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BioRxiv : the Preprint Server For... Jun 2024Social touch is critical for communication and to impart emotions and intentions. However, certain autistic individuals experience aversion to social touch, especially...
Social touch is critical for communication and to impart emotions and intentions. However, certain autistic individuals experience aversion to social touch, especially when it is unwanted. We used a novel social touch assay and Neuropixels probes to compare neural responses to social vs. non-social interactions in three relevant brain regions: vibrissal somatosensory cortex, tail of striatum, and basolateral amygdala. We find that wild type (WT) mice showed aversion to repeated presentations of an inanimate object but not of another mouse. Cortical neurons cared most about touch context (social vs. object) and showed a preference for social interactions, while striatal neurons changed their preference depending on whether mice could choose or not to interact. Amygdalar and striatal neurons were preferentially modulated by forced object touch, which was the most aversive. In contrast, the knockout (KO) model of autism found social and non-social interactions equally aversive and displayed more aversive facial expressions to social touch when it invaded their personal space. Importantly, when KO mice could choose to interact, neurons in all three regions did not discriminate social valence. Thus, a failure to differentially encode social from non-social stimuli at the circuit level may underlie social avoidance in autism.
PubMed: 38948773
DOI: 10.1101/2024.06.19.599778 -
Frontiers in Pharmacology 2024Neurodevelopmental disorders (NDDs) include a broad spectrum of pathological conditions that affect >4% of children worldwide, share common features and present a... (Review)
Review
Neurodevelopmental disorders (NDDs) include a broad spectrum of pathological conditions that affect >4% of children worldwide, share common features and present a variegated genetic origin. They include clinically defined diseases, such as autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), motor disorders such as Tics and Tourette's syndromes, but also much more heterogeneous conditions like intellectual disability (ID) and epilepsy. Schizophrenia (SCZ) has also recently been proposed to belong to NDDs. Relatively common causes of NDDs are copy number variations (CNVs), characterised by the gain or the loss of a portion of a chromosome. In this review, we focus on deletions and duplications at the 16p11.2 chromosomal region, associated with NDDs, ID, ASD but also epilepsy and SCZ. Some of the core phenotypes presented by human carriers could be recapitulated in animal and cellular models, which also highlighted prominent neurophysiological and signalling alterations underpinning 16p11.2 CNVs-associated phenotypes. In this review, we also provide an overview of the genes within the 16p11.2 locus, including those with partially known or unknown function as well as non-coding RNAs. A particularly interesting interplay was observed between MVP and MAPK3 in modulating some of the pathological phenotypes associated with the 16p11.2 deletion. Elucidating their role in intracellular signalling and their functional links will be a key step to devise novel therapeutic strategies for 16p11.2 CNVs-related syndromes.
PubMed: 38948459
DOI: 10.3389/fphar.2024.1407865 -
World Journal of Clinical Pediatrics Jun 2024Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. Metabolomic profiling has...
BACKGROUND
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.
AIM
To comprehensively explore metabolomic changes in children with ASD, integrating findings from various research articles, reviews, systematic reviews, meta-analyses, case reports, editorials, and a book chapter.
METHODS
A systematic search was conducted in electronic databases, including PubMed, PubMed Central, Cochrane Library, Embase, Web of Science, CINAHL, Scopus, LISA, and NLM catalog up until January 2024. Inclusion criteria encompassed research articles (83), review articles (145), meta-analyses (6), systematic reviews (6), case reports (2), editorials (2), and a book chapter (1) related to metabolomic changes in children with ASD. Exclusion criteria were applied to ensure the relevance and quality of included studies.
RESULTS
The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals. These metabolic biomarkers may serve as objective measures to support clinical assessments, improve diagnostic accuracy, and inform personalized treatment approaches. Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.
