Monthly Research Review October 2017

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


Gut microbiome in ADHD and its relation to neural reward anticipation. Full text. “Our results show increases in gut microbiome predicted function of dopamine precursor synthesis between ADHD cases and controls. This increase in microbiome function relates to decreased neural responses to reward anticipation. Decreased neural reward anticipation constitutes one of the hallmarks of ADHD.”

Impaired reproduction after exposure to ADHD drugs: Systematic review of animal studies. Full text. “Data on reproductive parameters in humans when treated with ADHD drugs is sparse and we have not found any long-term data that could elucidate whether ADHD drugs irreversibly impair the reproductive system. Children are being treated with ADHD drugs at an ever earlier age and sometimes continue with the drugs for decades although these long-term treatments are based on short-term studies. We consider it likely that the harms to the reproductive system seen in animals can also occur in humans.”

Do Omega-3/6 Fatty Acids Have a Therapeutic Role in Children and Young People with ADHD? Full text. “Whilst conventional medications have a role to play in the management of ADHD symptoms, new clinically trialled evidence indicates that omega-3/6 supplementation programmes can provide a promising adjunctive therapy, lowering the dose of psychopharmacologic medications needed and subsequently improving compliance with these. It also appears that parents are looking for complementary treatments for their children to use alongside traditional treatments.”

Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial.This is the first fully blinded randomized controlled trial of medication-free children with ADHD (7-12 years) assigned to either micronutrients or placebo in a 1:1 ratio, for 10 weeks. Based on clinician, parent and teacher report, those on micronutrients showed greater improvements in emotional regulation, aggression and general functioning compared to placebo.” Here is a link to the registered trial which lists the micronutrients used in the trial.


Going Gluten Free: the History and Nutritional Implications of Today’s Most Popular Diet. “Currently, about a quarter of the population reports keeping a GFD [gluten free diet] despite GRDs [gluten related disorders] affecting less than half of these individuals. Reduced intake of calcium, B vitamins, and fiber as well as enhanced consumption of fat and simple carbohydrates has consistently been reported and needs to be continually addressed. Although a necessity in proper management of GRDs, unforeseen nutritional complications may develop in patients who are gluten free for which enhanced physician awareness is vital to achieving optimal patient care.” This a typical review of the gluten free diet, stating that it affects half of these individuals and leads to nutritional deficiencies. Compare that to the two papers below.

Clinical and genetic profile of patients with seronegative coeliac disease: the natural history and response to gluten-free diet. Full text. “Over a 4-year period, among patients with gastrointestinal symptoms seen at our single tertiary-care referral centre, a definitive diagnosis of seronegative CD was established in 48. An interesting finding in our cohort was the high number of patients who improved their symptoms after a period of GFD and, more importantly, the restitutio ad integrum of intestinal mucosa observed in the majority of patients in the duodenal specimens obtained at the second upper endoscopy. Notably, patients with seronegative CD with stigmata of malabsorption experienced normalisation of laboratory parameters, especially haemoglobin and folate serum levels, according to restoration of the intestinal villi following GFD. These findings support our initial choice to recommend a GFD trial in patients with seronegative CD.”

The Gluten-Free Diet in the 3rd Millennium: Rules, Risks and Opportunities. Full text. “This review deals with the evolving gluten-free diet, optimal recommendations while considering the overall health of patients, and multi-factorial aspects of the permanent lifestyle change.”


Can melatonin prevent or improve metabolic side effects during antipsychotic treatments? Full text. “Metabolic effects of melatonin, both central and peripheral, direct and indirect, target most of the disor­ders reported during and after SGA [second-generation antipsychotics] treatment in children, adolescents, and adults.”

