Parenting stress and affective symptoms in parents of autistic children

We examined parenting stress and mental health status in parents of autistic children and assessed factors associated with such stress. Participants were parents of 188 autistic children diagnosed with DSM-IV criteria and parents of 144 normally developing children. Parents of autistic children reported higher levels of stress, depression, and anxiety than parents of normally developing children. Mothers of autistic children had a higher risk of depression and anxiety than that did parents of normally developing children. Mothers compared to fathers of autistic children were more vulnerable to depression. Age, behavior problems of autistic children, and mothers' anxiety were significantly associated with parenting stress.     

Demonstration of cerebral lateralisation disorder in autistic children: study of auditory reactivity by transcranial pulsed Doppler]

Transcranial Doppler Ultrasonographic recordings of the middle cerebral arteries were performed on children with autistic behavior (AUT), compared to retarded children without autistic behavior (NON-AUT) and normal children (NOR). Blood flow measurements (resistance index) were performed at rest and during auditory stimulations. Compared to NOR and NON-AUT, significant differences of the resistance index were found in AUT on the left side, thus suggesting differences in metabolic mechanisms evoked by auditory stimulations. This result confirms the hypothesis of abnormal development of cerebral lateralization in autism.     

Intestinal microflora of autistic children

Autistic behavior is often accompanied by numerous disturbing symptoms on the part of gastrointestinal system, such as abdominal pain, constipation or diarrhea. These problems are often connected with deregulation of physiological microflora in intestine. The aim of this study was to determine differences in intestinal microflora of autistic and healthy children. Strains of Clostridium spp. and enterococci were isolated more frequently from stool samples of autistic children and rarely lactobacilli. Quantitative differences were observed maliny among staphylococci, Candida spp. and Clostridium perfringens. Monitoring and stabilization of intestinal microflora and knowledge about role of particular strains in etiology of autistic disorders can increase the chances for appropriate therapy.     

Increased excretion of a lipid peroxidation biomarker in autism

It is thought that autism could result from an interaction between genetic and environmental factors with oxidative stress as a potential mechanism linking the two. One genetic factor may be altered oxidative-reductive capacity. This study tested the hypothesis that children with autism have increased oxidative stress. We evaluated children with autism for the presence of two oxidative stress biomarkers. Urinary excretion of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostane-F2alpha (8-iso-PGF2alpha) were determined in 33 children with autism and 29 healthy controls. 8-iso-PGF2alpha levels were significantly higher in children with autism. The isoprostane levels in autistic subjects were variable with a bimodal distribution. The majority of autistic subjects showed a moderate increase in isoprostane levels while a smaller group of autistic children showed dramatic increases in their isoprostane levels. There was a trend of an increase in 8-OHdG levels in children with autism but it did not reach statistical significance. There was no significant correlation between the levels of the biomarkers and vitamin intake, dietary supplements, medicine, medical disorders, or history of regression. These results suggest that the lipid peroxidation biomarker is increased in this cohort of autistic children, especially in the subgroup of autistic children.     

The evaluation of food allergy on behavior in autistic children

Background:

Despite many efforts, the etiology of autism remains unknown. Food allergy has been suggested as a pathogenic factor in Autism Spectrum Disorder (ASD). Our aim in this study was to determine whether food allergy could be considered as a risk factor for autistic children.

Methods:

Thirty-nine autistic children were examined by the skin prick test (SPT), and total serum IgE was evaluated by ELISA. SPTs were performed for egg whites, oranges, peanuts, tomatoes, tuna fish, walnuts, aubergines, melons, grapes, and cow milk. Parents and teachers were then asked to exclude these items from the childrens’ diets for six months. After the treatment period, the autistic children who tested positive for food allergies were re-assessed by a standard questionnaire to obtain further information about their medical histories.

Results:

Three of the study’s 39 autistic children (7.7%) tested positive on the SPT. Total serum IgE levels were elevated in 56.4% of the subjects (mean=164±24.5, cut-off >155 IU/ml). The results showed a decreased mean in the childrens’ autistic behaviors on the Children Autism Rating Scale (CARS) after both eight weeks and six months; however, this decrease was not statistically significant.

Conclusion:

Food allergy may play a role in the pathophysiology of autism. We conclude that avoidance of certain foods benefits the behavior of autistic children.Key Words: Autism, Food allergy, Skin prick test     

Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.     