CONCLUSION
Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy, guiding personalized treatment approaches, monitoring treatment response, and improving outcomes. Further research is needed to validate findings, establish standardized protocols, and overcome technical challenges in metabolomic analysis. By advancing our understanding of metabolic dysregulations in ASD, clinicians can improve the lives of affected individuals and their families.
PubMed: 38947988
DOI: 10.5409/wjcp.v13.i2.92737 -
Cureus May 2024This literature review aims to explore religiosity, faith, and related beliefs in autistic adolescents. The term religiosity was used interchangeably with various... (Review)
Review
This literature review aims to explore religiosity, faith, and related beliefs in autistic adolescents. The term religiosity was used interchangeably with various related concepts such as faith, spirituality, and religious beliefs, and a broader, multifaceted approach encompassing the cognitive, subjective, social, cultural, and emotional domains of religiosity is analyzed in this population subgroup. In alignment with the neurodiversity paradigm, this review endeavors to adopt an inclusive lens toward autism spectrum conditions, appreciating the spectrum of cognitive and behavioral differences and highlighting the importance of recognizing strengths and challenges alike, reflecting the nuanced discourse surrounding neurodiversity and autism spectrum conditions. However, terms such as "high-functioning autism" and "disorder" were used where needed to reflect the journals included in the review. A systematic search was conducted by accessing academic search engines such as APA PsycInfo, APA PsycArticles, APA PsycTests, and PubMed. Only peer-reviewed articles written in English and performed on human subjects were included using strict inclusion and exclusion criteria. Several recurring themes were identified from the 13 articles selected after review for relevance and quality. The most important finding was the association of different terminologies and features while exploring "religiosity in autism." Thirty-nine key themes were identified, which were grouped into six major themes. These were religious faith, spirituality, and its expression in autistic adolescents; religious behaviors and practices of autistic adolescents; cognition and religion in autistic teens; social and cultural influences on religiosity in autistic young ones; parents' and carers' influence, perspectives, and experiences about faith and spirituality on autistic adolescents; and perceived benefits of faith to autistic teens: parents and adolescent perspectives. Looking at the concept of religiosity and spirituality as a whole, it can be inferred from the available research included in this review that religiosity (cognitive abilities, behaviors, and experiences) in a subset of autistic adolescents (high-functioning autism) might not be significantly subdued as compared to neurotypical adolescents. However, there is not enough research to conclude the same or the opposite for autistic adolescents in general. When found, reserved religiosity could be attributed to a plethora of factors, and decreased mental ability or mentalization, empathy, or imagination did not seem to be the sole or primary predictors or contributors to religiosity. The role of culture, parents, carers, and religious affiliations was significant and might be a stronger contributor to religiosity and its expression than other previously argued predictors like mentalization. Many autistic teens and their carers regard religiosity and spirituality as essential domains in their and their children's lives, want their children to be given opportunities to be a part of religious groups and affiliations, and look forward to government, religious, and healthcare authorities actively supporting them in this domain. The findings call for policymakers, religious leaders, and stakeholders to devise strategies for inclusion and support for autistic adolescents. The possible role of religion as a resource and coping strategy for these children and their families is worth exploring.
PubMed: 38947705
DOI: 10.7759/cureus.61271 -
Cureus May 2024Background Autism spectrum disorder (ASD) is a psychopathologic disorder caused by several factors. The early signs include poor interaction and communication, delayed...