Autism Spectrum Disorder

The association between mercury levels and autism spectrum disorders: A systematic review and meta-analysis.The relationship between mercury and autism spectrum disorders (ASD) has always been a topic of controversy among researchers. This study aimed to assess the relationship between ASD and mercury levels in hair, urine, blood, red blood cells (RBC), and brain through a meta-analysis. The mercury level in whole blood, RBC, and brain was significantly higher in ASD patients than healthy subjects, whereas mercury level in hair was significantly lower in ASD patients than healthy subjects. The mercury level in urine was not significantly different between ASD patients and healthy subjects. Results of the current meta-analysis revealed that mercury is an important causal factor in the etiology of ASD. It seems that the detoxification and excretory mechanisms are impaired in ASD patients which lead to accumulation of mercury in the body. Future additional studies on mercury levels in different tissues of ASD patients should be undertaken.”

Psychiatric comorbidities and use of psychotropic medications in people with autism spectrum disorder in the United States.This study investigated psychotropic medication usage in two large, cohorts of people with autism spectrum disorder (ASD) throughout the calendar year 2014. This study identified a large number of children and adults in the US with autism spectrum disorder (autism) from employer-sponsored and government funded (Medicaid) health insurance data. Psychotropic medications were used by over two thirds of people, and four in ten people received two medications at the same time. The chances of receiving medication increased for individuals with other psychiatric conditions (e.g., ADHD), and also increased with age.”

Beta-carotene as a Novel Therapy for the Treatment of ‘Autistic Like Behavior’ in Animal Models of Autism.Autism-affected individuals are characterized by lower plasma oxytocin and its ectoenzyme regulator CD38. Oxytocin, a hypothalamic hormone secreted upon the release of CD38, plays a role in social behavior and bonding. All-trans retinoic acid is a potent inducer of CD38 and can be used as a novel therapeutic strategy in autism. We investigated the role of beta-carotene in rescuing autistic-like behavior in BALB/c and BTBR mice. Beta-carotene oral supplementation to BALB/c and BTBR mice at birth significantly reduced restricted and stereotyped behaviors and interests, increased social interactions and communication, CD38, and oxytocin, probably by enhancing brain neuroplasticity without toxicity. Thus, beta-carotene administered after birth to newborns of families predisposed to ‘autism’ has the potential to prevent/ameliorate “autistic like behavior”. These results support further clinical studies.”

Gastrointestinal dysfunctions as a risk factor for sleep disorders in children with idiopathic autism spectrum disorder: A retrospective cohort study.Sleep disorders often co-occur with autism spectrum disorder. They further exacerbate autism spectrum disorder symptoms and interfere with children’s and parental quality of life. This study examines whether gastrointestinal dysfunctions increase the odds of having sleep disorders in 610 children with idiopathic autism spectrum disorder, aged 2-18 years, from the Autism Genetic Resource Exchange research program. Early detection and treatment of gastrointestinal dysfunctions in autism spectrum disorder may be means to reduce prevalence and severity of sleep problems and improve quality of life and developmental outcomes in this population.”

When Asperger’s Disorder Came Out. Full text. “Removing the Asperger’s label, valued by patients for its distinctiveness from autism brings with it the potential to inflict iatrogenic harm. This paper demonstrates how the DSM-5 reclassification has the potential to threaten the identity of those affected, and discusses the problem of autism as a stigmatizing diagnostic label.”

Vitamin D, neurosteroids and autism. Full text. “Vitamin D had been for a long time investigated for its effects on bone metabolism. Recently has been observed that the incidence of some neurodevelopmental disorders (including autism) increases hand in hand with vitamin D deficiency. Indeed, vitamin D was reported to modulate the biosynthesis of neurotransmitters and neurotrophic factors; moreover, its receptor was found in the central nervous system. Vitamin D deficiency was therefore assessed as a risk factor for autism, however the biological mechanism has not yet been revealed. In our review we focused on potential connections among vitamin D, steroids and autism. Potential mechanisms of vitamin D action are also discussed.”

Food and the gut: relevance to some of the autisms.The notion of a gut-brain-behaviour axis has garnered support from various findings: an overrepresentation of functional and pathological bowel states, bowel and behavioural findings showing bidirectional associations, a possible relationship between diet, GI function and autism and recently, greater focus on aspects of the GI tract such as the collected gut microbiota in relation to autism. Gaps remain in our knowledge of the functions of the GI tract linked to autism, specifically regarding mechanisms of action onward to behavioural presentation. Set however within the context of diversity in the presentation of autism, science appears to be moving towards defining important GI-related autism phenotypes with the possibility of promising dietary and other related intervention options onward to improving quality of life.”

