Altered Neurotrophin, Neuropeptide, Cytokines and Nitric Oxide Levels in Autism

Introduction: Modifications in neurotrophins, neuropeptides, cytokines and nitric oxide (NO) levels in autism may represent different biological aspects of the disease. In the present study we investigate simultaneously all these variables as an attempt to clarify their interrelationships in autism. Methods: Plasma levels of vasoactive intestinal peptide (VIP), neurotrophin-3 (NT-3), cytokines and nitric oxide (NO) were determined in children with DSM-IV autistic disorder (n = 24) and in age- and gender-matched healthy controls (n = 24). VIP, NT-3, IFN-gamma and IL-1 beta levels were measured by ELISA, TNF-alpha, IL-10, IL-6, IL-4, IL-2 were evaluated by flow cytometry, and NO by Griess reaction. Results: Plasma levels of VIP, IFN-gamma and NO were significantly higher and NT-3 plasma levels were significantly lower in children with autism, compared to the healthy subjects. In children with autism there was a positive correlation between plasma levels of NO and IFN-gamma. Discussion: Our results indicate the presence of altered levels of neurotrophin and neuropeptide in infantile autism and provide additional evidence that higher levels of IFN-gamma may be associated with increased oxidative stress in autism.

A complex chromosomal rearrangement involving chromosomes 2, 5, and X in autism spectrum disorder

Here, we describe a female patient with autism spectrum disorder and dysmorphic features that harbors a complex genetic alteration, involving a de novo balanced translocation t(2;X)(q11;q24), a 5q11 segmental trisomy and a maternally inherited isodisomy on chromosome 5. All the possibly damaging genetic effects of such alterations are discussed. In light of recent findings on ASD genetic causes, the hypothesis that all these alterations might be acting in orchestration and contributing to the phenotype is also considered. (C) 2012 Wiley Periodicals, Inc.

The biopsychosocial processes in autism spectrum disorder

Abstract Background Autism is a disorder characterized by pervasive social and communicative impairments, repetitive and stereotyped behaviors and restricted interests. Its causes and effects have been researched from various neurocognitive theoretical perspectives and with the aid of neuroimaging technology. We aimed to describe biopsychosocial processes characteristic of the Autism Spectrum Disorders. Method Literature review using Medline and Scopus databases published between 2001 and 2011, with the keywords "autism", "theory of mind", "executive functions", "central coherence" and “fMRI”. Results The studies found were plotted and organized into tables and an explanatory diagram of the main findings was produced. Conclusions The most popular neurocognitive theories are still unable to fully explain the characteristics of the complications that autistic spectrum disorder causes to the quality of life of individuals living with autism. The association of clinical research and neuroimaging may contribute to a better understanding of the functioning of the brain affected by the disorder.

Comparação dos instrumentos Childhood Autism Rating Scale e Autism Behavior Checklist na identificação e caracterização de indivíduos com distúrbios do espectro autístico

OBJETIVO: Comparar as respostas dos instrumentos Childhood Autism Rating Scale e Autism Behavior Checklist na identificação e caracterização de indivíduos com Distúrbios do Espectro Autístico. MÉTODOS: Participaram 28 indivíduos que estavam em atendimento fonoaudiológico e possuíam diagnósticos inseridos no Espectro do Autismo. Todos foram avaliados por meio dos instrumentos Autism Behavior Checklist e Childhood Autism Rating Scale a partir de informações obtidas, respectivamente, com pais e terapeutas. Os dados foram analisados estatisticamente em relação à concordância das respostas obtidas. Foram considerados concordantes os resultados de alta ou moderada probabilidade para autismo no Autism Behavior Checklist e com autismo leve-moderado ou grave na Childhood Autism Rating Scale, e respostas de baixa probabilidade no Autism Behavior Checklist e sem autismo na Childhood Autism Rating Scale. RESULTADOS: Houve concordância na maior parte das respostas obtidas. Casos em que houve discordância entre os resultados obtidos a partir dos protocolos corroboram dados da literatura, evidenciando que os instrumentos podem não ser suficientes, quando aplicados isoladamente para a definição do diagnóstico. CONCLUSÃO: Enquanto a Childhood Autism Rating Scale pode não diagnosticar crianças efetivamente autistas, o Autism Behavior Checklist pode incluir como autistas, crianças com outros distúrbios. Portanto, recomenda-se o uso complementar dos dois instrumentos.

