Academic Journal
Effects of riluzole on excitation-inhibition imbalance and functional connectivity in 22q11.2 deletion syndrome: a multimodal 7-Tesla MRI study.
| Τίτλος: | Effects of riluzole on excitation-inhibition imbalance and functional connectivity in 22q11.2 deletion syndrome: a multimodal 7-Tesla MRI study. |
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| Συγγραφείς: | Sylvester AL; Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands. Electronic address: amy.sylvester@maastrichtuniversity.nl., Spapens JC; Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands., Tse DH; Scannexus BV, Maastricht, Netherlands; Max Planck Institute for Empirical Aesthetics, Frankfurt, Germany., Serrarens C; Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands; Changes GGZ, Breda, Netherlands., Kappert S; Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands., Soons N; Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands., Poser BA; Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands; Max Planck Institute for Human Development, Berlin, Germany., Linden DE; Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands., Ivanov D; Max Planck Institute for Empirical Aesthetics, Frankfurt, Germany; Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands., van Amelsvoort T; Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands., Vingerhoets C; Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands; Advisium 's Heeren Loo Zorggroep, Amersfoort, Netherlands. |
| Πηγή: | Psychiatry research. Neuroimaging [Psychiatry Res Neuroimaging] 2026 Oct; Vol. 362, pp. 112279. Date of Electronic Publication: 2026 Jun 27. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101723001 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7506 (Electronic) Linking ISSN: 09254927 NLM ISO Abbreviation: Psychiatry Res Neuroimaging Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier |
| Ιατρικοί όροι (MeSH): | Riluzole*/pharmacology , Riluzole*/therapeutic use , Gyrus Cinguli*/drug effects , Gyrus Cinguli*/diagnostic imaging , Gyrus Cinguli*/physiopathology , Gyrus Cinguli*/metabolism , DiGeorge Syndrome*/drug therapy , DiGeorge Syndrome*/diagnostic imaging , DiGeorge Syndrome*/physiopathology , DiGeorge Syndrome*/metabolism , DiGeorge Syndrome*/complications , Excitatory Amino Acid Antagonists*/pharmacology , Excitatory Amino Acid Antagonists*/therapeutic use, Magnetic Resonance Imaging/methods ; Glutamic Acid/metabolism ; gamma-Aminobutyric Acid/metabolism ; Neural Pathways/drug effects ; Neural Pathways/physiopathology ; Neural Pathways/diagnostic imaging ; Psychotic Disorders/drug therapy ; Psychotic Disorders/etiology ; Psychotic Disorders/physiopathology ; Humans ; Female ; Male ; Young Adult ; Magnetic Resonance Spectroscopy ; Adult ; Adolescent |
| Περίληψη: | 22q11.2 deletion syndrome (22q11.2DS) is associated with several psychiatric pathologies, including psychosis and cognitive impairment. This may be partially attributable to genetically-mediated imbalance of glutamatergic (excitatory) to GABAergic (inhibitory) neurotransmission, which could also modulate functional connectivity. Modifying excitation-inhibition balance with the antiglutamatergic drug riluzole may therefore treat psychotic and cognitive symptoms. Eight individuals with 22q11.2DS experiencing cognitive and/or psychotic symptoms received eight-weeks of placebo followed by eight-weeks of riluzole. After each intervention period, 7 Tesla magnetic resonance spectroscopy of the dorsal anterior cingulate cortex (dACC) and resting-state functional connectivity measurements were acquired, alongside cognitive and psychiatric assessment. Riluzole did not significantly alter dACC glutamate or GABA concentrations, or functional connectivity of the dACC. However, the ratio of dACC glutamate to GABA was significantly correlated with dACC - left insula functional connectivity post-riluzole (ρ = -0.96, p = 0.033, FDR corrected). Participants with higher glutamate after placebo had greater trend-level reductions in glutamate (ρ = -0.71, p = 0.06) post-riluzole. Exploratory analyses suggested potential associations between MRI and clinical measurements. Despite a lack of significant findings on primary outcome measures, this study demonstrates the feasibility of a multimodal MRI approach in clinical trials within 22q11.2DS, and identifies potential avenues for further research. (Copyright © 2026 The Author(s). Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no competing financial or personal interests that could be considered to have influenced the work reported in this paper. |
| Contributed Indexing: | Keywords: 22q11.2 deletion syndrome; Anterior cingulate; Functional connectivity; GABA; Glutamate; Riluzole |
| Substance Nomenclature: | 7LJ087RS6F (Riluzole) 3KX376GY7L (Glutamic Acid) 56-12-2 (gamma-Aminobutyric Acid) 0 (Excitatory Amino Acid Antagonists) |
| Entry Date(s): | Date Created: 20260630 Date Completed: 20260730 Latest Revision: 20260730 |
| Update Code: | 20260731 |
| DOI: | 10.1016/j.pscychresns.2026.112279 |
| PMID: | 42379018 |
| Βάση Δεδομένων: | MEDLINE |
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