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.     

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.     

Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV), for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of “autism”. The second aim was to compare cognitive profiles obtained on the third edition versus 4^th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger’s Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence.     

No increased circular inference in adults with high levels of autistic traits or autism

Autism spectrum disorders have been proposed to arise from impairments in the probabilistic integration of prior knowledge with sensory inputs. Circular inference is one such possible impairment, in which excitation-to-inhibition imbalances in the cerebral cortex cause the reverberation and amplification of prior beliefs and sensory information. Recent empirical work has associated circular inference with the clinical dimensions of schizophrenia. Inhibition impairments have also been observed in autism, suggesting that signal reverberation might be present in that condition as well. In this study, we collected data from 21 participants with self-reported diagnoses of autism spectrum disorders and 155 participants with a broad range of autistic traits in an online probabilistic decision-making task (the fisher task). We used previously established Bayesian models to investigate possible associations between autistic traits or autism and circular inference. There was no correlation between prior or likelihood reverberation and autistic traits across the whole sample. Similarly, no differences in any of the circular inference model parameters were found between autistic participants and those with no diagnosis. Furthermore, participants incorporated information from both priors and likelihoods in their decisions, with no relationship between their weights and psychiatric traits, contrary to what common theories for both autism and schizophrenia would suggest. These findings suggest that there is no increased signal reverberation in autism, despite the known presence of excitation-to-inhibition imbalances. They can be used to further contrast and refine the Bayesian theories of schizophrenia and autism, revealing a divergence in the computational mechanisms underlying the two conditions.     

血清ghrelin、NLRP3对老年抑郁症患者认知功能损害的诊断价值分析

摘要 目的：分析血清胃促生长素（ghrelin）、Nod样受体热蛋白结构域相关蛋白3（NLRP3）对老年抑郁症患者认知功能损害的诊断价值。方法：选择2020年1月至2021年10月在我院接受诊治的老年抑郁症患者90例作为抑郁症组,另选取同期精神健康老年志愿者50例作为对照组。根据抑郁症病情严重程度将老年抑郁症患者分为轻度组（n=32）、中度组（n=30）、重度组（n=28）,比较不同分组研究对象血清ghrelin、NLRP3水平变化。另根据老年抑郁症患者是否发生认知功能损害分为认知功能损害组和认知功能未损害组,收集患者一般人口学及临床资料,分析影响老年抑郁症患者认知功能发生损害的危险因素。采用受试者工作特征（ROC）曲线分析血清ghrelin、NLRP3对老年抑郁症患者认知功能损害的诊断价值。结果：重度组血清NLRP3炎症小体水平明显高于中度组,中度组血清NLRP3炎症小体水平明显高于轻度组,轻度组血清NLRP3炎症小体水平明显高于对照组（P<0.05）;重度组血清ghrelin水平明显低于中度组,中度组血清ghrelin水平明显低于轻度组,轻度组血清ghrelin水平明显低于对照组（P<0.05）。多因素Logistic回归分析结果显示,重大生活事件（意外事故、破产、至亲去世等）、合并糖尿病、血清ghrelin水平、独居、血清NLRP3炎症小体水平以及社会支持是老年抑郁症患者认知功能损害的影响因素（P<0.05）。血清NLRP3炎症小体、ghrelin单独以及联合诊断老年抑郁症患者认知功能损害的曲线下面积AUC（0.95CI）分别为0.723（0.506～0.922）、0.782（0.619～0.917）、0.863（0.721～0.981）。结论：血清NLRP3炎症小体水平在老年抑郁症患者中呈高表达、ghrelin水平呈现低表达,二者均是老年抑郁症患者认知功能损害的影响因素,且联合检测二者水平可辅助诊断老年抑郁症患者认知功能损害。     

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.     

Mechanical biomarkers of medial compartment knee osteoarthritis diagnosis and severity grading: Discovery phase

ObjectiveTo investigate, as a discovery phase, if 3D knee kinematics assessment parameters can serve as mechanical biomarkers, more specifically as diagnostic biomarker and burden of disease biomarkers, as defined in the Burden of Disease, Investigative, Prognostic, Efficacy of Intervention and Diagnostic classification scheme for osteoarthritis (OA) (Altman et al., 1986). These biomarkers consist of a set of biomechanical parameters discerned from 3D knee kinematic patterns, namely, flexion/extension, abduction/adduction, and tibial internal/external rotation measurements, during gait recording.Methods100 medial compartment knee OA patients and 40 asymptomatic control subjects participated in this study. OA patients were categorized according to disease severity, by the Kellgren and Lawrence grading system. The proposed biomarkers were identified by incremental parameter selection in a regression tree of cross-sectional data. Biomarker effectiveness was evaluated by receiver operating characteristic curve analysis, namely, the area under the curve (AUC), sensitivity and specificity.ResultsDiagnostic biomarkers were defined by a set of 3 abduction/adduction kinematics parameters. The performance of these biomarkers reached 85% for the AUC, 80% for sensitivity and 90% for specificity; the likelihood ratio was 8%. Burden of disease biomarkers were defined by a 3-decision tree, with sets of kinematics parameters selected from all 3 movement planes.ConclusionThe results demonstrate, as part of a discovery phase, that sets of 3D knee kinematic parameters have the potential to serve as diagnostic and burden of disease biomarkers of medial compartment knee OA.     

