Inflammation Effects on Brain Glutamate in Depression: Mechanistic Considerations and Treatment Implications.
There has been increasing interest in the role of glutamate in mood disorders, especially given the profound effect of the glutamate receptor antagonist ketamine in improving depressive symptoms in patients with treatment-resistant depression. One pathway by which glutamate alterations may occur in mood disorders involves inflammation. Increased inflammation has been observed in a significant subgroup of patients with mood disorders, and inflammatory cytokines have been shown to influence glutamate metabolism through effects on astrocytes and microglia. In addition, the administration of the inflammatory cytokine interferon-alpha has been shown to increase brain glutamate in the basal ganglia and dorsal anterior cingulate cortex as measured by magnetic resonance spectroscopy (MRS). Moreover, MRS studies in patients with major depressive disorder have revealed that increased markers of inflammation including C-reactive protein correlate with increased basal ganglia glutamate, which in turn was associated with anhedonia and psychomotor retardation. Finally, human and laboratory animal studies have shown that the response to glutamate antagonists such as ketamine is predicted by increased inflammatory cytokines. Taken together, these data make a strong case that inflammation may influence glutamate metabolism to alter behavior, leading to depressive symptoms including anhedonia and psychomotor slowing.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1365-B Clifton Road., 5th Floor, B5101, Atlanta, GA, 30322, USA.
Ebrahim
E
Haroon
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1365-B Clifton Road., 5th Floor, B5101, Atlanta, GA, 30322, USA. amill02@emory.edu.
Andrew H
AH
Miller
D000818:Animals; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid
Cytokines; Depression; Glia; Glutamate; Inflammation; Magnetic resonance imaging; Neuroimaging