Deficits In Social Interaction Research Articles

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

Novel splicing variant and gonadal mosaicism in DYRK1A gene identified by whole-genome sequencing in multiplex autism spectrum disorder families.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with considerable genetic heterogeneity. The disorder is clinically diagnosed based on DSM-5 criteria, featuring deficits in social communication and interaction, along with restricted and repetitive behaviours. Here, we performed whole-genome sequencing (WGS) on four individuals with ASD from two multiplex families (MPX), where more than one individual is affected, to identify potential single nucleotide variants (SNVs) and structural variants (SVs) in coding and non-coding regions. A rigorous bioinformatics pipeline was employed for variant detection, followed by segregation analysis. Our investigation revealed an unreported splicing variant in the DYRK1A gene (c.-77 + 2T > C; IVS1 + 2T > C; NM_001396.5), in heterozygote form in two affected children in one of the families (family B), which was absent in the healthy parents and siblings. This finding suggests the presence of gonadal mosaicism in one of the parents, representing the first documented instance of such inheritance for a variant in the DYRK1A gene associated with ASD. Furthermore, we identified a 50bp deletion in intron 9 of the DLG2 gene in two affected patients from the same family, confirmed by PCR and Sanger sequencing. In Family A, we identified potential candidate variants associated with ASD shared by the two patients. These findings enhance our understanding of the genetic landscape of ASD, particularly in MPX families, and highlight the utility of WGS in uncovering novel genetic contributions to neurodevelopmental disorders.

Assessment of 8-Hydroxy-2’-Deoxyguanosine (8-OH-dG) Level in Urine as a Urinary Marker of Oxidative Stress in Children with Autism Spectrum Disorder

Abstract Background Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction, restricted interest and repetitive behavior. Oxidative stress in response to environmental exposure plays a role in virtually every human disease and represents a significant avenue of research into the etiology of ASD. Objective The aim of this study was to asses 8-hydroxy-2’-deoxyguanosine (8-OH-dG) level in urine as a urinary marker of oxidative stress in children with autism spectrum disorder in comparison to sex and age matched healthy control group. Patients and Methods We included 51 children with autism (43 males and 8 females whose age ranged from 2 to 16 years). They were compared to 51 children of the same age as a control group. The diagnosis of autism was made based on the criteria of autistic disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSMV). In the patients group, detailed medical history included sociodemographic form and family history was taken for autistic group also Intelligence Quotient test IQ test and Childhood Autism Rating Scale (CARS) used to measure the severity of autism. In the study, 8-OHdG values in urine were investigated using the enzyme-linked immunosorbent assay (ELISA) method and Urinary creatinine was determined with the Beckham Coulter analyzer and was used to normalize all biochemical measurements then the urinary 8-OHdG/creatinine levels were corrected to the urinary concentration of creatinine. Results The median age was 9.9 in the ASD group and 9.1 in the control group (P = 0.256). In the ASD group, (8-OH-dG)/creatinine ratio values were found to be significantly higher than those of the controls (P < 0.001). but also No statistically significant correlation between (8-OH- dG)/creatinie ratio and CARS score or IQ score (P = 0,7). Conclusion The data from this study supported the hypothesis of the oxidant/antioxidant balance as a key piece that may contribute to the autistic pathology

Atypical local and global biological motion perception in children with attention deficit hyperactivity disorder

Perceiving biological motion (BM) is crucial for human survival and social interaction. Many studies have reported impaired BM perception in autism spectrum disorder, which is characterised by deficits in social interaction. Children with attention deficit hyperactivity disorder (ADHD) often exhibit similar difficulties in social interaction. However, few studies have investigated BM perception in children with ADHD. Here, we compared differences in the ability to process local kinematic and global configurational cues, two fundamental abilities of BM perception, between typically developing and ADHD children. We further investigated the relationship between BM perception and social interaction skills measured using the Social Responsiveness Scale and examined the contributions of latent factors (e.g. sex, age, attention, and intelligence) to BM perception. The results revealed that children with ADHD exhibited atypical BM perception. Local and global BM processing showed distinct features. Local BM processing ability was related to social interaction skills, whereas global BM processing ability significantly improved with age. Critically, general BM perception (i.e. both local and global BM processing) may be affected by sustained attentional ability in children with ADHD. This relationship was primarily mediated by reasoning intelligence. These findings elucidate atypical BM perception in ADHD and the latent factors related to BM perception. Moreover, this study provides new evidence that BM perception is a hallmark of social cognition and advances our understanding of the potential roles of local and global processing in BM perception and social cognitive disorders.

