Repetitive Behaviors Research Articles

Clinical, Cortical, Subcortical, and White Matter Features of Right Temporal Variant FTD.

Eight patients with right temporal variant FTD were prospectively recruited and underwent a standardised neuropsychological assessment, clinical MRI, and quantitative neuroimaging. Our voxelwise grey analyses captured bilateral anterior and mesial temporal grey matter atrophy with a clear right-sided predominance. Bilateral hippocampal involvement was also observed, as well as disease burden in the right insular and opercula regions. White matter integrity alterations were also bilateral in anterior temporal and sub-insular regions with a clear right-hemispheric predominance. Extra-temporal white matter alterations have also been observed in orbitofrontal and parietal regions. Significant bilateral but right-predominant thalamus, putamen, hippocampus, and amygdala atrophy was identified based on subcortical segmentation. The clinical profile of our patients was dominated by progressive indifference, decline in motivation, loss of interest in previously cherished activities, incremental social withdrawal, difficulty recognising people, progressive language deficits, increasingly rigid routines, and repetitive behaviours. Right temporal variant FTD has an insidious onset and may be mistaken for depression at symptom onset. It manifests in a combination of apathy, language, and behavioural features. Quantitative MR imaging captures a characteristic bilateral but right-predominant temporal imaging signature with extra-temporal frontal and parietal involvement.

Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism

Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.

Database-assisted screening of autism spectrum disorder related gene set

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication difficulties, along with repetitive behaviors. While genetic factors play a significant role in ASD, the precise genetic landscape remains complex and not fully understood, particularly in non-syndromic cases. The study performed an in silico comparison of three genetic databases. ClinVar, SFARI Gene, and AutDB were utilized to identify relevant gene subset and genetic variations associated with non-syndromic ASD. Gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) network analysis were conducted to elucidate the biological significance of the identified genes. The integrity of ASD-related gene subset and the distribution of their variations were statistically assessed. A subset of twenty overlapping genes potentially specific for non-syndromic ASD was identified. GSEA revealed enrichment of biological processes related to neuronal development and differentiation, synaptic function, and social skills, highlighting their importance in ASD pathogenesis. PPI network analysis demonstrated functional relationships among the identified genes. Analysis of genetic variations showed predominance of rare variants and database-specific distribution patterns. The results provide valuable insights into the genetic landscape of ASD and outline the genes and biological processes involved in the condition, while taking into account that the study relied exclusively on in silico analyses, which may be subject to biases inherent to database methodologies. Further research incorporating multi-omics data and experimental validation is warranted to enhance our understanding of non-syndromic ASD genetics and facilitate the development of targeted research, interventions and therapies.

Neurofibromin deficiency alters the patterning and prioritization of motor behaviors in a state-dependent manner.

Genetic disorders such as neurofibromatosis type 1 increase vulnerability to cognitive and behavioral disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder. Neurofibromatosis type 1 results from loss-of-function mutations in the neurofibromin gene and subsequent reduction in the neurofibromin protein (Nf1). While the mechanisms have yet to be fully elucidated, loss of Nf1 may alter neuronal circuit activity leading to changes in behavior and susceptibility to cognitive and behavioral comorbidities. Here we show that mutations decreasing Nf1 expression alter motor behaviors, impacting the patterning, prioritization, and behavioral state dependence in a Drosophila model of neurofibromatosis type 1. Loss of Nf1 increases spontaneous grooming in a nonlinear spatial and temporal pattern, differentially increasing grooming of certain body parts, including the abdomen, head, and wings. This increase in grooming could be overridden by hunger in food-deprived foraging animals, demonstrating that the Nf1 effect is plastic and internal state-dependent. Stimulus-evoked grooming patterns were altered as well, with nf1 mutants exhibiting reductions in wing grooming when coated with dust, suggesting that hierarchical recruitment of grooming command circuits was altered. Yet loss of Nf1 in sensory neurons and/or grooming command neurons did not alter grooming frequency, suggesting that Nf1 affects grooming via higher-order circuit alterations. Changes in grooming coincided with alterations in walking. Flies lacking Nf1 walked with increased forward velocity on a spherical treadmill, yet there was no detectable change in leg kinematics or gait. Thus, loss of Nf1 alters motor function without affecting overall motor coordination, in contrast to other genetic disorders that impair coordination. Overall, these results demonstrate that loss of Nf1 alters the patterning and prioritization of repetitive behaviors, in a state-dependent manner, without affecting motor coordination.

