Glial abnormalities in substance use disorders and depression: Does shared glutamatergic dysfunction contribute to comorbidity?. (January 2014)

• Record Type: Journal Article
• Authors: Niciu, Mark J.; Henter, Ioline D.; Sanacora, Gerard; Zarate, Carlos A.
• Is Part Of: World journal of biological psychiatry. Volume 15:Number 1(2014)
• Page Start: 2
• Page End: 16
• Publication Date: 2014-01
• Subjects: Biological psychiatry -- Periodicals; Biological Psychiatry -- Periodicals; 616.89
• DOI: 10.3109/15622975.2013.829585
• Languages: English
• ISSNs: 1562-2975

Abstract

<abstract> <title>Abstract</title> <p> <italic>Objectives.</italic> 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. <italic>Methods</italic>. 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. <italic>Results.</italic> 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. <italic>Conclusions.</italic> 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.</p> </abstract>