Monthly Research Review June 2018

Due to the sheer volume of research over the last few months, this research review focuses on some selected issues in ASD. Do go to the autism page of the website and look at the research. There is so much that has been published on infections in ASD, folate in pregnancy, mitochondrial dysfunction, relationship issues, glyphosate, and the list of topics goes on.

Autism Spectrum Disorder

Are therapeutic diets an emerging additional choice in autism spectrum disorder management?Therapeutic diets that have been used in children with autism include ketogenic and gluten/casein-free diet. We were able to identify 8 studies conducted in animal models of autism demonstrating a beneficial effect on neurophysiological and clinical parameters. Only 1 clinical study was found showing improvement in childhood autism rating scale after implementation of ketogenic diet. With regard to gluten/casein-free diet, 4 clinical studies were totally found with 2 of them showing a favorable outcome in children with autism. Furthermore, a combination of gluten-free and modified ketogenic diet in a study had a positive effect on social affect scores. No serious adverse events have been reported.”

Pediatric Scurvy: When Contemporary Eating Habits Bring Back the Past. Full text. “We report the case of a 3-years old child developing scurvy as consequence of strict selective diet; extensive and invasive investigations were undertaken before the correct diagnosis was considered. Despite being considered a rare condition, scurvy still exists nowadays, even in children with no apparent risk factors living in wealthy families. The increasing popularity of dietary restriction for children, especially those with allergies, may potentially enhance the occurrence of scurvy in apparently healthy children.”

The Relationship between Sleep Problems, Neurobiological Alterations, Core Symptoms of Autism Spectrum Disorder, and Psychiatric Comorbidities. Full article. “Children with Autism Spectrum Disorder (ASD) are at an increased risk for sleep disturbances, and studies indicate that between 50 and 80% of children with ASD experience sleep problems. These problems increase parental stress and adversely affect family quality of life. Studies have also suggested that sleep disturbances may increase behavioral problems in this clinical population. Although understanding the causes of sleep disorders in ASD is a clinical priority, the causal relationship between these two conditions remains unclear. Given the complex nature of ASD, the etiology of sleep problems in this clinical population is probably multi-factorial. In this overview, we discuss in detail three possible etiological explanations of sleep problems in ASD that can all contribute to the high rate of these symptoms in ASD. Specifically, we examine how neurobiological alterations, genetic mutations, and disrupted sleep architecture can cause sleep problems in individuals with ASD. We also discuss how sleep problems may be a direct result of core symptoms of ASD. Finally, a detailed examination of the relationship between sleep problems and associated clinical features and psychiatric comorbidities in individuals with ASD is described.”

Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD). Full article. “Review authors examined and compared the results of all five studies. They found weak evidence that children receiving the EIBI treatment performed better than children in the comparison groups after about two years of treatment on scales of adaptive behavior, intelligence tests, expressive language (spoken language), and receptive language (the ability to understand what is said). Differences were not found for the severity of autism symptoms or a child’s problem behavior. No study reported adverse events (deterioration in adaptive behaviour or autism symptom severity) due to treatment.”

Predictors of quality of life for autistic adults.There has been limited research into the lived experience of autistic adults. Using the World Health Organization quality of life measure, we found that autistic people (370) in the UK reported their quality of life to be lower than that of the general population. Better quality of life was associated with being in a relationship; those with a mental health condition had poorer quality of life. This research suggests some ways in which autistic people can be helped to improve their quality of life.”

Follow-Up of Children With Autism Spectrum Disorder 1 Year After Early Behavioral Intervention. Full article. “The effectiveness of early intensive behavioral intervention (EIBI) for children with autism spectrum disorders (ASDs) has been demonstrated by many studies and meta-analyses. Although it is considered an exemplary practice in several countries, few studies have investigated the maintenance of gains made in EIBI over time. Thirty-two children were assessed at posttreatment and 1-year follow-up after they attended a low-to-moderate-intensity (10 to 20 hr per week) EIBI program delivered by a public rehabilitation center. Between baseline and posttreatment, children showed significant gains in most areas of intellectual functioning and a significant decrease of autism symptom severity, but no change in adaptive behavior. Gains in intellectual functioning were maintained over a 1-year period after treatment termination, but autism symptom severity had increased to approximately pretreatment levels during that interval. Considerable individual variability was noted in the evolution of outcomes.”

Aging Well on the Autism Spectrum: An Examination of the Dominant Model of Successful Aging.Using survey data, a model of “aging well” was operationalised and applied to 92 autistic adults and 60 controls. A very small proportion (3.3%) of autistic adults were found to be aging well. Significantly less autistic adults were “maintaining physical and cognitive functioning” and “actively engaging with life” in comparison to controls.”