Assessing the COX-2/PGE2 Ratio and Anti-Nucleosome Autoantibodies as Biomarkers of Autism Spectrum Disorders: Using Combined ROC Curves to Improve Diagnostic Values.

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by restricted and repetitive behaviors as well as difficulties with social interaction. Numerous studies have revealed aberrant lipid mediators and autoimmunity as a recognized etiological cause of ASD that is amenable to therapeutic intervention. In this study, the relationship between the relative cyclooxygenase-2/prostaglandin E2 ratio (COX-2/PGE2) as a lipid mediator marker and anti-nucleosome autoantibodies as an autoimmunity marker of ASD was investigated using multiple regression and combined receiver operating characteristic (ROC) curve analyses. The study also sought to identify the linear combination of these variables that optimizes the partial area under the ROC curves. There were forty ASD children and forty-two age- and gender-matched controls included in the current study. Using combined ROC curve analysis, a notable increase in the area under the curve was seen in the patient group, using the control group as a reference group. Additionally, it was reported that the combined markers had improved specificity and sensitivity. This study demonstrates how the predictive value of particular biomarkers associated with lipid metabolism and autoimmunity in children with ASD can be measured using a ROC curve analysis. This technique should help us better understand the etiological mechanism of ASD and how it may adversely affect cellular homeostasis, which is essential to maintaining healthy metabolic pathways. Early diagnosis and intervention may be facilitated by this knowledge.

Characterising repetitive behaviours in children and adolescents with Down syndrome.

Individuals with intellectual disability, including people with Down syndrome (DS), often exhibit restricted and repetitive behaviours (RRBs). However, RRBs have not been deeply characterised in children and adolescents with DS. The study encompassed a cohort of 151 participants aged 4 to 18years with DS. RRBs were assessed utilising the Repetitive Behaviour Scale-Revised. Additionally, data pertaining to cognitive and adaptive functioning, linguistic abilities, sleep patterns and emotional/behavioural issues were gathered. Self-injurious behaviours were reported less frequently whereas parents most commonly endorsed items related to behaviours associated with the need for sameness and ritualistic behaviours. We observed very few gender differences, whereas some age-related differences emerged, with adolescents exhibiting higher scores in items related with higher-level RRBs. The analysis of the association between RRBs and clinical features revealed that RRBs were associated with parent-reported sleep difficulties, as well as with internalising and externalising problems. We also observed a negative correlation with IQ whereas associations with adaptive skills emerged mainly for lower-level RRBs, such as motor stereotypies. Finally, RRBs were negatively associated with linguistic abilities, both expressive and receptive. RRBs in children and adolescents with DS are of significant clinical interest due to their associations with various clinical dimensions. Therefore, psychological and neuropsychiatric assessment should include an accurate evaluation of RRBs for young people with DS.

Maternal choline supplementation modulates cognition and induces anti-inflammatory signaling in the prefrontal cortices of adolescent rats exposed to maternal immune activation

Maternal infection has long been described as a risk factor for neurodevelopmental disorders, especially autism spectrum disorders (ASD) and schizophrenia. Although many pathogens do not cross the placenta and infect the developing fetus directly, the maternal immune response to them is sufficient to alter fetal neurodevelopment, a phenomenon termed maternal immune activation (MIA). Low maternal choline is also a risk factor for neurodevelopmental disorders, and most pregnant people do not receive enough of it. In addition to its role in neurodevelopment, choline is capable of inducing anti-inflammatory signaling through a nicotinic pathway. Therefore, it was hypothesized that maternal choline supplementation would blunt the neurodevelopmental impact of MIA in offspring through long-term instigation of cholinergic anti-inflammatory signaling.To model MIA in rats, the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) was used to elicit a maternal antiviral innate immune response in dams both with and without choline supplementation. Offspring were reared to both early and late adolescent stages (postnatal days 28 and 50, respectively), where anxiety-related behaviors and cognition were examined. After behavioral testing, animals were euthanized, and their prefrontal cortices (PFCs) were collected for analysis. MIA offspring demonstrated sex-specific patterns of altered cognition and repetitive behaviors, which were modulated by maternal choline supplementation. Choline supplementation also bolstered anti-inflammatory signaling in the PFCs of MIA animals at both early and late adolescent stages. These findings suggest that maternal choline supplementation may be sufficient to blunt some of the behavioral and neurobiological impacts of inflammatory exposures in utero, indicating that it may be a cheap, safe, and effective intervention for neurodevelopmental disorders.

