Autism Spectrum Disorder In Females Research Articles

Imaging-genetics of sex differences in ASD: distinct effects of OXTR variants on brain connectivity

Autism spectrum disorder (ASD) is more prevalent in males than in females, but the neurobiological mechanisms that give rise to this sex-bias are poorly understood. The female protective hypothesis suggests that the manifestation of ASD in females requires higher cumulative genetic and environmental risk relative to males. Here, we test this hypothesis by assessing the additive impact of several ASD-associated OXTR variants on reward network resting-state functional connectivity in males and females with and without ASD, and explore how genotype, sex, and diagnosis relate to heterogeneity in neuroendophenotypes. Females with ASD who carried a greater number of ASD-associated risk alleles in the OXTR gene showed greater functional connectivity between the nucleus accumbens (NAcc; hub of the reward network) and subcortical brain areas important for motor learning. Relative to males with ASD, females with ASD and higher OXTR risk-allele-dosage showed increased connectivity between the NAcc, subcortical regions, and prefrontal brain areas involved in mentalizing. This increased connectivity between NAcc and prefrontal cortex mirrored the relationship between genetic risk and brain connectivity observed in neurotypical males showing that, under increased OXTR genetic risk load, females with ASD and neurotypical males displayed increased connectivity between reward-related brain regions and prefrontal cortex. These results indicate that females with ASD differentially modulate the effects of increased genetic risk on brain connectivity relative to males with ASD, providing new insights into the neurobiological mechanisms through which the female protective effect may manifest.

Neurogenetic Profiles of Risk and Resilience in Female Autism

Understanding sex differences in brain function and genetics is critical to delineating the systems biology of autism spectrum disorder (ASD), but female ASD is understudied. We integrate imaging and genetic data in a sex-balanced sample of ASD and neurotypical youth to evaluate the hypothesis that there are female-specific pathways of ASD risk and resilience. FMRI data reveal a neurofunctional profile of female ASD characterized by motor, striatal, and frontal involvement not observed in male ASD. Further, we observe greater recruitment of salience and executive control networks among neurotypical girls versus neurotypical boys and autistic girls, suggesting neural correlates of the “Female Protective Effect.” Larger copy number variants containing gene(s) expressed in striatal cortex in autistic girls versus boys suggest a female-specific etiological role for potential impacts to this brain region. Our findings advocate caution in drawing conclusions regarding autistic girls based on male-predominant samples.

Autism Heterogeneity in a Densely Sampled U.S. Population: Results From the First 1,000 Participants in the RI-CART Study.

The objective of this study was to establish a large, densely sampled, U.S. population-based cohort of people with autism spectrum disorder (ASD). The Rhode Island Consortium for Autism Research and Treatment (RI-CART) represents a unique public-private-academic collaboration involving all major points of service for families in Rhode Island affected by ASD. Diagnosis was based on direct behavioral observation via the Autism Diagnostic Observation Schedule, Second Edition. For the first 1,000 participants, ages ranged from 21 months to 64 years. Using Geographic Information System and published prevalence rates, the overall cohort is estimated to represent between 20% and 49% of pediatric age persons in Rhode Island with ASD, with demographics representative of U.S. Census. We observed a high rate of co-occurring medical and psychiatric conditions in affected individuals. Among the most prominent findings of immediate clinical importance, we found that females received a first diagnosis of ASD at a later age than males, potentially due to more advanced language abilities in females with ASD. In summary, this is the first analysis of a large, population-based U.S. cohort with ASD. Given the depth of sampling, the RI-CART study reflects an important new resource for studying ASD in a representative U.S. population. Psychiatric and medical comorbidities in ASD constitute a substantial burden and warrant adequate attention as part of overall treatment. Our study also suggests that new strategies for earlier diagnosis of ASD in females may be warranted. Autism Res 2020, 13: 474-488. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The Rhode Island Consortium for Autism Research and Treatment (RI-CART) represents a unique public-private-academic collaboration involving all major points of service for families in Rhode Island affected by autism spectrum disorder (ASD). In this article, we provide results from the first 1,000 participants, estimated to represent >20% of affected families in the state. Importantly, we find a later age at first diagnosis of ASD in females, which potentially calls attention to the need for improved early diagnosis in girls. Also, we report a high rate of co-occurring medical and psychiatric conditions in affected individuals.

