Early Life Origins of ASD and ADHD

Repetitive Behavior ◽

Density Lipoprotein ◽

Cost Effective ◽

Autism Spectrum ◽

Male Dominance ◽

High Rate ◽

Shared Risk

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction and communication and by the presence of restrictive, repetitive behavior. Attention deficit hyperactivity disorder (ADHD) is another common lifelong neurodevelopmental disorder characterized by three major presentations: predominantly hyperactive/impulsive, predominantly inattentive, and combined. Although ASD and ADHD are different clinical diagnoses, they share various common characteristics, including male dominance, early childhood onset, links to prenatal and perinatal factors, common comorbidity for each other, and, often, persistence into adulthood. They also have both unique and shared risk factors, which originate in early life and have lifelong implications on the affected individuals and families and society. While genetic factors contribute to ASD and ADHD risk, the environmental contribution to ASD and ADHD has been recognized as having potentially equal importance, which raises the hope for early prevention and intervention. Maternal folate levels, maternal metabolic syndrome, and metabolic biomarkers have been associated with the risk of childhood ASD; while maternal high-density lipoprotein, maternal psychosocial stress, and in utero exposure to opioids have been associated with the risk of childhood ADHD. As for shared factors, male sex, preterm birth, placental pathology, and early life exposure to acetaminophen have been associated with both ASD and ADHD. The high rate of comorbidity of ASD and ADHD and their many shared early life risk factors suggest that early identification and intervention of common early life risk factors may be cost-effective to lower the risk of both conditions. Efforts to improve maternal preconception, prenatal, and perinatal health will not only help reduce adverse reproductive and birth outcomes but will also help mitigate the risk of ASD and ADHD associated with those adverse early life events.

CHD8 regulates gut epithelial cell function and affects autism-related behaviours through the gut-brain axis

10.1101/2021.10.02.462735 ◽

2021 ◽

Author(s):

Ipsita Chaterjee ◽

Dmitriy Getselter ◽

Nasreen Ghaneem ◽

Shai Bel ◽

Evan Elliott

Keyword(s):

Epithelial Cells ◽

Cell Function ◽

Repetitive Behavior ◽

Autism Spectrum ◽

Direct Role ◽

Tuft Cells ◽

Core Symptoms ◽

The Relationship ◽

Specific Deletion

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by early onset deficits in social behavior and repetitive behavior. Chromodomain helicase DNA binding protein (CHD8) is one of the genes with the strongest association to autism. Alongside with the core symptoms of ASD, individuals with ASD are reported to have gastrointestinal (GI) problems, and a majority of individuals with CHD8 mutations display GI problems. However, the relationship between autism related genes, such as CHD8, gastrointestinal function, and autism related behaviours are yet very unclear. In the current study, we found that mice haploinsufficient for CHD8 have leaky gut, a dysregulated transcriptome in gut epithelial cells, decreased gut tuft cells and goblet cells, and an increase in microbial load. Specific deletion of CHD8 in gut epithelial cells induced an increase in anxiety-related behaviours in, a phenotype that is often observed in autism and full body knockdown of CHD8, in addition to decreased tuft cells. In addition, antibiotic treatment of CHD8 haploinsufficient mice attenuates sociability deficits. Therefore, the current study determines a pathway for autism-related GI deficits, and how these deficits may play a direct role in the development of autism-related behaviours.

Epigenomic convergence of genetic and immune risk factors in neurodevelopmental disorder cortex

10.1101/270827 ◽

2018 ◽

Cited By ~ 3

Author(s):

Vogel Ciernia A. ◽

Laufer B.I. ◽

Dunaway K.W. ◽

Hwang H. ◽

Mordaunt C.E. ◽

...

