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Ketamine-induced hippocampal functional connectivity alterations associated with clinical remission in major depression.

Fan Zhang, Chengyu Wang, Xiaofeng Lan, Weicheng Li, Yanxiang Ye, Haiyan Liu, Zhibo Hu, Zerui You, Yanling Zhou, Yuping Ning

Journal of Affective Disorders 2023 DOI: 10.1016/j.jad.2023.01.003 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 39
Population Patients with major depressive disorder
Intervention Ketamine
Dose 0.5 mg/kg
Duration Six infusions over 12 days
Measures MADRS, Receiver Operating Characteristic Curve analyses
Topics Depression Esketamine Ketamine
Key findings Ketamine treatment was associated with different changes in left rostral hippocampus functional connectivity with default mode and dorsal attention network regions in remitters versus nonremitters, and baseline connectivity in these regions predicted antidepressant response, most strongly for hippocampus-right angular gyrus connectivity (AUC 0.8179).

Abstract

Objective: Hippocampal functional connectivity (FC) alterations, which may happen following ketamine treatment, play a key role in major depression remission. This study aims to investigate the resting-state FC changes of the hippocampus associated with clinical remission after repeated ketamine infusions.

Methods: Forty-four major depressive patients received six intravenous ketamine (0.5 mg/kg) infusions in 12 days. The FC change of the hippocampus subregions following ketamine treatment was compared between remitters (MADRS score ≤ 10 post-treatment) and nonremitters. We also investigated whether baseline hippocampus FC predicted the antidepressant efficiency of ketamine using Receiver Operating Characteristic Curve analyses.

Results: Thirty-nine patients were included in the analysis. There were significant differences in change of left rostral hippocampus FC with the right angular gyrus (the key node of the default mode network, DMN), left inferior parietal cortex and the right superior parietal cortex (parts of the dorsal attention network, dAN) between remitters and nonremitters following ketamine treatment. Specifically, while the remitters showed significantly less negative hippocampus FC than the nonremitters at baseline, the FC significantly decreased in remitters but increased in nonremitters after ketamine injections. Moreover, baseline hippocampus FC with the above three regions predicted the antidepressant effect of ketamine, with the highest predictive strength identified in the hippocampus-right angular gyrus FC (Area-Under-Curve = 0.8179, p < 0.05).

Conclusion: Ketamine treat depression by modulating the left rostral hippocampus resting-state FC with the DMN and dAN. The FC between the hippocampus and parts of the DMN and dAN may show promising potential in predicting remission after ketamine treatment in MDD.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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