ReviewMolecular psychiatry2022
Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment.
Review in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 4 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- Neurophysiological profiles of patients with bipolar disorders as probed with transcranial magnetic stimulation: A systematic review.Neuropsychopharmacology reports · 2024Pooled it
- Associating Multimodal Neuroimaging Abnormalities With the Transcriptome and Neurotransmitter Signatures in Schizophrenia.Schizophrenia bulletin · 2023Pooled it
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Optimizing tDCS cognitive outcomes in schizophrenia: the role of dopaminergic tone and antipsychotic load.Translational psychiatry · 2026Trial
- Effects of Repetitive Transcranial Magnetic Stimulation on Upper Limb Motor Function and Serum Lipid Metabolomics in Patients With Ischemic Stroke: A Randomized Controlled Study.Brain and behavior · 2025Trial
- Effects of bilateral repetitive transcranial magnetic stimulation on prospective memory in patients with schizophrenia: A double-blind randomized controlled clinical trial.Neuropsychopharmacology reports · 2024Trial
- HD-tDCS modulation of the DLPFC-HPC-EC pathway to enhance working memory in schizophrenia: a TMS-EEG Study.Molecular psychiatry · 2026Article
- Functional impact of genetic background on variable expressivity in neurodevelopmental disorders.Nature communications · 2026Article
- Common molecular signatures: the role of BDNF, melatonin, and orexin in the ASD-schizophrenia continuum.Molecular biology reports · 2026Review
- A clinical control study of modified electroconvulsive therapy and sodium valproate as enhancement strategies for ultra-treatment-resistant schizophrenia.Schizophrenia research. Cognition · 2026Article
- Associations of neuromelanin in the substantia nigra with antipsychotic response in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Physical Therapies and Neuromodulation for Treatment-Resistant Schizophrenia: A Review of Potential Mechanisms, Efficacy, and Safety.Neuropsychiatric disease and treatment · 2026Review
- Elevated prolactin and association with treatment resistance indicators in first-hospitalized schizophrenia spectrum disorders: a real-world cohort study.BMC psychiatry · 2025Article
- A Multimodal Observational Case-Control Study Exploring Gut Microbiota-Hippocampus Alterations in Individuals With High Positive Schizotypy From the General Population.Biological psychiatry global open science · 2025Article
- Association of astrocyte-specific gene expression in the dorsolateral prefrontal cortex with clozapine treatment in schizophrenia.Translational psychiatry · 2025Article
- Effectiveness of deep brain stimulation in alleviating treatment-resistant schizophrenia: a systematic review.European journal of translational myology · 2025Article
- Ephrin-B2 deletion in GABAergic neurons induces cognitive deficits associated with single-nucleus transcriptomic differences in the prefrontal cortex.BMC biology · 2025Article
- An integrated framework for functional dissection of variable expressivity in genetic disorders.medRxiv : the preprint server for health sciences · 2025Article
- Reduced temporal variability of cortical excitation/inhibition ratio in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
24 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antipsychotic drugs are the mainstay in the treatment of schizophrenia. However, one-third of patients do not show adequate improvement in positive symptoms with non-clozapine antipsychotics. Additionally, approximately half of them show poor response to clozapine, electroconvulsive therapy, or other augmentation strategies. However, the development of novel treatment for these conditions is difficult due to the complex and heterogenous pathophysiology of treatment-resistant schizophrenia (TRS). Therefore, this review provides key findings, potential treatments, and a roadmap for future research in this area. First, we review the neurobiological pathophysiology of TRS, particularly the dopaminergic, glutamatergic, and GABAergic pathways. Next, the limitations of existing and promising treatments are presented. Specifically, this article focuses on the therapeutic potential of neuromodulation, including electroconvulsive therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Finally, we propose multivariate analyses that integrate various perspectives of the pathogenesis, such as dopaminergic dysfunction and excitatory/inhibitory imbalance, thereby elucidating the heterogeneity of TRS that could not be obtained by conventional statistics. These analyses can in turn lead to a precision medicine approach with closed-loop neuromodulation targeting the detected pathophysiology of TRS.
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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.