Steroid hormone pathways, vitamin D and autism: a systematic review.

The origins of the male preponderance in autism incidence remain unclear. The idea that perinatal factors associated with sex differentiation (e.g., steroid hormone pathways) may increase the possibility of the emergence of autism is complementary to the hypothesis that female individuals are intrinsically less likely to develop autism. Empirical evidence for the mechanistic roles of in utero steroid hormones in autism etiology is accumulating but inconsistent. We conducted a systematic review using rigorous criteria for the measurements of steroids and vitamin D exposure, to summarize the potential contributing roles of prenatal and early postnatal steroids and vitamin D alterations to the emergence of autism. We searched PubMed, PsychInfo, Scopus, and included 22 studies for qualitative synthesis. Among them, six studies examined the association of autism diagnoses in offspring and levels of steroids and precursor steroid hormones in the fetal environment, eight studies examined the associations between autism and maternal and fetal blood vitamin D levels during pregnancy and at birth, and eight studies examined the associations between offspring autism diagnoses and maternal hyperandrogenemia diagnosed before pregnancy. We identified promising and complex results regarding the relations between steroid metabolism and autism. The interpretation of findings was limited by the mostly observational study designs, insufficient investigation of the effects of offspring sex, confounders and their cumulative effects on the development of the child, and unclear impact of the timing of steroids exposure and their effects on fetal neurodevelopment.

Diagnostic Process for Autism Spectrum Disorder: A Meta-Analysis of Worldwide Clinical Practice Guidelines for the Initial Somatic Assessment.

(1) Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is highly associated with various somatic conditions that can be masked by the core symptoms of ASD and thus complicate the diagnosis. Identifying co-occurring somatic disorders is critical for providing effective healthcare and social services for ASD populations and influences their long-term outcomes. A systematic assessment of co-occurring somatic conditions is essential during this ASD diagnostic process. Therefore, this study aimed to identify the organization and content of the initial somatic assessment (ISA). (2) Methods: We conducted a systematic review of the clinical practice guidelines (CPG) for the ASD diagnostic process published between January 2005 and December 2019 in English and French and performed an appraisal following the Appraisal of Guidelines Research and Evaluation, second edition (AGREE-II). (3) Results: We selected 14 CPGs that were heterogeneous in quality, with methodological scores between 32.3 and 91.9. Clinical examinations are the first step in the ISA, and the participation of pediatric, neuropediatric, and genetic specialists was highly recommended by the majority of the CPGs. The recommendations included hearing screening tests (10/14), visual examinations (8/14), and systematic genetic investigations (4/14). The CPGs also described additional investigations that should be conducted based on numerous warning signs. (4) Conclusions: Screening for consensual international warning signs is necessary to perform a comprehensive and systematic ISA during the ASD diagnostic process. A "referral form" could be used to guide clinicians and improve the coordination process. This tool may reinforce epidemiological data on co-occurring somatic disorders in patients with ASD.

New Technologies as Promising Tools for Assessing Facial Emotion Expressions Impairments in ASD: A Systematic Review.

The ability to recognize and express emotions from facial expressions are essential for successful social interactions. Facial Emotion Recognition (FER) and Facial Emotion Expressions (FEEs), both of which seem to be impaired in Autism Spectrum Disorders (ASD) and contribute to socio-communicative difficulties, participate in the diagnostic criteria for ASD. Only a few studies have focused on FEEs processing and the rare behavioral studies of FEEs in ASD have yielded mixed results. Here, we review studies comparing the production of FEEs between participants with ASD and non-ASD control subjects, with a particular focus on the use of automatic facial expression analysis software. A systematic literature search in accordance with the PRISMA statement identified 20 reports published up to August 2020 concerning the use of new technologies to evaluate both spontaneous and voluntary FEEs in participants with ASD. Overall, the results highlight the importance of considering socio-demographic factors and psychiatric co-morbidities which may explain the previous inconsistent findings, particularly regarding quantitative data on spontaneous facial expressions. There is also reported evidence for an inadequacy of FEEs in individuals with ASD in relation to expected emotion, with a lower quality and coordination of facial muscular movements. Spatial and kinematic approaches to characterizing the synchrony, symmetry and complexity of facial muscle movements thus offer clues to identifying and exploring promising new diagnostic targets. These findings have allowed hypothesizing that there may be mismatches between mental representations and the production of FEEs themselves in ASD. Such considerations are in line with the Facial Feedback Hypothesis deficit in ASD as part of the Broken Mirror Theory, with the results suggesting impairments of neural sensory-motor systems involved in processing emotional information and ensuring embodied representations of emotions, which are the basis of human empathy. In conclusion, new technologies are promising tools for evaluating the production of FEEs in individuals with ASD, and controlled studies involving larger samples of patients and where possible confounding factors are considered, should be conducted in order to better understand and counter the difficulties in global emotional processing in ASD.

Social Anxiety in Children and Adolescents With Autism Spectrum Disorders Contribute to Impairments in Social Communication and Social Motivation.

BACKGROUND: Recognition of symptoms of Social anxiety (SA) may be difficult among individuals with Autism Spectrum Disorders (ASD) because of overlap between social anxiety and autistic symptomatology. The main aim of our study was thus to explore the association between symptoms of social anxiety and clinical characteristics of ASD in order to identify individuals experiencing concomitant ASD and social anxiety disorder. We also described the prevalence of SA in a sample of children and adolescents with ASD. METHOD: 79 children and adolescents with ASD (with and without intellectual disability) and 28-matched control participants were recruited in two French Expert Centers for ASD, coordinated by the Fundation FondaMental. Psychiatric comorbidities, anxiety disorders and depression were screened with standard tools (Liebowitz social anxiety scale, Hamilton Depression and Anxiety Rating Scale) and correlated to autistic features and social skills assessed with the social responsiveness scale 2 (SRS-2) and the repetitive behavior scale (RBS-R). We performed bivariate analysis between the social anxiety level and the scores measured with different clinical scales. We then adjusted the observed relationships with the alterations of SRS-2 and RBS-R scores. RESULTS: After adjustment, the level of social anxiety appeared as significantly associated with alterations in social reciprocity and particularly with the SRS-2 "social communication" and "social motivation" sub-scores, but not with RBS-R score. CONCLUSIONS: We confirm previous reports showing that individuals with ASD are at high risk for specific anxiety disorders. In particular, high levels of impairments in social motivation and social communication (SRS-2) are indicative of comorbid disorders namely, social anxiety and ASD. Our findings clearly inform diagnostic assessment in ASD and stress the need to take comorbid anxiety disorders into consideration to improve treatment of ASD. To further clarify the impact of social anxiety on social competences and socio-adaptive handicap, longitudinal studies and cluster analysis will be needed in the future.