1. Chen YB, Lin HY, Wang LJ, Hung KC, Brunoni AR, Chou PH, Tseng PT, Liang CS, Tu YK, Lin PY, Carvalho AF, Hsu CW, Ni HC. A network meta-analysis of non-invasive brain stimulation interventions for autism spectrum disorder: evidence from randomized controlled trials. Neurosci Biobehav Rev. 2024: 105807.

The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95% confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3+ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = -1.40, 95%CIs = -2.67 to -0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.

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2. Herrera ML, Paraíso-Luna J, Bustos-Martínez I, Barco Á. Targeting epigenetic dysregulation in autism spectrum disorders. Trends Mol Med. 2024.

Autism spectrum disorders (ASD) comprise a range of neurodevelopmental pathologies characterized by deficits in social interaction and repetitive behaviors, collectively affecting almost 1% of the worldwide population. Deciphering the etiology of ASD has proven challenging due to the intricate interplay of genetic and environmental factors and the variety of molecular pathways affected. Epigenomic alterations have emerged as key players in ASD etiology. Their research has led to the identification of biomarkers for diagnosis and pinpointed specific gene targets for therapeutic interventions. This review examines the role of epigenetic alterations, resulting from both genetic and environmental influences, as a central causative factor in ASD, delving into its contribution to pathogenesis and treatment strategies.

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3. Salabura C, Sourty A, Bat-Pitault F, Regnery K, Mayen S, Colson S. [Pain assessment for children and adolescents with autism spectrum disorders (ASD): A systematic review]. Encephale. 2024.

OBJECTIVE: Pain in children and adolescents with autism spectrum disorders remains underdiagnosed due to their inherent communication difficulties. The goal of this review is to identify the most suitable methods for assessing pain in this population and for evaluating the specific perceptions of, or behavioural reactions to, pain whilst considering disorder severity and specifiers (with or without accompanying intellectual impairment, with or without accompanying language impairment). METHOD: A systematic review and analysis of the international literature was conducted. RESULTS: Fourteen studies were selected. No difference was found in pain-related behaviours based on the age or gender of children or adolescents with autism. Three studies showed pain-related behaviours in autism spectrum disorders to be similar to control groups. Other studies showed specific behavioural responses in autism spectrum disorders with a longer physiological and behavioural recovery time associated with an episode of acute pain in this population. Similarly, the three studies that focused on sensory perceptions of pain all showed differences in the autism spectrum disorders population compared to control groups. In hospital or daily life contexts, studies essentially showed idiosyncratic expressions, hypervigilance, motor agitation, negative emotional reactions, or vocalizations. Regarding the association of autism severity with hyposensitivity to pain, the results remain unclear even when language disorders or intellectual disabilities are also present (in conjunction with autism). The Non-Communicative Children Pain Checklist and its translation into French and Italian showed good internal validity and was used by almost half of the studies in hetero-assessment, mostly by parents. Studies recommend the inclusion of parents in the assessment in order to optimise the evaluation process. Similarly, analysis of parent/child/caregiver interviews from the studies highlights the importance of personalizing pain assessment of children and adolescents, taking into account subject-specific characteristics, pathology, and context. CONCLUSION: An integrative and personalized approach to pain assessment appears to be the most appropriate for enhancing the understanding and detection of pain in individuals with autism spectrum disorders. This approach aligns well with a care setting where a nominated professional with a good expertise in autism is responsible for pain assessment. Given the complexity of identifying pain in individuals with autism, further qualitative studies, in conjunction with new pain exploration technologies, are considered necessary as well as a more extensive categorization of the population studies.

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4. Scarpitti MR, Pastore B, Tang W, Kearse MG. Characterization of ribosome stalling and no-go mRNA decay stimulated by the Fragile X protein, FMRP. J Biol Chem. 2024: 107540.

