Male Autism Spectrum Disorder Research Articles

Abnormal multimodal neuroimaging patterns associated with social deficits in male autism spectrum disorder.

Atypical social impairments (i.e., impaired social cognition and social communication) are vital manifestations of autism spectrum disorder (ASD) patients, and the incidence rate of ASD is significantly higher in males than in females. Characterizing the atypical brain patterns underlying social deficits of ASD is significant for understanding the pathogenesis. However, there are no robust imaging biomarkers that are specific to ASD, which may be due to neurobiological complexity and limitations of single-modality research. To describe the multimodal brain patterns related to social deficits in ASD, we highlighted the potential functional role of white matter (WM) and incorporated WM functional activity and gray matter structure into multimodal fusion. Gray matter volume (GMV) and fractional amplitude of low-frequency fluctuations of WM (WM-fALFF) were combined by fusion analysis model adopting the social behavior. Our results revealed multimodal spatial patterns associated with Social Responsiveness Scale multiple scores in ASD. Specifically, GMV exhibited a consistent brain pattern, in which salience network and limbic system were commonly identified associated with all multiple social impairments. More divergent brain patterns in WM-fALFF were explored, suggesting that WM functional activity is more sensitive to ASD's complex social impairments. Moreover, brain regions related to social impairment may be potentially interconnected across modalities. Cross-site validation established the repeatability of our results. Our research findings contribute to understanding the neural mechanisms underlying social disorders in ASD and affirm the feasibility of identifying biomarkers from functional activity in WM.

Sex differences in the flexibility of dynamic network reconfiguration of autism spectrum disorder based on multilayer network.

Dynamic network reconfiguration alterations in the autism spectrum disorder (ASD) brain have been frequently reported. However, since the prevalence of ASD in males is approximately 3.8 times higher than that in females, and previous studies of dynamic network reconfiguration of ASD have predominantly used male samples, it is unclear whether sex differences exist in dynamic network reconfiguration in ASD. This study used resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database, which included balanced samples of 64 males and 64 females with ASD, along with 64 demographically-matched typically developing control (TC) males and 64 TC females. The multilayer network analysis was used to explore the flexibility of dynamic network reconfiguration. The two-way analysis of variance was further performed to examine the sex-related changes in ASD in flexibility of dynamic network reconfiguration. A diagnosis-by-sex interaction effect was identified in the cingulo-opercular network (CON), central executive network (CEN), salience network (SN), and subcortical network (SUB). Compared with TC females, females with ASD showed lower flexibility in CON, CEN, SN, and SUB. The flexibility of CEN and SUB in males with ASD was higher than that in females with ASD. In addition, the flexibility of CON, CEN, SN, and SUB predicted the severity of social communication impairments and stereotyped behaviors and restricted interests only in females with ASD. These findings highlight significant sex differences in the flexibility of dynamic network reconfiguration in ASD and emphasize the importance of further study of sex differences in future ASD research.

Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Transcriptomic Analysis Reveals Sex-Based Differences in The Prefrontal Cortex of Autism Spectrum Disorder Patients.

The prevalence of neurological disorders often varies by sex, with conditions such as Alzheimer's disease and autism spectrum disorder (ASD) demonstrating notable differences in incidence. The aim of this study is to understand the molecular basis for these divergences in order to facilitate the creation of sex-specific therapeutic strategies. This study is a bioinformatic analysis of publicly available RNA sequencing datasets involving autism patients. The study utilized RNA sequencing data from postmortem human brains' prefrontal cortex, including 38 neurotypical controls and 34 individuals with ASD. The sequencing data was obtained from previously published papers, and we downloaded the raw data from SRA. We investigated the molecular basis of sex-biased presentation in ASD through comprehensive transcriptomic analysis. Comparative analysis of gene expression between male and female subjects, both autistic and unaffected, was conducted, using a significance level of ≤0.01. In autistic individuals, 136 genes demonstrated differential expression between sexes, predominantly upregulated in males, indicating a bias in male gene expression. Among these, 12 genes were identified as risk factors in the SFARI dataset. While most sex-biased genes were autosomal, expression differences on sex chromosomes were also observed in neurotypical subjects. Notable genes included TCF7L2, collagen family genes, and solute carrier family genes. In ASD males, extracellular matrix (ECM) organization emerged as a significant pathway, while immune-related processes were prominent in unaffected individuals. Our study highlights the impact of the ECM pathway in ASD, with notable differences between sexes, particularly in males. MIR424 shows promise as a potential biomarker for ASD in males. Recognizing the importance of sex differences in ASD transcriptomic research is crucial, as these variances provide insights into the disorder's pathophysiology and may guide the development of more personalized treatments for both sexes.

