Antidepressant effects of esketamine are associated with functional connectivity in the hippocampal subregion: A resting state magnetic resonance study.
Xiang Liu, Yumeng Liu, Jun Tu, Lifeng Li, Ting Long, Jiangping Li, Yingke Deng, Haijun Li, Dechang Peng, Guojiang Wu
Neuroscience July 8, 2025 DOI: 10.1016/j.neuroscience.2025.07.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 29 |
| Population | Patients with major depressive disorder |
| Intervention | Esketamine |
| Dose | six intravenous infusions |
| Duration | 2-week intervention |
| Topics | Depression Esketamine |
| Keywords | Functional connection Clinical depression Depressive illness Ketamine derivative Psychiatric medication Brain connectivity Neural networks Brain networks Hippocampal connectivity Neuroimaging Antidepressant treatment Depression therapy Mood improvement Psychiatric treatment Mental health treatment |
| Citations | 2 |
| Key findings | Esketamine treatment increased functional connectivity between the right caudal hippocampus and left cerebellum, precuneus, and middle temporal gyrus, with connectivity to the middle temporal gyrus negatively correlating with cognitive scores. |
Abstract
We aimed to investigate the relationship between changes in resting-state functional connectivity in a subregion of the hippocampus and the antidepressant effects of esketamine as well as to identify potential neuroimaging markers of the treatment outcomes. Twenty-nine patients with major depressive disorder (MDD) received six intravenous infusions of esketamine. All patients completed the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Baker Suicide Ideation Scale (BSI), and Montreal Cognitive Assessment Scale (MoCA) to assess emotional and cognitive recovery after treatment. At the same time, all participants underwent magnetic resonance imaging using seed point functional connectivity analysis to divide the hippocampus into two subregions (rostral hippocampus (rHipp) and caudal hippocampus (cHipp)). We found that 29 patients with MDD responded favorably to esketamine, with significant reductions in HAMA, HAMD, and BSI scores and significant increases in MoCA scores. After two weeks of treatment with esketamine, we found that the FC between the right cHipp and the left cerebellum_6, precuneus, and middle temporal gyrus (MTG) was significantly increased in patients with MDD. Correlation analysis showed that the FC values between the right cHipp subregion and the left MTG were negatively correlated with MoCA scores. The altered functional connectivity pattern in the hippocampal subregions in patients with MDD may be related to the regulatory mechanism of esketamine in improving depressive symptoms, mainly involving the default network and cortico-cerebellar loop. This study provides new insights into the antidepressant effects of esketamine and potential targets for the treatment of MDD.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 4
- Multiband ALFF in patients with major depressive disorder treated with esketamine and sertraline: A preliminary study Brain Research Bulletin October 6, 2026
- Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review Research Square May 27, 2026
- Effects of Intraoperative Esketamine–Dexmedetomidine Combination on Postpartum Depressive Symptoms and Neuropsychiatric Events Following Cesarean Delivery: A Randomized Controlled Trial Drug Design, Development and Therapy March 1, 2026
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
Cites 9
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Journal of Affective Disorders September 23, 2020
- Ketamine effects on default mode network activity and vigilance: A randomized, placebo‐controlled crossover simultaneous fMRI/EEG study Human Brain Mapping September 18, 2019
- Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Clinical Practice Among Patients With Treatment-Refractory Depression: An Observational Study. The Journal of Clinical Psychiatry February 1, 2023
- Modulation of the functional connectome in major depressive disorder by ketamine therapy. Psychological Medicine October 1, 2022
and 4 more in the library