Keyword(s):

Risk Factors ◽

Gene Networks ◽

De Novo ◽

Cell Types ◽

Developed Countries ◽

Autism Spectrum ◽

Regulatory Regions ◽

Human Cortex ◽

Genes And Environment

AbstractNeurodevelopmental disorders (NDDs) impact 7% to 14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into the gene networks, cell types, and developmental timing of NDD etiology. Whole-genome bisulfite sequencing was used to examine DNA methylation in 49 human cortex samples from three different NDDs (autism spectrum disorder, Rett syndrome, and Dup15q syndrome) and matched controls. Integration of methylation differences across NDDs with relevant genomic and genetic datasets revealed differentially methylated regions (DMRs) unique to each type of NDD but with shared regulatory functions in neurons and microglia. DMRs were significantly enriched for known NDD genetic risk factors, including both common inherited and rare de novo variants. Weighted region co-methylation network analysis revealed a module related to NDD diagnosis and enriched for microglial regulatory regions. Together, these results demonstrate an epigenomic signature of NDDs in human cortex shared with known genetic and immune etiological risk. Epigenomic insights into cell types and gene regulatory regions will aid in defining therapeutic targets and early biomarkers at the interface of genetic and environmental NDD risk factors.

Research of the Causes and Risk Factors of Autism in the Western Region of Algeria

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i6.4563 ◽

2020 ◽

Vol 10 (6) ◽

pp. 91-98

Author(s):

Hayet Mehida ◽

Samira Meziani ◽

Wahiba Mehida ◽

Khalida Zemri ◽

Imene Bekhaled ◽

...

Keyword(s):

Risk Factors ◽

Clinical Symptoms ◽

Fetal Distress ◽

Autism Spectrum ◽

Western Region ◽

Male Predominance ◽

Autism Spectrum Disorder Risk ◽

The Western Region ◽

Causes And Risk Factors

Introduction Autism is a neurodevelopmental disorder that manifests before 3 years old and affects many areas, communication, social interactions and behaviors. In Algeria, there has not yet been a regional or national epidemiological investigation concerning autism spectrum disorders. Materials and methods: Our study was carried about 100 patients ( autistic children) in the western region of Algeria, in order to determine the differents risk factors involved in the onset of autism syndrome. Results and discussion: The obtained results indicate a male predominance with a sex ratio of 4: 1 and the degree of reached is average in 44% of patients. 42% of the patients are youngsters. Parents' worry about their children begins between 24 and 36 months. The parents' advanced age at conception, stress, presence of certain pathologies and drug intake by mothers, as well as fetal distress at birth and children's exposure to screens were the main risk factors. Repetitive movements, lack of social communication, language delay, and lack of visual fixation were the main clinical symptomatology. Conclusion: This study allowed us to detect the main factors associated with the onset of autism. However, the results obtained cannot be generalized to the entire population. Keywords: Autism, autism spectrum disorder, risk factors, clinical symptoms, western region of Algeria.

Nuclear Peroxisome Proliferator-Activated Receptors (PPARs) as Therapeutic Targets of Resveratrol for Autism Spectrum Disorder

International Journal of Molecular Sciences ◽

10.3390/ijms20081878 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1878 ◽

Cited By ~ 8

Author(s):

Rita Barone ◽

Renata Rizzo ◽

Giovanni Tabbì ◽

Michele Malaguarnera ◽

Richard E. Frye ◽

...

Keyword(s):

Peroxisome Proliferator Activated Receptors

Repetitive Behavior ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Mitochondrial Fatty Acid Oxidation ◽

Mitochondrial Fatty Acid ◽

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by defective social communication and interaction and restricted, repetitive behavior with a complex, multifactorial etiology. Despite an increasing worldwide prevalence of ASD, there is currently no pharmacological cure to treat core symptoms of ASD. Clinical evidence and molecular data support the role of impaired mitochondrial fatty acid oxidation (FAO) in ASD. The recognition of defects in energy metabolism in ASD may be important for better understanding ASD and developing therapeutic intervention. The nuclear peroxisome proliferator-activated receptors (PPAR) α, δ, and γ are ligand-activated receptors with distinct physiological functions in regulating lipid and glucose metabolism, as well as inflammatory response. PPAR activation allows a coordinated up-regulation of numerous FAO enzymes, resulting in significant PPAR-driven increases in mitochondrial FAO flux. Resveratrol (RSV) is a polyphenolic compound which exhibits metabolic, antioxidant, and anti-inflammatory properties, pointing to possible applications in ASD therapeutics. In this study, we review the evidence for the existing links between ASD and impaired mitochondrial FAO and review the potential implications for regulation of mitochondrial FAO in ASD by PPAR activators, including RSV.