Low serum levels of 25-hydroxyvitamin D (25-OHD) in children with autism

Objective: To confirm previous evidence suggesting an association between autism and low vitamin D serum levels. Methods: This preliminary exploratory study assessed the circulating levels of 25-hydroxyvitamin D (25-OHD) in pediatric patients with autism and in typically developing controls from Juiz de Fora, Brazil. Results: Serum levels of 25-OHD were lower in children with autism (26.48 ± 3.48 ng mL-1) when compared to typically developing subjects (40.52 ± 3.13 ng mL-1) (p < 0.001). Conclusion: Our findings attest to the importance of vitamin supplementation during pregnancy and in the treatment of children with autism, who tend to present low vitamin D consumption rates.

Analysis of Copy Number Variants identifies new candidate genes for Autism Spectrum Disorder and Intellectual Disability

Autism spectrum disorder (ASD) and Intellectual Disability (ID) are complex neuropsychiatric disorders characterized by extensive clinical and genetic heterogeneity and with overlapping risk factors. The aim of my project was to further investigate the role of Copy Numbers Variants (CNVs), identified through genome-wide studies performed by the Autism Geome Project (AGP) and the CHERISH consortium in large cohorts of ASD and ID cases, respectively. Specifically, I focused on four rare genic CNVs, selected on the basis of their impact on interesting ASD/ID candidate genes: a) a compound heterozygous deletion involving CTNNA3, predicted to cause the lack of functional protein; b) a 15q13.3 duplication containing CHRNA7; c) a 2q31.1 microdeletion encompassing KLHL23, SSB and METTL5; d) Lastly, I investigated the putative imprinting regulation of the CADPS2 gene, disrupted by a maternal deletion in two siblings with ASD and ID. This study provides further evidence for the role of CTNNA3, CHRNA7, KLHL23 and CADPS2 as ASD and/or ID susceptibility genes, and highlights that rare genetic variation contributes to disease risk in different ways: some rare mutations, such as those impacting CTNNA3, act in a recessive mode of inheritance, while other CNVs, such as those occurring in the 15q13.3 region, are implicated in multiple developmental and/or neurological disorders possibly interacting with other susceptibility variants elsewhere in the genome. On the other hand, the discovery of a tissue-specific monoallelic expression for the CADPS2 gene, implicates the involvement of epigenetic regulatory mechanisms as risk factors conferring susceptibility to ASD/ID.

The biological basis of autism spectrum disorders: evaluation of oxidative stress and erytrocyte membrane alterations

This case-control study involved a total of 29 autistic children (Au) aged 6 to 12 years, and 28 gender and age-matched typically developing children (TD). We evaluated a high number of peripheral oxidative stress parameters, erythrocyte and lymphocyte membrane functional features and membrane lipid composition of erythrocyte. Erythrocyte TBARS, Peroxiredoxin II, Protein Carbonyl Groups and urinary HEL and isoprostane levels were elevated in AU (confirming an imbalance of the redox status of Au); other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma Total antioxidant capacity and plasma carbonyl groups, erythrocyte SOD and catalase activities) were unchanged, whilst peroxiredoxin I showed a trend of elevated levels in red blood cells of Au children. A very significant reduction of both erythrocyte and lymphocyte Na+, K+-ATPase activity (NKA), a reduction of erythrocyte membrane fluidity, a reduction of phospatydyl serine exposition on erythrocyte membranes, an alteration in erythrocyte fatty acid membrane profile (increase in MUFA and in ω6/ω3 ratio due to decrease in EPA and DHA) and a reduction of cholesterol content of erythrocyte membrane were found in Au compared to TD, without change in erythrocyte membrane sialic acid content and in lymphocyte membrane fluidity. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity, and ADOS and CARS score are inversely related to peroxiredoxin II levels. Oxidative stress and erythrocyte structural and functional alterations may play a role in the pathogenesis of Autism Spectrum Disorders and could be potentially utilized as peripheral biomarkers.

