Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic review
Treatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms...
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| Language: | English |
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Elsevier
2025-09-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825003196 |
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| author | Claudia Pisanu Rosana Carvalho Silva Mattia Meattini Massimo Gennarelli Bernhard T. Baune Alessio Squassina Alessandra Minelli |
| author_facet | Claudia Pisanu Rosana Carvalho Silva Mattia Meattini Massimo Gennarelli Bernhard T. Baune Alessio Squassina Alessandra Minelli |
| author_sort | Claudia Pisanu |
| collection | DOAJ |
| description | Treatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However, the molecular underpinnings of these effects are not yet understood. This systematic review aimed to synthesize evidence from human and in vitro studies evaluating transcriptional changes associated with ketamine and esketamine treatment, to identify potential biomarkers and clarify molecular pathways relevant to their antidepressant properties. A systematic search conducted on PubMed and Scopus identified 12 studies assessing RNA expression following ketamine or esketamine treatment in patients with unipolar or bipolar depression or in human-derived cell models. Eligibility and quality were evaluated using PRISMA guidelines and a modified version of Downs and Black checklist. Twelve studies met inclusion criteria, only one of which explored the effect of esketamine, while all others focused on racemic ketamine. Five studies examined peripheral blood gene expression in patients with TRD, while seven assessed mRNA changes in vitro using human-derived cells. Transcriptome and candidate gene expression studies revealed modulation of genes and pathways related to glutamatergic signaling (GRM2, GRIN2D), immune regulation (STAT3, CCL22, IL6), and neuroplasticity (IGF2). No consistent peripheral biomarkers emerged, but transcriptional profiling revealed dynamic molecular responses to ketamine and esketamine. Ketamine and esketamine induce diverse transcriptional changes implicating neuroplastic, inflammatory, and metabolic pathways. Transcriptomic profiling offers a promising approach for uncovering biomarkers and mechanisms of antidepressant response, warranting further multi-omics, large-scale studies. |
| format | Article |
| id | doaj-art-bd8833410e7a424dbb2c6f995da69557 |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-bd8833410e7a424dbb2c6f995da695572025-08-20T03:44:24ZengElsevierPharmacological Research1096-11862025-09-0121910789410.1016/j.phrs.2025.107894Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic reviewClaudia Pisanu0Rosana Carvalho Silva1Mattia Meattini2Massimo Gennarelli3Bernhard T. Baune4Alessio Squassina5Alessandra Minelli6Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09124, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia 25123, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia 25123, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia 25123, Italy; Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia 25125, ItalyDepartment of Psychiatry and Psychotherapy, University of Münster, Münster 48149, Germany; Department of Psychiatry, Melbourne Medical School, University of Melbourne, Parkville, VIC 3010, Australia; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3052, AustraliaDepartment of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09124, Italy; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia B3H 2E2, CanadaDepartment of Molecular and Translational Medicine, University of Brescia, Brescia 25123, Italy; Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia 25125, Italy; Correspondence to: Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Viale Europa 11, Brescia 25123, ItalyTreatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However, the molecular underpinnings of these effects are not yet understood. This systematic review aimed to synthesize evidence from human and in vitro studies evaluating transcriptional changes associated with ketamine and esketamine treatment, to identify potential biomarkers and clarify molecular pathways relevant to their antidepressant properties. A systematic search conducted on PubMed and Scopus identified 12 studies assessing RNA expression following ketamine or esketamine treatment in patients with unipolar or bipolar depression or in human-derived cell models. Eligibility and quality were evaluated using PRISMA guidelines and a modified version of Downs and Black checklist. Twelve studies met inclusion criteria, only one of which explored the effect of esketamine, while all others focused on racemic ketamine. Five studies examined peripheral blood gene expression in patients with TRD, while seven assessed mRNA changes in vitro using human-derived cells. Transcriptome and candidate gene expression studies revealed modulation of genes and pathways related to glutamatergic signaling (GRM2, GRIN2D), immune regulation (STAT3, CCL22, IL6), and neuroplasticity (IGF2). No consistent peripheral biomarkers emerged, but transcriptional profiling revealed dynamic molecular responses to ketamine and esketamine. Ketamine and esketamine induce diverse transcriptional changes implicating neuroplastic, inflammatory, and metabolic pathways. Transcriptomic profiling offers a promising approach for uncovering biomarkers and mechanisms of antidepressant response, warranting further multi-omics, large-scale studies.http://www.sciencedirect.com/science/article/pii/S1043661825003196RNA expressionKetamineEsketamineSystematic reviewBiomarkersDepression |
| spellingShingle | Claudia Pisanu Rosana Carvalho Silva Mattia Meattini Massimo Gennarelli Bernhard T. Baune Alessio Squassina Alessandra Minelli Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic review Pharmacological Research RNA expression Ketamine Esketamine Systematic review Biomarkers Depression |
| title | Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic review |
| title_full | Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic review |
| title_fullStr | Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic review |
| title_full_unstemmed | Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic review |
| title_short | Effect of ketamine and esketamine on RNA expression and its relevance for depression: A systematic review |
| title_sort | effect of ketamine and esketamine on rna expression and its relevance for depression a systematic review |
| topic | RNA expression Ketamine Esketamine Systematic review Biomarkers Depression |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825003196 |
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