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.     

The autistic neuron: troubled translation?

Autism is a complex genetic disorder, but single-gene disorders with a high prevalence of autism offer insight into its pathogenesis. Recent evidence suggests that some molecular defects in autism may interfere with the mechanisms of synaptic protein synthesis. We propose that aberrant synaptic protein synthesis may represent one possible pathway leading to autistic phenotypes, including cognitive impairment and savant abilities.     

Disrupted neural synchronization in toddlers with autism

Autism is often described as a disorder of neural synchronization. However, it is unknown how early in development synchronization abnormalities emerge and whether they are related to the development of early autistic behavioral symptoms. Here, we show that disrupted synchronization is evident in the spontaneous cortical activity of naturally sleeping toddlers with autism, but not in toddlers with language delay or typical development. Toddlers with autism exhibited significantly weaker interhemispheric synchronization (i.e., weak "functional connectivity" across the two hemispheres) in putative language areas. The strength of synchronization was positively correlated with verbal ability and negatively correlated with autism severity, and it enabled identification of the majority of autistic toddlers (72%) with high accuracy (84%). Disrupted cortical synchronization, therefore, appears to be a notable characteristic of autism neurophysiology that is evident at very early stages of autism development.     

Iodine in autism spectrum disorders

ObjectiveThe aim of our study was to assess the iodine status of Polish boys with severe autism compared to their healthy peers and evaluate the relationship between urinary iodine, thyroid hormones, body mass index and Autism Spectrum Disorder (ASD) symptomatology.Subjects and methodsTests were performed in 40 boys with ASD and 40 healthy boys, aged 2–17 from the same geographic region in Poland. Urinary iodine (UI), free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), BMI, and individual symptoms measured by the Childhood Autism Rating Scale (CARS) were correlated.Validated ion chromatography method with pulsed amperometric detection was applied for the determination of urinary iodine after optimized alkaline digestion in a closed system assisted with microwaves.Results19 out of 40 children with ASD had mild to moderate iodine deficiency. Statistically significant lower levels of UI, fT3 and fT4 and higher levels of TSH were found in the autistic group when compared with the control group. Concentration of iodine in urine was negatively associated with clinician’s general impression for children between 11 and 17 years. Emotional response, adaptation to environmental change, near receptor responsiveness, verbal communication, activity level, and intellectual functioning are more associated with UI than other symptoms listed in CARS.ConclusionThe severity of certain symptoms in autism is associated with iodine status in maturing boys. Thyroid hormones were within normal reference ranges in both groups while urinary iodine was significantly lower in autistic boys suggesting that further studies into the nonhormonal role of iodine in autism are required.     

Metal and essential element levels in hair and association with autism severity

BackgroundAutism Spectrum Disorder (ASD) is a complex disorder with heterogeneous etiology and wide clinical severity which supports the needs of recognizing biological and clinical features in patient subsets. The present study aimed to understand possible associations between the hair levels of metals and essential elements and some specific features of ASD measured by the Autism Diagnostic Observation Schedule (ADOS) that represents the gold-standard instrument to objectively confirm ASD diagnosis.MethodsA cross-sectional study was performed in the province of Catania (Sicily, South Italy). Forty-eight subjects with ASD (70.8% male), aged from 2 to 17 years were studied. Metals (Li, Be, Al, Ni, As, Mo, Cd, Hg, U, Pb) and essential trace elements (Cr, Co, Mn, Zn, Cu, Se) were quantified in hair by inductively coupled plasma mass spectrometry analysis. Participants were characterized by measuring the severity of autism symptoms and cognitive levels.ResultsA significant and positive correlation was found between hair metal burden (lead, aluminum, arsenic and cadmium levels) and severity of ASD symptoms (social communication deficits and repetitive, restrictive behaviors). Hair zinc level were inversely related with age while there was a negative, significant association between hair zinc level and severity of autistic symptoms (defective functional play and creativity and increase of stereotyped behavior). Lead, molybdenum and manganese hair levels were inversely correlated with cognitive level (full intelligence quotient) in ASD individuals.ConclusionsThe present study suggests the importance to combine metallomics analysis with pertinent disease features in ASD to identify potential environmental risk factors on an individual level possibly in the early developmental period.     

