Autism Spectrum Disorder Risk Research Articles

Mendelian randomization analyses reveal causal relationships between brain functional networks and risk of psychiatric disorders

Mendelian randomization analyses reveal causal relationships between brain functional networks and risk of psychiatric disorders

Prenatal & Perinatal Risk Factors of Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is lifelong neurodevelopmental disorder characterized by impairments in social function, communication, and certain behaviors. The etiology of ASD is unclear & it is believed to be multi-factorial, among those several prenatal & perinatal factors are found to be significant. So, the necessity of this study is to detect the presence of known risk factors of ASD which in turn may help in the early diagnosis and intervention for better long-term outcomes. Objective: To find out prenatal and perinatal risk factors of ASD. Method: A case control study was conducted with 112 cases of ASD and 201 controls of 2-6 years of age. The study was carried out in Center for Neurodevelopment and Autism in Children (CNAC), in the department of Paediatrics, Bangabandhu Sheikh Mujib Medical University and Autism Welfare Foundation (AWF). ASD was diagnosed by DSM-IV TR criteria. Mothers were interviewed and data were collected by semistructured questionnaires. Results: Total 5 risk factors were identified as the risk factors of ASD. They were: advanced paternal age (OR=2.84) and maternal age (OR=1.87); male baby (OR=2.01); environmental stress during pregnancy (OR=1.61) and preterm delivery (OR=1.80). Conclusions: It is concluded that advanced paternal age, maternal age, male baby, environmental stress during pregnancy and preterm delivery are associated with increased risk of ASD. BANGLADESH J CHILD HEALTH 2022; VOL 46 (3) : 115-121

Cross-Cultural Generalizability of the First Year Inventory for Early ASD Screening in China.

The First Year Inventory (FYI) is a parent report screening measure, aimed at identifying the risk of autism spectrum disorder (ASD) in 12-month-old infants. This study aimed to investigate the utility of FYI within the Chinese community and develop a short version, encompassing both a low-risk sample and a high-risk sample comprising infants with older siblings diagnosed with ASD. Parents of 53 high-risk (HR) infants and 519 low-risk (LR) infants, aged 11 to 13 months, were recruited. After comparing response distributions across Chinese and American samples, a new factorial structure was developed according to the factor analyses. The construct validity and internal consistency of the two FYI versions were examined. The implementation of FYI in the HR sample was also assessed. Noteworthy disparities in response distribution were observed between the Chinese and American samples. Both FYI 2.0 and the FYI short version demonstrated moderate construct validity and internal consistency, with the FYI short version exhibiting better predictive ability in the HR sample. Significant lower risk scores was observed in the HR sample compared to the LR sample. These findings substantiate the applicability and validity of the Chinese short version of FYI. Future research should include follow-up assessments with the Chinese sample to evaluate cutoff scores, considering the cutoff between sensitivity and specificity and the sample?s characteristics.

Cortical dysmorphology and reduced cortico-collicular projections in an animal model of autism spectrum disorder.

Autism spectrum disorder is a neurodevelopmental disability that includes sensory disturbances. Hearing is frequently affected and ranges from deafness to hypersensitivity. In utero exposure to the antiepileptic valproic acid is associated with increased risk of autism spectrum disorder in humans and timed valproic acid exposure is a biologically relevant and validated animal model of autism spectrum disorder. Valproic acid-exposed rats have fewer neurons in their auditory brainstem and thalamus, fewer calbindin-positive neurons, reduced ascending projections to the midbrain and thalamus, elevated thresholds, and delayed auditory brainstem responses. Additionally, in the auditory cortex, valproic acid exposure results in abnormal responses, decreased phase-locking, elevated thresholds, and abnormal tonotopic maps. We therefore hypothesized that in utero, valproic acid exposure would result in fewer neurons in auditory cortex, neuronal dysmorphology, fewer calbindin-positive neurons, and reduced connectivity. We approached this hypothesis using morphometric analyses, immunohistochemistry, and retrograde tract tracing. We found thinner cortical layers but no changes in the density of neurons, smaller pyramidal and non-pyramidal neurons in several regions, fewer neurons immunoreactive for calbindin-positive, and fewer cortical neurons projecting to the inferior colliculus. These results support the widespread impact of the auditory system in autism spectrum disorder and valproic acid-exposed animals and emphasize the utility of simple, noninvasive auditory screening for autism spectrum disorder.

