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Empathizing, systemizing, and empathizing-systemizing difference can be linked to autistic traits in the general adult population and those with autism spectrum disorder (ASD), but these profiles and associations remain unclear in children with ASD, with and without intellectual disability (ASD + ID; ASD-noID). We recruited three groups including 160 boys with ASD (73 ASD + ID; 87 ASD-noID) and 99 typically developing (TD) boys (6-12 years). We measured empathizing, systemizing, and empathizing-systemizing difference using the parent-reported child Empathy and Systemizing Quotient (EQ-C/SQ-C). We measured autistic traits using the Social Responsiveness Scale (SRS). Among the three groups, children with ASD + ID and ASD-noID scored lower on the EQ-C and SQ-C than TD children (all p < 0.001). There was no difference in the EQ-C between children with ASD + ID and ASD-noID (16.59 ± 5.53 vs. 16.23 ± 5.85, p = 0.973), and the difference in the SQ-C attenuated to null when adjusting for intelligence between children with ASD-noID and TD children (18.89 ± 7.80 vs. 24.15 ± 6.73, p = 0.089). Children with ASD + ID scored higher on empathizing-systemizing difference than TD children but lower than children with ASD-noID (all p < 0.05). Negative associations between EQ-C and all autistic traits, null associations between SQ-C and all autistic traits, and positive associations between empathizing-systemizing difference and all autistic traits were found in all groups. We observed differences in empathizing, systemizing, and empathizing-systemizing difference and the consistency of their associations with autistic traits among the three groups. Our findings provide implication that behavioral interventions of ASD should consider the balance of empathizing and systemizing. LAY SUMMARY: We examined the profiles of empathizing, systemizing, and empathizing-systemizing difference in children with autism spectrum disorder, with and without intellectual disability (ASD + ID; ASD-noID), and typically developing (TD) children aged 6-12 years. We observed differences in these profiles and the consistency of their associations with autistic traits among the three groups. Empathizing and empathizing-systemizing difference, rather than systemizing, were associated with autistic traits within the three groups. Our findings provide implication that behavioral interventions of ASD should consider these imbalance profiles., (© 2022 International Society for Autism Research and Wiley Periodicals LLC.)

Prenatal testosterone (pT) is a crucial component in physiological masculinization in humans. In line with the Prenatal Sex Steroid Theory of autism, some studies have found a positive correlation between pT and autistic traits in childhood. However, effects in adolescence have not been explored. Hormonal and environmental changes occurring during puberty may alter the strength or the nature of prenatal effects on autistic traits. The current study examines if pT relates to autistic traits in a non-clinical sample of adolescents and young adults (N = 97, 170 observations; age 13-21 years old). It also explores pT interactions with pubertal stage and timing. PT concentrations were measured from amniotic fluid extracted in the 2nd trimester of gestation via amniocentesis conducted for clinical purposes. Autistic traits were measured by self- and parent-reports on the Autism Spectrum Quotient (AQ) which provides a total score and 5 sub-scores (social skills, communication, imagination, attention switching and attention to detail). Self-reported pubertal stage was regressed on age to provide a measure of relative timing. We found no statistical evidence for a direct association between pT and autistic traits in this adolescent sample (males, females or full sample). Exploratory analyses suggested that pT correlated positively with autistic traits in adolescents with earlier puberty-onset, but statistical robustness of this finding was limited. Further exploratory post-hoc tests suggested the pT-by-pubertal timing interaction was stronger in males relative to females, in self-reported compared to parent-reported AQ and specifically for social traits. These findings require replication in larger samples. Findings have implications for understanding the effects of pT on human behavior, specifically existence of effects in adolescence., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent evidence suggests that, contrary to traditional views, empathy difficulties may not be a core feature of autism; but are rather due to co-occurring alexithymia. Empathy, alexithymia and autistic traits have yet to be examined concurrently in children. Therefore, we examined the co-occurrence of empathy difficulties and alexithymia in 59 typically developing and 5 autistic children. Multiple measures (self-report, parent-report and a behavioural task) were used to evaluate empathy and to assess differences in self- and parent-reports using multiple regressions. Alexithymia was found to predict empathy significantly better than autistic traits, providing support for the alexithymia hypothesis. From a therapeutic perspective, results suggest autistic children who screen positive for elevated alexithymic traits may benefit from additional support targeting emotion identification., (© 2021. The Author(s).)

Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.

Background: Oxytocin administration, which may be of therapeutic value for individuals with social difficulties, is likely to affect endogenous levels of other socially relevant hormones. However, to date, the effects of oxytocin administration on endogenous hormones have only been examined in neurotypical individuals. The need to consider multi-hormone interactions is particularly warranted in oxytocin trials for autism due to evidence of irregularities in both oxytocin and sex steroid systems., Methods: In this double-blind cross-over study, saliva samples were collected from 16 autistic and 29 neurotypical women before and after intranasal administration of 24 IU oxytocin or placebo. Oestradiol, testosterone, and oxytocin levels were quantified in saliva samples. Participants also completed the Autism-Spectrum Quotient (AQ) and Empathy Quotient (EQ) questionnaires., Results: Distinct patterns of change in testosterone and oestradiol levels pre- to-post-administration were observed in autistic relative to neurotypical women (ANCOVA, p < 0.05 main effect of Group), controlling for sample collection time. The mean percent change oestradiol was + 8.8% for the autism group and - 13.0% for the neurotypical group (t = 1.81, p = 0.08), while the mean percent change testosterone was + 1.1% in the autism group and - 12.6% in the neurotypical group (t = 1.26, p = 0.22). In the oxytocin condition, the mean percent change oestradiol was + 12.6% in the autism group and - 6.9% in the neurotypical group (t = 1.78, p = 0.08), while the mean percent change testosterone was + 14.4% in the autism group and - 15.2% in the neurotypical group (t = 3.00, p = 0.006). Robust regression confirmed that group differences in percent change hormone levels were not driven by a small number of influential individuals. Baseline hormone levels did not differ between groups when considered individually. However, baseline testosterone relative to oestradiol (T:E2 ratio) was higher in autistic women (p = 0.023, Cohen's d = 0.63), and this ratio correlated positively and negatively with AQ and EQ scores, respectively, in the combined sample., Limitations: Further studies with larger and more diverse autistic sample are warranted to confirm these effects., Conclusions: This study provides the first evidence that oxytocin influences endogenous testosterone levels in autistic individuals, with autistic women showing increases similar to previous reports of neurotypical men. These findings highlight the need to consider sex steroid hormones as a variable in future oxytocin trials.

Prior work has revealed sex/gender-dependent autistic characteristics across behavioural and neural/biological domains. It remains unclear whether and how neural sex/gender differences are related to behavioural sex/gender differences in autism. Here, we examined whether atypical neural responses during mentalizing and self-representation are sex/gender-dependent in autistic adults and explored whether 'camouflaging' (acting as if behaviourally neurotypical) is associated with sex/gender-dependent neural responses. In total, N  = 119 adults (33 typically developing males, 29 autistic males, 29 typically developing females and 28 autistic females) participated in a task-related functional magnetic resonance imaging paradigm to assess neural activation within right temporo-parietal junction and ventromedial prefrontal cortex during mentalizing and self-representation. Camouflaging in autism was quantified as the discrepancy between extrinsic behaviour in social-interpersonal contexts and intrinsic status. While autistic men showed hypoactive right temporo-parietal junction mentalizing and ventromedial prefrontal cortex self-representation responses compared to typically developing men, such neural responses in autistic women were not different from typically developing women. In autistic women only, increasing camouflaging was associated with heightened ventromedial prefrontal cortex self-representation response. There is a lack of impaired neural self-representation and mentalizing in autistic women compared to typically developing women. Camouflaging is heightened in autistic women and may relate to neural self-representation response. These results reveal brain-behaviour relations that help explain sex/gender-heterogeneity in social brain function in autism.

