Elsevier

Biological Psychiatry

Volume 73, Issue 12, 15 June 2013, Pages 1172-1179
Biological Psychiatry

Review
From Pathophysiology to Novel Antidepressant Drugs: Glial Contributions to the Pathology and Treatment of Mood Disorders

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Several structural and cellular changes, including marked glial anomalies, have been observed in association with major depressive disorder. Here we review these cellular alterations and highlight the importance of glial cell pathology, especially astroglial dysfunction, in the pathophysiology of neuropsychiatric disorders with a particular interest in major depressive disorder. The functional role of astrocytes in glutamate uptake and glutamate/glutamine cycling is discussed, as is the deleterious effects of chronic stress on glial cell function. Lastly, we discuss the effect of antidepressants on glial cell function and the possibility of targeting glial cells in the quest to develop novel therapeutics.

Section snippets

Introduction to Glial Cells

Since their discovery more than 150 years ago (3), glial cells have largely been considered relatively unimportant in brain physiology, serving primarily as the “glue” of the brain. However, relatively recent discoveries elucidating the critical role of glial cells in a host of physiological processes implicate glial cell pathology as a potential contributor to many different neuropsychiatric disorders.

Historically, glial cells have been classified into three major subgroupings, astrocytes,

Human Data

Following-up on initial neuroimaging studies showing that the volume of the subgenual part of Brodmann area 24 is reduced in familial forms of MDD and bipolar disorder (BD), Ongur et al. (14) used unbiased stereological techniques to demonstrate that the numbers of glia were reduced in both MDD and BD. The most prominent reductions were evident in subgroups of subjects with familial MDD or BD who exhibited marked (24% and 41%, respectively) reductions in the number of glial cells compared with

Targeting Astroglial Function in the Development of Novel Antidepressant Treatments

Together these findings suggest that astrocytes, especially astrocytic glutamate uptake and metabolism, might serve as a viable target for mood and anxiety disorder drug development. Riluzole, a benzothiazole drug that is currently approved by the US Food and Drug Administration for the treatment of amyotrophic lateral sclerosis and shown to have neuroprotective actions in a broad range of conditions (73), has been shown to facilitate glial-mediated glutamate clearance. Several studies have now

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