Clinical Presentation Of Autism Spectrum Disorders Research Articles

Sex differences in autism-like behavior and dopaminergic neurons in substantia nigra of juvenile mice prenatally exposed to valproate.

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication and repetitive and restricted behaviors. Sex dimorphism in the brain, including midbrain dopaminergic circuits, can explain differences in social behavior impairment and stereotypic behaviors between male and female individuals with ASD. These abnormal patterns may be due to alterations in dopamine synthesis in the ventral tegmental area (VTA) and substantia nigra (SN). We used an autism-like mouse model by prenatal valproic acid (VPA) exposure. CD1 pregnant female mice were injected with 500mg/kg VPA or 0.9% NaCl as a vehicle on gestational day 12.5. In the offspring, on postnatal day 31, we examined the social and repetitive behaviors and the number of tyrosine hydroxylase (TH)-positive cells in VTA and SN by sex. Male VPA mice showed impaired social behavior and increased repetitive behaviors when compared to male vehicles. In females, we did not find statistically significant differences in social or repetitive behaviors between the groups. Male VPA mice had fewer TH+ cells in the SN than control-vehicle mice. Interestingly, no cellular changes were observed between females. This study supports the notion that sex dimorphism of certain brain regions is involved in the etiopathogenesis and clinical presentation of ASD.

Association of OXTR, AVPR1a, LNPEP, and CD38 Genes' Expression with the Clinical Presentation of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social interactions, communication, and behavior. Although the predominant genetic predisposition to ASD seems beyond doubt, its exact nature remains unclear. In the context of social cognition disorders and the basis of ASD, the oxytocinergic and vasopresynergic systems arouse great interest among researchers. The aim of the present study was to analyze gene expression levels for oxytocin and vasopressin receptors, as well as CD38 protein and oxytocinase, in the context of the clinical picture of autism spectrum disorders. The study included 90 people, of whom 63 were diagnosed with ASD based on anamnesis, mental status testing, and the ADOS-2 protocol. The results obtained in the presented study indicate that the balance between the levels of expression of the CD38 gene and the oxytocinase gene plays a key role in the risk and clinical presentation of ASD. In a hypothetical scenario, an imbalance in the expression of CD38 and LNPEP could potentially lead to alterations in the concentrations of oxytocin and vasopressin. At the same time, the most frequently studied genes-AVPR1a and OXTR-seem to be at best of marginal importance for the risk of ASD.

Examine sex differences in autism spectrum disorder in school-aged children and adolescents with fluent language.

There are noteworthy sex disparities in the prevalence of autism spectrum disorders (ASD), while findings regarding the sex differences in core symptoms are inconsistent. There are few relevant studies on sex differences in mainland China. This study was dedicated to a deeper understanding of the impact of sex differences on the clinical presentation of ASD with fluent language. We retrospectively studied 301 children with ASD (58 females) and utilized raw scores from the ADI-R and ADOS and the intelligence quotient (IQ) to measure symptomatology. Based on the Full-Scale IQ (FS-IQ), a binary split of average, above-average IQ (high-IQ), and below-average IQ (low IQ) occurs at 85. Across the entire sample, males and females are comparable in the FS-IQ, while males scored higher in the Perceptual Reasoning Index (PRI) (F = 7.812, p = 0.006). ADI-R did not find any statistically significant sex differences in the diagnostic cutoff score satisfaction or the raw domain scores. While a significant effect of sex on ADOS social affect domain scores was found in the total sample [λ = 0.970, partial η2 = 0.030, F (3,295) = 3.019, p = 0.030]. Tests of between-subjects effects revealed that males scored higher than females mainly in the ADOS reciprocal social interaction subcategory (partial η2 = 0.022, F = 6.563, p = 0.011). Stratified analysis revealed that the effect of sex on ADOS reciprocal social interaction subcategory scores only significant in the low-IQ children with ASD (partial η2 = 0.092, F = 10.088, p = 0.002). In general, overall cognitive functioning is similar across males and females with ASD, while males have a higher perceptual reasoning ability. Females with ASD are more likely to have comorbid intellectual impairment than males, and they could require additional intervention support. Autistic children with low IQs are more likely to exhibit sex differences in their core symptoms than children with high IQs. Intelligence plays a key role in sex-based differences in the core symptoms of ASD.

