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.
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.
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