Altered glutamate concentration in major depressive disorder during antidepressant treatment: A glutamate CEST MRI study

18/09/2026

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Baseline: MDD patients showed lower GluCEST MTRasym in left hippocampus and bilateral prefrontal cortex versus healthy controls.
After 8 weeks of SSRI treatment, MTRasym increased in bilateral hippocampus and prefrontal cortex compared with baseline.
Treatment-related MTRasym changes in left hippocampus and left prefrontal cortex correlated with HAMD-17 total, sleep disturbance and retardation scores.

Psychol Med. 2026 Sep 17;56:e278. doi: 10.1017/S0033291726105571.

ABSTRACT

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) represent an effective treatment for major depressive disorder (MDD). This study employed glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) to compare glutamate-sensitive signals in the prefrontal cortex and hippocampus of MDD patients before and after SSRI treatment.

METHODS: The study included 35 unmedicated MDD patients and 39 healthy controls (HCs) who underwent baseline GluCEST imaging, using magnetization transfer ratio asymmetry (MTR_asym) values to reflect regional glutamate levels. Twenty MDD patients completed follow-up GluCEST imaging after 8 weeks of SSRI treatment. Depressive symptoms were assessed using the Hamilton Rating Depression Scale (HAMD).

RESULTS: At baseline, the MTR_asym values in the left hippocampus and bilateral prefrontal cortex were significantly lower in MDD patients compared to the HCs. Following SSRI treatment, the 20 MDD patients who completed follow-up showed significantly increased MTR_asym values in the bilateral hippocampus and bilateral prefrontal cortex relative to baseline. Uncorrected correlation analyses showed that treatment-related differences in MTR_asym values in the left hippocampus and left prefrontal cortex were associated with changes in HAMD-17 total score, sleep disturbance, and retardation scores.

CONCLUSIONS: GluCEST imaging suggested abnormal glutamate-sensitive signals in the prefrontal cortex and hippocampus of patients with MDD. SSRI treatment was associated with increased GluCEST signals across all regions of interest. The observed associations between regional GluCEST signal changes and symptom changes further suggest a potential role of glutamatergic-related modulation in the therapeutic effects of SSRIs.

PMID:42750362 | DOI:10.1017/S0033291726105571

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