Dysfunction In Autism Research Articles

The occurrence and development of autism from the perspective of perceptual ecology

This paper discusses three theoretical models to explain the occurrence and development of autism disorders. The psychological model regards developmental disorders or psychopathological disorders of autistic patients as the manifestation of impaired mental activities, the neurobiological model mainly considers specific brain structure damage and its effect on behavioral dysfunction in autism. The ecological model doesnt directly study the mind or brain, instead it tries to explain the behavior of autistic people by studying their interactions with the environment. This paper will mainly focus on the ecological model of autism, autism is a process in humans life development, people who is suffer from autism, the influences of this disease will along with the entire lifetime, autism is not caused by a moment, but is a life through process. Compared with psychological model and neurobiological model, the ecological model view of autism based on perceptual ecology theory highlights the interaction between individuals and the environment, which indicates that autism can also effect by environment, outside components can consider as triggers of autism as well.

Circuit-level theories for sensory dysfunction in autism: convergence across mouse models.

Individuals with autism spectrum disorder (ASD) exhibit a diverse range of behavioral features and genetic backgrounds, but whether different genetic forms of autism involve convergent pathophysiology of brain function is unknown. Here, we analyze evidence for convergent deficits in neural circuit function across multiple transgenic mouse models of ASD. We focus on sensory areas of neocortex, where circuit differences may underlie atypical sensory processing, a central feature of autism. Many distinct circuit-level theories for ASD have been proposed, including increased excitation-inhibition (E-I) ratio and hyperexcitability, hypofunction of parvalbumin (PV) interneuron circuits, impaired homeostatic plasticity, degraded sensory coding, and others. We review these theories and assess the degree of convergence across ASD mouse models for each. Behaviorally, our analysis reveals that innate sensory detection behavior is heightened and sensory discrimination behavior is impaired across many ASD models. Neurophysiologically, PV hypofunction and increased E-I ratio are prevalent but only rarely generate hyperexcitability and excess spiking. Instead, sensory tuning and other aspects of neural coding are commonly degraded and may explain impaired discrimination behavior. Two distinct phenotypic clusters with opposing neural circuit signatures are evident across mouse models. Such clustering could suggest physiological subtypes of autism, which may facilitate the development of tailored therapeutic approaches.

Impaired cecal motility and secretion alongside expansion of gut-associated lymphoid tissue in the Nlgn3R451C mouse model of autism

Individuals with Autism Spectrum Disorder (ASD; autism) commonly present with gastrointestinal (GI) illness in addition to core diagnostic behavioural traits. The appendix, or cecum in mice, is important for GI homeostasis via its function as a key site for fermentation and a microbial reservoir. Even so, the role of the appendix and cecum in autism-associated GI symptoms remains uninvestigated. Here, we studied mice with an autism-associated missense mutation in the post-synaptic protein neuroligin-3 (Nlgn3R451C), which impacts brain and enteric neuronal activity. We assessed for changes in cecal motility using a tri-cannulation video-imaging approach in ex vivo preparations from wild-type and Nlgn3R451C mice. We investigated cecal permeability and neurally-evoked secretion in wild-type and Nlgn3R451C tissues using an Ussing chamber set-up. The number of cecal patches in fresh tissue samples were assessed and key immune populations including gut macrophages and dendritic cells were visualised using immunofluorescence. Nlgn3R451C mice displayed accelerated cecal motor complexes and reduced cecal weight in comparison to wildtype littermates. Nlgn3R451C mice also demonstrated reduced neurally-evoked cecal secretion in response to the nicotinic acetylcholine receptor agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP), but permeability was unchanged. We observed an increase in the number of cecal patches in Nlgn3R451C mice, however the cellular morphologies of key immune populations studied were not significantly altered. We show that the R451C nervous system mutation leads to cecal dysmotility, impaired secretion, and neuro-immune alterations. Together, these results suggest that the R451C mutation disrupts the gut-brain axis with GI dysfunction in autism.

Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism.

ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective mothers and child/mother control pairs and possible correlations to ASD severity and loss of adaptive abilities. Of the 84 studied individuals, 42 children (23 ASD and 19 neurotypical) and their paired mothers underwent clinical and neuropsychological evaluations. ASD severity was analysed with standardised tests. Adaptive functioning was studied with ABAS-II and GAC index. Plasma anti-env responses of HERV-K, -H and -W were tested with indirect ELISA. ASD and neurotypical children did not differ in age, gender, comorbidities and anti-HERV responses. In children with ASD, anti-HERV levels were not correlated to ASD severity, while a significant inverse correlation was found between anti-HERV-W-248-262 levels and adaptive/social abilities. Upregulation of anti-HERV-W response correlates to dysfunctional social and adaptive competences in ASD but not in controls, suggesting anti-HERV response plays a role in the appearance of peculiar ASD symptoms.

PTEN Regulates Mitochondrial Biogenesis via the AKT/GSK-3β/PGC-1α Pathway in Autism

Autism spectrum disorder (ASD) is a widespread, complex and serious neurodevelopmental disorder. Complex genetic and environmental factors are thought to contribute to the development of ASD. Genome-wide association analysis has identified multiple autism-related genes. Mutation of the phosphatase and tensin homolog (Pten) is closely related to autism and accounts for 5–17% of cases of autism. However, the detailed mechanism is still unclear. Recently, mitochondrial dysfunction was tightly associated with ASD pathogenesis, such as developmental degeneration, learning and various behavioral disorders. The mitochondrial DNA (mtDNA) copy number in children with autism is also significantly increased. The correlation between Pten and mitochondrial dysfunction in autism is still unknown. In this study, we examined how Pten regulates mitochondrial biogenesis through the AKT/GSK-3β/PGC-1α signaling pathways. We found that PTEN could dephosphorylate AKT to inhibit its activity, leading to decreased GSK3β phosphorylation. This decrease in GSK3β phosphorylation, which could activate itself, increased PGC-1α phosphorylation to promote its degradation and then regulated mitochondrial biogenesis by NRF-1 and TFAM downstream of PGC-1α. In the Valproic acid (VPA) induced autism mouse model, the PTEN protein level was significantly decreased while PGC-1α and COX IV levels were increased in the hippocampus and cortex. Our data suggest that there is a correlation between PTEN and mitochondrial dysfunction and this correlation may be a potential mechanism of ASD.

5-Aminoisoquinolinone, a PARP-1 Inhibitor, Ameliorates Immune Abnormalities through Upregulation of Anti-Inflammatory and Downregulation of Inflammatory Parameters in T Cells of BTBR Mouse Model of Autism.

Autism spectrum disorder (ASD) covers a range of neurodevelopmental disorders involving impairments in communication and repetitive and stereotyped patterns of behavior and reciprocal social interaction. 5-Aminoisoquinolinone (5-AIQ), a PARP-1 inhibitor, has neuroprotective and anti-inflammatory effects. We investigated the influence of 5-AIQ-treatment in BTBR T+ Itpr3tf/J (BTBR) mice as an autism model and used flow cytometry to assess the effect of 5-AIQ on FOXP3, Helios, GATA3, IL-9, IL-10 and IL-17A production by CXCR6+ and CD4+ T cells in the spleen. We also confirmed the effect of 5-AIQ treatment on expression of FOXP3, Helios, GATA3, IL-17A, IL-10, and IL-9 mRNA and protein expression levels in the brain tissue by quantitative PCR and western blotting. Our results demonstrated that 5-AIQ-treated BTBR mice had significantly increased numbers of CXCR6+FOXP3+, CXCR6+IL-10+, and CXCR6+Helios+ cells and decreased numbers of CD4+GATA3+, CD4+IL-9+, and CD4+IL-17A+ cells as compared with those in untreated BTBR mice. Our results further demonstrated that treatment with 5-AIQ in BTBR mice increased expression for FOXP3, IL-10, and Helios, and decreased expression for GATA3, IL-17A, and IL-9 mRNA. Our findings support the hypotheses that 5-AIQ has promising novel therapeutic effects on neuroimmune dysfunction in autism and is associated with modulation of Treg and Th17 cells.

