Transient peripheral blood transcriptomic response to ketamine treatment in children with ADNP syndrome.
Ariela S. Buxbaum Grice, Laura G Sloofman, Tess Levy, Hannah Walker, Gauri Ganesh, Miguel Rodriguez de Los Santos, Pardis Amini, Joseph D. Buxbaum, Alexander Kolevzon, Ana Kostic, Michael S. Breen
Translational Psychiatry July 25, 2024 DOI: 10.1038/s41398-024-03005-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Longitudinal transcriptomic study Open-label Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Individuals with ADNP syndrome |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Single infusion with follow-up from immediately after to 1 week post-treatment |
| Topics | Ketamine Esketamine |
| Keywords | Genetics Molecular biology Pediatric medicine |
| Citations | 3 |
| Key findings | Ketamine induces transient, monocyte-enriched gene expression changes involving immune activation and metabolic suppression in individuals with ADNP syndrome. |
Abstract
Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD) and is due to mutations in the ADNP gene. Ketamine treatment has emerged as a promising therapeutic option for ADNP syndrome, showing safety and apparent behavioral improvements in a first open label study. However, the molecular perturbations induced by ketamine remain poorly understood. Here, we investigated the longitudinal effect of ketamine on the blood transcriptome of 10 individuals with ADNP syndrome. Transcriptomic profiling was performed before and at multiple time points after a single low-dose intravenous ketamine infusion (0.5 mg/kg). We show that ketamine triggers immediate and profound gene expression alterations, with specific enrichment of monocyte-related expression patterns. These acute alterations encompass diverse signaling pathways and co-expression networks, implicating upregulation of immune and inflammatory-related processes and down-regulation of RNA processing mechanisms and metabolism. Notably, these changes exhibit a transient nature, returning to baseline levels 24 hours to 1 week after treatment. These findings enhance our understanding of ketamine's molecular effects and lay the groundwork for further research elucidating its specific cellular and molecular targets. Moreover, they contribute to the development of therapeutic strategies for ADNP syndrome and potentially, ASD more broadly.
Comparable studies
Other observational and cohort studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Taming the Ketamine Tiger Volunteers from a prison population | 2010 | Observational study | n = 20 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine | 2013 | Observational cohort | n = 30 |
| Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder | 2014 | Observational cohort | n = 108 |
| 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 |
Citations in the library
Cites 8
- Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression Translational Psychiatry May 9, 2023
- Whole blood transcriptional signatures associated with rapid antidepressant response to ketamine in patients with treatment resistant depression Translational Psychiatry January 10, 2022
- An open-label study evaluating the safety, behavioral, and electrophysiological outcomes of low-dose ketamine in children with ADNP syndrome. HGG advances October 13, 2022
- Transcriptional Activation, Deactivation and Rebound Patterns in Cortex, Hippocampus and Amygdala in Response to Ketamine Infusion in Rats Frontiers in Molecular Neuroscience May 30, 2022
- Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine Translational Psychiatry February 24, 2021
and 3 more in the library