La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)
The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)
Humans , Child, Preschool , Child , Adolescent , Educational Technology , Autism Spectrum Disorder , Autistic Disorder
La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)
The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)
Humans , Child, Preschool , Child , Adolescent , Educational Technology , Autism Spectrum Disorder , Autistic Disorder
BACKGROUND: Autistic children often experience socioemotional difficulties relating to emotion regulation and mental health problems. Supports for autistic children involve the use of adapted interventions that target emotion regulation and social skills, alongside mental health symptoms. The Secret Agent Society Small Group (SAS: SG), an adapted cognitive behavioural program, has demonstrated efficacy through lab-delivered randomized control trials. However, research is still needed on its effectiveness when delivered by publicly funded, community-based autism providers under real-world ecologically valid conditions, especially within the context of a pandemic. The COVID-19 pandemic has disrupted access to community-based supports and services for autistic children, and programs have adapted their services to online platforms. However, questions remain about the feasibility and clinical utility of evidence-based interventions and services delivered virtually in community-based settings. METHODS: The 9-week SAS: SG program was delivered virtually by seven community-based autism service providers during 2020-2021. The program included the use of computer-based games, role-playing tasks, and home missions. Caregivers completed surveys at three timepoints: pre-, post-intervention, and after a 3-month follow-up session. Surveys assessed caregivers' perception of the program's acceptability and level of satisfaction, as well as their child's social and emotional regulation skills and related mental health challenges. RESULTS: A total of 77 caregivers (94% gender identity females; Mean = 42.1 years, SD = 6.5 years) and their children (79% gender identity males; Mean = 9.9 years, SD = 1.3 years) completed the SAS: SG program. Caregivers agreed that the program was acceptable (95%) and were highly satisfied (90%). Caregivers reported significant reduction in their child's emotion reactivity from pre- to post-intervention (-1.78 (95% CI, -3.20 to -0.29), p = 0.01, d = 0.36), that continued to decrease after the 3-month booster session (-1.75 (95% CI, -3.34 to -0.16), p = 0.02, d = 0.33). Similarly, improvements in anxiety symptoms were observed (3.05 (95% CI, 0.72 to 5.36), p = 0.006, d = 0.39). CONCLUSIONS: As online delivery of interventions for autistic children remains popular past the pandemic, our findings shed light on future considerations for community-based services, including therapists and agency leaders, on how best to tailor and optimally deliver virtually based programming. TRIAL REGISTRATION: This study has been registered with ISRCTN Registry (ISRCTN98068608) on 15/09/2023. The study was retroactively registered.
Autistic Disorder , COVID-19 , Cognitive Behavioral Therapy , Humans , COVID-19/epidemiology , Male , Female , Child , Autistic Disorder/therapy , Autistic Disorder/psychology , Cognitive Behavioral Therapy/methods , SARS-CoV-2 , Pandemics , Adult , Emotional Regulation
Mental health issues are markedly increased in individuals with autism, making it the number one research priority by stakeholders. There is a crucial need to use personalized approaches to understand the underpinnings of mental illness in autism and consequently, to address individual needs. Based on the risk factors identified in typical mental research, we propose the following themes central to mental health issues in autism: sleep difficulties and stress. Indeed, the prevalence of manifold circadian disruptions and sleep difficulties in autism, alongside stress related to sensory overload, forms an integral part of autistic symptomatology. This proof-of-concept study protocol outlines an innovative, individualised approach towards investigating the interrelationships between stress indices, sleep and circadian activation patterns, and sensory sensitivity in autism. Embracing an individualized methodology, we aim to collect 14 days of data per participant from 20 individuals with autism diagnoses and 20 without. Participants' sleep will be monitored using wearable EEG headbands and a sleep diary. Diurnal tracking of heart rate and electrodermal activity through wearables will serve as proxies of stress. Those objective data will be synchronized with subjective experience traces collected throughout the day using the Temporal Experience Tracing (TET) method. TET facilitates the quantification of relevant aspects of individual experience states, such as stress or sensory sensitivities, by providing a continuous multidimensional description of subjective experiences. Capturing the dynamics of subjective experiences phase-locked to neural and physiological proxies both between and within individuals, this approach has the potential to contribute to our understanding of critical issues in autism, including sleep problems, sensory reactivity and stress. The planned strives to provide a pathway towards developing a more nuanced and individualized approach to addressing mental health in autism.
