Substance use disorders (SUDs) frequently co-occur with other psychiatric illnesses. Conversely, primary psychiatric disorders can be mistaken for, or masked by, substance misuse. Several epidemiological surveys have demonstrated that co-occurring psychiatric disorders and SUDs are associated with a greater burden of illness and poorer longitudinal course (Mueser et al. 1998; Ziedonis 2004; Niciu et al. 2009); furthermore, clinical features alone are insufficient to diagnose depressive episode subtype in substance-abusing populations (Niciu et al. 2009). With the exception of genetic studies of depression and alcohol dependence (Kertes et al. 2011; Su et al. 2011; Edwards et al. 2012), few preclinical or clinical neuroscience investigations of dual disorders have been conducted. A number of hypotheses, however, have been proposed to explain their shared aetiology and pathophysiology, as there is considerable overlap in neural circuitry and neurotransmitter systems. In particular, the glutamatergic system is critically important in both depressive disorders and SUDs, especially impaired glial (astrocytes, microglia, and oligodendrocytes) home ostasis (Kalivas 2009; Valentine et al. 2009). This review discusses glial cell dysfunction in depressive disorders and SUDs, and attempts to synthesize neuronal-glial glutamatergic dysfunction in their comorbidity.