Non Invasive Tools for Early Detection of Autism Spectrum Disorders

Autism Spectrum Disorders (ASDs) describe a set of neurodevelopmental disorders. ASD represents a significant public health problem. Currently, ASDs are not diagnosed before the 2nd year of life but an early identification of ASDs would be crucial as interventions are much more effective than specific therapies starting in later childhood. To this aim, cheap an contact-less automatic approaches recently aroused great clinical interest. Among them, the cry and the movements of the newborn, both involving the central nervous system, are proposed as possible indicators of neurological disorders. This PhD work is a first step towards solving this challenging problem. An integrated system is presented enabling the recording of audio (crying) and video (movements) data of the newborn, their automatic analysis with innovative techniques for the extraction of clinically relevant parameters and their classification with data mining techniques. New robust algorithms were developed for the selection of the voiced parts of the cry signal, the estimation of acoustic parameters based on the wavelet transform and the analysis of the infant’s general movements (GMs) through a new body model for segmentation and 2D reconstruction. In addition to a thorough literature review this thesis presents the state of the art on these topics that shows that no studies exist concerning normative ranges for newborn infant cry in the first 6 months of life nor the correlation between cry and movements. Through the new automatic methods a population of control infants (“low-risk”, LR) was compared to a group of “high-risk” (HR) infants, i.e. siblings of children already diagnosed with ASD. A subset of LR infants clinically diagnosed as newborns with Typical Development (TD) and one affected by ASD were compared. The results show that the selected acoustic parameters allow good differentiation between the two groups. This result provides new perspectives both diagnostic and therapeutic.

Social Cognition And Functional Brain Imaging: Extending The Broader Autism Phenotype

Evidence suggests that the social cognition deficits prevalent in autism spectrum disorders (ASDs) are widely distributed in first degree and extended relatives. This ¿broader autism phenotype¿ (BAP) can be extended into non-clinical populations and show wide distributions of social behaviors such as empathy and social responsiveness ¿ with ASDs exhibiting these behaviors on the lower ends of the distributions. Little evidence has previously shown relationships between self-report measures of social cognition and more objective tasks such as face perception in functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs). In this study, three specific hypotheses were addressed: a) increased social ability, as measured by an increased Empathy Quotient, decreased Social Responsiveness Scale (SRS-A) score, and increased Social Attribution Task score, will predict increased activation of the fusiform gyrus in response to faces as compared to houses; b) these same measures will predict N170 amplitude and latency showing decreased latency and increased amplitude for faces as compared to houses with increased social ability; c) increased amygdala volume will predict increased fusiform gyrus activation when viewing faces as compared to houses. Findings supported all of the hypotheses. Empathy scores significantly predicted both right FFG activation [F(1,20) = 4.811, p = .041, ß = .450, R2 = 0.20] and left FFG activation [F(1,20) = 7.70, p = .012, ß = .537, R2 = 0.29]. Based on ERP results increased right lateralization face-related N170 was significantly predicted by the EQ [F(1,54) = 6.94, p = .011, ß = .338, R2 = 0.11]. Finally, total amygdala volume significantly predicted right [F(1,20) = 7.217, p = .014, ß = .515, R2 = 0.27] and left [F(1,20) = 36.77, p < .001, ß = .805, R2 = 0.65] FFG activation. Consistent with the a priori hypotheses, traits attributed to the BAP can significantly predict neural responses to faces in a non-clinical population. This is consistent with the face processing deficits seen in ASDs. The findings presented here contribute to the extension of the BAP from unaffected relatives of individuals with ASDs to the general population. These findings also give continued evidence in support of a continuous distribution of traits found in psychiatric illnesses in place of a traditional, dichotomous ¿all-or-nothing¿ diagnostic framework of neurodevelopmental and neuropsychiatric disorders.

INCREASING PARTICIPATION IN THE CLASSROOM FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS

Active participation is as essential a skill to children with autism as it is for children without autism, as children are expected to engage in these skills both in and outside the classroom. Without participation skills, children are at a disadvantage when it comes to school and other settings, such as extracurricular activities and the workforce. Recent research has shown that there are interventions available that aim to improve the social skills of children in the home and in the school. These interventions can be delivered in varying forms with the primary caregiver as the interventionist, the specialist as the interventionist, and naturalistic interventions. The purpose of this study was to investigate one of the naturalistic interventions, the Competent Learner Model, and determine its effects on the participation and social skills of students with autism. Three middle school male students diagnosed with autism from a rural northeast middle school participated in the study. They were assessed using the Competent Learner Repertoire Assessments of the Competent Learner Model and the adaptive measures of the Vineland-II and ABAS-II. The results showed improvement for one of the three students and little to no improvement for the other two students.

