Monthly Research Review September 2017

This month I have included research into ADHD , as well as the usual ASD research review.

ADHD

The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test.  “In the group of children given 6 months of magnesium supplementation, independently of other mental disorders coexisting with hyperactivity, an increase in magnesium contents in hair and a significant decrease of hyperactivity of those examined has been achieved, compared to their clinical state before supplementation and compared to the control group which had not been treated with magnesium.”

Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies.In summary, there is evidence that n-3 PUFAs supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD, and that these youth have a deficiency in n-3 PUFAs levels. Our findings provide further support to the rationale for using n-3 PUFAs as a treatment option for ADHD.”

Does Artificial Food Coloring Contribute to ADHD in Children? Highly recommended reading for those that still don’t think that food colours contribute to hyperactivity in children.

Antidepressant Use in Pregnancy and the Risk of Attention Deficit with or without Hyperactivity Disorder in Children.  “Antidepressant (AD) use during the 2nd or 3rd trimester of pregnancy was associated with an increased risk. More specifically, tricyclic use was associated with an increased risk of ADHD; SSRI and SNRI use were not associated with increased ADHD risk.”

Autism Spectrum Disorder

Dietary Supplement for Core Symptoms of Autism Spectrum Disorder: Where Are We Now and Where Should We Go? Full text. “Most studies were small and short term, and there is little evidence to support effectiveness of dietary supplements for children with ASD.” I encourage parents to read the full article, there are subgroups of children that do benefit from a gluten free diet and supplements. If anyone bothers to go to the references and read the studies, the abstracts DO NOT reflect the results of the study.

Oxytocin and social functioning. Full text. “Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin’s role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed.”

Children with autism spectrum disorder who improve with fever: Insights from the Simons Simplex Collection.This study explored characteristics of children with ASD who are reported to improve during fever. Parents of 17% of children with ASD report improvements across a range of domains during fever including cognition, communication, repetitive behaviors, social interaction, and behavior. Children who are reported to improve during fever have significantly lower non-verbal cognitive skills and language levels and more repetitive behaviors. Understanding the profiles of children who improve during episodes of fever may provide insights into new treatments for ASD.”

Behavioral Phenotype of ASD Preschoolers with Gastrointestinal Symptoms or Food Selectivity.This study investigated the prevalence and type of gastrointestinal (GI) and food selectivity (FS) symptoms in 163 preschoolers with ASD, and their possible links with core ASD features and emotional/behavioural problems. The GI plus FS group presented with Sleep Problems, Self-injurious Behaviors and Anxiety Problems. Results indicated the need for early identification of GI disturbances and FS in order to design tailored intervention for these symptoms frequently associated to challenging behaviours in ASD.”

Parents Suggest Which Indicators of Progress and Outcomes Should be Measured in Young Children with Autism Spectrum Disorder.Measurement in research with young children tends to focus on core impairments in ASD. We conducted a systematic review of qualitative studies of what matters to parents. Parent advisory groups completed structured activities to explore their perceptions of the relative importance of a wide range of outcome constructs. Their highest ranked outcomes impacted directly on everyday life and functioning (anxiety, distress, hypersensitivity, sleep problems, happiness, relationships with brothers and sisters, and parent stress).”

Bone Mineral Density in Boys Diagnosed with Autism Spectrum Disorder: A Case-Control Study.Boys with ASD had significantly lower spine BMD compared to controls but this was not correlated with any biochemical markers, dietary intake of calcium and vitamin D, elimination diet status, or GI symptomology. Reduced BMD in 4-8 year old boys with ASD appears to involve factors other than nutrient intake and GI status, and requires further study.”

Gastrointestinal symptoms in autism spectrum disorder: A review of the literature on ascertainment and prevalence.We reviewed studies having to do with autism spectrum disorder and the gastrointestinal system, dating back to 1980. We found that the median prevalence of constipation was 22.2%, diarrhea 13.0%, and any symptom 46.8%. All symptoms had a wide range of estimates across studies. GI symptoms were associated with characteristics of the study, including who measured the GI symptoms. We call for the development of a reliable and valid GI questionnaire for studies of ASD.”

Influence of gut microbiota on neuropsychiatric disorders. Full text “Alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson’s disease. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health.”

