Using Organoids to Model Sex Differences in the Human Brain.

Sex differences are widespread during neurodevelopment and play a role in neuropsychiatric conditions such as autism, which is more prevalent in males than females. In humans, males have been shown to have larger brain volumes than females with development of the hippocampus and amygdala showing prominent sex differences. Mechanistically, sex steroids and sex chromosomes drive these differences in brain development, which seem to peak during prenatal and pubertal stages. Animal models have played a crucial role in understanding sex differences, but the study of human sex differences requires an experimental model that can recapitulate complex genetic traits. To fill this gap, human induced pluripotent stem cell-derived brain organoids are now being used to study how complex genetic traits influence prenatal brain development. For example, brain organoids from individuals with autism and individuals with X chromosome-linked Rett syndrome and fragile X syndrome have revealed prenatal differences in cell proliferation, a measure of brain volume differences, and excitatory-inhibitory imbalances. Brain organoids have also revealed increased neurogenesis of excitatory neurons due to androgens. However, despite growing interest in using brain organoids, several key challenges remain that affect its validity as a model system. In this review, we discuss how sex steroids and the sex chromosomes each contribute to sex differences in brain development. Then, we examine the role of X chromosome inactivation as a factor that drives sex differences. Finally, we discuss the combined challenges of modeling X chromosome inactivation and limitations of brain organoids that need to be taken into consideration when studying sex differences.

Sex differences are a contributing factor in neuropsychiatric conditions such as autism, which is more prevalent in males. Sex differences occur through interactions between sex steroid hormones such as estrogen and testosterone and sex chromosomes (chrX and chrY). Human stem cell­derived brain organoids are laboratory models that mimic brain development. For example, in individuals with neurodevelopmental conditions, brain organoids have revealed an imbalance of neuron populations compared with neurotypical individuals. In this review, we discuss sex steroid and sex chromosome influences on brain development and challenges of this model that need to be taken into account when studying sex differences.

Sleep disturbance, suicidal ideation and psychosis-risk symptoms in individuals at clinical high risk for psychosis.

Insomnia and suicidal ideation (SI) are common in schizophrenia, including in individuals at clinical high-risk for psychosis (CHR-P). Previous studies have found associations between sleep disturbance, SI, and psychopathology in schizophrenia. We explored these associations in a CHR-P cohort. We leveraged data from CHR-P individuals in the North American Prodrome Longitudinal Studies (NAPLS-3) (n = 688) cohort. We investigated relationships between sleep disturbance (Scale of Prodromal Symptoms [SOPS]; Calgary Depression Scale for Schizophrenia [CDSS], and the Pittsburgh Sleep Quality Index [PSQI]), suicidal ideation (CDSS), and psychosis-risk symptoms. The prevalence of terminal insomnia, sleep disturbance, and SI in NAPLS3 was 25 %, 69 %, and 29 %, respectively. After controlling for potential confounders, multiple indices of sleep disturbance (SOPS, PSQI: OR = 1.05-1.40) were significant indicators of concurrent SI. Terminal insomnia was not associated with conversion to psychosis. Multiple indices of sleep problems were associated with higher total and subscale psychosis-risk symptom scores (ß = 0.09-0.39). Sleep problems are prevalent and associated with SI and more severe psychosis-risk symptoms in CHR-P individuals. These findings underscore the importance of designing longitudinal intervention studies to investigate whether the treatment of sleep disturbances may reduce suicidality and symptoms in this population.

Sublingual microcirculatory alterations in Chagas disease: an observational study in an endemic rural population.