Background Autism spectrum disorder (ASD) is a psychopathologic disorder caused by several factors. The early signs include poor interaction and communication, delayed milestones, and repeated behavior patterns. This study aimed to assess the relationship between screen time and ASD severity and investigate the types of electronic devices associated with ASD in children aged four to six years in Arar City, Kingdom of Saudi Arabia (KSA). Methodology A cross-sectional study was conducted in primary healthcare centers (PHCs) in Arar City, KSA. The study enrolled all parents with children aged four to six years attending the PHCs in Arar City, KSA. Results The total sample size was 199 participants. Regarding the relationship between screen time exposure and ASD, there were variable screen time exposure durations, with 22.6% of children exposed for less than an hour, 30.7% for one to two hours, and 46.7% for more than two hours. Moreover, the type of electronic devices to which children were exposed varied, with smartphones being the most prevalent (68.3%). In terms of the age of children since exposure to electronic devices, the data indicated that 30.2% were exposed before the age of two, 35.2% between two and three years, and 34.7% after three years of age. Regarding the relationship with sociodemographic characteristics, there was a statistically significant relationship with the mother's age at birth (p = 0.050), mother's education level (p = 0.009), father's education level (p = 0.049), whether the child was suffering from any chronic or neurological disease (p = 0.008), age since the child was exposed to electronic devices (p = 0.049), and screen time exposure duration (p = 0.040). Conclusions The study highlights the significant association between screen time exposure and the development of ASD in children. Public awareness of this associated risk among caregivers is recommended to follow the protective guidelines. Further research and interventions are needed to better understand and address the impact of screen media use on children's neurodevelopment and overall well-being.
PubMed: 38947650
DOI: 10.7759/cureus.61447 -
IScience Jun 2024Mechanistic target of rapamycin complex 1 (mTORC1) is an integration hub for extracellular and intracellular signals necessary for brain development. Hyperactive mTORC1...
Mechanistic target of rapamycin complex 1 (mTORC1) is an integration hub for extracellular and intracellular signals necessary for brain development. Hyperactive mTORC1 is found in autism spectrum disorder (ASD) characterized by atypical reactivity to sensory stimuli, among other symptoms. In Tuberous sclerosis complex (TSC) inactivating mutations in the or genes result in hyperactivation of the mTORC1 pathway and ASD. Here, we show that lack of light preference of the TSC zebrafish model, is caused by aberrant processing of light stimuli in the left dorsal habenula and fish have impaired function of the left dorsal habenula, in which neurons exhibited higher activity and lacked habituation to the light stimuli. These characteristics were rescued by rapamycin. We thus discovered that hyperactive mTorC1 caused aberrant habenula function resulting in lack of light preference. Our results suggest that mTORC1 hyperactivity contributes to atypical reactivity to sensory stimuli in ASD.
PubMed: 38947496
DOI: 10.1016/j.isci.2024.110149 -
MedRxiv : the Preprint Server For... Jun 2024Despite their importance, little is known about how social drivers of health shape communicative outcomes in autism. Even less is known when considering the intersection...
UNLABELLED
Despite their importance, little is known about how social drivers of health shape communicative outcomes in autism. Even less is known when considering the intersection of race and language impairment. An understanding of factors in communicative outcomes is key for characterizing developmental trajectories and informing supports. This cross-sectional observational study examined the role of social drivers of health in communicative outcomes of racially and ethnically minoritized autistic adolescents and adults. Participants ages 13 to 30 ( = 73) completed a behavioral assessment protocol, including language and nonverbal cognitive skills, as well as social drivers of health (sense of community, unmet services, barriers to services). Correlational analyses revealed associations between social drivers of health on social communication impairment and real-world communication. Generalized linear mixed-effects modeling revealed that language predicted real-world communication, but sense of community predicted social communication impairment. Findings point to the importance of assessing both individual differences and social drivers of health in outcomes in autism research. Future work should focus on social drivers of health in larger-scale analyses of outcomes in minoritized autistic individuals during the transition to adulthood, considering supports that align with service eligibility and person-centered outcomes.
LAY ABSTRACT
Where people live, work, and spend their time is important. Environments can have more or less services or differ in how much they help people feel like they belong to their community. These parts of the environment are called social drivers of health. Social drivers of health are important for outcomes in autism, but we do not know much about them in racially and ethnically minoritized autistic teens or adults. We recruited 73 minoritized autistic teens and adults ages 13 to 30 years and 52 caregivers (parents, grandparents, sibling) to our study. Teens and adults did language and NVIQ tests on Zoom. Teens, adults, and caregivers also answered questionnaires. Sense of community was important for social communication impairment, and language was important for real-world communication. These findings tell us two things. First, thinking about how to create supportive communication environments for autistic teens and adults is important. Second, understanding how social drivers of health shape outcomes is important. In the future, we should focus on how improving environments can help minoritized autistic teens and adults meet their communication goals.
