Deficits In Autism Spectrum Disorder Research Articles

Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice.

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.

Correction to: to the Roots of Theory of Mind Deficits in Autism Spectrum Disorder: A Narrative Review

Correction to: to the Roots of Theory of Mind Deficits in Autism Spectrum Disorder: A Narrative Review

Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.

The hippocampus is one of the brain areas affected by autism spectrum disorder (ASD). Individuals with ASD typically have impairments in hippocampus-dependent learning, memory, language ability, emotional regulation, and cognitive map creation. However, the pathological changes in the hippocampus that result in these cognitive deficits in ASD are not yet fully understood. In the present review, we will first summarize the hippocampal involvement in individuals with ASD. We will then provide an overview of hippocampal structural and functional abnormalities in genetic, environment-induced, and idiopathic animal models of ASD. Finally, we will discuss some pharmacological and non-pharmacological interventions that show positive impacts on the structure and function of the hippocampus in animal models of ASD. A further comprehension of hippocampal aberrations in ASD might elucidate their influence on the manifestation of this developmental disorder and provide clues for forthcoming diagnostic and therapeutic innovation.

The role of physical activity and sport in children and adolescents with autism spectrum disorder (ASD)

Abstract: Background: Various health-related benefits of physical activity (PA) in children and adolescents have been reported, with suggestions that PA could effectively address certain deficits found in autism spectrum disorder (ASD). However, there remains insufficient engagement in PA among individuals with ASD, and barriers to accessing PA persist. Objective: This study aims to review PA interventions (types, frequencies, and durations) in ASD over the last five years and discuss their effects. Methods: Searches were conducted in the PubMed database from October to December 2022 using Mesh Terms: “adolescent” OR “children” AND “sport” OR “physical activity” AND “mental health” AND/OR “autism.” Results were critically appraised using PEDro and Cochrane’s ROB-2, categorized into five stages to assess potential bias. Results: A total of ten papers were included and appraised, examining various types of PA. Primary benefits observed in children and adolescents included the development of social skills, reduction of autistic traits, regulation of emotions, and management of behaviour and cognition. Conclusions: Evidence indicates that PA can effectively address some neuropsychological deficits in ASD. Additionally, managing and protecting against metabolic conditions through PA can significantly enhance overall health.

Design and methodology for a proof of mechanism study of individualized neuronavigated continuous Theta burst stimulation for auditory processing in adolescents with autism spectrum disorder.

It has been suggested that aberrant excitation/inhibition (E/I) balance and dysfunctional structure and function of relevant brain networks may underlie the symptoms of autism spectrum disorder (ASD). However, the nomological network linking these constructs to quantifiable measures and mechanistically relating these constructs to behavioral symptoms of ASD is lacking. Herein we describe a within-subject, controlled, proof-of-mechanism study investigating the pathophysiology of auditory/language processing in adolescents with ASD. We utilize neurophysiological and neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) metrics of language network structure and function. Additionally, we apply a single, individually targeted session of continuous theta burst stimulation (cTBS) as an experimental probe of the impact of perturbation of the system on these neurophysiological and neuroimaging outcomes. MRS, fMRI, and MEG measures are evaluated at baseline and immediately prior to and following cTBS over the posterior superior temporal cortex (pSTC), a region involved in auditory and language processing deficits in ASD. Also, behavioral measures of ASD and language processing and DWI measures of auditory/language network structures are obtained at baseline to characterize the relationship between the neuroimaging and neurophysiological measures and baseline symptom presentation. We hypothesize that local gamma-aminobutyric acid (GABA) and glutamate concentrations (measured with MRS), and structural and functional activity and network connectivity (measured with DWI and fMRI), will significantly predict MEG indices of auditory/language processing and behavioral deficits in ASD. Furthermore, a single session of cTBS over left pSTC is hypothesized to lead to significant, acute changes in local glutamate and GABA concentration, functional activity and network connectivity, and MEG indices of auditory/language processing. We have completed the pilot phase of the study (n=20 Healthy Volunteer adults) and have begun enrollment for the main phase with adolescents with ASD (n=86; age 14-17). If successful, this study will establish a nomological network linking local E/I balance measures to functional and structural connectivity within relevant brain networks, ultimately connecting them to ASD symptoms. Furthermore, this study will inform future therapeutic trials using cTBS to treat the symptoms of ASD.

