Meta-analysis-tested formal models of potential mechanisms underlying females’ low autism-spectrum-disorder diagnosis rate compared to males’

BackgroundWhy is autism spectrum disorder (ASD) less prevalent among females than males? We constructed a statistical model for each of both existing classes of theories, and derived competing predictions for the essentialist expression hypothesis (females express less severe ASD traits so are diagnosed less) against the constructivist perception hypothesis (females’ expressions are socially perceived as less severe so are diagnosed less). Specifically, if the expression hypothesis is true, based on our models, diagnosed females should show less severe symptoms than their male counterparts, whereas the reverse should happen if the perception hypothesis is true.MethodWe conducted a meta-analysis (Data point N = 117,778 participant N = 16,209) on the differences in ASD symptom severity between females and males diagnosed with ASD, across age groups, IQ ranges, diagnostic criteria, and assessment tools.ResultsWe found strong new evidence that ASD-diagnosed females and males differ little in symptom severity, even in the face of a found publication bias in favor of reporting males’ symptoms relative to females’ and the common understanding of ASD as a so-called male disorder.ConclusionsWe argue the finding supports both classes of theories, implying that they are similar in size, though different in directions, in creating sex differences in symptom severity for diagnosed individuals. The sex disparity in ASD prevalence likely results from both the biological expression of, and the social perception toward individuals’ ASD symptoms.     

Le devenir autiste au féminin : difficultés diagnostiques et ressources subjectives. Une revue de littérature

ObjectivesThe scientific literature shows that Autism Spectrum Disorder (ASD) in women may be differentiated by a number of factors, thus impacting how many women are diagnosed with ASD, particularly in adulthood. According to recent data, the prevalence of ASD diagnosis is 3 males to 1 female. Several authors have attempted to explain this ratio by pointing to possible subjective resources that allow women to avoid the autistic manifestations measured by standard tools. In particular, certain “camouflage strategies” would not be detected during the usual assessments. However, these strategies have certain disadvantages, particularly in terms of identity construction.MethodWe conducted a literature review on the characteristics and expressions of the female autism phenotype and on so-called “camouflage” strategies. In this context, we translated into French the Camouflaging Autistic Traits Questionnaire (CAT-Q), developed and validated by Hull and colleagues (2019), in order to encourage its scientific evaluation in the context of research on the diagnosis of ASD for women.ResultsWe have identified several reasons for the diagnostic issues encountered by women with autism: the androcentric nature of autism research; gender bias; diagnostic complexity because of the many co-morbidities; and inadequate diagnostic instruments and settings. The evolution of autism in women also implies that personality construction modulates the expression of these disorders.DiscussionThis work opens up both a reflection on the need for improvement of diagnostic procedures and tools for all autistic subjects, as well as a clinical interest in their psychic resources. We also suggest that the use of a projective test could help to circumvent some of the biases present in the habitual tools.ConclusionThese discussions should be pursued to raise awareness of the relationship between autism and gender. Advancing the modelling of camouflage strategies would make it possible to propose adaptations in clinical and diagnostic practices and to respond to the important issues surrounding the population of women with autism, perhaps more globally to participate in rethinking the heterogeneity and definitions of autism.     

Psychopharmacologic intervention for adults with autism spectrum disorder: A systematic literature review

BackgroundThe increased recognition of psychiatric and behavioural disorder in adults with autism spectrum disorder (ASD) has been associated with more frequent use of psychopharmacologic intervention in this population. However, limited evidence supports the effectiveness of these interventions for adults with ASD.ObjectiveTo review and synthesise the evidence regarding the effectiveness of psychotropic medication in reducing behavioural disturbance in adults with ASD.Data sources and study selectionElectronic literature search of PubMed plus manual reference checks of all articles on psychopharmacology in adults with ASD published in the English language between 1985 and 2015.Results and conclusionsA total of 43 studies were included in the analysis. The results indicate that only two medications, fluoxetine and risperidone, can be considered as promising evidence-based practices for adults with ASD. Given the rising prevalence of ASD, along with increased use of psychopharmacologic intervention in this population, there is a clear need for methodologically rigorous research to establish the effectiveness of these interventions. The subsequent establishment of clinical guidelines for medication use in this population is essential.     

Tic disorders in children and adolescents: does the clinical presentation differ in males and females? A report by the EMTICS group

Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females.