Posterior default mode network is associated with the social performance in male children with autism spectrum disorder: A dynamic causal modeling analysis based on triple-network model.

The triple-network model has been widely applied in neuropsychiatric disorders including autism spectrum disorder (ASD). However, the mechanism of causal regulations within the triple-network and their relations with symptoms of ASD remains unclear. 81 male ASD and 80 well matched typically developing control (TDC) were included in this study, recruited from Autism Brain Image Data Exchange-I datasets. Spatial reference-based independent component analysis was used to identify the anterior and posterior part of default-mode network (aDMN and pDMN), salience network (SN), and bilateral executive-control network (ECN) from resting-state functional magnetic resonance imaging data. Spectral dynamic causal model and parametric empirical Bayes with Bayesian model reduction/average were adopted to explore the effective connectivity (EC) within triple-network and the relationship between EC and autism diagnostic observation schedule (ADOS) scores. After adjusting for age and site effect, ASD and TDC groups both showed inhibition patterns. Compared with TDC, ASD group showed weaker self-inhibition in aDMN and pDMN, stronger inhibition in pDMN→aDMN, weaker inhibition in aDMN→LECN, pDMN→SN, LECN→SN, and LECN→RECN. Furthermore, negative relationships between ADOS scores and pDMN self-inhibition strength, as well as with the EC of pDMN→aDMN were observed in ASD group. The present study reveals imbalanced effective connections within triple-networks in ASD children. More attentions should be focused at the pDMN, which modulates the core symptoms of ASD and may serve as an important region for ASD diagnosis and the target region for ASD treatments.

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.

Screening for Autism Spectrum Disorder in Children and Adolescents With Leber's Congenital Amaurosis

PurposeTo investigate autism spectrum disorder (ASD) indicators in children with Leber congenital amaurosis (LCA). MethodsCross-sectional, correlational, and prospective study. Participants included patients aged 2 to 16 years with LCA confirmed by genetic testing. There were 20 individuals with ciliopathies (LCA cilio) and 26 with other gene mutations (LCA other). The instrument used for ASD screening was the Autism Behavior Checklist (ABC). Marginal descriptive analyses, non-parametric tests, and a linear regression model were conducted. ResultsOf the 46 participants, 6 had ASD scores. There was no statistically significant correlation between the different groups (LCA cilio and LCA other) (p=0.438). There was no statistically significant correlation between age and ASD (p=0.308). However, there was a statistically significant correlation between visual acuity and ASD (p=0.008) and between male gender and ASD (p=0.025). ConclusionsThis study suggests that there is no correlation between LCA cilio, LCA other and ASD. These findings bring new insights to the existing literature, which previously lacked robust data on the relationship between LCA and ASD. These data demonstrate that visual acuity plays a crucial role in the development of children with visual impairment as poorer visual acuity is associated with a higher incidence of ASD. Based on this study, early interventions can be designed, especially for individuals without light perception, with the aim of maximizing their developmental outcomes. Furthermore, such data indicates that any improvement in visual acuity outcomes in treatment clinical trials become relevant for child development.

Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder

To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.

Trends in behavioral management techniques for dental treatment of patients with autism spectrum disorder: a 10-year retrospective analysis.