PubMed: 38947098
DOI: 10.1101/2024.06.17.24309053 -
MedRxiv : the Preprint Server For... Jun 2024Auditory processing disorder (APD) has been studied in both research and clinic settings, but the relation between the two has not been addressed. In a longitudinal...
PURPOSE
Auditory processing disorder (APD) has been studied in both research and clinic settings, but the relation between the two has not been addressed. In a longitudinal research study (SICLiD), we found that children with clinically normal audiometry who had caregiver-reported listening difficulties (LiD), with or without clinically assessed APD, performed poorly on both listening and cognitive tests. Specific questions asked here were, for the children with LiD, what other neurodevelopmental clinical conditions were identified, what interventions were used by different clinical providers, and how clinical practice was predicted by research results.
METHODS
Study setting was a large, research-led, tertiary pediatric hospital. Electronic medical records of 74 children aged 6-13 years, recruited into SICLiD and assigned to an LiD group based on a validated and reliable caregiver report (ECLiPS), were independently reviewed. Focus was on clinical assessments and interventions following appointments provided in the Hospital Divisions of Audiology, Occupational Therapy, Psychology (Developmental and Behavioral Pediatrics), and Speech-Language Pathology (SLP), prior to participation in SICLiD. Descriptive statistics on clinical encounters, identified conditions, and interventions were compared with quantitative, standardized performance on SICLiD assessments of listening and cognitive function. SICLiD z-scores were compared for participants with and without each clinical condition using univariate and logistic prediction analyses.
RESULTS
Most (86%) of the children with LiD had been evaluated by at least one clinical service. Overall, 24 assessment categories related to LiD, including APD, were identified. Most common conditions were attention (32%), language (28%), hearing (18%), anxiety (16%), and autism spectrum (6%) disorders. Performance on SICLiD measures varied significantly between providers, conditions, and interventions. Significant relationships between SICLiD and clinical conditions were mostly caregiver-reported items from the ECLiPS or the Children's Communication Checklist (CCC-2). Other significant correlations were scarce, but included the SCAN composite score, which predicted clinical language and attention, but not other auditory abilities or APD. SICLiD data combined with caregiver reports provided reliable predictions of all clinical conditions except APD.
CONCLUSIONS
The variety of disciplines, assessments, conditions and interventions revealed here supports previous studies showing that LiD and APD are multifaceted problems of neurodevelopment. Comparisons between clinical- and research-based assessments suggest a diagnostic path that prioritizes caregiver reports and selected psychometric tests for screening and diagnostic purposes.
PubMed: 38946985
DOI: 10.1101/2024.06.12.24308837 -
Animal Models and Experimental Medicine Jul 2024Hypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T during pregnancy. The fetus relies entirely on the mother's T...
BACKGROUND
Hypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T during pregnancy. The fetus relies entirely on the mother's T hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism-like behavior of IMH offspring.
METHODS
The animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T, T, and thyroid-stimulating hormone (TSH) were detected using enzyme-linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open-field test, three-chamber sociability test, and Morris water maze, to explore the autistic-like behavior of 40-day-old offspring rats.
RESULTS
The ELISA test showed that the serum T and TSH concentrations in the model group were normal compared with the negative control group, whereas the T concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly.
CONCLUSION
The animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic-like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.
PubMed: 38946346
DOI: 10.1002/ame2.12459 -
Brain and Behavior Jul 2024
Topics: Humans; Autistic Disorder; Quality of Life
PubMed: 38945821
DOI: 10.1002/brb3.3572