     

Conduct disorder in adolescent females: current state of research and study design of the FemNAT-CD consortium

Conduct disorder (CD) is a common and highly impairing psychiatric disorder of childhood and adolescence that frequently leads to poor physical and mental health outcomes in adulthood. The prevalence of CD is substantially higher in males than females, and partly due to this, most research on this condition has used all-male or predominantly male samples. Although the number of females exhibiting CD has increased in recent decades, the majority of studies on neurobiological measures, neurocognitive phenotypes, and treatments for CD have focused on male subjects only, despite strong evidence for sex differences in the aetiology and neurobiology of CD. Here, we selectively review the existing literature on CD and related phenotypes in females, focusing in particular on sex differences in CD symptoms, patterns of psychiatric comorbidity, and callous–unemotional personality traits. We also consider studies investigating the neurobiology of CD in females, with a focus on studies using genetic, structural and functional neuroimaging, psychophysiological, and neuroendocrinological methods. We end the article by providing an overview of the study design of the FemNAT-CD consortium, an interdisciplinary, multi-level and multi-site study that explicitly focuses on CD in females, but which is also investigating sex differences in the causes, developmental course, and neurobiological correlates of CD.

     

Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis

Purpose

Exposure to prenatal stress has been reported to affect the risk of adverse neurodevelopmental outcomes in the offspring; however, there is currently no clear consensus. The aim of this systematic review and meta-analysis was to examine the existing literature on the association between prenatal stress and autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) in the offspring.

Methods

Based on a registered protocol, we searched several electronic databases for articles in accordance with a detailed search strategy. We performed this study following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).

Results

Prenatal stress was significantly associated with an increased risk of both ASD (pooled OR 1.64 [95% CI 1.15–2.34]; I² = 90%; 15 articles) and ADHD (pooled OR 1.72 [95% CI 1.27–2.34]; I² = 85%; 12 articles).

Conclusions

This study suggests that prenatal stress may be associated with ASD and ADHD; however, several limitations in the reviewed literature should be noted including significant heterogeneity and there is a need for carefully controlled future studies in this area.

     

Evaluation of the ADHD Rating Scale in Youth with Autism

Scientists and clinicians regularly use clinical screening tools for attention deficit/hyperactivity disorder (ADHD) to assess comorbidity without empirical evidence that these measures are valid in youth with autism spectrum disorder (ASD). We examined the prevalence of youth meeting ADHD criteria on the ADHD rating scale fourth edition (ADHD-RS-IV), the relationship of ADHD-RS-IV ratings with participant characteristics and behaviors, and its underlying factor structure in 386, 7–17 year olds with ASD without intellectual disability. Expected parent prevalence rates, relationships with age and externalizing behaviors were observed, but confirmatory factor analyses revealed unsatisfactory fits for one-, two-, three-factor models. Exploratory analyses revealed several items cross-loading on multiple factors. Implications of screening ADHD in youth with ASD using current diagnostic criteria are discussed.     

Autistic spectrum disorders: A review of clinical features,theories and diagnosis

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders that is among the most severe in terms of prevalence, morbidity and impact to the society. It is characterized by complex behavioral phenotype and deficits in both social and cognitive functions. Although the exact cause of ASD is still not known, the main findings emphasize the role of genetic and environmental factors in the development of autistic behavior. Environmental factors are also likely to interact with the genetic profile and cause aberrant changes in brain growth, neuronal development, and functional connectivity. The past few years have seen an increase in the prevalence of ASD, as a result of enhanced clinical tests and diagnostic tools. Despite growing evidence for the involvement of endogenous biomarkers in the pathophysiology of ASD, early detection of this disorder remains a big challenge. This paper describes the main behavioral and cognitive features of ASD, as well as the symptoms that differentiate autism from other developmental disorders. An attempt will be made to integrate all the available evidence which point to reduced brain connectivity, mirror neurons deficits, and inhibition–excitation imbalance in individuals with ASD. Finally, this review discusses the main factors involved in the pathophysiology of ASD, and illustrates some of the most important markers used for the diagnosis of this debilitating disorder.     