Autistic Disorder , Circadian Rhythm , Stress, Psychological , Humans , Autistic Disorder/physiopathology , Autistic Disorder/psychology , Circadian Rhythm/physiology , Stress, Psychological/physiopathology , Sleep Quality , Male , Female , Adult , Adolescent , Sleep/physiology , Heart Rate/physiology , Young Adult , Electroencephalography
Although most individuals who carry the Fragile X premutation allele, defined as 55-200 CGG repeats on the X-linked FMR1 gene (Fragile X Messenger Ribonucleoprotein 1 gene), do not meet diagnostic criteria for autism spectrum disorder, there is a suggestion of increased behaviors associated with subtle autistic traits. More autism associated characteristics have been reported among adults than children. This may highlight a possible worsening developmental trajectory, variable findings due to research quality or differences in number of studies done in adults vs children, rather than true developmental changes. This review is designed to examine the neurodevelopmental profile associated with the premutation allele from a developmental perspective, focused on autistic traits.
Fragile X Mental Retardation Protein , Fragile X Syndrome , Humans , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , Child , Alleles , Autism Spectrum Disorder/genetics , Adult , Autistic Disorder/genetics
Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.
Behavior, Animal , Extracellular Vesicles , Mesenchymal Stem Cells , MicroRNAs , NF-kappa B , Signal Transduction , MicroRNAs/metabolism , MicroRNAs/genetics , Animals , Extracellular Vesicles/metabolism , NF-kappa B/metabolism , Mesenchymal Stem Cells/metabolism , Autistic Disorder/genetics , Autistic Disorder/metabolism , Microglia/metabolism , Male , Mice , Toll-Like Receptor 4/metabolism , Inflammation/pathology , Mice, Inbred C57BL , Lipopolysaccharides
Prior work examined how minimally verbal (MV) children with autism used their gestural communication during social interactions. However, interactions are exchanges between social partners. Examining parent-child social interactions is critically important given the influence of parent responsivity on children's communicative development. Specifically, parent responses that are semantically contingent to the child's communication plays an important role in further shaping children's language learning. This study examines whether MV autistic children's (N = 47; 48-95 months; 10 females) modality and form of communication are associated with parent responsivity during an in-home parent-child interaction (PCI). The PCI was collected using natural language sampling methods and coded for child modality and form of communication and parent responses. Findings from Kruskal-Wallis H tests revealed that there was no significant difference in parent semantically contingent responses based on child communication modality (spoken language, gesture, gesture-speech combinations, and AAC) and form of communication (precise vs. imprecise). Findings highlight the importance of examining multiple modalities and forms of communication in MV children with autism to obtain a more comprehensive understanding of their communication abilities; and underscore the inclusion of interactionist models of communication to examine children's input on parent responses in further shaping language learning experiences.
Autistic Disorder , Communication , Parent-Child Relations , Humans , Female , Male , Child , Child, Preschool , Autistic Disorder/psychology , Gestures , Parents , Language Development , Speech
Autistic people exhibit atypical use of prior information when processing simple perceptual stimuli; yet, it remains unclear whether and how these difficulties in using priors extend to complex social stimuli. Here, we compared autistic people without accompanying intellectual disability and nonautistic people in their ability to acquire an "emotional prior" of a facial expression and update this prior to a different facial expression of the same identity. Participants performed a two-interval same/different discrimination task between two facial expressions. To study the acquisition of the prior, we examined how discrimination was modified by the contraction of the perceived facial expressions toward the average of presented stimuli (i.e., regression to the mean). At first, facial expressions surrounded one average emotional prior (mostly sad or angry), and then the average switched (to mostly angry or sad, accordingly). Autistic people exhibited challenges in facial discrimination, and yet acquired the first prior, demonstrating typical regression-to-the-mean effects. However, unlike nonautistic people, autistic people did not update their perception to the second prior, suggesting they are less flexible in updating an acquired prior of emotional expressions. Our findings shed light on the perception of emotional expressions, one of the most pressing challenges in autism.
