ArticleMolecular psychiatry2021
Subtypes of schizophrenia identified by multi-omic measures associated with dysregulated immune function.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Gray Matter Volume Abnormalities in Schizophrenia: Comparisons Between P-Value and Effect Size Inference Frameworks Using Mega- and Meta-Analyses.Schizophrenia bulletin · 2026Pooled it
- Concomitant pathologies and their impact on schizophrenia: a narrative overview of current evidence.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Psychosis as a multisystem disorder of aberrant aging.npj aging · 2026Review
- Beyond data and technology: the need for new thinking to enable the era of precision prevention.BMC medicine · 2026Review
- Transcriptomic analysis in autism spectrum disorder suggests three molecular subtypes with distinct phenotypic profiles and functional pathways.Communications biology · 2026Article
- Relevance of polymorphisms in TLR2/4 genes and their association with plasma cytokines for schizophrenia.Genes and immunity · 2026Article
- Machine learning-based predictive models and subtypes patterns in peripheral blood of schizophrenia based on a machine learning computational framework.Schizophrenia (Heidelberg, Germany) · 2026Article
- Functional implications of polygenic risk for schizophrenia in human neurons.Nature communications · 2026Article
- Morphological alterations of the thymus gland in individuals with schizophrenia.Molecular psychiatry · 2025Article
- Therapeutic Horizons: Gut Microbiome, Neuroinflammation, and Epigenetics in Neuropsychiatric Disorders.Cells · 2025Review
- Imaging Biomarker Studies of Antipsychotic-Naïve First-Episode Schizophrenia in China: Progress and Future Directions.Schizophrenia bulletin · 2025Review
- Can artificial intelligence be the future solution to the enormous challenges and suffering caused by Schizophrenia?Schizophrenia (Heidelberg, Germany) · 2025Review
- Schizophrenia Studies From China: How They Help Extend the Understanding of the Illness.Schizophrenia bulletin · 2025Article
- Immunophenotypes in psychosis: is it a premature inflamm-aging disorder?Molecular psychiatry · 2024Review
- Unraveling multi-scale neuroimaging biomarkers and molecular foundations for schizophrenia: A combined multivariate pattern analysis and transcriptome-neuroimaging association study.CNS neuroscience & therapeutics · 2024Article
- Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm.Nature communications · 2024Article
- Eosinophils and Cognitive Impairment in Schizophrenia: A New Perspective.Journal of blood medicine · 2024Review
- DNA methylation and the opposing NMDAR dysfunction in schizophrenia and major depression disorders: a converging model for the therapeutic effects of psychedelic compounds in the treatment of psychiatric illness.Molecular psychiatry · 2023Review
- Two neurostructural subtypes: results of machine learning on brain images from 4,291 individuals with schizophrenia.medRxiv : the preprint server for health sciences · 2023Article
- Dissociation between neuroanatomical and symptomatic subtypes in schizophrenia.European psychiatry : the journal of the Association of European Psychiatrists · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic modifications are plausible molecular sources of phenotypic heterogeneity across schizophrenia patients. The current study investigated biological heterogeneity in schizophrenia using peripheral epigenetic profiles to delineate illness subtypes independent of their phenomenological manifestations. We applied epigenome-wide profiling with a DNA methylation array from blood samples of 63 schizophrenia patients and 59 healthy controls. Non-negative matrix factorization (NMF) and k-means clustering were performed to identify DNA methylation-related patient subtypes. The validity of the partition was tested by assessing the profile of the T cell receptor (TCR) repertoires. The uniqueness of the identified subtypes in relation to brain structural and clinical measures were evaluated. Two distinct patterns of DNA methylation profiles were identified in patients. One subtype (60.3% of patients) showed relatively limited changes in methylation levels and cell composition compared to controls, while a second subtype (39.7% of patients) exhibited widespread methylation level alterations among genes enriched in immune cell activity, as well as a higher proportion of neutrophils and lower proportion of lymphocytes. Differentiation of the two patient subtypes was validated by TCR repertoires, which paralleled the partition based on DNA methylation profiles. The subtype with widespread methylation modifications had higher symptom severity, performed worse on cognitive measures, and displayed greater reductions in fractional anisotropy of white matter tracts and evidence of gray matter thickening compared to the other subtype. Identification of a distinct subtype of schizophrenia with unique molecular, cerebral, and clinical features provide a novel parcellation of the schizophrenia syndrome with potential to guide development of individualized therapeutics.
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