Structure-based developmental toxicity and ASD-phenotypes of bisphenol A analogues in embryonic zebrafish.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has become more prevalent in recent years. Environmental endocrine disruptor bisphenol A (BPA) has been linked to ASD. BPA analogues (BPs) are structure-modified substitutes widely used as safer alternatives in consumer products, yet few studies have explored the developmental neurotoxicity (DNT) of BPA analogues. In the present study, we used the larval zebrafish model to assess the DNT effects of BPA and its analogues. Our results showed that many BPA analogues are more toxic than BPA in the embryonic zebrafish assay regarding teratogenic effect and mortality, which may partially due to differences in lipophilicity and/or different substitutes of structural function groups such as CF3, benzene, or cyclohexane. At sublethal concentrations, zebrafish embryos exposed to BPA or BPs also displayed reduced prosocial behavior in later larval development, evidenced by increased nearest neighbor distance (NND) and the interindividual distance (IID) in shoaling, which appears to be structurally independent. An in-depth analysis of BPA, bisphenol F (BPF), and bisphenol S (BPS) revealed macrocephaly and ASD-like behavioral deficits resulting from exposures to sublethal concentrations of these chemicals. The ASD-like behavioral deficits were characterized by hyperactivity, increased anxiety-like behavior, and decreased social contact. Mechanistically, accelerated neurogenesis that manifested by increased cell proliferation, the proportion of newborn mature neurons, and the number of neural stem cells in proliferation, as well as upregulated genes related to the K+ channels, may have contributed to the observed ASD-like morphological and behavioral alterations. Our findings indicate that BPF and BPS may also pose significant risks to ASD development in humans and highlight the importance of a comprehensive assessment of DNT effects for all BPA analogues in the future.

GABAA Receptors and Maternally Derived Taurine Regulate the Temporal Specification of Progenitors of Excitatory Glutamatergic Neurons in the Mouse Developing Cortex.

Temporal specification of the neural progenitors (NPs) producing excitatory glutamatergic neurons is essential for histogenesis of the cerebral cortex. Neuroepithelial cells, the primary NPs, transit to radial glia (RG). To coincide with the transition, NPs start to differentiate into neurons, undergoing a switch from symmetric to asymmetric cell division. After the onset of neurogenesis, NPs produce layer-specific neurons in a defined order with precise timing. Here, we show that GABAA receptors (GABAARs) and taurine are involved in this regulatory mechanism. Foetal exposure to GABAAR-antagonists suppressed the transition to RG, switch to asymmetric division, and differentiation into upper-layer neurons. Foetal exposure to GABAAR-agonists caused the opposite effects. Mammalian foetuses are dependent on taurine derived from the mothers. GABA and taurine function as endogenous ligands for GABAARs. Ca2+ imaging showed that NPs principally responded to taurine but not GABA before E13. The histological phenotypes of the taurine transporter knockout mice resembled those of the mice foetally exposed to GABAAR-antagonists. Foetal exposure to GABAAR-modulators resulted in considerable alterations in offspring behavior like core symptoms of autism. These results show that taurine regulates the temporal specification of NPs and that disrupting the taurine-receptor interaction possibly leads to neurodevelopmental disorders.

Sensory symptoms associated with autistic traits and anxiety levels in children aged 6-11 years.

BACKGROUND: Autism spectrum conditions (ASC) and quantitative autistic traits (QATs) are associated with sensory symptoms, which may contribute to anxiety and adversely affect social and cognitive development. Although sensory symptoms can occur across all senses, the relative roles of specific sensory modalities as contributors to the autistic phenotype and to anxiety are not well understood. The objective of this study was to examine which sensory symptoms were most predictive of high anxiety. METHODS: We recruited 257 female primary caregivers of children aged 6 to 11 years (49% girls) to a questionnaire study comprising parent-report measures for classical QATs (social, communicative, and rigid), autism-related sensorimotor symptoms (visual, auditory, tactile, olfactory, gustatory, vestibular, proprioceptive, and motor), and anxiety symptoms. First, Bayesian stochastic search variable selection (SSVS) was used to identify the most probable sensorimotor predictors of specific QATs as well as diagnosed ASC. Then, the selected predictors were used in another SSVS, using anxiety symptoms as a dependent variable, to identify which of the autism-relevant sensorimotor symptoms were most robustly predictive of anxiety. Finally, the effect sizes of anxiety-related sensory symptoms were estimated with linear regressions. RESULTS: We found that auditory symptoms and motor difficulties were most predictive of ASC diagnosis. Developmental motor difficulties were also strongly related to all individual QATs, whereas auditory symptoms were more selectively predictive of rigid traits. Tactile symptoms robustly predicted social interaction QATs, and proprioceptive symptoms predicted communicative QATs. Anxiety outcomes were most strongly predicted by difficulties with auditory and olfactory processing. CONCLUSIONS: The results support the clinical importance of being alert to complaints about sounds and hearing in neurodevelopmental populations, and that auditory processing difficulties may be evaluated as an early marker of poor mental health in children with and without diagnosed autism. Olfactory processing differences appeared to be an anxiety marker less strongly associated with ASC or QATs, while motor difficulties were highly autism-relevant but not equally strongly associated with anxiety outcomes. We suggest that future studies may focus on the mechanisms and consequences of neurodevelopmental central auditory processing dysfunction and its potential relationship to anxiety disorders.