Anger , Autistic Disorder , Facial Expression , Humans , Female , Male , Adult , Anger/physiology , Autistic Disorder/psychology , Young Adult , Learning/physiology , Social Perception , Adolescent , Emotions/physiology , Discrimination, Psychological/physiology
Importance: Finding effective and scalable solutions to address diagnostic delays and disparities in autism is a public health imperative. Approaches that integrate eye-tracking biomarkers into tiered community-based models of autism evaluation hold promise for addressing this problem. Objective: To determine whether a battery of eye-tracking biomarkers can reliably differentiate young children with and without autism in a community-referred sample collected during clinical evaluation in the primary care setting and to evaluate whether combining eye-tracking biomarkers with primary care practitioner (PCP) diagnosis and diagnostic certainty is associated with diagnostic outcome. Design, Setting, and Participants: Early Autism Evaluation (EAE) Hub system PCPs referred a consecutive sample of children to this prospective diagnostic study for blinded eye-tracking index test and follow-up expert evaluation from June 7, 2019, to September 23, 2022. Participants included 146 children (aged 14-48 months) consecutively referred by 7 EAE Hubs. Of 154 children enrolled, 146 provided usable data for at least 1 eye-tracking measure. Main Outcomes and Measures: The primary outcomes were sensitivity and specificity of a composite eye-tracking (ie, index) test, which was a consolidated measure based on significant eye-tracking indices, compared with reference standard expert clinical autism diagnosis. Secondary outcome measures were sensitivity and specificity of an integrated approach using an index test and PCP diagnosis and certainty. Results: Among 146 children (mean [SD] age, 2.6 [0.6] years; 104 [71%] male; 21 [14%] Hispanic or Latine and 96 [66%] non-Latine White; 102 [70%] with a reference standard autism diagnosis), 113 (77%) had concordant autism outcomes between the index (composite biomarker) and reference outcomes, with 77.5% sensitivity (95% CI, 68.4%-84.5%) and 77.3% specificity (95% CI, 63.0%-87.2%). When index diagnosis was based on the combination of a composite biomarker, PCP diagnosis, and diagnostic certainty, outcomes were concordant with reference standard for 114 of 127 cases (90%) with a sensitivity of 90.7% (95% CI, 83.3%-95.0%) and a specificity of 86.7% (95% CI, 70.3%-94.7%). Conclusions and Relevance: In this prospective diagnostic study, a composite eye-tracking biomarker was associated with a best-estimate clinical diagnosis of autism, and an integrated diagnostic model including PCP diagnosis and diagnostic certainty demonstrated improved sensitivity and specificity. These findings suggest that equipping PCPs with a multimethod diagnostic approach has the potential to substantially improve access to timely, accurate diagnosis in local communities.
Autistic Disorder , Biomarkers , Eye-Tracking Technology , Primary Health Care , Humans , Male , Female , Child, Preschool , Primary Health Care/methods , Prospective Studies , Infant , Biomarkers/blood , Biomarkers/analysis , Autistic Disorder/diagnosis , Sensitivity and Specificity
Autism spectrum disorder (ASD) is a developmental disorder with a rising prevalence and unknown etiology presenting with deficits in cognition and abnormal behavior. We hypothesized that the investigation of the synaptic component of prefrontal cortex may provide proteomic signatures that may identify the biological underpinnings of cognitive deficits in childhood ASD. Subcellular fractions of synaptosomes from prefrontal cortices of age-, brain area-, and postmortem-interval-matched samples from children and adults with idiopathic ASD vs. controls were subjected to HPLC-tandem mass spectrometry. Analysis of data revealed the enrichment of ASD risk genes that participate in slow maturation of the postsynaptic density (PSD) structure and function during early brain development. Proteomic analysis revealed down regulation of PSD-related proteins including AMPA and NMDA receptors, GRM3, DLG4, olfactomedins, Shank1-3, Homer1, CaMK2α, NRXN1, NLGN2, Drebrin1, ARHGAP32, and Dock9 in children with autism (FDR-adjusted P < 0.05). In contrast, PSD-related alterations were less severe or unchanged in adult individuals with ASD. Network analyses revealed glutamate receptor abnormalities. Overall, the proteomic data support the concept that idiopathic autism is a synaptopathy involving PSD-related ASD risk genes. Interruption in evolutionarily conserved slow maturation of the PSD complex in prefrontal cortex may lead to the development of ASD in a susceptible individual.
