ArticlePsychopharmacology2019
Altered glutamatergic response and functional connectivity in treatment resistant schizophrenia: the effect of riluzole and therapeutic implications.
Article in Psychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 9 of them syntheses that pooled it.
What it found
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Who cites it
31 citing papers in PubMed, 9 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Pooled it
- Greater Choline-Containing Compounds and Myo-inositol in Treatment-Resistant Versus Responsive Schizophrenia: ABiological psychiatry. Cognitive neuroscience and neuroimaging · 2024Pooled it
- Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.Molecular psychiatry · 2023Pooled it
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Meta-analytic evidence of elevated choline, reduced N-acetylaspartate, and normal creatine in schizophrenia and their moderation by measurement quality, echo time, and medication status.NeuroImage. Clinical · 2023Pooled it
- A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia.CNS drugs · 2022Guideline
- Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis ofMolecular psychiatry · 2022Pooled it
- A systematic review of neuropsychiatric and cognitive assessments used in clinical trials for amyotrophic lateral sclerosis.Journal of neurology · 2021Pooled it
- Medial Prefrontal Cortex Glutamate Is Reduced in Schizophrenia and Moderated by Measurement Quality: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.Biological psychiatry · 2021Pooled it
- Does a monoclonal antibody targeting immune cells affect glutamatergic level in schizophrenia? A multimodal PET/MRS brain imaging study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Trial
- Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study.Journal of psychopharmacology (Oxford, England) · 2020Trial
- Elucidating the Complex Etiology of Schizophrenia: Comprehensive Insights into the Therapeutic Roles of Natural Compounds and Pharmacological Interventions.Current pharmaceutical design · 2026Review
- Resting-state EEG and MEG gamma frequencies in schizophrenia: a systematic review and exploratory power-spectrum metanalysis.Schizophrenia (Heidelberg, Germany) · 2025Review
- Pharmacological Interventions for Negative Symptoms in Schizophrenia: A Systematic Review of Randomised Control Trials.Biomedicines · 2025Review
- Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.Translational psychiatry · 2025Review
- Plant-derived polyphenolic compounds for managing schizophrenia: mechanisms and therapeutic potential.Frontiers in pharmacology · 2025Review
- Sulcal variability in anterior lateral prefrontal cortex contributes to variability in reasoning performance among young adults.Brain structure & function · 2024Article
- Alterations of serum neuropeptide levels and their relationship to cognitive impairment and psychopathology in male patients with chronic schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- A selective review of inhibitors of protein kinase C gamma: a neuroplasticity-related common pathway for psychiatric illness.Frontiers in drug delivery · 2024Review
- D-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal neurons in a neurodevelopmental mouse model for schizophrenia.Nature communications · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleAnterior cingulate cortex (ACC) glutamatergic abnormalities are reported in treatment-resistant schizophrenia (TRS) and implicated in functional dysconnectivity and psychopathology. Preclinical evidence indicates riluzole reduces synaptic glutamate. However, it is unknown whether riluzole can modulate glutamate metabolite levels and associated functional connectivity in TRS.
objectivesTo examine the relationship between glutamatergic function and cortical connectivity and determine if riluzole can modulate glutamate metabolite levels and cortical functional connectivity in TRS.
methodsNineteen TRS patients and 18 healthy volunteers (HV) underwent magnetic resonance imaging consisting of MR spectroscopy measuring ACC glutamate plus glutamine (Glx), fMRI measuring resting ACC-functional connectivity, and arterial spin labelling measuring regional cerebral blood flow (rCBF), and clinical measures. They then received 50 mg riluzole twice daily for 2 days when imaging was repeated.
resultsBaseline (pre-riluzole) Glx levels were correlated directly with negative symptom severity (r = 0.49; p = 0.03) and inversely with verbal learning in TRS (r = - 0.63; p = 0.002), but not HV (r = - 0.24; p = 0.41). Connectivity between the ACC and anterior prefrontal cortex (aPFC) was correlated with verbal learning in TRS (r = 0.49; p = 0.04), but not HV (r = 0.28; p = 0.33). There was a significant group × time interaction effect on Glx levels (p < 0.05) and on ACC connectivity to the aPFC (p < 0.05, FWE-corrected). Riluzole decreased Glx and increased ACC-aPFC connectivity in TRS relative to HV. Change in Glx correlated inversely with change in ACC-aPFC connectivity in TRS (r = - 0.52; p = 0.02) but not HV (r = 0.01; p = 0.98). Riluzole did not alter rCBF (p > 0.05), indicating absence of a non-specific blood flow effect.
conclusionResults indicate glutamatergic function and cortical connectivity are linked to symptoms and cognitive measures and that it is possible to pharmacologically modulate them in TRS.
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