The Level and Nature of Autistic Intelligence II: What about Asperger Syndrome?

A distinctively uneven profile of intelligence is a feature of the autistic spectrum. Within the spectrum, Asperger individuals differ from autistics in their early speech development and in being less likely to be characterized by visuospatial peaks. While different specific strengths characterize different autistic spectrum subgroups, all such peaks of ability have been interpreted as deficits: isolated, aberrant, and irreconcilable with real human intelligence. This view has recently been challenged by findings of autistic strengths in performance on Raven's Progressive Matrices (RPM), an important marker of general and fluid intelligence. We investigated whether these findings extend to Asperger syndrome, an autistic spectrum subgroup characterized by verbal peaks of ability, and whether the cognitive mechanisms underlying autistic and Asperger RPM performance differ. Thirty-two Asperger adults displayed a significant advantage on RPM over Wechsler Full-Scale and Performance scores relative to their typical controls, while in 25 Asperger children an RPM advantage was found over Wechsler Performance scores only. As previously found with autistics, Asperger children and adults achieved RPM scores at a level reflecting their Wechsler peaks of ability. Therefore, strengths in RPM performance span the autistic spectrum and imply a common mechanism advantageously applied to different facets of cognition. Autistic spectrum intelligence is atypical, but also genuine, general, and underestimated.     

Parental bonding in the treatment of autistic behavior

Ten autistic children were treated by an ethologically influenced family therapy. All had been screened using routine neurological and biochemical tests. At the beginning and at the end of a 12-month period of treatment, standard sampling techniques were used to measure various parameters of their behavior. Two children improved rapidly with the disappearance of autistic behavior, six improved to varying degrees, and two showed no change. The overall results of the entire group showed significant improvement in most of the items evaluated.     

Understanding and Determining the Etiology of Autism

Worldwide, the rate of autism has been steadily rising. There are several environmental factors in concert with genetic susceptibilities that are contributing to this rise. Impaired methylation and mutations of mecp2 have been associated with autistic spectrum disorders, and related Rett syndrome. Genetic polymorphisms of cytochrome P450 enzymes have also been linked to autism, specifically CYP27B1 that is essential for proper vitamin D metabolism. Vitamin D is important for neuronal growth and neurodevelopment, and defects in metabolism or deficiency have been implicated in autistic individuals. Other factors that have been considered include: maternally derived antibodies, maternal infection, heavy metal exposure, folic acid supplementation, epigenetics, measles, mumps, rubella vaccination, and even electromagnetic radiation. In each case, the consequences, whether direct or indirect, negatively affect the nervous system, neurodevelopment, and environmental responsive genes. The etiology of autism is a topic of controversial debate, while researchers strive to achieve a common objective. The goal is to identify the cause(s) of autism to understand the complex interplay between environment and gene regulation. There is optimism that specific causes and risk factors will be identified. The results of future investigations will facilitate enhanced screening, prevention, and therapy for “at risk” and autistic patients.     

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.     

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.     

Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities

Background  

A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin) in blood platelets (platelet hyperserotonemia). The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor.     

Identification of Biomarkers of Impaired Sensory Profiles among Autistic Patients

BackgroundAutism is a neurodevelopmental disorder that displays significant heterogeneity. Comparison of subgroups within autism, and analyses of selected biomarkers as measure of the variation of the severity of autistic features such as cognitive dysfunction, social interaction impairment, and sensory abnormalities might help in understanding the pathophysiology of autism.ResultsWhile none of the studied markers correlated with CARS and SRS as measure of cognitive and social impairments, six markers significantly correlated with sensory profiles of autistic patients. Multiple regression analysis identifies a combination of PGES, mPGES-1, and PE as best predictors of the degree of sensory profile impairment. Library identification resulted in 100% correct assignments of both autistic and control participants based on either set 1 or 2 biomarkers together with a satisfactory rate of assignments in case of sensory profile impairment using different sets of biomarkers.ConclusionThe two selected sets of biomarkers were effective to separate autistic from healthy control subjects, demonstarting the possibility to accurately predict the severity of autism using the selected biomarkers. The effectiveness of the identified libraries lied in the fact that they were helpful in correctly assigning the study population as control or autistic patients and in classifying autistic patients with different degree of sensory profile impairment.     

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.     

