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Hormones and Behavior Jun 2024Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive...
Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence of endocrine and reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within the hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore the reproductive health disparities in ASD using an animal model of autism, the C58/J inbred mouse strain, with a focus on reproductive performance and hormonal profiles compared to the C57BL/6J control strain. Our findings revealed that the estrous cycle in C58/J females is disrupted, as evidenced by a lower frequency of complete cycles and a lack of cyclical release of estradiol and progesterone compared to control mice. C58/J females also exhibited poor performance in several reproductive parameters, including reproductive lifespan and fertility index. Furthermore, estrogen receptor alpha content showed a marked decrease in the hypothalamus of C58/J mice. These alterations in the estrous cycle, hormonal imbalances, and reduced reproductive function imply dysregulation in the HPO axis. Additionally, our in-silico study identified a group of genes involved in infertility carrying single-nucleotide polymorphisms (SNPs) in the C58/J strain, which also have human orthologs associated with autism. These findings could offer valuable insights into the molecular underpinnings of neuroendocrine axis disruption and reproductive issues observed in ASD.
PubMed: 38909429
DOI: 10.1016/j.yhbeh.2024.105593 -
Scientific Reports Jun 2024Interpersonal coordination is a key determinant of successful social interaction but can be disrupted when people experience symptoms related to social anxiety or...
Interpersonal coordination is a key determinant of successful social interaction but can be disrupted when people experience symptoms related to social anxiety or autism. Effective coordination rests on individuals directing their attention towards interaction partners. Yet little is known about the impact of the attentional behaviours of the partner themselves. As the gaze of others has heightened salience for those experiencing social anxiety or autism, addressing this gap can provide insight into how symptoms of these disorders impact coordination. Using a novel virtual reality task, we investigated whether partner gaze (i.e., direct vs. averted) influenced the emergence of interpersonal coordination. Results revealed: (i) spontaneous coordination was diminished in the averted (cf. direct) gaze condition; (ii) spontaneous coordination was positively related to symptoms of social anxiety, but only when partner gaze was averted. This latter finding contrasts the extant literature and points to the importance of social context in shaping the relationship between symptoms of psychopathology and interpersonal coordination.
Topics: Humans; Male; Female; Adult; Interpersonal Relations; Young Adult; Fixation, Ocular; Attention; Social Interaction; Anxiety; Adolescent; Autistic Disorder
PubMed: 38906960
DOI: 10.1038/s41598-024-65139-5 -
PCN Reports : Psychiatry and Clinical... Jun 2024Given the escalating prevalence of autism spectrum disorder (ASD), the persistent paucity of child psychiatrists in Japan, and the need to prepare for unforeseen...
AIM
Given the escalating prevalence of autism spectrum disorder (ASD), the persistent paucity of child psychiatrists in Japan, and the need to prepare for unforeseen situations, such as the COVID-19 pandemic, it is essential to establish a reliable screening tool. This study aims to validate the Infant Behavior Checklist (IBC) developed by Japanese experts and determine its appropriate cut-off score.
METHODS
A total of 354 clinic-referred children, along with their caregivers, participated in this research. Clinical records, including diagnoses established through the sub-structured diagnostic interviews, and the IBC assessments, were subjected to rigorous statistical analysis.
RESULTS
Among the 24 items, six failed to reach significance to differentiate ASD from non-ASD cases. The Cronbach's alpha coefficient for the IBC was calculated at 0.77. The IBC total score for ASD cases was significantly higher than that of non-ASD cases. With the chosen cut-off score, the IBC demonstrated an area under the ROC curve of 0.803, along with sensitivity, specificity, positive predictive value, and negative predictive value of 8.03, 0.79, 0.69, 0.34, and 0.94, respectively.
CONCLUSION
The IBC exhibits satisfactory internal consistency and content and discriminant validity. The high sensitivity and other associated indices for the optimal cut-off score of the IBC affirm its validity as a screening instrument for ASD. Nevertheless, further investigations are warranted to ascertain the clinical utility of the IBC.