BACKGROUND: Chagas disease is a systemic illness with widespread microvascular involvement. Experimental and clinical studies suggest that functional and structural microcirculatory abnormalities might be relevant to the disease progression. OBJECTIVES: To show the presence of sublingual microcirculatory alterations in patients with chronic Chagas disease. METHODS: This was a cross-sectional study including adult patients with serologic diagnosis of Chagas disease (n = 41) and control volunteers with negative serology (n = 38), from an endemic rural population. Study participants underwent clinical, electrocardiographic, echocardiographic, and sublingual videomicroscopic assessment. Videos were acquired by a sidestream-dark-field (SDF) imaging device and evaluated by a software-assisted analysis (AVA 3.2 software). FINDINGS: Most of Chagas disease patients were in the indeterminate phase (n = 34) and had lower heart rate and more echocardiographic abnormalities than control group (50 vs. 26%, p = 0.03). They also exhibited higher small microvessels total and perfused vascular density (20.12 ± 2.33 vs. 19.05 ± 2.25 and 20.03 ± 2.28 vs. 19.01 ± 2.25 mm/mm2, p < 0.05 for both). Other microvascular variables did not differ between groups. MAIN CONCLUSIONS: Patients with chronic Chagas disease exhibited increases in sublingual total and perfused microvascular density. Angiogenesis might be the underlying mechanism. The videomicroscopic assessment of mucosal sublingual microcirculation might be an additional tool in the monitoring of Chagas disease.

Integrating genomic variants and developmental milestones to predict cognitive and adaptive outcomes in autistic children.

Although the first signs of autism are often observed as early as 18-36 months of age, there is a broad uncertainty regarding future development, and clinicians lack predictive tools to identify those who will later be diagnosed with co-occurring intellectual disability (ID). Here, we developed predictive models of ID in autistic children (n=5,633 from three cohorts), integrating different classes of genetic variants alongside developmental milestones. The integrated model yielded an AUC ROC=0.65, with this predictive performance cross-validated and generalised across cohorts. Positive predictive values reached up to 55%, accurately identifying 10% of ID cases. The ability to stratify the probabilities of ID using genetic variants was up to twofold greater in individuals with delayed milestones compared to those with typical development. These findings underscore the potential of models in neurodevelopmental medicine that integrate genomics and clinical observations to predict outcomes and target interventions.

Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology.

BACKGROUND: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Population modelling, often referred to as normative modelling, provides a unified framework for studying age-specific and sex-specific divergences in brain development. METHODS: Here we used population modelling and a large, multi-site neuroimaging dataset (N = 4255 after quality control) to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of average brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). RESULTS: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume, that was localised to the superior temporal cortex, whereas individuals with ADHD showed more global increases in cortical thickness, but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. CONCLUSIONS: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence.

An axis of genetic heterogeneity in autism is indexed by age at diagnosis and is associated with varying developmental and mental health profiles.

There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h2 SNP = 0.12, s.e.m = 0.01), and is associated with two moderately correlated (rg = 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.

Moral foundations in autistic people and people with systemizing minds.

BACKGROUND: Do autistic people share the same moral foundations as typical people? Here we built on two prominent theories in psychology, moral foundations theory and the empathizing-systemizing (E-S) theory, to observe the nature of morality in autistic people and systemizers. METHODS: In dataset 1, we measured five foundations of moral judgements (Care, Fairness, Loyalty, Authority, and Sanctity) measured by the Moral Foundations Questionnaire (MFQ) in autistic (n = 307) and typical people (n = 415) along with their scores on the Empathy Quotient (EQ) and Systemizing Quotient (SQ). In dataset 2, we measured these same five foundations along with E-S cognitive types (previously referred to as "brain types") in a large sample of typical people (N = 7595). RESULTS: Autistic people scored the same on Care (i.e., concern for others) as typical people (h1). Their affective empathy (but not their cognitive empathy) scores were positively correlated with Care. Autistic people were more likely to endorse Fairness (i.e., giving people what they are owed, and treating them with justice) over Care (h2). Their systemizing scores were positively correlated with Fairness. Autistic people or those with a systemizing cognitive profile had lower scores on binding foundations: Loyalty, Authority, and Sanctity (h3). Systemizing in typical people was positively correlated with Liberty (i.e., hypervigilance against oppression), which is a sixth moral foundation (h4). Although the majority of people in all five E-S cognitive types self-identified as liberal, with a skew towards empathizing (h5), the percentage of libertarians was highest in systemizing cognitive types (h6). E-S cognitive types accounted for 2 to 3 times more variance for Care than did sex. LIMITATIONS: Our study is limited by its reliance on self-report measures and a focus on moral judgements rather than behavior or decision-making. Further, only dataset 2 measured political identification, therefore we were unable to assess politics in autistic people. CONCLUSIONS: We conclude that some moral foundations in autistic people are similar to those in typical people (despite the difficulties in social interaction that are part of autism), and some are subtly different. These subtle differences vary depending on empathizing and systemizing cognitive types.

