Exploring the heterogeneity of brain structure in autism spectrum disorder based on individual structural covariance network

Cerebral Cortex, Год журнала: 2023, Номер 33(12), С. 7311 - 7321

Опубликована: Фев. 22, 2023

Autism spectrum disorder (ASD) is characterized by highly structural heterogeneity. However, most previous studies analyzed between-group differences through a covariance network constructed based on the ASD group level, ignoring effect of between-individual differences. We gray matter volume-based individual differential (IDSCN) using T1-weighted images 207 children (ASD/healthy controls: 105/102). heterogeneity and among subtypes obtained K-means clustering analysis evidently different edges relative to healthy controls. The relationship between distortion coefficients (DCs) calculated at whole-brain, intra- interhemispheric levels clinical symptoms was then examined. Compared with control group, showed significantly altered mainly involved in frontal subcortical regions. Given IDSCN ASD, we 2 subtypes, positive DCs were different. Intra- negative can predict severity repetitive stereotyped behaviors 1 2, respectively. These findings highlight crucial role regions necessity studying from perspective

Язык: Английский

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Genetic relationship between the immune system and autism

Brain Behavior & Immunity - Health, Год журнала: 2023, Номер 34, С. 100698 - 100698

Опубликована: Ноя. 3, 2023

Autism spectrum disorder (ASD) is a common and complex neurodevelopmental condition. The pathophysiology of ASD poorly defined; however, it includes strong genetic component there increasing evidence to support role immune dysregulation. Nonetheless, unclear which phenotypes link through genetics. Hence, we investigated the correlation between diverse classes conditions markers; if these immune-related factors specific autistic-like traits in population. We estimated global local correlations (n = 55,420) 11 14,256-755,406) using genome-wide association study summary statistics. Subsequently, polygenic scores (PGS) for were calculated population-based sample 2487) associated five (i.e., attention detail, childhood behaviour, imagination, rigidity, social skills), total score. Sex-stratified PGS analyses also performed. At level, was positively correlated with allergic diseases (ALG), negatively lymphocyte count, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) (FDR-p 0.01-0.02). RA, C-reactive protein, granulocytes counts (p 5.8 × 10-6-0.002). In general population sample, increased liability SLE, ALG, levels, captured by PGS, autistic score rigidity behaviour 0.03). conclusion, demonstrated relationship immunity that depends on type phenotype considered; some increase likelihood whereas others may potentially help build resilience. Also, this be restricted loci dimensions (e.g., rigidity).

Язык: Английский

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Measures of tonic and phasic activity of the locus coeruleus—norepinephrine system in children with autism spectrum disorder: An event‐related potential and pupillometry study

Autism Research, Год журнала: 2022, Номер 15(12), С. 2250 - 2264

Опубликована: Сен. 26, 2022

A growing body of research suggests that locus coeruleus-norepinephrine (LC-NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] event-related potential [ERP]) indices provide meaningful insights about nature LC-NE ASD. Twenty-four children ASD 27 age- nonverbal-IQ matched typically developing (TD) completed two experiments: (1) a resting eye-tracking task to measure diameter, (2) three-stimulus oddball paradigm responsivity using PDR ERP. Consistent prior reports, our results indicate exhibit increased reduced (PDR ERP) activity compared their TD peers. For groups, decreased was associated diameter. Lastly, were primarily related measures attention-deficit/hyperactivity (ADHD), not ASD, symptomatology. These findings expand understanding neurophysiological differences present demonstrate aberrant activation be atypical arousal behaviorally-relevant information

Язык: Английский

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The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings

Molecular Autism, Год журнала: 2023, Номер 14(1)

Опубликована: Окт. 4, 2023

Abstract Background Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical autism variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD modulated associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed (1) investigate between-group autistic without ADHD, (2) link these variances putative genomic underpinnings. Methods We examined cortical thickness (CT) surface area (SA) their associations a sample 533 from Longitudinal European Project. Using general linear model including main effects an ASD-by-ADHD interaction, we which degree ADHD modulates autism-related neuroanatomy. Further, leveraging spatial gene expression data Allen Human Brain Atlas, identified genes whose patterns resemble our neuroimaging findings. Results In addition significant for fronto-temporal, limbic, occipital regions, observed interaction left precentral gyrus right frontal measures CT SA, respectively. Moreover, + differed those without. Both were enriched ASD—but not ADHD-related genes. Limitations Although employed multicenter design overcome single-site recruitment limitations, size N = 25 only group relatively small compared other subgroups, limits generalizability results. Also, assigned subjects into positive groupings according DSM-5 rating scale. While this sufficient obtaining research diagnosis approach did take account long symptoms have been present, typically considered when assessing setting. Conclusion Thus, findings suggest that neuroanatomy significantly may specific neuroanatomical underpinnings potentially mediated atypical expression.

