Autism Research最新文献

Autism is more frequently diagnosed in males than females. One possible explanation for this discrepancy is that autistic females may be overlooked because they show different, subtler signs of autism. For example, sex differences have been reported in pragmatic abilities. However, studying these sex differences is challenging, because diagnosed autistic females may not represent all autistic females—many remaining undiagnosed. To address this issue, our study included adolescent females at increased likelihood for autism: sisters of autistic individuals. Adolescence is a key period when autism-related difficulties often become more visible. We compared the pragmatic abilities of 76 female participants aged between 9 and 16 years old across three groups: autistic, nonautistic, and sisters of diagnosed autistic individuals. Participants completed a semistructured, spoken narrative task, which was analyzed for coherence and fluency. Their caregivers completed several questionnaires to assess both pragmatic abilities and global difficulties. At the group level, caregiver reports indicated an in-between position for sisters: they experienced more pragmatic-related difficulties than nonautistic participants but fewer than autistic participants. Narratives revealed no differences between sisters and nonautistic participants, with one exception: they gave fewer causal explanations of characters' mental states. Individual profiles of sisters revealed a heterogeneous group, varying from no difficulties at all to pragmatic profiles closely resembling those of autistic females.

Despite the substantial evidence base for poor sleep in autism, sleep problems are frequently under-identified and inefficiently managed. This is, in part, due to the fact that available tools do not comprehensively capture the specific sleep phenotypes in autism. The Sleep Disturbance Scale for Children (SDSC) is one of the highest ranked pediatric sleep assessment tools, yet it is scarcely used in autism research. Consequently, the utility of the SDSC for characterizing sleep disturbances in autism remains unknown. This study explored the factor structure of the SDSC in a sample of 513 autistic youth, aged 3–18 years (mean: 10.5 years; SD: 3.7; 18.7% female) drawn from the Healthy Brain Network secondary dataset. Fit of the previously derived SDSC factor structure was appraised using the confirmatory application of the exploratory structural equation modeling. Results indicated a five-factor solution comprising disorders of initiating and maintaining sleep, disorders of arousal, disorders of excessive somnolence (DoES), sleep breathing disorders, and sleep–wake transition disorders (SWTD) provided an excellent fit for the data. The derived factor solution was stable across sex and age. Notably, all sleep subscales were significantly positively associated with internalizing and externalizing behaviors, while age was significantly associated with DoES (r = 0.15) and SWTD (r = −0.18). This study provides the first validation of the SDSC in a large sample of well-characterized autistic youth showing distinct patterns of associations with key clinical correlates. Findings are consistent with independent reviews, suggesting the SDSC may provide a more effective way to screen for sleep disturbances in autistic individuals.

In the emerging literature on aging and autism, a consistently replicated finding is a significantly increased risk for Parkinson's disease (PD), up to six times higher. Also, atypical dopamine activity has been observed in autistic individuals and animal models. The only FDA-approved medications for ASD are the atypical antipsychotic medications, which inhibit postsynaptic dopaminergic and serotonergic transmission to treat irritability. Studies using resting state functional magnetic resonance imaging (rsfMRI) show disruption in striatal circuits in ASD. However, no studies have examined the striatal PD biomarker with dopamine transporter (DaT) single photon emission computed tomography (SPECT) imaging in adults with ASD. In this pilot study, we aimed to evaluate DaT SPECT in 18–24-year-old individuals with ASD and perform a pilot investigation of functional connectivity (FC) between the striatum and other brain areas. Four of the 12 participants had definite abnormalities or possible abnormalities in striatal DaT uptake. Participants were then separated into abnormal and normal DaT groups. In the exploratory analysis, the abnormal DaT group showed greater striatal FC to the paracingulate region compared with the normal DaT group. These pilot findings should be cautiously interpreted. Larger studies are needed to explore their link to behavioral outcomes and potential in predicting treatment responses. Examining how these findings evolve with age is also crucial, given evidence of the heightened risk of PD in ASD.