Patients with autism spectrum disorder (ASD) present challenges in dental treatment cooperation owing to deficits in communication skills and social interaction. Behavioral guidance, sedation, and general anesthesia may be employed to ensure the quality of dental care for individuals with ASD. This study aimed to examine the trends in dental treatment for patients with ASD who visited the Department of Pediatric Dentistry at Dankook University Jukjeon Dental Hospital, an oral health center for the disabled in the Gyeonggi region, over the past 10 years. This study utilized the order communication system to gather data on sex, age, cooperation level, number of quadrants treated, and administration of sedation or general anesthesia for patients with ASD who visited the Department of Pediatric Dentistry at Dankook University Jukjeon Dental Hospital between January 2013 and December 2022. The total number of patients with ASD increased annually, possibly due to an increase in ASD prevalence and the hospital's designation as a center for disabled oral health. General anesthesia was predominant before 2017, with a shift towards N2O-O2 sedation. The most common age group for sedation or general anesthesia was 6-9 years, with a higher prevalence in males than in females. Notably, N2O-O2 and midazolam sedation resulted in better cooperation and fewer treated teeth than general anesthesia. This study highlights the evolving trends in dental treatment for individuals with ASD, indicating a shift towards outpatient methods, particularly N2O-O2 sedation. The sex distribution aligns with national statistics, emphasizing a higher prevalence of ASD in males than in females. These findings underscore the need for further research to establish evidence-based guidelines for optimal dental care strategies tailored to the unique needs of individuals with ASD.

Glial cells are affected more than interneurons by the loss of Engrailed 2 gene in the mouse cerebellum.

Glial cells play a pivotal role in the inflammatory processes, which are common features of several neurodevelopmental and neurodegenerative disorders. Their major role in modulating neuroinflammation underscores their significance in these conditions. Engrailed-2 knockout mice (En2-/- ) are considered a valuable model for autism spectrum disorder (ASD) due to their distinctive neuroanatomical and behavioral traits. Given the higher prevalence of ASD in males, our objective was to investigate glial and interneuron alterations in the cerebellum of En2-/- mice compared with wild-type (WT) mice in both sexes. We employed immunohistochemical analysis to assess cell density for all cell types studied and analyzed the area (A) and shape factor (SF) of microglia cell bodies. Our findings revealed the following: (a) In WT mice, the density of microglia and astrocytes was higher in females than in males, while interneuron density was lower in females. Notably, in En2-mutant mice, these differences between males and females were not present. (b) In both male and female En2-/- mice, astrocyte density exceeded that in WT mice, with microglia density being greater only in females. (c) In WT females, microglia cell bodies exhibited a larger area and a lower shape factor compared to WT males. Remarkably, the En2 mutation did not appear to influence these sex-related differences. (d) In both male and female En2-/- mice, we observed a consistent pattern: microglia cell bodies displayed a larger area and a smaller shape factor. Given the ongoing debate surrounding the roles of glia and sex-related factors in ASD, our observations provide valuable insights into understanding how an ASD-associated gene En2 affects specific cell types in the cerebellum.

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.

How neurotypical listeners recognize emotions expressed through vocal cues by speakers with high-functioning autism.

We conducted an investigation to explore how neurotypical (NT) listeners perceive the emotional tone of voice in sentences spoken by individuals with high-functioning autism spectrum disorders (ASD) and NT speakers. The investigation included both male and female speakers from both groups. In Study 1, NT listeners were asked to identify the emotional prosody (anger, fear, happiness, surprise or neutral) conveyed by the speakers. Results revealed that emotional expressions produced by male ASD speakers were generally less accurately recognized compared to male NT speakers. In contrast, emotions expressed by female ASD speakers were more accurately categorized compared to female NT speakers, except when expressing fear. This suggests that female ASD speakers may not express emotional prosody in the same way as their male counterparts. In Study 2, a subset of produced materials was rated for valence, voice modulation, and voice control to supplement Study 1 results: Female ASD speakers sounded less negative when expressing fear compared to female NT speakers. Male ASD speakers were perceived as less positive than NT speakers when expressing happiness. Voice modulation also differed between groups, showing a tendency for ASD speakers to follow different display rules for both positive emotions (happiness and surprise) tested. Finally, male ASD speakers were rated to use voice cues less appropriately compared to NT male speakers, an effect less pronounced for female ASD speakers. Together, the results imply that difficulties in social interactions among individuals with high-functioning ASD could be due to non-prototypical voice use of male ASD speakers and emphasize that female individuals do not show the same effects.