Loss of functional fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS) and is the leading monogenic cause of autism spectrum disorders and intellectual disability. FMRP is most notably a translational repressor and is thought to inhibit translation elongation by stalling ribosomes as FMRP-bound polyribosomes from brain tissue are resistant to puromycin and nuclease treatment. Here, we present data showing that the C-terminal non-canonical RNA-binding domain of FMRP is essential and sufficient to induce puromycin-resistant mRNA•ribosome complexes. Given that stalled ribosomes can stimulate ribosome collisions and no-go mRNA decay (NGD), we tested the ability of FMRP to drive NGD of its target transcripts in neuroblastoma cells. Indeed, FMRP and ribosomal proteins, but not poly(A)-binding protein, were enriched in isolated nuclease-resistant disomes compared to controls. Using siRNA knockdown and RNA-seq, we identified 16 putative FMRP-mediated NGD substrates, many of which encode proteins involved in neuronal development and function. Increased mRNA stability of 4 putative substrates was also observed when either FMRP was depleted or NGD was prevented via RNAi. Taken together, these data support that FMRP stalls ribosomes but only stimulates NGD of a small select set of transcripts, revealing a minor role of FMRP that would be misregulated in FXS.

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5. Schembri E, Jouve E, Poinso F, Encely L, Viellard M, Fernandez A, Guivarch J. Evaluation of a medically coordinated care program in the management of autism. Encephale. 2024.

Autism spectrum disorders (ASD) are neurodevelopmental disorders of varying intensity and disability. The reference health strategy in France for the care of young children with autism is day care hospital (DCH). As the number of places in DCH is insufficient, medically coordinated care programs by the mental health consultation centers (MHCC) are being developed in response. OBJECTIVES: Our objective is to evaluate the effectiveness of a medically coordinated care program in a MHCC versus the care in DCH of child psychiatry. METHODS: Non-inferiority retrospective study comparing the evolution after one year of care of 20 ASD children divided into two groups DCH and MHCC. In the DCH ASD group, the child is taken care of two half-days a week in a day hospital with individual educational care. In the MHCC ASD group, the child benefits from a medically coordinated care program. The medical care is reinforced by more frequent and longer consultations with guidance offered to parents. In both groups, the child receives speech therapy and psychomotor therapy in private practice at the same rate. Comparison is made using a composite criterion associating CARS-2 and VABS-II. Non-inferiority of the medically coordinated care program in autism in reference to DCH was tested on the difference between the changes (DCH group variation – MHCC group variation) with a non-inferiority threshold of 10% of the initial value of each score. RESULTS: We observed a reduction in autism severity at the CARS-2 and a moderate improvement in socio-adaptive behavior at the VABS-II in both groups. This trend was even more pronounced in the MHCC group than in the DCH group, but only the greater reduction in CARS-2 severity in the MHCC was statistically significant. CONCLUSIONS: As it is necessary to integrate the two scales into the composite criterion, it is not possible to retain the non-inferiority of the MHCC with care program. However, both those children followed in DCH and those in the MHCC care program progress. This shows the relevance of the care offered at the MHCC for children suffering from ASD, in the context of a growing lack of space in DCH. The continuation of this research work through multicenter studies with larger numbers could demonstrate the non-inferiority of coordinated care programs in the MHCC versus DCH. It would also allow subgroups to be set up, taking into account the initial characteristics of the children in order to have more precise indications concerning the relevance of each treatment.

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6. Sivayokan B, King C, Mali I, Payne M, Strating H, Warnes E, Bossmann SH, Plakke B. Aerobic Exercise Improves Cognitive Flexibility and Modulates Regional Volume Changes in a Rat Model of Autism. Behav Brain Res. 2024: 115136.

Gestational exposure to valproic acid (VPA) is a risk factor for autism spectrum disorder (ASD). Rodents exposed to VPA in utero display common features of ASD, including volumetric dysregulation in higher-order cognitive regions like the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus. Exercise has been shown in elderly populations to boost cognition and to buffer against brain volume losses with age. This study employed an adolescent treadmill exercise intervention to facilitate cognitive flexibility and regional brain volume regulation in rats exposed to VPA during gestation. It was found that exercise improved performance on extra-dimensional shifts of attention on a set-shifting task, which is indicative of improved cognitive flexibility. Exercise decreased frontal cortex volume in females, whereas in males exercise increased the ventral hippocampus. These findings suggest that aerobic exercise may be an effective intervention to counteract the altered development of prefrontal and hippocampal regions often observed in ASD.

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