Dorsolateral Prefrontal Cortex , Proteomics , Humans , Child , Male , Female , Adult , Dorsolateral Prefrontal Cortex/metabolism , Child, Preschool , Autism Spectrum Disorder/metabolism , Autism Spectrum Disorder/genetics , Synapses/metabolism , Adolescent , Young Adult , Autistic Disorder/metabolism , Autistic Disorder/genetics , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , Synaptosomes/metabolism , Prefrontal Cortex/metabolism , Post-Synaptic Density/metabolism
Adolescence has been characterized as a period of risky and possibly suboptimal decision-making, yet the development of decision-making in autistic adolescents is not well understood. To investigate decision-making in autism, we evaluated performance on 2 computerized tasks capturing decision-making under explicit risk and uncertainty in autistic and non-autistic adolescents/young adults ages 12-22 years. Participants completed the Game of Dice Task (32 IQ-matched participant pairs) to assess decision-making under explicit risk and the modified Iowa Gambling Task (35 IQ-matched pairs) to assess decision-making under uncertainty. Autistic participants overall made riskier decisions than non-autistic participants on the Game of Dice Task, and the odds of making riskier decisions varied by age and IQ. In contrast, the autistic group showed comparable levels of learning over trial blocks to the non-autistic group on the modified Iowa Gambling Task. For both tasks, younger autistic participants performed poorer than their non-autistic counterparts, while group differences diminished in older ages. This age-related pattern suggests positive development during adolescence on risk assessment and decision-making in autism but also implies differential developmental trajectories between groups. These findings also suggest differential performance by the risk type, with additional complex influences of IQ and fluid cognition, which warrants further investigations.
Autistic Disorder , Decision Making , Humans , Adolescent , Decision Making/physiology , Male , Young Adult , Female , Uncertainty , Child , Autistic Disorder/psychology , Risk-Taking , Neuropsychological Tests , Gambling/psychology
Autism is characterized by atypical social communication styles. To investigate whether individuals with high autistic traits could still have effective social communication among each other, we compared the behavioral patterns and communication quality within 64 dyads of college students paired with both high, both low, and mixed high-low (HL) autistic traits, with their gender matched. Results revealed that the high-high (HH) autistic dyads exhibited atypical behavioral patterns during conversations, including reduced mutual gaze, communicational turns, and emotional sharing compared with the low-low and/or HL autistic dyads. However, the HH autistic dyads displayed enhanced interpersonal neural synchronization during social communications measured by functional near-infrared spectroscopy, suggesting an effective communication style. Besides, they also provided more positive subjective evaluations of the conversations. These findings highlight the potential for alternative pathways to effectively communicate with the autistic community, contribute to a deeper understanding of how high autistic traits influence social communication dynamics among autistic individuals, and provide important insights for the clinical practices for supporting autistic people.
Autistic Disorder , Communication , Spectroscopy, Near-Infrared , Humans , Male , Female , Young Adult , Autistic Disorder/psychology , Autistic Disorder/physiopathology , Interpersonal Relations , Social Behavior , Social Interaction , Brain/physiopathology , Brain/physiology , Adult , Cortical Synchronization/physiology , Adolescent
Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.
Brain , Humans , Adult , Autism Spectrum Disorder/therapy , Precision Medicine/methods , Precision Medicine/trends , Transcranial Magnetic Stimulation/methods , Autistic Disorder/therapy , Autistic Disorder/physiopathology , Autistic Disorder/psychology , Transcranial Direct Current Stimulation/methods
Autism spectrum disorder has been emerging as a growing public health threat. Early diagnosis of autism spectrum disorder is crucial for timely, effective intervention and treatment. However, conventional diagnosis methods based on communications and behavioral patterns are unreliable for children younger than 2 years of age. Given evidences of neurodevelopmental abnormalities in autism spectrum disorder infants, we resort to a novel deep learning-based method to extract key features from the inherently scarce, class-imbalanced, and heterogeneous structural MR images for early autism diagnosis. Specifically, we propose a Siamese verification framework to extend the scarce data, and an unsupervised compressor to alleviate data imbalance by extracting key features. We also proposed weight constraints to cope with sample heterogeneity by giving different samples different voting weights during validation, and used Path Signature to unravel meaningful developmental features from the two-time point data longitudinally. We further extracted machine learning focused brain regions for autism diagnosis. Extensive experiments have shown that our method performed well under practical scenarios, transcending existing machine learning methods and providing anatomical insights for autism early diagnosis.
