Connectivity alterations in autism reflect functional idiosyncrasy DOI Creative Commons
Oualid Benkarim, Casey Paquola, Bo‐yong Park

и другие.

Communications Biology, Год журнала: 2021, Номер 4(1)

Опубликована: Сен. 15, 2021

Abstract Autism spectrum disorder (ASD) is commonly understood as an alteration of brain networks, yet case-control analyses against typically-developing controls (TD) have yielded inconsistent results. Here, we devised a novel approach to profile the inter-individual variability in functional network organization and tested whether such idiosyncrasy contributes connectivity alterations ASD. Studying multi-centric dataset with 157 ASD 172 TD, obtained robust evidence for increased relative TD default mode, somatomotor attention but also reduced lateral temporal cortices. Idiosyncrasy age significantly correlated symptom severity Furthermore, while patterns were not ASD-related cortical thickness alterations, they co-localized expression risk genes. Notably, could demonstrate that atypical closely overlapped are measurable conventional designs may, thus, be principal driver inconsistency autism connectomics literature. These findings support important interactions between heterogeneity signatures. Our provide biomarkers study development may consolidate prior research on variable nature connectome level anomalies autism.

Язык: Английский

Autism spectrum disorder DOI
Catherine Lord, Traolach Brugha, Tony Charman

и другие.

Nature Reviews Disease Primers, Год журнала: 2020, Номер 6(1)

Опубликована: Янв. 16, 2020

Язык: Английский

Процитировано

1168

New insights into the development of the human cerebral cortex DOI Creative Commons
Zoltán Molnár, Gavin J. Clowry, Nenad Šestan

и другие.

Journal of Anatomy, Год журнала: 2019, Номер 235(3), С. 432 - 451

Опубликована: Авг. 2, 2019

The cerebral cortex constitutes more than half the volume of human brain and is presumed to be responsible for neuronal computations underlying complex phenomena, such as perception, thought, language, attention, episodic memory voluntary movement. Rodent models are extremely valuable investigation development, but cannot provide insight into aspects that unique or highly derived in humans. Many psychiatric neurological conditions have developmental origins studied adequately animal models. has some genetic, molecular, cellular anatomical features, which need further explored. Anatomical Society devoted its summer meeting topic Human Brain Development June 2018 tackle these important issues. was organized by Gavin Clowry (Newcastle University) Zoltán Molnár (University Oxford), held at St John's College, Oxford. participants provided a broad overview structure context scaling relationships across brains mammals, conserved principles recent changes lineage. Speakers considered how progenitors diversified generate an increasing variety cortical neurons. formation earliest circuits generated neurons subplate discussed together with their involvement neurodevelopmental pathologies. Gene expression networks susceptibility genes associated diseases were compared can identified organoids developed from induced pluripotent stem cells recapitulate vivo development. New views on specification glutamatergic pyramidal γ-aminobutyric acid (GABA)ergic interneurons. With advancement various imaging methods, histopathological observations now linked normal diseases. Our review gives general evaluation exciting new developments areas. much enlarged association greater interconnectivity areas each other expanded thalamus. relative enlargement upper layers, enhanced diversity function inhibitory interneurons transient layer during Here we highlight studies address differences emerge development focusing diverse facets our evolution.

Язык: Английский

Процитировано

321

Autism spectrum heterogeneity: fact or artifact? DOI Creative Commons
Laurent Mottron, Danilo Bzdok

Molecular Psychiatry, Год журнала: 2020, Номер 25(12), С. 3178 - 3185

Опубликована: Апрель 30, 2020

Abstract The current diagnostic practices are linked to a 20-fold increase in the reported prevalence of ASD over last 30 years. Fragmenting autism phenotype into dimensional “autistic traits” results alleged recognition autism-like symptoms any psychiatric or neurodevelopemental condition and individuals decreasingly distant from typical population, prematurely dismisses relevance threshold. Non-specific socio-communicative repetitive DSM 5 criteria, combined with four quantitative specifiers as well all their possible combinations, render limitless variety presentations consistent categorical diagnosis ASD. We propose several remedies this problem: maintain line research on prototypical autism; limit heterogeneity compatible situations phenotypic overlap validated etiological link reintroduce qualitative properties specifiers, language, intelligence, comorbidity, severity criteria used diagnose replacement “social” “repetitive” criteria; use these features clinical intuition experts machine-learning algorithms differentiate coherent subgroups today’s spectrum; study separately, then compare them; question autistic nature

Язык: Английский

Процитировано

253

Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology DOI Creative Commons
Cristina Cheroni, Nicolò Caporale, Giuseppe Testa

и другие.

