Autism Spectrum Disorder In Females Research Articles

HLA-A, -B, -C and -DRB1 Association with Autism Spectrum Disorder Risk: A Sex-Related Analysis in Italian ASD Children and Their Siblings.

Autism Spectrum disorders (ASD) are diagnosed more often in males than in females, by a ratio of about 3:1; this is likely to be due to a difference in risk burden between the sexes and/or to "compensatory skills" in females, that may delay the diagnosis of ASD. Identifying specific risk factors for ASD in females may be important in facilitating early diagnosis. We investigated whether HLA- class I: -A, -B, -C and class II -DRB1 alleles, which have been suggested to play a role in the development of ASD, can be considered as sex-related risk/protective markers towards the ASD. We performed HLA allele genotyping in 178 Italian children with ASD, 94 healthy siblings, and their parents. HLA allele distribution was compared between children with ASD, sex-matched healthy siblings, and a cohort of healthy controls (HC) enrolled in the Italian bone marrow donor registry. Allele transmission from parents to children with ASD and their siblings was also assessed. Our findings suggest that HLA-A*02, B*38, and C*12 alleles are more frequently carried by females with ASD compared to both HC and healthy female siblings, indicating these alleles as potential risk factors for ASD in females. Conversely, the HLA-A*03 allele was more commonly transmitted to healthy female siblings, suggesting it might have a protective effect. Additionally, the HLA-B*44 allele was found to be more prevalent in boys with ASD, indicating it is a potential risk factor for male patients. This is the first Italian study of sex-related HLA association with ASD. If confirmed, these results could facilitate early ASD diagnosis in female patients, allowing earlier interventions, which are crucial in the management of neurodevelopmental disorders.

Females with autism spectrum disorders show stronger DNA methylation signatures than males in perinatal tissues.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental conditions currently diagnosed by behavioral assessment in childhood, with reported underdiagnosis in females. Though diagnosis in early life is linked to improved outcomes, we currently lack objective screening tools for newborns. To address this gap, we sought to identify a sex-specific DNA methylation signature for ASD using perinatal tissues that reflect dysregulation in the brain. DNA methylation was assayed from ASD and typically developing (TD) newborn blood, umbilical cord blood, placenta, and post-mortem cortex samples using whole genome bisulfite sequencing (WGBS) in a total of 511 samples. We found that methylation levels of differentially methylated regions (DMRs) differentiated samples by ASD diagnosis in females more than males across the perinatal tissues. We tested three theories for ASD sex differences in newborn blood, finding epigenetic support for an X chromosome-related female protective effect, as well as a high replication rate of DMRs (48.1%) in females across two independent cohorts. In our pan-tissue analysis, three genes (X-linked BCOR, GALNT9, OPCML) mapped to ASD DMRs replicated in all four female tissues. ASD DMRs from all tissues were enriched for neuro-related processes (females) and SFARI ASD-risk genes (females and males). Overall, we found a highly replicated methylation signature of ASD in females across perinatal tissues that reflected dysregulation in the brain and involvement of X chromosome epigenetics. This comparative study of perinatal tissues shows the promise of newborn blood DNA methylation biomarkers for early detection of females at risk for ASD and emphasizes the importance of sex-stratification in ASD studies.

Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients. In the study, we specifically explored the role of the OXT signaling pathway in a VPA-induced female rat’s model of autism. The data showed that there was an increase of either oxytocin or its receptor expressions in both the hippocampus and the prefrontal cortex of VPA-induced female offspring. To determine if the excess of OXT signaling contributed to autism symptoms in female rats, exogenous oxytocin and oxytocin receptor antagonists Atosiban were used in the experiment. It was found that exogenous oxytocin triggered autism-like behaviors in wild-type female rats by intranasal administration. More interestingly, several autism-like deficits including social interaction, anxiety, and repeat stereotypical sexual behavior in the VPA female offspring were significantly attenuated by oxytocin receptor antagonists Atosiban. Moreover, Atosiban also effectively improved the synaptic plasticity impairment induced by VPA in female offspring. Our results suggest that oxytocin receptor antagonists significantly improve autistic-like behaviors in a female rat model of valproic acid-induced autism.

