Pubmed du 16/12/23
1. Barger B. Epidemiology with psychometric spirit: MoBa leads autism’s interdisciplinary future-a commentary on Havdahl et al. (2023). J Child Psychol Psychiatry;2023 (Dec 15)
Havdahl et al.’s (2023) Norwegian Mother, Father and Child Cohort Study (MoBa) skill loss study stands out for their creative consideration of scale items to gain a better understanding of skill loss/regression. This commentary outlines how the MoBa team continues to challenge the field by conducting « basic » measurement analyses with their public health longitudinal population data. Their creative use of items, validity-oriented analyses, and transparent reporting of item correlations emulates early-stage scale development in psychometric research, and sets the stage for considering how psychometricians and epidemiologists might more directly work with each other to improve early autism identification research.
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2. Ellul P, Maruani A, Peyre H, Vantalon V, Hoareau D, Tiercelin H, Rosenzwajg M, Klatzmann D, Delorme R. Abnormal neutrophil-to-lymphocyte ratio in children with autism spectrum disorder and history of maternal immune activation. Sci Rep;2023 (Dec 16);13(1):22424.
Maternal immune activation (MIA), related to autoimmune/inflammatory diseases or acute infections, during the two first trimesters of pregnancy is a risk factor for autism spectrum disorders (ASD) in offspring. In mice, MIA has a long-term impact on offspring’s immune equilibrium resulting in a pro-inflammatory phenotype. We therefore hypothesized that children with ASD and a history of MIA could display a similar phenotype specifically assessed by a higher neutrophil to lymphocyte ratio (NLR). In this study, we used a retrospective sample of 231 dyads involving children with ASD and their mothers. Among ASD patients, 12% had a history of MIA. The multivariate analysis revealed a significant association between NLR in children with ASD and maternal history of MIA (F = 2.27, p = 0.03). Using a categorical approach, we observed an abnormal NLR (over 3) in 7.4% of children with ASD MIA+ compared to 1.9% for MIA-. Our study supports the hypothesis suggesting an impact of MIA on the risk of ASD. Further studies could contribute to the development of biomarkers in MIA+ ASD and enable the development of targeted immunomodulatory therapies.
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3. Erickson CA, Shaffer RC, Will M, Schmitt LM, Horn P, Hirst K, Pedapati EV, Ober N, Tumuluru RV, Handen BL, Beversdorf DQ. Brief Report: A Double-Blind, Placebo-Controlled, Crossover, Proof-of-Concept Study of Minocycline in Autism Spectrum Disorder. J Autism Dev Disord;2023 (Dec 15)
Neuroinflammatory mechanisms have been implicated in the pathophysiology of autism spectrum disorder (ASD). Minocycline is a matrix metalloproteinase inhibitor 9 (MMP9) inhibitor tetracycline antibiotic with known anti-inflammatory properties. In preclinical animal models of ASD, minocycline has demonstrated potential positive effects on phenotypes that may have relevance to ASD. We conducted the first placebo-controlled study of minocycline in ASD. This double-blind, placebo-controlled crossover trial employed four week treatment periods with a two week washout period. Twenty-four 12-22 year olds (mean age 17.4 years; range 12.9-22.5 years) with ASD were enrolled. Overall minocycline was well tolerated. No minocycline-associated clinical changes were noted with treatment on any performance or clinician or caregiver completed measures were noted. We hypothesize that either minocycline does not have potential therapeutic effects in ASD or our project was underpowered to define potential subject subgroups who may potentially respond positively to this drug.
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4. Green J. Debate: Responses to commentaries – neurodiversity, autism and healthcare. Child Adolesc Ment Health;2023 (Dec 16)
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5. Guo Y, Li J, Xie W, Huang H, Li JJ, Lin W, Lu YQ. Generation of an integration-free induced pluripotent stem cell line, FJMUUHi002-A, from a Rett syndrome patient with a heterozygous mutation p. R133C in MeCP2. Stem Cell Res;2023 (Dec 1);74:103268.
The human iPS cell line, hiPS-RTT (FJMUi002-A), is derived from peripheral blood mononuclear cells (PBMCs) from a 12-year-old female RTT patient carrying a heterozygous p. R133C (c.397C > T) mutation in the MeCP2 gene. The hiPS-RTT cell line was generated by non-integrative reprogramming vectors encoding OCT3/4, SOX2, KLF4, and c-MYC and was free of genomically integrated reprogramming genes. The hiPS-RTT cell line had a normal karyotype, expressed pluripotency markers, and had capacity to form three germ layers in vitro and in vivo, which offering a useful resource to study the pathogenesis and treatment strategies of RTT.