The 'PSILAUT' protocol: an experimental medicine study of autistic differences in the function of brain serotonin targets of psilocybin.

BACKGROUND: The underlying neurobiology of the complex autism phenotype remains obscure, although accumulating evidence implicates the serotonin system and especially the 5HT2A receptor. However, previous research has largely relied upon association or correlation studies to link differences in serotonin targets to autism. To directly establish that serotonergic signalling is involved in a candidate brain function our approach is to change it and observe a shift in that function. We will use psilocybin as a pharmacological probe of the serotonin system in vivo. We will directly test the hypothesis that serotonergic targets of psilocybin - principally, but not exclusively, 5HT2A receptor pathways-function differently in autistic and non-autistic adults. METHODS: The 'PSILAUT' "shiftability" study is a case-control study autistic and non-autistic adults. How neural responses 'shift' in response to low doses (2 mg and 5 mg) of psilocybin compared to placebo will be examined using multimodal techniques including functional MRI and EEG. Each participant will attend on up to three separate visits with drug or placebo administration in a double-blind and randomized order. RESULTS: This study will provide the first direct evidence that the serotonin targets of psilocybin function differently in the autistic and non-autistic brain. We will also examine individual differences in serotonin system function. CONCLUSIONS: This work will inform our understanding of the neurobiology of autism as well as decisions about future clinical trials of psilocybin and/or related compounds including stratification approaches. TRIAL REGISTRATION: NCT05651126.

Polygenic scores for autism are associated with neurite density in adults and children from the general population.

Genetic variants linked to autism are thought to change cognition and behaviour by altering the structure and function of the brain. Although a substantial body of literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic variants are linked to changes in cortical macro- and micro-structure. We investigated this using neuroimaging and genetic data from adults (UK Biobank, N = 31,748) and children (ABCD, N = 4,928). Using polygenic scores and genetic correlations we observe a robust negative association between common variants for autism and a magnetic resonance imaging derived phenotype for neurite density (intracellular volume fraction) in the general population. This result is consistent across both children and adults, in both the cortex and in white matter tracts, and confirmed using polygenic scores and genetic correlations. There were no sex differences in this association. Mendelian randomisation analyses provide no evidence for a causal relationship between autism and intracellular volume fraction, although this should be revisited using better powered instruments. Overall, this study provides evidence for shared common variant genetics between autism and cortical neurite density.

Potential Mechanisms Underlying Suicidality in Autistic People with Attention Deficit/Hyperactivity Disorder: Testing Hypotheses from the Interpersonal Theory of Suicide.

Background: Autistic people with co-occurring attention deficit/hyperactivity disorder (ADHD) appear to be at heightened risk of suicide. To understand why, we explored two explanatory mechanisms from the interpersonal theory of suicide: first, that co-occurring ADHD might be associated with greater risk through greater thwarted belongingness and perceived burdensomeness and, secondly, that hyperactive/impulsive features might incur additional risk through their association with painful and provocative events, which are suggested to create "capability" for suicide. Methods: Autistic adults (n = 314) completed an online survey including measures of thwarted belongingness, perceived burdensomeness, painful and provocative events, acquired capability for suicide, and ADHD features. Creating an overall index of likely ADHD, we examined associations between likely ADHD, suicide ideation, and lifetime suicide attempts through the parallel mediators of thwarted belongingness, perceived burdensomeness, anxiety, and depression. In several models, we then examined hyperactive, impulsive, and inattentive features as predictors of exposure to painful and provocative events and subsequent capability for suicide, and examined whether these two variables, sequentially or individually, mediated an association with lifetime suicide attempts. Results: Likely ADHD was associated with past-year suicide ideation through greater depression and perceived burdensomeness, which also mediated its association with more suicide attempts. Hyperactive and impulsive features were associated with exposure to painful and provocative events and through this acquired suicide capability. Both features were associated with more numerous suicide attempts through these two mediators sequentially, and through exposure to painful and provocative events alone. Conclusions: These data suggest that suicidality in autistic people with ADHD may be partially related to perceived burdensomeness and to acquired suicide capability after exposure to painful and provocative events. However, as we observed a pathway to suicidality associated with painful and provocative events alone, it is likely that there are also other explanatory mechanisms for the influence of traumatic events on suicide risk.

