Molecular architecture of the altered cortical complexity in autism DOI Creative Commons
Makliya Mamat, Yiyong Chen,

Wenwen Shen

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Abstract Autism Spectrum Disorder (ASD) is characterized by difficulties in social interaction, communication challenges, and repetitive behaviors. Despite extensive research, the molecular mechanisms underlying these neurodevelopmental abnormalities remain elusive. We integrated microscale brain gene expression data with macroscale MRI from 1829 participants, including individuals ASD healthy controls, Brain Imaging Data Exchange (ABIDE) I II. Using fractal dimension (FD) as an index for quantifying cortical complexity, we identified significant regional alterations ASD, within left temporoparietal, peripheral visual, right central somatomotor (including insula), ventral attention networks. Partial least squares (PLS) regression analysis revealed sets associated complexity changes, enriched biological functions related to synaptic transmission, plasticity, mitochondrial dysfunction, chromatin organization. Cell-specific analyses, protein-protein interaction (PPI) network temporal profiling further elucidated dynamic landscape alterations. These findings indicate that ASD-related are closely linked specific genetic pathways. The combined of neuroimaging transcriptomic enhances our understanding how factors contribute structural changes ASD.

Language: Английский

The cell-type underpinnings of the human functional cortical connectome DOI
Xi-Han Zhang,

Kevin M. Anderson,

Hao-Ming Dong

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Language: Английский

Citations

9
Molecular architecture of the altered cortical complexity in autism DOI Creative Commons
Makliya Mamat, Yiyong Chen,

Wenwen Shen

et al.

Molecular Autism, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 6, 2025

Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication challenges, and repetitive behaviors. Despite extensive research, the molecular mechanisms underlying these neurodevelopmental abnormalities remain elusive. We integrated microscale brain gene expression data with macroscale MRI from 1829 participants, including individuals ASD typically developing controls, autism imaging exchange I II. Using fractal dimension as an index for quantifying cortical complexity, we identified significant regional alterations ASD, within left temporoparietal, peripheral visual, right central somatomotor (including insula), ventral attention networks. Partial least squares regression analysis revealed sets associated complexity changes, enriched biological functions related to synaptic transmission, plasticity, mitochondrial dysfunction, chromatin organization. Cell-specific analyses, protein–protein interaction network temporal profiling further elucidated dynamic landscape alterations. These findings indicate that ASD-related are closely linked specific genetic pathways. The combined of neuroimaging transcriptomic enhances our understanding how factors contribute structural changes ASD.

Language: Английский

Citations

0
Identification of Hub Genes Involved in Early-onset Schizophrenia: From Genetic Susceptibility to Predicted Regulated Gene Expression DOI
Jen-Pang Wang, Sung‐Liang Yu, Po‐Chang Hsiao

et al.

Published: Jan. 20, 2025

Abstract BACKGROUND Despite a high heritability of schizophrenia (SZ), only limited variance was attributed to gene loci or the polygenic risk score in genome-wide association studies (GWAS). Early-onset SZ, more homogeneous SZ subtype, may aid bridging genotype-phenotype gap and identification its hub genes is critical for early intervention clinical practice. We aimed examine expression (GeRS) patients from both multiplex simplex families identify early-onset perform enrichment analysis understand biological functions genes. METHODS Based on GWAS genotype data with (223 372 late-onset) those (matched sex onset age), GeRSs (SZ-GeRSs) were estimated using SNP-expression prediction model derived existing brain tissues psychiatric disorders. Module-based SZ-GeRS summed over empirically clusters, network conducted genes, used functional mapping. RESULTS Among 13 modules coexpression analyses postmortem brains disorders, meta-analysis revealed that associations existed GeRS module 10 subset, M10sub-GeRS (adjusted odds ratio [aOR] = 1.38, 95% CI 1.22–1.57), six M10hub-GeRS (aOR 1.22, 1.07–1.39), after adjustment covariates. Functional mapping their excitatory neurons immune-regulatory pathways. CONCLUSIONS helps schizophrenia, sheds light possible roles pathophysiology. These findings will enhance understanding etiology contribute screening personalized prevention efforts.

Language: Английский

Citations

0
Benchmarking macaque brain gene expression for horizontal and vertical translation DOI Creative Commons
Andrea I. Luppi, Zhen-Qi Liu, Justine Y. Hansen

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(9)

Published: Feb. 28, 2025

The spatial patterning of gene expression shapes cortical organization and function. macaque is a fundamental model organism in neuroscience, but the translational potential rests on assumption that it good proxy for patterns corresponding proteins (vertical translation) orthologous human genes (horizontal translation). Here, we systematically benchmark regional cortex against (i) receptor density vivo ex microstructure (ii) expression. We find moderate cortex-wide correspondence between protein density, which improves by considering layer-specific Half examined exhibit significant correlation across cortex. Interspecies greater unimodal than transmodal cortex, recapitulating evolutionary expansion gene-protein macaque. These results showcase limitations transcriptomics discovery within species.