Research Letter: Folic acid supplementation and intake of folate in pregnancy in relation to offspring risk of autism spectrum disorder. Full text. “In conclusion, we were not able to substantiate a hypothesized beneficial effect on child risk of ASD by maternal folic acid supplementation in the periconceptional period.”

A Randomized, Placebo-Controlled Trial of Metformin for the Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorder: Open-Label Extension.A previous study reported on a 16-week placebo-controlled, randomized clinical trial (RCT) of metformin for weight stabilization in 61 children and adolescents 6 to 17 years old with autism spectrum disorder who were prescribed atypical antipsychotics. The present study describes the results of a 16-week open-label extension. Fifty-two participants from the acute trial (85%) entered the extension; 22 had been on metformin during the initial RCT and 30 had been on placebo. Participants who initially had been taking metformin during the 16-week RCT maintained prior decreases in BMI z-scores but did not have additional weight loss. Three participants discontinued treatment because of an adverse event. No significant changes were noted on metabolic measures, although the decrease in hemoglobin A1c was large (~1 mmol) and consistent across the acute and open-label phases. Metformin can be effective for decreasing weight gain associated with atypical antipsychotic use and maintaining prior improvement in children and adolescents with autism spectrum disorder.”

Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: A randomized controlled trial. “The findings provide support for larger randomized trials of omega fatty acid supplementation for children at risk of sensory processing difficulties, especially those born preterm.”

Effect of vitamin A supplementation on gut microbiota in children with autism spectrum disorders – a pilot study. Full text. “There were significant increases in the proportion of Bacteroidetes/Bacteroidales and decreases in Bifidobacterium after the VAI, accompanying significant increases in autism biomarkers, while no significant changes were observed in autism symptoms. These findings indicated that VA could regulate gut microbiota and benefit children with ASD partly.”

Gut Dysbiosis in Animals Due to Environmental Chemical Exposures. Full text. “In this review, we will first consider the current knowledge of how endocrine disrupting chemicals (EDCs), heavy metals, air pollution, and nanoparticles can influence the gut microbiome. The second part of the review will consider how potential environmental chemical-induced gut microbiome changes might subsequently induce pathophysiological responses in the host.”

Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder. Full text. “In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA [folic acid] intake during the first month of pregnancy.”

Randomized trial of omega-3 for autism spectrum disorders: Effect on cell membrane composition and behavior.Primary outcome measures were erythrocyte membrane FA composition and TAS. Secondary outcome measures were Social Responsiveness Scale and Clinical Global Impression-Severity. Treatment with w3 improved the erythrocyte membrane w6/w3 ratio without changing TAS. There was a within subjects significant improvement in Social Motivation and Social Communication subscales scores, with a moderate to large effect size, but no treatment effect (treatment-placebo order).”

Iron deficiency parameters in autism spectrum disorder: clinical correlates and associated factors. Full text. “Hemoglobin levels of children with ASD were lower than healthy children, but this was not sufficient to result in anemia. Hemoglobin levels of children with severe ASD were lower than children with mild-moderate ASD and IDA [irin deficiency anaemia] was higher in severe ASD patients. We also indicated that there was a significant correlation between hematocrit levels of children with ASD and CARS, AuBC, and AbBC total scores.”

Subcutaneous injections of aluminum at vaccine adjuvant levels activate innate immune genes in mouse brain that are homologous with biomarkers of autism. Full text. “Aluminum (Al) is an environmental toxin with demonstrated negative impact on human health, especially the nervous system, to which humans are regularly exposed. Compared to dietary Al of which only ~0.25% is absorbed into systemic circulation, Al from vaccines may be absorbed at over 50% efficiency in the short term and at nearly 100% efƒiciency long-term. Al adjuvant promotes brain inflammation and males appear to be more susceptible to Al’s toxic effects.”