Preconception Risk Factors for Autism Spectrum Disorder—A Pilot Study

Brain Sciences ◽

10.3390/brainsci10050293 ◽

2020 ◽

Vol 10 (5) ◽

pp. 293

Author(s):

Hankus Magdalena ◽

Kazek Beata ◽

Paprocka Justyna ◽

Kapinos-Gorczyca Agnieszka ◽

Magdalena Szczepara-Fabian ◽

...

Keyword(s):

Risk Factors ◽

Mental Illness ◽

Neurological Diseases ◽

Potential Effect ◽

Autism Spectrum ◽

Oral Contraception ◽

Spectrum Disorder ◽

Healthy Children

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of multifactorial etiology. Preconception risk factors are still poorly understood. A survey on preconception risk factors for ASD was conducted among parents of 121 ASD patients aged 3–12 years and parents of 100 healthy children aged 3–12 years. The exclusion criteria were as follows: the presence of associated problems such as intellectual disability, epilepsy or other genetic and neurological diseases. Thirteen parameters were considered, a few among which were conception problems, conception with assisted reproductive techniques, the use and duration of oral contraception, the number of previous pregnancies and miscarriages, time since the previous pregnancy (in months), the history of mental illness in the family (including ASD), other chronic diseases in the mother or father and maternal and paternal treatment in specialist outpatient clinics. Three factors statistically significantly increased the risk of developing ASD: mental illness in the mother/mother’s family (35.54% vs. 16.0%, p = 0.0002), maternal thyroid disease (16.67% vs. 5.0%, p = 0.009) and maternal oral contraception (46.28% vs. 29.0%, p = 0.01). Children of mothers with thyroid disorders or with mental illness in relatives should be closely monitored for ASD. Further studies are warranted to assess a potential effect of oral contraception on the development of offspring.

Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex

Cerebral Cortex ◽

10.1093/cercor/bhz115 ◽

2019 ◽

Vol 30 (2) ◽

pp. 640-655 ◽

Cited By ~ 7

Author(s):

A Vogel Ciernia ◽

B I Laufer ◽

H Hwang ◽

K W Dunaway ◽

C E Mordaunt ◽

...

Keyword(s):

Risk Factors ◽

Cytosine Methylation ◽

System Development ◽

Expression Patterns ◽

Developed Countries ◽

Autism Spectrum ◽

Nervous System Development ◽

Human Cortex ◽

Genes And Environment

Abstract Neurodevelopmental disorders (NDDs) affect 7–14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into NDD etiology. Whole-genome bisulfite sequencing was used to examine DNA cytosine methylation in 49 human cortex samples from 3 different NDDs (autism spectrum disorder, Rett syndrome, and Dup15q syndrome) and matched controls. Integration of methylation changes across NDDs with relevant genomic and genetic datasets revealed differentially methylated regions (DMRs) unique to each type of NDD but with shared regulatory functions in neurons and microglia. NDD DMRs were enriched within promoter regions and for transcription factor binding sites with identified methylation sensitivity. DMRs from all 3 disorders were enriched for ontologies related to nervous system development and genes with disrupted expression in brain from neurodevelopmental or neuropsychiatric disorders. Genes associated with NDD DMRs showed expression patterns indicating an important role for altered microglial function during brain development. These findings demonstrate an NDD epigenomic signature in human cortex that will aid in defining therapeutic targets and early biomarkers at the interface of genetic and environmental NDD risk factors.

Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice

Nature Communications ◽

10.1038/s41467-021-23843-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Qian Wang ◽

Ying Kong ◽

Ding-Yu Wu ◽

Ji-Hong Liu ◽

Wei Jie ◽

...

Keyword(s):

Repetitive Behavior ◽

Autism Spectrum ◽

Conditional Knockout ◽

Spectrum Disorder ◽

Null Mutant ◽

Intracellular Ca ◽

Null Mutant Mice

AbstractAutism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD.

Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations

Nature Communications ◽

10.1038/s41467-021-25532-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Elliott Rees ◽

Hugo D. J. Creeth ◽

Hai-Gwo Hwu ◽

Wei J. Chen ◽

Ming Tsuang ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Neurodevelopmental Disorders ◽

Developmental Disorders ◽

De Novo ◽

Autism Spectrum ◽

Increase Risk ◽

Spectrum Disorders ◽

Using Data ◽

Shared Risk

AbstractPeople with schizophrenia are enriched for rare coding variants in genes associated with neurodevelopmental disorders, particularly autism spectrum disorders and intellectual disability. However, it is unclear if the same changes to gene function that increase risk to neurodevelopmental disorders also do so for schizophrenia. Using data from 3444 schizophrenia trios and 37,488 neurodevelopmental disorder trios, we show that within shared risk genes, de novo variants in schizophrenia and neurodevelopmental disorders are generally of the same functional category, and that specific de novo variants observed in neurodevelopmental disorders are enriched in schizophrenia (P = 5.0 × 10−6). The latter includes variants known to be pathogenic for syndromic disorders, suggesting that schizophrenia be included as a characteristic of those syndromes. Our findings imply that, in part, neurodevelopmental disorders and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology, and support the hypothesis that at least some forms of schizophrenia lie on a continuum of neurodevelopmental disorders.

Gut microbiota on gender bias in autism spectrum disorder

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0042 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Xia Hao ◽

Jiao Pan ◽

Xiumei Gao ◽

Shiyu Zhang ◽

Yue Li

Keyword(s):

Gut Microbiota ◽

Repetitive Behavior ◽

Specific Treatment ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Communication Disorder ◽

Gender Dimorphism ◽

Men And Women

AbstractAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Its three core symptoms are social communication disorder, communication disorder, narrow interest and stereotyped repetitive behavior. The proportion of male and female autistic patients is 4:1. Many researchers have studied this phenomenon, but the mechanism is still unclear. This review mainly discusses the related mechanism from the perspective of gut microbiota and introduces the influence of gut microbiota on the difference of ASD between men and women, as well as how gut microbiota may affect the gender dimorphism of ASD through metabolite of microbiota, immunity, and genetics, which provide some useful information for those who are interested in this research and find more gender-specific treatment for autistic men and women.

Autism spectrum disorder screening in children aged 16-30 months using the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R)

Paediatrica Indonesiana ◽

10.14238/pi61.5.2021.247-52 ◽

2021 ◽

Vol 61 (5) ◽

pp. 247-52

Author(s):

Clarissa Josephine Aditya ◽

Jenni Kim Dahliana ◽

Ariani Dewi Widodo ◽

Rini Sekartini

Keyword(s):

Risk Factors ◽

High Risk ◽

Significant Risk ◽

Autism Spectrum ◽

Male Gender ◽

Spectrum Disorder ◽

Screening Tools ◽

History Of

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a global prevalence of 7.6 in 1,000 children. The Modified Checklist for Autism in Toddlers - Revised (M-CHAT-R) is one of many screening tools for ASD. It is fast, easy to use, and has been translated and validated in the Indonesian language. Objective To determine the prevalence of ASD in Indonesia and its risk factors. Methods A cross-sectional study was conducted from March to October 2020. In the first protocol (March to July 2020), 219 children aged 16-30 months from 20 hospital walk-in clinics in five districts of Jakarta were included. Subjects’ parents filled out the M-CHAT-R questionnaire during their visit. A series of questions were asked to provide information about probable risk factors associated with ASD: gender, family history of ASD, preterm birth, low birth weight (LBW), and history of seizures. The second protocol (August to October 2020) was completed by parents via an online form, where 746 children aged 16-30 months were enrolled. Therefore, a total of 965 subjects were eligible for statistical analysis. Results Of 965 subjects, 56.58% were males. Subjects’ mean of age was 22.59 (SD 4.15) months. M-CHAT-R screening showed that 34 (3.52%) subjects were at high risk of developing ASD. Only male gender was significantly associated with ASD. Conclusion We screened for ASD in healthy 16-30-month-old Indonesian children. The rate of high-risk M-CHAT-R score was 3.52%. Male gender was a significant risk factor for high-risk M-CHAT-R results.