Genetic Causes and Modifiers of Autism Spectrum Disorder

Frontiers in Cellular Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: Aug. 20, 2019

Autism Spectrum Disorder (ASD) is one of the most prevalent neurodevelopmental disorders, affecting an estimated 1 in 59 children. ASD highly genetically heterogeneous and may be caused by both inheritable de novo gene variations. In past decade, hundreds genes have been identified that contribute to serious deficits communication, social cognition, behavior patients often experience. However, these only account for 10-20% cases, with similar pathogenic variants diagnosed on very different levels spectrum. this review, we will describe genetic landscape discuss how modifiers such as copy number variation, single nucleotide polymorphisms, epigenetic alterations likely play a key role modulating phenotypic spectrum patients. We also consider can alter convergent signaling pathways lead impaired neural circuitry formation. Lastly, review sex-linked clinical implications. Further understanding mechanisms crucial comprehending developing novel therapies.

Language: Английский

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Maternal immune activation and neuroinflammation in human neurodevelopmental disorders

Nature Reviews Neurology, Journal Year: 2021, Volume and Issue: 17(9), P. 564 - 579

Published: Aug. 2, 2021

Language: Английский

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Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

Translational Psychiatry, Journal Year: 2021, Volume and Issue: 11(1)

Published: Jan. 21, 2021

Abstract Inflammation is increasingly recognized as a cause or consequence of common problems humanity including obesity, stress, depression, pollution and disease states such autoimmunity, asthma, infection. Maternal immune activation (MIA), triggered by both acute systemic chronic inflammation, hypothesized to be one the mechanisms implicated in pathogenesis neurodevelopmental disorders (NDD). Although there substantial preclinical evidence support MIA hypothesis, human disparate. We performed systematic review on studies examining associations between maternal inflammatory offspring NDDs (autism spectrum disorder- ASD, attention deficit hyperactivity disorder-ADHD, Tourette syndrome-TS). 32 meta-analyses 26 additional individual were identified. associated with ASD include gestational diabetes mellitus, pre-eclampsia, pollution, autoimmune diseases, ADHD smoking, low socioeconomic status (SES), disease, asthma. TS SES, diseases. Diverse pregnancy are NDDs. Given increased prevalence NDDs, urgent need explore relative cumulative risk factors mechanisms. Defining preventable high-risk pregnancies could mitigate expression severity

Language: Английский

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Immune Dysfunction and Autoimmunity as Pathological Mechanisms in Autism Spectrum Disorders

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: Nov. 13, 2018

Autism spectrum disorders (ASD) are a group of heterogeneous neurological that highly variable and clinically characterized by deficits in social interactions, communication, stereotypical behaviors. Prevalence has risen from 1 10,000 1972 to 59 children the United States 2014. This rise prevalence could be due part better diagnoses awareness, however, these together cannot solely account for such significant rise. While causative connections have not been proven majority cases, many current studies focus on combined effects genetics environment. Strikingly, distinct picture immune dysfunction emerged supported independent over past decade. Many players immune-ASD puzzle may mechanistically contributing pathogenesis disorders, including skewed cytokine responses, differences total numbers frequencies cells their subsets, neuroinflammation, adaptive innate dysfunction, as well altered levels immunoglobulin presence autoantibodies which found substantial number individuals with ASD. review summarizes latest research linking ASD, autoimmunity discusses evidence potential autoimmune component

Language: Английский

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Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China

Scientific Reports, Journal Year: 2018, Volume and Issue: 8(1)

Published: Sept. 12, 2018

Abstract Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders. Recent studies reported that children with ASD have altered gut microbiota profiles compared typical development (TD) children. However, few on bacteria been conducted in China. Here, order to elucidate changes fecal ASD, 16S rRNA sequencing was and the (V3-V4) gene tags were amplified. We investigated differences between 35 6 TD At phylum level, group indicated significant increase Bacteroidetes/Firmicutes ratio. genus we found relative abundance Sutterella , Odoribacter Butyricimonas much more abundant whereas Veillonella Streptococcus decreased significantly control group. Functional analysis demonstrated butyrate lactate producers less In addition, downloaded association data microbe–disease from human database constructed disease network including using our microbiome results. this based microbe similarity diseases, positively correlated periodontal, negatively related type 1 diabetes. Therefore, these results suggest microbe-based able predict novel connection other diseases may play role revealing pathogenesis ASD.