Gender dysphoria and autism spectrum disorder: A narrative review

Abstract

The current literature shows growing evidence of a link between gender dysphoria (GD) and autism spectrum disorder (ASD). This study reviews the available clinical and empirical data. A systematic search of the literature was conducted using the following databases: PubMed, Web of Science, PsycINFO and Scopus; utilizing different combinations of the following search terms: autism, autism spectrum disorder (ASD), Asperger’s disorder (AD), co-morbidity, gender dysphoria (GD), gender identity disorder (GID), transgenderism and transsexualism. In total, 25 articles and reports were selected and discussed. Information was grouped by found co-occurrence rates, underlying hypotheses and implications for diagnosis and treatment. GD and ASD were found to co-occur frequently – sometimes characterized by atypical presentation of GD, which makes a correct diagnosis and determination of treatment options for GD difficult. Despite these challenges there are several case reports describing gender affirming treatment of co-occurring GD in adolescents and adults with ASD. Various underlying hypotheses for the link between GD and ASD were suggested, but almost all of them lack evidence.     

A Systematic Review of People with Autism Spectrum Disorder and the Criminal Justice System

This paper provides a systemic review of the available literature on people with autism spectrum disorder (ASD) in the criminal justice system (CJS). The review considers two main types of study: those that examined the prevalence of people with ASD in the CJS and those that examined the prevalence of offending in populations with ASD. In addition, types of offences in people with ASD, co-morbid psychiatric diagnoses, and characteristics of people with ASD who commit offences (including predisposing factors) are considered. A combination of search terms was used in a variety of databases in order to find all of the available literature on this topic, and research studies were included based on specified inclusion and exclusion criteria. It was found that whilst there is an emerging literature base on this topic, there are a wide variety of methodologies used, making direct comparison difficult. Nevertheless it can be concluded so far that people with ASD do not seem to be disproportionately over-represented in the CJS, though they commit a range of crimes and seem to have a number of predisposing features. There is poor evidence of the presence of comorbid psychiatric diagnoses (except in mental health settings) amongst offenders with ASD, and little evidence of the oft-asserted over-representation of certain kinds of crimes. It is recommended that further research of good quality is required in this area, rather than studies that examine populations that are not representative of all those with ASD.     

Psychiatric comorbidity in patients with pediatric bipolar disorder – A systematic review

Background

A growing body of evidence suggests that pediatric bipolar disorder (PBD) frequently co-occurs with comorbid psychiatric disorders that may impact functioning.

Objective

To review existing literature on the prevalence of psychiatric comorbidity and general functioning in patients with a primary diagnosis of PBD.

Methods

We performed a systematic literature search on the PubMed, Embase and PsycInfo databases on November 16th, 2022. We included original papers on patients ≤18 years with primary PBD and any comorbid psychiatric disorder, diagnosed according to a validated diagnostic tool. Risk of bias of the individual studies was assessed using the STROBE checklist. We calculated weighted means to assess the comorbidity prevalence. The review complied with PRISMA statement guidelines.

Results

Twenty studies with a total study population of 2722 patients with PBD were included (mean age = 12.2 years). We found an overall high prevalence of comorbidity in patients with PBD. The most common comorbidities were attention-deficit-hyperactivity disorder (ADHD) (60%) and oppositional defiant disorder (ODD) (47%). Anxiety disorders, obsessive–compulsive disorder, conduct disorder, tic disorders and substance-related disorders affected between 13.2% and 29% of patients, while one in 10 had comorbid mental retardation or autism spectrum disorder (ASD). The prevalence of comorbid disorders was lower in studies that assessed the current prevalence in patients in full or partial remission. General functioning was overall not specifically decreased in patients with comorbidity.

Conclusions

Comorbidity across a broad range of disorders was high in children diagnosed with PBD, especially regarding ADHD, ASD, behavioral and anxiety disorders including OCD. Future original studies should assess current prevalence of comorbidities in patients with PBD who are in remission to obtain more reliable estimates of psychiatric comorbidity in this patient group. The review highlights the clinical and scientific importance of comorbidity in PBD.     

Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder: Systematic Review and Meta-Analysis

Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase databases. Any studies on children with CMV infection and ASD were evaluated for eligibility and three observational studies were included in meta-analysis. Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31, 95% CI 3.07–41.66) was indicated, too few events (0–2 events) in all included studies imposed serious limitations. There is urgent need for further studies to clarify this issue.     

Predictors of an earlier diagnosis of Autism Spectrum Disorder in children and adolescents: a systematic review (1987–2017)

Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder in which the first signs generally emerge at approximately 12 months of age but its diagnosis is feasible only from the age of 18 months. According to the literature, the average age of diagnosis ranges from 2.7 to 7.2 years, which raises the question of factors associated with early diagnosis as a condition for early intervention.