In vivo translocator protein in females with autism spectrum disorder: a pilot study

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)—a mitochondrial protein—in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET–MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.

Autism: Clinical impacts and late diagnosis in women - Literature review

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder, marked by deficits in communication and social interaction and restricted and repetitive behavior patterns. With the expansion of information dissemination about autism and improvements in diagnostic methods, the prevalence of the disorder has increased considerably in recent decades. However, because autism has multiple facets and different presentations, diagnosis is still a challenge, especially in females, where there are singularities that further undermine suspicions, leading to underdiagnosis. Given this, there are multiple questions about the causes and implications of these factors in the diagnosis of autistic girls and women. Thus, the objective of this research is to verify the causal factors and clinical implications associated with the difficulty in diagnosing ASD in females. This is a narrative bibliographic review, in which research was carried out in established databases. In general, it is noted that the diagnosis of autism in girls and women can be impacted by genetic, developmental, psychological, social and cultural influences, involving factors such as subtlety of symptoms, capacity for social adaptability, lack of studies, failure to diagnostic methodologies and instruments, as well as stereotypes and prejudices. Understanding these elements is essential to broaden the perspective of girls and women with ASD, highlight their particularities and ensure that they receive early diagnosis and treatment.

Mutations associated with autism lead to similar synaptic and behavioral alterations in both sexes of male and female mouse brain

Autism spectrum disorder (ASD) is a neurodevelopmental disorder based on synaptic abnormalities. The estimated prevalence rate of male individuals diagnosed with ASD prevails over females is in a proportion of 4:1. Consequently, males remain the main focus in ASD studies in clinical and experimental settings. Meanwhile, some studies point to an underestimation of this disorder in females. In this work, we studied the sex differences of the synaptic and behavioral phenotypes of ASD mouse models. Juvenile male and female Shank3Δ4–22 and Cntnap2−/− mutant mice and their WT littermates were used in the experiments. The animals were subjected to a Three-Chamber Sociability Test, then euthanized, and the whole cortex was used for the evaluation of the synaptic phenotype. Protein levels of glutamatergic (NR1) and GABAergic (GAD1 and VGAT) neuronal markers were measured. Protein level of synaptophysin (Syp) was also measured. Dendritic spine density in somatosensory neurons was analyzed by Golgi staining methods. Spine Density and GAD1, NR1, VGAT, and Syp levels were significantly reduced in Shank3Δ4–22 and Cntnap2−/− mice compared to the control group irrespective of sex, indicating impaired synaptic development in the mutant mice. These results were consistent with the lack of differences in the three-chamber sociability test between male and female mice. In conclusion, female ASD mice of both mutations undergo similar synaptic aberrations as their male counterparts and need to be studied along with the male animals. Finally, this work urges the psychiatry scientific community to use both sexes in their investigations.

The teacher-student relationship: A comparative study of the report of students with autism spectrum disorder and typical development

The teacher-student relationship (TSR) is an important factor for promoting academic success. Even though students with autism spectrum disorder (ASD) experience more educational difficulties, the TSR in ASD students has been understudied, and there is a significant empirical gap in the perception that ASD adolescent students themselves have of their relationships with their teachers. The present study followed a non-experimental, correlational, cross-sectional and comparative design to analyze the TSR in ASD adolescents in comparison to the TSR of their typically developing (TD) peers. Sixty-four students (33 females, 31 males) who were in their first year of secondary school ( participated in the study. 32 of them had ASD and 32 had TD. The TSR subscale of the SEI was applied (Appleton et al., 2006). The results show significant interaction effects between student condition and gender, where female ASD students reported a worse relationship than their male ASD peers. These findings differ from existing research indicating that ASD students experience worse TSR and that female students experience better relationships than male students. The important role of the existing school integration program in Chilean schools, and guidelines for future research to explain the gender differences found in this study are discussed.