Association between maternal genitourinary infections and the risk of attention deficit hyperactivity disorder and autism spectrum disorder in children according to a systematic review

Introduction. Autism spectrum disorders and attention deficit hyperactivity disorder are among the most significant and widespread mental disorders that manifest in childhood and adolescence. Their etiology and pathogenesis have not been studied enough and most likely a complex of factors leads to their formation. Among other things, data are accumulating on the role of various hazards and diseases of the mother, which increase the risk of neuropsychiatric disorders in offspring. These include genitourinary infections, whose contribution to the development of autism spectrum disorders and attention deficit hyperactivity disorder has not yet been systematically studied.Aim. To establish the contribution of maternal genitourinary infections to the formation of autism spectrum disorders and attention deficit hyperactivity disorder in children.Materials and methods. An electronic search was conducted in the Scopus and Pubmed databases to obtain relevant literature by August 2022. The search strategy included a combination of keywords and MESH terms: urogenital infections, and autism, and autism spectrum disorders, and attention deficit hyperactivity disorder, and maternal infections.Results. On this topic 10 papers have been identified in the available literature – 6 on autism spectrum disorders and 4 on attention deficit hyperactivity disorder. In all the papers on attention deficit hyperactivity disorder included in the analysis, an association between genitourinary infections and neuropsychiatric disorders was revealed. In the case of autism spectrum disorders, the data obtained were more contradictory. The heterogeneity of the available data (different designs, different deficits and approaches to the diagnosis of genitourinary infections) did not allow for a meta-analysis.Conclusions. Genitourinary infections play a pathogenetic role in the formation of attention deficit hyperactivity disorder, while the effect of genitourinary infections on the development of autism spectrum disorders seems less unambiguous. It is necessary to continue work in this area with a more unified design to form practical recommendations for the prevention of neuropsychiatric disorders.

Quantitative proteomics of dorsolateral prefrontal cortex reveals an early pattern of synaptic dysmaturation in children with idiopathic autism.

Autism spectrum disorder (ASD) is a developmental disorder with a rising prevalence and unknown etiology presenting with deficits in cognition and abnormal behavior. We hypothesized that the investigation of the synaptic component of prefrontal cortex may provide proteomic signatures that may identify the biological underpinnings of cognitive deficits in childhood ASD. Subcellular fractions of synaptosomes from prefrontal cortices of age-, brain area-, and postmortem-interval-matched samples from children and adults with idiopathic ASD vs. controls were subjected to HPLC-tandem mass spectrometry. Analysis of data revealed the enrichment of ASD risk genes that participate in slow maturation of the postsynaptic density (PSD) structure and function during early brain development. Proteomic analysis revealed down regulation of PSD-related proteins including AMPA and NMDA receptors, GRM3, DLG4, olfactomedins, Shank1-3, Homer1, CaMK2α, NRXN1, NLGN2, Drebrin1, ARHGAP32, and Dock9 in children with autism (FDR-adjusted P < 0.05). In contrast, PSD-related alterations were less severe or unchanged in adult individuals with ASD. Network analyses revealed glutamate receptor abnormalities. Overall, the proteomic data support the concept that idiopathic autism is a synaptopathy involving PSD-related ASD risk genes. Interruption in evolutionarily conserved slow maturation of the PSD complex in prefrontal cortex may lead to the development of ASD in a susceptible individual.

