Background And Objective: Ketamine may work as an anti-inflammatory agent, and it increases the levels of vascular endothelial growth factor (VEGF) in patients with treatment-resistant depression. However, whether genes related to pro-inflammatory and anti-inflammatory cytokines and VEGF may predict the treatment response to ketamine remains unknown.Therefore the aim of this study was to analyze whether specific genes related to inflammatory processes and VEGF were associated with treatment response to low-dose ketamine in patients with treatment-resistant depression.
Methods: Based on the genome data from our clinical trial, this study was a secondary analysis of candidate genes correlated with different timepoints of depressive symptoms. In total, 65 patients with treatment-resistant depression (n = 21 for ketamine 0.5 mg/kg, 20 for ketamine 0.2 mg/kg, and 24 for normal saline) were genotyped for 684,616 single nucleotide polymorphisms. Genes associated with 80 cytokines (i.e., interleukin [IL]-1, IL-6, tumor necrosis factor-α, and adiponectin) and VEGF (i.e., VEGF and VEGF receptors) were selected for the gene-based genome-wide association study on the antidepressant effect of a ketamine infusion.
Results: Specific single nucleotide polymorphisms, including rs2540315 and rs75746675 in IL1R1 and rs79568085 in VEGFC, were related to the rapid (within 240 min) antidepressant effect of a ketamine infusion; specific single nucleotide polymorphisms, such as Affx-20131665 in PIGF and rs8179353, rs8179353, and rs8179353 in TNFRSF8, were associated with the sustained (up to 2 weeks) antidepressant effect of low-dose (combined 0.5 mg/kg and 0.2 mg/kg) ketamine.
Conclusions: Our findings further revealed that genes related to both anti-inflammatory and pro-inflammatory cytokines (i.e., IL-1, IL-2, IL-6, tumor necrosis factor-α, C-reactive protein, and adiponectin) and VEGF-FLK signaling predicted the treatment response to a ketamine infusion in patients with treatment-resistant depression. The synergic modulation of inflammatory and VEGF systems may contribute to the antidepressant effect of ketamine.
Clinical Trial Registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number: UMIN000016985.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s40263-023-00989-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma microRNA Levels After Electroconvulsive Therapy in Treatment-Resistant Depressed Patients.
J ECT
January 2025
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia.
Objectives: Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD), even though the molecular mechanisms underlying its efficacy remain largely unclear. This study aimed, for the first time, to analyze plasma levels of miRNAs, key regulators of gene expression, in TRD patients undergoing ECT to investigate potential changes during treatment and their associations with symptom improvement.
Methods: The study involved 27 TRD patients who underwent ECT.
Autoimmune Encephalitis in Catatonic and Treatment-Resistant Psychotic Patients Referred to Electroconvulsive Therapy: Two Case Reports and Systematic Review.
J ECT
December 2024
From the Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy.
Autoimmune encephalitis (AE) tends to manifest as a mixture of neuropsychiatric and somatic symptoms, either of which may predominate, and often shows a progressive clinical course sometimes leading to life-threatening conditions. Catatonic and psychotic syndromes, regardless of whether associated with dysautonomia, are common manifestations of AE, especially concerning the anti-NMDAR subtype. Several autoantibodies targeting different neuronal epitopes have been linked to specific clinical manifestations and their detection is embedded in some of the diagnostic criteria for AE.
View Article and Find Full Text PDFProbing the Neurodynamic Mechanisms of Cognitive Flexibility in Depressed Individuals with Autism Spectrum Disorder.
J Child Adolesc Psychopharmacol
January 2025
Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Autism spectrum disorder (ASD) is characterized by deficits in social behavior and executive function (EF), particularly in cognitive flexibility. Whether transcranial magnetic stimulation (TMS) can improve cognitive outcomes in patients with ASD remains an open question. We examined the acute effects of prefrontal TMS on cortical excitability and fluid cognition in individuals with ASD who underwent TMS for refractory major depression.
View Article and Find Full Text PDFInhibiting H3K27 Demethylases Downregulates CREB-CREBBP, Overcoming Resistance in Relapsed Acute Lymphoblastic Leukemia.
Cancer Med
January 2025
Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Background: CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti-tumor effects have previously been demonstrated for GSK-J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers.
View Article and Find Full Text PDFPrimary Cerebral Lymphoma With Isolated Vitreoretinal and Cerebral Recurrences Without Meningeosis: A Case Report.
Cureus
December 2024
Treatment Resistant Schizophrenia Outpatient Clinic, Júlio de Matos Hospital, São José Local Health Unit, Clinical Academic Center of Lisbon, Lisbon, PRT.
Primary central nervous system lymphoma (PCNSL) is a diffuse, large B-cell lymphoma affecting the brain, spinal cord, leptomeninges, or eyes. A patient with a recurrence of a previous PCNSL manifesting as an isolated vitreoretinal disease without central nervous system (CNS) involvement and a second cerebral recurrence without vitreoretinal involvement has not yet been reported. The patient is an 86-year-old man with PCNSL of the left cerebellum diagnosed at the age of 82 years and treated with suboccipital trepanation and resection of the lesion followed by chemotherapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!