Is Taurine a Biomarker in Autistic Spectrum Disorder?The causes of autistic spectrum disorder (ASD) are not clear but a high heritability implicates an important role for genetic factors. Reports also implicate oxidative stress and inflammation in the etiology of ASD. Thus, taurine, a well-known antioxidant and regulator of inflammation, was investigated here using the sera from both girls and boys with ASD as well as their siblings and parents. 21 out of 66 children with ASD had low taurine concentrations. Since taurine has anti-oxidant activity, children with ASD with low taurine concentrations will be examined for abnormal mitochondrial function. Our data imply that taurine may be a valid biomarker in a subgroup of ASD.”

Neuropsychological Characteristics of Children with Mixed Autism and ADHD. Full text. “Our study showed significant differences in the neuropsychological characteristics of children with ASD + ADHD compared to those with ASD only. Children with ASD + ADHD showed higher symptoms of anxiety, worse working memory, and less empathy, as measured by the “Reading the Mind in the Eyes.” This suggests that having ADHD brings further challenges to individuals with ASD and may negatively impact their management and outcome. Our findings may have implications for clinical assessment as well as for intervention.”

Co-Occurrence of ASD and ADHD Traits in an Adult Population.A significant correlation was found between ADHD and autistic traits. In particular, higher inattention and overall ADHD scores were associated with self-reported deficits in communication and social skills. Our findings are similar to results from studies on clinical populations, suggesting that ADHD and ASD might share common etiology.”

Hydrogen breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in autism. “The aim of this study is to assess the prevalence of small intestinal bacterial overgrowth (SIBO) by hydrogen breath test in patients with autism spectrum disorders (ASD) with respect to a consistent control group. SIBO was significantly associated with worse symptoms of autism, demonstrating that children with SIBO may significantly contribute to symptoms of autism.”

Role of mycotoxins in the pathobiology of autism: A first evidence.Among xenobiotics, mycotoxins are worldwide contaminants of food that provoke toxicological effects, crucially resembling several symptoms associated with autism such as oxidative stress, intestinal permeability, and inflammation. Here, we focused on a group of mycotoxins to test their role in the manifestation of autism. Ochratoxin A (OTA), gliotoxin, zearalenone, and sphingosine/sphinganine ratio were determined by LC analysis in sera and urines. Our results are the first describing a possible role of OTA in the pathobiology of autism. Recalling the male prevalence of ASD (male/female = 4-5/1), it is noted that, in animal models, OTA exerts its neurotoxicity especially in males. A personalized diet coupled with probiotic administration, especially OTA adsorbing Lactobacillus, could ameliorate autistic symptoms in OTA-positive patients.”

Folate metabolism abnormalities in autism: potential biomarkers.Autism spectrum disorder (ASD) has been linked to abnormalities in folate metabolism. Polymorphisms in folate genes may act in complex polygenic ways to increase the risk of developing ASD. Autoantibodies that block folate transport into the brain have been associated with ASD and children with ASD and these autoantibodies respond to high doses of a reduced form of folate known as folinic acid (leucovorin calcium). Some of the same abnormalities are also found in mothers of children with ASD and supplementing folate during preconception and gestational periods reduces the risk to the offspring from developing ASD. These data suggest that folate pathway abnormalities may be a major metabolic disturbance underlying ASD that can be leveraged as biomarkers to improve symptoms and prevent ASD.”

Recent developments in understanding the role of the gut microbiota in brain health and disease. Full text. “There is a growing appreciation of the role of the gut microbiota in all aspects of health and disease, including brain health. Indeed, roles for the bacterial commensals in various psychiatric and neurological conditions, such as depression, autism, stroke, Parkinson’s disease, and Alzheimer’s disease, are emerging. Microbiota dysregulation has been documented in all of these conditions or in animal models thereof. Moreover, depletion or modulation of the gut microbiota can affect the severity of the central pathology or behavioral deficits observed in a variety of brain disorders. Additionally, recent preclinical and clinical evidence suggest that targeting the microbiota through prebiotic, probiotic, or dietary interventions may be an effective “psychobiotic” strategy for treating symptoms in mood, neurodevelopmental disorders, and neurodegenerative diseases.”

