title: Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link.
abstract: OBJECTIVE
  A growing body of research suggests that the prevalence of major depressive disorder (MDD) in children and youth with type 1 diabetes mellitus is significantly higher than that of youth without type 1 diabetes and is associated with increased illness severity. The objective of this article is to review the current literature on the pathophysiology of these two common diseases with respect to potential areas of overlapping biological dysfunction.
  
  
  METHODS
  A search of English language articles published between 1966 and 2010 was conducted and augmented with manual review of reference lists from the identified publications.
  
  
  RESULTS
  The evidence suggests plausible mechanisms whereby a biological relationship between type 1 diabetes and MDD may exist. These include the effects of circulating cytokines associated with autoimmune diabetes, the direct impact of insulin deficiency on neurogenesis/neurotransmitter metabolism, the effects of the chronic hyperglycaemic state, occurrence of iatrogenic hypoglycaemia and the impact of basal hyperactivity of the hypothalamic-pituitary-adrenal axis.
  
  
  CONCLUSIONS
  Shared biological vulnerabilities may be implicated in the comorbidity of type 1 diabetes and MDD. Further research is warranted to determine the magnitude of associations and confirm their observation in clinical populations.
authors.affiliation: Department of Psychiatry, The Hospital for Sick Children, Rm 1145 Burton Wing, 555 University Avenue, Toronto, ON, Canada, M5G 1X8. daphne.korczak@sickkids.ca
authors.forename: D J
authors.initials: DJ
authors.lastname: Korczak
authors.forename: S
authors.initials: S
authors.lastname: Pereira
authors.forename: K
authors.initials: K
authors.lastname: Koulajian
authors.forename: A
authors.initials: A
authors.lastname: Matejcek
authors.forename: A
authors.initials: A
authors.lastname: Giacca
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000378:metabolism