Immunoexcitotoxicity as the central mechanism of etiopathology and treatment of autism spectrum disorders: A possible role of fluoride and aluminum. Full article. “Our review suggests that most autism spectrum disorder (ASD) risk factors are connected, either directly or indirectly, to immunoexcitotoxicity. Chronic brain inflammation is known to enhance the sensitivity of glutamate receptors and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity over a prolonged period. Neuroscience studies have clearly shown that sequential systemic immune stimulation can activate the brain’s immune system, microglia, and astrocytes, and that with initial immune stimulation, there occurs CNS microglial priming. Children are exposed to such sequential immune stimulation via a growing number of environmental excitotoxins, vaccines, and persistent viral infections. We demonstrate that fluoride and aluminum (Al3+) can exacerbate the pathological problems by worsening excitotoxicity and inflammation. While Al3+ appears among the key suspicious factors of ASD, fluoride is rarely recognized as a causative culprit. A long-term burden of these ubiquitous toxins has several health effects with a striking resemblance to the symptoms of ASD. In addition, their synergistic action in molecules of aluminofluoride complexes can affect cell signaling, neurodevelopment, and CNS functions at several times lower concentrations than either Al3+ or fluoride acting alone. Our review opens the door to a number of new treatment modes that naturally reduce excitotoxicity and microglial priming.”

Recognizing the Problem of Suicidality in Autism Spectrum Disorder.Until recently, suicidality in autism spectrum disorder (ASD) was rarely discussed. A cluster of recent articles, including an article by Culpin et al. in this issue (see following study below), has highlighted not only that suicidal thoughts and suicide attempts can occur in adolescents and young adults with ASD, but also that suicidality is likely more common in ASD than in the general population. Retrospectively, the lack of focus on suicidality in ASD seems surprising when self-injurious behavior has long been a focus of attention in ASD. The emerging studies indicate that the increased risk of self-injurious behavior in younger and less cognitively able children with ASD is matched by an increased risk of suicidality in those at a more advanced developmental level.”

Autistic Traits and Suicidal Thoughts, Plans, and Self-Harm in Late Adolescence: Population-Based Cohort Study.To examine the hypothesis that autism spectrum disorders (ASD) diagnosis and traits in childhood are associated with suicidal thoughts, plans and self-harm at 16 years, and that any observed associations are explained by depression at 12 years. Children with impaired social communication had a higher risk of self-harm with suicidal intent, suicidal thoughts, and suicidal plans by age 16 years as compared to those without. Approximately 32% of the total estimated association between social communication impairment and self-harm was explained by depressive symptoms at 12 years. Social communication impairments are an important autistic trait in relation to suicidality.”

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years – Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. Full text. “For 2014, the overall prevalence of ASD among the 11 ADDM sites was 16.8 per 1,000 (one in 59) children aged 8 years. The latest findings from the ADDM Network provide evidence that the prevalence of ASD is higher than previously reported estimates and continues to vary among certain racial/ethnic groups and communities. With prevalence of ASD ranging from 13.1 to 29.3 per 1,000 children aged 8 years in different communities throughout the United States, the need for behavioral, educational, residential, and occupational services remains high, as does the need for increased research on both genetic and nongenetic risk factors for ASD.”

An update on pharmacotherapy of autism spectrum disorder in children and adolescents. Full article. “To date, no medication is proven to be effective in treating core symptoms of autism spectrum disorder (ASD). Psychotropic medications are widely used to target emotional and behavioural symptoms in ASD. Currently, only risperidone and aripiprazole have been approved by the US Food and Drug Administration (FDA) for treatment of irritability associated with ASD in children and adolescents. However, associated metabolic side-effects are concerning. Evidence supports use of methylphenidate and atomoxetine for attention deficit hyperactivity disorder (ADHD) symptoms and clonidine and guanfacine ER appear to be helpful. SSRIs are poorly tolerated and lack evidence in reducing restricted repetitive behaviours (RRB), anxiety, and depression.”

Prenatal Exposure to Acetaminophen and Risk for Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies. Full article. “Acetaminophen is the most commonly used analgesic and antipyretic during pregnancy. Evidence of neuro-disruptive properties is accumulating. The available data is of observational nature only. Studies differed gravely in exposure and outcome assessment. Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD and hyperactivity symptoms.”

Why is vitamin B6 effective in alleviating the symptoms of autism?Vitamin B6 is widely used to treat the symptoms observed in autism. Vitamin B6 is beneficial for about half of autistic individuals in decreasing behavioral problems. Although the exact pathogenesis is not defined, it is evident that certain neurotransmitter systems are impaired in the brains of autistic patients, causing the symptoms observed in the disease. In fact, impairment of many neurotransmitter systems has been reported, including GABA, serotonin, dopamine, and noradrenalin. Furthermore, vitamin B6 is important for the synthesis of many neurotransmitters, including GABA, serotonin, dopamine, noradrenalin, histamine, glycine, and d-serine, indicating that vitamin B6 supplementation may enhance many neurotransmitter systems. Thus, vitamin B6 supplementation can treat the impaired neurotransmitter systems in a given patient, even if the actual impaired neurotransmitter systems are not defined in that patient.”