Язык: Английский

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Cerebellum and social abilities: A structural and functional connectivity study in a transdiagnostic sample

Human Brain Mapping, Год журнала: 2024, Номер 45(10)

Опубликована: Июль 11, 2024

The cerebellum has been involved in social abilities and autism. Given that the is connected to cortex via cerebello-thalamo-cortical loop, connectivity between cortical regions interactions, is, right temporo-parietal junction (rTPJ) studied individuals with autism, who suffer from prototypical deficits abilities. However, existing studies small samples of categorical, case-control comparisons have yielded inconsistent results due inherent heterogeneity suggesting investigating how clinical dimensions are related cerebellar-rTPJ functional might be more relevant. Therefore, our objective was study rTPJ, focusing on its association a dimensional perspective transdiagnostic sample. We analyzed structural magnetic resonance imaging (MRI) MRI (fMRI) scans obtained during naturalistic films watching large dataset, Healthy Brain Network (HBN), examined cerebellum-rTPJ measured responsiveness scale (SRS). conducted univariate seed-to-voxel analysis, multivariate canonical correlation analysis (CCA), predictive support vector regression (SVR). included 1404 subjects (age: 10.516 ± 3.034, range: 5.822-21.820, 506 females) 414 11.260 3.318 years, 6.020-21.820, 161 females). Our CCA model revealed significant connectivity, full-scale IQ (FSIQ) SRS scores. this effect primarily driven by FSIQ as suggested SVR analysis. also demonstrated specificity rTPJ influence anatomy association. suggest there complex relationship performance IQ. This specific largely these two regions. PRACTITIONER POINTS: cerebellum-right temporoparietal pediatric found Cerebellum

Язык: Английский

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11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults

Molecular Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 4, 2024

Язык: Английский

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Patterns of Brain Maturation in Autism and Their Molecular Associations

JAMA Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 16, 2024

Importance In the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles neurodevelopmental conditions, including autism, remains unclear. Objectives To examine if, differently relation each other how these differences are associated with molecular/genomic mechanisms symptomatology. Design, Setting, Participants This study was an analysis of one largest deep-phenotyped, case-control, longitudinal (2 assessments separated by approximately 12-24 months) structural magnetic resonance imaging cognitive-behavioral autism datasets (EU-AIMS Longitudinal European Autism Project [LEAP]; dates, February 2014-November 2017) out-of-sample validation Brain Development Imaging Study (BrainMapASD) independent cohort. Analyses were performed during 2022 2023 period. multicenter included autistic children, adolescents, adults. Autistic participants if they had existing diagnosis ( DSM-IV / International Statistical Classification Diseases Related Health Problems, Tenth Revision or DSM-5 criteria). co-occurring psychiatric conditions (except psychosis/bipolar disorder) those taking regular medications included. Exposures Neuroanatomy participants. Main Outcomes Measures Intraindividual changes surface area cortical thickness over time, analyzed via surface-based morphometrics. Results A total 386 individuals LEAP cohort (6-31 years at first visit; 214 individuals, mean [SD] age, 17.3 [5.4] years; 154 male [72.0%] 172 16.35 [5.7] 108 [62.8%]) 146 BrainMapASD (11-18 49 14.31 [2.4] 42 [85.7%] 97 14.10 [2.5] 58 [59.8%]). Maturational between-group established that mostly driven sensorimotor (eg, across features, absolute loadings early visual cortex ranged from 0.07 0.11, whereas dorsolateral prefrontal 0.005 0.06). Neurodevelopmental transcriptomically enriched genes expressed several cell types various stages, candidate downregulated regulating synaptic transmission; enrichment odds ratio =3.7; P =2.6 × −10 ). more neurotypical, less autismlike maturational profile fewer social difficulties typical sensory processing (false discovery rate <.05; Pearson r ≥0.17). replicated independently collected Conclusions Relevance this case-control suggest development involved complex interplay temporally sensitive molecular mechanisms, may be both lower-order sensory) higher-order social) features autism. Thus, examining provide analytic framework neurobiological origins neurodevelopmental/mental health conditions.

Язык: Английский

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A Genetic Bridge Between Medicine and Neurodiversity for Autism

Annual Review of Genetics, Год журнала: 2024, Номер 58(1), С. 487 - 512

Опубликована: Ноя. 25, 2024

Autism represents a large spectrum of diverse individuals with varying underlying genetic architectures and needs. For some individuals, single de novo or ultrarare variant has effect on the intensity specific dimensions phenotype, while, for others, combination thousands variants commonly found in general population are involved. The impact up to 30% autistic presenting intellectual disability, significant speech delay, motor and/or seizures. common shared those attention-deficit/hyperactivity disorder, major depressive disorders, greater educational attainment, higher cognitive performance, suggesting overlapping architectures. modulate function chromatin remodeling synaptic proteins that influence connectivity neuronal circuits and, interaction environment each individual, subsequent personal trajectory child. Overall, this heterogeneity mirrors phenotypic diversity provides helpful bridge between biomedical neurodiversity perspectives. We propose participative multidisciplinary research should use information understand better assessment, treatments, accommodations autism families need.

Язык: Английский

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Interpretable and integrative deep learning for discovering brain-behaviour associations

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 17, 2025

Recent advances highlight the limitations of classification strategies in machine learning that rely on a single data source for understanding, diagnosing and predicting psychiatric syndromes. Moreover, approaches based solely clinician labels often fail to capture complexity variability these conditions. research underlines importance considering multiple dimensions span across different These developments have led more comprehensive studying conditions incorporate diverse sources such as imaging, genetics, symptom reports. Multi-view unsupervised frameworks, particularly deep models, present promising solutions integrating analysing complex datasets. Such models contain generative capabilities which facilitate exploration relationships between views. In this study, we propose robust framework interpreting combines digital avatars with stability selection assess relationships. We apply Healthy Brain Network cohort includes clinical behavioural scores brain imaging features, uncovering consistent set brain-behaviour interactions. associations link cortical measurements obtained from structural MRI reports evaluating symptoms. Our effectively identifies relevant stable associations, even incomplete datasets, while isolating interest confounding factors.

Язык: Английский

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Systematic Review and Meta-Analysis: Phenotypic Correlates of the Autism Polygenic Score

JAACAP Open, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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