Level of Trace Elements (Copper,Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism

Autism is a multi-factorial pathology observed in children with altered levels of essential and elevated levels of toxic elements. There are also studies reporting a decrease in nutritional trace elements in the hair and nail of autistic children with healthy controls; moreover, bioelements have been shown to play an important role in the central nervous system. Therefore, the purpose of the present study was to assess the levels of trace elements like copper (Cu), zinc (Zn), magnesium (Mg), and selenium (Se) and toxic elements like mercury (Hg), and lead (Pb) in the hair and nail samples of autistic children and to evaluate whether the level of these elements could be correlated with the severity of autism. The subjects of the study were 45 autistic children with different grades of severity (low (LFA), medium (MFA), and high (HFA) functioning autism) according to Childhood Autism Rating Scale, n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were 4-12 years of age. The study observed a valid indication of Cu body burden in the autistic children. The children with different grades of autism showed high significance (p < 0.001) in the level of copper in their hair and nail samples when compared to healthy controls. The level of Cu in the autistic children could be correlated with their degree of severity (more the Cu burden severe is autism). The study showed a significant elevation (p < 0.001) in the levels of toxic metals Pb and Hg in both hair and nail samples of autistic children when compared to healthy control group. The elevation was much pronounced in LFA group subjects when compared among autistic groups MFA and HFA. The levels of trace elements Mg and Se were significantly decreased (p < 0.001) in autistic children when compared to control. The trace element Zn showed significant variation in both hair and nails of LFA group children when compared to control group and other study groups. The significant elevation in the concentration of Cu, Pb, and Hg and significant decrease in the concentration of Mg and Se observed in the hair and nail samples of autistic subjects could be well correlated with their degrees of severity.     

Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism

Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we conducted a serological study of measles-mumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods. ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73-75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Thus the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism.     

Interhemispheric differences in the spectral power and coherence of EEG rhythms in children with autism spectrum disorders

Electroencephalographic examination of boys aged 4–9 years with autism spectrum disorders (ASDs) showed spectral power values and coherence in high-frequency bands (20–60 Hz) in various brain areas were higher than normal. Differences in spectral power were greater in the anterior areas of the left hemisphere; differences in coherence, in the right anterior and posterior areas. Interhemispheric differences typical of healthy subjects were absent in the children with ASDs. The spectral power of the θ rhythm was lower in autism, especially in the left hemisphere. The spectral power of the α rhythm in the autistic children was lower than normal, especially in the posterior areas of the left hemisphere. The μ rhythm was higher than normal in spectral power and was localized in the right, rather than left, anterior areas. The children were examined again after corrective procedures. The α-rhythm spectral power increased (became closer to the norm) in the left posterior areas, while the γ-rhythm spectral power decreased (became closer to the norm) in the right anterior areas in some of the autistic children. The electrophysiological changes were associated with improved psychological testing results, especially in nonverbal measures.     

Tactile sensitivity of normal and autistic children

Many children with autistic spectrum disorders have unusual reactions to certain sensory stimuli. These reactions vary along a hyper- to hypo-responsivity continuum. For example, some children overreact to weak sensory input, but others do not respond negatively to even strong stimuli. It is typically assumed that this deviant responsivity is linked to sensitivity, although the particular stage of sensory processing affected is not known. Psychophysical vibrotactile thresholds of six male children (age: 8–12) who were diagnosed to have autistic spectrum disorders and six normal male children (age: 7–11) were measured by using a two-alternative forced-choice task. The tactile stimuli were sinusoidal displacements and they were applied on the terminal phalanx of the left middle finger of each subject. By using a forward-masking paradigm, 40- and 250-Hz thresholds of the Pacinian tactile channel and 40-Hz threshold of the Non-Pacinian I tactile channel were determined. There was no significant difference between the thresholds of autistic and normal children, and the autistic children had the same detection and masking mechanisms as the normal children. The sensory responsivity of each subject was tested by clinical questionnaires, which showed again no difference between the two subject groups. Furthermore, no significant correlations could be found between the questionnaire data and the psychophysical thresholds. However, there was a high correlation between the data from the tactile and emotional subsets of the questionnaires. These results support the hypothesis that the hyper- and hypo-responsivity to touch, which is sometimes observed in autistic spectrum disorders, is not a perceptual sensory problem, but may probably be emotional in origin.     

Tactile sensitivity of normal and autistic children

Many children with autistic spectrum disorders have unusual reactions to certain sensory stimuli. These reactions vary along a hyper- to hypo-responsivity continuum. For example, some children overreact to weak sensory input, but others do not respond negatively to even strong stimuli. It is typically assumed that this deviant responsivity is linked to sensitivity, although the particular stage of sensory processing affected is not known. Psychophysical vibrotactile thresholds of six male children (age: 8-12) who were diagnosed to have autistic spectrum disorders and six normal male children (age: 7-11) were measured by using a two-alternative forced-choice task. The tactile stimuli were sinusoidal displacements and they were applied on the terminal phalanx of the left middle finger of each subject. By using a forward-masking paradigm, 40- and 250-Hz thresholds of the Pacinian tactile channel and 40-Hz threshold of the Non-Pacinian I tactile channel were determined. There was no significant difference between the thresholds of autistic and normal children, and the autistic children had the same detection and masking mechanisms as the normal children. The sensory responsivity of each subject was tested by clinical questionnaires, which showed again no difference between the two subject groups. Furthermore, no significant correlations could be found between the questionnaire data and the psychophysical thresholds. However, there was a high correlation between the data from the tactile and emotional subsets of the questionnaires. These results support the hypothesis that the hyper- and hypo-responsivity to touch, which is sometimes observed in autistic spectrum disorders, is not a perceptual sensory problem, but may probably be emotional in origin.     

