Objective: This study employs glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging to investigate changes in cerebral glutamate (Glu) neurotransmitters within the prefrontal-hippocampal circuit of major depressive disorder (MDD) patients before and after selective serotonin reuptake inhibitor (SSRI) treatment. 

Methods:Thirty-five medication-naïve MDD patients and 39 healthy controls (HCs) underwent baseline GluCEST imaging.Twenty MDD patients completed follow-up scans after 8 weeks of SSRI treatment. Baseline differences in the asymmetric magnetization transfer ratio (MTR_asym) in bilateral hippocampal and prefrontal regions were assessed using ANCOVA, controlling for age and sex. Longitudinal changes were evaluated with paired t-tests. Correlations between MTR_asym values and Hamilton Depression Scale (HAMD) scores were analyzed.

Results: The MTR_asym of the left hippocampus and bilateral prefrontal cortex in patients with MDD during the baseline period was significantly lower than that in the HC group(all P<0.05). After SSRI treatment, the MTR_asym of the bilateral hippocampus and the bilateral frontal lobe in 20 cases of MDD was significantly increased compared with the baseline period(all P<0.05).The results of the correlation analysis indicated that the change value of MTR_asym in the left prefrontal lobe before and after treatment was significantly positively correlated with the change score of factor 5 (sleep disturbance) of HAMD-17(r=0.489,P=0.040); The change value of MTR_asym in the left hippocampus before and after treatment was significantly positively correlated with the change score of factor 4 (retardation) of HAMD-17(r=0.477，P=0.045).

Conclusion:GluCEST imaging revealed abnormal Glu levels in the prefrontal-hippocampal circuit in MDD, which increased after SSRI treatment, providing neuro-metabolic evidence for MDD diagnosis and treatment mechanisms.