3 RARE HEMIZYGOUS MUTATIONS WITHIN CHROMOSOME X NON-PSEUDOAUTOSOMAL REGIONS CONTRIBUTE MALE-SPECIFIC AUTISM RISK

Autism spectrum disorder (ASD) is consistently diagnosed 3 to 5 times more frequently in males than females, a dramatically sex-biased prevalence that suggests the involvement of sex-differential biological factors in modulating risk. The genomic scale of transcriptomic analyses of human brain tissue can provide an unbiased approach for identifying genes and associated functional processes at the intersection of sex-differential and ASD-impacted neurobiology. Several studies characterizing gene expression changes in the ASD brain have been published in recent years with increasing sample size and cellular resolution. These studies report several convergent patterns across data sets and genetically heterogeneous samples in the ASD brain, including elevated expression of gene sets associated with glial and immune function, and reduced expression of gene sets associated with neuronal and synaptic functions. Assessment of neurotypical cortex tissue has reported parallel patterns by sex, with male-elevated expression of overlapping sets of glial/immune-related genes and female-biased expression of neuron-associated genes, suggesting potential roles for these cell types in sex-differential ASD risk mechanisms. However, validating and further exploring these mechanisms is challenged by the available data, as existing studies of ASD brain include a limited number of female ASD donors and focus predominantly on cortex regions not known to show pronounced sex-differential morphology or function. With this review, we summarize convergent findings from several landmark studies of the transcriptome in ASD brain and their relationship to sex-differential gene expression, and we discuss limitations and remaining questions regarding transcriptomic analysis of sex differences in ASD.

Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism

BackgroundFragile X syndrome (FXS) is a genetic disorder that is highly comorbid with anxiety and autism spectrum disorder (ASD). Elevated negative affect in young children has been associated with increased risk for both anxiety and ASD; however, these relations remain poorly understood in FXS.MethodsThe present prospective longitudinal study examined the trajectory of negative affect from infancy through preschool in males and females with FXS and typical development and its relation to anxiety and ASD.ResultsResults indicate a complex association reflecting group, developmental, and sex effects. Specifically, the group with FXS displayed a trajectory of increasing negative affect across age that was distinct from the typical controls. This atypical trajectory of negative affect in FXS was driven by sex effects in that males showed lower negative affect during infancy followed by steep increases across the toddler and preschool years whereas the females displayed a flatter trajectory. Finally, elevated negative affect predicted anxiety symptoms in males, but not females, with no relationship to ASD in males or females with FXS.ConclusionsThe current work addresses the importance of studying the development of psychopathology in a specific neurogenetic population. Temperamental negative affect was shown to be an important early marker for anxiety in young children with FXS, with subtle differences observed between males and females.

Sex Differences in the Amygdala Resting-State Connectome of Children With Autism Spectrum Disorder

BackgroundMultifactorial liability models predict greater dissimilarity in the neural phenotype of autism spectrum disorder (ASD) in female individuals than in male individuals, while gender incoherence and extreme male brain models predict attenuated sex differences in ASD. The amygdala is an informative target to explore these models because it is implicated in both the neurobiology of ASD and sex differences in typical development. MethodsThis study investigated amygdala resting-state functional connectivity in a cohort of 116 children with ASD (36 female) and 58 typically developing children (27 female) 2 to 7 years of age during natural sleep. First, multivariate distance matrix regression assessed global sex and diagnostic differences across the amygdala connectome. Second, univariate general linear models identified regions with mean connectivity differences. ResultsMultivariate distance matrix regression revealed greater differences between typically developing children and those with ASD in females than in males, consistent with multifactorial liability models, and attenuated sex differences in the left amygdala connectome of children with ASD in a pattern consistent with the gender incoherence model. Univariate analysis identified similar sex differences in dorsomedial and ventral prefrontal cortices, lingual gyrus, and posterior cingulate cortex, but also noted that lower amygdala connectivity with superior temporal sulcus is observed across sexes. ConclusionsThis study provides evidence that compared with sex-matched control subjects, ASD manifests differently in the brain at the time of diagnosis and prior to the influence of compensatory mechanisms in male and female children, consistent with multifactorial liability models, and that ASD is associated with reduced sex differences in a pattern consistent with gender incoherence models.