Interactions of genetic risks for autism and the broad autism phenotypes.

Common polygenic risk and de novo variants (DNVs) capture a small proportion of autism spectrum disorder (ASD) liability, and ASD phenotypic heterogeneity remains difficult to explain. Integrating multiple genetic factors contribute to clarifying the risk and clinical presentation of ASD. In our study, we investigated the individual and combined effects of polygenic risk, damaging DNVs (including those in ASD risk genes), and sex among 2,591 ASD simplex families in the Simons Simplex Collection. We also explored the interactions among these factors, along with the broad autism phenotypes of ASD probands and their unaffected siblings. Finally, we combined the effects of polygenic risk, damaging DNVs in ASD risk genes, and sex to explain the total liability of ASD phenotypic spectrum. Our findings revealed that both polygenic risk and damaging DNVs contribute to an increased risk for ASD, with females exhibiting higher genetic burdens than males. ASD probands that carry damaging DNVs in ASD risk genes showed reduced polygenic risk. The effects of polygenic risk and damaging DNVs on autism broad phenotypes were inconsistent; probands with higher polygenic risk exhibited improvement in some behaviors, such as adaptive/cognitive behaviors, while those with damaging DNVs exhibited more severe phenotypes. Siblings with higher polygenic risk and damaging DNVs tended to have higher scores on broader autism phenotypes. Females exhibited more severe cognitive and behavioral problems compared to males among both ASD probands and siblings. The combination of polygenic risk, damaging DNVs in ASD risk genes, and sex explained 1-4% of the total liability of adaptive/cognitive behavior measurements. Our study revealed that the risk for ASD and the autism broad phenotypes likely arises from a combination of common polygenic risk, damaging DNVs (including those in ASD risk genes), and sex.

Polish Adaptation of the Social Communication Questionnaire (SCQ) and Female Autism Phenotype: An Investigation of Potentially Sex-Biased Items in the Screening Assessment and Their Impact on Scores.

Standardized screening assessments and sex differences in autism spectrum disorder (ASD) are still under-explored in Poland. This study investigated the differences between Polish ASD females and males based on the responses provided by parents/caregivers to a Polish adaptation of the Social Communication Questionnaire, SCQ Lifetime and SCQ Current. The study included 90 ASD participants from Mental Health Services and Autism Clinics in Poland with no intellectual disability and no profound communication difficulties. Parents provided information on the SCQ items which were compared under three domains of the Autism Diagnostic Interview-Revised (ADI-R). Four SCQ items with the examples were investigated. No significant differences were found between the two sexes in the three domains. The repetitive use of objects declined with age in ASD males. Although the findings of the present study did not reveal substantial gender biases in the Polish adaptation of the SCQ, it is necessary to take into account potential gender differences in the clinical presentation of ASD and in the adaptation of screening and diagnostic tools.

Altered Autonomic Functions and Gut Microbiome in Individuals with Autism Spectrum Disorder (ASD): Implications for Assisting ASD Screening and Diagnosis.