Multisensory integration deficits in Schizophrenia and Autism evidenced in behaviour but not event related potentials

The process of integrating information from different sensory channels, known as multisensory integration (MSI) was assessed in two disorders, Autism Spectrum Disorder (ASD) and Schizophrenia (SCZ). 32 healthy controls (HC), 35 SCZ patients, and 23 ASD patients performed an audiovisual (AV) synchronous target detection task while reaction time (RT) and scalp recorded electrophysiological (EEG) activity were measured. MSI in the AV condition resulted in faster and less variable RTs compared to the unimodal conditions. Using our novel bootstrap method, MSI gain was observed in 78 % of HC, 26 % of ASD, and 48 % of SCZ patients. At the neural level, MSI in the AV condition resulted in larger amplitude of sensory evoked responses and cognitive P3 response compared to the corresponding unimodal conditions. These neural effects of MSI were not related to the behavioural MSI gain identified at the individual level and could not explain the deficits in behavioural MSI of patient groups. In conclusion, a robust MSI gain deficit in RT was observed in both patient groups that was not reflected in early perceptual and cognitive electro-cortical responses, suggesting that behavioural MSI deficits in ASD and SCZ may arise at late processing stages such as response selection.

Social Behavior in Animal Models of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and stereotyped, repetitive patterns of behaviors, limited interests, and cognitive impairment. Especially, social deficit has been considered a core feature of ASD. Because of the limitations of the experimental approach in humans, valid animal models are essential in an effort to identify novel therapeutics for social deficits in ASD. The genetic and environmental factors are clinically relevant to the pathophysiology of ASD. Epidemiological studies demonstrate environmental interventions such as prenatal exposure to valproic acid (VPA). Prenatal exposure to VPA represents a robust model of ASD exhibiting face, construct, and predictive validity. Here, we introduce protocols of the social interaction test and the three-chamber test for evaluating social deficits in mice prenatally exposed to VPA.

Abnormal functional connectivity of the reward network is associated with social communication impairments in autism spectrum disorder: A large-scale multi-site resting-state fMRI study

BackgroundThe social motivation hypothesis proposes that the social deficits of autism spectrum disorder (ASD) are related to reward system dysfunction. However, functional connectivity (FC) patterns of the reward network in ASD have not been systematically explored yet. MethodsThe reward network was defined as eight regions of interest (ROIs) per hemisphere, including the nucleus accumbens (NAc), caudate, putamen, anterior cingulate cortex (ACC), ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), amygdala, and insula. We computed both the ROI-wise resting-state FC and seed-based whole-brain FC in 298 ASD participants and 348 typically developing (TD) controls from the Autism Brain Imaging Data Exchange I dataset. Two-sample t-tests were applied to obtain the aberrant FCs. Then, the association between aberrant FCs and clinical symptoms was assessed with Pearson's correlation or Spearman's correlation. In addition, Neurosynth Image Decoder was used to generate word clouds verifying the cognitive functions of the aberrant pathways. Furthermore, a three-way multivariate analysis of variance (MANOVA) was conducted to examine the effects of gender, subtype and age on the atypical FCs. ResultsFor the within network analysis, the left ACC showed weaker FCs with both the right amygdala and left NAc in ASD compared with TD, which were negatively correlated with the Autism Diagnostic Observation Schedule (ADOS) total scores and Social Responsiveness Scale (SRS) total scores respectively. For the whole-brain analysis, weaker FC (i.e., FC between the left vmPFC and left calcarine gyrus, and between the right vmPFC and left precuneus) accompanied by stronger FC (i.e., FC between the left caudate and right insula) were exhibited in ASD relative to TD, which were positively associated with the SRS motivation scores. Additionally, we detected the main effect of age on FC between the left vmPFC and left calcarine gyrus, of subtype on FC between the right vmPFC and left precuneus, of age and age-by-gender interaction on FC between the left caudate and right insula. ConclusionsOur findings highlight the crucial role of abnormal FC patterns of the reward network in the core social deficits of ASD, which have the potential to reveal new biomarkers for ASD.