Chronic subconvulsive activity during early postnatal life produces autistic behavior in the absence of neurotoxicity in the juvenile weanling period

The diagnosis of autism spectrum disorder (ASD) varies from very mild to severe social and cognitive impairments. We hypothesized that epigenetic subconvulsive activity in early postnatal life may contribute to the development of autistic behavior in a sex-related manner. Low doses of kainic acid (KA) (25–100 μg) were administered to rat pups for 15 days beginning on postnatal (P) day 6 to chronically elevate neuronal activity. A battery of classical and novel behavioral tests was used, and sex differences were observed. Our novel open handling test revealed that ASD males nose poked more often and ASD females climbed and escaped more frequently with age. In the social interaction test, ASD males were less social than ASD females who were more anxious in handling and elevated plus maze (EPM) tasks. To evaluate group dynamics, sibling and non-sibling control and experimental animals explored 3 different shaped novel social environments. Control pups huddled quickly and more frequently in all environments whether they socialized with littermates or non-siblings compared to ASD groups. Non-sibling ASD pups were erratic and huddled in smaller groups. In the object recognition test, only ASD males spent less time with the novel object compared to control pups. Data suggest that chronic subconvulsive activity in early postnatal life leads to an ASD phenotype in the absence of cell death. Males were more susceptible to developing asocial behaviors and cognitive pathologies, whereas females were prone to higher levels of hyperactivity and anxiety, validating our postnatal ASD model apparent in the pre-juvenile period.

Altered Neural Connectivity in Females, But Not Males with Autism: Preliminary Evidence for the Female Protective Effect from a Quality-Controlled Diffusion Tensor Imaging Study.

Previous studies using diffusion tensor imaging (DTI) to investigate white matter (WM) structural connectivity have suggested widespread, although inconsistent WM alterations in autism spectrum disorder (ASD), such as greater reductions in fractional anisotropy (FA). However, findings may lack generalizability because: (a) most have focused solely on the ASD male brain phenotype, and not sex‐differences in WM integrity; (b) many lack stringent and transparent data quality control such as controlling for head motion in analysis. This study addressed both issues by using Tract‐Based Spatial Statistics (TBSS) to separately compare WM differences in 81 ASD (56 male, 25 female; 4–21 years old) and 39 typically developing (TD; 23 males, 16 females; 5–18 years old) children and young people, carefully group‐matched on sex, age, cognitive abilities, and head motion. ASD males and females were also matched on autism symptom severity. Two independent‐raters completed a multistep scan quality assurance to remove images that were significantly distorted by motion artifacts before analysis. ASD females exhibited significant widespread reductions in FA compared to TD females, suggesting altered WM integrity. In contrast, no significant localized or widespread WM differences were found between ASD and TD males. This study highlights the importance of data quality control in DTI, and outlines important sex‐differences in WM alterations in ASD females. Future studies can explore the extent to which neural structural differences might underlie sex‐differences in ASD behavioral phenotype, and guide clinical interventions to be tailored toward the unique needs of ASD females and males. Autism Res 2019, 12: 1472–1483. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.Lay SummaryPrevious Diffusion Tensor Imaging (DTI) studies have found atypical brain structural connectivity in males with autism, although findings are inconclusive in females with autism. To investigate potential sex‐differences, we studied males and females with and without autism who showed a similar level of head movement during their brain scan. We found that females with autism had widespread atypical neural connectivity than females without autism, although not in males, highlighting sex‐differences.

Neuropsychiatric phenotypes and a distinct constellation of ASD features in 3q29 deletion syndrome: results from the 3q29 registry