Autonomic dysfunction in autism: The roles of anxiety, depression, and stress.

The autonomic nervous system (ANS) is responsible for the functioning of the heart, bladder, pupils and several other bodily functions. Therefore, when the ANS functions abnormally, individuals can experience a number of physical symptoms, including dizziness, abnormal sweating and digestive difficulties. Currently, it is unclear if autistic adults experience ANS dysfunction. Therefore, in this study, we investigated whether autistic adults report more ANS-related physical symptoms, indicating greater ANS dysfunction, and whether this may be related to autism, or rather anxiety, depression, or stress. The findings suggest that ANS dysfunction, where found in autism, is due to co-occurring stress and anxiety. We therefore propose that treating stress and anxiety may be an effective way to ameliorate ANS-related health problems in autistic adults.

An Autism-Associated Mutation Impairs Neuroligin-4 Glycosylation and Enhances Excitatory Synaptic Transmission in Human Neurons.

Neuroligins (NLGNs) are a class of postsynaptic cell adhesion molecules that interact with presynaptic neurexins (NRXNs) and regulate synapse function. NLGN4 is a member of the NLGN family and consists of a unique amino acid sequence in humans that is not evolutionarily well conserved in rodents. The human-specific NLGN4 gene has been reported to be mutated in many patients with autism and other neurodevelopmental disorders. However, it remained unclear how these mutations might alter the molecular properties of NLGN4 and affect synaptic transmission in human neurons. Here, we describe a severely autistic male patient carrying a single amino acid substitution (R101Q) in the NLGN4 gene. When expressed in HEK293 cells, the R101Q mutation in NLGN4 did not affect its binding affinity for NRXNs or its capacity to form homodimers. This mutation, however, impaired the maturation of NLGN4 protein by inhibiting N-linked glycosylation at an adjacent residue (N102), which is conserved in all NLGNs. As a result, the R101Q substitution significantly decreased the surface trafficking of NLGN4 and increased its retention in the endoplasmic reticulum and Golgi apparatus. In human neurons derived from male stem cell lines, the R101Q mutation also similarly reduced the synaptic localization of NLGN4, resulting in a loss-of-function phenotype. This mutation-induced trafficking defect substantially diminished the ability of NLGN4 to form excitatory synapses and modulate their functional properties. Viewed together, our findings suggest that the R101Q mutation is pathogenic for NLGN4 and can lead to synaptic dysfunction in autism.

Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats.

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations, which are major neuropathological hallmarks responsible for autism. Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate. Rat models of autism were established by intracerebroventricular injection of propionic acid. These rat models had memory dysfunction, decreased muscle coordination and gait imbalance. Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines, oxidative stress and lipid biomarkers. Oral administration of 10, 20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner. These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism. This study was approved by the RITS/IAEC, SIRSA, HARYANA on March 3, 2014 (approval No. RITS/IAEC/2014/03/03).

Exploratory study of dorsal visual stream dysfunction in autism; A case series

BackgroundRobust neuroscientific evidence supports the existence of an association between autism and a visual motion processing deficit, arising from dysfunction of the dorsal visual stream, a pathway connecting the primary visual and parieto-occipital cortices. The neuro-ophthalmic consequences of dorsal visual stream dysfunction (DVSD) are well-described but seldom reported: simultanagnosia, optic ataxia (OA), and gaze apraxia. MethodThe clinical records of thirteen motor-impaired autistic children, with clinical diagnoses of DVSD, were retrospectively reviewed six years after DVSD diagnosis to determine the frequency and severity of their neuro-visual impairment. Two measures to rate severity of visual perceptual impairment were employed: frequency of parent-reported behaviours denoting impaired visual function, given as mean individual Cerebral Visual Impairment Inventory Scores (CVIS), and severity of age-inappropriate configural disruption of drawings, rated on Beery-VMI Visual Motor Integration standard scores (VMIS). Applying the 90th percentile cut-off CVIS of 0.74 for the typical population as marker of normal visual function a CVIS ≥ 2.5 indicated very severe impairment. Evidence was also sought for a correlation between central OA and severe motor coordination impairment (MCI), rated by the Beery Motor Coordination assessment, using method agreement analysis. ResultsSignificant correlation between CVIS and VMIS was determined by linear regression analysis: r = -0.81 [95% CI -0.94 to -0.47], p=0.0008. Agreement for MCI≤ 5th percentile with central OA, determined by Cohen’s weighted Kappa statistic (K), was significant: K = 1[95% CI: 0.46–1.54], p=0.0002. ConclusionsWe conclude that mechanisms driving OA (which is defined as ‘impaired visually guided movement’) may underpin severe motor impairment, in autism. CVIS and VMIS may be useful indicators of severity of spatial cognitive impairment.

