ReviewTrends in neurosciences2008
Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia.
Review in Trends in neurosciences, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 546 papers, 7 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
546 citing papers in PubMed, 7 syntheses or guidelines pooled it, 1,015 citations in OpenAlex.
- Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Pooled it
- Memantine for the Treatment of Primary Negative Symptoms in Schizophrenia: A Meta-analysis of Randomized Controlled Trials.Clinical drug investigation · 2025Pooled it
- Resting-state gamma power in schizophrenia: a systematic review and meta-analysis.Frontiers in psychiatry · 2025Pooled it
- Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.Molecular neurobiology · 2022Pooled it
- Hippocampal volume and hippocampal neuron density, number and size in schizophrenia: a systematic review and meta-analysis of postmortem studies.Molecular psychiatry · 2021Pooled it
- Pre-frontal parvalbumin interneurons in schizophrenia: a meta-analysis of post-mortem studies.Journal of neural transmission (Vienna, Austria : 1996) · 2019Pooled it
- Verbal learning and hippocampal dysfunction in schizophrenia: A meta-analysis.Neuroscience and biobehavioral reviews · 2018Pooled it
- Functional gradient reorganization and transcriptomic signatures underlying 1 Hz rTMS treatment in first-episode schizophrenia following right orbitofrontal cortex stimulation.NeuroImage. Clinical · 2026Trial
- Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin.Molecular psychiatry · 2024Trial
- Modulation of hippocampal activity in schizophrenia with levetiracetam: a randomized, double-blind, cross-over, placebo-controlled trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- Altered relationship between cortisol response to social stress and mediotemporal function during fear processing in people at clinical high risk for psychosis: a preliminary report.European archives of psychiatry and clinical neuroscience · 2022Trial
- A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis.Translational psychiatry · 2020Trial
- Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Trial
- Oxytocin modulates hippocampal perfusion in people at clinical high risk for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Trial
- Selective mGluBiological psychiatry global open science · 2026Article
- Closed-Loop Neuromodulation for Brain Fatigue: From Real-Time Biomarkers to Adaptive Intervention.International journal of molecular sciences · 2026Review
- Toward a Pluralistic Model for the Schizophrenia Spectrum-Dopamine and Beyond.JAMA psychiatry · 2026Review
- Gestational Hypoxia Disrupts Medial Ganglionic Eminence Progenitor Dynamics and Interneuron Development in Schizophrenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glutamatergic Modulators in Schizophrenia: Are We Ready to Move Beyond the Narrow Focus on Dopamine? A Potential Paradigm Shift in Psychopharmacology.Alpha psychiatry · 2026Article
- Disrupted hierarchical functional brain organization in affective and psychotic disorders: insights from functional brain gradients.Translational psychiatry · 2026Article
486 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 6 institutions in 1 country.
Funding
Abstract
Many risk genes interact synergistically to produce schizophrenia and many neurotransmitter interactions have been implicated. We have developed a circuit-based framework for understanding gene and neurotransmitter interactions. NMDAR hypofunction has been implicated in schizophrenia because NMDAR antagonists reproduce symptoms of the disease. One action of antagonists is to reduce the excitation of fast-spiking interneurons, resulting in disinhibition of pyramidal cells. Overactive pyramidal cells, notably those in the hippocampus, can drive a hyperdopaminergic state that produces psychosis. Additional aspects of interneuron function can be understood in this framework, as follows. (i) In animal models, NMDAR antagonists reduce parvalbumin and GAD67, as found in schizophrenia. These changes produce further disinhibition and can be viewed as the aberrant response of a homeostatic system having a faulty activity sensor (the NMDAR). (ii) Disinhibition decreases the power of gamma oscillation and might thereby produce negative and cognitive symptoms. (iii) Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.