Tag: Autism

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Orexin receptor antagonists for sleep disturbance in attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review

BackgroundSleep disturbance is among the commonest and most impairing comorbidities of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Melatonin has the strongest evidence base, but its action is chronobiotic, its maintenance effect inconsistent, and adult evidence sparse. Orexin receptor antagonists reduce wake drive rather than induce sedation, a mechanistically distinct alternative.MethodsReported in accordance with PRISMA 2020. PubMed, Europe PMC, OpenAlex and ClinicalTrials.gov were searched on 23 September 2026 using three complementary concept searches with backward citation tracking; Embase and PsycINFO were not searched. Screening applied a mechanical rule, and every candidate was assessed at full text by two independent reviewers. Eligible reports described a person with diagnosed ADHD or ASD given an orexin receptor antagonist, with a sleep, behavioural, cognitive or safety outcome. Risk of bias was appraised at domain level and certainty against the GRADE domains without categorical ratings. Pooling was precluded by heterogeneity and by the absence of comparable controlled effect estimates.ResultsEight reports representing seven patient groups described 41 exposed participants, 25 with ADHD and 16 with ASD. No completed trial provides peer-reviewed or registry-posted diagnosis-specific outcomes. The strongest signal is a one-month open-label study of daridorexant 50 mg in 24 adults with ADHD and insomnia, where median insomnia severity fell from 16 to 8 and actigraphic total sleep time rose by about 24 minutes, both surviving correction, and 62.5% responded; no cognitive outcome survived correction, one worsened, and the favourable attention results required excluding sleep non-responders. In ASD the evidence is case reports and small series confounded by co-medication, the only comparison-group report being null. No report provides ADHD-stratified paediatric outcomes. Of two registered trials one is recruiting and one completed, the latter’s sponsor releasing top-line data without diagnosis-stratified outcomes.ConclusionOrexin receptor antagonism is a mechanistically coherent approach to sleep disturbance in ADHD and ASD, but no appraisable, diagnosis-specific controlled evidence supports its use, and the evidence is too sparse and biased for causal inference. The signal that sleep gains may accompany attention gains requires a randomised test. Routine use cannot be recommended, and off-label prescribing requires individualised specialist assessment.
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“Like a never-ending performance of myself”: trans autistic experiences of identity, camouflaging and the complex closet

IntroductionBoth camouflaging and closeting one self conceal identity traits that are deemed undesirable or reprehensible by society at large. They serve as a mean of survival in a world that discriminates against autistic and trans people, but frequently lead to exhaustion and disconnect. This study aims to better understand how autistic trans/gender-diverse individuals experience both camouflaging of their autistic traits and closeting of their trans identity, as well as the effects this has on their mental health and sense of self.MethodsWe analyzed the lived experience of 20 autistic trans/gender-diverse (TGD) individuals aged 15 to 48. Two questionnaires were administered through an online form: (i) A Spanish adaptation of the Gender-Diversity and Autism Questionnaire (Strang et al., 2023) and (ii) a qualitative questionnaire about gender identity and life experiences. Data analysis was conducted using Reflexive Thematic Analysis (Braun & Clarke, 2006; 2023).ResultsFollowing the qualitative analysis of the material, three major themes were constructed: Theme 1, “Trans autistic minds under pressure: ‘I was being denied my right to just be’”; Theme 2, “‘Acting like someone I don’t know how to be’: Camouflaging and closeting behaviors at the intersection”, and Theme 3, “Long-term effects: ‘Disconnected from myself and shunned from the world’”.DiscussionParticipants reported high levels of stress and trauma-related symptoms. They often felt like suppressing themselves was their only choice, even if it came at the expense of their own well-being. In order to alleviate their suffering, a more neuro- and trans-affirming society is needed.
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Integration of an FDA-Authorized Digital Autism Diagnostic Tool Into an Outpatient Developmental Pediatrics Workflow: Preliminary Quality Improvement Study

<strong>Background:</strong> Long wait times and specialist shortages delay autism spectrum disorder (ASD) diagnosis, often beyond the period when early intervention is most effective. Digital diagnostic tools may help increase diagnostic capacity by supporting clinicians in delivering timely autism evaluations within routine outpatient care. <strong>Objective:</strong> This study aimed to conduct a preliminary assessment of the integration of a digital autism diagnostic device (Canvas Dx) into an outpatient developmental pediatrics workflow, including a descriptive evaluation of agreement between device outputs and specialist clinical diagnoses and an exploration of clinician and caregiver experience. <strong>Methods:</strong> A single-center, prospective quality improvement study evaluated the implementation and performance of Canvas Dx in a specialty developmental pediatrics clinic. Canvas Dx is a Food and Drug Administration (FDA)–authorized digital ASD diagnostic device approved for use in children aged 18 to 72 months with caregiver or health care provider concern for developmental delay. Eligible children were consecutively prescribed Canvas Dx during the study period and completed the assessment as part of routine clinical care. Device diagnostic outputs were compared with the final specialist clinical diagnoses. Clinician and caregiver feedback was collected to explore their experience with the assessment process and perceived workflow impact via poststudy surveys that captured both structured quantitative questions and open-ended qualitative questions. <strong>Results:</strong> A total of 28 children were included (mean age 52.2, SD 13.8 months; 7/28, 25% female), with an autism prevalence of 67.9% (19/28) based on specialist diagnosis. The device generated a determinate result for 22 (78.6%) participants. Among participants with determinate device results, sensitivity was 94.1% (95% CI 73%-99%) and specificity was 80% (95% CI 37.6%-96.4%). Positive predictive value was 94.1% (95% CI 73%-99%), and negative predictive value was 80% (95% CI 37.6-96.4%) when compared with specialist diagnosis. These estimates were imprecise, particularly for specificity and negative predictive value, because of the small number of participants without an ASD diagnosis. Clinicians reported improved insights and ease of use during evaluation visits, and caregivers reported high satisfaction with the assessment process. <strong>Conclusions:</strong> This preliminary quality improvement assessment demonstrates the feasibility of integrating Canvas Dx into a routine outpatient developmental pediatrics workflow and provides initial descriptive data on agreement with specialist diagnostic determinations and clinician and caregiver experience. Given the small sample size and resulting imprecision of diagnostic performance estimates, these findings should be interpreted as preliminary and used to inform larger prospective evaluations of diagnostic performance and workflow impact.
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Trends in Autism Spectrum Disorder Cumulative Incidence and Incidence Density: A Systematic Review