Association between parental psychiatric disorders and risk of offspring autism spectrum disorder: a Swedish and Finnish population-based cohort study

Roughly more than one in six adults worldwide suffer from psychiatric conditions. Sporadic studies have associated parental psychiatric disorders with autism spectrum disorder in offspring. Comprehensively examining the association between parental psychiatric disorders and offspring autism spectrum disorder is needed to guide health policies, and to inform etiologic studies. We included all children born in Sweden and Finland 1997-2016. Diagnoses were clinically ascertained from National Registers through 2017. We calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for autism spectrum disorder in offspring of fathers and mothers with psychiatric disorders, in both parents jointly and across co-occurring conditions. Among 2,505,842 children, 33,612 were diagnosed with autism spectrum disorder, of which 20% had a parent with psychiatric disorders. The risk of autism spectrum disorder was increased across all psychiatric disorders in fathers (Sweden: aHR=2.02, 95% CI=1.92-2.12; Finland: aHR=1.63, 95% CI=1.50-1.77), mothers (Sweden: aHR=2.34, 95% CI=2.24-2.43; Finland aHR=2.12, 95% CI=1.92-2.28), or both parents (Sweden: aHR=3.76, 95% CI=3.48-4.07; Finland aHR=3.61, 95% CI=3.20-4.07), compared to neither parents. Co-occurrence of parental psychiatric disorders further increased risk (e.g., Sweden: for one, two or≥three different diagnostic categories compared to no diagnosis, in fathers aHR=1.81, 2.07, 2.52; in mothers aHR=2.05, 2.63, 3.57). Psychiatric disorders in both parents conveyed the highest risk of offspring autism spectrum disorder, followed by mothers and then fathers. The risk increased with number of co-occurring disorders. All parental psychiatric disorders were associated with increased the risk of autism spectrum disorder. To reliably assess the risk of autism spectrum disorder in children, a comprehensive history incorporating the full range of parental psychiatric disorders is needed beyond solely focusing on familial autism spectrum disorder. Swedish-Research-Council-2021-0214.

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability

The Role of Dietary Patterns and Nutritional Supplements in the Management of Mental Disorders in Children and Adolescents: An Umbrella Review of Meta-Analyses: Le rôle des habitudes alimentaires et des suppléments nutritionnels dans la prise en charge des troubles mentaux chez les enfants et les adolescents : une méta-revue de méta-analyses.

In recent years, the relationship between nutrition and mental health has gained considerable interest. We identified, synthesized, and appraised all meta--analyses of randomized controlled trials (RCTs) and observational studies reporting on the efficacy of dietary patterns and nutrient supplements in the prevention and treatment of mental disorders in children and adolescents. Systematic research in MEDLINE, PsycINFO, Scopus, and Cochrane Database of Systematic Reviews was completed on 8 January 2024. Our research found 24 meta-analyses: 14 on RCTs, 8 on observational studies, and 2 combining both. Emerging evidence suggests that omega-3, in particular eicosapentaenoic acid, and Vitamin D may have adjunctive benefits in the treatment of attention deficit hyperactivity disorder (ADHD), while no evidence was found for autism spectrum disorder (ASD). Observational data also indicated that prenatal folic acid supplementation (>400 μg daily) was associated with a reduced risk of ASD in offspring. In terms of dietary habits, several meta-analyses of observational data revealed that healthy dietary patterns (rich in fruits, vegetables, and fibre, low in saturated fats) during the prenatal period, childhood, and adolescence were linked to a significantly reduced risk of internalizing disorders and externalizing disorders. Conversely, unhealthy dietary habits (high in sugars, saturated animal fats, and industrial foods, low in fruits, vegetables, and fibre) are associated with an elevated risk of these mental health issues. However, the number of available studies on dietary interventions for the treatment of depression, ASD, and ADHD was limited, and the results obtained were either nonsignificant or contradictory. Our findings emphasize the need to establish clear causal relationships between dietary habits and the risk of mental illness in children and adolescents. Moreover, further investigation of the benefits observed with some nutrient supplements (such as omega-3 and vitamin D for ADHD) through larger-scale RCTs is imperative to establish more robust conclusions.

Association of Breastfeeding Duration with Neurodevelopmental Outcomes in an Enriched Familial Likelihood Cohort for Autism Spectrum Disorder.