BackgroundThe 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20 to 40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described.MethodsWe ascertained individuals with 3q29 deletion syndrome (3q29Del, “cases,” n = 93, 58.1% male) and typically developing controls (n = 64, 51.6% male) through the 3q29 registry (https://3q29deletion.patientcrossroads.org). Self-report of neuropsychiatric illness was evaluated for 93 cases. Subsets of participants were evaluated with the Social Responsiveness Scale (SRS, n = 48 cases, 56 controls), Social Communication Questionnaire (n = 33 cases, 46 controls), Autism Spectrum Screening Questionnaire (n = 24 cases, 35 controls), and Achenbach Behavior Checklists (n = 48 cases, 57 controls).Results3q29Del cases report a higher prevalence of autism diagnoses versus the general population (29.0% vs. 1.47%, p < 2.2E− 16). Notably, 3q29 deletion confers a greater influence on risk for ASD in females (OR = 41.8, p = 4.78E− 05) than in males (OR = 24.6, p = 6.06E− 09); this is aligned with the reduced male:female bias from 4:1 in the general population to 2:1 in our study sample. Although 71% of cases do not report a diagnosis of ASD, there is evidence of significant social disability (3q29Del SRS T-score = 71.8, control SRS T-score = 45.9, p = 2.16E− 13). Cases also report increased frequency of generalized anxiety disorder compared to controls (28.0% vs. 6.2%, p = 0.001), which is mirrored by elevated mean scores on the Achenbach diagnostic and statistical manual-oriented sub-scales (p < 0.001). Finally, cases show a distinct constellation of ASD features on the SRS as compared to idiopathic ASD, with substantially elevated Restricted Interests and Repetitive Behaviors, but only mild impairment in Social Motivation.ConclusionsOur sample of 3q29Del is significantly enriched for ASD diagnosis, especially among females, and features of autism may be present even when an ASD diagnosis is not reported. Further, the constellation of ASD features in this population is distinct from idiopathic ASD, with substantially less impaired social motivation. Our study implies that ASD evaluation should be the standard of care for individuals with 3q29Del. From a research perspective, the distinct ASD subtype present in 3q29Del is an ideal entry point for expanding understanding of ASD.

Visual attention to faces in children with autism spectrum disorder: are there sex differences?

BackgroundThe male bias in autism spectrum disorder (ASD) diagnoses is well documented. As a result, less is known about the female ASD phenotype. Recent research suggests that conclusions drawn from predominantly male samples may not accurately capture female behavior. In this study, we explore potential sex differences in attention to social stimuli, which is generally reported to be diminished in ASD. Population-based sex differences in attention to faces have been reported, such that typically developing (TD) females attend more to social stimuli (including faces) from infancy through adulthood than TD males. It is yet unknown whether population-based sex differences in the face domain are preserved in ASD.MethodsA dynamic, naturalistic infrared eye-tracking paradigm measured attention to social stimuli (faces) in 74 school-aged males and females with ASD (male N = 23; female N = 19) and without ASD (male N = 16; female N = 16). Two kinds of video stimuli were presented that varied in social content: rich social scenes (dyadic play between two children) and lean social scenes (parallel play by two children).ResultsResults revealed a significant 3-way interaction between sex, diagnosis, and condition after controlling for chronological and mental age. ASD females attended more to faces than ASD males in the socially lean condition. This effect was not found in the typically developing (TD) group. ASD males attended less to faces regardless of social context; however, ASD females only attended significantly less to faces compared to TD females in the socially rich condition. TD males and ASD females did not differ in their attention to faces in either condition.ConclusionsThis study has implications for how the field understands core social deficits in children with ASD, which should ideally be benchmarked against same-sex peers (male and female). Social attention in ASD females fell on a continuum—greater than their ASD male peers, but not as great as TD females. Overall, their social attention mirrored that of TD males. Improved understanding of the female social phenotype in ASD will enhance early screening and diagnostic efforts and will guide the development of sex-sensitive experimental paradigms and social interventions.

Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case-control study.

