title: Major depressive disorder and type II diabetes mellitus: mechanisms underlying risk for Alzheimer's disease.
abstract: Objectives/Introduction: Major Depressive Disorder is associated age-related medical conditions (e.g., diabetes mellitus type II, Alzheimer's disease) that frequently manifest at an earlier age, contributing to excess and premature mortality. The foregoing observation provides the impetus to further refine potential mechanisms and molecular pathways subserving these disorders in order to more effectively treat these clinical populations by aiming to reduce and prevent cognitive impairment as well as downstream neurodegeneration.
  
  
  METHODS
  A review of computerized databases was performed to identify original studies that investigated the impact of the independent and comorbid association of major depressive disorder and type II diabetes mellitus on cognitive function and conversion to Alzheimer's disease. English-written articles were selected for review based on the adequacy of sample size, the use of standardized diagnostic instruments, and validated assessment measures.
  
  
  RESULTS
  Individuals with persistent neuropsychiatric illness account for a disproportionate overall burden of disability mediated largely by decrements in cognitive performance. Mixed results from epidemiological and clinical studies suggest that insulin may mediate and/or moderate risk for cognitive dysfunction in subsets of individuals. Moreover, physiological changes, such as insulin resistance and the activation of neuroimmunoinflammatory systems result in glial and neuroendangerment.
  
  
  CONCLUSIONS
  Disturbances in the metabolic milieu exert a neurotoxic effect on the central nervous system and poses a hazard to other organ systems.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Cha
authors.forename: Andre F
authors.initials: AF
authors.lastname: Carvalho
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rosenblat
authors.forename: Muna M
authors.initials: MM
authors.lastname: Ali
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: D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology*; D016208:Databases, Factual; D003865:Major Depressive Disorder / Q000150:complications* / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology; D018450:Disease Progression; D006801:Humans