PubMed: 38904062
DOI: 10.1002/pcn5.212 -
Frontiers in Psychiatry 2024Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate...
BACKGROUND
Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD).
METHODS
Mice were subjected to social isolation during postnatal days 21-35 (P21-P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression.
RESULTS
In adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found.
CONCLUSION
Our study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior.
PubMed: 38903649
DOI: 10.3389/fpsyt.2024.1403476 -
Cureus May 2024Introduction Considering the scarcity of research that directly investigates the differences between genders in their response to applied behavior analysis (ABA) therapy...
Introduction Considering the scarcity of research that directly investigates the differences between genders in their response to applied behavior analysis (ABA) therapy for individuals diagnosed with autism spectrum disorder (ASD), the objective of this study is twofold. First, it aims to reinforce the male-to-female ratio reported in existing scientific literature, thereby contributing to a broader understanding of gender distribution in ABA therapy for ASD. Second, it seeks to identify gender-based differences in aggregate target behaviors at various time intervals using three distinct datasets. The goal is to determine if gender influences the effectiveness of ABA therapy for ASD, which could inform future therapeutic strategies. Ultimately, this study strives to enhance our understanding of gender disparities in ABA therapy response among ASD individuals and hopes to improve therapeutic outcomes for all, regardless of gender. Materials and methods Three to five behavioral technicians per child collected daily general target mastery data for 263 individuals with autism. This data was gathered using a large N design through retrospective chart reviews within the "Catalyst" tracking software (DataFinch Technologies, Atlanta, USA). Three separate datasets were collected from June 7, 2023 to January 7, 2024. Behavior analysts employed a mixed model of discrete trial training, mass trials, and naturalistic environment treatment over seven months. General target mastery data was assembled for 259 children and four adults, with seven data instances missing. Descriptive statistics encompassed central tendency and dispersion measures, including the data distribution's mean, standard deviation, median, and range. Non-parametric inferential analysis was performed with the Mann-Whitney U test. Results Mann-Whitney U computations resulted in non-significant gender differences on all gender comparisons for the three datasets covering the seven-month timeframe. Dataset #1: Time 1-(U=727.5, p=0.846, ή2=0.0002, Time 2-(U=736, p=0.910, ή2=0.00005), Time 3-(U=687.5, p=0.569, ή2=0.001) Dataset #2: Time 1-(U=781, p=0.383, ή2=0.003), Time 2-(U=819.5, p=0.585, ή2=0.001), Time 3-(U=825, p=0.618, ή2=0.001) Dataset #3: Time 1-(U=395, p=0.198, ή2=0.007), Time 2-(U=373.5, p=0.365, ή2 =0.003), Time 3-(U=363, p=0.471, ή2=0.002), Time 4-(U=366.5, p=0.436, ή2 =0.003), Time 5-(U=371, p=0.391, ή2=0.003), Time 6-(U=394, p=0.208, ή2=0.007), Time 7-(U=373, p=0.373, ή2=0.003), Time 8-(U=371.5, p=0.387, ή2=0.003), Time 9-(U=464.5, p=0.512, ή2=0.002), Time 10-(U=356.5, p=0.546, ή2=0.002), Time 11-(U=357.5, p=0.535, ή2=0.002), Time 12-(U=350.5, p=0.346, ή2=0.004) Conclusions This study suggests no significant gender differences in response to ABA therapy among individuals with autism, indicating its potential effectiveness for both genders. However, these findings should be interpreted cautiously due to statistical uncertainties reflected in the broad confidence intervals as they hint at possible substantial gender differences. Further research, including an extension study, must confirm these results and understand potential gender nuances in ABA therapy response. This could help tailor more effective, personalized therapeutic strategies for individuals with autism.
PubMed: 38903347
DOI: 10.7759/cureus.60794 -
Frontiers in Neurology 2024This study aimed to investigate the clinical effects of Orff music therapy on children with Autism Spectrum Disorder (ASD) from the perspectives of parents, evaluators,...
