Monthly Research Review April 2017

This month I have included some research into ADHD, vitamin D, melatonin and mental health, as well as the usual ASD research review.


Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: A randomized controlled trial. Full text. “This study investigated the effects of supplementation with EPA- or DHA-rich oil on literacy, cognition, and behavior of children with ADHD symptoms. An increased erythrocyte DHA over 4 mo was associated with improved word reading and oppositional behavior in the entire sample, and this effect was much stronger in the subgroup with learning difficulties, who also showed associations between increased DHA and measurements of divided attention and parent-rated behavior. Increased EPA and total u-3 PUFA levels were associated with decreased anxiety/shyness.”

Mental Health

Vitamin D Deficiency in Obsessive-Compulsive Disorder Patients with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections: A Case Control Study. Full text. “Previous studies have indicated that vitamin D deficiency is common in psychiatric patients, particularly in those with neuropsychiatric disorders such as autism and schizophrenia. There has been an increasing interest in immune-related neuropsychiatric symptoms that are triggered by group A beta-hemolytic streptococcal infections. In this study, we aimed to compare the serum levels of vitamin D between obsessive-compulsive disorder (OCD) patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and control subjects. This study supports the hypothesis that an association between vitamin D metabolism and PANDAS-related OCD exists.”


Classical conditioning for preserving the effects of short melatonin treatment in children with delayed sleep: a pilot study. Full text. “Melatonin treatment is effective in treating sleep onset problems in children with delayed melatonin onset, but effects usually disappear when treatment is discontinued. In this pilot study, we investigated whether classical conditioning might help in preserving treatment effects of melatonin in children with sleep onset problems, with and without comorbid attention deficit hyperactivity disorder (ADHD) or autism. Melatonin treatment was effective in advancing dim light melatonin onset and reducing sleep onset problems, and positive effects were found on health and behavior problems. After stopping melatonin, sleep returned to baseline levels. We found that for children without comorbidity in the experimental group, sleep latency and sleep start delayed less in the stop week, which suggests an effect of classical conditioning. However, classical conditioning seems counterproductive in children with ADHD or autism.

Vitamin D

Vitamin D deficiency and diabetes. Vitamin D deficiency has been linked to the onset of diabetes. Vitamin D deficiency contributes to both the initial insulin resistance and the subsequent onset of diabetes caused by β-cell death. Vitamin D acts to reduce inflammation, which is a major process in inducing insulin resistance. What is remarkable is just how many cellular processes are maintained by Vitamin D. When Vitamin D is deficient, many of these processes begin to decline and this sets the stage for the onset of diseases such as diabetes.”

 High prevalence of vitamin D deficiency in 2–17 year olds presenting with acute fractures in southern Australia. Full text. “One third of all participants, and the majority participants who had one or more risk factor(s) for vitamin D deficiency, were vitamin D deficient. Based on our findings we recommend that vitamin D status be assessed in all children with risk factor of vitamin D deficiency living in urban environments at higher latitudes presenting with fractures.”

Vitamin D supplementation effective in preventing acute respiratory tract infections. Studies have consistently shown low levels of vitamin D make people more susceptible to respiratory infections. Acute respiratory infections are a major cause of ill health and mortality. Observational studies have shown that people with low levels of 25-hydroxyvitamin D, the major circulating vitamin D metabolite, are susceptible to respiratory infection.

 Autism Spectrum Disorder

Simplifying study of fever’s dramatic relief of autistic behavior.Dramatic relief of autistic behavior by infectious fever continues to tantalize parents and practitioners, yet researchers still hesitate to study its physiology/biochemistry, fearing stress and heat of brain imaging, contagion, and fever’s complexity. Yet what could be more revealing than a common event that virtually ‘normalizes’ autistic behavior for a time? This paper proposes study of three simplified scenarios: (1) improvements appearing hours before fever, (2) return of autistic behavior soon after fever, (3) improvements persisting long after fever. Each scenario limits some risk – and some explanation – inviting triangulation of decisive factor(s) in relief and recurrence. Return of autistic behavior after fever may be most revealing. The complex mechanisms that generated fever have all abated; simpler cooling mechanisms prevail – how many plausible explanations can there be? The decisive factor in fever’s benefit is concluded to be water drawn/carried from brain myelin and astrocytes by osmolytes glutamine and taurine released from muscles and brain; the decisive factor in return of autistic behavior after fever is return of water.”