The influence of exercise intensity on comorbid anxious behavior in psychiatric conditions

Many experts have extensively studied the potential of exercise as a treatment option for psychiatric conditions, including depression and autism spectrum disorder (ASD). Despite their core symptoms, these conditions exhibits comparable component traits, an anxiety. In this study, we explored the effect of exercise on behavioral abnormalities in psychiatric conditions, focusing on its intensity and emotional resilience. Shank3B knockout (KOSED) mice displaying self-injurious repetitive behavior and C57BL/6J mice, susceptible to stress as ASD and depression model, respectively, were subjected to moderate-intensity exercise (ME) for 2 weeks. ME mitigated the core symptoms (excessive grooming traits and behavioral despair) but did not exert a significant anxiolytic effect. Notably, exercise intensity has emerged as a critical determinant of its efficacy, as evidenced by a lower ventilation threshold and anxiolytic effect mediated by low-intensity exercise. The findings substantiate the notion that exercise is promising as a disease-modifying treatment, but intensity matters for emotional resilience.Graphical

Association of Sensory Subtypes on Adaptive & Repetitive Behavior in Autistic Children Ages 6 to 18 Years

Abstract Date Presented 03/21/24 Sensory subtypes were applied to repetitive and adaptive behavior measures for autistic children ages 6 to 18 years. The extreme-mixed subtype, with elevated sensory response, had more repetitive behaviors and lower adaptive behaviors. Primary Author and Speaker: Sabrina Kabakov Additional Authors and Speakers: Karla Ausderau Contributing Authors: Olivia Surgent, Emily Skaletski, John Sideris, Brittany Travers

Farm Animal-Assisted Therapy Using Farm Animals for Individuals with Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a developmental disorder that affects an individual's ability to communicate, create social relationships, and regulate sensory input and repetitive behaviors. An uncommon intervention used in ASD treatment is farm animal-assisted therapy (AAT). AAT interventions focus on the use of animals in adjunct to achieve goals and outcomes. Farm AAT is defined as the use of farm animals such as cows, sheep, goats, horses, and pigs in AAT interventions. There is a lack of evidence on the use of farm animals and their benefits within the scope of AAT and in recreational therapy. The purpose of this study was to provide evidence, from the perspective of parents, of the potential benefits of farm AAT as a recreational therapy intervention for individuals with ASD. Data collection using a semi-structured interview guide was conducted over the phone with parents who participated in family session programs at the study location. Five participants were selected who matched the inclusion criteria for this study. The findings from this study reported that there were increases in social behaviors, regulation of behaviors, and a sense of normalcy for the children. The findings from this study provide a foundation for future research related to farm AAT such as evidenced-based curriculums and practices. The data provide therapists and parents with an understanding of the potential benefits that are gained from participation in farm AAT interventions.

An alpha 5-GABAA receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in rats exposed to valproic acid in utero.