Background: Autism prevalence in the West is approximately 1% of school age children. Autism prevalence in China has been reported to be lower than in the West. This is likely due to at least two reasons: (1) most studies in China only included the special school population, overlooking the mainstream school population; and (2) most studies in China have not used contemporary screening and diagnostic methods. To address this, we tested total autism prevalence (mainstream and special schools) in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities., Methods: The study included a three-step process: (1) screening; (2) clinical assessment of 'screen positives' plus controls; and (3) research diagnostic assessment of those meeting clinical threshold for concerns at step 2. Prevalence estimates per 10,000 children aged 6-10 years old were weighted for study design using diagnostic criteria applied at the research assessment stage., Results: In Jilin City, 77 cases of autism were identified from a total population of 7258, equating to a prevalence of 108 per 10,000 (95% confidence interval (CI) 89, 130). In Shenzhen City: 21,420 children were screened and 35 cases of autism were identified, resulting in a mainstream prevalence of 42 per 10,000 (95% CI 20-89). In Jiamusi City, 16,358 children were screened, with 10 autism cases being identified, with a mainstream prevalence of 19 per 10,000 (95% CI 10-38)., Conclusions: Results from Jilin City, where both mainstream and special school data were available, revealed a similar prevalence of autism in China to the West, at around 1%. Results from Shenzhen and Jiamusi cities, where only mainstream data were available, prevalence is also in line with Western estimates. In all three cities, new cases of autism were identified by the study in mainstream schools, reflecting current under-diagnosis. Non-significant variation across different cities is seen indicating the need to explore potential variation of autism across diverse Chinese regions with large sample sizes to achieve a fully robust national picture., Competing Interests: This study was approved by the Research Ethics Committee at the Chinese University of Hong Kong and the Peking University Institutional Review Board. Consent was provided to participants via the screening package before participating. Participants were asked to indicate whether they continued to consent at the end of the study.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Autobiographical descriptions and clinician observations suggest that some individuals with autism, particularly females, 'camouflage' their social communication difficulties, which may require considerable cognitive effort and lead to increased stress, anxiety and depression. Using data from 60 age- and IQ-matched men and women with autism (without intellectual disability), we operationalized camouflaging in adults with autism for the first time as the quantitative discrepancy between the person's 'external' behavioural presentation in social-interpersonal contexts (measured by the Autism Diagnostic Observation Schedule) and the person's 'internal' status (dispositional traits measured by the Autism Spectrum Quotient and social cognitive capability measured by the 'Reading the Mind in the Eyes' Test). We found that the operationalized camouflaging measure was not significantly correlated with age or IQ. On average, women with autism had higher camouflaging scores than men with autism (Cohen's d = 0.98), with substantial variability in both groups. Greater camouflaging was associated with more depressive symptoms in men and better signal-detection sensitivity in women with autism. The neuroanatomical association with camouflaging score was largely sex/gender-dependent and significant only in women: from reverse inference, the most correlated cognitive terms were about emotion and memory. The underlying constructs, measurement, mechanisms, consequences and heterogeneity of camouflaging in autism warrant further investigation.

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as use of 'at-risk' language, communicating study findings to parents and the future perspective of enrolled infants when they reach adulthood. This study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism and practitioners in health and education settings across 11 European countries. Survey respondents (n = 2317) were positively disposed towards early autism research, and there was significant overlap in their priorities for the field and preferred language to describe infant research participants. However, there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase 'at-risk' to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account., (© The Author(s) 2016.)

We investigate the broader autism phenotype (BAP) in siblings of individuals with autism spectrum conditions (ASC). Autistic traits were measured in typical controls (n = 2,000), siblings (n = 496), and volunteers with ASC (n = 2,322) using the Autism-Spectrum Quotient (AQ), both self-report and parent-report versions. Using cluster analysis of AQ subscale scores, two sibling subgroups were identified for both males and females: a cluster of low-scorers and a cluster of high-scorers. Results show that while siblings as a group have intermediate levels of autistic traits compared to control individuals and participants with ASC, when examined on a cluster level, the low-scoring sibling group is more similar to typical controls while the high-scoring group is more similar to the ASC clinical group. Further investigation into the underlying genetic and epigenetic characteristics of these two subgroups will be informative in understanding autistic traits, both within the general population and in relation to those with a clinical diagnosis. Autism Res 2016, 9: 658-665. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research., (© 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.)