Assessment and diagnosis of autism in adulthood is a growing area of interest for both clinical and research practice. In this commentary, we present a thematic analysis following the first International Society for Autism Research Special Interest Group (SIG) focused on assessment and diagnosis of autism in adulthood. An increasing recognition of missed or misdiagnosed autistic adults is highlighted throughout the commentary. Recommendations for reducing barriers in diagnostic processes are reviewed, including improving existing adult autism measures and developing new ones, especially self-report/interview tools capturing what cannot be externally observed; providing more information about the process ahead of time and better post-diagnostic support; better assessment of psychosocial and mental health histories; training to promote clinicians' understanding of adult autism; and the importance of considering culture. Professional and government bodies should support the development of neuroaffirming, client-centered practice guidelines that actively include input and co-design from autistic adults.

Functional gastrointestinal disorders (FGIDs) are prevalent in children with autism and can interact with the neuropsychiatric symptoms bidirectionally. Moreover, FGIDs may affect feeding to jeopardize nutritional intake. Existing research often overlooks the heterogeneity of FGIDs. Understanding the clinical correlates of individual FGID subtypes may clarify the underlying gut-brain interactions to guide management. This study compared the core autistic symptoms, co-occurring psychopathologies, feeding behavior and dietary intake among 737 Chinese children with autism (mean age = 7.76 years; 642 males and 95 females) who either experienced no FGID or experienced one of the three subtypes of ROME-IV FGID. FGIDs were present in 19.8% of participants and MANCOVA revealed distinct clinical profiles across FGID subtypes. Functional abdominal pain disorders (FAPD) were associated with more severe neuropsychiatric symptoms, including restricted and repetitive behavior, anxiety, sensory hyperresponsiveness, externalizing behavior, and feeding patterns of emotional under-eating, slowness in eating, and increased satiety response. Functional defecation disorders (FDD) were characterized by food fussiness, slowness in eating, increased satiety response, and decreased intake of water, protein and fiber. With a small sample size of six, functional nausea and vomiting disorders (FNVD) were associated with emotional overeating. These findings suggest FGID subtypes involve distinct gut-brain interactions. Sensory dysregulation may underlie the link between FAPD and neuropsychiatric symptoms, while food fussiness in FDD may contribute to constipation via reduced fiber and water intake. The management of FGIDs in autism should be tailored to specific subtypes and their clinical correlates.

Activity-Dependent Neuroprotective Protein (ADNP) is a putative transcription factor that differentially interacts with proteins involved in chromatin remodeling, thereby controlling neuronal differentiation. The protein contains nine zinc fingers, a bipartite nuclear localization signal (NLS), and a homeobox domain with a heterochromatin protein 1 interaction motif, ensuring nuclear association with DNA and chromatin. De novo variants in ADNP cause autism comorbid with intellectual disability in the Helsmoortel–Van der Aa syndrome. ADNP interacts with components of the SWI/SNF in HEK293T cells but has also been reported as part of the repressive ChAHP complex in mouse embryonic stem cells. Although converging evidence suggests a role in chromatin remodeling, Hi-C experiments failed to detect major alterations in 3D chromatin structure. We therefore investigated ADNP's role in epigenetic regulation and identified the chromatin scaffolding protein WDR5 and HDAC2 as interaction partners. Structural modeling revealed two N-terminal methyltransferase domains, suggesting catalytic activity via SAM to SAH conversion. Immunoprecipitated fractions containing wild-type ADNP exhibited methyltransferase activity, which was reduced by nonsense variants. ADNP was expressed in histone-enriched cerebellar fractions in mice and a Helsmoortel–Van der Aa autopsy case, with male-specific reduction of the H3K79me1 modification. At the DNA level, wild-type ADNP induced CpG hypermethylation. However, most variants caused CpG hypomethylation, supporting a loss-of-function mechanism, while NLS variants showed additional hypermethylation, suggesting a gain-of-function effect linked to apoptosis and microtubule transport. Taken together, we identified an ADNP-WDR5-HDAC2 protein complex involved in epigenetic regulation, with ADNP exhibiting methyltransferase activity in overexpression systems.