ArticleNeuron2013
Imaging patients with psychosis and a mouse model establishes a spreading pattern of hippocampal dysfunction and implicates glutamate as a driver.
Article in Neuron, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 310 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
310 citing papers in PubMed, 4 syntheses or guidelines pooled it, 559 citations in OpenAlex.
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD.Psychopharmacology · 2025Pooled it
- Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review.Frontiers in neuroanatomy · 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
- Hippocampal subregion abnormalities in schizophrenia: A systematic review of structural and physiological imaging studies.Neuropsychopharmacology reports · 2018Pooled it
- Diazepam modulates hippocampal CA1 functional connectivity in people at clinical high-risk for psychosis.Psychological medicine · 2025Trial
- Effects of diazepam on hippocampal blood flow in people at clinical high risk for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 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
- Network-Based Spreading of Gray Matter Changes Across Different Stages of Psychosis.JAMA psychiatry · 2023Trial
- Hippocampal Subfield Volumes Predict Disengagement from Maintenance Treatment in First Episode Schizophrenia.Schizophrenia bulletin · 2023Trial
- Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial.Military Medical Research · 2022Trial
- Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia.Molecular psychiatry · 2022Trial
- 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
- Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Trial
- 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
- Cannabidiol attenuates insular dysfunction during motivational salience processing in subjects at clinical high risk for psychosis.Translational psychiatry · 2019Trial
- Oxytocin modulates hippocampal perfusion in people at clinical high risk for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Trial
- Acute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital.The Journal of clinical psychiatry · 2018Trial
- Prevalent and characteristic alterations in blood-brain transcriptomic-functional imaging coupling in schizophrenia.Molecular psychiatry · 2026Article
- Impaired contingency judgement in mice under ketamine: an implication for an altered sense of agency in schizophrenia.Psychopharmacology · 2026Article
- Unsupervised Clustering of ACC and Hippocampal Metabolites Identifies Subgroups in Antipsychotic-Naïve First-Episode Psychosis.Schizophrenia bulletin · 2026Article
250 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
video abstractThe hippocampus in schizophrenia is characterized by both hypermetabolism and reduced size. It remains unknown whether these abnormalities are mechanistically linked. Here we addressed this question by using MRI tools that can map hippocampal metabolism and structure in patients and mouse models. In at-risk patients, hypermetabolism was found to begin in CA1 and spread to the subiculum after psychosis onset. CA1 hypermetabolism at baseline predicted hippocampal atrophy, which occurred during progression to psychosis, most prominently in similar regions. Next, we used ketamine to model conditions of acute psychosis in mice. Acute ketamine reproduced a similar regional pattern of hypermetabolism, while repeated exposure shifted the hippocampus to a hypermetabolic basal state with concurrent atrophy and pathology in parvalbumin-expressing interneurons. Parallel in vivo experiments using the glutamate-reducing drug LY379268 and direct measurements of extracellular glutamate showed that glutamate drives both neuroimaging abnormalities. These findings show that hippocampal hypermetabolism leads to atrophy in psychotic disorder and suggest glutamate as a pathogenic driver.
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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.