Autoimmunity, Autoantibodies, and Autism Spectrum Disorder.It is becoming increasingly accepted that ASD is no longer defined simply as a behavioral disorder, but rather as a highly complex and heterogeneous biological disorder. Although research has focused on the identification of genetic abnormalities, emerging studies increasingly suggest that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in ASD.”

Identification of likely associations between cerebral folate deficiency and complex genetic- and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach.Recently, cerebral folate deficiency (CFD) was suggested to be involved in the pathogenesis of autism spectrum disorders (ASD). However, the exact role of folate metabolism in the pathogenesis of ASD, identification of underlying pathogenic mechanisms and impaired metabolic pathways remain unexplained. Two independent interaction modules (comprising three pathways) covering enzymes encoded by ASD-related genes and folate cofactors utilizing enzymes were generated. Module 1 suggested possible interference of CFD with serine and lysine metabolism, while module 2 identified correlations with purine metabolism and inosine monophosphate production. Since our approach was primarily conceived as a proof of principle, further amendments of the presented initial model are necessary to obtain additional actionable outcomes.”

Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Full pdf. “According to recent evidence, up to 40-50% of variance in autism spectrum disorder (ASD) liability might be determined by environmental factors. The reviews on nutritional elements have been inconclusive about the detrimental effects of deficiency in folic acid and omega 3, but vitamin D seems to be deficient in patients with ASD. The studies on toxic elements have been largely limited by their design, but there is enough evidence for the association between some heavy metals (most important inorganic mercury and lead) and ASD that warrants further investigation. Mechanisms of the association between environmental factors and ASD are debated but might include non-causative association (including confounding), gene-related effect, oxidative stress, inflammation, hypoxia/ischemia, endocrine disruption, neurotransmitter alterations, and interference with signaling pathways.”

Relationship between selenium, lead, and mercury in red blood cells of Saudi autistic children.Environmental contribution to ASD is due in large part to the sensitivity of the developing brain to external exposures such as lead (Pb), and mercury (Hg) as toxic heavy metals or due to a poor detoxification ability as the phenotype of this disorder. Selenium (Se) as an antioxidant element that counteracts the neurotoxicity of Hg, and Pb, presumably through the formation of nontoxic complexes. In the present study, Pb, Hg, and Se were measured in red blood cells (RBCs) of 35 children with ASD and 30 age- and gender-matched healthy control children. The obtained data demonstrates a significant elevation of Hg and Pb together with a significant decrease in the Se levels in RBCs of patients with ASD when compared to the healthy controls. The ratios of Se to both Pb and Hg were remarkably altered, being indicative of heavy metal neurotoxicity in patients with ASD. In conclusion, the present study indicates the importance of Se for prevention and/or therapy of heavy metal neurotoxicity.

Personal experiences of the Criminal Justice System by individuals with autism spectrum disorders.The processes of arrest, investigation, trial and imprisonment are often extremely difficult for individuals with autism spectrum disorders. The majority of those given a custodial sentence coped well in prison, probably due to the high levels of structure and firm frameworks in that environment. Explanation factors associated with the offences indicated that autism spectrum disorder characteristics such as misunderstandings, obsessions and idiosyncratic beliefs and/or behaviours were frequently involved, but stress was the most common explanation provided by the participants. The findings suggest limited understanding of autism spectrum disorders within the Criminal Justice System which needs to be significantly improved in order to secure their legal protection.”

Behavioral improvements in a valproic acid rat model of autism following vitamin D supplementation.The aim was to identify the effects of early vitamin D supplementation on autism-like behaviors (ASD) induced by valproic acid (VPA, an anti-convulsant and a mood stabilizer) in rats. 10 male Wistar rat pups with prenatal exposure to saline were in control group, and 20 Pups with prenatal exposure to VPA were divided into ASD-N (0.9% saline treated) and ASD-D group (vitamin D 80,000 IU/kg treated) on postnatal day 12. The repetitive behavior of the ASD-N group exhibited a negative linear relationship with serum 25(OH)D3 on PND 42. In conclusion, early vitamin D supplementation in infant rat with ASD induced by VPA significantly improved development and behavior of rats related with ASD.”