Claims of an “autism epidemic” imply a true increase in ASD occurrence and changing underlying risk yet largely rely on rising prevalence estimates rather than incidence. Both measures are influenced by diagnostic practices, service access, documentation, and ascertainment; prevalence is additionally affected by service-related migration. Incidence studies follow a defined population previously not identified, to examine outcomes over a specified period and study area; incidence is more likely to capture temporal changes in underlying risk.

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Case Report: A novel hemizygous nonsense variant in PPP1R3F gene associated with developmental delay, intellectual disability and autism spectrum disorder

BackgroundPPP1R3F deficiency syndrome is an extremely rare, recently identified X-linked recessive neurodevelopmental disorder. It is caused by hemizygous variants in the PPP1R3F gene, which encodes a glycogen-targeting subunit of the brain-specific protein phosphatase 1 (PP1). Dysfunction of PPP1R3F disrupts glycogen metabolism in astrocytes, leading to insufficient energy supply to synapses during critical periods of brain development and subsequently causing neurodevelopmental abnormalities. Only a small number of cases of PPP1R3F deficiency syndrome have been reported to date, which significantly limits our comprehensive understanding of the clinical features of the disease and the relationship between genetic variants and clinical manifestations in patients.MethodsWhole-exome sequencing (WES) was performed on a Chinese male presenting with intellectual disability (ID), developmental delay (DD), and autism spectrum disorder (ASD). Sanger sequencing was then used to identify and determine the origins of the variant. We evaluated the pathogenicity of the identified variant following the established ACMG/AMP guidelines. Additionally, we conducted a thorough review of previously reported cases to summarize the variants and clinical features of PPP1R3F deficiency syndrome.ResultsWe identified a novel hemizygous nonsense variant [NM_033215.5: c.907C>T, p.(Gln303*)] in the PPP1R3F gene in the proband, which was inherited from his mother. The patient we described here exhibited clinical phenotypes similar to those associated with PPP1R3F gene variants but lacked other reported multisystem manifestations, such as epilepsy, brain abnormalities, and dysmorphic features. An analysis of the 15 variants and their associated phenotypes in 15 patients from both the current and previous studies demonstrates that PPP1R3F gene variants can lead to a variety of phenotypic deficits, and a clear genotype–phenotype correlation has not yet been established. Despite the high variability in some clinical manifestations, the core phenotypic features of PPP1R3F variants include varying degrees of ID, DD, speech delay, dysmorphic facial features, and ASD.ConclusionOur findings support DD, ID, ASD, and speech impairment as core features of PPP1R3F deficiency syndrome, while also highlighting the extensive clinical variability. This study further expanded the genetic and phenotypic spectrum associated with PPP1R3F deficiency syndrome.
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A progenitor with immature Bergmann glia-like characteristics in the developing cerebellar cortex

The cerebellum is an ancient brain component, conserved across mammalian species, that has classically played roles in regulating muscle tone, limb coordination, and equilibrium, as well as in non-motor functions, such as language, cognition, and emotion. Recently, we reported Nestin-expressing cells in the cerebellar cortex of ferret neonates that showed a proliferative potency defined by proliferating cell nuclear antigen (PCNA) immunostaining. We called these cells “internal granular progenitor (IGP).” IGPs were found to be abundant in the internal granular layer adjacent to the Purkinje cell layer and extended GFAP-immunopositive radials progressed through the molecular and external granular layers, forming an immature Bergmann glia-like morphology. The tracking of BrdU-labeling revealed that IGPs differentiated into granular neurons, Bergmann glia, and/or astrocytes. As such, we propose that IGPs may be neural progenitors with an immature Bergmann glia-like morphology that appear in the developing cerebellar cortex, and could serve as another source of granular neurons distinct from external granular progenitors. Further research on IGPs is expected to provide new perspectives for the future investigation of cerebellar corticohistogensis, particularly the difference between motor and non-motor cerebellar regions, and how the abnormal development of IGPs relates to neurodevelopmental disorders associated with non-motor cerebellar function, such as autism spectrum disorder.