Vitamin D appears essential for normal neurodevelopment and cognitive and behavioral function. We examined neonatal vitamin D in relation to the child's later diagnosis of autism spectrum disorder (ASD) or developmental delay (DD). Children aged 24-60 months enrolled in the population-based CHARGE case-control study were evaluated clinically for ASD (n = 357), DD (n = 134), or typical development (TD, n = 234) at the MIND Institute (Sacramento, CA) using standardized assessments. Total 25-hydroxyvitamin D (25[OH]D) was measured using sensitive isotope dilution liquid chromatography-tandem mass spectrometry in archived dried blood spots collected for the California Department of Public Health's Newborn Screening Program. Multinomial logistic regression was used to calculate ORs as measures of the associations between 25 nmol/L change in 25(OH)D and ASD and DD. Associations between 25(OH)D and scores on Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales were assessed using robust linear regression. Effect modification was examined using stratified models and interaction product terms. Unadjusted mean (SD) 25(OH)D was lower for DD (73.2 [37.6]) than for TD (82.7 [39.3]) and ASD (80.1 [37.4]). After adjustment for maternal prepregnancy body mass index and education, a 25 nmol/L increase in total 25(OH)D was not associated with ASD (OR = 0.97; CI: 0.87-1.08) or DD (OR = 0.91; 95% CI: 0.78-1.06). Neonatal 25(OH)D was associated with significantly reduced ASD only in females (adjusted OR = 0.74; 95% CI: 0.55-0.99, Pinteraction = 0.03), and significantly reduced DD only in non-Hispanic white children (adjusted OR = 0.79; 95% CI: 0.63-0.98, Pinteraction = 0.11 for Hispanic, Pinteraction = 0.31 for other), driven by DD children with trisomy 21. This study provides evidence that neonatal vitamin D could be associated with ASD in females and with DD in non-Hispanic white children. Autism Res 2019, 12: 976-988. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Vitamin D appears essential for brain development and function. We examined neonatal total 25-hydroxyvitamin D (25[OH]D) measured in dried blood spots in relation to later diagnoses of autism spectrum disorder (ASD) or developmental delay (DD) and related assessment scores. Higher neonatal 25(OH)D was associated with a 26% reduction in the odds for ASD only in females. After taking into account factors that could contribute to vitamin D status, a significant association with 21% reduced odds for DD was found only in non-Hispanic white children. Though results were nonsignificant overall, certain subgroups might benefit from higher neonatal vitamin D.

Sex Differences in Resting-State Functional Connectivity of the Cerebellum in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is more prevalent in males than females, but the underlying neurobiology of this sex bias remains unclear. Given its involvement in ASD, its role in sensorimotor, cognitive, and socio-affective processes, and its developmental sensitivity to sex hormones, the cerebellum is a candidate for understanding this sex difference. The current study used resting-state functional magnetic resonance imaging (fMRI) to investigate sex-dependent differences in cortico-cerebellar organization in ASD. We collected resting-state fMRI scans from 47 females (23 ASD, 24 controls) and 120 males (56 ASD, 65 controls). Using a measure of global functional connectivity (FC), we ran a linear mixed effects analysis to determine whether there was a sex-by-diagnosis interaction in resting-state FC. Subsequent seed-based analyses from the resulting clusters were run to clarify the global connectivity effects. Two clusters in the bilateral cerebellum exhibited a diagnosis-by-sex interaction in global connectivity. These cerebellar clusters further showed a pattern of interaction with regions in the cortex, including bilateral fusiform, middle occipital, middle frontal, and precentral gyri, cingulate cortex, and precuneus. Post hoc tests revealed a pattern of cortico-cerebellar hyperconnectivity in ASD females and a pattern of hypoconnectivity in ASD males. Furthermore, cortico-cerebellar FC in females more closely resembled that of control males than that of control females. These results shed light on the sex-specific pathophysiology of ASD and are indicative of potentially divergent neurodevelopmental trajectories for each sex. This sex-dependent, aberrant cerebellar connectivity in ASD might also underlie some of the motor and/or socio-affective difficulties experienced by members of this population, but the symptomatic correlate(s) of these brain findings remain unknown.Clinical Trial Registration: www.ClinicalTrials.gov, NIH Clinical Study Protocol 10-M-0027 (ZIA MH002920-09) identifier #NCT01031407

Characters with autism spectrum disorder in fiction: where are the women and girls?

Purpose Fiction has the potential to dispel myths and helps improve public understanding and knowledge of the experiences of under-represented groups. Representing the diversity of the population allows individuals to feel included, connected with and understood by society. Whether women and girls with autism spectrum disorder (ASD) are adequately and accurately represented in fictional media is currently unknown. The paper aims to discuss this issue. Design/methodology/approach Internet and library searches were conducted to identify female characters with ASD in works of fiction. Examples of such works were selected for further discussion based on their accessibility, perceived historical and cultural significance and additional characteristics that made the work particularly meaningful. Findings The search highlighted a number of female characters with ASD across a range of media, including books, television, film, theatre and video games. Many were written by authors who had a diagnosis of the condition themselves, or other personal experience. Pieces largely portrayed characters with traits that are highly recognised within the academic literature. However, some also appeared to endorse outdated myths and stereotypes. Existing works appear to preferentially portray high functioning autistic women, with limited representation of those whom also have intellectual disability. Originality/value This is the first exploration of the depiction of ASD in females within fiction. There is a need for more works of fiction responsibly depicting females with ASD, as this can help reduce stigma, develop public awareness and recognition and increase representation.