OBJECTIVE
This study aimed to investigate the clinical effects of Orff music therapy on children with Autism Spectrum Disorder (ASD) from the perspectives of parents, evaluators, and therapists.
METHODS
93 children with ASD aged 3-6 years participated in the study. They were divided into an observation group ( = 48) receiving comprehensive rehabilitation intervention including Orff music therapy, and a control group ( = 45) receiving only comprehensive rehabilitation intervention. The Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Psycho-educational Profile-3rd edition (PEP-3) were used for assessments before and after the intervention.
RESULTS
There were no significant demographic differences between the two groups. Both groups showed significant improvements in Sensory, Relating, Language, CVP, EL, RL, VMI, AE, SR, and CARS scores at T1, T2, and T3 (T1 vs. T2, T2 vs. T3, T1 vs. T3) (all < 0.05). The observation group demonstrated significant changes in Body and Object use and FM, while the control group showed some changes in these domains. Social and self-help, GM, CMB, and CVB also significantly improved in both groups after 6 months of intervention (all < 0.05). In terms of different time intervals, the observation group showed greater improvements in Sensory, Relating, Language, CARS scores, EL, RL, and SR compared to the control group (all < 0.05). The improvement levels in Body and Object use, CVP, FM, VMI, and AE did not differ significantly between the two groups in the T1-T2 interval, but were significantly higher in the observation group in the T2-T3 and T1-T3 intervals (all < 0.05). The magnitude of changes in Social and self-help, GM, CMB, and CVB did not differ significantly between the groups.
CONCLUSION
Orff music therapy showed significant improvements in language expression, language comprehension, social skills, cognitive abilities, imitation abilities, emotional expression and fine motor in children with ASD. These findings provide support for the use of Orff music therapy as an effective intervention for children with ASD.
PubMed: 38903168
DOI: 10.3389/fneur.2024.1387060 -
Italian Journal of Pediatrics Jun 2024Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics supplementation has a protective effect on ASD remains controversial. This meta-analysis aimed to analyze the outcome of probiotics in the treatment of ASD children.
METHODS
The Pubmed, Cochrane Library, Web of Science and Embase were searched until Sep 2022. Randomized controlled trials (RCTs) relevant to the probiotics and placebo treatment on ASD children were screened. Quality assessment of the included RCTs was evaluated by the Cochrane collaboration's tool. The primary outcomes were ASD assessment scales, including ABC (aberrant behavior checklist) and CBCL (child behavior checklist) for evaluating the behavior improvement, SRS (social responsiveness scale) for social assessment, DQ (developmental quotient) for physical and mental development and CGI-I (clinical global impression improvement) for overall improvement. The secondary outcome was total 6-GSI (gastrointestinal severity index).
RESULTS
In total, 6 RCTs from 6 studies with 302 children were included in the systemic review. Total 6-GSI (MD=-0.59, 95%CI [-1.02,-0.17], P < 0.05) decreased significantly after oral administration of probiotics. Whereas, there was no statistical difference in ABC, CBCL, SRS, DQ and CGI-I between probiotics and placebo groups in ASD children.
CONCLUSION
Probiotics treatment could improve gastrointestinal symptoms, but there was no significant improvement in ASD.