Research to date in mainland China has mainly focused on children with autistic disorder rather than Autism Spectrum Conditions and the diagnosis largely depended on clinical judgment without the use of diagnostic instruments. Whether children who have been diagnosed in China before meet the diagnostic criteria of Autism Spectrum Conditions is not known nor how many such children would meet these criteria. The aim of this study was to evaluate children with a known diagnosis of autism in mainland China using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised to verify that children who were given a diagnosis of autism made by Chinese clinicians in China were mostly children with severe autism. Of 50 children with an existing diagnosis of autism made by Chinese clinicians, 47 children met the diagnosis of autism on the Autism Diagnostic Observation Schedule algorithm and 44 children met the diagnosis of autism on the Autism Diagnostic Interview-Revised algorithm. Using the Gwet's alternative chance-corrected statistic, the agreement between the Chinese diagnosis and the Autism Diagnostic Observation Schedule diagnosis was very good (AC1 = 0.94, p < 0.005, 95% confidence interval (0.86, 1.00)), so was the agreement between the Chinese diagnosis and the Autism Diagnostic Interview-Revised (AC1 = 0.91, p < 0.005, 95% confidence interval (0.81, 1.00)). The agreement between the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised was lower but still very good (AC1 = 0.83, p < 0.005)., (© The Author(s) 2015.)

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.

Autism spectrum conditions (autism) affect ~1% of the population and are characterized by deficits in social communication. Oxytocin has been widely reported to affect social-communicative function and its neural underpinnings. Here we report the first evidence that intranasal oxytocin administration improves a core problem that individuals with autism have in using eye contact appropriately in real-world social settings. A randomized double-blind, placebo-controlled, within-subjects design is used to examine how intranasal administration of 24 IU of oxytocin affects gaze behavior for 32 adult males with autism and 34 controls in a real-time interaction with a researcher. This interactive paradigm bypasses many of the limitations encountered with conventional static or computer-based stimuli. Eye movements are recorded using eye tracking, providing an objective measurement of looking patterns. The measure is shown to be sensitive to the reduced eye contact commonly reported in autism, with the autism group spending less time looking to the eye region of the face than controls. Oxytocin administration selectively enhanced gaze to the eyes in both the autism and control groups (transformed mean eye-fixation difference per second=0.082; 95% CI:0.025-0.14, P=0.006). Within the autism group, oxytocin has the most effect on fixation duration in individuals with impaired levels of eye contact at baseline (Cohen's d=0.86). These findings demonstrate that the potential benefits of oxytocin in autism extend to a real-time interaction, providing evidence of a therapeutic effect in a key aspect of social communication.

Sex differences have been reported in autistic traits and systemizing (male advantage), and empathizing (female advantage) among typically developing individuals. In individuals with autism, these cognitive-behavioural profiles correspond to predictions from the "extreme male brain" (EMB) theory of autism (extreme scores on autistic traits and systemizing, below average on empathizing). Sex differences within autism, however, have been under-investigated. Here we show in 811 adults (454 females) with autism and 3,906 age-matched typical control adults (2,562 females) who completed the Empathy Quotient (EQ), the Systemizing Quotient-Revised (SQ-R), and the Autism Spectrum Quotient (AQ), that typical females on average scored higher on the EQ, typical males scored higher on the SQ-R and AQ, and both males and females with autism showed a shift toward the extreme of the "male profile" on these measures and in the distribution of "brain types" (the discrepancy between standardized EQ and SQ-R scores). Further, normative sex differences are attenuated but not abolished in adults with autism. The findings provide strong support for the EMB theory of autism, and highlight differences between males and females with autism.