Scene construction and autobiographical memory retrieval in autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) frequently exhibit difficulties in retrieving autobiographical memories (AMs) of specific events from their life. Such memory deficits are frequently attributed to underlying disruptions in self-referential or social cognition processes. This makes intuitive sense as these are hallmarks of ASD. However, an emerging literature suggests that parallel deficits also exist in ASD individuals' ability to reconstruct the rich spatial contexts in which events occur. This is a capacity known as scene construction, and in typically developing individuals is considered a core process in retrieving AMs. In this review, we discuss evidence of difficulties with scene construction in ASD, drawing upon experiments that involve AM retrieval, other forms of mental time travel, and spatial navigation. We also highlight aspects of extant data that cannot be accounted for using purely social explanations of memory deficits in ASD. We conclude by identifying key questions raised by our framework and suggest how they might be addressed in future research.

The Effectiveness of Art Therapy on Social Development in Children with Autism Spectrum Disorders

People with Autism Spectrum Disorder (ASD) are characterized by having problems with communication, behaviors, and social interactions. Art therapy (AT) is recognized as an effective way to deal with the difficulties of ASD since it is accessible and applicable. The application of AT at an early age can raise the possibility that one with ASD can improve the symptoms. Past studies suggested that two main deficits of ASD are psychosocial problems and social-reward processing problems. The mechanisms that make AT effective are still unclear. Communication, sense of self, eye contact, tolerance of unexpected consequences, establishing of social relationships, and decrease in anxiety level can support the development of social skills. Incorporating behavioral techniques into AT can exert a greater influence on the enhancement of problem behaviors. The means, goals, outcomes, and factors that work for AT are discussed and become essential elements of AT. The application of art materials, the artwork of children, and the attachment of art therapists can contribute to the progress of forming relationships, facilitating interactions, and alleviating self-stimulatory behaviors as well as anxiety levels. Follow-up observations and transformations of AT are recommended to be completed in future research. This review can provide some suggestions for the development of intervention programs at schools.

Alteration of the large-scale white-matter functional networks in autism spectrum disorder.

Autism spectrum disorder is a neurodevelopmental disorder whose core deficit is social dysfunction. Previous studies have indicated that structural changes in white matter are associated with autism spectrum disorder. However, few studies have explored the alteration of the large-scale white-matter functional networks in autism spectrum disorder. Here, we identified ten white-matter functional networks on resting-state functional magnetic resonance imaging data using the K-means clustering algorithm. Compared with the white matter and white-matter functional network connectivity of the healthy controls group, we found significantly decreased white matter and white-matter functional network connectivity mainly located within the Occipital network, Middle temporo-frontal network, and Deep network in autism spectrum disorder. Compared with healthy controls, findings from white-matter gray-matter functional network connectivity showed the decreased white-matter gray-matter functional network connectivity mainly distributing in the Occipital network and Deep network. Moreover, we compared the spontaneous activity of white-matter functional networks between the two groups. We found that the spontaneous activity of Middle temporo-frontal and Deep network was significantly decreased in autism spectrum disorder. Finally, the correlation analysis showed that the white matter and white-matter functional network connectivity between the Middle temporo-frontal network and others networks and the spontaneous activity of the Deep network were significantly correlated with the Social Responsiveness Scale scores of autism spectrum disorder. Together, our findings indicate that changes in the white-matter functional networks are associated behavioral deficits in autism spectrum disorder.

Altered dynamic network interactions in children with ASD during face recognition revealed by time-varying EEG networks.