Towards Identifying Genetic Biomarkers for Gastrointestinal Dysfunction in Autism.

This study investigated genetic biomarkers for gastrointestinal dysfunction symptoms in order to provide further information on the genetic risk for GI dysfunction associated with autism. The single nucleotide polymorphisms of sixty participants with autism and/or gastrointestinal dysfunction were analyzed. The autism group had a moderate statistical significance for the Prolactin (PRL) (OR 6.35, p value 0.069) and Interleukin 10 (IL-10) (OR 0.25, p value 0.087) SNPs. The GI dysfunction group had a strong statistical significance for the Cluster of Differentiation 38 (CD38) (OR 6.88, p value 0.005) and oxytocin receptor (OXTR) (OR 0.27, p value 0.036) SNPs. The potential use of PRL, IL-10, CD38, and OXTR SNP expression as biomarkers for GI dysfunction in autism warrants further research.

Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3.

Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brothers with autism and an R451C mutation in Nlgn3 encoding the synaptic adhesion protein, neuroligin‐3. We confirm the presence of an array of synaptic genes in the murine GI tract and investigate the impact of impaired synaptic protein expression in mice carrying the human neuroligin‐3 R451C missense mutation (NL3R451C). Assessing in vivo gut dysfunction, we report faster small intestinal transit in NL3R451C compared to wild‐type mice. Using an ex vivo colonic motility assay, we show increased sensitivity to GABAA receptor modulation in NL3R451C mice, a well‐established Central Nervous System (CNS) feature associated with this mutation. We further show increased numbers of small intestine myenteric neurons in NL3R451C mice. Although we observed altered sensitivity to GABAA receptor modulators in the colon, there was no change in colonic neuronal numbers including the number of GABA‐immunoreactive myenteric neurons. We further identified altered fecal microbial communities in NL3R451C mice. These results suggest that the R451C mutation affects small intestinal and colonic function and alter neuronal numbers in the small intestine as well as impact fecal microbes. Our findings identify a novel GI phenotype associated with the R451C mutation and highlight NL3R451C mice as a useful preclinical model of GI dysfunction in autism. Autism Res 2019, 12: 1043–1056. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryPeople with autism commonly experience gastrointestinal problems, however the cause is unknown. We report gut symptoms in patients with the autism‐associated R451C mutation encoding the neuroligin‐3 protein. We show that many of the genes implicated in autism are expressed in mouse gut. The neuroligin‐3 R451C mutation alters the enteric nervous system, causes gastrointestinal dysfunction, and disrupts gut microbe populations in mice. Gut dysfunction in autism could be due to mutations that affect neuronal communication.