Abnormal individualized peak functional connectivity toward potential repetitive transcranial magnetic stimulation treatment of autism spectrum disorder.

Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging has been widely applied to guide precise repetitive transcranial magnetic stimulation (rTMS). The left, right, and bilateral dorsolateral prefrontal cortices (DLPFC) have been used as rTMS treatment target regions for autism spectrum disorder (ASD), albeit with moderate efficacy. Thus, we aimed to develop an individualized localization method for rTMS treatment of ASD. We included 266 male ASDs and 297 male typically-developed controls (TDCs) from the Autism Brain Imaging Data Exchange Dataset. The nucleus accumbens (NAc) was regarded as a promising effective region, which was used as a seed and individualized peak FC strength in the DLPFC was compared between ASD and TDC. Correlation analysis was conducted between individualized peak FC strength and symptoms in ASD. We also investigated the spatial distribution of individualized peak FC locations in the DLPFC and conducted voxel-wise analysis to compare NAc-based FC between the two groups. ASD showed stronger peak FC in the right DLPFC related to TDC (Cohen's d = -.19, 95% CI: -0.36 to -0.03, t = -2.30, p = .02). Moreover, negative correlation was found between the peak FC strength in the right DLPFC and Autism Diagnostic Observation Schedule (ADOS) scores, which assessed both the social communication and interaction (r = -.147, p = .04, uncorrected significant), and stereotyped behaviors and restricted interests (r = -.198, p = .02, corrected significant). Peak FC locations varied substantially across participants. No significant differences in NAc-based FC in the DLPFC were found in the voxel-wise comparison. Our study supports the use of individualized peak FC-guided precise rTMS treatment of male ASD. Moreover, stimulating the right DLPFC might alleviate core symptoms of ASD.

Brain perivascular spaces and autism: clinical and pathogenic implications from an innovative volumetric MRI study.

Our single-center case-control study aimed to evaluate the unclear glymphatic system alteration in autism spectrum disorder (ASD) through an innovative neuroimaging tool which allows to segment and quantify perivascular spaces in the white matter (WM-PVS) with filtering of non-structured noise and increase of the contrast-ratio between perivascular spaces and the surrounding parenchyma. Briefly, files of 65 ASD and 71 control patients were studied. We considered: ASD type, diagnosis and severity level and comorbidities (i.e., intellectual disability, attention-deficit hyperactivity disorder, epilepsy, sleep disturbances). We also examined diagnoses other than ASD and their associated comorbidities in the control group. When males and females with ASD are included together, WM-PVS grade and WM-PVS volume do not significantly differ between the ASD group and the control group overall. We found, instead, that WM-PVS volume is significantly associated with male sex: males had higher WM-PVS volume compared to females (p = 0.01). WM-PVS dilation is also non-significantly associated with ASD severity and younger age (< 4 years). In ASD patients, higher WM-PVS volume was related with insomnia whereas no relation was found with epilepsy or IQ. We concluded that WM-PVS dilation can be a neuroimaging feature of male ASD patients, particularly the youngest and most severe ones, which may rely on male-specific risk factors acting early during neurodevelopment, such as a transient excess of extra-axial CSF volume. Our findings can corroborate the well-known strong male epidemiological preponderance of autism worldwide.

Resting-State Activity in Children: Replicating and Extending Findings of Early Maturation of Alpha Rhythms in Autism Spectrum Disorder.