Kami-shoyo-san ameliorates sociability deficits in ovariectomized mice, a putative female model of autism spectrum disorder, via facilitating dopamine D1 and GABAA receptor functions

Ethnopharmacological relevanceKami-shoyo-san (KSS) is a Kampo formula used clinically for menopause-related symptoms in Japan. However, the effect of KSS on autism spectrum disorder (ASD), a developmental disorder with a higher prevalence in males than in females, has not been reported yet. Aim of the studyIt is accepted generally that dysfunction in the GABAergic system is associated with pathogenesis of ASD. In our previous study, a decrease in brain allopregnanolone (ALLO), a positive allosteric GABAA receptor modulator, induced ASD-like symptoms such as impaired sociability-related performance and increased repetitive self-grooming behavior in male mice, and that KSS ameliorated these behavioral abnormalities via GABAA receptor- and dopamine D1 receptor-mediated mechanisms. In this study, to better understand a gender difference in the prevalence of ASD, we examined whether dissection of ovary (OVX), a major organ secreting progesterone in females, causes ASD-like behaviors in a manner dependent on brain ALLO levels, and if so, how KSS affects the behaviors. Materials and methodsSix-week-old ICR female mice received ovariectomy, and KSS (74 mg/kg and 222 mg/kg, p.o.) were treated before 1 h starting each behavioral test. The sociability, social anxiety-like behavior, and self-grooming behavior were analyzed by the resident-intruder test, mirror chamber test, and open field test, respectively. After finishing the behavioral experiment, the ALLO content in the brain was measured by ELISA. Furthermore, we examined the effects of OVX on the neuro-signaling pathways in the prefrontal cortex and striatum by Western blotting. ResultsThe results revealed that OVX induced sociability deficits and social anxiety-related behaviors, but not repetitive self-grooming behavior, and that these behavioral changes were accompanied not only by a decrease of brain ALLO levels, but also by impairment of CREB- and CaMKIIα-mediated neuro-signaling in the prefrontal cortex. Moreover, the administration of KSS had no effect on the brain ALLO level, but significantly ameliorated the OVX-induced behavioral and neurochemical changes via facilitation of GABAA receptor and dopamine D1 receptor-mediated neurotransmission. ConclusionsThese findings suggest that a decrease in gonadal hormone-derived ALLO plays a major role in ASD-like behaviors in female mice and that KSS is beneficial for the treatment of ASD in females.

Circumscribed interests in autism: are there sex differences?

PurposeSex differences in circumscribed interests (CI) may delay diagnosis for females with autism spectrum disorder (ASD); therefore, it is important to characterize sex differences in CI to determine if differential approaches to diagnostic assessment are warranted for females with ASD. The purpose of this paper is to examine sex differences in parent-reported quantity, content and functional impairment of children’s interests.Design/methodology/approachParent responses to the Interests Scale were analyzed using descriptive statistics and ANOVAs to determine diagnostic (ASD vs typical development (TD)) and sex differences between four groups of children ages six to ten years: ASD males, ASD females, TD males and TD females.FindingsGroups were comparable on the quantity of interests reported on the Interests Scale. Children with ASD demonstrated significantly more nonsocial interests and had greater functional impairment associated with their interests than TD children. A significant diagnosis×sex effect was found for the number of interests in folk psychology. Descriptively, males with ASD were more likely to have a primary interest in the traditionally male category of physics than females with ASD whose primary interest mainly fell into the categories of TV or the more traditionally female category of psychology.Originality/valueThese findings strengthen the results of Turner-Brown et al. (2011) by replicating their findings that children with ASD have more nonsocial interests and greater functional impairments related to their interests compared to TD children in a sample that is balanced on biological sex. However, there are distinctions between males and females with ASD in their primary interests that have implications for diagnostic assessment.