Language: Английский

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Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 20, 2023

Autism spectrum disorder (ASD) is a common neurodevelopmental with onset in childhood. The mechanisms underlying ASD are unclear. In recent years, the role of microglia and astrocytes has received increasing attention. Microglia prune synapses or respond to injury by sequestrating site expressing inflammatory cytokines. Astrocytes maintain homeostasis brain microenvironment through uptake ions neurotransmitters. However, molecular link between and, remains unknown. Previous research shown significant ASD, reports increased numbers reactive postmortem tissues animal models ASD. Therefore, an enhanced understanding roles essential for developing effective therapies. This review aimed summarize functions their contributions

Language: Английский

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Dysregulation of Cortical Neuron DNA Methylation Profile in Autism Spectrum Disorder

Cerebral Cortex, Journal Year: 2017, Volume and Issue: 27(12), P. 5739 - 5754

Published: Sept. 6, 2017

Autism Spectrum Disorder (ASD) is a complex neuropsychiatric syndrome whose etiology includes genetic and environmental components. Since epigenetic marks are sensitive to insult, they may be involved in the development of ASD. Initial brain studies have suggested dysregulation However, due cellular heterogeneity brain, these not determined if there true change neuronal signature. Here, we report genome-wide methylation study on fluorescence-activated cell sorting-sorted nuclei from frontal cortex 16 male ASD 15 control subjects. Using 450 K BeadArray, identified 58 differentially methylated regions (DMRs) that included loci associated GABAergic system genes, particularly ABAT GABBR1, brain-specific MicroRNAs. Selected DMRs were validated by targeted Next Generation Bisulfite Sequencing. Weighted gene correlation network analysis detected 3 co-methylation modules which significantly correlated enriched for genomic underlying neuronal, GABAergic, immune genes. Finally, an overlap ASD-related with neurodevelopment DMRs. This investigation identifies alterations DNA pattern cortical neurons, providing further evidence disorder-relevant tissues biology

Language: Английский

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Genetics and epigenetics of autism: A Review

Psychiatry and Clinical Neurosciences, Journal Year: 2017, Volume and Issue: 72(4), P. 228 - 244

Published: Sept. 23, 2017

Autism is a developmental disorder that starts before age 3 years, and children with autism have impairment in both social interaction communication, restricted, repetitive, stereotyped patterns of behavior, interests, activities. There strong heritable component spectrum (ASD) as studies shown parents who child ASD 2–18% chance having second ASD. The prevalence been increasing during the last decades much research has carried out to understand etiology, so develop novel preventive treatment strategies. This review aims at summarizing latest related ASD, focusing not only on genetics but also some epigenetic findings autism/ASD. Some promising areas using transgenic/knockout animals ideas potential prevention strategies will be discussed.

Language: Английский

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Association of Food Allergy and Other Allergic Conditions With Autism Spectrum Disorder in Children

JAMA Network Open, Journal Year: 2018, Volume and Issue: 1(2), P. e180279 - e180279

Published: June 8, 2018

IMPORTANCEThe prevalence of autism spectrum disorder (ASD) in US children has increased during the past decades.Immunologic dysfunction recently emerged as a factor associated with ASD.Although ASD are more likely to have gastrointestinal disorders, little is known about association between food allergy and ASD.OBJECTIVE To examine other allergic conditions children.DESIGN, SETTING, AND PARTICIPANTS This population-based, cross-sectional study used data from National Health Interview Survey collected 1997 2016.The analysis was performed 2018.All eligible aged 3 17 years were included.Food allergy, respiratory skin defined based on an affirmative response questionnaire by parent or guardian.MAIN OUTCOMES MEASURES Reported diagnosed physician health professional.RESULTS included 199 520 (unweighted mean [SD] age, 10.21 [4.41] years; 102 690 boys [51.47%]; 55 476 Hispanic [27.80%], 97 200 non-Hispanic white [48.72%], 30 760 black [15.42%], 16 084 race [8.06%]).Among them, 8734(weighted prevalence, 4.31%) had 24 555 (12.15%) 19 399 (9.91%) allergy.A diagnosis reported 1868 (0.95%).The weighted food, respiratory, allergies higher (11.25%, 18.73%, 16.81%, respectively) compared without (4.25%, 12.08%, 9.84%, respectively).In analyses adjusting for sex, race/ethnicity, family highest education level, income geographical region, mutual adjustment conditions, associations remained significant.The odds ratio (OR) (OR, 2.29; 95% CI, 1.87-2.81),respiratory 1.28; 1.10-1.50),and 1.50; 1.28-1.77)when comparing these those without. CONCLUSIONS RELEVANCEIn nationally representative sample children, significant positive common particular found.Further investigation warranted elucidate causality underlying mechanisms.

Language: Английский

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Epigenetics of Autism Spectrum Disorder

Advances in experimental medicine and biology, Journal Year: 2017, Volume and Issue: unknown, P. 63 - 90

Published: Jan. 1, 2017

Language: Английский

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