B - 21 What Does BASC-3 Tell us about ASD in Females.

This study explored parent endorsements on Behavior Assessment System for Children, Third Edition (BASC-3) for females diagnosed with Autism Spectrum Disorder (ASD) and how they differ by age group. Data for 121 females (mean age 9.94) was collected between 2022 and 2023 for ages 2-5 (N = 21), 6-11 (N = 55), and 12-21(N = 45). Participants (White = 66%, Hispanic = 12%, Black = 5%, Biracial = 10%, and other = 5.8%) at a private group practice serving suburban and rural counties completed a standard neuropsychological evaluation for ASD. Seven subscales from the BASC-3 were analyzed; four subscales with strong theoretical relationships with ASD and three exploratory scales. A between-subjects ANOVA was conducted to compare the effect of age on BASC-3 for selected subscales. There was a significant effect of age on Externalizing Problems [F(2, 118) = 9.01, p < 0.001, η2= 0.13], Internalizing Problems [F(2, 118) = 6.63, p = 0.002, η2= 0.10], Atypicality [F(2, 118) = 15.07, p < 0.001, η2= 0.20], and Adaptive Skills [F(2, 118) = 4.39, p = 0.015, η2= 0.07]. Post hoc comparisons indicated significant differences across age groups on most scales, but especially for 6-11 ages. However, no significant differences were noted for Withdrawal, Developmental Social Disorder, and ASD probability. Age plays a significant role in the symptomatic presentation of ASD. Parents endorse more problematic behaviors for ages 6 to 11 than other age groups. Moreover, atypicality was the only subscale that showed differential elevations, but all theoretically relevant subscales were at risk. Females with ASD are equally as likely to demonstrate internalizing and externalizing behaviors.

A Potential Biomarker of Brain Activity in Autism Spectrum Disorders: A Pilot fNIRS Study in Female Preschoolers

Autism spectrum disorder (ASD) refers to a neurodevelopmental condition whose detection still remains challenging in young females due to the heterogeneity of the behavioral phenotype and the capacity of camouflage. The availability of quantitative biomarkers to assess brain function may support in the assessment of ASD. Functional Near-infrared Spectroscopy (fNIRS) is a non-invasive and flexible tool that quantifies cortical hemodynamic responses (HDR) that can be easily employed to describe brain activity. Since the study of the visual phenotype is a paradigmatic model to evaluate cerebral processing in many neurodevelopmental conditions, we hypothesized that visually-evoked HDR (vHDR) might represent a potential biomarker in ASD females. We performed a case-control study comparing vHDR in a cohort of high-functioning preschooler females with ASD (fASD) and sex/age matched peers. We demonstrated the feasibility of visual fNIRS measurements in fASD, and the possibility to discriminate between fASD and typical subjects using different signal features, such as the amplitude and lateralization of vHDR. Moreover, the level of response lateralization was correlated to the severity of autistic traits. These results corroborate the cruciality of sensory symptoms in ASD, paving the way for the validation of the fNIRS analytical tool for diagnosis and treatment outcome monitoring in the ASD population.

Stratification of Children with Autism Spectrum Disorder Through Fusion of Temporal Information in Eye-gaze Scan-Paths

