Glial abnormalities in substance use disorders and depression: does shared glutamatergic dysfunction contribute to comorbidity?

World J Biol Psychiatry. 2014 Jan;15(1):2-16. doi: 10.3109/15622975.2013.829585. Epub 2013 Sep 12.

Abstract

Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Comorbidity*
  • Depressive Disorder / epidemiology
  • Depressive Disorder / metabolism*
  • Depressive Disorder / physiopathology
  • Glutamates / physiology*
  • Humans
  • Neuroglia / pathology*
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / physiopathology*

Substances

  • Glutamates