Atypical local and global biological motion perception in children with attention deficit hyperactivity disorder

Perceiving biological motion (BM) is crucial for human survival and social interaction. Many studies have reported impaired BM perception in autism spectrum disorder, which is characterised by deficits in social interaction. Children with attention deficit hyperactivity disorder (ADHD) often exhibit similar difficulties in social interaction. However, few studies have investigated BM perception in children with ADHD. Here, we compared differences in the ability to process local kinematic and global configurational cues, two fundamental abilities of BM perception, between typically developing and ADHD children. We further investigated the relationship between BM perception and social interaction skills measured using the Social Responsiveness Scale and examined the contributions of latent factors (e.g. sex, age, attention, and intelligence) to BM perception. The results revealed that children with ADHD exhibited atypical BM perception. Local and global BM processing showed distinct features. Local BM processing ability was related to social interaction skills, whereas global BM processing ability significantly improved with age. Critically, general BM perception (i.e. both local and global BM processing) may be affected by sustained attentional ability in children with ADHD. This relationship was primarily mediated by reasoning intelligence. These findings elucidate atypical BM perception in ADHD and the latent factors related to BM perception. Moreover, this study provides new evidence that BM perception is a hallmark of social cognition and advances our understanding of the potential roles of local and global processing in BM perception and social cognitive disorders.

Stabilizing axin leads to optic nerve hypoplasia in a mouse model of autism

Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.

Parent-Mediated Behavioural Intervention in Children with Autism Spectrum Disorder: A Scoping Review

ABSTRACT Children with autism spectrum disorder (ASD) exhibit deficits in social interaction and communication, show repetitive behaviours, and have restricted interests. They are at high risk of developing challenging behaviours, which can hinder social relationships, academic achievement, language skills, overall adaptive development, and also increase the risk of abuse in educational settings. This scoping review addresses the limited focus on parent-mediated behavioural intervention (PMBI) for managing challenging behaviours in children with ASD. Using the Arksey and O’Malley scoping review framework, we retrieved articles published between 2011 and 2022 from SCOPUS, ERIC, and SAGE Publications. Twelve articles met the inclusion criteria. Five themes emerged from the review regarding parents adopting PMBI: (1) performing functional behaviour analysis and developing behaviour intervention plans; (2) applying modification strategies and techniques of antecedent, behaviours and consequence; (3) establishing parent-child secure attachment relationship with child’s lead, positive and natural reinforcement; (4) decreasing child’s challenging behaviours; (5) improving child’s compliance, social responsiveness, and prosocial behaviours. The findings highlight parents as primary intervention agent, emphasising the importance of parental involvement in supporting their child’s development. This review suggests developing cost-effective parent education training programmes to support PMBI as part of comprehensive interventions for children with ASD.

Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social interaction deficits, communication impairments, repetitive behaviors, and sensory sensitivities. While the etiology of ASD is multifaceted, abnormalities in glutamatergic neurotransmission and synaptic plasticity have been implicated. This study investigated the role of metabotropic glutamate receptor 8 (mGlu8) in modulating long-term potentiation (LTP) in a rat model of ASD induced by prenatal valproic acid (VPA) exposure. To induce an animal model with autism-like characteristics, pregnant rats received an intraperitoneal injection of 500 mg/kg of sodium valproate (NaVPA) on embryonic day 12.5. High-frequency stimulation was applied to the perforant path-dentate gyrus (PP-DG) synapse to induce LTP, while the mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) was administered into the DG. The results revealed that VPA-exposed rats exhibited reduced LTP compared to controls. DCPG had contrasting effects, inhibiting LTP in controls and enhancing it in VPA-exposed rats. Moreover, reduced social novelty preference index (SNPI) in VPA-exposed rats was reversed by intra-DG administration of S-3,4-DCPG. In conclusion, our study advances our understanding of the complex relationship between glutamatergic neurotransmission, synaptic plasticity, and VPA-induced autism model. The findings suggest that mGlu8 receptor dysfunction plays a role in the impaired synaptic plasticity seen in ASD.