Background: Looking pattern differences are shown to separate individuals with Autism Spectrum Disorder (ASD) and Typically Developing (TD) controls. Recent studies have shown that, in children with ASD, these patterns change with intellectual and social impairments, suggesting that patterns of social attention provide indices of clinically meaningful variation in ASD. Method: We conducted a naturalistic study of children with ASD (n = 55) and typical development (TD, n = 32). A battery of eye-tracking video stimuli was used in the study, including Activity Monitoring (AM), Social Referencing (SR), Theory of Mind (ToM), and Dyadic Bid (DB) tasks. This work reports on the feasibility of spatial and spatiotemporal scanpaths generated from eye-gaze patterns of these paradigms in stratifying ASD and TD groups. Algorithm: This article presents an approach for automatically identifying clinically meaningful information contained within the raw eye-tracking data of children with ASD and TD. The proposed mechanism utilizes combinations of eye-gaze scan-paths (spatial information), fused with temporal information and pupil velocity data and Convolutional Neural Network (CNN) for stratification of diagnosis (ASD or TD). Results: Spatial eye-gaze representations in the form of scanpaths in stratifying ASD and TD (ASD vs. TD: DNN: 74.4%) are feasible. These spatial eye-gaze features, e.g., scan-paths, are shown to be sensitive to factors mediating heterogeneity in ASD: age (ASD: 2–4 y/old vs. 10–17 y/old CNN: 80.5%), gender (Male vs. Female ASD: DNN: 78.0%) and the mixture of age and gender (5–9 y/old Male vs. 5–9 y/old Female ASD: DNN:98.8%). Limiting scan-path representations temporally increased variance in stratification performance, attesting to the importance of the temporal dimension of eye-gaze data. Spatio-Temporal scan-paths that incorporate velocity of eye movement in their images of eye-gaze are shown to outperform other feature representation methods achieving classification accuracy of 80.25%. Conclusion: The results indicate the feasibility of scan-path images to stratify ASD and TD diagnosis in children of varying ages and gender. Infusion of temporal information and velocity data improves the classification performance of our deep learning models. Such novel velocity fused spatio-temporal scan-path features are shown to be able to capture eye gaze patterns that reflect age, gender, and the mixed effect of age and gender, factors that are associated with heterogeneity in ASD and difficulty in identifying robust biomarkers for ASD.

Lactiplantibacillus plantarum ST-III-fermented milk improves autistic-like behaviors in valproic acid-induced autism spectrum disorder mice by altering gut microbiota.

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder with a rising incidence. More and more studies have shown that abnormal microbiota composition may aggravate the behavioral symptoms and biological signs of ASD, and interventions of probiotics and diet have emerged as a potential improvement measure. Lactiplantibacillus plantarum ST-III-fermented milk was applied as an oral intervention in a valproic acid (VPA)-induced ASD mice model, and the effect of probiotic intake on autistic-related behaviors and gut microbiota composition was evaluated by behavioral tests and 16S rRNA gene sequencing. Gender specificity was shown in VPA-induced behavioral abnormalities in a mouse model, and L. plantarum ST-III-fermented milk was effective in ameliorating the impaired social interaction in male ASD mouse models, but not for the anxiety behavior exhibited by female ASD mouse models. Meanwhile, dietary changes were found to be the main cause of the altered gut microbiota in mice, and additional intake of L. plantarum ST-III-fermented milk seemed to improve autistic-like behaviors in male ASD mouse models by modulating specific gut microbes. These findings suggest that L. plantarum ST-III-fermented milk may play a beneficial role in improving the behavioral symptoms of ASD and is expected to be one of the candidate functional foods for ASD.

A sex-dependent computer-aided diagnosis system for autism spectrum disorder using connectivity of resting-state fMRI

Objective. Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with the main symptoms of social communication disabilities. ASD is more than four times more common among males than females. The diagnosis of ASD is currently a subjective process by experts the same for males and females. Various studies have suggested the use of brain connectivity features for the diagnosis of ASD. Also, sex-related biological factors have been shown to play a role in ASD etiology and influence the brain connectivity. Therefore, proposing an accurate computer-aided diagnosis system (CADS) for ASD which considers the sex of subjects seems necessary. In this study, we present a sex-dependent connectivity-based CADS for ASD using resting-state functional magnetic resonance imaging. The proposed CADS classifies ASD males from normal males, and ASD females from normal females. Approach. After data preprocessing, group independent component analysis (GICA) was applied to obtain the resting-state networks (RSNs) followed by applying dual-regression to obtain the time course of each RSN for each subject. Afterwards, functional connectivity measures of full correlation and partial correlation and the effective connectivity measure of bivariate Granger causality were computed between time series of RSNs. To consider the role of sex differences in the classification process, male, female, and mixed groups were taken into account, and feature selection and classification were designed for each sex group separately. At the end, the classification accuracy was computed for each sex group. Main results. In the female group, a classification accuracy of 93.3% was obtained using full correlation while in the male group, a classification accuracy of 86.7% was achieved using both full correlation and bivariate Granger causality. Also, in the mixed group, a classification accuracy of 83.3% was obtained using full correlation. Significance. This supports the importance of considering sex in diagnosing ASD patients from normal controls.

Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved, considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.

Self injuries in adolescence, an unusual clinical presentation of autism

IntroductionAlthough autism is only twice more common in men than women in general population, in clinical samples women are underrepresented. This difference may be due to a poor sensitivity of current diagnostic criteria of autism related to females. We present a 13-year-old woman referred to the adolescent psychiatric unit for anxiety, self injuries and suicidal ideation. After careful assessment of current symptoms and neurodevelopmental milestones, deficits in emotional-comunicational reciprocity, nonverbal comunication and relationships emerged, as well as inflexible adherence to routines and restricted interests. The diagnose of autism spectrum disorder was made and the patient started a specific treatment.ObjectivesTo review the clinical features of autism spectrum disorders in adolescent females and its differential diagnosis.MethodsReview of the literature on autism spectrum disorders in female and its specific features.ResultsThe “Female Autism Phenotype” is a group features that are more common in autistic women, as opposed to the classic symptoms of autism in men. Some of these differential characteristics are: fewer social impairments and higher levels of social motivation; more age and gender appropriate restricted and repetitive interests; more internalizing rather than externalizing symptoms; and a tendency towards camouflagingConclusions- Autism in women is frequently underdiagnosed. - Females express autism in ways that not allways meet the current diagnostic criteria. - The “Female Autism Phenotype” has been proposed as an specific way of expression of autism in females.DisclosureNo significant relationships.

Women and Girls with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is characterized by a triad of difficulties including altered communication, impairements in social internactions, as well as restricted interests and repetitive behaviours. It used to be known as a predominantly male disorder, but recent research has shown that the male/female ratio is trending downward and that the actual estimate is about 3:1. Until now, diagnostic criteria have been developed based on research conducted primarily in male populations. However, in recent years, female autism has attracted scientific interest, revealing some unique features in the presentation of this disorder in girls and women. This presentation will focus on gender differences and characteristics of ASD in females, including personal descriptions and experiences of women diagnosed with ASD.DisclosureNo significant relationships.

The female protective effect against autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n= 1,707) had higher rates of ASD than siblings of male ASD cases (n= 6,270; p<1.0×10-10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n= 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n= 5,926; 0.08 polygenic risk score [PRS] SD; p= 7.0×10-7). Further, male unaffected siblings under-inherited polygenic risk (n= 1,519; p= 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD's common inherited influences.

Sex Differences in Autism Spectrum Disorder: Diagnostic, Neurobiological, and Behavioral Features.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a worldwide prevalence of about 1%, characterized by impairments in social interaction, communication, repetitive patterns of behaviors, and can be associated with hyper- or hypo-reactivity of sensory stimulation and cognitive disability. ASD comorbid features include internalizing and externalizing symptoms such as anxiety, depression, hyperactivity, and attention problems. The precise etiology of ASD is still unknown and it is undoubted that the disorder is linked to some extent to both genetic and environmental factors. It is also well-documented and known that one of the most striking and consistent finding in ASD is the higher prevalence in males compared to females, with around 70% of ASD cases described being males. The present review looked into the most significant studies that attempted to investigate differences in ASD males and females thus trying to shade some light on the peculiar characteristics of this prevalence in terms of diagnosis, imaging, major autistic-like behavior and sex-dependent uniqueness. The study also discussed sex differences found in animal models of ASD, to provide a possible explanation of the neurological mechanisms underpinning the different presentation of autistic symptoms in males and females.