Advanced glycation endproducts, dityrosine and arginine transporter dysfunction in autism - a source of biomarkers for clinical diagnosis

BackgroundClinical chemistry tests for autism spectrum disorder (ASD) are currently unavailable. The aim of this study was to explore the diagnostic utility of proteotoxic biomarkers in plasma and urine, plasma protein glycation, oxidation, and nitration adducts, and related glycated, oxidized, and nitrated amino acids (free adducts), for the clinical diagnosis of ASD.MethodsThirty-eight children with ASD (29 male, 9 female; age 7.6 ± 2.0 years) and 31 age-matched healthy controls (23 males, 8 females; 8.6 ± 2.0 years) were recruited for this study. Plasma protein glycation, oxidation, and nitration adducts and amino acid metabolome in plasma and urine were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning methods were then employed to explore and optimize combinations of analyte data for ASD diagnosis.ResultsWe found that children with ASD had increased advanced glycation endproducts (AGEs), Nε-carboxymethyl-lysine (CML) and Nω-carboxymethylarginine (CMA), and increased oxidation damage marker, dityrosine (DT), in plasma protein, with respect to healthy controls. We also found that children with ASD had increased CMA free adduct in plasma ultrafiltrate and increased urinary excretion of oxidation free adducts, alpha-aminoadipic semialdehyde and glutamic semialdehyde. From study of renal handling of amino acids, we found that children with ASD had decreased renal clearance of arginine and CMA with respect to healthy controls. Algorithms to discriminate between ASD and healthy controls gave strong diagnostic performance with features: plasma protein AGEs—CML, CMA—and 3-deoxyglucosone-derived hydroimidazolone, and oxidative damage marker, DT. The sensitivity, specificity, and receiver operating characteristic area-under-the-curve were 92%, 84%, and 0.94, respectively.ConclusionsChanges in plasma AGEs were likely indicative of dysfunctional metabolism of dicarbonyl metabolite precursors of AGEs, glyoxal and 3-deoxyglucosone. DT is formed enzymatically by dual oxidase (DUOX); selective increase of DT as an oxidative damage marker implicates increased DUOX activity in ASD possibly linked to impaired gut mucosal immunity. Decreased renal clearance of arginine and CMA in ASD is indicative of increased arginine transporter activity which may be a surrogate marker of disturbance of neuronal availability of amino acids. Data driven combination of these biomarkers perturbed by proteotoxic stress, plasma protein AGEs and DT, gave diagnostic algorithms of high sensitivity and specificity for ASD.

Increased glia density in the caudate nucleus in williams syndrome: Implications for frontostriatal dysfunction in autism.

Williams syndrome (WS) is a rare neurodevelopmental disorder with a well-described, known genetic etiology. In contrast to Autism Spectrum Disorders (ASD), WS has a unique phenotype characterized by global reductions in IQ and visuospatial ability, with relatively preserved language function, enhanced reactivity to social stimuli and music, and an unusual eagerness to interact socially with strangers. A duplication of the deleted region in WS has been implicated in a subset of ASD cases, defining a spectrum of genetic and behavioral variation at this locus defined by these opposite extremes in social behavior. The hypersociability characteristic of WS may be linked to abnormalities of frontostriatal circuitry that manifest as deficits in inhibitory control of behavior. Here, we examined the density of neurons and glia in associative and limbic territories of the striatum including the caudate, putamen, and nucleus accumbens regions in Nissl stained sections in five pairs of age, sex, and hemisphere-matched WS and typically-developing control (TD) subjects. In contrast to what is reported in ASD, no significant increase in overall neuron density was observed in this study. However, we found a significant increase in the density of glia in the dorsal caudate nucleus, and in the ratio of glia to neurons in the dorsal and medial caudate nucleus in WS, accompanied by a significant increase in density of oligodendrocytes in the medial caudate nucleus. These cellular abnormalities may underlie reduced frontostriatal activity observed in WS, with implications for understanding altered connectivity and function in ASD. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 531-545, 2018.

Cadherin-10 Maintains Excitatory/Inhibitory Ratio through Interactions with Synaptic Proteins.

Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded by CDH10 within the ASD risk locus 5p14.1, maintains both excitatory and inhibitory synaptic scaffold structure in cultured cortical neurons from rats of both sexes. Cadherin-10 localizes to both excitatory and inhibitory synapses in neocortex, where it is organized into nanoscale puncta that influence the size of their associated PSDs. Knockdown of cadherin-10 reduces excitatory but increases inhibitory synapse size and strength, altering the E/I ratio in cortical neurons. Furthermore, cadherin-10 exhibits differential participation in complexes with PSD-95 and gephyrin, which may underlie its role in maintaining the E/I ratio. Our data provide a new mechanism whereby a protein encoded by a common ASD risk factor controls E/I ratios by regulating excitatory and inhibitory synapses in opposing directions.SIGNIFICANCE STATEMENT The correct balance between excitatory/inhibitory (E/I) is crucial for normal brain function and is altered in psychiatric disorders such as autism. However, the molecular mechanisms that underlie this balance remain elusive. To address this, we studied cadherin-10, an adhesion protein that is genetically linked to autism and understudied at the cellular level. Using a combination of advanced microscopy techniques and electrophysiology, we show that cadherin-10 forms nanoscale puncta at excitatory and inhibitory synapses, maintains excitatory and inhibitory synaptic structure, and is essential for maintaining the correct balance between excitation and inhibition in neuronal dendrites. These findings reveal a new mechanism by which E/I balance is controlled in neurons and may bear relevance to synaptic dysfunction in autism.

Role of the cerebellum in high stages of motor planning hierarchy.

Motor planning is not a monolithic process, and distinct stages of motor planning are responsible for encoding different levels of abstractness. However, how these distinct components are mapped into different neural substrates remains an open question. We studied one of these high-level motor planning components, defined as second-order motor planning, in a patient (R.G.) with an extremely rare case of cerebellar agenesis but without any other cortical malformations. Second-order motor planning dictates that when two acts must be performed sequentially, planning of the second act can influence execution of the first. We used an optoelectronic system for kinematic analysis to compare R.G.'s performance with age-matched controls in a second-order motor planning task. The first act was to reach for an object, and the second was to place it into a small or large container. Our results showed that despite the expected difficulties in fine-motor skills, second-order motor planning (i.e., the ability to modulate the first act as a function of the nature of the second act) was preserved even in the patient with congenital absence of the cerebellum. These results open new intriguing speculations about the role of the cerebellum in motor planning abilities. Although prudence is imperative when suggesting conclusions made on the basis of single-case findings, this evidence suggests fascinating hypotheses about the neural circuits that support distinct stages of the motor planning hierarchy, and regarding the functional role of second-order motor planning in motor cognition and its potential dysfunction in autism.NEW & NOTEWORTHY Traditionally, the cerebellum was considered essential for motor planning. By studying an extremely rare patient with cerebellar agenesis and a group of neurotypical controls, we found that high stages of the motor planning hierarchy can be preserved even in this patient with congenital absence of the cerebellum. Our results provide interesting insights that shed light on the neural circuits supporting distinct levels of motor planning. Furthermore, the results are intriguing because of their potential clinical implications in autism.

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms.

Autism spectrum disorder (ASD), the fastest growing developmental disability in the United States, represents a group of neurodevelopmental disorders characterized by impaired social interaction and communication as well as restricted and repetitive behavior. The underlying cause of autism is unknown and therapy is currently limited to targeting behavioral abnormalities. Emerging studies suggest a link between mitochondrial dysfunction and ASD. Here, we review the evidence demonstrating this potential connection. We focus specifically on biochemical links, genetic-based associations, non-energy related mechanisms, and novel therapeutic strategies.

Cysteinyl leukotriene correlated with 8-isoprostane levels as predictive biomarkers for sensory dysfunction in autism.