Exit interviews from two randomised placebo-controlled phase 3 studies with caregivers of young children with autism spectrum disorder

IntroductionAutism spectrum disorder (ASD) is characterised by difficulty with social communication and restricted, repetitive patterns of behaviour. This study aimed to improve understanding of the ASD patient experience with the treatment (bumetanide) regarding the changes in core symptoms and to assess changes considered as meaningful. To achieve this, qualitative interviews were conducted with caregivers of patients in two phase 3 clinical trials (NCT03715153; NCT03715166) of a novel ASD treatment.MethodsCaregivers were invited to participate in one interview after completion of the pivotal phase 3 study; for those of them who continued treatment after study completion, a second interview was held 3 months after trial completion. The interviews were conducted by qualitative researchers and followed a semi-structured interview guide. The interviews focused on patients’ ASD symptoms and their impact on their daily life before enrolment, and on any symptom changes patients experienced during the trial.ResultsOut of the 13 eligible patients’ caregivers, 11 were interviewed up to two times at clinical sites in the UK, Spain, and Italy. The caregivers reported impairments in a wide range of skills: deficits in communication and social interaction; restricted, repetitive patterns of behaviour, interests, or activities; and cognitive, emotional, and motor impairments. Compared to before the trial initiation, caregivers also reported improvements in the following domains: communication, interaction with others, cognition, aggression, emotions, repetitive movements, eating, and sleeping.ConclusionThe exit interviews provided a rich source of qualitative data, allowing a deeper understanding of caregivers’ and patients’ experience of the disease and allowing us to understand what constitutes a meaningful change. These data also helped identify important experiences that may inform the patient-reported outcome measurement strategy for future trials in ASD.

Unraveling the Spectrum: A Comprehensive Review of Autism Spectrum Disorder in India.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social interaction, communication difficulties, and repetitive behaviors that profoundly impact the lives of affected individuals and their families. This article provides a comprehensive overview of ASD, focusing on screening, diagnosis, and intervention strategies. Early signs of ASD can manifest in infancy, but parents may not recognize them until their child falls behind in meeting social milestones. This delay in recognition is often due to a lack of awareness, societal stigma, and limited knowledge about developmental and behavioral disorders. Globally, ASD prevalence is increasingpotentially due to broader diagnostic criteria, increased awareness, and improved screening practices. Screening for ASD is crucial for early identification and intervention. Various tools are available such as the Modified Checklist for Autism in Toddlers (M-CHATs), Trivandrum Autism Behavioral Checklist (TABC), and the Social Communication Questionnaire (SCQ). Diagnosing ASD involves using established criteria such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and specific diagnostic tools like the Autism Diagnostic Observation Schedule (ADOS) and the Indian Scale for the Assessment of Autism (ISAA). Interventions for ASD should be multidisciplinary, involving professionals such as developmental pediatricians, psychologists, psychiatrists, special educators, occupational therapists, physiotherapists, speech therapists, and social workers. Applied behavior analysis (ABA), naturalistic developmental behavioral interventions (NDBIs), and parent-mediated treatment are among the evidence-based approaches. Additionally, speech-language therapy, motor therapy, and sensory integration therapy play vital roles in addressing the diverse needs of individuals with ASD. Medical interventions should be used alongside behavioral and environmental strategies. Early screening, accurate diagnosis, and tailored interventions are essential for improving the lives of individuals with ASD. A multidisciplinary approach and increased awareness are crucial in addressing the growing prevalence of ASD worldwide.

Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo.

Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.