Levetiracetam is associated with decrease in subclinical epileptiform discharges and improved cognitive functions in pediatric patients with autism spectrum disorder. Full text. “Subclinical epileptiform discharges (SEDs) are common in pediatric patients with autism spectrum disorder (ASD), but the effect of antiepileptic drugs on SEDs in ASD remains inconclusive. This physician-blinded, prospective, randomized controlled trial investigated an association between the anticonvulsant drug levetiracetam and SEDs in children with ASD. Levetiracetam appears to be effective for controlling SEDs in pediatric patients with ASD and was also associated with improved behavioral and cognitive functions.”

Maternal SSRI exposure increases the risk of autistic offspring: A meta-analysis and systematic review.Selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressants used to preclude maternal pregnancy depression. There is a growing body of literature assessing the association of prenatal exposure to SSRIs with autism spectrum disorder (ASD). The present systematic review and meta-analysis reviewed the medical literature and pooled the results of the association of prenatal exposure to SSRIs with ASD. The evidence from the present study suggests that prenatal exposure to SSRIs is associated with a higher risk of ASD.”

Characterizing psychiatric comorbidity in children with autism spectrum disorder receiving publicly funded mental health services.Non-autism spectrum disorder diagnoses were assessed using an adapted Mini-International Neuropsychiatric Interview, parent version. Approximately 92% of children met criteria for at least one non-autism spectrum disorder diagnosis (78% attention deficit hyperactivity disorder, 58% oppositional defiant disorder, 56% anxiety, 30% mood).”

Problems managed and medications prescribed during encounters with people with autism spectrum disorder in Australian general practice.This study describes the problems managed and medications prescribed by general practitioners in Australia during encounters where an autism spectrum disorder was recorded. At ‘autism spectrum disorder’ encounters, there was a significantly higher management rate of psychological problems, and significantly lower management rates of skin, respiratory and general/unspecified problems, than at ‘non-autism spectrum disorder’ encounters. The rate of psychological medication prescription was significantly higher at ‘autism spectrum disorder’ encounters than at ‘non-autism spectrum disorder’ encounters. The most common medications prescribed at ‘autism spectrum disorder’ encounters were antipsychotics and antidepressants.”

Health Concerns and Health Service Utilization in a Population Cohort of Young Adults with Autism Spectrum Disorder.Individuals with autism spectrum disorder (ASD) have many health needs that place demands on the health service sector. Young adults with ASD were more likely to have almost all the examined clinical health issues and health service use indicators compared to peers without developmental disability. They were more likely to have at least one psychiatric diagnosis, and visit the family physician, pediatrician, psychiatrist, and emergency department for psychiatric reasons, compared to peers with other developmental disability.”

The overlap between autistic spectrum conditions and borderline personality disorder. Full text. “Similar to ASC [Autism Spectrum Conditions], BPD [Borderline Personality Disorder] patients have elevated autistic traits and a strong drive to systemize, suggesting an overlap between BPD and ASC.”

Autism-spectrum disorders in adolescence and adulthood: focus on sexuality.Just like their typically developing counterparts, individuals with ASD show the whole range of normal-to-problematic sexual behaviors. Improving sexual knowledge could lead to less inappropriate sexual behaviors and could improve sexual health as part of a healthy and satisfying life.”

Prescription Trends of Psychotropics in Children and Adolescents with Autism Based on Nationwide Health Insurance Data. Full text. “Psychotropic drugs were used for less than one-third of patients newly diagnosed with autism, and prescription differed by sex and age. Increased diagnostic incidence is associated with an increased prescription of psychotropic drugs. Atypical antipsychotics were the most commonly used, followed by antidepressants.”

Bone Mineral Density in Boys Diagnosed with Autism Spectrum Disorder: A Case-Control Study.This study compared bone mineral density (BMD) of the spine obtained by dual-energy X-ray absorptiometry (DEXA), nutritional status, biochemical markers, and gastrointestinal (GI) symptoms in 4-8 year old boys with Autism Spectrum Disorder (ASD) with a group of age-matched, healthy boys without ASD. 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.”

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!