title: Glial abnormalities in substance use disorders and depression: does shared glutamatergic dysfunction contribute to comorbidity?
abstract: OBJECTIVE
  Preclinical and clinical research in neuropsychiatric disorders, particularly mood and substance use disorders, have historically focused on neurons; however, glial cells-astrocytes, microglia, and oligodendrocytes - also play key roles in these disorders.
  
  
  METHODS
  Peer-reviewed PubMed/Medline articles published through December 2012 were identified using the following keyword combinations: glia, astrocytes, oligodendrocytes/glia, microglia, substance use, substance abuse, substance dependence, alcohol, opiate, opioid, cocaine, psychostimulants, stimulants, and glutamate.
  
  
  RESULTS
  Depressive and substance use disorders are highly comorbid, suggesting a common or overlapping aetiology and pathophysiology. Reduced astrocyte cell number occurs in both disorders. Altered glutamate neurotransmission and metabolism - specifically changes in the levels/activity of transporters, receptors, and synaptic proteins potentially related to synaptic physiology - appear to be salient features of both disorders. Glial cell pathology may also underlie the pathophysiology of both disorders via impaired astrocytic production of neurotrophic factors. Microglial/neuroinflammatory pathology is also evident in both depressive and substance use disorders. Finally, oligodendrocyte impairment decreases myelination and impairs expression of myelin-related genes in both substance use and depressive disorders.
  
  
  CONCLUSIONS
  Glial-mediated glutamatergic dysfunction is a common neuropathological pathway in both substance use and depression. Therefore, glutamatergic neuromodulation is a rational drug target in this comorbidity.
authors.affiliation: Yale University Department of Psychiatry/Connecticut Mental Health Center (CMHC), Clinical Neuroscience Research Unit (CNRU) , New Haven, CT , USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.forename: Ioline D
authors.initials: ID
authors.lastname: Henter
authors.forename: Gerard
authors.initials: G
authors.lastname: Sanacora
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D015897:Comorbidity; D003866:Depressive Disorder / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D005971:Glutamates / Q000502:physiology*; D006801:Humans; D009457:Neuroglia / Q000473:pathology*; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D005971:Glutamates
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