Autism spectrum disorders (ASDs) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory balance due to a functional loss of GABAergic interneurons are proposed to underlie these symptoms. Increasing the postsynaptic effects of GABA with compounds that selectively modulate GABAergic receptors could be a potential target for treating ASD symptoms. In addition, deficits in GABAergic interneurons have been linked to dopamine (DA) system dysregulation, and, despite conflicting evidence, abnormalities in the DA system activity may underly some ASD symptoms. Here, we investigated whether the positive allosteric modulator of α5-containing GABAA receptors (α5-GABAARs) SH-053-2'F-R-CH3 (10 mg/kg) attenuates behavioral abnormalities in rats exposed to valproic acid (VPA) in utero, an established risk factor for autism. We also evaluated if animals exposed to VPA in utero present changes in the ventral tegmental area (VTA) DA system activity using in vivo electrophysiology and if SH-053-2'F-R-CH3 could attenuate these changes. SH-053-2'F-R-CH3 was administered intraperitoneally 30 min before each behavioral test and electrophysiology. In utero VPA exposure caused male and female rats to present increased repetitive behavior (self-grooming) in early adolescence and deficits in social interaction in adulthood. Male, but not female VPA rats, also presented deficits in recognition memory as adults. SH-053-2'F-R-CH3 attenuated the impairments in sociability and cognitive function in male VPA-exposed rats without attenuating the decreased social interaction in females. Adult male and female VPA-exposed rats also showed an increased VTA DA neuron population activity, which was not changed by SH-053-2'F-R-CH3. Despite sex differences, our findings indicate that α5-GABAARs positive allosteric modulators may effectively attenuate some core ASD symptoms.

Non-suicidal self-injury in trichotillomania and skin picking disorder.

Trichotillomania and skin picking disorder have been characterized as body-focused repetitive behavior (BFRB) disorders (i.e., repetitive self-grooming behaviors that involve biting, pulling, picking, or scraping one's own hair, skin, lips, cheeks, or nails). Trichotillomania and skin picking disorder have also historically been classified, by some, as types of compulsive self-injury as they involve repetitive hair pulling and skin picking, respectively. The question of the relationship of these disorders to more conventional forms of self-injury such as cutting or self-burning remains incompletely investigated. The objective of this study was to examine the relationship of these two disorders with non-suicidal self-injury (NSSI). Adults with trichotillomania (n=93) and skin picking (n=105) or both (n=82) were recruited from the general population using advertisements and online support groups and completed an online survey. Participants completed self-report instruments to characterize clinical profiles and associated characteristics. In addition, each participant completed a mental health history questionnaire. Of the 280 adults with BFRB disorders, 141 (50.1%) reported a history of self-injury independent of hair pulling and skin picking. Participants with a history of self-injury reported significantly worse pulling and picking symptoms (p<.001) and were significantly more likely to have co-occurring alcohol problems (p<.001), borderline personality disorder (p<.001), buying disorder (p<.001), gambling disorder (p<.001), compulsive sex behavior (p<001), and binge eating disorder (p=.041). NSSI appears common in trichotillomania and skin picking disorder and may be part of a larger constellation of behaviors associated with impulse control or reward-related dysfunction.

Advances in Pediatric Obsessive-Compulsive Disorder (OCD) Treatment: A Comprehensive Narrative Review.

Obsessive-compulsive disorder (OCD), characterized by persistent, intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), can significantly impact a child's daily functioning, academic performance, and overall quality of life. As the prevalence of pediatric OCD continues to rise, there is a critical demand for evidence-based treatments that not only alleviate symptoms but also enhance the quality of life for affected children and adolescents. By identifying gaps in knowledge and suggesting directions for future research, this narrative review contributes to the ongoing discourse on pediatric OCD treatments. Ultimately, the synthesis of evidence aims to enhance our understanding and inform best practices in the compassionate and effective management of OCD in children and adolescents.The aim of this study is to provide a comprehensive overview of current trends and emerging strategies in the treatment of pediatric obsessive-compulsive disorder (OCD) and highlights the significance of tailoring treatment approaches to individual patient needs, considering factors such as symptom severity and treatment response. Concentrating on interventions supported by empirical evidence, the review delves into cognitive-behavioral therapy (CBT), pharmacotherapy, the synergistic effects of these modalities, and inventive therapeutic approaches, all while considering the distinctive developmental aspects pertinent to pediatric populations.We conducted this review by searching for titles in the PubMed database from 2013 to present. Our comprehensive literature review focused on advancements in treating pediatric OCD, using keywords like "Obsessive-compulsive disorder," "Pediatric," "treatment," "CBT," "SSRI," "Pharmacotherapy," and "combination therapy." While both pharmacotherapy and CBT show individual efficacy, the combination of these approaches appears to be more effective, especially for medication non-responders with no prior exposure to CBT, despite some mixed findings. These findings contribute significantly to the ongoing discussion on optimizing combined therapy strategies tailored to the complexities of pediatric OCD.