Face perception and facial emotional expression recognition ability: Both unique predictors of the broader autism phenotype.

Autism spectrum disorder (ASD) and the broader autistic phenotype (BAP) have been suggested to be associated with perceptual-cognitive difficulties processing human faces. However, the empirical results are mixed, arguably, in part due to inadequate samples and analyses. Consequently, we administered the Cambridge Face Perception Test (CFPT), the Reading the Mind in the Eyes Test (RMET), a vocabulary test, and the Autism Quotient (AQ) to a sample of 318 adults in the general community. Based on a disattenuated path analytic modelling strategy, we found that both face perception ability (ß = -.21) and facial emotional expression recognition ability (ß = -.27) predicted uniquely and significantly the Communication dimension of AQ. Vocabulary failed to yield a significant, direct effect onto the Communication dimension of the AQ. We conclude that difficulties perceiving information from the faces of others may contribute to difficulties in nonverbal communication, as conceptualised and measured within the context of BAP.

Centering the Inner Experience of Autism: Development of the Self-Assessment of Autistic Traits.

Current tools for identifying autism are critiqued for their lack of specificity and sensitivity, especially in autistic people who are older, have higher verbal ability or significant compensatory skills, and are not cisgender boys. This may reflect the following: the historical focus of autism research on White (cisgender) male, upper and middle class children; limited interest in the inner, lived experience of autism; and the predominance of a deficit-based model of autism. We report here on the first attempt of which we are aware to develop a clinical self-report measure of autistic traits as described by autistic people. We believe this is an advance in methodology because prior work in the development of autistic trait/diagnostic measures has prioritized the perspectives of nonautistic clinicians and scientists. The measure was developed under the leadership of two autistic researchers and constructed by leveraging descriptions of autism by autistic people to generate items designed to encompass the range of the autistic experience, using strength-based, accessible language. The team utilized iterative feedback from a panel of autistic experts to refine and enhance the measure, called the Self Assessment of Autistic Traits (SAAT). It is intended for people 16 years or older and uses a format that is designed to increase its accessibility and acceptability for autistic respondents. Future work will report on the preliminary psychometrics of the SAAT, with a long-term goal of advancing our understanding of the inner autistic experience and enhancing the clinical and scientific assessment of autism.

Why is this topic important?: Some people, especially older people, and those who can "mask" their autism, are missed by the current autism assessment tools. This can keep them from getting supports or getting connected to autistic communities. This can harm their well-being and independence. The tools we currently have to assess autism are important, but they were not developed with people who represent the full range of genders, ages, abilities, and cultural identities that characterize autism. Furthermore, current tools emphasize behaviors that other people observe, for example, making eye contact, and do not fully explore the lived or inner experience of autism. What is the purpose of this article?: This article describes the first attempt we know of to begin developing a self-report measure of autistic traits as described by autistic people. What did the authors do?: The authors started by reading what autistic people had to say about autism. They used those readings to come up with initial ideas about autistic experience. Then they used those ideas to write questions for a questionnaire about autistic traits. They asked autistic experts to review the questionnaire and made changes based on what they said. How did the authors work together?: This project was led by two autistic researchers who worked with a team of nonautistic researchers experienced in different research methods. A panel of autistic experts, including both autistic scientist and community leaders, also provided important input. Some of those methods were community-based research, Delphi panels, cognitive interviewing, and measure development. The research team made decisions together. The autistic researchers made the final decisions if there was disagreement. What did they produce?: They produced a preliminary version of the Self Assessment of Autistic Traits (SAAT). The SAAT is a questionnaire that asks if a person has common autistic experiences and traits. It has 58 items that are written with the aim of being respectful and using accessible language. The questionnaire is designed to work with common autistic thinking styles. How will this help autistic adults now or in the future?: The long-term goal is to create a reliable and valid self-report questionnaire that people 16 years old and older can complete to measure their autistic traits. We believe that this could be an important tool for advancing our understanding of the inner autistic experience of autism. This could improve how we assess autistic adults and how we research and think about autism.