Molecular Autism, Год журнала: 2020, Номер 11(1)

Опубликована: Сен. 10, 2020

The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds genes, converging at functional level on selective biological domains such as epigenetic regulation synaptic function, have been identified to be either causative or risk factors autism. other exposure chemicals that are widespread in environment, endocrine disruptors, has associated with adverse effects human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap regulatory pathways perturbed by mutations factors, depicting convergences interplays susceptibility toxic insults. pervasive nature chemical poses pivotal challenges for neurotoxicological studies, agencies, policy makers. This highlights emerging need developing new integrative models, biomonitoring, epidemiology, experimental, computational tools, able capture real-life scenarios encompassing interaction chronic mixture substances individuals' backgrounds. In this review, we address intertwined roles lesions Specifically, outline transformative potential stem cell coupled omics analytical approaches increasingly single resolution, tools experimentally dissect pathogenic mechanisms underlying disorders, well improve developmental neurotoxicology assessment.

Язык: Английский

Процитировано

198

Uncovering the Genetic Architecture of Major Depression DOI Creative Commons
Andrew M. McIntosh, Patrick F. Sullivan, Cathryn M. Lewis

и другие.

Neuron, Год журнала: 2019, Номер 102(1), С. 91 - 103

Опубликована: Апрель 1, 2019

Язык: Английский

Процитировано

150

Genomics, convergent neuroscience and progress in understanding autism spectrum disorder DOI
Helen Rankin Willsey, A. Jeremy Willsey, Belinda Wang

и другие.

Nature reviews. Neuroscience, Год журнала: 2022, Номер 23(6), С. 323 - 341

Опубликована: Апрель 19, 2022

Язык: Английский

Процитировано

145

Toward Neurosubtypes in Autism DOI Creative Commons
Seok‐Jun Hong, Joshua T Vogelstein, Alessandro Gozzi

и другие.

Biological Psychiatry, Год журнала: 2020, Номер 88(1), С. 111 - 128

Опубликована: Апрель 22, 2020

Язык: Английский

Процитировано

142

Multi-omic profiling of the developing human cerebral cortex at the single-cell level DOI Creative Commons
Kaiyi Zhu, Jaroslav Bendl, Samir Rahman

и другие.

Science Advances, Год журнала: 2023, Номер 9(41)

Опубликована: Окт. 12, 2023

The cellular complexity of the human brain is established via dynamic changes in gene expression throughout development that mediated, part, by spatiotemporal activity cis-regulatory elements (CREs). We simultaneously profiled and chromatin accessibility 45,549 cortical nuclei across six broad developmental time points from fetus to adult. identified cell type-specific domains which highly correlated with expression. Differentiation pseudotime trajectory analysis indicates at CREs precedes transcription structure play a critical role neuronal lineage commitment. In addition, we mapped temporally specific genetic loci implicated neuropsychiatric traits, including schizophrenia bipolar disorder. Together, our results describe complex regulation composition stages determination shed light on impact alterations disease.

Язык: Английский

Процитировано

61

High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways DOI Creative Commons
Hellen Weinschutz Mendes,

Uma Neelakantan,

Yunqing Liu

и другие.

Cell Reports, Год журнала: 2023, Номер 42(3), С. 112243 - 112243

Опубликована: Март 1, 2023

Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel vivo functional analysis 10 ASD genes at behavioral, structural, and circuit levels zebrafish mutants, revealing both unique overlapping effects loss function. Whole-brain mapping identifies forebrain cerebellum as most significant contributors brain size differences, while regions involved sensory-motor control, particularly dopaminergic regions, are associated with altered baseline activity. Finally, show global increase microglia resulting function select implicating neuroimmune dysfunction key pathway biology.

Язык: Английский

Процитировано

47

Genetic Advances in Autism DOI Creative Commons
Anita Thapar, Michael Rutter

Journal of Autism and Developmental Disorders, Год журнала: 2020, Номер 51(12), С. 4321 - 4332

Опубликована: Сен. 17, 2020

Abstract In the last 40 years, there has been a huge increase in autism genetics research and rapidly growing number of discoveries. We now know is one most highly heritable disorders with negligible shared environmental contributions. Recent discoveries also show that rare variants large effect size as well small common gene all contribute to risk. These challenge traditional diagnostic boundaries highlight heterogeneity autism. this review, we consider some key findings are shaping current understanding what these mean for clinicians.

Язык: Английский

Процитировано

124