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.     

Social cognitive impairment and autism: what are we trying to explain?

Early psychological theories of autism explained the clinical features of this condition in terms of perceptual and sensory processing impairments. The arrival of domain-specific social cognitive theories changed this focus, postulating a ‘primary’ and specific psychological impairment of social cognition. Across the years, evidence has been growing in support of social cognitive and social attention explanations in autism. However, there has also been evidence for general non-social cognitive impairments in representational understanding, attention allocation and sensory processing. Here, I review recent findings and consider the case for the specificity and primacy of the social cognitive impairment, proposing that we should focus more explicitly on clinically valid features for insights on the integration of ‘social’ and ‘non-social’ cognition.     

Maternal and offspring methylenetetrahydrofolate‐reductase genotypes interact in a mouse model to induce autism spectrum disorder‐like behavior

Individuals with autism constitute a variable population whose members are spread along the autism spectrum. Subpopulations within that spectrum exhibit other conditions, such as anxiety, intellectual disabilities, hyperactivity and epilepsy, with different severities and co‐occurrences. Among the genes associated with the increased risk for autism is the methylenetetrahydrofolate‐reductase (MTHFR) 677C>T polymorphism, which impairs one‐carbon (C1) metabolic pathway efficiency. The frequency of the MTHFR677TT homozygote is markedly higher among autism patients and their mothers than in the general population. Here, we report on the Mthfr heterozygous knockout (KO) mouse as a rodent model of autism that shows the contributions of maternal and offspring genotypes to the development of autistic‐like behaviors. Maternal Mthfr‐deficiency was associated with developmental delays in morphogenic features and sensory‐motor reflexes in offspring. In the adult male mouse, behaviors representing core autism symptoms, such as repetitive behavior and restricted interest, were affected by maternal genotype while social behaviors were affected by both maternal and offspring genotypes. In females and males, behaviors associated with autism such as memory impairment, social aggression and anxiety were affected by both the maternal and offspring Mthfr genotypes, with sex‐dependent differences. Mthfr‐deficient male mice with observable impacts on behavior presented a particular laminar disturbance in parvalbumin interneuron density and innervation in superficial and deep layers of the cingulate cortex. This mouse model of autism will help to elucidate the molecular mechanisms that predispose a significant subgroup of autistic patients to abnormal development and to distinguish between the in‐utero and autonomous factors involved in autism.     

精神分裂症患者童年创伤与认知功能损害、敌意归因偏向和自我怜悯能力的相关性研究

摘要 目的：探讨精神分裂症患者童年创伤与认知功能损害、敌意归因偏向和自我怜悯能力的相关性。方法：选取2019年3月至2021年6月我院收治的70例精神分裂症患者（精神分裂症组）和53例社区健康志愿者（对照组）。采用童年创伤问卷（CTQ）、中文版精神分裂症认知功能成套测验（MCCB）、中文版模棱两可、目的和敌意问卷（AIHQ-C）、中文版自我怜悯量表（SCS-C）评估所有受试人员的童年创伤、认知功能、敌意归因偏向和自我怜悯能力。Pearson相关分析精神分裂症患者CTQ评分与MCCB、AIHQ-C、SCS-C评分的相关性。结果：精神分裂症组CTQ各分量表评分及总分、AIHQ-C各项目评分及总分均高于对照组（P＜0.05）;精神分裂症组MCCB各项目评分及总分、SCS-C各因子（自我友善、普遍人性、正念）评分及总分均低于对照组（P＜0.05）。Pearson相关性分析结果显示,精神分裂症患者CTQ总分与MCCB总分、SCS-C总分呈负相关（r=-0.327、-0.470,P＜0.05）,与AIHQ-C总分呈正相关（r=0.362,P＜0.05）。结论：精神分裂症患者的童年心理创伤水平较高,且与当前认知功能受损、敌意归因偏向和自我怜悯水平降低有关。     

Metaphorical and Associative Thinking in Healthy Children and in Children with Asperger's Syndrome at Different Ages

The study of healthy children and patients with childhood autism (Asperger's syndrome) showed that metaphorical thinking is normally efficient at the age of 7–8 years and that autistic children have an impaired ability to understand metaphors and idioms widely used in verbal communication. The deficit of metaphorical thinking in autism is thought to be due to a decreased activity of the right hemisphere. In a study of associative thinking, healthy schoolchildren displayed a high degree of association between words describing sensual objects and autistic patients displayed an impairment of objective associations and a predominance of proper names, which is indicative of the left-hemispheric type of association. The impairment of the speech and mental activity (metaphorical and associative thinking) testified to changes in the interhemispheric interaction in autistic children, which is likely to show up in a decreased functional activity of the right hemisphere and an increased activity of the left hemisphere.     