Resting-state alpha brain rhythms provide a foundation for basic as well as higher-order brain processes. Research suggests atypical maturation of the peak frequency of resting-state alpha activity (= PAF) in autism spectrum disorder (ASD). The present study examined resting-state alpha activity in young school-aged children, obtaining magnetoencephalographic (MEG) eyes-closed resting-state data from 47 typically developing (TD) males and 45 ASD males 6.0 to 9.3 years old. Results confirmed a higher PAF in ASD versus TD, and demonstrated that alpha power differences between groups were linked to the shift of PAF in ASD. Additionally, a higher PAF was associated with better cognitive performance in TD but not ASD. Finding thus suggested functional consequences of group differences in resting-state alpha activity.

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.

Measurement invariance of the Autism Impact Measure (AIM) across sex in children with autism spectrum disorder.

Measurement invariance, or the degree to which an instrument measures constructs consistently across subgroups, is critical for appropriate interpretations of measures. Given sex differences in the phenotypic and clinical presentation of autism spectrum disorder (ASD), it is particularly important to examine measurement invariance in autism instruments to ensure that ASD measures are not biased toward the more common male ASD phenotype. This study represents an important preliminary investigation evaluating the measurement equivalence of the Autism Impact Measure (AIM) across children and adolescents with ASD. The results indicated that the AIM demonstrated measurement invariance at the configural, metric, and scalar levels across sex in all five domains, including Repetitive Behavior, Communication, Atypical Behavior, Social Reciprocity, and Peer Interaction. These results suggest that ASD core symptoms assessed by the AIM were similar among male and female groups. In addition, the latent means for all five factors were not statistically significantly different across sex groups, revealing no systematic differences on any of the AIM subscales for males and females. Overall, this study showed that the AIM detects core ASD symptoms across all five areas equivalently in males and females and is not biased toward males with 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.

Effects of age on the hippocampus and verbal memory in adults with autism spectrum disorder: Longitudinal versus cross-sectional findings.

Research studying aging in adults with autism spectrum disorder (ASD) is growing, but longitudinal work is needed. Autistic adults have increased risk of dementia, altered hippocampal volumes and fornix integrity, and verbal memory difficulties compared with neurotypical (NT) adults. This study examined longitudinal aging in middle-age adults with ASD versus a matched NT group, and compared findings with cross-sectional age effects across a broad adult age range. Participants were 194 adults with (n=106; 74 male) and without (n=88; 52 male) ASD, ages 18-71. Participants (n=45; 40-70 age range) with two visits (2-3 years apart) were included in a longitudinal analysis. Hippocampal volume, fornix fractional anisotropy (FA), and verbal memory were measured via T1-weighted MRI, diffusion tensor imaging, and the Rey Auditory Verbal Learning Test, respectively. Longitudinal mixed models were used for hippocampal system variables and reliable change index categories were used for Auditory Verbal Learning Test analyses. Multivariate regression was used for cross-sectional analyses. Middle-age adults with ASD had greater longitudinal hippocampal volume loss and were more likely to show clinically meaningful decline in short-term memory, compared with NT. In contrast, cross-sectional associations between increasing age and worsening short-term memory were identified in NT, but not autistic adults. Reduced fornix FA and long-term memory in ASD were found across the broad cross-sectional age range. These preliminary longitudinal findings suggest accelerated hippocampal volume loss in ASD and slightly higher rates of clinically-meaningful decline in verbal short-term memory. Contradictory cross-sectional and longitudinal results underscore the importance of longitudinal aging research in autistic adults. LAY SUMMARY: Autistic adults have increased risk of dementia, differences in brain memory structures, and difficulty with memory compared with neurotypical (NT) adults. However, there are no publications that follow the same middle-age autistic adults over time to see how their brain and memory change. Our preliminary findings in a small middle-age autism sample suggest a key memory brain structure, the hippocampus, may shrink faster over 2-3 years compared with NT, and short-term memory may become more challenging for some. Across a broad adult range, autistic adults also had reduced integrity of connections to the hippocampus and greater challenges with long-term memory. In our larger sample across a broad age range, the results did not hint at this aforementioned pattern of accelerated aging. This underscores the importance of more aging research in autism, and especially research where people are followed over time.