Few data on healthcare services for individuals with Autism Spectrum Conditions (ASC) are available from mainland China. This article is based on findings from 69 semi-structured interviews with parents of children with ASC in three intervention centres. The respondents are from 19 regions in mainland China. A service-mapping questionnaire containing 50 questions is developed and used as an interview schedule for service mapping. The pathway to diagnosis and intervention for children with ASC is presented according to parents' experience. The findings report considerable delay along the pathway which may be partly due to the under-developed service system. Several cultural issues are identified which may also contribute to the delay, such as the perception of mental illness, folk beliefs equating delayed development of language skills in early childhood with future high intelligence, and the state-imposed one-child policy. Delays in recognising ASC and a lack of support are also considered to be associated with the considerable financial burden placed on parents of children with ASC in mainland China., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Qualitative semi-structured interviews were conducted with service providers regarding the current healthcare provision and education services for children with Autism Spectrum Conditions (ASC) and their families in mainland China. 10 service providers described the current policy and identified unmet needs within current practice. Providers perceived that children with ASC were an important but under-served group in mainland China. Two levels of service provision related to ASC were identified: (1) healthcare services mainly provided by government authorities; (2) education services mainly provided by the parents of children with ASC. Little cooperation was reported between the two types of providers. The structure of service provision for ASC is under-developed. There is an important need to establish coherent healthcare and education policies to support children with ASC and their families., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The male bias in autism spectrum conditions (ASC) has led to females with ASC being under-researched. This lack of attention to females could hide variability due to sex that may explain some of the heterogeneity within ASC. In this study we investigate four key cognitive domains (mentalizing and emotion perception, executive function, perceptual attention to detail, and motor function) in ASC, to test for similarities and differences between males and females with and without ASC (n = 128 adults; n = 32 per group). In the mentalizing and facial emotion perception domain, males and females with ASC showed similar deficits compared to neurotypical controls. However, in attention to detail and dexterity involving executive function, although males with ASC showed poorer performance relative to neurotypical males, females with ASC performed comparably to neurotypical females. We conclude that performance in the social-cognitive domain is equally impaired in male and female adults with ASC. However, in specific non-social cognitive domains, performance within ASC depends on sex. This suggests that in specific domains, cognitive profiles in ASC are modulated by sex.

This article is an author response to three previous commentaries on 'Fetal testosterone and autistic traits' (Auyeung et al., 2009).

Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has also been suggested that autism may be an extreme manifestation of some male-typical traits, both in terms of cognition and neuroanatomy. In this paper, we examine the possibility of a link between autistic traits and fT levels measured in amniotic fluid during routine amniocentesis. Two instruments measuring number of autistic traits (the Childhood Autism Spectrum Test (CAST) and the Child Autism Spectrum Quotient (AQ-Child)) were completed by these women about their children (N=235), ages 6-10 years. Intelligence Quotient (IQ) was measured in a subset of these children (N=74). fT levels were positively associated with higher scores on the CAST and AQ-Child. This relationship was seen within sex as well as when the sexes were combined, suggesting this is an effect of fT rather than of sex per se. No relationships were found between overall IQ and the predictor variables, or between IQ and CAST or AQ-Child. These findings are consistent with the hypothesis that prenatal androgen exposure is related to children exhibiting more autistic traits. These results need to be followed up in a much larger sample to test if clinical cases of ASC have elevated fT.

The Autism Spectrum Quotient-Children's Version (AQ-Child) is a parent-report questionnaire that aims to quantify autistic traits in children 4-11 years old. The range of scores on the AQ-Child is 0-150. It was administered to children with an autism spectrum condition (ASC) (n = 540) and a general population sample (n = 1,225). Results showed a significant difference in scores between those with an ASC diagnosis and the general population. Receiver-operating-characteristic analyses showed that using a cut-off score of 76, the AQ-Child has high sensitivity (95%) and specificity (95%). The AQ-Child showed good test-retest reliability and high internal consistency. Factor analysis provided support for four of the five AQ-Child design subscales. Future studies should evaluate how the AQ-C performs in population screening.