Pubmed du 13/08/23
1. Annamneedi A, Gora C, Dudas A, Leray X, Bozon V, Crepieux P, Pellissier LP. Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders. Br J Pharmacol;2023 (Aug 13)
Autism spectrum disorders (ASD) are diagnosed in 1/100 children worldwide, based on two core symptoms, deficits in social interaction and communication and stereotyped behaviours. G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors that transduce extracellular signals to convergent intracellular signalling and downstream cellular responses that are commonly dysregulated in ASD. Despite hundreds of GPCRs being expressed in the brain, only 23 are genetically associated with ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR, vasopressin V(1A) , V(1B) , metabotropic glutamate mGlu(5) , mGlu(7) , GABA(B2) , dopamine D(1) , D(2) , D(3) , serotoninergic 5-HT(1B) , β(2) -adrenoceptor, cholinergic M(3) , adenosine A(2A) , A(3) , angiotensin AT(2) , cannabinoid CB(1) , chemokine CX(3) CR1, orphan GPR37, GPR85 and olfactory OR1C1, OR2M4, OR2T10, OR52M1. Here, we review the therapeutic potential of these 23 GPCRs, 5-HT(2A) and 5-HT(7) for ASD. For each GPCR, we discuss its genetic association, genetic and pharmacological manipulation in animal models, pharmacopeia for core symptoms of ASD and rank them based on these factors. Among these GPCRs, we highlight that D(2) , 5-HT(2A) , CB(1) , OTR and V(1A) are the most promising targets for ASD. We discuss that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD. Their therapeutic potential has only begun as multiple GPCRs could mitigate ASD.
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2. Bagnall R, Russell A, Brosnan M, Maras K. Autistic adults’ inclination to lie in everyday situations. Autism;2023 (Aug 12):13623613231183911.
Differences in social communication and understanding others’ mental states may mean that autistic adults are less likely to deceive others than non-autistic individuals. We investigated whether autistic and non-autistic adults differ in their inclination to lie and which psychological factors are involved in the inclination to lie. We found that autistic and non-autistic groups reported a similar inclination to lie, and the extent to which participants viewed lying as acceptable helped to explain their inclination to deceive others. However, the other underlying psychological factors associated with deception inclination differed between autistic and non-autistic groups. Autistic adults’ belief about their ability to lie and also how quickly they could lie helped to explain whether they were more or less inclined to lie. For non-autistic adults, their memory and ability to understand others’ mental states helped to explain their lie inclination. We discuss these findings and recommend areas for future research.
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3. Bilder DA, Worsham W, Sullivan S, Esplin MS, Burghardt P, Fraser A, Bakian AV. Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism. Mol Autism;2023 (Aug 12);14(1):30.
BACKGROUND: Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism. OBJECTIVE: This study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure. STUDY DESIGN: Early second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N = 68) and without (N = 68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure. RESULTS: Increased estradiol was significantly associated with autism only in males (AOR = 1.13 per 100 pg/ml, 95% CI 1.01-1.27, p = 0.036) and only term pregnancies (AOR = 1.17 per 100 pg/ml, 95% CI 1.04-1.32, p = 0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR = 0.65 per 50 nmol/L, 95% CI 0.55-0.78, p < 0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure. LIMITATIONS: The relative racial and ethnic homogeneity of Utah's population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power. CONCLUSION: Both elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester.
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4. Larrington-Spencer H. Accessing health care autistically: a routine nasojejunal tube replacement. Lancet Gastroenterol Hepatol;2023 (Sep);8(9):787-788.
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5. Le Donne I, Attanasio M, Bologna A, Vagnetti R, Masedu F, Valenti M, Mazza M. Autism and intention attribution test: a non-verbal evaluation with comic strips. Ann Gen Psychiatry;2023 (Aug 12);22(1):29.
