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

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

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1
Yale University Department of Psychiatry/Connecticut Mental Health Center (CMHC), Clinical Neuroscience Research Unit (CNRU) , New Haven, CT , USA.

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.

PMID:
24024876
PMCID:
PMC4180366
DOI:
10.3109/15622975.2013.829585
[Indexed for MEDLINE]
Free PMC Article
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