ArticleAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics2019
Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality/asymmetry in schizophrenia and bipolar disorder.
Article in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.Human brain mapping · 2022Pooled it
- Dissecting the Epigenetic Changes Induced by Non-Antipsychotic Mood Stabilizers on Schizophrenia and Affective Disorders: A Systematic Review.Frontiers in pharmacology · 2020Pooled it
- Postmortem evidence of brain inflammatory markers in bipolar disorder: a systematic review.Molecular psychiatry · 2020Pooled it
- Machine learning-based integration identifies a 10-gene predictive signature and its classification patterns in schizophrenia.European archives of psychiatry and clinical neuroscience · 2026Article
- Lactate-Mediated Brain Acidosis Drives Epigenetic Dysregulation of TGFB2 and Associated Gene Networks in Schizophrenia and Bipolar Disorder.International journal of molecular sciences · 2026Article
- From metabolic substrate to epigenetic regulation: roles and mechanisms of lactylation in brain health and disease.Frontiers in molecular neuroscience · 2026Review
- Disrupted genes and pathways in schizophrenia: a robust analysis of the brain and blood.BMC psychiatry · 2025Article
- Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- Lactylation and Central Nervous System Diseases.Brain sciences · 2025Review
- Reply to: "Correspondence to bipolar disorder-iPSC derived neural progenitor cells exhibit dysregulation of store-operated CaMolecular psychiatry · 2025Article
- Article
- The brain-bone axis: unraveling the complex interplay between the central nervous system and skeletal metabolism.European journal of medical research · 2024Review
- Epigenome Defines Aberrant Brain Laterality in Major Mental Illnesses.Brain sciences · 2024Review
- Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases.Biomedicines · 2024Review
- Review
- Identification of key long non-coding RNA-associated competing endogenous RNA axes in Brodmann Area 10 brain region of schizophrenia patients.Frontiers in psychiatry · 2022Article
- Early Detection and Prevention of Schizophrenic Psychosis-A Review.Brain sciences · 2021Review
- Cataloging recent advances in epigenetic alterations in major mental disorders and autism.Epigenomics · 2021Article
- Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder.Molecular psychiatry · 2021Article
- Integrative In Silico Analysis of Genome-Wide DNA Methylation Profiles in Schizophrenia.Journal of molecular neuroscience : MN · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Although the loss of brain laterality is one of the most consistent modalities in schizophrenia (SCZ) and bipolar disorder (BD), its molecular basis remains elusive. Our limited previous studies indicated that epigenetic modifications are key to the asymmetric transcriptomes of brain hemispheres. We used whole-genome expression microarrays to profile postmortem brain samples from subjects with SCZ, psychotic BD [BD[+]] or non-psychotic BD [BD(-)], or matched controls (10/group) and performed whole-genome DNA methylation (DNAM) profiling of the same samples (3-4/group) to identify pathways associated with SCZ or BD[+] and genes/sites susceptible to epigenetic regulation. qRT-PCR and quantitative DNAM analysis were employed to validate findings in larger sample sets (35/group). Gene Set Enrichment Analysis (GSEA) demonstrated that BMP signaling and astrocyte and cerebral cortex development are significantly (FDR q < 0.25) coordinately upregulated in both SCZ and BD[+], and glutamate signaling and TGFβ signaling are significantly coordinately upregulated in SCZ. GSEA also indicated that collagens are downregulated in right versus left brain of controls, but not in SCZ or BD[+] patients. Ingenuity Pathway Analysis predicted that TGFB2 is an upstream regulator of these genes (p = .0012). While lateralized expression of TGFB2 in controls (p = .017) is associated with a corresponding change in DNAM (p ≤ .023), lateralized expression and DNAM of TGFB2 are absent in SCZ or BD. Loss of brain laterality in SCZ and BD corresponds to aberrant epigenetic regulation of TGFB2 and changes in TGFβ signaling, indicating potential avenues for disease prevention/treatment.
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