The current report supports a role for CD38 in conferring risk for ASD. Notably, our study shows that this gene is not only associated with low functioning ASD but that CD38 expression is markedly reduced in LBC derived from ASD subjects compared to "unaffected" parents, strengthening the connection between oxytocin and ASD.

No abstract

Recent work has led to the identification of several susceptibility genes for autism spectrum disorder (ASD) and an increased appreciation of the importance of rare and de novo mutations. Some of the mutations may be very hard to detect using current strategies, especially if they are located in regulatory regions. We present a new approach to identify functional mutations that exploit the fact that many rare mutations disrupt the expression of genes from a single parental chromosome. The method incorporates measurement of the relative expression of the two copies of a gene across the genome using single nucleotide polymorphism arrays. Allelic expression has been successfully used to study common regulatory polymorphisms; however, it has not been implemented as a screening tool for rare mutation. We tested the potential of this approach by screening for monoallelic expression in lymphoblastoid cell lines derived from a small ASD cohort. After filtering regions shared across multiple samples, we identified genes showing monoallelic expression in specific ASD samples. Validation by quantitative sequencing demonstrated that the genes (or only part of them) are monoallelic expressed. The genes included both previously suspected risk factors for ASD and novel candidates. In one gene, named autism susceptibility candidate 2 (AUTS2), we identified a rare duplication that is likely to be the cause of monoallelic expression. Our results demonstrate the ability to identify rare regulatory mutations using genome-wide allelic expression screens, capabilities that could be expanded to other diseases, especially those with suspected involvement of rare dominantly acting mutations.

Deficits in social behavior in mice lacking the CD38 gene have been attributed to impaired secretion of oxytocin. In humans, similar deficits in social behavior are associated with autistic spectrum disorder (ASD), for which genetic variants of CD38 have been pinpointed as provisional risk factors. We sought to explore, in an in vitro model, the feasibility of the theory that restoring the level of CD38 in ASD patients could be of potential clinical benefit. CD38 transcription is highly sensitive to several cytokines and vitamins. One of these, all-trans retinoic acid (ATRA), a known inducer of CD38, was added during cell culture and tested on a large sample of N = 120 lymphoblastoid cell (LBC) lines from ASD patients and their parents. Analysis of CD38 mRNA levels shows that ATRA has an upmodulatory potential on LBC derived from ASD patients as well as from their parents. The next crucial issue addressed in our study was the relationship between levels of CD38 expression and psychological parameters. The results obtained indicate a positive correlation between CD38 expression levels and patient scores on the Vineland Adaptive Behavior Scale. In addition, analysis of the role of genetic polymorphisms in the dynamics of the molecule revealed that the genotype of a single-nucleotide polymorphism (rs6449182; C>G variation) in the CpG island of intron 1, harboring the retinoic-acid response element, exerts differential roles in CD38 expression in ASD and in parental LBC. In conclusion, our results provide an empirical basis for the development of a pharmacological ASD treatment strategy based on retinoids.

Objective To examine trajectories of psychological distress in mothers of children born very preterm (VPT, <30 weeks gestation) and full term from 2 to 13 years after the birth, and examine predictors of maternal psychological distress over time within the VPT group. Methods Mothers of children born VPT (n = 159) and full term (n = 71) completed questionnaires assessing their psychological distress when their child was 2, 7, and 13 years of age. Mixed models were used to examine differences between groups in maternal psychological distress over time. Family social risk, child neonatal medial risk, child sex, multiple pregnancy, and child’s neurodevelopmental impairment in early childhood were examined as potential predictors of maternal psychological distress within the VPT group. Results Mothers of children born VPT displayed elevated psychological distress compared with mothers of full-term children, and this difference was consistent over time. Higher family social risk was associated with elevated maternal psychological distress throughout childhood across all time-points. There was evidence that mothers of children at higher neonatal medical risk displayed increasing psychological distress over time. Conclusions Mothers of children born VPT show prolonged psychological distress. Mothers from socially disadvantaged background and those whose child has neonatal medical complications may require extensive support to prevent prolonged psychological distress and promote optimal outcomes for children and families.

The current study aimed to investigate the Autism Diagnostic Interview-Revised (ADI-R) algorithms for toddlers and young preschoolers (Kim and Lord, J Autism Dev Disord 42(1):82–93, 2012) in a non-US sample from ten sites in nine countries (n = 1,104). The construct validity indicated a good fit of the algorithms. The diagnostic validity was lower, with satisfactorily high specificities but moderate sensitivities. Young children with clinical ASD and lower language ability were largely in the mild-to-moderate or moderate-to-severe concern ranges of the ADI-R, nearly half of the older and phrase speech ASD-group fell into the little-to-no concern range. Although broadly the findings support the toddler algorithms, further work is required to understand why they might have different properties in different samples to further inform research and clinical use.

No abstract

Stability and change in early autism spectrum disorder risk were examined in a cohort of 99 preterm infants (⩽34 weeks of gestation) using the Autism Observation Scale for Infants at 8 and 12 months and the Autism Diagnostic Observation Schedule-Toddler Module at 18 months. A total of 21 infants were identified at risk by the Autism Observation Scale for Infants at 8 months, and 9 were identified at risk at 12 months, including 4 children who were not previously identified. At 18 months, eight children were identified at risk for autism spectrum disorder using the Autism Diagnostic Observation Schedule-Toddler Module, only half of whom had been identified using the original Autism Observation Scale for Infants cutoffs. Results are discussed in relation to early trajectories of autism spectrum disorder risk among preterm infants as well as identifying social-communication deficiencies associated with the early preterm behavioral phenotype.