Prefrontal Cortex Responses to Social Video Stimuli in Young Children with and without Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting individuals worldwide and characterized by deficits in social interaction along with the presence of restricted interest and repetitive behaviors. Despite decades of behavioral research, little is known about the brain mechanisms that influence social behaviors among children with ASD. This, in part, is due to limitations of traditional imaging techniques specifically targeting pediatric populations. As a portable and scalable optical brain monitoring technology, functional near infrared spectroscopy (fNIRS) provides a measure of cerebral hemodynamics related to sensory, motor, or cognitive function. Here, we utilized fNIRS to investigate the prefrontal cortex (PFC) activity of young children with ASD and with typical development while they watched social and nonsocial video clips. The PFC activity of ASD children was significantly higher for social stimuli at medial PFC, which is implicated in social cognition/processing. Moreover, this activity was also consistently correlated with clinical measures, and higher activation of the same brain area only during social video viewing was associated with more ASD symptoms. This is the first study to implement a neuroergonomics approach to investigate cognitive load in response to realistic, complex, and dynamic audiovisual social stimuli for young children with and without autism. Our results further confirm that new generation of portable fNIRS neuroimaging can be used for ecologically valid measurements of the brain function of toddlers and preschool children with ASD.

Gut Microbiota in Autism Spectrum Disorder: A Systematic Review

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with stereotyped behavior and deficits in communication and social interaction. There is increasing evidence of the implication of gut microbiota in ASD. We conducted a systematic review to summarize previously published data to compare the profile of gut microbiota between autistic and neurotypical subjects. The outcomes of interventions such as prebiotics, probiotics, and microbiota transplantation therapy to overcome the symptomatology of ASD were also discussed. The current review allows us to associate gut microbiota dysbiosis and ASD. To date, there is still little consensus on which bacterial species are consistently altered in individuals with autism. Further studies are required to obtain stronger evidence of the relationship between gut microbiota and the severity of ASD conjointly with the effectiveness of dietary/probiotic interventions in reducing autistic behaviors compared to their healthy siblings.

Hyperglycemia as a gestational factor associated with Autism Spectrum Disorder: a review of the literature

Introduction: Autism Spectrum Disorder is a neurodevelopmental disorder characterized by deficits in social interaction, communication, and repetitive behaviors. The etiology, which has been the subject of studies, is influenced by a range of factors, including genetic, environmental, and gestational aspects. Methods: This article aims to review the literature, exploring the gestational causes associated with ASD, concentrating on intrauterine hyperglycemia. Results: The analysis reveals a scarcity of empirical studies, highlighting the need for additional research, especially in the Brazilian context. Conclusion: The results show that hyperglycemia during pregnancy can increase the risk of ASD, highlighting the importance of further research in this area.

Interaction of serotonin/GLP-1 circuitry in a dual preclinical model for psychiatric disorders and metabolic dysfunction

Isolation of rodents throughout adolescence is known to induce many behavioral abnormalities which resemble neuropsychiatric disorders. Separately, this paradigm has also been shown to induce long-term metabolic changes consistent with a pre-diabetic state. Here, we investigate changes in central serotonin (5-HT) and glucagon-like peptide 1 (GLP-1) neurobiology that dually accompany behavioral and metabolic outcomes following social isolation stress throughout adolescence. We find that adolescent-isolation mice exhibit elevated blood glucose levels, impaired peripheral insulin signaling, altered pancreatic function, and fattier body composition without changes in bodyweight. These mice further exhibited disruptions in sleep and enhanced nociception. Using bulk and spatial transcriptomic techniques, we observe broad changes in neural 5-HT, GLP-1, and appetitive circuits. We find 5-HT neurons of adolescent-isolation mice to be more excitable, transcribe fewer copies of Glp1r (mRNA; GLP-1 receptor), and demonstrate resistance to the inhibitory effects of the GLP-1R agonist semaglutide on action potential thresholds. Surprisingly, we find that administration of semaglutide, commonly prescribed to treat metabolic syndrome, induced deficits in social interaction in group-housed mice and rescued social deficits in isolated mice. Overall, we find that central 5-HT circuitry may simultaneously influence mental well-being and metabolic health in this model, via interactions with GLP-1 and proopiomelanocortin circuitry.