Transcranial direct current stimulation as an augmentation therapy in patients with obsessive-compulsive disorder: A case series

Obsessive-compulsive disorder (OCD) is characterized by intrusive, distressing thoughts and/or repetitive behaviors. Transcranial direct current stimulation (tDCS) is a promising neuromodulation technique for augmenting pharmacotherapy in OCD. This case series identified patients diagnosed with OCD, who showed residual symptoms even after two adequate trials of pharmacotherapy corroborated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (score of eight and above taken as cutoff). tDCS was given in the form of two milliamperes current with anode at SMA and cathode at the right orbitofrontal area, for twenty minutes, for six sessions (one session per day) in addition to pharmacotherapy. Clinical assessment was performed using the Y BOCS at baseline and post treatment. The results revealed a reduction in OCD symptom severity in all the patients (as per both subjective report and Y-BOCS scores). The patients did not have any severe adverse effects. tDCS appears to be a potential augmentation therapy for individuals with OCD. However, further research is warranted to optimize stimulation parameters and elucidate the long-term effects of tDCS as part of a comprehensive treatment approach for OCD.

Sensory processing associated with subcategories of restricted and repetitive behaviors in Japanese children and adolescents with autism spectrum disorder

Sensory processing associated with subcategories of restricted and repetitive behaviors in Japanese children and adolescents with autism spectrum disorder

Characteristics and correlates of aggressive behavior in autistic youths.

This study aimed to characterize aggressive behaviors in autistic youths and to identify the social environment variables most strongly linked with aggression in this clinical population. Participants were 2142 caregivers of autistic youths (ages 6.0-17.9) recruited from autism research centers across the United States. Caregivers completed self-report and behavior rating inventories that assessed both verbal and physical aggression as well as characteristics of the individual youths (sleep quality, gastrointestinal [GI] symptoms, and autism characteristics) and their families (caregiver stress, global family functioning, and sibling relations), peers (emotional bonding, number of friends), schools (academic functioning), and neighborhoods (perceived community safety). We used descriptive analyses to identify which aggressive acts were most common among autistic youths, and we performed bivariate correlations and multiple linear regression analyses to determine which characteristics of the youths and their social environments were most strongly linked with youth aggression. Verbally aggressive youth behaviors were endorsed by caregivers most frequently. Youth age and sex were not associated with verbal or physical aggression. A combination of youth and social environment characteristics accounted for 42.6% of the variance in verbal aggression and 26.0% of the variance in physical aggression. Thus, those characteristics most strongly linked with verbal and physical aggression were strained sibling relations, caregiver stress, youth sleep problems, and youth repetitive and restrictive behaviors. Viewed together, the results suggest that aggressive behaviors in autistic youths are associated with multiple characteristics pertaining to the individual youths and their immediate social environments. Implications for treatment and research are discussed.

Autologous umbilical cord blood infusion for the treatment of autism in young children: A within-subjects open label study on safety (assessed via caregiver report) and efficacy.

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24-72 months. A pre-post treatment within-subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland-3), Stanford Binet Intelligence Scale (SB-5), Expressive One-Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder-Behavior Inventory, Repetitive Behavior Scale-Revised, Sensory Experience Questionnaire (SEQ-2.1), Child Behavior Checklist, Clinical Global Impression-Severity and Improvement (CGI-I) Scales, and eye-gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0-6 months was the control period, and 6-18 months the follow-up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post-thaw sample. There were no significant differences in Vineland-3, SB-5, BOSCC, and SEQ-2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI-I scores of 2-3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within-subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions.

Environmental enrichment reduces restricted repetitive behavior by altering gray matter microstructure.