In this systematic review, we aim to identify clinical, social, and environmental factors associated with the age at which the diagnosis of ASD is confirmed in children. A literature search was performed in the Pubmed, Web of Sciences, PsycInfo, and Cochrane databases. Among the 530 publications identified, 50 were selected according to the inclusion criteria. This review focuses on studies conducted in 21 countries using data collected over a period from 1987 to 2017. These studies were published before December 31st, 2019. The results suggest that the diagnosis of ASD occurs earlier if there is a delay in social communication or the presence of intellectual disability. There is a low level of evidence concerning associations between the age at diagnosis and sex, race, parental education, or socioeconomic status and accessibility to health care. Further studies using large and well-characterized data sets are needed to simultaneously explore clinical and socio-environmental factors involved in early diagnosis.

     

Autism spectrum disorder is associated with an increased risk of development of underweight in children and adolescents: A systematic review and meta-analysis

Background & AimsMultiple observational studies have examined the association between autism spectrum disorder (ASD) and underweight, yet the evidence remains ambiguous. We examined the pooled prevalence and relative risk of developing underweight among children with ASD in a systematic review and meta-analysis and examined the effects of potential risk factors in a meta-regression.MethodsProQuest, PubMed, Scopus and Web of Science databases were systematically searched and screened per the PRISMA guidelines. DerSimonian–Laird random-effects meta-analyses were performed using the ‘meta’ package in R to determine the pooled prevalence and the relative risk of underweight among children with ASD. Meta-regression analyses examined the moderator effects of risk factors.ResultsUnderweight had a prevalence of 6.5% (95% CI, 5.1–8.2) among children with ASD overall (29 study groups). Children with ASD possessed a 28.5% (8 studies) greater risk of being underweight vs. neurotypical controls. Meta-regression analyses revealed that non-Caucasian origin and male sex may increase the risk of being underweight in children with ASD.ConclusionsChildren with ASD seem to be at an increased risk of being underweight, which may further impair the clinical outcomes and quality of life. Clinicians need to vigilantly monitor weight and height among children with ASD to prevent underweight and associated complications. Future studies should aim to establish factors that may contribute to the development of underweight among children with ASD.     

2D:4D Ratio and Autism Spectrum Disorder in Brunei Darussalam

Background

Despite the global increase in the prevalence of autism spectrum disorders (ASD), relevant research studies are lacking in Brunei Darussalam. Various studies have shown a significant association between a lowered 2D:4D ratio (ratio of second digit/index finger to the fourth digit/ring finger) and ASD, making it one of the potential phenotypic biomarkers for early detection of autism, which is important for early intervention and management.

Objective

The objective of this study is to explore the association between 2D:4D ratio and ASD in Brunei Darussalam, as a potential tool to complement early ASD diagnosis.

Methods

We conducted a case–control study comprising 28 ASD and 62 typically developing (TD) children in the case and control group, respectively (age range: 3–11 years old; median age: 6 years old). Median 2D:4D ratios were measured, compared and analysed between the two groups. Logistic regression models were used to explore potential associations between the median 2D:4D ratio and ASD in respective gender, for both left and right hands, independently.

Results

Our study shows that the median 2D:4D ratio of left hand in ASD males is significantly lower than those in TD males, after adjusting for ethnicity and age [Odds Ratio (OR)?=?0.57 (95% Confidence Interval (CI): 0.31–0.96); p?=?0.044]. For females, there is no association of ASD with the median left hand 2D:4D ratio [OR?=?3.09 (95% CI: 0.98–19.86); p?=?0.144] or the median right hand 2D:4D ratio [OR?=?1.23 (95% CI: 0.42–3.88); p?=?0.702]. Our study also shows a significant positive correlation and/or a reduced asymmetry between the average 2D:4D ratio of left hands and right hands in ASD males (Pearson’s correlation (r)?=?0.48; 95% CI: 0.076–0.75, p?=?0.023).