Autism spectrum disorder (ASD) is a complex neurological and developmental disorder, and a growing body of literature suggests the presence of autonomic nervous system (ANS) dysfunction in individuals with ASD. ANS is part of the "gut brain axis", which consists of an intricate interplay between the gut microbiome, mucosal immune system, enteric nervous system, ANS, and central processes receiving input from the vagus nerve. Measurements of the gut microbiome and the autonomic indices can serve as non-invasive markers of the status of the gut-brain axis in ASD. To our knowledge, no previous studies have explored the relationship between ANS and gut microbiome in individuals with ASD. Furthermore, while previous studies investigated the use of autonomic indices and gut microbiome independently as markers of ASD-related comorbidities, such as anxiety, cardiovascular issues, and gastrointestinal dysfunction, the use of combined autonomic indices and gut microbiome factors to classify ASD and control subjects has not been explored. In this study, we characterized autonomic function of a group of individuals with ASD in comparison to their paired, first-degree relative controls. Second, we explored the ASD gut-brain-axis through the relationship between gut microbiome markers and autonomic indices, as well as the correlation between the gut-brain-axis and clinical presentation of ASD. Lastly, this study explores the predictive capability of gut-brain-axis biomarkers (including autonomic and microbiome indices) in subtyping ASD cases, serving as a starting point to investigate the possibility of assisting in ASD screening and diagnosis that still heavily relies on psychological testing, which may be based on highly subjective standards.

Clustering of co-occurring conditions in autism spectrum disorder during early childhood: A retrospective analysis of medical claims data.

Individuals with autism spectrum disorder (ASD) are frequently affected by co-occurring medical conditions (COCs), which vary in severity, age of onset, and pathophysiological characteristics. The presence of COCs contributes to significant heterogeneity in the clinical presentation of ASD between individuals and a better understanding of COCs may offer greater insight into the etiology of ASD in specific subgroups while also providing guidance for diagnostic and treatment protocols. This study retrospectively analyzed medical claims data from a private United States health plan between years 2000 and 2015 to investigate patterns of COC diagnoses in a cohort of 3,278 children with ASD throughout their first 5 years of enrollment compared to 279,693 children from the general population without ASD diagnoses (POP cohort). Three subgroups of children with ASD were identified by k-means clustering using these COC patterns. The first cluster was characterized by generally high rates of COC diagnosis and comprised 23.7% (n = 776) of the cohort. Diagnoses of developmental delays were dominant in the second cluster containing 26.5% (n = 870) of the cohort. Children in the third cluster, making up 49.8% (n = 1,632) of the cohort, had the lowest rates of COC diagnosis, which were slightly higher than rates observed in the POP cohort. A secondary analysis using these data found that gastrointestinal and immune disorders showed similar longitudinal patterns of prevalence, as did seizure and sleep disorders. These findings may help to better inform the development of diagnostic workup and treatment protocols for COCs in children with ASD. Autism Res 2019, 12: 1272-1285. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Medical conditions that co-occur with autism spectrum disorder (ASD) vary significantly from person to person. This study analyzed patterns in diagnosis of co-occurring conditions from medical claims data and observed three subtypes of children with ASD. These results may aid with screening for co-occurring conditions in children with ASD and with understanding ASD subtypes.

PPARγ agonists: potential treatment for autism spectrum disorder by inhibiting the canonical WNT/β-catenin pathway.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. No curative treatments are available for ASD. Pharmacological treatments do not address the core ASD behaviors, but target comorbid symptoms. Dysregulation of the core neurodevelopmental pathways is associated with the clinical presentation of ASD, and the canonical WNT/β-catenin pathway is one of the major pathways involved. The canonical WNT/β-catenin pathway participates in the development of the central nervous system, and its dysregulation involves developmental cognitive disorders. In numerous tissues, the canonical WNT/β-catenin pathway and peroxisome proliferator-activated receptor gamma (PPARγ) act in an opposed manner. In ASD, the canonical WNT/β-catenin pathway is increased while PPARγ seems to be decreased. PPARγ agonists present a beneficial effect in treatment for ASD children through their anti-inflammatory role. Moreover, they induce the inhibition of the canonical WNT/β-catenin pathway in several pathophysiological states. We focus this review on the hypothesis of an opposed interplay between PPARγ and the canonical WNT/β-catenin pathway in ASD and the potential role of PPARγ agonists as treatment for ASD.