Why is this an important issue?: Suicide is a leading cause of premature death in autistic people, but we still know little about why autistic people are at greater risk and how we can help. Recent findings suggest that autistic people with co-occurring attention deficit/hyperactivity disorder (ADHD) are at even higher risk, but we do not yet understand why. What was the purpose of this study?: This research examined two potential explanations for higher risk of suicide in autistic people with co-occurring ADHD. First, we expected that because these individuals are often very isolated and struggle with independence and employment, they might be more vulnerable to two risk factors for suicide: "thwarted belongingness," the feeling of being alienated from other people, and "perceived burdensomeness," the feeling that one is a burden to others. We also expected that hyperactive/impulsive features associated with ADHD might make people more likely to experience painful and dangerous events. Exposure to events like this is suggested to make people less frightened of dying by suicide and more able to attempt to end their lives. This is called "acquiring capability" for suicide. What did the researchers do?: We asked 314 autistic adults to complete an online survey including measures of thwarted belongingness, perceived burdensomeness, exposure to painful and dangerous events, and acquired capability for suicide. They also completed a scale measuring ADHD features, and symptoms of depression and anxiety. We then looked at which of these factors, if any, explained suicide risk in autistic people with co-occurring ADHD. What were the results of the study?: Our data suggest that autistic people with co-occurring ADHD might be at greater risk of suicide ideation and attempts because they are more likely to experience depression and to feel like a burden to others. We also found that people with high degrees of hyperactive/impulsive features were more likely to experience painful and dangerous events, and, therefore, had greater capability for suicide­because of this, they were more likely to have attempted suicide more times in the past. Exposure to these kinds of traumatic events also increased the risk of suicide all by itself. What do these findings add to what was already known?: Very little is known about why autistic people with co-occurring ADHD might be at even higher risk of suicide than people with either ADHD or autism alone. No studies have examined explanations for suicide in this subgroup. What are potential weaknesses in the study?: Because this study looked at a snapshot of participants' current states, we cannot be sure of the direction of relationships between variables. For example, it might be that experiences of surviving suicide attempts actually make people feel more depressed and more like a burden afterward, rather than these feelings being the risk factors that contributed to suicide attempts. How will these findings help autistic adults now or in the future?: These findings indicate feelings and experiences that are relevant to suicide risk in autistic people with co-occurring ADHD, which might thus be important to target in interventions.

Fetal brain growth and infant autistic traits.

BACKGROUND: Structural differences exist in the brains of autistic individuals. To date only a few studies have explored the relationship between fetal brain growth and later infant autistic traits, and some have used fetal head circumference (HC) as a proxy for brain development. These findings have been inconsistent. Here we investigate whether fetal subregional brain measurements correlate with autistic traits in toddlers. METHODS: A total of 219 singleton pregnancies (104 males and 115 females) were recruited at the Rosie Hospital, Cambridge, UK. 2D ultrasound was performed at 12-, 20- and between 26 and 30 weeks of pregnancy, measuring head circumference (HC), ventricular atrium (VA) and transcerebellar diameter (TCD). A total of 179 infants were followed up at 18-20 months of age and completed the quantitative checklist for autism in toddlers (Q-CHAT) to measure autistic traits. RESULTS: Q-CHAT scores at 18-20 months of age were positively associated with TCD size at 20 weeks and with HC at 28 weeks, in univariate analyses, and in multiple regression models which controlled for sex, maternal age and birth weight. LIMITATIONS: Due to the nature and location of the study, ascertainment bias could also have contributed to the recruitment of volunteer mothers with a higher than typical range of autistic traits and/or with a significant interest in the neurodevelopment of their children. CONCLUSION: Prenatal brain growth is associated with toddler autistic traits and this can be ascertained via ultrasound starting at 20 weeks gestation.

