Clinical studies have found abnormal
levels of glutamate in MDD. For example, one of the earliest study done by the department
of clinical psychiatry, University of Milan in Italy found that levels of
glutamate plasma were higher in patients with mood disorders (Altamura, Moro et
al.,1993)4. Another study conducted in 2009 that looked into the relationship
between plasma Glx levels and MDD in diagnosed subjects found that glutamate
and glutamine play an influential role in depression (Saygin et al., 2009)5,19,16.
A more direct methods of evaluating glutamate dysfunction in the brain has been
done using MRS. For instance, proton MRS showed a reduction of
glutamate/glutamine levels in the hippocampus (Block, Von Widdern et al., 2009)6.
Additional MRS studies of brain area around the prefrontal cortex decided that
depressed patients showed diminishing Glx levels in ROIs (Hasler, Tumonis et
al., 2007)6. Moreover, postmortem studies have found changes in the
expression of NMDA receptor subunits in MDD patients. for example, a study
conducted in 2014 by the Department of Psychiatry, University of Pittsburgh,
found Abnormal glutamate receptor expression in the medial temporal lobe in
patients with MDD and mood disorders (Szebeni, Crawford et al., 2014)7,11,16.
Recent studies focusing on the NMDA
receptor and its antagonists, ketamine, have showed a rapid antidepressant
effect. Also, low-dose I.V infusion of ketamine produces fast and sustained therapy
for MDD patients (Hao X, Zhu X et al,. 2016)8,2,13,17.