Restricted, repetitive behaviors are common symptoms in neurodevelopmental disorders including autism spectrum disorder. Despite being associated with poor developmental outcomes, repetitive behaviors remain poorly understood and have limited treatment options. Environmental enrichment attenuates the development of repetitive behaviors, but the exact mechanisms remain obscure. Using the C58 mouse model of repetitive behavior, we performed diffusion tensor imaging to examine microstructural alterations associated with the development of repetitive behavior and its attenuation by environmental enrichment. The C57BL/6 mouse strain, which displays little or no repetitive behavior, was used as a control group. We observed widespread differences in diffusion metrics between C58 mice and C57BL/6 mice. In juvenile C58 mice, repetitive motor behavior displayed strong negative correlations with fractional anisotropy in multiple gray matter regions, whereas in young adult C58 mice, high repetitive motor behavior was most strongly associated with lower fractional anisotropy and higher radial diffusivity in the striatum. Environmental enrichment increased fractional anisotropy and axial diffusivity throughout gray matter regions in the brains of juvenile C58 mice and overlapped predominantly with cerebellar and sensory regions associated with repetitive behavior. Our results suggest environmental enrichment reduces repetitive behavior development by altering gray matter microstructure in the cerebellum, medial entorhinal cortex, and sensory processing regions in juvenile C58 mice. Under standard laboratory conditions, early pathology in these regions appears to contribute to later striatal and white matter dysfunction in adult C58 mice. Future studies should examine the role these regions play in the development of repetitive behavior and the relationship between sensory processing and cerebellar deficits and repetitive behavior.

Age and sex-dependent gut alterations in mice induced by neonatal immune activation with lipopolysaccharide

Neonatal immune activation (NIA) through exposure to lipopolysaccharide (LPS) induces adult behavioral changes in rodents that resemble symptoms of developmental disorders, such as autism spectrum disorder. The neonatal timing of LPS exposure appears to play a crucial role in determining the nature and extent of long-term changes. This study aims to explore whether a 3-day LPS-NIA triggers sex- and age-related changes in gut function, potentially linking LPS-NIA to gastrointestinal dysfunction. Male and female Swiss mice received intraperitoneal injections of LPS or saline on postnatal days (PN) 3, 5, and 7. At PN35 (juvenile) and PN70 (adult), gut inflammation and oxidative stress were evaluated in addition to assessments of working memory, depressive-like symptoms, sociability, and repetitive behavior. Gut examination showed elevated C-X-C motif chemokine receptor 3 (CXCR3) in LPS-NIA mice, while MyD88 and Zonulin expressions were significantly higher only in adult LPS-NIA females. Interleukin (IL)-23 expression increased in juvenile and adult male and juvenile female LPS-NIA mice. Oxidative changes included decreased duodenal reduced glutathione (GSH) in juvenile females and ileal GSH in adult females exposed to LPS-NIA. Regarding behavioral alterations, adult LPS-NIA females exhibited depressive-like behavior. Working memory deficits were observed across all LPS-NIA groups. Only juvenile LPS-NIA females increased grooming, while rearing was higher in adult LPS-NIA mice of both sexes. The findings imply that LPS-NIA impacts intestinal barrier function and causes gut inflammatory alterations that are sex- and age-specific. These findings pave the way for exploring potential mechanisms that could contribute to LPS-induced gastrointestinal disturbances among individuals with ASD.

The neurobiological mechanisms underlying the effects of exercise interventions in autistic individuals.

Autism spectrum disorder is a pervasive and heterogeneous neurodevelopmental condition characterized by social communication difficulties and rigid, repetitive behaviors. Owing to the complex pathogenesis of autism, effective drugs for treating its core features are lacking. Nonpharmacological approaches, including education, social-communication, behavioral and psychological methods, and exercise interventions, play important roles in supporting the needs of autistic individuals. The advantages of exercise intervention, such as its low cost, easy implementation, and high acceptance, have garnered increasing attention. Exercise interventions can effectively improve thecore features and co-occurring conditions of autism, buttheunderlying neurobiological mechanisms are unclear. Abnormal changes in the gut microbiome, neuroinflammation, neurogenesis, and synaptic plasticity may individually or interactively be responsible for atypical brain structure and connectivity, leading to specific autistic experiences and characteristics. Interestingly, exercise can affect these biological processes and reshape brain network connections, which may explain how exercise alleviates core features and co-occurring conditions in autistic individuals. In this review, we describe the definition, diagnostic approach, epidemiology, and current support strategies for autism; highlight the benefits of exercise interventions; and call for individualized programs for different subtypes of autistic individuals. Finally, the possible neurobiological mechanisms by which exercise improves autistic features are comprehensively summarized to inform the development of optimal exercise interventions and specific targets to meet the needs of autistic individuals.