孤独症儿童生存质量、睡眠质量现状调查及睡眠障碍的影响因素分析

摘要 目的：分析孤独症儿童生存质量、睡眠质量现状,探讨其睡眠障碍的影响因素。方法：选择2017年1月至2019年12月期间我院收治的孤独症儿童100例作为研究组,另选同期于我院进行体检的健康儿童100例作为对照组,分别应用生存质量简易量表、社会支持评定量表、儿童睡眠质量调查问卷调查两组生存质量、社会支持情况、睡眠质量。应用单因素及多因素Logistic回归分析孤独症儿童睡眠障碍的影响因素。结果：研究组儿童生存质量简易量表的主观标准评分、客观标准评分及社会支持评定量表的主观支持评分、客观支持评分、对社会支持的利用度评分、总分均显著低于对照组（P＜0.05）。研究组入睡困难、睡眠不安、间断睡眠、夜惊、夜间尿床、打鼾、梦呓、梦游、张口呼吸、夜间磨牙、睡眠出汗发生率均显著高于对照组（P＜0.05）,两组梦魇发生率比较无统计学差异（P>0.05）。研究组患儿中存在睡眠障碍的46例,无睡眠障碍的54例。单因素分析显示,睡眠障碍组父母关系差、家族精神病史、新生儿窒息史、出生体重<2500 g比例显著高于无睡眠障碍组（P＜0.05）。多因素Logistic回归分析显示,父母关系差、有家族精神疾病史、有新生儿期窒息史、出生体重<2500 g是孤独症儿童睡眠障碍的危险因素（P＜0.05）。结论：与健康儿童相比,孤独症儿童生存质量、社会支持情况较差,睡眠障碍发生率也较高,父母关系差、有家族精神疾病史、有新生儿期窒息史、出生体重<2500 g是孤独症儿童睡眠障碍的危险因素。     

Magnesium profile in autism

The aim of the present study was to determine and compare plasma and erythrocyte concentrations of magnesium in 12 autistic children (10 boys, 2 girls), 17 children with other autistic spectrum disorders (14 boys, 3 girls), 5 girls with classic Rett syndrome, and 14 normal children (7 boys, 7 girls) of the same age. No differences in intracellular Mg were found between controls and pathological subjects; however, autistic children and children with other autistic spectrum disorders had significantly lower plasma concentrations of Mg than normal subjects (p=0.013 and p=0.02, respectively). Although our study population was small, we conclude that children with autistic spectrum disorders require special dietary management. If these cases are diagnosed at an early stage, they can be helped through diet.     

Urinary oxidative stress markers in children with autism

Abstract

Oxidative stress caused by increased production of free radicals and impaired functions of antioxidants remains as the major factor associated with the pathophysiology of many neuropsychiatric diseases.

Objective

The objective of the present study was to analyze the oxidative stress markers in urine sample since the collection of blood from these children is highly meticulous and also to evaluate whether these urinary markers can be correlated with the severity of autism.

Methods

The subjects of the study were 45 autistic children with different grades of severity (low functioning autism (LFA), medium functioning autism (MFA), and high functioning autism (HFA) according to Childhood Autism Rating Scale (CARS), n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were of age 4–12 years. We determined the urinary levels of oxidative stress markers like thiobarbituric acid-reacting substances, lipid hydroperoxides, 4-hydroxy nonenal, protein carbonyls, sulfhydryl groups, total antioxidant capacity, total peroxide content, oxidative stress index, and also UA/Cr ratio in autistic children.

Results

The study observed a significant elevation in the level of oxidative stress markers in autistic children when compared with normal children. The level of antioxidants excreted in urine was found to be significantly low in autistic children. These findings when correlated with the degrees of severity, oxidative stress markers showed positive correlation with increasing order of severity (LFA > MFA > HFA), whereas antioxidants showed negative correlation.

Discussion

The study reveals that the urinary levels of oxidative stress markers can be considered as the measure of oxidative stress index in autistic children. The significant correlation between the severity of autism with urinary lipid peroxidation products also support the use of oxidative stress markers and antioxidants as biomarkers of autism.     