Deleterious effect of sustained neuroinflammation in pediatric traumatic brain injury

IntroductionDespite improved management of traumatic brain injury (TBI), it still leads to lifelong sequelae and disability, particularly in children. Chronic neuroinflammation (the so-called tertiary phase), in particular, microglia/macrophage and astrocyte reactivity, is among the main mechanisms suspected of playing a role in the generation of lesions associated with TBI. The role of acute neuroinflammation is now well understood, but its persistent effect and impact on the brain, particularly during development, are not. Here, we investigated the long-term effects of pediatric TBI on the brain in a mouse model. MethodsPediatric TBI was induced in mice on postnatal day (P) 7 by weight-drop trauma. The time course of neuroinflammation and myelination was examined in the TBI mice. They were also assessed by magnetic resonance, functional ultrasound, and behavioral tests at P45. ResultsTBI induced robust neuroinflammation, characterized by acute microglia/macrophage and astrocyte reactivity. The long-term consequences of pediatric TBI studied on P45 involved localized scarring astrogliosis, persistent microgliosis associated with a specific transcriptomic signature, and a long-lasting myelination defect consisting of the loss of myelinated axons, a decreased level of myelin binding protein, and severe thinning of the corpus callosum. These results were confirmed by reduced fractional anisotropy, measured by diffusion tensor imaging, and altered inter- and intra-hemispheric connectivity, measured by functional ultrasound imaging. In addition, adolescent mice with pediatric TBI showed persistent social interaction deficits and signs of anxiety and depressive behaviors. ConclusionsWe show that pediatric TBI induces tertiary neuroinflammatory processes associated with white matter lesions and altered behavior. These results support our model as a model for preclinical studies for tertiary lesions following TBI.

Subthalamic Nucleus Stimulation Modulates Cognitive Theory of Mind in Parkinson's Disease.

Theory of mind (ToM), the ability to infer others' mental state, is essential for social interaction among human beings. It has been widely reported that both cognitive (inference of knowledge) and affective (inference of emotion) components of ToM are disrupted in Parkinson's disease (PD). Previous studies usually focused on the involvement of the prefrontal cortex. This study investigated the causal role of the subthalamic nucleus (STN), a key hub of the fronto-basal ganglia loops, in ToM. Thirty-four patients with idiopathic PD (15 women, aged 62.2 ± 8.3 years) completed a Yoni task with deep brain stimulation (DBS) ON and OFF. The Yoni task was designed to separate the cognitive and affective components of ToM. Volumes of tissue activated (VTA) were computed for three subregions of the STN. DBS showed insignificant effects on ToM inference costs at the group level, which may be due to the large interindividual variability. The associative VTA correlated with the cognitive inference cost change but not the affective inference cost change. Patients with greater associative STN stimulation infer more slowly on cognitive ToM. Stimulating associative STN can adversely affect cognitive ToM in PD patients, especially in patients with a wide range of stimulation (≥0.157) or cognitive decline (Montreal Cognitive Assessment < 26). The associative STN plays a causal role in cognitive ToM in patients with PD. However, stimulating the associative STN likely impairs cognitive ToM and potentially leads to social interaction deficits in PD. © 2024 International Parkinson and Movement Disorder Society.

Aflatoxin B1 exposure exacerbates chemokine receptor expression in the BTBR T+ Itpr3tf/J Mouse Model, unveiling insights into autism spectrum disorder: A focus on brain and spleen