Thinking globally to meet local needs: autism spectrum disorders in Africa and other low-resource environments.

Most people with autism spectrum disorders (ASDs) live in low and middle-income countries, yet almost everything we know about ASD comes from high-income countries. Here we review recent research from Africa, with some references to research in other low-resource environments. We examine publications on screening and diagnosis, intervention, clinical presentation of ASD, cultural perspectives, and neuroscience and technology. Open-access screening and diagnostic tools represent a positive, but nontrivial, future goal. Recent efforts at 'low intensity' community-based interventions are encouraging, but many significant scalability challenges remain. Proposals that ASD in Africa is more severe and overrepresented in high socioeconomic families are likely to be attributable to ascertainment biases and the absence of standardized phenotyping tools. Cultural perspectives and innovative use of technology and neuroscience have the potential to generate novel strategies of global relevance, but research priorities have to be determined by local needs. To have a real impact on clinical services, training, and research in local communities, clinician-scientists should start by thinking globally. ASD research in Africa and other low-resource environments remains limited and of questionable quality and highlights the need to build high-quality research capacity in these low-resource environments.

The diagnostic boundary between autism spectrum disorder, intellectual developmental disorder and schizophrenia spectrum disorders

Purpose– During the last few years the prevalence of autism and Autism Spectrum Disorder (ASD) has increased greatly. A recurring issue is the overlap and boundaries between Intellectual Developmental Disorder (IDD), ASD and Schizophrenia Spectrum Disorders (SSD). In clinical practice with people with IDD, the alternative or adjunctive diagnosis of ASD or SSD is particularly challenging. The purpose of this paper is to define the boundaries and overlapping clinical characteristics of IDD, ASD and SSD; highlight the most relevant differences in clinical presentation; and provide a clinical framework within which to recognize the impact of IDD and ASD in the diagnosis of SSD.Design/methodology/approach– A systematic mapping of the international literature was conducted on the basis of the following questions: first, what are considered to be core and overlapping aspects of IDD, ASD and SSD; second, what are the main issues in clinical practice; and third, can key diagnostic flags be identified to assist in differentiating between the three diagnostic categories?Findings– Crucial clinical aspects for the differentiation resulted to be age of onset, interest towards others, main positive symptoms, and anatomical anomalies of the central nervous system. More robust diagnostic criteria and semeiological references are desirable.Originality/value– The present literature mapping provides a comprehensive description of the most relevant differences in the clinical presentation of ASD and SSD in persons with IDD.

A Review of the Role of Female Gender in Autism Spectrum Disorders

This paper reviews the literature exploring gender differences associated with the clinical presentation of autism spectrum disorders (ASD). The potentially mediating effect of comorbid psychopathology, biological and neurodevelopmental implications on these gender differences is also discussed. A vastly heterogeneous condition, while females on the lower-functioning end of the spectrum appear to be more severely affected, an altered clinical manifestation of the disorder among high-functioning females may consequently result in many being un- or mis-diagnosed. To date, there is strong bias in the literature towards the clinical presentation of ASD in males. It is imperative that future research explores gender differences across the autism spectrum, in order to improve researchers', clinicians' and the public's understanding of this debilitating disorder.

"The presentation and classification of anxiety in autism spectrum disorder": Commentary.

The dramatic increase in the detected prevalence of autism spectrum disorders (ASDs) in children over the past two decades is due, in large measure, to a broader case definition and more effective case finding. The similarities and differences in clinical presentation of ASDs and anxiety disorders have prompted great interest in anxiety in children with ASDs. In the absence of validated biological markers or diagnostic tests for anxiety disorders in this population, we rely on clinical observation, parent reports, and the child's verbal expression. The language and cognitive deficits in children with ASDs, however, hinder the application of assessments used in typically developing children. Because intervention research relies on reliable outcome measurement, better measurement of anxiety in children with ASDs is warranted.

Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males.