BackgroundAutism is a neurodevelopmental disorder that clinically presented as cognitive deficits, social impairments and sensory dysfunction. An increasing body of evidence has shown that oxidative stress and inflammation are involved in the pathophysiology of autism. Recording biomarkers as measure of the severity of autistic features might help in understanding the pathophysiology of autism.MethodsThis study investigates the plasma levels of 8-isoprostane and Cysteinyl leukotrienes (CysLTs) in 44 autistic children and 40 healthy controls. The recruited autistic patients were assessed for behavior, cognitive and sensory deficits by using different autism severity rating scales, including the Childhood Autism Rating Scales (CARS), Social responsiveness scale (SRS) and Short Sensory Profile (SSP). Receiver Operating Characteristics analysis (ROC) of the obtained data was performed to measure the predictive value of 8-isoprostane and Cysteinyl leukotrienes (CysLTs) as oxidative stress- related parameters. Pearson’s correlations between the measured parameters was also performed.ResultsThe concentrations of 8-isoprostane and CysLTs in autistic patients were significantly higher than those in controls. While cognitive and social impairments did not show any significant differences, the SSP results were strongly correlated with the levels of both of the biomarkers assessed. However, autistic children showed improvements in oxidative stress status (as determined by 8-isoprostane levels) at increasing ages.ConclusionThis study indicates that 8-isoprostane and CysLTs can be used as markers for the early recognition of autistic patients through sensory deficits phenotypes which might help early intervention.

Bayesian Community Detection in the Space of Group-Level Functional Differences.

We propose a unified Bayesian framework to detect both hyper- and hypo-active communities within whole-brain fMRI data. Specifically, our model identifies dense subgraphs that exhibit population-level differences in functional synchrony between a control and clinical group. We derive a variational EM algorithm to solve for the latent posterior distributions and parameter estimates, which subsequently inform us about the afflicted network topology. We demonstrate that our method provides valuable insights into the neural mechanisms underlying social dysfunction in autism, as verified by the Neurosynth meta-analytic database. In contrast, both univariate testing and community detection via recursive edge elimination fail to identify stable functional communities associated with the disorder.

Impaired activity of monoamine oxidase A in the brain of children with autism

Event Abstract Back to Event Impaired activity of monoamine oxidase A in the brain of children with autism Ved Chauhan1*, Feng Gu1 and Abha Chauhan1 1 NYS Institute for Basic Research in Developmental Disabilities, Department of Neurochemistry, United States Autism is a neurodevelopmental disorder characterized by abnormal social and behavioral abnormalities. Extensive evidence from our and other groups has suggested oxidative stress and mitochondrial dysfunction in autism. Monoamine oxidase A (MAOA), a mitochondrial-bound enzyme, catalyzes the oxidation of endogenous amine-containing neurotransmitters such as serotonin and norepinephrine. The role of MAOA in autism is of particular interest because this enzyme affects the levels of serotonin, which are known to be abnormal in some individuals with autism. In comparison to other alleles of MAOA, the 3-repeat allele is associated with reduced transcription and therefore, reduced activity of MAOA. A few studies have reported an association of the low-activity, 3-repeat MAOA-uVNTR allele with autism. In this study, we analyzed the MAOA activity in the cerebellum and frontal cortex from autistic subjects and age-matched control subjects. In the cerebellum, the activity of MAOA was significantly lower in autism than in control subjects. When the subjects were divided into two subgroups according to their ages: children (ages 4-12 years) and adults (ages 13-38 years), a significant decrease in the activity of MAOA in cerebellum was observed in only children with autism but not in adult autistic group. In the frontal cortex, the MAOA activity in autistic children group was also reduced by 30% than in controls, but there was no significant difference. These results suggest that the brain MAOA activity is lower in autistic children than in control subjects. Lower MAOA activity will cause increase in the levels of related neurotransmitters, such as serotonin, which is one of the most important neurotransmitters influencing behavior and has been reported to have critical relationship with autism. Keywords: Cerebellum, autism, enzyme, frontal cortex, Monoamine oxidase A Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Chauhan V, Gu F and Chauhan A (2016). Impaired activity of monoamine oxidase A in the brain of children with autism. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00168 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Prof. Ved Chauhan, NYS Institute for Basic Research in Developmental Disabilities, Department of Neurochemistry, Staten Island, New York, United States, ved.chauhan@opwdd.ny.gov Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ved Chauhan Feng Gu Abha Chauhan Google Ved Chauhan Feng Gu Abha Chauhan Google Scholar Ved Chauhan Feng Gu Abha Chauhan PubMed Ved Chauhan Feng Gu Abha Chauhan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.