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Esketamine combined with sertraline for brain altered regional homogeneity in patients with major depressive disorder: A preliminary study.

Xiang Liu, Ziyi Hua, Yongqiang Shu, Lifeng Li, Shan Xia, Jiangping Li, Haijun Li, Ailan Wan, Dechang Peng, Guojiang Wu

Brain research bulletin November 13, 2025 DOI: 10.1016/j.brainresbull.2025.111637 via PubMed

Summary

AI-generated from the abstract

In patients with major depressive disorder, a two-week course of intravenous esketamine combined with sertraline led to improvements in anxiety, depression, suicidal ideation, and cognitive scores. Brain imaging revealed that before treatment, patients had abnormal spontaneous brain activity compared to healthy individuals, with increased regional homogeneity in several brain regions and decreased homogeneity in others. After treatment, the local consistency of the left middle temporal gyrus reversed toward normal levels. Changes in this region correlated with anxiety scale scores, suggesting it may be a key hub linked to depression severity and recovery.

Study at a glance

Characteristics Observational cohort Peer reviewed
Sample size 27
Population Patients with major depressive disorder and healthy individuals
Interventions esketamine sertraline
Dose 0.25 mg/kg
Duration 2-week intervention
Topics Depression Esketamine
Keywords Antidepressants Reho Sertraline
Citations 1
Key finding After two weeks of esketamine combined with sertraline, the left middle temporal gyrus showed a reversal of abnormal regional homogeneity toward normal levels, and these changes correlated with anxiety scores.

Abstract

This study aims to explore the relationship between the antidepressant effects of drugs (esketamine combined with sertraline) and brain function changes in patients with major depressive disorder. A total of 27 patients with major depressive disorder (MDD) and 27 healthy individuals were included in the study. All MDD patients received a 2-week course of intravenous esketamine infusion (0.25 mg/kg) combined with sertraline. We assessed patients' post-treatment emotional and cognitive recovery using the Hamilton Anxiety Scale, Hamilton Depression Scale, Beck Suicide Ideation Scale, and Montreal Cognitive Assessment Scale. Additionally, all participants underwent magnetic resonance imaging (MRI) scans, with local consistency techniques employed to evaluate changes in brain spontaneous activity before and after treatment. Finally, correlation analysis was used to assess the relationship between the characteristics of spontaneous brain activity in MDD patients and clinical scales. We found that the Reho values of certain brain regions in MDD patients differed from those in the healthy group, primarily manifested as increased regional homogeneity (Reho) values in the right superior frontal gyrus, right precentral gyrus, right middle occipital gyrus, and left middle temporal gyrus; and decreased Reho values in the right middle temporal gyrus, bilateral temporal lobes, and right posterior cerebellar lobe. After two weeks of drug treatment, we observed a reversal in the local consistency of the left middle temporal gyrus (L-MTG), which tended toward normal levels. Additionally, we observed significant improvements in anxiety, depression symptoms, suicidal ideation, and MoCA scores in MDD patients post-treatment. Furthermore, changes in Reho values in the left middle temporal gyrus (L-MTG) were significantly correlated with scores on clinical assessment scales (HAMA). Patients with MDD exhibit imbalances in spontaneous brain activity. The L-MTG, as a key hub of the default mode network and salience network, is associated with the severity of depression and recovery after treatment.

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