Conclusions

There is significant association between a lowered median 2D:4D ratio of the left hand (in males only) and ASD diagnosis. Once validated in a larger sample size, a lowered median 2D:4D ratio on the left hand may be a potential tool to complement ASD diagnosis for males in our study population. There is no association between the median 2D:4D ratio (left or right hands) and ASD in females, which could be due to the small female sample size and/or the possibility of different aetiology for ASD in females. Reduced asymmetry between the average 2D:4D ratio of left and right hands observed in ASD males only (not in ASD females) also suggests the importance of considering gender-specific biomarkers for ASD diagnosis.

     

A review of the quality of primary caregiver-implemented communication intervention research for children with ASD

BackgroundMost children with autism spectrum disorder (ASD) spend most of their waking hours at home with their caregivers; thus, involving caregivers in interventions may increase communication interaction opportunities across time and settings.MethodIn this review, an analysis of the quality of the research on communication interventions implemented or mediated by caregivers of children with ASD was conducted based on the What Works Clearinghouse guidelines (Kratochwill et al., 2010) and adapted by Maggin et al. (2013).ResultsAbout one-third of studies included in this review were found to meet the design standards, indicating that those studies utilized a high quality of research design. The studies that failed to meet the design standards were primarily those that lacked sufficient interobserver agreement data collected in each condition, thus, not meeting the minimum quality thresholds. To evaluate an overall effectiveness, a total of 31 single-case experiments were evaluated with the evidence standards. As a result, about half of the experiments were found to have either strong or moderate evidence of an effect.ConclusionsThe findings in this review suggest issues that need to be addressed in the field related to quality of designs in single-case research on primary caregiver-implemented communication interventions for children with ASD. Limitations and implications for future research and for practitioners are discussed.     

Self-harm: a transdiagnostic marker of psychopathology and suicide risk during the COVID-19 pandemic?

There is a growing number of young people, diagnosed with an autism-spectrum disorder (ASD), transitioning to adulthood. Among this number, individuals without an intellectual disability have significant adaptive deficits and need individualized care and support services to better target vocational, social, and educational prospects and outcomes. Group-based interventions, including patient education, social-skills training, and cognitive–behavioral therapy, are widely used in clinical settings to improve the daily life and prospects of ASD individuals facing the challenge of transitioning to adulthood. We performed a systematic review of studies concerning the efficiency of group-based educational interventions with a focus on the transition to adulthood for young, ASD individuals without intellectual disability (ID). As a result of this systematic search, 21 studies out of 163 were found to be eligible for inclusion. We observed considerable heterogeneity across the studies, in terms of effect sizes and intervention design, delivery, and the comparison of controls. Strong evidence was found in favor of social-skills training and cognitive–behavioral therapy interventions. Professionals should consider group-based psychoeducational intervention to be an appropriate and relevant service for young subjects with ASD without ID transitioning to adulthood. Further research is needed on larger samples using multicentric designs to validate efficacy before generalization.

     

Brief Report: Predictors of Teacher-Rated Academic Competence in a Clinic Sample of Children With and Without Autism Spectrum Disorder

The rising prevalence of autism spectrum disorder (ASD) necessitates a greater understanding of the academic experience of diagnosed children. The present study investigates several predictors of teacher-reported academic competence among a sample of elementary school children. All children in the sample were referred for an ASD evaluation and approximately half received a diagnosis. Children with and without ASD did not differ on overall academic competence, social skills, or problem behaviors. Regression analyses indicated that cognitive ability, social skills, and problem behaviors accounted for significant variance in academic competence. Moderation analyses indicated that the relations between the predictors and academic competence were comparable for children with and without ASD. Implications and future directions are discussed.

     

Sex Differences in Age at Onset and Presentation of Trichotillomania and Trichobezoar: A 120-Year Systematic Review of Cases

Trichotillomania (hair-pulling disorder) has high female preponderance. It has been suggested that onset in early childhood represents a distinct developmental subtype that is characterized by higher prevalence of males compared to later onset cases. However, the empirical literature is scarce. We conducted a systematic review of case reports to examine the distribution of age at onset/presentation in males and females with trichotillomania or trichobezoar (a mass of hair in the gastrointestinal tract resulting from ingesting hair). We identified 1065 individuals with trichotillomania and 1248 with trichobezoar. In both samples, males, compared to females, had earlier age at presentation and greater proportion of cases in early childhood. These sex differences remained after potential confounding variables were accounted for. The results showed similar sex differences for age at onset, which was reported in 734 and 337 of the trichotillomania and trichobezoar cases, respectively. The findings may reflect neurodevelopmental underpinnings in early childhood trichotillomania.