Language: Английский

Citations

0
Genetic, transcriptomic, metabolic, and neuropsychiatric underpinnings of cortical functional gradients DOI Creative Commons
Bin Wan, Yong He, Varun Warrier

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Functional gradients capture the organization of functional activity in cerebral cortex, delineating transitions from sensory to higher-order association areas. While group-level gradient patterns are well-characterized, biological mechanisms underlying individual variability remain poorly understood. Here, we integrate genetic, transcriptomic, and metabolic data across large-scale cohorts investigate basis their relevance neuropsychiatric conditions. Using twin-based heritability analyses genome-wide studies (GWAS) over 30,000 individuals based on three datasets, identified consistent five genetic loci associated with organization. These linked sixteen genes involved pathways, gene expression spatially correlating gradients. Furthermore, observed significant associations between cardiovascular biomarkers architecture. Polygenic risk scores for conditions, including schizophrenia, bipolar disorder, post-traumatic stress were significantly loadings, suggesting shared influences mental health risk. Our findings highlight a complex interplay variation, processes, brain function, offering new insights into foundations its implications vulnerability.

Language: Английский

Citations

0
Atypical brain maturation in psychosis is associated with long-term cognitive decline and symptom progression DOI Creative Commons

Claudio Alemán-Morillo,

Natalia García-San-Martín, Richard A.I. Bethlehem

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

ABSTRACT Background Clinical progression during psychosis has been closely associated with grey matter abnormalities resulting from atypical brain development. However, the complex interplay between psychopathology and neurodiversity challenges identifying neuroanatomical features that anticipate long-term cognitive symptomatic decline. Here, we collected MRI, cognitive, data 165 healthy controls 357 drug-naïve or minimally medicated FEP individuals were followed up 1,3,5 10 years after first episode. (1778 MRI scans assessments in total). Using normative modelling, derived subject-specific centile scores for cortical volume to investigate deviations their relationship deterioration. The association maps further characterized by examining cytoarchitectural neurobiological attributes using atlases. Aims To longitudinal exploring outcomes, as well underpinnings. Results centiles showed a widespread reduction at treatment initiation, analysis showing an increase time, indicating convergence toward normal maturation trajectories. Interestingly, this effect was reduced highly individuals. Additionally, found impairments experienced early stages correlated mitigated time. Positive symptomatology negatively regional centiles, higher benefited most treatment. Cytoarchitectural analyses revealed related FEP, function, specific molecular features, such serotonin receptor densities heteromodal areas. Conclusions Collectively, these findings underscore potential use of centile-based modelling better understanding how development contributes clinical neurodevelopmental conditions.

Language: Английский

Citations

0
Genetic neurocognitive profile of autism unveiled with gene transcription DOI Creative Commons

Yingxing Zhang,

Fangfang Li,

Hongli Wu

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106925 - 106925

Published: April 1, 2025

How neurocognitive processes elaborate phenotypic heterogeneity within autism spectrum disorder (ASD) remains unknown. Applying the principal component analysis to Neurosynth database, we established profiles characterize of ASD, revealing a cortical hierarchical axis that separates temporal cortex from other networks. By integrating with transcriptomic data, found gene sets shaping patterns are enriched in ASD-related biological and ASD pathogenic risk. Using data-driven approach, identified topographic network for comprising temporal, frontal, somatosensory, visual cortices, its signatures differentiating between regions over neurodevelopment. Additionally, functional reorganization has occurred as central node. Collectively, our results reveal spatially covarying profiles, emphasizing influence underlying genetic mechanism on ASD.

Language: Английский

Citations

0
Neurogenetic phenotypes of learning-dependent plasticity for improved perceptual decisions DOI Creative Commons
Liz Yuanxi Lee, Joseph J. Ziminski, Polytimi Frangou

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: May 21, 2025

Language: Английский

Citations

0
The relation between cortical gene expression and the neural correlates of risky behavior DOI
Shu Liu, Abdel Abdellaoui, Guido van Wingen

et al.

Nature Mental Health, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

Language: Английский

Citations

1
X chromosome inactivation; motor difficulties in 16p11.2 duplication and deletion; oligodendroglia DOI
Jill Adams

The Transmitter, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0