Sex Differences on the ADOS-2.

The sex difference in the prevalence of autism spectrum disorder (ASD) may be magnified by sex differences on diagnostic measures. The current study compared autistic males and females on items on the gold-standard diagnostic measure, the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). In a sample of 8-to-17-year old autistic individuals from research (n = 229) and clinical settings (n = 238), females were less likely to show atypicalities on most items related to social-communication behaviors and on total and subscale scores. When controlling for overall intensity of symptomatology, no sex differences survived statistical corrections. Diagnostic criteria and/or gold-standard assessments may be less sensitive to female presentations of ASD and/or autistic females may exhibit fewer or less intense behaviors characteristic of ASD.

Transdiagnostic and sex differences in cognitive profiles of autism spectrum disorder and attention-deficit/hyperactivity disorder.

An increasing number of studies have shown that autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share symptoms and aetiologies. However, transdiagnostic comparisons between ASD and ADHD is complicated due to the sex differences within each condition. To clarify the similarities and differences in the cognitive functioning between ASD and ADHD, while considering potential sex differences, this study compared cognitive profiles assessed by the WAIS-III between the four groups created by orthogonally combining diagnosis and sex based on the data from 277 ASD males, 86 ASD females, 99 ADHD males and 64 ADHD females. The analysis revealed three major findings. First, performance IQ and perceptual organization index were higher in ADHD males than in ASD males and ADHD females. Second, Gaussian mixture model fitting revealed two clusters underlying the distribution of subindex scores. The percentage of being classified into the cluster that scored lower in all the subindices was higher in females than in males irrespective of diagnosis. Third, feature importance for classification of ASD and ADHD yielded by random forest classifier, a supervised machine learning algorithm, revealed that autism quotient was most informative feature in classifying ASD and ADHD in males, while the discrepancy between verbal and performance intelligence quotient was in females, indicating that the set of behavioral features contributing to classification differs between males and females. Thus, these findings indicate that sex as well as diagnosis is critical in determining the cognitive profiles of people with ASD and ADHD. LAY SUMMARY: The present study compared profiles of cognitive functions measured by Wechsler Adult Intelligence Scale between males and females with ASD and ADHD. The analyses revealed clear sex differences in cognitive functions in both ASD and ADHD and that the set of cognitive functions useful in classifying ASD and ADHD differed between males and females. Thus, biological sex seems to be a critical factor in determining the cognitive profiles of people with ASD and ADHD.

Phenotypic differences between female and male individuals with suspicion of autism spectrum disorder

BackgroundAlthough autism spectrum disorder (ASD) is a common developmental disorder, our knowledge about a behavioral and neurobiological female phenotype is still scarce. As the conceptualization and understanding of ASD are mainly based on the investigation of male individuals, females with ASD may not be adequately identified by routine clinical diagnostics. The present machine learning approach aimed to identify diagnostic information from the Autism Diagnostic Observation Schedule (ADOS) that discriminates best between ASD and non-ASD in females and males.MethodsRandom forests (RF) were used to discover patterns of symptoms in diagnostic data from the ADOS (modules 3 and 4) in 1057 participants with ASD (18.1% female) and 1230 participants with non-ASD (17.9% % female). Predictive performances of reduced feature models were explored and compared between females and males without intellectual disabilities.ResultsReduced feature models relied on considerably fewer features from the ADOS in females compared to males, while still yielding similar classification performance (e.g., sensitivity, specificity).LimitationsAs in previous studies, the current sample of females with ASD is smaller than the male sample and thus, females may still be underrepresented, limiting the statistical power to detect small to moderate effects.ConclusionOur results do not suggest the need for new or altered diagnostic algorithms for females with ASD. Although we identified some phenotypic differences between females and males, the existing diagnostic tools seem to sufficiently capture the core autistic features in both groups.