Topics: Humans; Probiotics; Autism Spectrum Disorder; Child; Randomized Controlled Trials as Topic; Treatment Outcome; Gastrointestinal Microbiome
PubMed: 38902804
DOI: 10.1186/s13052-024-01692-z -
Psychiatry Research Jun 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide range of symptoms that include deficits in social cognition and difficulties with social...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide range of symptoms that include deficits in social cognition and difficulties with social interactions. Neural oscillations in the EEG gamma band have been proposed as an important candidate neurobiological marker of higher order cognitive processes and social interactions. We investigated resting-state gamma-activity of patients with ASD (n=23) in order to delineate alterations as compared to typically developing (TD) subjects (n=24). EEG absolute power was examined in the gamma (30-100Hz) frequency band. We found significantly reduced spectral power across the entire gamma range in the ASD group. The decrease was most pronounced over the inferior-frontal and temporo-parietal junction areas. We also found a significant decrease in gamma-activity over the dorsolateral prefrontal cortex, especially in the left side. Since these brain areas have been associated with social functioning, the reduced gamma-activity in ASD may represent a cortical dysfunction that could underlie a diminished capacity to interpret socially important information, thereby interfering with social functioning. The alterations we found may lend support for an improved diagnosis. Furthermore, they can lead to focused therapies, by targeting the dysfunctional brain activity to improve social cognitive and interaction abilities that are compromised in ASD.
PubMed: 38901364
DOI: 10.1016/j.psychres.2024.116040 -
Cell Reports Jun 2024Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to...
Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3-mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We apply an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in humans and mice. We unexpectedly discover an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts are altered in Shank3-mutant mice and postmortem brain tissues from individuals with autism spectrum disorder. The enhanced SHANK3 transcriptome significantly improves the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest that both deterministic and stochastic transcription of the genome is associated with SHANK family genes.
PubMed: 38900637
DOI: 10.1016/j.celrep.2024.114376 -
Behavioral and Brain Functions : BBF Jun 2024Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication,...
BACKGROUND
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication, restricted interests that can be accompanied by repetitive behavior, and disturbances in social behavior. This study investigated brain mechanisms that contribute to sociability deficits and sex differences in an ASD animal model.
METHODS
Sociability was measured in C58/J and C57BL/6J mice using the 3-chamber social choice test. Bulk RNA-Seq and snRNA-Seq identified transcriptional changes in C58/J and C57BL/6J amygdala within which DMRseq was used to measure differentially methylated regions in amygdala.
RESULTS
C58/J mice displayed divergent social strata in the 3-chamber test. Transcriptional and pathway signatures revealed immune-related biological processes differ between C58/J and C57BL/6J amygdala. Hypermethylated and hypomethylated genes were identified in C58/J versus C57BL/6J amygdala. snRNA-Seq data in C58/J amygdala identified differential transcriptional signatures within oligodendrocytes and microglia characterized by increased ASD risk gene expression and predicted impaired myelination that was dependent on sex and sociability. RNA velocity, gene regulatory network, and cell communication analysis showed diminished oligodendrocyte/microglia differentiation. Findings were verified using Bulk RNA-Seq and demonstrated oxytocin's beneficial effects on myelin gene expression.
LIMITATIONS
Our findings are significant. However, limitations can be noted. The cellular mechanisms linking reduced oligodendrocyte differentiation and reduced myelination to an ASD phenotype in C58/J mice need further investigation. Additional snRNA-Seq and spatial studies would determine if effects in oligodendrocytes/microglia are unique to amygdala or if this occurs in other brain regions. Oxytocin's effects need further examination to understand its' potential as an ASD therapeutic.
CONCLUSIONS
Our work demonstrates the C58/J mouse model's utility in evaluating the influence of sex and sociability on the transcriptome in concomitant brain regions involved in ASD. Our single-nucleus transcriptome analysis elucidates potential pathological roles of oligodendrocytes and microglia in ASD. This investigation provides details regarding regulatory features disrupted in these cell types, including transcriptional gene dysregulation, aberrant cell differentiation, altered gene regulatory networks, and changes to key pathways that promote microglia/oligodendrocyte differentiation. Our studies provide insight into interactions between genetic risk and epigenetic processes associated with divergent affiliative behavior and lack of positive sociability.
Topics: Animals; Male; Microglia; Mice; Amygdala; Female; Oligodendroglia; Autism Spectrum Disorder; Mice, Inbred C57BL; Social Behavior; Gene Expression Profiling; Phenotype; Sex Characteristics; Transcriptome; Disease Models, Animal; Oxytocin
PubMed: 38898502
DOI: 10.1186/s12993-024-00240-3