, M5T 2S8, Canada. Roger.McIntyre@uhn.ca.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
mesh_terms: D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D006801:Humans; D008687:Metformin / Q000627:therapeutic use*; D019964:Mood Disorders / Q000150:complications*; D018697:Nootropic Agents / Q000627:therapeutic use*
chemical_list: D018697:Nootropic Agents; D008687:Metformin