Genetic and Molecular Correlates of Cortical Thickness Alterations in Adults with Obsessive-Compulsive Disorder: A Transcription-Neuroimaging Association Analysis DOI Creative Commons
Xiao Hu, Da Zhang,

Chang Teng

et al.

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

Published: Jan. 3, 2024

Abstract Although numerous neuroimaging studies have shown neural alterations in individuals with obsessive-compulsive disorder (OCD), a psychiatric characterised by intrusive cognitions and repetitive behaviours, the molecular mechanisms linking brain structural changes gene expression remain poorly understood. By combining Allen Human Brain Atlas dataset data from Meta-Analysis (ENIGMA) consortium independent cohorts, this study performed partial least squares regression enrichment analysis to probe correlation between transcription cortical thickness variation adults OCD. The map of case–control differences was spatially correlated weighted combination genes enriched for neurobiologically relevant ontology terms, preferentially expressed across different cell types layers. These were specifically tissue, spanning nearly all developmental stages. Protein-protein interaction revealed that these coded network proteins encompassing several highly interactive hubs. findings bridge gap structure transcriptome OCD, fostering an integrative understanding potential biological mechanisms.

Language: Английский

Microglial contribution to the pathology of neurodevelopmental disorders in humans DOI Creative Commons
Rugilė Matulevičiūtė,

Elizabeth Toyin Akinluyi,

Tim A.O. Muntslag

et al.

Acta Neuropathologica, Journal Year: 2023, Volume and Issue: 146(5), P. 663 - 683

Published: Sept. 1, 2023

Abstract Microglia are the brain’s resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter telencephalic wall by 4th postconceptional week colonise fetal in a manner that spatiotemporally tracks key neurodevelopmental humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human warranting further focus on condition, particularly as emerging critically involved pathological signature cognitive disorders. In this article, review evidence supporting microglial involvement basic focusing species. We next concur neuropathological demonstrating whether contribute to aetiology two disorders: autism spectrum conditions schizophrenia. Next, highlight recent technologies have revolutionised our understanding biology with these tools can help us elucidate at unprecedented resolution links conclude reviewing current treatment approaches shown most promise towards targeting disorders suggest novel avenues future consideration.

Language: Английский

Citations

24
Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome DOI Creative Commons
Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel

et al.

npj Genomic Medicine, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 4, 2023

Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery cancer in afflicted NDDs, such as intellectual disorders, autism, and schizophrenia, which may bias numbers. As NDD-associated mutations, most cases, they germline while mutations sporadic, emerging during life. However, somatic mosaicism spur cancer-related germline. NDDs share proteins, pathways, mutations. Here we ask (i) exactly features share, (ii) how, despite their commonalities, differ clinical outcomes. To tackle these questions, employed a statistical framework followed network analysis. Our thorough exploration reconstructed disease-specific networks, transcriptome levels profiles autism spectrum disorder (ASD) cancers, point signaling strength key factor: strong promotes cell proliferation cancer, weaker (moderate) impacts differentiation ASD. Thus, strength, not activating decide outcome.

Language: Английский

Citations

24
Outdoor air pollution and brain development in childhood and adolescence DOI
Megan M. Herting, Katherine L. Bottenhorn, Devyn L. Cotter

et al.

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(8), P. 593 - 607

Published: July 24, 2024

Language: Английский

Citations

14
Autism- and intellectual disability-associated MYT1L mutation alters human cortical interneuron differentiation, maturation, and physiology DOI Creative Commons
Ramachandran Prakasam, Julianna Determan, Gareth Chapman

et al.

Stem Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102421 - 102421

Published: Feb. 1, 2025

Language: Английский

Citations

1
A Systematic Review of Air Pollution Exposure and Brain Structure and Function during Development DOI Creative Commons

Jessica Morrel,

Michelle Dong,

Michael A. Rosario

et al.

Environmental Research, Journal Year: 2025, Volume and Issue: unknown, P. 121368 - 121368

Published: March 1, 2025

Language: Английский

Citations

1
Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide DOI Creative Commons
Ruth Nussinov, Bengi Ruken Yavuz, Habibe Cansu Demirel

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 2, 2024

The connection and causality between cancer neurodevelopmental disorders have been puzzling. How can the same cellular pathways, proteins, mutations lead to pathologies with vastly different clinical presentations? And why do individuals disorders, such as autism schizophrenia, face higher chances of emerging throughout their lifetime? Our broad review emphasizes multi-scale aspect this type reasoning. As these examples demonstrate, rather than focusing on a specific organ system or disease, we aim at new understanding that be gained. Within framework, our calls attention computational strategies which powerful in discovering connections, causalities, predicting outcomes, are vital for drug discovery. Thus, centering features, draw rapidly increasing data molecular level, including mutations, isoforms, three-dimensional structures, expression levels respective disease-associated genes. Their integrated analysis, together chromatin states, delineate how, despite being connected, differ, how symptoms. Here, seek uncover cancer, pediatric tumors, tantalizing questions raises.