Autism Spectrum Disorder , Brain , Deep Learning , Early Diagnosis , Humans , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/diagnosis , Infant , Brain/diagnostic imaging , Brain/pathology , Magnetic Resonance Imaging/methods , Child, Preschool , Male , Female , Autistic Disorder/diagnosis , Autistic Disorder/diagnostic imaging , Autistic Disorder/pathology , Unsupervised Machine Learning
Attentional reorienting is dysfunctional not only in children with autism spectrum disorder (ASD), but also in infants who will develop ASD, thus constituting a potential causal factor of future social interaction and communication abilities. Following the research domain criteria framework, we hypothesized that the presence of subclinical autistic traits in parents should lead to atypical infants' attentional reorienting, which in turn should impact on their future socio-communication behavior in toddlerhood. During an attentional cueing task, we measured the saccadic latencies in a large sample (total enrolled n = 89; final sample n = 71) of 8-month-old infants from the general population as a proxy for their stimulus-driven attention. Infants were grouped in a high parental traits (HPT; n = 23) or in a low parental traits (LPT; n = 48) group, according to the degree of autistic traits self-reported by their parents. Infants (n = 33) were then longitudinally followed to test their socio-communicative behaviors at 21 months. Results show a sluggish reorienting system, which was a longitudinal predictor of future socio-communicative skills at 21 months. Our combined transgenerational and longitudinal findings suggest that the early functionality of the stimulus-driven attentional network-redirecting attention from one event to another-could be directly connected to future social and communication development.
Attention , Parents , Humans , Male , Female , Infant , Attention/physiology , Parents/psychology , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/psychology , Social Behavior , Communication , Longitudinal Studies , Autistic Disorder/psychology , Autistic Disorder/physiopathology , Cues , Saccades/physiology , Adult
The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors.
Amygdala , Magnetic Resonance Imaging , Visual Cortex , Humans , Amygdala/diagnostic imaging , Amygdala/physiopathology , Male , Female , Infant , Visual Cortex/diagnostic imaging , Visual Cortex/physiopathology , Visual Cortex/growth & development , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Autistic Disorder/genetics , Autistic Disorder/physiopathology , Autistic Disorder/diagnostic imaging , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/diagnostic imaging , Genetic Predisposition to Disease/genetics
Associations between maternal immune dysregulation (including autoimmunity and skewed cytokine/chemokine profiles) and offspring neurodevelopmental disorders such as autism have been reported. In maternal autoantibody-related autism, specific maternally derived autoantibodies can access the fetal compartment to target eight proteins critical for neurodevelopment. We examined the relationship between maternal autoantibodies to the eight maternal autoantibody-related autism proteins and cytokine/chemokine profiles in the second trimester of pregnancy in mothers of children later diagnosed with autism and their neonates' cytokine/chemokine profiles. Using banked maternal serum samples from 15 to 19 weeks of gestation from the Early Markers for Autism Study and corresponding banked newborn bloodspots, we identified three maternal/offspring groups based on maternal autoantibody status: (1) mothers with autoantibodies to one or more of the eight maternal autoantibody-related autismassociated proteins but not a maternal autoantibody-related autism-specific pattern, (2) mothers with a known maternal autoantibody-related autism pattern, and (3) mothers without autoantibodies to any of the eight maternal autoantibody-related autism proteins. Using a multiplex platform, we measured maternal second trimester and neonatal cytokine/chemokine levels. This combined analysis aimed to determine potential associations between maternal autoantibodies and the maternal and neonatal cytokine/chemokine profiles, each of which has been shown to have implications on offspring neurodevelopment independently.