Enhancing emotion recognition in young autistic children with or without attention-deficit/hyperactivity disorder in Hong Kong using a Chinese App version of The Transporters.

TRIAL REGISTRATION: This study was registered with the German Clinical Trials Register - Deutschen Register Klinischer Studien (DRKS) on 23 December 2018. The Trial Registration Number (TRN) is DRKS00016506. LAY ABSTRACT: The Transporters App is an intervention programme with 15 animated episodes that teach emotion recognition skills to autistic children between 4 and 6 years of age. Each episode contains a story depicting social interactions between characters in the form of a vehicle, with human faces grafted on to each of them. Each episode teaches a specific emotion in a story context. Autistic children watched at least three episodes at home for about 15 min daily for a month, with parental guidance. Its automated, home-based format is cost-saving and readily accessible. This study translated The Transporters to a Cantonese-Chinese version. Results showed a significant improvement in emotion recognition following viewing The Transporters in a group of Hong Kong Chinese autistic children, between 4 and 6 years of age, with and without attention-deficit/hyperactivity disorder (n = 48) relative to a control group (n = 24). A non-autistic group (n = 23) showed that the autistic children scored lower in emotion recognition pre-intervention. Post-intervention, the autistic children had improved in emotion recognition to the level of the non-autistic children. The autistic children in the intervention groups also generalized their learning to novel situations/characters not taught within The Transporters. There was no dosage effect, with the standard recommended number of episodes viewed being sufficient to achieve significant improvement. This study confirms the effectiveness of The Transporters for Chinese autistic children and contributes to the literature/practice by expanding the range of applicability of The Transporters to autistic children with attention-deficit/hyperactivity disorder, which is important given the high rate of co-occurrence between autism and attention-deficit/hyperactivity disorder.

Sublingual microcirculatory alterations in Chagas disease: an observational study in an endemic rural population

BACKGROUND Chagas disease is a systemic illness with widespread microvascular involvement. Experimental and clinical studies suggest that functional and structural microcirculatory abnormalities might be relevant to the disease progression. OBJECTIVES To show the presence of sublingual microcirculatory alterations in patients with chronic Chagas disease. METHODS This was a cross-sectional study including adult patients with serologic diagnosis of Chagas disease (n = 41) and control volunteers with negative serology (n = 38), from an endemic rural population. Study participants underwent clinical, electrocardiographic, echocardiographic, and sublingual videomicroscopic assessment. Videos were acquired by a sidestream-dark-field (SDF) imaging device and evaluated by a software-assisted analysis (AVA 3.2 software). FINDINGS Most of Chagas disease patients were in the indeterminate phase (n = 34) and had lower heart rate and more echocardiographic abnormalities than control group (50 vs. 26%, p = 0.03). They also exhibited higher small microvessels total and perfused vascular density (20.12 ± 2.33 vs. 19.05 ± 2.25 and 20.03 ± 2.28 vs. 19.01 ± 2.25 mm/mm2, p < 0.05 for both). Other microvascular variables did not differ between groups. MAIN CONCLUSIONS Patients with chronic Chagas disease exhibited increases in sublingual total and perfused microvascular density. Angiogenesis might be the underlying mechanism. The videomicroscopic assessment of mucosal sublingual microcirculation might be an additional tool in the monitoring of Chagas disease.

Is the association between mothers' autistic traits and childhood autistic traits moderated by maternal pre-pregnancy body mass index?