This study aimed to compare the breastfeeding (BF) duration of the younger siblings of children with ASD in an enriched-likelihood cohort for autism spectrum disorder (ASD), and to determine whether longer BF duration was associated with differences in neurodevelopmental outcomes in this cohort. Information on BF practices was collected via surveys in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. Developmental evaluations, including the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule, were conducted by expert clinicians. Participants' neurodevelopmental outcome was classified by an algorithm into three groups: typical development, ASD, and non-typical development. The median duration of BF was 10.70months (interquartile range of 12.07months). There were no significant differences in the distribution of duration of BF among the three neurodevelopmental outcome categories. Children in this enriched-likelihood cohort who were breastfed for > 12months had significantly higher scores on cognitive testing compared to those who were breastfed for 0-3months. There was no significant difference in ASD symptomatology or ASD risk based on BF duration.

Genetically identified mediators associated with increased risk of stroke and cardiovascular disease in individuals with autism spectrum disorder

Growing evidence suggested that individuals with autism spectrum disorder (ASD) associated with stroke and cardiovascular disease (CVD). However, the causal association between ASD and the risk of stroke and CVD remains unclear. To validate this, we performed two-sample Mendelian randomization (MR) and two-step mediation MR analyses, using relevant genetic variants sourced from the largest genome-wide association studies (GWASs). Two-sample MR evidence indicated causal relationships between ASD and any stroke (OR = 1.1184, 95% CI: 1.0302–1.2142, P < 0.01), ischemic stroke (IS) (OR = 1.1157, 95% CI: 1.0237–1.2160, P = 0.01), large-artery atherosclerotic stroke (LAS) (OR = 1.2902, 95% CI: 1.0395–1.6013, P = 0.02), atrial fibrillation (AF) (OR = 1.0820, 95% CI: 1.0019–1.1684, P = 0.04), and heart failure (HF) (OR = 1.1018, 95% CI: 1.0007–1.2132, P = 0.05). Additionally, two-step mediation MR suggested that type 2 diabetes mellitus (T2DM) partially mediated this effect (OR = 1.14, 95%CI: 1.02–1.28, P = 0.03). The mediated proportion were 10.96% (95% CI: 0.58%–12.10%) for any stroke, 11.77% (95% CI: 10.58%–12.97%) for IS, 10.62% (95% CI: 8.04%–13.20%) for LAS, and 7.57% (95% CI: 6.79%–8.36%) for HF. However, no mediated effect was observed between ASD and AF risk. These findings have implications for the development of prevention strategies and interventions for stroke and CVD in patients with ASD.

Association of cerebral palsy with autism spectrum disorder and attention-deficit/hyperactivity disorder in children: a large-scale nationwide population-based study

ObjectiveTo examine the association of cerebral palsy with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), providing evidence for interdisciplinary medical service for children with cerebral palsy.DesignA large-scale nationwide population-based...

Multigenerational Association Between Smoking and Autism Spectrum Disorder: Findings from a Nation-Wide Prospective Cohort Study.

Animal studies have shown that exposure to cigarette smoke during pregnancy can induce neurobehavioral anomalies in multiple subsequent generations. However, little work has examined such effects in humans. We examined the risk of grandchild autism spectrum disorder (ASD) in association with grandmother smoking during pregnancy, using data from 53,562 mothers and grandmothers, and 120,267 grandchildren in the Nurses' Health Study II using nurse reporting in 1999 of her mother's smoking. Grandchildren's ASD diagnoses were reported by the mothers in 2005 and 2009. Among grandmothers, 13,383 (25.0%) smoked during pregnancy, and 509 (0.4%) grandchildren were diagnosed with ASD. The adjusted odds ratio (aOR) of ASD for grandmother smoking during pregnancy was 1.52 (95% confidence limit [CI]: 1.06, 2.20). Results were similar with direct grandmother reporting in 2001 of her smoking during pregnancy from the Nurses' Mothers Cohort Study subgroup (n=22,167 grandmothers, 49,917 grandchildren) and stronger among grandmothers who smoked ≥15 cigarettes per day during pregnancy (aOR=1.93; 95% CI: 1.10, 3.40; n=1,895 grandmothers, 4,212 grandchildren). Results were similar when adjusted for mother's smoking during pregnancy. There was no association with grandfather's smoking as reported by the grandmother. Our results suggest potential persistent impact of gestational exposure to environmental insults across three generations.