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant difficulties in social interaction, communication, and repeated stereotypic behaviour. Aflatoxin B1 (AFB1) is the most potent and well-known mycotoxin in various food sources. Despite its propensity to generate significant biochemical and structural changes in human and animal tissues, the influence of AFB1 on ASD has yet to be thoroughly studied. Mounting evidence indicates that chemokine receptors play a crucial function in the central nervous system and are implicated in developing several neuroinflammatory disorders. Chemokine receptors in individuals with ASD were elevated in the anterior cingulate gyrus astrocytes, cerebellum, and brain. MethodsThe BTBR T+Itpr3tf/J (BTBR) mice are inbred strains that exhibit strong and consistently observed deficits in social interactions, characterized by excessive self-grooming and limited vocalization in social contexts. We examined the impact of AFB1 on CCR3-, CCR7-, CCR9-, CXCR3-, CXCR4-, and CXCR6-expressing I-A/I-E+ cells in the spleen of the BTBR mouse model of autism. We evaluated the mRNA levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 chemokine receptors in the brain. ResultsThe exposure to AFB1 in BTBR mice resulted in a significant rise in the number of I-A/I-E+CCR3+, I-A/I-E+CCR7+, I-A/I-E+CCR9+, I-A/I-E+CXCR3+, I-A/I-E+CXCR4+, and I-A/I-E+CXCR6+ cells. Furthermore, exposure to AFB1 increased mRNA expression levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 in the brain. ConclusionsThese findings highlight that AFB1 exposure increases the expression of chemokine receptors in BTBR mice, indicating the necessity for further research into AFB1's role in the development of ASD.

Autism: Clinical impacts and late diagnosis in women - Literature review

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder, marked by deficits in communication and social interaction and restricted and repetitive behavior patterns. With the expansion of information dissemination about autism and improvements in diagnostic methods, the prevalence of the disorder has increased considerably in recent decades. However, because autism has multiple facets and different presentations, diagnosis is still a challenge, especially in females, where there are singularities that further undermine suspicions, leading to underdiagnosis. Given this, there are multiple questions about the causes and implications of these factors in the diagnosis of autistic girls and women. Thus, the objective of this research is to verify the causal factors and clinical implications associated with the difficulty in diagnosing ASD in females. This is a narrative bibliographic review, in which research was carried out in established databases. In general, it is noted that the diagnosis of autism in girls and women can be impacted by genetic, developmental, psychological, social and cultural influences, involving factors such as subtlety of symptoms, capacity for social adaptability, lack of studies, failure to diagnostic methodologies and instruments, as well as stereotypes and prejudices. Understanding these elements is essential to broaden the perspective of girls and women with ASD, highlight their particularities and ensure that they receive early diagnosis and treatment.

Perinatal exposure to atazanavir-based antiretroviral regimens in a mouse model leads to differential long-term motor and cognitive deficits dependent on the NRTI backbone.

Combination antiretroviral therapy (ART) use in pregnancy has been pivotal in improving maternal health and reducing perinatal HIV transmission. However, children born HIV-exposed uninfected fall behind their unexposed peers in several areas including neurodevelopment. The contribution of in utero ART exposure to these deficits is not clear. Here we present our findings of neurocognitive outcomes in adult mice exposed in utero to ART. Dams were treated with a combination of ritonavir-boosted atazanavir with either abacavir plus lamivudine (ABC/3TC + ATV/r) or tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC + ATV/r), or water as a control, administered daily from day of plug detection to birth. Offspring underwent a battery of behavioral tests that investigated motor performance and cognition starting at 6-weeks of age and ending at 8 months. Changes in brain structure were assessed using magnetic resonance imaging and immunohistochemistry. Expression of genes involved in neural circuitry and synaptic transmission were assessed in the hippocampus, a region strongly associated with memory formation, using qPCR. Pups exposed to TDF/FTC + ATV/r showed increased motor activity and exploratory drive, and deficits in hippocampal-dependent working memory and social interaction, while pups exposed to ABC/3TC + ATV/r showed increased grooming, and deficits in working memory and social interaction. Significant volumetric reductions in the brain were seen only in the ABC/3TC + ATV/r group and were associated with reduced neuronal counts in the hippocampus. Altered neurotransmitter receptor mRNA expression as well as changes in expression of the neurotrophic factor BDNF and its receptors were observed in both ART-exposed groups in a sex-dependent manner. In our model, in utero ART exposure had long-term effects on brain development and cognitive and motor outcomes in adulthood. Our data show that neurological outcomes can be influenced by the type of nucleoside reverse transcriptase inhibitor backbone of the regimen and not just the base drug, and display sex differences.