Although the electrophysiological event-related potential in face processing (e.g. N170) is widely accepted as a face-sensitivity biomarker that is deficient in children with autism spectrum disorders, the time-varying brain networks during face recognition are still awaiting further investigation. To explore the social deficits in autism spectrum disorder, especially the time-varying brain networks during face recognition, the current study analyzed the N170, cortical activity, and time-varying networks under 3 tasks (face-upright, face-inverted, and house-upright) in autism spectrum disorder and typically developing children. The results revealed a smaller N170 amplitude in autism spectrum disorder compared with typically developing, along with decreased cortical activity mainly in occipitotemporal areas. Concerning the time-varying networks, the atypically stronger information flow and brain network connections across frontal, parietal, and temporal regions in autism spectrum disorder were reported, which reveals greater effort was exerted by autism spectrum disorder to obtain comparable performance to the typically developing children, although the amplitude of N170 was still smaller than that of the typically developing children. Different brain activation states and interaction patterns of brain regions during face processing were discovered between autism spectrum disorder and typically developing. These findings shed light on the face-processing mechanisms in children with autism spectrum disorder and provide new insight for understanding the social dysfunction of autism spectrum disorder.

The enteric nervous system deficits in autism spectrum disorder.

Gastrointestinal (GI) disorders are common comorbidities in individuals with autism spectrum disorder (ASD), and abnormalities in these issues have been found to be closely related to the severity of core behavioral deficits in autism. The enteric nervous system (ENS) plays a crucial role in regulating various aspects of gut functions, including gastrointestinal motility. Dysfunctional wiring in the ENS not only results in various gastrointestinal issues, but also correlates with an increasing number of central nervous system (CNS) disorders, such as ASD. However, it remains unclear whether the gastrointestinal dysfunctions are a consequence of ASD or if they directly contribute to its pathogenesis. This review focuses on the deficits in the ENS associated with ASD, and highlights several high-risk genes for ASD, which are expressed widely in the gut and implicated in gastrointestinal dysfunction among both animal models and human patients with ASD. Furthermore, we provide a brief overview of environmental factors associated with gastrointestinal tract in individuals with autism. This could offer fresh perspectives on our understanding of ASD.

Empathy deficits, callous-unemotional traits and structural underpinnings in autism spectrum disorder and conduct disorder youth.

Distinct empathy deficits are often described in patients with conduct disorder (CD) and autism spectrum disorder (ASD) yet their neural underpinnings and the influence of comorbid Callous-Unemotional (CU) traits are unclear. This study compares the cognitive (CE) and affective empathy (AE) abilities of youth with CD and ASD, their potential neuroanatomical correlates, and the influence of CU traits on empathy. Adolescents and parents/caregivers completed empathy questionnaires (N = 148 adolescents, mean age = 15.16 years) and T1 weighted images were obtained from a subsample (N = 130). Group differences in empathy and the influence of CU traits were investigated using Bayesian analyses and Voxel-Based Morphometry with Threshold-Free Cluster Enhancement focusing on regions involved in AE (insula, amygdala, inferior frontal gyrus and cingulate cortex) and CE processes (ventromedial prefrontal cortex, temporoparietal junction, superior temporal gyrus, and precuneus). The ASD group showed lower parent-reported AE and CE scores and lower self-reported CE scores while the CD group showed lower parent-reported CE scores than controls. When accounting for the influence of CU traits no AE deficits in ASD and CE deficits in CD were found, but CE deficits in ASD remained. Across all participants, CU traits were negatively associated with gray matter volumes in anterior cingulate which extends into the mid cingulate, ventromedial prefrontal cortex, and precuneus. Thus, although co-occurring CU traits have been linked to global empathy deficits in reports and underlying brain structures, its influence on empathy aspects might be disorder-specific. Investigating the subdimensions of empathy may therefore help to identify disorder-specific empathy deficits.

Cognitive control in adults with high-functioning autism spectrum disorder: a study with event-related potentials.