Immunological cytokine profiling identifies TNF-α as a key molecule dysregulated in autistic children. Full text. “Our results provide further support for altered innate immunity being an important autism pathogenic factor, with autistic children showing increased blood TNF-α concentrations associated with symptom severity, and decreased expression of the THRIL gene involved in regulating TNF-α.

Current nutritional approaches in managing autism spectrum disorder: A review.The link between nutrition and autism spectrum disorder (ASD), which is a complex developmental disorder manifesting itself in significant delays or deviation in interaction and communication, has provided a fresh point of view and signals that nutrition may have a role in the aetiology of ASD, as well as play an active role in treatment by alleviating symptoms. The research put forward that in individuals with ASD, while gluten-free/casein-free and ketogenic diets, camel milk, curcumin, probiotics, and fermentable foods can play a role in alleviating ASD symptoms, consumption of sugar, additives, pesticides, genetically modified organisms, inorganic processed foods, and hard-to-digest starches may aggravate symptoms. This review emphasizes the value of identifying current nutritional approaches specific to individuals with ASD and integrating their effects on symptoms to the conversation and presents suggestions for future research designed to identify medical nutrition therapies targeting this population to better understand the link between ASD and nutrition.” So, it seems that the benefit of using a nutritional approach in the treatment of ASD just continues to grow in strength.

Brief Report: What Happens When I Can No Longer Support My Autistic Relative? Worries About the Future for Family Members of Autistic Adults.Very little is known about autism and adulthood. Family members are often the primary support for autistic adults and frequently express concerns about what the future will hold and what support will be available for their relative. 120 family members of autistic adults completed an online survey exploring concerns about the future for their relative. The most endorsed concerns were “etheir needs won’t be met ” (77% worried weekly), “whether they will be happy” (72% worried weekly) and “who will care for them” (58% worried weekly).”

The putative role of environmental aluminium in the development of chronic neuropathology in adults and children. How strong is the evidence and what could be the mechanisms involved? Full text. “The conceptualisation of autistic spectrum disorder and Alzheimer’s disease has undergone something of a paradigm shift in recent years and rather than being viewed as single illnesses with a unitary pathogenesis and pathophysiology they are increasingly considered to be heterogeneous syndromes with a complex multifactorial aetiopathogenesis, involving a highly complex and diverse combination of genetic, epigenetic and environmental factors. One such environmental factor implicated as a potential cause in both syndromes is aluminium, as an element or as part of a salt, received, for example, in oral form or as an adjuvant. Such administration has the potential to induce pathology via several routes such as provoking dysfunction and/or activation of glial cells which play an indispensable role in the regulation of central nervous system homeostasis and neurodevelopment. Other routes include the generation of oxidative stress, depletion of reduced glutathione, direct and indirect reductions in mitochondrial performance and integrity, and increasing the production of proinflammatory cytokines in both the brain and peripherally. The mechanisms whereby environmental aluminium could contribute to the development of the highly specific pattern of neuropathology seen in Alzheimer’s disease are described. Also detailed are several mechanisms whereby significant quantities of aluminium introduced via immunisation could produce chronic neuropathology in genetically susceptible children. Accordingly, it is recommended that the use of aluminium salts in immunisations should be discontinued and that adults should take steps to minimise their exposure to environmental aluminium.”

Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms.Early intervention is critical for children with ASD, and the present study presents pilot data on a clinical trial of omega-3 and -6 fatty acid supplementation and language development, a secondary trial outcome, in children at risk for ASD. We randomized 31 children to receive an omega-3 and -6 supplement or a placebo for 3 months, and measured their language abilities at baseline and after supplementation. Gesture use, but not word production, increased for children in the treatment group more than children in the placebo group. These results suggest possible effectiveness of omega-3 and -6 supplementation for language development in children at risk for ASD.”

Prevalence of Sleep Abnormalities in Indian Children With Autism Spectrum Disorder: A Cross-Sectional Study. “Nearly three fourths of children with ASD have sleep abnormalities with a possible effect on the behavioral phenotype. The polysomnographic findings provide further insight with opportunity for pharmacological interventions. Screening for sleep problems is imperative for the appropriate management and overall improvement in quality of life in children with ASD.”