The PRECISE-DYAD protocol: linking maternal and infant health trajectories in sub-Saharan Africa

Background PRECISE-DYAD is an observational cohort study of mother-child dyads running in urban and rural communities in The Gambia and Kenya. The cohort is being followed for two years and includes uncomplicated pregnancies and those that suffered pregnancy hypertension, fetal growth restriction, preterm birth, and/or stillbirth. Methods The PRECISE-DYAD study will follow up ~4200 women and their children recruited into the original PRECISE study. The study will add to the detailed pregnancy information and samples in PRECISE, collecting additional biological samples and clinical information on both the maternal and child health. Women will be asked about both their and their child’s health, their diets as well as undertaking a basic cardiology assessment. Using a case-control approach, some mothers will be asked about their mental health, their experiences of care during labour in the healthcare facility. In a sub-group, data on financial expenditure during antenatal, intrapartum, and postnatal periods will also be collected. Child development will be assessed using a range of tools, including neurodevelopment assessments, and evaluating their home environment and quality of life. In the event developmental milestones are not met, additional assessments to assess vision and their risk of autism spectrum disorders will be conducted. Finally, a personal environmental exposure model for the full cohort will be created based on air and water quality data, combined with geographical, demographic, and behavioural variables. Conclusions The PRECISE-DYAD study will provide a greater epidemiological and mechanistic understanding of health and disease pathways in two sub-Saharan African countries, following healthy and complicated pregnancies. We are seeking additional funding to maintain this cohort and to gain an understanding of the effects of pregnancies outcome on longer-term health trajectories in mothers and their children.

Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by severe deficits in social communication and interaction, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid or acetaminophen, or ingestion of propionic acid, can increase the risk of ASD. Recently, epigenetic influences on ASD have come to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here, we specifically focus on the molecular influences of the abovementioned chemicals on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. We conclude that a better understanding of these phenomena can lead to more effective interventions in ASD.

A systematic review of maternal exposures and the risk of autism spectrum disorders in their infants

Background Maternal exposures associated with autism spectrum disorder remain poorly understood. Objective The purpose of this systematic review was to assess the current understanding of maternal exposures and their associations with increased or decreased risk of infant autism. Study Design We searched Ovid MEDLINE databases and reference lists in 2021 for studies looking at maternal factors analyzed for an association with ASD. The primary outcome was autism or autism spectrum disorder diagnosis. Exposures were grouped as biomarkers, environmental, occupational, medication, genetic variability, and maternal illnesses and conditions. PRISMA guidelines were followed. Descriptive summary statistics were evaluated. Results Of 433 reports identified, 47 studies published between 2006 and 2021 fulfilled the inclusion criteria. Exposures consistently associated with a significant increased risk of autism spectrum disorder outcomes included: benzoate, 10-hydroxydecanoate, methyl jasmonate, 1-methylhistidine, nonanoic acid, organohalogens, ornithine, polyunsaturated fatty acids, agricultural pesticides, heavy metals (arsenic, cadmium, chromium, lead, low levels of manganese, tin), cigarette smoking, hypotaurine, indoor household pesticides, methanol, newborn complications at delivery, occupational exposures, solvents, strontium, urate, antibiotics, placental differently methylated regions, diabetes, maternal fever, maternal depression, androgen-associated conditions and psychiatric disorders. Factors consistently associated with a significant decreased risk included: quinoline, air conditioning, cesium, copper, 3-hydroxybutanic acid, maternal fruit consumption, mercury, and phenylalanine. Conclusions This review provides evidence that there are several potential pregnancy exposures and biomarkers associated with an autism spectrum disorder diagnosis in children. Genetic mutations may play role in impact of exposures’ risks. Continued work on identifying potential exposures and biomarkers is needed to better counsel pregnant individuals.