Little is known about cognitive control in adults with high-functioning forms of autism spectrum disorder because previous research focused on children and adolescents. Cognitive control is crucial to monitor and readjust behavior after errors to select contextually appropriate reactions. The congruency effect and conflict adaptation are measures of cognitive control. Post-error slowing, error-related negativity and error positivity provide insight into behavioral and electrophysiological correlates of error processing. In children and adolescent with autism spectrum disorder deficits in cognitive control and error processing have been shown by changes in post-error slowing, error-related negativity and error positivity in the flanker task. We performed a modified Eriksen flanker task in 17 adults with high-functioning autism spectrum disorder and 17 healthy controls. As behavioral measures of cognitive control and error processing, we included reaction times and error rates to calculate congruency effects, conflict adaptation, and post-error slowing. Event-related potentials namely error-related negativity and error positivity were measured to assess error-related brain activity. Both groups of participants showed the expected congruency effects demonstrated by faster and more accurate responses in congruent compared to incongruent trials. Healthy controls exhibited conflict adaptation as they obtained performance benefits after incongruent trials whereas patients with autism spectrum disorder did not. The expected slowing in reaction times after errors was observed in both groups of participants. Individuals with autism spectrum disorder demonstrated enhanced electrophysiological error-processing compared to healthy controls indicated by increased error-related negativity and error positivity difference amplitudes. Our findings show that adults with high-functioning autism spectrum disorder do not show the expected upregulation of cognitive control in response to conflicts. This finding implies that previous experiences may have a reduced influence on current behavior in these patients which possibly contributes to less flexible behavior. Nevertheless, we observed intact behavioral reactions after errors indicating that adults with high-functioning autism spectrum disorder can flexibly adjust behavior in response to changed environmental demands when necessary. The enhancement of electrophysiological error-processing indicates that adults with high-functioning autism spectrum disorder demonstrate an extraordinary reactivity toward errors reflecting increased performance monitoring in this subpopulation of autism spectrum disorder patients.

The Novel Somatosensory Nose-Poke Adapted Paradigm (SNAP) Is an Effective Tool to Assess Differences in Tactile Sensory Preferences in Autistic-Like Mice.

One of the most prevalent deficits in autism spectrum disorder (ASD) are sensitivities to sensory stimuli. Despite the prevalence of sensory deficits in autism, there are few paradigms capable of easily assessing sensory behaviors in ASD-like mouse models. We addressed this need by creating the Somatosensory Nose-poke Adapted Paradigm (SNAP), which consists of an elevated platform with 6 holes in the center, half of which are lined with sandpaper and half are smooth, requiring mice to use their whiskers to sense the texture. The SNAP paradigm assesses tactile sensory preferences as well as stereotypy, anxiety, and locomotion. We used two wild-type (neurotypical) mouse strains, C57BL/6J (C57) inbred and CD-1 outbred mice, and two ASD mouse models, BTBR (a model of idiopathic ASD) and Cntnap2 -/- mice (a model of syndromic ASD). We found that both ASD models produced more nose pokes into the rough condition than the smooth condition, suggesting an increased preference for complex tactile stimulation when compared with the neurotypical groups, wherein no differences were observed. Furthermore, we found increased stereotypy and time spent in the center, suggestive of decreased anxiety, only for BTBR mice compared with the other mouse strains. Overall, SNAP is an easy to implement task to assess the degree of preference for complex tactile stimulation in ASD mouse models that can be further modified to exclude possible confounding effects of novelty or anxiety on the sensory preferences.

Behavioural deficits of autism spectrum disorder and associations with different gene clusters: a study with the whole-genome transmission disequilibrium test

BackgroundAutism spectrum disorder (ASD) is a diverse neurodevelopmental disease primarily distinguished by limited and stereotyped activities as well as impaired social interaction. Due to the high heritability of ASD, research...

Neural and Behavioral Differences in Speech Perception for Children With Autism Spectrum Disorders Within an Audiovisual Context.

Reduced use of visible articulatory information on a speaker's face has been implicated as a possible contributor to language deficits in autism spectrum disorders (ASD). We employ an audiovisual (AV) phonemic restoration paradigm to measure behavioral performance (button press) and event-related potentials (ERPs) of visual speech perception in children with ASD and their neurotypical peers to assess potential neural substrates that contribute to group differences. Two sets of speech stimuli, /ba/-"/a/" ("/a/" was created from the /ba/ token by a reducing the initial consonant) and /ba/-/pa/, were presented within an auditory oddball paradigm to children aged 6-13 years with ASD (n = 17) and typical development (TD; n = 33) within two conditions. The AV condition contained a fully visible speaking face; the pixelated (PX) condition included a face, but the mouth and jaw were PX, removing all articulatory information. When articulatory features were present for the /ba/-"/a/" contrast, it was expected that the influence of the visual articulators would facilitate a phonemic restoration effect in which "/a/" would be perceived as /ba/. ERPs were recorded during the experiment while children were required to press a button for the deviant sound for both sets of speech contrasts within both conditions. Button press data revealed that TD children were more accurate in discriminating between /ba/-"/a/" and /ba/-/pa/ contrasts in the PX condition relative to the ASD group. ERPs in response to the /ba/-/pa/ contrast within both AV and PX conditions differed between children with ASD and TD children (earlier P300 responses for children with ASD). Children with ASD differ in the underlying neural mechanisms responsible for speech processing compared with TD peers within an AV context.