Coenzyme Q10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders.Antioxidants and oxidative stress can participate in pathobiochemical mechanisms of autism spectrum disorders (ASDs). The aim was to identify the effects of early CoQ10 supplementation on oxidative stress in children with ASDs. CoQ10 supportive therapy was determined after three months with daily dose 2 ͯ 30 mg improved oxidative stress in the children with ASDs. Based on the results, high doses of CoQ10 can improve gastrointestinal problems and sleep disorders in children with ASDs with an increase in the CoQ10 of the serum.”

A comparison of blood metal levels in autism spectrum disorder and unaffected children in Shenzhen of China and factors involved in bioaccumulation of metals.The present study compared blood plasma metals in children with autism spectrum disorder (ASD) with those in unaffected children in Shenzhen (China). The results showed that children with ASD had higher Pb, Hg, and Cd than unaffected children, while essential elements Zn, Se, and Mn showed an opposite pattern. Moreover, the children exposed to passive smoking had higher Cd than those without the exposure. Positive associations were found between levels of Hg or Pb and seafood consumption as well as body mass index (BMI).”

Therapeutic use of carbohydrate-restricted diets in an autistic child; a case report of clinical and 18FDG PET findings. Full article. “The ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that has been used successfully in the treatment of refractory epilepsies for almost 100 years. There has been accumulating evidence to show that the KD may provide a therapeutic benefit in autism spectrum disorders, albeit by a yet-unknown mechanism. We report a case of a 6-year-old patient with high-functioning autism and subclinical epileptic discharges who responded poorly to several behavioural and psychopharmacological treatments. The patient was subsequently placed on the KD due to significant glucose hypometabolism in the brain as revealed by an 18FDG PET. As soon as one month after starting the KD, the patient’s behavior and intellect improved (in regard to hyperactivity, attention span, abnormal reactions to visual and auditory stimuli, usage of objects, adaptability to changes, communication skills, fear, anxiety, and emotional reactions); these improvements continued until the end of the observation period at 16 months on the KD. The 18FDG PET, measured at 12 months on the KD, revealed that 18F-FDG uptake decreased markedly and diffusely in the whole cerebral cortex with a relatively low reduction in basal ganglia in comparison to the pre-KD assessment. It warrants further investigation if the 18FDG PET imaging could serve as a biomarker in identifying individuals with autism who might benefit from the KD due to underlying abnormalities related to glucose hypometabolism.”

Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: Three cases report.Clinical trials, including case reports, case-control studies, and a double-blinded randomized clinical study, have suggested that high-dose vitamin D3 regimens may ameliorate the core symptoms of ASD. Vitamin D3 supplementation was effective in about three-quarters of children with ASD. To further investigate the relationship between vitamin D and ASD symptoms in vitamin D-responsive autistic children, changes in symptoms were assessed in three children with ASD who were given vitamin D3 supplementation followed by a long interruption. The core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL. Overall, these results showed that the core symptoms of ASD fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD.”

Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology? Full article. “The present paper may suggest the need to broaden horizons and the study target on ASD, including oxidative stress, neurotransmitters evaluation, and sympathetic activity measurements. There is increasing evidence that ASD patients show excessive ROS [reactive oxygen species] production as reported by many studies.”

Clostridium Bacteria and Autism Spectrum Conditions: A Systematic Review and Hypothetical Contribution of Environmental Glyphosate Levels. Full article. “Researchers have shown evidence regarding the impact of gut bacteria on neurological outcomes, altering behavior and potentially affecting the onset and/or severity of psychiatric disorders. Pesticides and agrotoxics are also included among this long list of ASD-related environmental stressors. Of note, ingestion of glyphosate (GLY), a broad-spectrum systemic herbicide, can reduce beneficial bacteria in the gastrointestinal tract microbiota without exerting any effects on the Clostridium population, which is highly resistant to this herbicide. In the present study, (i) we performed a systematic review to evaluate the relationship between Clostridium bacteria and the probability of developing and/or aggravating autism among children. Two independent researches selected the studies and analyzed the data. The results of the present systematic review demonstrate an interrelation between Clostridium bacteria colonization of the intestinal tract and autism. Finally, (ii) we also hypothesize about how environmental GLY levels may deleteriously influence the gut-brain axis by boosting the growth of Clostridium bacteria in autistic toddlers.”

Sleep disturbances are associated with specific sensory sensitivities in children with autism. Full article. “Sleep disturbances are associated with specific sensory sensitivities in children with autism. While it is often assumed that sensitivities in all sensory domains are similarly associated with sleep problems, our results suggest that hypersensitivity towards touch exhibits the strongest relationship with sleep disturbances when examining children autism. We speculate that hypersensitivity towards touch interferes with sleep onset and maintenance in a considerable number of children with autism who exhibit severe sleep disturbances. This may indicate the existence of a specific sleep disturbance mechanism that is associated with sensitivity to touch.”

For more research into ASD that your medical professional is not reading. Just follow the link to my Autism page, and scroll down to Current Research – Selected research articles of interest.

Be informed, NOT misinformed!