Disturbance of the Glutamatergic System in Mood Disorders

The role of glutamatergic system in the neurobiology of mood disorders draws increasing attention, as disturbance of this system is consistently implicated in mood disorders including major depressive disorder and bipolar disorder. Thus, the glutamate hypothesis of mood disorders is expected to complement and improve the prevailing monoamine hypothesis, and may indicate novel therapeutic targets. Since the contribution of astrocytes is found to be crucial not only in the modulation of the glutamatergic system but also in the maintenance of brain energy metabolism, alterations in the astrocytic function and neuroenergetic environment are suggested as the potential neurobiological underpinnings of mood disorders. In the present review, the evidence of glutamatergic abnormalities in mood disorders based on postmortem and magnetic resonance spectroscopy (MRS) studies is presented, and disrupted energy metabolism involving astrocytic dysfunction is proposed as the underlying mechanism linking altered energy metabolism, perturbations in the glutamatergic system, and pathogenesis of mood disorders.