Neurofeedback for Autistic Spectrum Disorder: A Review of the Literature

There is a need for effective interventions to address the core symptoms and problems associated with autistic spectrum disorder (ASD). Behavior therapy improves communication and behavioral functioning. Additional treatment options include psychopharmacological and biomedical interventions. Although these approaches help children with autistic problems, they may be associated with side effects, risks or require ongoing or long-term treatment. Neurofeedback is a noninvasive approach shown to enhance neuroregulation and metabolic function in ASD. We present a review of the literature on the application of Neurofeedback to the multiple problems associated with ASD. Directions for future research are discussed.     

Pathophysiological role of nitric oxide and adrenomedullin in autism

Several studies indicate that nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. Adrenomedullin (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. We hypothesized that NO and AM activities have been affected in autistic patients and aimed to examine these molecules. Twenty-six autistic patients and 22 healthy control subjects were included in this study. AM and total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31). Certainly, this subject needs much further research investigating autistic patients in earlier periods of life and with subtypes of the disorder.     

Molecular dissection of the amygdala and its relevance to autism

The limbic system, and in particular the amygdala, have been implicated in autism. The amygdala is a complex structure that in rodents consists of at least 12 different nuclei or subnuclei. A comparative analysis of amygdala neuroanatomy in normal vs. autistic brains would be aided by the availability of molecular markers to unambiguously recognize these different amygdala substructures. Here we report on the development of methods to identify genes enriched in the central, lateral and medial nuclei of the rodent amygdala. Our results suggest that laser-capture microdissection of specific amygdala subnuclei, when combined with linear amplification of cRNA probes for oligonucleotide microarray hybridization, can efficiently identify genes whose expression is confined to these substructures. Importantly, many of these genes were missed in previous gene expression-profiling experiments using whole amygdala tissue. The isolation of human orthologs of these subnucleus-specific genes, and/or the application of these methods directly to human tissue, may provide useful markers for characterizing neuropathological correlates of autism, as well as for identifying molecular differences between normal and autistic brains.     

EEG abnormalities, epilepsy and regression in autism: a review

Autism is associated with a high frequency of epileptiform EEG abnormalities (prevalence range 10.3-72.4%) and epilepsy (prevalence range 0-44.5%). A significant subgroup of autistic children (20-49%) experience autistic regression. The relationship among EEG abnormalities, epilepsy, and regression in autistic patients is not yet well understood. In this review, the current knowledge of the relationship is summarized. The evidence from clinical studies does not support the view that EEG abnormalities play a role in autistic regression. The majority of studies also failed to find any significant relationship between epilepsy and autistic regression. However, some results indicated that the higher the prevalence of epilepsy in the sample, the greater the probability of there being a significant association between epilepsy and autistic regression. Further research on the topic is needed.     

Views on Researcher-Community Engagement in Autism Research in the United Kingdom: A Mixed-Methods Study

There has been a substantial increase in research activity on autism during the past decade. Research into effective ways of responding to the immediate needs of autistic people is, however, less advanced, as are efforts at translating basic science research into service provision. Involving community members in research is one potential way of reducing this gap. This study therefore investigated the views of community involvement in autism research both from the perspectives of autism researchers and of community members, including autistic adults, family members and practitioners. Results from a large-scale questionnaire study (n = 1,516) showed that researchers perceive themselves to be engaged with the autism community but that community members, most notably autistic people and their families, did not share this view. Focus groups/interviews with 72 participants further identified the potential benefits and remaining challenges to involvement in research, especially regarding the distinct perspectives of different stakeholders. Researchers were skeptical about the possibilities of dramatically increasing community engagement, while community members themselves spoke about the challenges to fully understanding and influencing the research process. We suggest that the lack of a shared approach to community engagement in UK autism research represents a key roadblock to translational endeavors.     

Common and Distinct Impacts of Autistic Traits and Alexithymia on Social Reward

According to the social motivation hypothesis of autism, individuals with high levels of autistic traits experience reduced levels of reward from social interactions. However, empirical evidence to date has been mixed, with some studies reporting lower levels of social reward in individuals with Autism Spectrum Disorder (ASD), and others finding no difference when compared to typically developing controls. Alexithymia, a subclinical condition associated with the reduced ability to identify and describe one’s own emotions, has been found to account for other affective difficulties observed inconsistently in individuals with ASD. The current study used a nonclinical sample (N = 472) to explore the associations between autistic traits and the value of six types of social reward, as measured by the Social Reward Questionnaire. In addition, we measured alexithymia to assess if this accounted for associations between autistic traits and social reward. There were three main findings. Firstly, higher levels of autistic traits were associated with significantly less enjoyment of admiration and sociability, and adding alexithymia to these models did not account for any additional variance. Secondly, both autistic traits and alexithymia were uniquely associated with reduced levels of enjoyment of prosocial interactions and sexual relationships. Thirdly, autistic traits were associated with higher levels of enjoyment of passivity and negative social potency, but these associations were no longer significant once alexithymia was taken into account, suggesting that co-occurring alexithymia accounted for these apparent associations. Overall, the current findings provide a novel and more nuanced picture of the relationship between autistic traits and social reward.     