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6. Iannuccelli M, Vitriolo A, Licata L, Lo Surdo P, Contino S, Cheroni C, Capocefalo D, Castagnoli L, Testa G, Cesareni G, Perfetto L. Curation of causal interactions mediated by genes associated with autism accelerates the understanding of gene-phenotype relationships underlying neurodevelopmental disorders. Mol Psychiatry;2023 (Dec 15)
Autism spectrum disorder (ASD) comprises a large group of neurodevelopmental conditions featuring, over a wide range of severity and combinations, a core set of manifestations (restricted sociality, stereotyped behavior and language impairment) alongside various comorbidities. Common and rare variants in several hundreds of genes and regulatory regions have been implicated in the molecular pathogenesis of ASD along a range of causation evidence strength. Despite significant progress in elucidating the impact of few paradigmatic individual loci, such sheer complexity in the genetic architecture underlying ASD as a whole has hampered the identification of convergent actionable hubs hypothesized to relay between the vastness of risk alleles and the core phenotypes. In turn this has limited the development of strategies that can revert or ameliorate this condition, calling for a systems-level approach to probe the cross-talk of cooperating genes in terms of causal interaction networks in order to make convergences experimentally tractable and reveal their clinical actionability. As a first step in this direction, we have captured from the scientific literature information on the causal links between the genes whose variants have been associated with ASD and the whole human proteome. This information has been annotated in a computer readable format in the SIGNOR database and is made freely available in the resource website. To link this information to cell functions and phenotypes, we have developed graph algorithms that estimate the functional distance of any protein in the SIGNOR causal interactome to phenotypes and pathways. The main novelty of our approach resides in the possibility to explore the mechanistic links connecting the suggested gene-phenotype relations.
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7. Szabó J, Mlynár M, Feješ A, Renczés E, Borbélyová V, Ostatníková D, Celec P. Intranasal oxytocin in a genetic animal model of autism. Mol Psychiatry;2023 (Dec 15)
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly characterized by deficient sociability and repetitive behaviors. Effective treatment for the core symptoms of ASD is still lacking. Behavioral interventions show limited effectiveness, while pharmacotherapy focuses on the amelioration of secondary symptomatology. Oxytocin (OXT) is a neuropeptide known for its prosocial impact, making it a candidate drug for ASD treatment. Its alleviating effect has been and still is widely researched, but outcomes reported by clinical studies are ambiguous. We examined the effect of daily intranasal OXT (0.8 IU/kg) administration for 4 weeks on the ASD-like phenotype in Shank3(-/-) adult mice. Animals treated with OXT spent twice as much time interacting with the social partner as early as after 2 weeks of treatment. Furthermore, OXT-treated mice exhibited reduced explorative behavior by 50%, after 4 weeks of treatment, and a 30% reduction in repetitive behavior, 4 weeks after treatment termination. One-fold higher sociability and 30% reduced exploration due to OXT lasted up to 4 weeks following the treatment termination. However, social disinterest was elevated by roughly 10% as well, indicating a form of social ambivalence. Obtained results support the therapeutic potential of intranasally administered OXT in alleviating social shortfalls in a genetic model of ASD. Subsequent research is necessary to elucidate the benefits and risks of the long-term OXT administration, as well as its applicability in other ASD models and the potential treatment effect on social communication, which was not measured in the present study.
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8. Szlamka Z, Ahmed I, Genovesi E, Kinfe M, Hoekstra RA, Hanlon C. Conceptualising the empowerment of caregivers raising children with developmental disabilities in Ethiopia: a qualitative study. BMC Health Serv Res;2023 (Dec 15);23(1):1420.
BACKGROUND: Caregivers of children with developmental disabilities (DDs) in Ethiopia experience stigma and exclusion. Due to limited existing services and substantial barriers to accessing care, they often lack support. Caregiver empowerment could help address injustices that hinder their capacity to support their child as they would like. The aim of this study was to explore the meaning and potential role of empowerment for caregivers raising a child with a DD and how empowerment was situated in relation to other priorities in service development. METHODS: This was a qualitative phenomenological study. Semi-structured interviews were conducted in Amharic and English with caregivers of children with a DD (n = 15), clinicians (n = 11), community-based health extension workers (n = 5), representatives of non-governmental organisations working with families with DDs (n = 17), and representatives of local authorities in health, education, and social care (n = 15). Data were analysed thematically. RESULTS: Three main themes were developed: « Barriers to exercising caregivers’ agency »; « Whose decision is it to initiate empowerment? »; and « Supporting caregivers through support groups ». Caregiver capacity to do what they thought was best for their child was undermined by poverty, a sense of hopelessness, experience of domestic abuse and multiple burdens experienced by those who were single mothers. Caregivers were nonetheless active in seeking to bring about change for their children. Caregivers and professionals considered support groups to be instrumental in facilitating empowerment. Participants reflected that caregiver-focused interventions could contribute to increasing caregivers’ capacity to exercise their agency. A tension existed between a focus on individualistic notions of empowerment from some professionals compared to a focus on recognising expertise by experience identified as vital by caregivers. Power dynamics in the context of external funding of empowerment programmes could paradoxically disempower. CONCLUSION: Caregivers of children with DDs in Ethiopia are disempowered through poverty, stigma, and poor access to information and resources. Shifting power to caregivers and increasing their access to opportunities should be done on their own terms and in response to their prioritised needs.
