Rudling M, Portugal AM, Bölte S, Falck-Ytter T.

JCPP Adv. 2023 Jan 11;3(1):e12135. doi: 10.1002/jcv2.12135. eCollection 2023 Mar.

ABSTRACT

BACKGROUND: Pragmatic language is key for adaptive communication, but often compromised in neurodevelopmental conditions such as autism spectrum disorder (ASD). Decontextualized language-to talk about events and things beyond here and now-develops early in childhood and can be seen as a pre-pragmatic ability. Little is known about the factors that contribute to decontextualized language use in toddlers and whether these are different from factors contributing to general language development.

METHODS: We studied longitudinal associations between parent-rated core language and non-verbal socio-communicative abilities at 14 months of age, and decontextualized language use at 24 months of age in children with typical and elevated likelihood of ASD (total N = 303). Using twin modelling, we also investigated genetic and environmental contributions on decontextualized language and grammar use in two-year-old twin pairs (total N = 374).

RESULTS: Core language ability was a strong predictor of later decontextualized language use in both children with and without an elevated likelihood of ASD. In contrast, social communication was only a significant predictor of decontextualized language use for children with low levels of core language. This pattern was specific to decontextualized language, and not replicated in prediction of concurrent grammatical ability. Further, there was a large genetic influence on decontextualized language at 2 years of age, which mostly overlapped with the genetic influences on grammatical ability. Shared environment influences were significant for grammatical ability, but not found on decontextualized language. In children with an elevated likelihood of ASD, decontextualized language use was negatively associated with autistic symptoms.

CONCLUSIONS: This study suggests that decontextualized language is developmentally associated with, yet dissociable from, more general language development measured as grammatical ability. Already at 2 years of age, parental ratings of decontextualized language is associated to clinician-rated symptoms of ASD.

PMID:37431312 | PMC:PMC10241459 | DOI:10.1002/jcv2.12135

Lombardi L, Le Clerc S, Wu CL, Bouassida J, Boukouaci W, Sugusabesan S, Richard JR, Lajnef M, Tison M, Le Corvoisier P, Barau C, Banaschewski T, Holt R, Durston S, Persico AM, Oakley B, Loth E, Buitelaar J, Murphy D, Leboyer M, Zagury JF, Tamouza R.

Transl Psychiatry. 2023 Jul 6;13(1):244. doi: 10.1038/s41398-023-02550-y.

ABSTRACT

Autism spectrum disorders (ASD) are neurodevelopmental conditions that are for subsets of individuals, underpinned by dysregulated immune processes, including inflammation, autoimmunity, and dysbiosis. Consequently, the major histocompatibility complex (MHC)-hosted human leukocyte antigen (HLA) has been implicated in ASD risk, although seldom investigated. By utilizing a GWAS performed by the EU-AIMS consortium (LEAP cohort), we compared HLA and MHC genetic variants, single nucleotide polymorphisms (SNP), and haplotypes in ASD individuals, versus typically developing controls. We uncovered six SNPs, namely rs9268528, rs9268542, rs9268556, rs14004, rs9268557, and rs8084 that crossed the Bonferroni threshold, which form the underpinnings of 3 independent genetic pathways/blocks that differentially associate with ASD. Block 1 (rs9268528-G, rs9268542-G, rs9268556-C, and rs14004-A) afforded protection against ASD development, whilst the two remaining blocks, namely rs9268557-T, and rs8084-A, associated with heightened risk. rs8084 and rs14004 mapped to the HLA-DRA gene, whilst the four other SNPs located in the BTNL2 locus. Different combinations amongst BTNL2 SNPs and HLA amino acid variants or classical alleles were found either to afford protection from or contribute to ASD risk, indicating a genetic interplay between BTNL2 and HLA. Interestingly, the detected variants had transcriptional and/or quantitative traits loci implications. As BTNL2 modulates gastrointestinal homeostasis and the identified HLA alleles regulate the gastrointestinal tract in celiac disease, it is proposed that the data on ASD risk may be linked to genetically regulated gut inflammatory processes. These findings might have implications for the prevention and treatment of ASD, via the targeting of gut-related processes.

PMID:37407551 | PMC:PMC10322870 | DOI:10.1038/s41398-023-02550-y

Rolland T, Cliquet F, Anney RJL, Moreau C, Traut N, Mathieu A, Huguet G, Duan J, Warrier V, Portalier S, Dry L, Leblond CS, Douard E, Amsellem F, Malesys S, Maruani A, Toro R, Børglum AD, Grove J, Baron-Cohen S, Packer A, Chung WK, Jacquemont S, Delorme R, Bourgeron T.

Nat Med. 2023 Jun 26. doi: 10.1038/s41591-023-02408-2. Online ahead of print.

ABSTRACT

While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in individuals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 individuals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support individuals carrying these variants.

PMID:37365347 | DOI:10.1038/s41591-023-02408-2