Transient peripheral blood transcriptomic response to ketamine treatment in children with ADNP syndrome.
Ketamine
/ pharmacology
Humans
Male
Transcriptome
/ drug effects
Child
Female
Autism Spectrum Disorder
/ drug therapy
Child, Preschool
Nerve Tissue Proteins
/ genetics
Intellectual Disability
/ drug therapy
Developmental Disabilities
/ genetics
Gene Expression Profiling
Adolescent
Homeodomain Proteins
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
25 Jul 2024
25 Jul 2024
Historique:
received:
02
08
2023
accepted:
02
07
2024
revised:
26
06
2024
medline:
26
7
2024
pubmed:
26
7
2024
entrez:
25
7
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39054328
doi: 10.1038/s41398-024-03005-8
pii: 10.1038/s41398-024-03005-8
doi:
Substances chimiques
Ketamine
690G0D6V8H
Nerve Tissue Proteins
0
ADNP protein, human
0
Homeodomain Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
307Informations de copyright
© 2024. The Author(s).
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