Genetic predictors of celiac disease, lactose intolerance, and vitamin D function and presence of peptide morphins in urine of children with neurodevelopmental disorders.Gastrointestinal disturbances, nutritional deficiencies, and food intolerances are frequently observed in children with neurodevelopmental disorders (NDD). Intestinal peptide permeability was estimated in NDD patients and healthy children by measuring the level of peptides in urine using high-performance liquid chromatography. Levels of opioid peptides, casomorphin 8, and gluten exorphin C were significantly elevated in urine samples of NDD patients. We have also found that lower serum levels of vitamin D (25-OH) showed association with childhood autism (CHA), a subgroup of NDD. We hypothesize that vitamin D might be important for the development of CHA.”

The Putative Role of Environmental Mercury in the Pathogenesis and Pathophysiology of Autism Spectrum Disorders and Subtypes.Environmental mercury is neurotoxic at doses well below the current reference levels considered to be safe, with evidence of neurotoxicity in children exposed to environmental sources including fish consumption and ethylmercury-containing vaccines. Possible neurotoxic mechanisms of mercury include direct effects on sulfhydryl groups, pericytes and cerebral endothelial cells, accumulation within astrocytes, microglial activation, induction of chronic oxidative stress, activation of immune-inflammatory pathways and impairment of mitochondrial functioning. (Epi-)genetic factors which may increase susceptibility to the toxic effects of mercury in ASD include the following: a greater propensity of males to the long-term neurotoxic effects of postnatal exposure and genetic polymorphisms in glutathione transferases and other glutathione-related genes and in selenoproteins. Furthermore, immune and inflammatory responses to immunisations with mercury-containing adjuvants are strongly influenced by polymorphisms in the human leukocyte antigen (HLA) region and by genes encoding effector proteins such as cytokines and pattern recognition receptors. Some epidemiological studies investigating a possible relationship between high environmental exposure to methylmercury and impaired neurodevelopment have reported a positive dose-dependent effect. Retrospective studies, on the other hand, reported no relationship between a range of ethylmercury-containing vaccines and chronic neuropathology or ASD. On the basis of these results, we would argue that more clinically relevant research is required to examine whether environmental mercury is associated with ASD or subtypes. Specific recommendations for future research are discussed.”

Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis. Full text. “Antiepileptic drugs (AEDs) are used by pregnant women for various conditions, such as epilepsy, pain syndromes, psychiatric disorders and chronic migraine. AED use during pregnancy is associated with risks to the fetus as these drugs can cross the placenta or may be transferred to the infant through breast feeding and may be associated with adverse neurodevelopment outcomes. Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen.”

Background lead and mercury exposures: Psychological and behavioral problems in children.The potential harm from exposure to nonessential metals, particularly mercury (Hg) and lead (Pb), has been the focus of research for years. Initial interest focused on relatively high exposures; however, recent evidence suggests that even background exposures might have adverse consequences for child development. With increasing Pb levels, children exhibit higher levels of hostile distrust and oppositional defiant behaviors, were more dissatisfied and uncertain about their emotions, and had difficulties with communication. These significant associations were found within a range of blood Pb levels from 0.19 to 3.25 μg/dL, well below the “reference value” for children of >5μg/dL. This study is the first to demonstrate an association between very low-level Pb exposure and fundamental psychological mechanisms that might explain prior associations with more complex outcomes such as delinquency. Analyses of vagal reactivity yielded entirely novel associations suggesting that Hg may increase autism spectrum behaviors in children with sustained vagal tone during acute stress.”

Twenty-Five Year Survival of Children with Intellectual Disability in Western Australia.Although children with intellectual disability experience higher mortality at all ages compared with those without intellectual disability, the greatest burden is for those with severe intellectual disability. However, even children with mild to moderate intellectual disability have increased risk of death compared with unaffected children.”

Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias: A hypothesis. Full text. “Could 10-20% of autism be prevented? We hypothesize that nonsyndromic or “essential” autism involves extreme male bias in infants who are genetically normal, but they develop deficiency of carnitine and perhaps other nutrients in the brain causing autism that may be amenable to early reversal and prevention. That brain carnitine deficiency might cause autism is suggested by reports of severe carnitine deficiency in autism and by evidence that TMLHE deficiency – a defect in carnitine biosynthesis – is a risk factor for autism.”