Examining The Genetic, Social-Cognitive, And Neural Correlates Of Autism Spectrum Disorder Behaviors In Typically Developing Chi

Autism spectrum disorders (ASD) are pervasive developmental disorders that affect approximately 1 in 50 children (Blumberg et al., 2013). Due to the social nature of the deficits that characterize the disorders, many have classified them as disorders of social cognition, which is the process that individuals use in order to successfully interact with members of their own species (Frith & Frith, 2007). Previous research has typically neglected the spectrum nature of ASD in favor of a more categorical approach of ¿autistic¿ versus ¿non-autistic,¿ but the spectrum requires a more continuous approach. Thus, the present study sought to examine the genetic, social-cognitive, and neural correlates of ASD-like traits as well as the relationship between these dimensions in typically developing children. Parents and children completed several quantitative measures examining several areas of social-cognitive functioning, including theory of mind and social functioning, restricted/repetitive behaviors and interests, and adaptive/maladaptive functioning. Children were also asked to undergo an EEG and both parents and children contributed a saliva sample that was used to sequence four single nucleotide polymorphisms (SNPs) of the OXTR gene, rs1042778, rs53576, rs2254298, and rs237897. We successfully demonstrated a significant relationship between behavioral measures of social-cognition and differences in face perception via the N170. However, the directionality of these relationships varied based on the behavioral measure and particular N170 difference scores. We also found support for the associations between the G_G allelic combination of rs1042778 and the A_A and A_G allelic combinations of rs2254298 and increased ASD-like behavior with decreased social-cognitive functioning. In contrast, our results contradict previous findings with rs237897 and imply that individuals with the A_A and A_G genotypes are less similar to those with ASD and have higher social cognitive functioning than those with the G_G genotype. In conclusion, we have demonstrated the existence of ASD-like traits in typically developing children and have shown a link between behavioral, genetic, and neural correlates of social-cognition. These findings demonstrate the importance of considering autism as a spectrum disorder and provide support for the move to a more continuous approach to neurodevelopmental disorders.

Facial affect recognition training in autism: can we animate the fusiform gyrus?

One of the most consistent findings in the neuroscience of autism is hypoactivation of the fusiform gyrus (FG) during face processing. In this study the authors examined whether successful facial affect recognition training is associated with an increased activation of the FG in autism. The effect of a computer-based program to teach facial affect identification was examined in 10 individuals with high-functioning autism. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) changes in the FG and other regions of interest, as well as behavioral facial affect recognition measures, were assessed pre- and posttraining. No significant activation changes in the FG were observed. Trained participants showed behavioral improvements, which were accompanied by higher BOLD fMRI signals in the superior parietal lobule and maintained activation in the right medial occipital gyrus.

An fMRI-study of locally oriented perception in autism: altered early visual processing of the block design test

Autism has been associated with enhanced local processing on visual tasks. Originally, this was based on findings that individuals with autism exhibited peak performance on the block design test (BDT) from the Wechsler Intelligence Scales. In autism, the neurofunctional correlates of local bias on this test have not yet been established, although there is evidence of alterations in the early visual cortex. Functional MRI was used to analyze hemodynamic responses in the striate and extrastriate visual cortex during BDT performance and a color counting control task in subjects with autism compared to healthy controls. In autism, BDT processing was accompanied by low blood oxygenation level-dependent signal changes in the right ventral quadrant of V2. Findings indicate that, in autism, locally oriented processing of the BDT is associated with altered responses of angle and grating-selective neurons, that contribute to shape representation, figure-ground, and gestalt organization. The findings favor a low-level explanation of BDT performance in autism.

Functional imbalance of visual pathways indicates alternative face processing strategies in autism

OBJECTIVE: To investigate whether autistic subjects show a different pattern of neural activity than healthy individuals during processing of faces and complex patterns. METHODS: Blood oxygen level-dependent (BOLD) signal changes accompanying visual processing of faces and complex patterns were analyzed in an autistic group (n = 7; 25.3 [6.9] years) and a control group (n = 7; 27.7 [7.8] years). RESULTS: Compared with unaffected subjects, autistic subjects demonstrated lower BOLD signals in the fusiform gyrus, most prominently during face processing, and higher signals in the more object-related medial occipital gyrus. Further signal increases in autistic subjects vs controls were found in regions highly important for visual search: the superior parietal lobule and the medial frontal gyrus, where the frontal eye fields are located. CONCLUSIONS: The cortical activation pattern during face processing indicates deficits in the face-specific regions, with higher activations in regions involved in visual search. These findings reflect different strategies for visual processing, supporting models that propose a predisposition to local rather than global modes of information processing in autism.