Published: Jan. 1, 2024
Language: Английский
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: March 3, 2025
Major depressive disorder (MDD) is a widespread psychiatric condition, recognized as the third leading cause of global disease burden in 2008. In context MDD, alterations synaptic transmission within prefrontal cortex (PFC) are associated with PFC hypoactivation, key factor cognitive function and mood regulation. Given high energy demands central nervous system, these changes suggest metabolic imbalance MDD patients. However, cellular mechanisms underlying this dysregulation remain not fully elucidated. This study employs single-nucleus RNA sequencing (snRNA-seq) data to predict dorsolateral (DLPFC) Our analysis revealed cell type-specific patterns, notably disruption oxidative phosphorylation carbohydrate metabolism DLPFC Gene set enrichment based on human phenotype ontology predicted serum lactate levels patients, corroborated by observed decrease patients compared 47 age-matched healthy controls (HCs). transcriptional offers novel insights into disturbances dynamics hypoactivation. These findings instrumental for comprehending pathophysiology may guide development innovative therapeutic strategies.
Language: Английский
Citations
1
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4452 - 4452
Published: April 18, 2024
Schizophrenia is a significant worldwide health concern, affecting over 20 million individuals and contributing to potential reduction in life expectancy by up 14.5 years. Despite its profound impact, the precise pathological mechanisms underlying schizophrenia continue remain enigmatic, with previous research yielding diverse occasionally conflicting findings. Nonetheless, one consistently observed phenomenon brain imaging studies of patients disruption white matter, bundles myelinated axons that provide connectivity rapid signalling between regions. Myelin produced specialised glial cells known as oligodendrocytes, which have been shown be disrupted post-mortem analyses patients. Oligodendrocytes are generated throughout major population oligodendrocyte progenitor (OPC), essential for matter plasticity. Notably, decline specific subpopulation OPC has identified principal factor loss aging brain, suggesting this may also schizophrenia. In review, we analysed genomic databases pinpoint intersections identify shared cognitive dysfunction.
Language: Английский
Citations
5
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: May 6, 2025
ABSTRACT Autism Spectrum Disorder (ASD) presents profound clinical and etiological heterogeneity, complicating the identification of core pathophysiological mechanisms. Single-cell RNA sequencing (scRNA-seq) offers cellular resolution but integrating findings across diverse studies remains challenging. Here, we constructed a unified single-cell reference framework by scRNA-seq data from 11 distinct genetic environmental ASD animal models, encompassing over 300.000 cells various brain regions developmental stages. Comparative analyses revealed convergent differentially expressed genes (DEGs) neuronal glial populations. Cross-model comparisons validated integration, showing significant concordance between dataset individual studies, particularly for populations, demonstrating how models like valproic acid exposure recapitulate some transcriptomic alterations seen in models. Cell communication support widespread excitatory-inhibitory imbalance with predicted signaling involving ligands Pdgfa Reln . Furthermore, identified dysfunction, notably downregulation crucial functional astrocytes signatures metabolic dysregulation mature oligodendrocytes. Cross-referencing SFARI database confirmed overlap high-confidence risk genes, notable dysregulated specific cell types included Ermn (upregulated multiple glia), Foxg1 (downregulated L5/6 NP neurons) Mef2c MEIS2-like interneurons). Comparison human postmortem conserved dysregulation, highlighting enrichment presynaptic/postsynaptic translation processes neurons (implicating CACNAIA , GRIN2B CAMK2A ribosomal proteins) along neurodevelopmental disorder pathways oligodendrocytes, NRXN DLGAP gene networks. This integrative study provides unprecedented insight into molecular pathologies underlying ASD, establishing valuable resource understanding shared mechanisms identifying new potential therapeutic targets.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 16, 2025
Many genes are linked to psychiatric disorders, but genome-wide association studies (GWAS) and differential gene expression (DGE) analyses in post-mortem brain tissue often implicate distinct sets. This disconnect impedes therapeutic development, which relies on integrating genetic genomic insights. We address this issue using a novel multivariate technique that reduces DGE bias by leveraging co-expression networks controlling for confounds such as drug exposure. Deep RNA sequencing was performed bulk sgACC from individuals with bipolar disorder (BD; N=35), major depression (MDD; N=51), schizophrenia (SCZ; N=44), controls (N=55). Toxicology data dimensionality reduced multiple correspondence analysis; case-control then analyzed 1) traditional 2) group regularized canonical correlation analysis (GRCCA) - regression method accounts feature interdependence. Gene set enrichment compared results established neuropsychiatric risk genes, ontology pathways, cell type enrichments. GRCCA revealed significant SCZ ( P perm =0.001; no BD or MDD association), the resulting weight vector correlated SCZ-control t-statistics R =0.53; <0.05). Both methods indicated down-regulation of immune microglial upregulation ion transport excitatory neuron genes. However, at both transcript level showed stronger enrichments (FDR<0.05). Notably, were enriched GWAS-implicated (FDR<0.05), while not. These findings identify SCZ-specific pattern highlights implicates neuro-immune thus demonstrating utility approaches integrate signals.
Language: Английский
Citations
0
European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown
Published: July 19, 2024
Language: Английский
Citations
2
Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
Language: Английский
Citations
2
The World Journal of Biological Psychiatry, Journal Year: 2023, Volume and Issue: 25(1), P. 54 - 64
Published: Sept. 19, 2023
Objectives We have postulated that common changes in gene expression after treatment with different therapeutic classes of psychotropic drugs contribute to their mechanisms action.
Language: Английский
Citations
4
Advances in neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 165 - 191
Published: Jan. 1, 2024
Language: Английский
Citations
1
Biological Psychiatry Global Open Science, Journal Year: 2024, Volume and Issue: 5(2), P. 100415 - 100415
Published: Nov. 10, 2024
Noncoding RNAs comprise most of the transcriptome and represent an emerging area research. Among them, small nucleolar (snoRNAs) have emerged as a promising target because they been associated with development evolution several diseases, including psychiatric disorders. snoRNAs are expressed in brain, some showing brain-specific expression that indicates specific roles brain development, function, dysfunction. However, role conditions affect needs further investigation to be better understood. This scoping review summarizes existing literature on studies investigated psychiatry offers insight into potential pathophysiological mechanisms future
Language: Английский
Citations
1
Genes & Genomics, Journal Year: 2024, Volume and Issue: 46(9), P. 1071 - 1084
Published: July 31, 2024
Language: Английский
Citations
0