An update on anesthetics and impact on the brain.While anesthetics are indispensable clinical tools and generally considered safe and effective, a growing concern over the potential neurotoxicity of anesthesia or specific anesthetic agents has called into question the safety of general anesthetics, especially when administered at extremes of age. Exposure to general anesthetics is potentially harmful to the human brain, and the consequent long-term cognitive deficits should be classified as an iatrogenic pathology, and considered a public health problem.”

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Full text. “Emerging evidence suggests that the neuropeptide oxytocin, which regulates mammalian social functioning, may be a promising treatment for ASD. However, prior oxytocin treatment trials in ASD patients have produced equivocal results, perhaps because of variability in patients’ underlying neuropeptide biology. Here we provide evidence that oxytocin treatment improves social abilities in children with ASD and that individuals with the lowest pretreatment blood oxytocin concentrations benefit the most from oxytocin administration. These findings reveal a personalized component to oxytocin treatment which may have important implications for accurately testing oxytocin’s therapeutic potential, both for ASD and for a broad range of developmental and psychiatric disorders in which patients exhibit social impairments.”

Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial. Full text. “The safety and activity of low-dose suramin showed promise as a novel approach to treatment of ASD in this small study.”

The role of probiotics in children with autism spectrum disorder: A prospective, open-label study.After probiotic supplementation, the stool PCR of autistic children showed increases in the colony counts of Bifidobacteria and Lactobacilli levels, with a significant reduction in their body weight as well as significant improvements in the severity of autism (assessed by the ATEC), and gastrointestinal symptoms (assessed by the 6-GSI) compared to the baseline evaluated at the start of the study. We concluded that probiotics have beneficial effects on both behavioral and GI manifestations of ASD. Probiotics (a non-pharmacological and relatively risk-free option) could be recommended for children with ASD as an adjuvant therapy.”

Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice. Full text. “This is the first report to show that a WD [Western Diet] can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.”

General practice encounters for young patients with autism spectrum disorder in Australia.This study compared the patient demographics and reasons for encounter in general practice for patients <25 years with and without an autism spectrum disorder identified as a reason for encounter and/or problem managed. At autism spectrum disorder (vs non-autism spectrum disorder) encounters, there were more psychological, general and unspecified, and social reasons for encounter and fewer preventive and acute health reasons for encounter. People with an autism spectrum disorder have complex health care needs that require a skilled general practice workforce.”

Increased Hyperacusis with Risperidone in an Autistic Child. Full text. “In the literature, there is only one case on hyperacusis that worsened with risperidone in a 5-year-old girl with autism. Here we represent the case of an 11-year-old boy with autism, in whom hyperacusis worsened with risperidone, decreased after the discontinuation of the medication, and re-occurred after the prescription of the drug again. Although auditory hypersensitivity tends to affect the child’s daily life negatively and is found to be correlated with behavioral problems in autistic patients, we still know very little about its etiology, treatment, and conditions related to it.”

Anxiety Levels in Children with Autism Spectrum Disorder: A Meta-Analysis. Full text. “The study findings highlight the importance of more research in order to fully understand the nature and development of anxiety in children with ASD. More specifically, the results suggest that especially high-functioning adolescents with ASD may be at risk for developing anxiety disorders. Therefore, it seems important to carefully follow and monitor children with ASD transcending to adolescence.”

Medical comorbidities in children and adolescents with autism spectrum disorders and attention deficit hyperactivity disorders: a systematic review.This thorough literature search provides an overview of relevant articles on medical comorbidity in ADHD and/or ASD, and shows that medical disorders in these children and adolescents appear to be widespread. Those who work with children with ASD and/or ADHD should be well aware of this and actively promote routine medical assessment.”

Behavioral regression in 2 patients with autism spectrum disorder and attention-deficit/hyperactivity disorder after oral surgery performed with a general anesthetic.The authors describe postoperative behavioral changes in 2 patients with autism spectrum disorder and attention deficit hyperactivity disorder that the patients’ caretakers described as regression. In both cases, behaviors representative of autism spectrum disorder and attention deficit hyperactivity disorder worsened after uncomplicated oral surgery after receipt of a general anesthetic in the operating room. In both cases, behavioral changes caused great difficulties for the patients and caretakers and were difficult to address.”

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!