FAMILY HISTORY OF PSYCHOLOGICAL DISORDERS MODERATES THE ASSOCIATION BETWEEN PRENATAL MATERNAL STRESS AND RISK OF AUTISM

The increase in number of cases with autism spectrum disorder (ASD) requires further investigation to the etiology of it, which is not fully understood. It is suggested that children who are vulnerable to psychological disorders more likely to develop ASD when experience prenatally stress than children who do not. The researcher sought to conduct a natural experiment by collecting data from a sample derived from population lived in a region that experienced number of the worst civil wars in Libya. The sample consisted of 38 parents of children with ASD and 40 parents of typical children living in south Tripoli. These children were in utero during the civil wars that happened in 2011, 2014, and 2019. A case-control study was carried out comparing the two groups in terms of family history of psychological disorders. The child’s sex, parents’ age, and birth complications were controlled. Conditional logistic regression models were utilized to examine whether family history of psychological disorders predicted ASD. Findings from this study indicated that: children with ASD were more likely to have relatives with psychological disorders than those without ASD; the proportion of relatives with psychological disorders was significantly higher among children with ASD than those without ASD; there was significant associations between ASD and parents’, grandparents’, uncles’, aunts’ psychological disorders, having a first-degree relative suffers from a psychological disorder was associated with increase in odds of ASD. ,having second-degree relatives with a psychological disorder was significantly associated with increase odds of ASD, psychological disorders in first degree relatives and second degree relatives had comparable effect on the risk of ASD, when first degree relatives and second degree relatives affected the risk of ASD did not increase compared to the presence of a psychological disorder in either relatives

Food, nutrition, and autism: from soil to fork

Food and nutrition-related factors have the potential to impact development of autism spectrum disorder (ASD) and quality of life for people with ASD, but gaps in evidence exist. On 10 November 2022, Tufts University’s Friedman School of Nutrition Science and Policy and Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships of food and nutrition with ASD. This meeting report summarizes the presentations and deliberations from the meeting. Topics addressed included prenatal and child dietary intake, the microbiome, obesity, food-related environmental exposures, mechanisms and biological processes linking these factors and ASD, food-related social factors, and data sources for future research. Presentations highlighted evidence for protective associations with prenatal folic acid supplementation and ASD development, increases in risk of ASD with maternal gestational obesity, and the potential for exposure to environmental contaminants in foods and food packaging to influence ASD development. The importance of the maternal and child microbiome in ASD development or ASD-related behaviors in the child was reviewed, as was the role of discrimination in leading to disparities in environmental exposures and psychosocial factors that may influence ASD. The role of child diet and high prevalence of food selectivity in children with ASD and its association with adverse outcomes were also discussed. Priority evidence gaps identified by participants include further clarifying ASD development, including biomarkers and key mechanisms; interactions among psychosocial, social, and biological determinants; interventions addressing diet, supplementation, and the microbiome to prevent and improve quality of life for people with ASD; and mechanisms of action of diet-related factors associated with ASD. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and ASD.

Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada

BackgroundIncreasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). MethodsWe conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012–2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). ResultsWe linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944–1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953–1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903–1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833–0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. ConclusionsThis study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

Autism spectrum disorder profiles in RASopathies: Asystematic review.

RASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk, while for other RASopathies this association has been studied less. No specific ASD profile has been delineated so far for RASopathies or a specific RASopathy individually. We conducted a systematic review to investigate whether a specific RASopathy is associated with a specific ASD profile, or if RASopathies altogether have a distinct ASD profile compared to idiopathic ASD (iASD). We searched PubMed, Web of Science, and Open Grey for data about ASD features in RASopathies and potential modifiers. We included 41 articles on ASD features in NF1, Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Individuals with NF1, NS, CS, and CFC on average have higher ASD symptomatology than healthy controls and unaffected siblings, though less than people with iASD. There is insufficient evidence for a distinct ASD phenotype in RASopathies compared to iASD or when RASopathies are compared with each other. We identified several potentially modifying factors of ASD symptoms in RASopathies. Our systematic review found no convincing evidence for a specific ASD profile in RASopathies compared to iASD, or in a specific RASopathy compared to other RASopathies. However, we identified important limitations in the research literature which may also account for this result. These limitations are discussed and recommendations for future research are formulated.