Features of the spectral power of the EEG rhythms in autistic children and their relation with the progress of different symptoms in schizophrenia

Right hemispheric dominance of the baseline alpha-band spectral power was revealed in 5-7 years boys with autism. This feature persisted during performance of a cognitive task (counting). Also, boys with autism showed lowered level of the alpha spectral power as compared with healthy children. In healthy children, the gamma spectral power increased during performance of the cognitive task as compared to baseline state. Autistic persons showed higher values of the gamma spectral power as compared with normal boys. Boys with autism showed less expressed changes in the gamma spectral power during the cognitive task than healthy children. The reduced spectral power of the alpha band in autistic boys may serve as a precursor of conversion from autism to schizophrenia. Higher level of the gamma spectral power in autistic boys is characteristic also of schizophrenic patients with positive symptoms. Lowered levels of fast rhythms reactivity revealed in autistic boys and the same effect earlier described in schizophrenic adults probably have the similar nature.     

Visual and somatosensory event-related brain potentials in autistic children and three different control groups

Event-related potentials (ERPs) to visual and somatosensory stimuli, generated during an oddball task, were obtained in a group of autistic children and 3 control groups (normal, attention-deficit, and dyslectic children, respectively). The task included the presentation of standard, deviant, and novel stimuli and had a (between-group) passive vs. active (counting) condition. Research questions were whether (a) autistic children differ from other children with respect to the processing of visual and/or somatosensory stimuli, as measured in the amplitude of the N1, mismatch activity, and P3, (b) autistic children specifically have problems in the processing in distal (visual) stimuli, compared to the processing of proximal (somatosensory) stimuli, and (c) autistic children have an atypical lateralization pattern of ERP activity. Only in the autistic group a task effect on the visual P2N2 (mismatch activity) and larger P3s to novels than to deviants were found, in both the visual and the somatosensory modality. There also was a smaller occipital P3 to visual standard stimuli in the passive condition in the autistic group than in 2 control groups. We concluded that autistics (a) differ from several other groups of children with respect to the visual P2N2 and the visual and somatosensory P3, (b) show abnormalities in the processing of both proximal and distal stimuli, and (c) show no indication of abnormal lateralization of ERPs.     

Real-time PCR quantitation of clostridia in feces of autistic children

Based on the hypothesis that intestinal clostridia play a role in late-onset autism, we have been characterizing clostridia from stools of autistic and control children. We applied the TaqMan real-time PCR procedure to detect and quantitate three Clostridium clusters and one Clostridium species, C. bolteae, in stool specimens. Group- and species-specific primers targeting the 16S rRNA genes were designed, and specificity of the primers was confirmed with DNA from related bacterial strains. In this procedure, a linear relationship exists between the threshold cycle (CT) fluorescence value and the number of bacterial cells (CFU). The assay showed high sensitivity: as few as 2 cells of members of cluster I, 6 cells of cluster XI, 4 cells of cluster XIVab, and 0.6 cell of C. bolteae could be detected per PCR. Analysis of the real-time PCR data indicated that the cell count differences between autistic and control children for C. bolteae and the following Clostridium groups were statistically significant: mean counts of C. bolteae and clusters I and XI in autistic children were 46-fold (P = 0.01), 9.0-fold (P = 0.014), and 3.5-fold (P = 0.004) greater than those in control children, respectively, but not for cluster XIVab (2.6 x 10(8) CFU/g in autistic children and 4.8 x 10(8) CFU/g in controls; respectively). More subjects need to be studied. The assay is a rapid and reliable method, and it should have great potential for quantitation of other bacteria in the intestinal tract.     

Investigation of antioxidant enzymes in children with autistic disorder

Impaired antioxidant mechanisms are unable to inactivate free radicals that may induce a number of pathophysiological processes and result in cell injury. Thus, any abnormality in antioxidant defence systems could affect neurodevelopmental processes and could have an important role in the etiology of autistic disorder. The plasma levels of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and erythrocyte levels of GSH-Px were investigated in 45 autistic children and compared with 41 normal controls. Levels of erythrocyte SOD, erythrocyte and plasma GSH-Px were assayed spectrophotometrically. Activities of erythrocyte SOD, erythrocyte and plasma GSH-Px in autistic children were significantly lower than normals. These results indicate that autistic children have low levels of activity of blood antioxidant enzyme systems; if similar abnormalities are present in brain, free radical accumulation could damage brain tissue.     

Detection of antinuclear and antilaminin antibodies in autistic children who received thimerosal-containing vaccines

Autism, a neurodevelopmental disorder, may involve autoimmune pathogenesis. Since mercury is potentially a risk factor for autoimmunity, we conducted a study of mercury-induced antinuclear and antilaminin antibodies in autistic and normal children who had been pre-administered with thimerosal-containing vaccines. Laboratory analysis by different immunoassays showed that the serum level of these two autoimmune markers did not significantly differ between autistic and normal children. This finding suggests that the mercury as in thimerosal-containing vaccines is likely not related to autoimmune phenomenon in autism.