Language: Английский

Citations

7
Denovo variants in POGZ and YY1 genes: The novel mega players for neurodevelopmental syndromes in two unrelated consanguineous families DOI Creative Commons
Behjat Ul Mudassir,

Mujaddid Mudassir,

Jamal B. Williams

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0315597 - e0315597

Published: Jan. 8, 2025

Novel denovo variants of exome sequences are major cause pathogenic neurodevelopmental disorders with a dominant genetic mechanism that emphasize their heterogeneity and complex phenotypes. White Sutton syndrome Gabriele-de-Vries congenital neuro-impairments overlap severe intellectual disability, microcephaly, convulsions, seizures, delayed development, dysmorphism faces, retinal diseases, movement autistic traits. POGZ gene codes for pogo transposable element-derived zinc-finger protein YY1 regulates transcription, chromatin, RNA-binding proteins have been associated syndromes, in recent data. We present probands two unrelated consanguineous families complicated, unexplained neurocognitive syndromic characteristics clinically undiagnosed. Objectives the study were to identify altered genetics underlying molecular pathological pathways both patients. Whole sequencing identifies novel, missense variant NM_015100.4: c.776 C>T (p. Pro259Leu) exons 19 non-frameshift NM_003403.5: c.141_143delGGA Glu47del) exon 1 eight years five-month-old girl seven months old boy residing Rawalpindi Chakwal districts Punjab, Pakistan respectively. Protein modelling identified predicts size conformation modifications mutated amino acid residues lead damaging effects conserved domains expressed as neurological pathophysiology. The widens diversely ethnic highly inbred pool population spontaneously originated deleterious mutations contributes continuously expanding phenotypic canvas. Molecular identification personalized diagnosis patients suffering from complicated phenotypes, better care, management day-to-day activities prolonged life span utmost hopes.

Language: Английский

Citations

0
Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution DOI Creative Commons
Claire‐Marie Vacher, Alex Tsompanidis, Morgan R. Firestein

et al.

Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Abstract The placenta is a fetal endocrine organ that secretes many neuroactive factors, including steroids, play critical roles in brain development. study of the placenta‐brain axis and links between placental function development represents an emerging research area dubbed “neuroplacentology.” drives circulating steroids to very high levels during gestation. Recent studies have highlighted role shaping specific structures behaviors. This review uses cross‐species framework discuss genomic in‐utero environmental changes, conditions alter steroidogenesis, leading changes early developmental trajectories relevant for psychiatric such as autism, sex‐linked manner.

Language: Английский

Citations

0
Machine learning techniques for predicting neurodevelopmental impairments in premature infants: a systematic review DOI Creative Commons
Arantxa Ortega-Leon, Daniel Urda, Ignacio J. Turias

et al.

Frontiers in Artificial Intelligence, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 20, 2025

Background and objective Very preterm infants are highly susceptible to Neurodevelopmental Impairments (NDIs), including cognitive, motor, language deficits. This paper presents a systematic review of the application Machine Learning (ML) techniques predict NDIs in premature infants. Methods comparative analysis existing studies from January 2018 December 2023, highlighting their strengths, limitations, future research directions. Results We identified 26 that fulfilled inclusion criteria. In addition, we explore potential ML algorithms discuss commonly used data sources, clinical neuroimaging data. Furthermore, omics as contemporary approach employed, other diagnostic contexts is proposed. Conclusions limitations emphasized significance employing multimodal models explored various alternatives address reviewed studies. The insights derived this guide researchers clinicians toward improving early identification intervention strategies for vulnerable population.

Language: Английский

Citations

0
A human iPSC-derived midbrain neural stem cell model of prenatal opioid exposure and withdrawal: A proof of concept study DOI Creative Commons
Rhea Sullivan,

Quinn Ahrens,

Sara Mills‐Huffnagle

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0319418 - e0319418

Published: April 1, 2025

A growing body of clinical literature has described neurodevelopmental delays in infants with chronic prenatal opioid exposure and withdrawal. Despite this, the mechanism how opioids impact developing brain remains unknown. Here, we developed an vitro model morphine withdrawal using healthy human induced pluripotent stem cell (iPSC)-derived midbrain neural progenitors monolayer. To optimize our model, identified that a longer induction regional patterning period increases expression canonical receptors mu kappa compared to shorter protocol ( OPRM1 , two-tailed t-test, p = 0.004; OPRK1 0.0003). Next, showed derived from iPSC also have scant toll-like receptor 4 (TLR4) expression, key player neonatal syndrome pathophysiology. During withdrawal, differentiating experience cyclic adenosine monophosphate overshoot exposed vehicle 0.0496) conditions 0.0136, 1-way ANOVA). Finally, alters proportions differentiated progenitor fates (2-way ANOVA, F 16.05, < 0.0001). Chronic increased nestin positive 0.0094), decreased neuronal nuclear antigen neurons (NEUN) 0.0047) those vehicle. Morphine glial fibrillary acidic protein cells astrocytic lineage 0.044), NEUN-positive 0.0001) only. Applications this paradigm include mechanistic studies underscoring fate commitments early neurodevelopment during

Language: Английский

Citations

0