BACKGROUND: Previous studies showed that there is a positive association between mothers' and children's autistic traits. We also tested if this association is more pronounced in mothers with a higher pre-pregnancy body mass index (BMI). METHOD: The study was embedded in two cohorts with information available for 4,659 participants from the Generation R and for 179 participants from the Cambridge Ultrasound Siblings and Parents Project (CUSP) cohort. In both cohorts, maternal autistic traits were assessed using the short form of the Autism Spectrum Quotient, and information about maternal height and weight before pregnancy was obtained by questionnaire. Child autistic traits were assessed with the short form of Social Responsiveness Scale in Generation R (M = 13.5 years) and with the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in the CUSP cohort (M = 1.6 years). RESULT: Higher maternal autistic traits were associated with higher autistic traits in toddlerhood (CUSP cohort; ßadjusted = 0.20, p < 0.01), in early childhood (Generation R; ßadjusted = 0.19, p < 0.01), and in early adolescence (Generation R; ßadjusted = 0.16, p < 0.01). Furthermore, a higher maternal pre-pregnancy BMI was associated with higher child autistic traits, but only in Generation R (ßadjusted = 0.03, p < 0.01). There was no significant moderating effect of maternal pre-pregnancy BMI on the association between autistic traits of mothers and children, neither in Generation R nor in CUSP. In addition, child autistic traits scores were significantly higher in mothers who were underweight and in mothers who were overweight compared to mothers with a healthy weight. CONCLUSION: We confirm the association between maternal and child autistic traits in toddlerhood, early childhood, and early adolescence. Potential interacting neurobiological processes remain to be confirmed.

Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology.

Background: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Normative modelling provides a unified framework for studying age-specific and sex-specific divergences in neurodivergent brain development. Methods: Here we use normative modelling and a large, multi-site neuroimaging dataset to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of typical brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). Results: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume localised to the superior temporal cortex, whereas individuals with ADHD showed more global effects of cortical thickness increases but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. Conclusions: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence.

Measuring the Autistic Women's Experience (AWE).

We developed a Dutch questionnaire called the Autistic Women's Experience (AWE) and compared its psychometric properties to the Autism Spectrum Quotient (AQ). Whilst attenuated gender differences on the AQ have been widely replicated, this instrument may not fully capture the unique experience of autistic women. The AWE was co-developed with autistic women to include items that reflect autistic women's experience. We investigated the AWE (49 items) and compared it with the AQ (50 items) in Dutch autistic individuals (N = 153, n = 85 women) and in the general population (N = 489, n = 246 women) aged 16+. Both the AQ and AWE had excellent internal consistency and were highly and equally predictive of autism in both women and men. Whilst there was a gender difference on the AQ among non-autistic people (men > women), there was no gender difference among autistic people, confirming all earlier studies. No gender differences were detected on the AWE overall scale, yet subtle gender differences were observed on the subscales. We conclude that the AQ is valid for both genders, but the AWE provides an additional useful perspective on the characteristics of autistic women. The AWE needs further validation in independent samples using techniques that allow for testing gender biases, as well as a confirmatory factor analysis in a larger sample.

Does Having a Sibling Affect Autistic People's Empathy?

This study examined whether autistic people with siblings score higher on measures of empathy than those without siblings. Cohorts of autistic children (n = 939; mean age = 7.35 years (SD = 2.15)) and autistic adults (n = 736; mean age = 37 years (SD = 12.39)) from the Cambridge Autism Research Database (CARD) were each divided into two groups: with or without siblings. Empathy was measured using the children version of the Empathy Quotient (EQ) (parent-report) for children. For adults, the EQ (self-report version) and the Reading the Mind in the Eyes Test (RMET) were used. Contrary to the hypothesis, autistic children without siblings scored higher on EQ than those with siblings (t(283.70) = 4.20, p < .001; d = 0.50). In adults, there was no difference between autistic adults with and without siblings on both measures, but there was an interaction effect between sex and group on the RMET (f(1732) = 4.10, p = 0.04): whilst autistic males without siblings on average scored lower than females, autistic males with siblings on average performed similarly to females. Future research should investigate the possible effect of siblings on autistic males' empathy performance in a larger cohort of autistic individuals. Children's empathic abilities may be underestimated by their parents when they have siblings due to a contrast effect.