Ubiquitin protein ligase E3A (UBE3A) regulates signaling pathways associated with autism spectrum disorders (ASDs). As an E3 ligase, UBE3A ubiquitinates and promotes the degradation of proteins crucial for regulating synaptic plasticity and learning. Loss-of-function mutations in UBE3A result in Angelman Syndrome, while gain-of-function or duplications contribute to ASDs and Dup15q Syndrome.

Fragile X syndrome (FXS) is the most common inherited intellectual disability, caused by the loss of fragile X mental retardation protein (FMRP), which regulates neuronal signaling and plasticity. FXS patients and Fmr1 knockout (KO) mice exhibit sensory hypersensitivity, hyperarousal, and hippocampus-dependent learning deficits. Dysregulated metabotropic glutamate receptor (mGluR) and muscarinic acetylcholine receptor (mAChR) signaling, along with reduced kainate receptor (KAR) function, have been implicated in FXS pathophysiology. Activation of these signaling pathways induce gamma-frequency network oscillations hippocampal slices in vitro. However, their specific contribution to aberrant gamma oscillations in FXS remains unclear.

Despite high rates of autism spectrum disorder (ASD), understanding of pathophysiology is limited. The RAS-mitogen-activated protein kinase (RAS-MAPK) pathway plays a crucial role in ASD and is altered in children with Noonan syndrome (NS). Children with NS offer a unique model to disentangle genetic and neurological underpinnings of ASD.

Fragile X Syndrome (FXS) is the most prevalent inherited intellectual disability disorder linked to the X chromosome, and currently lacks an approved specific treatment. Preclinical and some clinical studies have suggested metformin may have therapeutic potential for FXS based on its mechanisms related to the disorder's pathophysiology.

Suicide has been reported as a leading cause of premature death in autistic populations. Additionally, risk of suicidality is often found to increase with age in the general population. Despite this, suicidality has seldom been explored in autistic populations in midlife and old age. This study investigates the self-reported prevalence of self-harm and suicidality in autistic people in midlife and old age compared to an age- and gender-ratio comparable non-autistic group.

Camouflaging autistic traits is suggested to increase stress and the risk of autistic burnout. However, the relationship with psychological and biological markers of stress and the influence of familial factors on this relationship remain unclear.

The dearth of tools to quantify and track growth in social communication ability has been a barrier to understanding and monitoring treatment outcomes for neurodevelopmental disorders. We undertook a multi-staged, multisite study to create the Developmental Assessment of Social Communication Ability (DASCA), a new measure explicitly developed as a clinical outcome assessment for monitoring change-both over the course of development and in response to treatment.

Neuronal connectivity is refined throughout development by the proliferation and pruning of axons in cerebral white matter, and progressive axon myelination that enables rapid communication across brain regions. Differences in connectivity have been observed in autism spectrum disorder (ASD), including changes in white matter volume and connectivity. In the prefrontal cortex, this includes imbalances between short- and long-ranging axons, consistent with a pattern of local hyperconnectivity, and long-range hypoconnectivity. Alterations in temporal lobe white matter development-critical for social behavior-may contribute to atypical neural connectivity.

Specific learning disorders (SLDs) affect approximately 5% of school-age children. In France, genetic investigations of complex non-syndromic SLD cases include chromosomal microarray analysis and fragile X syndrome testing. However, the examples of genes being described in intellectual disability or autism spectrum disorder and also reported in patients with complex and severe SLDs are multiplying. International efforts using exome sequencing have identified monogenic diseases that explain severe SLDs in some instances. The aim of our study was to investigate the value of exome sequencing in children with SLDs without intellectual disability and autism spectrum disorder.

Difficulties with non-verbal communication, including atypical use of facial expressions, are a core feature of autism. Quantifying atypical use of facial expressions during naturalistic social interactions in a reliable, objective, and direct manner is difficult, but potentially possible with facial analysis computer vision algorithms that identify facial expressions in video recordings.

Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are neurodevelopmental conditions caused by genetic variants leading to upregulated signaling in the RAS-MAPK pathway. While previous research has focused on genetic variability in cognitive and cardiac phenotypes, behavioral phenotypes, and their correlations across genetic variants and within the PTPN11 gene remain poorly characterized.

Fragile X syndrome (FXS) is characterized by cortical hyperexcitability, a core neurophysiological feature that contributes to sensory hypersensitivity, cognitive dysfunction, and other disabling symptoms. This disruption in excitatory-inhibitory balance is a key pharmacological target, yet reliable biomarkers to quantify it noninvasively remain limited. Spectral slope, derived from the aperiodic component of the EEG power spectrum, has emerged as a potential index of cortical excitability. Here, we evaluated spectral slope and theta-alpha peak frequency in individuals with FXS to assess their utility as candidate neurophysiological biomarkers.

Structural alterations in subcortical brain regions-including the amygdala, hippocampus, basal ganglia, and cerebral ventricles-have been linked to various clinical features of autism spectrum disorder (ASD). However, volumetric features among these regions in autistic individuals across the lifespan remain poorly understood. This cross-sectional study aimed to investigate age-associated volumetric deviations in these clinically implicated subcortical regions of autistic individuals and neurotypical controls, and to examine the structural interrelationships within each group.

Autistic individuals generally exhibit real-world executive function (EF) difficulties and perform poorly on EF tasks. However, while autistic traits are distributed continuously throughout the general population, the relationships between autistic traits and EF among nonclinical individuals remain unclear. Here, we conducted complementary meta-analyses to clarify the relationships between autistic traits and various aspects of EF in the general population.

When faced with many options to choose from, humans typically need to explore the utility of new choice options. People with an autism diagnosis or elevated autism traits are thought to avoid exploring such unknown options, but it remains unclear how autism affects exploration in decision spaces with many options.

Sensory processing requires selectivity to salient sensory input. Many autistic individuals report different sensory processing, which has been associated with altered sensory selectivity. The locus-coeruleus norepinephrine (LC-NE) system modulates the neuronal gain of sensory input, which represents a neurophysiological mechanism of sensory selectivity. In autistic individuals, we hypothesized that LC-NE tonic upregulation reduces sensory selectivity and underlies different sensory processing.

Difficulty in social inferences is a core feature in autism spectrum disorders (ASD). On the behavioral level, it remains unclear whether reasoning about others' mental states (Theory of Mind, ToM) and empathic responses to others' physical states may be similarly or differentially affected in autism. On the neural level, these inferences typically engage distinct brain networks (ToM versus Pain networks), but their functional specialization remains not well understood in autism. This study aimed to investigate the functional specialization, heterogeneity, and brain-behavior relationships of the ToM and Pain networks in autistic compared to neurotypical (NT) participants. We hypothesized differential functional network specialization (i.e., functional connectivity), increased heterogeneity, and less typical network responses specifically in the ToM network, with relatively similar responses in the Pain network in ASD.

Angelman Syndrome (AS) is a severe neurodevelopmental disorder with only symptomatic treatment currently available. The primary cause of AS is loss of functional UBE3A protein. This can be caused by deletions in the maternal 15q11-q13 region, maternal AS-imprinting center defects (mICD), paternal uniparental disomy of chromosome 15 (UPD) or mutations within the UBE3A gene. Current mouse models are Ube3a-centric and do not address expression changes of other genes in the 15q11-q13 locus on the pathophysiology of AS. This limits the ability to discern differences in therapeutic responses to current UBE3A-targeting strategies and hampers the identification of novel therapeutics/co-therapeutics.

Motor challenges are highly prevalent within autism, and increased postural sway has been consistently demonstrated in autistic youth. However, the extent to which sway anomalies extend into adulthood remains understudied. This study aimed to investigate whether increased postural sway is altered in autistic adults compared to neurotypical controls using established sway metrics including sway area and path, as well as rambling-trembling decomposition—an approach that differentiates the postural sway signal into central and peripheral nervous system components.