Autism as a neurodevelopmental disorder affecting communication and learning in early childhood: prenatal origins, post-natal course and effective educational support

Colwyn Trevarthen, working on autism, discussed the importance of time, rhythm and temporal processing in brain function. The brains of new born infants show highly coherent and coordinated patterns of activity over time, and their rhythms are remarkably similar to those of adults. Since the cortex has not yet developed, this coordination must be subcortical in origin. The likely source is the emotional motor system. He noted that the cerebellum might regulate the intricate timing of the development and expression of emotional communication. He also pointed out that emotional and motivational factors have often been seriously neglected in psychology (largely owing to a misplaced focus on 'cognition' as some isolated entity) and emphasized the potential importance of empathetic support and music therapy in helping autistic children.     

Upregulation of Ras/Raf/ERK1/2 signaling and ERK5 in the brain of autistic subjects

Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. A number of studies have shown that the Ras/Raf/ERK1/2 (extracellular signal-regulated kinase) signaling pathway plays important roles in the genesis of neural progenitors, learning and memory. Ras/Raf/ERK1/2 and ERK5 have also been shown to have death-promoting apoptotic roles in neural cells. Recent studies have shown a possible association between neural cell death and autism. In addition, two recent studies reported that a deletion of a locus on chromosome 16, which included the mitogen-activated protein kinase 3 (MAPK3) gene that encodes ERK1, is associated with autism. Most recently, our laboratory detected that Ras/Raf/ERK1/2 signaling activities were significantly enhanced in the brain of BTBR mice that model autism, as they exhibit many autism-like behaviors. We thus hypothesized that Ras/Raf/ERK1/2 signaling and ERK5 could be abnormally regulated in the brain of autistic subjects. In this study, we show that the expression of Ras protein was significantly elevated in the frontal cortex of autistic subjects. C-Raf phosphorylation was increased in the frontal cortex, while both C-Raf and A-Raf activities were enhanced in the cerebellum of autistic subjects. We also detected that both the protein expression and activities of ERK1/2 were significantly upregulated in the frontal cortex of autistic subjects, but not in the cerebellum. Furthermore, we showed that ERK5 protein expression is upregulated in both frontal cortex and cerebellum of autistic subjects. These results suggest that the upregulation of Ras/Raf/ERK1/2 signaling and ERK5 activities mainly found in the frontal cortex of autistic subjects may be critically involved in the pathogenesis of autism.     

Relationship Between Sonic Hedgehog Protein, Brain-Derived Neurotrophic Factor and Oxidative Stress in Autism Spectrum Disorders

The etiology of autism spectrum disorders (ASD) is not well known but oxidative stress has been suggested to play a pathological role. We report here that the serum levels of Sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) might be linked to oxidative stress in ASD. By using the whole blood or polymorphonuclear leukocytes, we demonstrated that autistic children produced a significantly higher level of oxygen free radicals (OFR). In addition, we found significantly higher levels of serum SHH protein in children with mild as well as severe form of autism. We also found that the serum level of BDNF was significantly reduced in autistic children with mild form of the disorder but not with severe form of the disorder. Our findings are the first to report a correlation between SHH, BDNF and OFR in autistic children, suggesting a pathological role of oxidative stress and SHH in autism spectrum disorders.     

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.     

3. Personality Factors in Thinking

Many authors would agree that thinking is never separate from needs, motives, and emotions. But in light of their theoretical positions, different investigators have solved this problem in quite different ways. Some, such as Bleuler (1912), have contrasted "autistic" thinking with "realistic" thinking; others, such as T. Rib0 (1906), have posited a special "logic of feelings" that is in contrast to ordinary logic. The connection between thinking and affect has been viewed as the coexistence of two special forms of thinking, one affective and the other logical, there being two interconnected but separate spheres - thinking and feeling.     

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.