Risperidone-induced alopecia in a child with autism spectrum disorder

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder. Risperidone appears to be effective in associated behavioral problems with ASD. Alopecia can be drug induced and has been associated with several psychotropic medicines. Antipsychotics would seem to act by triggering a premature telogen or resting phase, resulting in hair loss. We report a female patient ASD developing alopecia following risperidone use. To the best of our knowledge, this is the first report of alopecia induced by risperidone during treatment of self-injurious behaviours in a child female patient with ASD.

Risperidone-induced alopecia in a child with autism spectrum disorder

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder. Risperidone appears to be effective in associated behavioral problems with ASD. Alopecia can be drug induced and has been associated with several psychotropic medicines. Antipsychotics would seem to act by triggering a premature telogen or resting phase, resulting in hair loss. We report a female patient ASD developing alopecia following risperidone use. To the best of our knowledge, this is the first report of alopecia induced by risperidone during treatment of self-injurious behaviours in a child female patient with ASD.

Oxytocin levels and sex differences in autism spectrum disorder with severe intellectual disabilities

There were few reports of oxytocin (OXT) concentrations of autism spectrum disorder (ASD) patients with severe intellectual disabilities. We measured serum OXT concentrations in 79 hospitalized patients with severe intellectual disabilities (16–60 years old, 50 males and 29 females, 54 ASD patients) and investigated the associations between serum OXT concentration, symptom scores, sex differences, and autism spectrum disorder. There were no significant effects of diagnosis, severity of intellectual disabilities, and total score of the Japanese version of the Aberrant Behavior Checklist (ABC-J), the Childhood Autism Rating Scale-Tokyo Version (CARS-TV), and the Japanese version of the Repetitive Behavior Scale-Revised (RBS-R). However, there were sex differences in the correlations between OXT concentrations and subscale scores in the ASD group. The male ASD group (n = 39) showed negative correlations between RBS-R Self-injurious and Sameness subscale scores and serum OXT concentrations. In the female ASD group(n = 15), CARS-TV Nonverbal communication subscale scores and RBS-R Compulsive subscale scores were seen to positively correlate with serum OXT concentrations. These findings suggest that OXT functions differ in males and females with severe intellectual disabilities and that OXT partly affects autism and related to some of the repetitive behaviors and nonverbal communication, in ASD patients with severe intellectual disabilities.

Sex Differences Along the Autism Continuum: A Twin Study of Brain Structure.

Females might possess protective mechanisms regarding autism spectrum disorder (ASD) and require a higher detrimental load, including structural brain alterations, before developing clinically relevant levels of autistic traits. This study examines sex differences in structural brain morphology in autism and autistic traits using a within-twin pair approach. Twin design inherently controls for shared confounders and enables the study of gene-independent neuroanatomical variation. N = 148 twins (62 females) from 49 monozygotic and 25 dizygotic same-sex pairs were included. Participants were distributed along the whole continuum of autism including twin pairs discordant and concordant for clinical ASD. Regional brain volume, surface area, and cortical thickness were computed. Within-twin pair increases in autistic traits were related to decreases in cortical volume and surface area of temporal and frontal regions specifically in female twin pairs, in particular regions involved in social communication, while only two regions were associated with autistic traits in males. The same pattern was detected in the monozygotic twin pairs only. Thus, non-shared environmental factors seem to impact female more than male cerebral architecture associated with autistic traits. Our results are in line with the hypothesis of a female protective effect in autism and highlights the need to study ASD in females separately from males.

Brief Report: Sex Differences in ASD Diagnosis-A Brief Report on Restricted Interests and Repetitive Behaviors.

Previous research found repetitive and restricted behaviors (RRBs) were less predictive of Autism Spectrum Disorder (ASD) in females, indicating the diagnostic construct may not adequately describe RRB presentations in females. This mixed-methods study investigated the female presentation of RRBs, namely restricted interests, in a clinic sample of 125 participants (n = 40 female; ages 2-83 years; 75 ASD). RRB severity did not differ between sexes, t = 1.69, p = 0.094, though male participants scored higher on the Restricted Behavior subscale. Qualitatively, females demonstrated a narrower range of restricted interests and expressed them in a socially oriented manner compared to males. The results suggest unique quantitative and qualitative sex differences in RRB profiles that could shed light on the female ASD phenotype.