老年2型糖尿病患者血清BGP、ghrelin、YKL-40水平与胰岛素抵抗及认知功能损害的关系研究

摘要 目的：研究老年2型糖尿病（T2DM）患者血清骨钙素（BGP）、生长激素释放多肽（ghrelin）及人软骨糖蛋白-39（YKL-40）水平与胰岛素抵抗及认知功能损害的关系。方法：选择2018年1月～2019年12月我院收治的老年T2DM患者100例记作病变组,选择同期于我院进行体检的老年健康志愿者100例作为对照组。比较两组血清BGP、ghrelin及YKL-40水平,血糖、血脂、胰岛素抵抗相关指标及简易智力状态检查量表（MMSE）评分情况,并分析各指标的相关性。结果：病变组血清BGP、ghrelin水平低于对照组,而YKL-40水平高于对照组（P＜0.05）。病变组空腹血糖（FPG）、糖化血红蛋白（HbA1c）水平及胰岛素抵抗指数（HOMA-IR）均高于对照组,而空腹胰岛素（FINS）水平低于对照组（P＜0.05）。病变组除语言、延迟记忆评分与对照组对比差异无统计学意义（P＞0.05）,其他各项MMSE评分均低于对照组（P＜0.05）。经Pearson相关性分析可得：老年T2DM患者血清BGP、ghrelin水平和FPG、HbA1c、HOMA-IR均呈负相关,与FINS及MMSE评分均呈正相关（P＜0.05）;而血清YKL-40水平和FPG、HbA1c、HOMA-IR均呈正相关,与FINS及MMSE评分均呈负相关（P＜0.05）。结论：老年T2DM患者的血清BGP、ghrelin存在明显低表达,而血清YKL-40水平呈明显高表达,且上述血清学指标水平均与胰岛素抵抗和认知功能损害密切相关。     

Dialysable lymphocyte extract (DLyE) in infantile onset autism: A pilot study

40 infantile autistic patients were studied. They ranged from 6 years to 15 years of age at entry. 22 were cases of classical infantile autism; whereas 18 lacked one or more clinical defects associated with infantile autism (“pseudoautism”). Of the 22 with classic autism, 21 responded to transfer factor (TF) treatment by gaining at least 2 points in symptoms severity score average (SSSA); and 10 became normal in that they were main-streamed in school and clinical characteristics were fully normalized. Of the 18 remaining, 4 responded to TF, some to other therapies. After cessation of TF therapy, 5 in the autistic group and 3 of the pseudo-autistic group regressed, but they did not drop as low as baseline levels.     

Cytokines profile and peripheral blood mononuclear cells morphology in Rett and autistic patients

A potential role for immune dysfunction in autism spectrum disorders (ASD) has been well established. However, immunological features of Rett syndrome (RTT), a genetic neurodevelopmental disorder closely related to autism, have not been well addressed yet.By using multiplex Luminex technology, a panel of 27 cytokines and chemokines was evaluated in serum from 10 RTT patients with confirmed diagnosis of MECP2 mutation (typical RTT), 12 children affected by classic autistic disorder and 8 control subjects. The cytokine/chemokine gene expression was assessed by real time PCR on mRNA of isolated peripheral blood mononuclear cells (PBMCs). Moreover, ultrastructural analysis of PBMCs was performed using transmission electron microscopy (TEM).Significantly higher serum levels of interleukin-8 (IL-8), IL-9, IL-13 were detected in RTT compared to control subjects, and IL-15 shows a trend toward the upregulation in RTT. In addition, IL-1β and VEGF were the only down-regulated cytokines in autistic patients with respect to RTT. No difference in cytokine/chemokine profile between autistic and control groups was detected. These data were also confirmed by ELISA real time PCR. At the ultrastructural level, the most severe morphological abnormalities were observed in mitochondria of both RTT and autistic PBMCs.In conclusion, our study shows a deregulated cytokine/chemokine profile together with morphologically altered immune cells in RTT. Such abnormalities were not quite as evident in autistic subjects. These findings indicate a possible role of immune dysfunction in RTT making the clinical features of this pathology related also to the immunology aspects, suggesting, therefore, novel possible therapeutic interventions for this disorder.