Assessment of Visual Motor Integration via Hand-Drawn Imitation: A Pilot Study

Copious evidence shows that impaired visual–motor integration (VMI) is intrinsically linked to the core deficits of autism spectrum disorder (ASD) and associated with an anomalous social capability. Therefore, an effective evaluation method of visual–motor behaviour can provide meaningful insight into the evaluation of VMI towards social capability. The current pilot study aims to explore the appropriate quantified metrics for evaluating VMI ability based on a hand-drawn imitation protocol. First, a simple and interesting hand-drawn protocol was designed, and six healthy participants were recruited to perform the task. Then, based on the collected hand–eye behaviour data, several metrics were applied to infer the participant’s social capability and VMI in engagement and visual–motor complexity based on hand–eye properties with Hausdorff distance and cross-recurrence quantification analysis (CRQA). Finally, those quantified metrics were verified through statistical significance. This study proposed a set of quantitative metrics to construct a comprehensive VMI evaluation, including outcome and progress measures. The results revealed the proposed method as a directly interpretable indicator providing a promising computational framework and biomarker for VMI evaluation, paving the way for its future use in ASD diagnosis and guiding intervention.

Saliva versus plasma cytokines as possible predictors of autism severity

The autism spectrum disorders (ASD) are now widely accepted as a pervasive, complex, heterogeneous neurodevelopmental disorders with multiple etiologies, subtypes, and developmental trajectories. There are no available and effective biomarkers for them. Immune dysfunction is seen as an important risk factor contributing to the neurodevelopmental deficit in ASD, and is signified, among other things, by an imbalance of cytokines in the brain and on the periphery. In recent years, saliva has been proposed as a biological material for diagnosing ASD, due to the accessibility and non-invasiveness of the method for its production. However, the question of whether salivary cytokine levels may be used as effective early biomarkers for autism requires further research, including saliva versus plasma/serum comparisons.Aim: a comparative analysis of the levels of cytokines: IL-6, IFNγ, TNFα, IL-1β, IL-4, IL-10, in saliva and blood plasma to identify possible markers of ASD and their severity in children.The study included 11 children with typical neurodevelopment (TDC) and 55 children with ASD, among whom 37 children had mild or moderate autism (according to CARS), and 18 children had severe autism. Samples of unstimulated mixed saliva and venous blood were simultaneously collected from all children. Salivary concentrations of cytokines: IL-6, IFNγ, TNFα, IL-1β, IL-4, IL-10 were determined by multiplex Luminex™ analysis. Plasma levels of cytokines were assessed by ELISA. Differences between groups were tested using the Kruskal-Wallis U-test with post-hoc Conover-Inman comparisons, between samples (saliva/ plasma) are using the Wilcoxon signed-rank test. The correlation between the concentrations of cytokines in plasma and saliva was determined using linear regression by the RMA method.In all examined groups, the levels of IL-6, IFNγ and IL-10 in saliva were significantly lower, and TNFα, IL-1β and IL-4 were higher than the corresponding levels of the same cytokines in plasma. Regardless of health/ disease status, no significant correlations were found between salivary and plasma cytokine levels in children. IL-1β levels were significantly lower and IL-10 levels were higher in the saliva of both groups of children with ASD compared with TDC. No significant differences in salivary cytokine concentrations were found between children with mild and severe ASD.Thus, salivary cytokines can be used as markers of ASD in children, but not the severity of the condition. The absence of correlations in the levels of some pro/anti-inflammatory cytokines between saliva and blood plasma may probably indicate a special immunological status of an ecological niche, the oral cavity.