BACKGROUND: Despite autism spectrum disorder (ASD) and mentalization being two words often associated in the literature, the assessment of this ability in individuals with ASD in the clinical setting is still limited. Indeed, there are no standardized Theory of Mind (ToM) tests that are adaptable to different cognitive profiles, such as individuals with language poverty, and intellectual or memory impairments. This study proposes a non-verbal test (Intentions Attribution-Comic Strip Test; IA-CST) to evaluate the ability to infer the intentions of others, a basic component of ToM, in the clinical setting. METHOD: In Study 1, the test was administered to 261 healthy individuals and we performed structural validation using Exploratory Graph Analysis. In Study 2, the final version of the test was administered to 32 individuals with ASD to assess the known group validity of the measure by comparing their scores with a sample of IQ-matched controls. Moreover, we performed logistic regression and ROC curve to preliminarily assess the diagnostic performance of the IA-CST. RESULTS: The IA-CST resulted in a 3-dimension measure with good structural stability. Group comparison indicated that the ASD group shows significantly lower performance in intention attribution but not in inferring causal consequences. The test demonstrated known group validity and that, preliminarily, it is suitable for implementation within the clinical practice. CONCLUSIONS: The results support the IA-CST as a valid non-verbal task for evaluating intentions attribution in the clinical setting. Difficulties in ToM are early and relevant in ASD, so assessing these aspects is valuable for structuring individualized and evidence-based interventions.
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6. Neufeld J, Maier S, Revers M, Reisert M, Kuja-Halkola R, Tebartz van Elst L, Bölte S. Reduced brain connectivity along the autism spectrum controlled for familial confounding by co-twin design. Sci Rep;2023 (Aug 12);13(1):13124.
Previous studies on brain connectivity correlates of autism have often focused on selective connections and yielded inconsistent results. By applying global fiber tracking and utilizing a within-twin pair design, we aimed to contribute to a more unbiased picture of white matter connectivity in association with clinical autism and autistic traits. Eighty-seven twin pairs (n = 174; 55% monozygotic; 24 with clinical autism) underwent diffusion tensor imaging. Linear regressions assessed within-twin pair associations between structural brain connectivity of anatomically defined brain regions and both clinical autism and autistic traits. These were explicitly adjusted for IQ, other neurodevelopmental/psychiatric conditions and multiple testing, and implicitly for biological sex, age, and all genetic and environmental factors shared by twins. Both clinical autism and autistic traits were associated with reductions in structural connectivity. Twins fulfilling diagnostic criteria for clinical autism had decreased brainstem-cuneus connectivity compared to their co-twins without clinical autism. Further, twins with higher autistic traits had decreased connectivity of the left hippocampus with the left fusiform and parahippocampal areas. These associations were also significant in dizygotic twins alone. Reduced brainstem-cuneus connectivity might point towards alterations in low-level visual processing in clinical autism while higher autistic traits seemed to be more associated with reduced connectivity in networks involving the hippocampus and the fusiform gyrus, crucial especially for processing of faces and other (higher order) visual processing. The observed associations were likely influenced by both genes and environment.
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7. Stancioiu F, Bogdan R, Dumitrescu R. Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD). Life (Basel);2023 (Aug 13);13(8)
Autistic spectrum disease (ASD) is an increasingly common diagnosis nowadays with a prevalence of 1-2% in most countries. Its complex causality-a combination of genetic, immune, metabolic, and environmental factors-is translated into pleiomorphic developmental disorders of various severity, which have two main aspects in common: repetitive, restrictive behaviors and difficulties in social interaction varying from awkward habits and verbalization to a complete lack of interest for the outside world. The wide variety of ASD causes also makes it very difficult to find a common denominator-a disease biomarker and medication-and currently, there is no commonly used diagnostic and therapeutic strategy besides clinical evaluation and psychotherapy. In the CORDUS clinical study, we have administered autologous cord blood to ASD kids who had little or no improvement after other treatments and searched for a biomarker which could help predict the degree of improvement in each patient. We have found that the neuron-specific enolase (NSE) was elevated above the normal clinical range (less than 16.3 ng/mL) in the vast majority of ASD kids tested in our study (40 of 41, or 97.5%). This finding opens up a new direction for diagnostic confirmation, dynamic evaluation, and therapeutic intervention for ASD kids.
