ReviewInternational journal of molecular sciences2025
Molecular Underpinning of Treatment-Resistant Schizophrenia: A Putative Different Neurobiology from Treatment-Responsive Schizophrenia.
Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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
2 citing papers in PubMed.
- Transcranial focused ultrasound stimulation in schizophrenia: current evidence, mechanisms, and future directions.Frontiers in psychiatry · 2026Review
- Special Issue "Molecular Underpinnings of Schizophrenia Spectrum Disorders".International journal of molecular sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment-resistant schizophrenia (TRS) affects up to one in three individuals with schizophrenia and is associated with a significant clinical, social, and economic burden. Different from treatment-responsive forms, TRS appears to involve other biological mechanisms extending beyond dopaminergic dysfunctions. This review outlines current knowledge on the molecular and cellular basis of TRS, focusing on alterations in glutamate signaling, imbalances between excitatory and inhibitory activity, disruptions in D-amino acid metabolism, and evidence of neuroinflammation, oxidative stress, and mitochondrial or endoplasmic reticulum dysfunction. Data from genomics, proteomics, metabolomics, preclinical models, and postmortem studies suggest that TRS may have a peculiar neurobiological substrate. Further, multimodal brain imaging studies reveal differences in brain structure, white matter integrity, and network connectivity when compared to treatment-responsive individuals. Altogether, these findings support a shift from the traditional dopamine hypothesis toward a more comprehensive model that includes multiple immune, metabolic, and synaptic factors. Understanding the possible interplay of these complex mechanisms may lead to the identification of potential biomarkers that may help to predict antipsychotic response, as well as the development of more targeted treatments. Early recognition and a deeper biological insight into TRS are essential for improving care and guiding personalized therapeutic strategies.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.