Autistic Disorder , Autoantibodies , Chemokines , Cytokines , Humans , Female , Autoantibodies/blood , Autoantibodies/immunology , Pregnancy , Cytokines/blood , Infant, Newborn , Autistic Disorder/immunology , Autistic Disorder/blood , Adult , Chemokines/blood , Chemokines/immunology , Male , Pregnancy Trimester, Second/immunology , Pregnancy Trimester, Second/blood
While fronto-posterior underconnectivity has often been reported in autism, it was shown that different contexts may modulate between-group differences in functional connectivity. Here, we assessed how different task paradigms modulate functional connectivity differences in a young autistic sample relative to typically developing children. Twenty-three autistic and 23 typically developing children aged 6 to 15 years underwent functional magnetic resonance imaging (fMRI) scanning while completing a reasoning task with visuospatial versus semantic content. We observed distinct connectivity patterns in autistic versus typical children as a function of task type (visuospatial vs. semantic) and problem complexity (visual matching vs. reasoning), despite similar performance. For semantic reasoning problems, there was no significant between-group differences in connectivity. However, during visuospatial reasoning problems, we observed occipital-occipital, occipital-temporal, and occipital-frontal over-connectivity in autistic children relative to typical children. Also, increasing the complexity of visuospatial problems resulted in increased functional connectivity between occipital, posterior (temporal), and anterior (frontal) brain regions in autistic participants, more so than in typical children. Our results add to several studies now demonstrating that the connectivity alterations in autistic relative to neurotypical individuals are much more complex than previously thought and depend on both task type and task complexity and their respective underlying cognitive processes.
Autistic Disorder , Brain , Magnetic Resonance Imaging , Semantics , Humans , Child , Male , Adolescent , Female , Autistic Disorder/physiopathology , Autistic Disorder/diagnostic imaging , Autistic Disorder/psychology , Brain/diagnostic imaging , Brain/physiopathology , Brain Mapping , Space Perception/physiology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging
Previous studies in autism spectrum disorder demonstrated an increased number of excitatory pyramidal cells and a decreased number of inhibitory parvalbumin+ chandelier interneurons in the prefrontal cortex of postmortem brains. How these changes in cellular composition affect the overall abundance of excitatory and inhibitory synapses in the cortex is not known. Herein, we quantified the number of excitatory and inhibitory synapses in the prefrontal cortex of 10 postmortem autism spectrum disorder brains and 10 control cases. To identify excitatory synapses, we used VGlut1 as a marker of the presynaptic component and postsynaptic density protein-95 as marker of the postsynaptic component. To identify inhibitory synapses, we used the vesicular gamma-aminobutyric acid transporter as a marker of the presynaptic component and gephyrin as a marker of the postsynaptic component. We used Puncta Analyzer to quantify the number of co-localized pre- and postsynaptic synaptic components in each area of interest. We found an increase in the number of excitatory synapses in upper cortical layers and a decrease in inhibitory synapses in all cortical layers in autism spectrum disorder brains compared with control cases. The alteration in the number of excitatory and inhibitory synapses could lead to neuronal dysfunction and disturbed network connectivity in the prefrontal cortex in autism spectrum disorder.
Membrane Proteins , Prefrontal Cortex , Synapses , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Humans , Male , Female , Synapses/pathology , Synapses/metabolism , Adult , Middle Aged , Autism Spectrum Disorder/metabolism , Autism Spectrum Disorder/pathology , Young Adult , Adolescent , Child , Autistic Disorder/metabolism , Autistic Disorder/pathology , Neural Inhibition/physiology , Vesicular Glutamate Transport Protein 1/metabolism
BACKGROUND: Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course. METHOD: The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females). RESULTS: Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development. LIMITATIONS: Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic. CONCLUSIONS: Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles.
Depression , Humans , Female , Male , Adolescent , Depression/epidemiology , Child , Longitudinal Studies , Autism Spectrum Disorder/psychology , Autism Spectrum Disorder/epidemiology , Autistic Disorder/psychology , Autistic Disorder/epidemiology , Puberty/psychology