Association of Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorders with Mean Platelet Volume and Vitamin D. Full text. “The hematological parameters of the patients, including MPV [Mean Platelet Volume], vitamin B12, and vitamin D, were assessed. There was no statistically significant difference in hematological parameters between the groups, but there were significant differences in terms of vitamin D and vitamin B12. The patient groups showed lower levels of vitamin B12 and vitamin D. In the ADHD group, there was a negative correlation between both vitamins and MPV. Both ADHD and ASDs may accompany increased risk for cardiovascular disease due to the presence of vitamin B12 and D deficiency.”

Shorter sleep duration is associated with social impairment and comorbidities in ASD. Sleep disturbance, particularly insomnia, is common in children with autism spectrum disorders (ASD). Furthermore, disturbed sleep affects core symptoms and other related comorbidities. Severity scores for social/communication impairment and restricted and repetitive behaviors (RRB) were increased, and IQ scores were decreased, for children reported to sleep ≤420 minutes per night (lower 5th percentile) compared to children sleeping ≥660 minutes (upper 95th percentile). Our results indicate that reduced amounts of sleep are related to more severe symptoms in children with ASD.”

Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder. Full text. “Our findings identify distinctive mucosal microbial signatures in ASD children with FGID [functional gastrointestinal disorders] that correlate with cytokine and tryptophan homeostasis. Future studies are needed to establish whether these disease-associated Clostridiales species confer early pathogenic signals in children with ASD and FGID.”

Tightening the Case for Gut Microbiota in Autism-Spectrum Disorder. Editorial. Full text. “The study by Luna et al in this issue of Cellular and Molecular Gastroenterology and Hepatology tightens the case for a microbial hub and serotonin and cytokine spokes in the gastrointestinal dysfunction of ASD. Compared with ASD-unaffected children, children with ASD and gastrointestinal dysfunction had increased mucosal tissue levels of select microbial taxa, mainly members of the genus Clostridium.”

The Impact of Dynamic Seating on Classroom Behavior of Students with Autism Spectrum. Full text. “The aim of this study was to compare the effectiveness of dynamic seating devices on improving a students’ in-seat and on-task behaviors and decreasing autism related behaviors within the classroom setting. This study proposes that ball seating in the classroom causes an increase of 86.7% in in-seat behaviors of ASD students. Therapy balls provide sitting and moving concurrently, which may satisfy sensory needs. As a result of normalizing arousal levels and regulating sensory inputs with rocking and bouncing on a ball, students with autism could be satisfied physiologically and would not need to engage in selfstimulatory behaviors. Furthermore, the teachers’ reports supported the use of balls and air cushions for the students in class. Accordingly, the students were calmer when compared to the use of common chairs.”

L-Methylfolate supplementation in a child with autism and methyltetrahydrofolate reductase, enzyme gene C677TT allele.Errors in folate metabolism may play a role in the pathology of autism spectrum disorders because of increased vulnerability to oxidative stress. We report a case where L-methylfolate supplementation improved symptoms of aggression and disruptive behavior in a child with autism who tested positive for the C677TT allele of the methyltetrahydrofolate reductase enzyme gene. To our knowledge, this is the first report of L-methylfolate administration in this situation. Further controlled studies of L-methylfolate in this population are warranted.”

Metabolic Dysfunction Underlying Autism Spectrum Disorder and Potential Treatment Approaches. Full text. “Recent studies have increasingly implicated mitochondrial dysfunction in ASD. The fact that mitochondria are an integral part of diverse cellular functions and are susceptible to many insults could explain how a wide range of factors can contribute to a consistent behavioral phenotype in ASD. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD), used for nearly a century to treat medically intractable epilepsy, has been shown to enhance mitochondrial function through a multiplicity of mechanisms and affect additional molecular targets that may address symptoms and comorbidities of ASD. Here, we review the evidence for the use of metabolism-based therapies such as the KD in the treatment of ASD as well as emerging co-morbid models of epilepsy and autism.”

Aggressive behaviors and treatable risk factors of preschool children with autism spectrum disorder.Aggressive behaviors of children with ASD were significantly associated with two treatable factors: sleep problems and ADHD symptoms. These findings have substantial clinical implications: treatment of these two risk factors may be helpful in managing aggressive behavior in children with ASD.”

The association between parents’ ratings of ASD symptoms and anxiety in a sample of high-functioning boys and adolescents with Autism Spectrum Disorder. For pre-adolescents, high levels of tension in social situations were associated with 3.5-times greater likelihood of having GAD; for adolescents, experiencing difficulty in changes in routine was associated with a 10-fold increase in risk of GAD.”

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!