Should I trust you? Autistic traits predict reduced appearance-based trust decisions.

Facial impressions of trustworthiness guide social decisions in the general population, as shown by financial lending in economic Trust Games. As an exception, autistic boys fail to use facial impressions to guide trust decisions, despite forming typical facial trustworthiness impressions (Autism, 19, 2015a, 1002). Here, we tested whether this dissociation between forming and using facial impressions of trustworthiness extends to neurotypical men with high levels of autistic traits. Forty-six Caucasian men completed a multi-turn Trust Game, a facial trustworthiness impressions task, the Autism-Spectrum Quotient, and two Theory of Mind tasks. As hypothesized, participants' levels of autistic traits had no observed effect on the impressions formed, but negatively predicted the use of those impressions in trust decisions. Thus, the dissociation between forming and using facial impressions of trustworthiness extends to the broader autism phenotype. More broadly, our results identify autistic traits as an important source of individual variation in the use of facial impressions to guide behaviour. Interestingly, failure to use these impressions could potentially represent rational behaviour, given their limited validity.

An atypical autistic phenotype associated with a 2q13 microdeletion: a case report.

BACKGROUND: Autism spectrum disorders are serious neurodevelopmental disorders that affect approximately 1% of the population. These disorders are substantially influenced by genetics. Several recent linkage analyses have examined copy number variations associated with autism risk. Microdeletion of the 2q13 region is considered a pathogenic copy number variation. This microdeletion is involved in developmental delays, congenital heart defects, dysmorphism, and various psychiatric disorders, including autism spectrum disorders. There are only 34 reported cases with this chromosomal deletion, and five cases of autism spectrum disorders have been identified among them. The autistic phenotype associated with this microdeletion has never been described. CASE PRESENTATION: We describe the case of a 44-month-old Caucasian girl with the 2q13 microdeletion and autism spectrum disorders with global development delay but no associated organ anomalies. We examined the autistic phenotype using different workups and observed an atypical phenotype defined by relatively preserved relational competency and imitation abilities. CONCLUSIONS: The main contribution of this case report is the precise description of the autistic phenotype in the case of this deletion. We observed some atypical clinical features that could be markers of this genetic anomaly. We have discussed the pathophysiology of autism associated with this microdeletion and its incomplete penetrance and variable expressivity.

Over-Selectivity is Related to Autism Quotient and Empathizing, But not to Systematizing.

The relationships of autism quotient (AQ), systematizing (SQ), and empathizing (EQ), with over-selectivity were explored to assess whether over-selectivity is implicated in complex social skills, which has been assumed, but not experimentally examined. Eighty participants (aged 18-60) were trained on a simultaneous discrimination task (AB+CD-), and tested in extinction on the degree to which they had learned about both elements of the reinforced (AB) compound. Higher AQ and lower EQ scorers demonstrated greater over-selectivity, but there was no relationship between SQ and over-selectivity. These results imply that high AQ scorers perform similarly to individuals with ASD on this cognitive task, and that over-selectivity may be related to some complex social skills, like empathy.

Sex-Related Cognitive Profile in Autism Spectrum Disorders Diagnosed Late in Life: Implications for the Female Autistic Phenotype.

Females with high-functioning ASD are known to camouflage their autistic symptoms better than their male counterparts, making them prone to being under-ascertained and delayed in diagnostic assessment. Thus far the underlying cognitive processes that enable such successful socio-communicative adaptation are not well understood. The current results show sex-related differences in the cognitive profile of ASD individuals, which were diagnosed late in life exclusively. Higher verbal abilities were found in males (n = 69) as opposed to higher processing speed and better executive functions in females with ASD (n = 38). Since both sexes remained unidentified during childhood and adolescence, these results are suggestive for sex-distinctive cognitive strategies as an alternative to typically-developed reciprocal social behavior and social mimicry in high functioning ASD.

Reduced accuracy and sensitivity in the perception of emotional facial expressions in individuals with high autism spectrum traits.

Autism spectrum disorder (ASD) is among other things characterized by specific impairments in emotion processing. It is not clear, however, to what extent the typical decline in affective functioning is related to the specific autistic traits. We employed The Autism Spectrum-Quotient (AQ) to quantify autistic traits in a group of 500 healthy individuals and investigate whether we could detect similar difficulties in the perception of emotional expressions in a broader autistic phenotype. The group with high AQ score was less accurate and needed higher emotional content to recognize emotions of anger, disgust, and sadness. Our findings demonstrate a selective impairment in identification of emotional facial expressions in healthy individuals that is primarily related to the extent of autistic traits.