Monthly Research Review March 2017

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


Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine.ADHD medication may be associated with cardiovascular effects. Since increased BP [blood pressure] and HR [heart rate] in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.”

Sleep Problems as Predictors in Attention-Deficit Hyperactivity Disorder: Causal Mechanisms, Consequences and Treatment. Full pdf. “Previous studies have attempted to clarify the bidirectional relationship between ADHD and sleep problems, proposing a potential role for sleep problems as early predictors of ADHD. Sleep deprivation, sleep-disordered breathing, and circadian rhythm disturbances have been extensively studied, yielding evidence with regard to their induction of ADHD-like symptoms. The long-term consequences of sleep problems in individuals with ADHD include obesity, poor academic performance, and disrupted parent-child interactions. Early intervention has been proposed as an approach to preventing these debilitating outcomes of ADHD.”

Mental Health

Clinical Use of Curcumin in Depression: A Meta-Analysis.Six clinical trials with a total of 377 patients were reviewed, comparing the use of curcumin to placebo. In patients with depression, the pooled standardized mean difference from baseline Hamilton Rating Scale for Depression scores support the significant clinical efficacy of curcumin in ameliorating depressive symptoms. Significant anti-anxiety effects were also reported in 3 of the trials. Notably, no adverse events were reported in any of the trials.”

Effects of Acute Blueberry Flavonoids on Mood in Children and Young Adults. Full pdf. “These randomised, placebo-controlled, double-blind studies investigated the effects of acute consumption of a flavonoid-rich wild blueberry drink on the mood of healthy children and young adults. In both studies, increased Positive Affect was observed 2 h after consumption of the flavonoid-rich WBB drink (significant drink by session interaction). The flavonoid drink had no effect on Negative Affect. The effect of flavonoids on mood was consistent across two populations, at two different time points (morning and afternoon), and in a between- and within-subject design. Thus, the positive effect of blueberry flavonoids on Positive Affect appears to be robust to variations in experimental design.”

The effects of probiotics on depressive symptoms in humans: a systematic review.In the last decade, research has revealed an extensive bidirectional communication network between the gastrointestinal tract and the central nervous system, referred to as the “gut-brain axis.” Advances in this field have linked psychiatric disorders to changes in the microbiome, making it a potential target for novel antidepressant treatments. Ten studies met criteria and were analyzed for effects on mood, anxiety, and cognition. Five studies assessed mood symptoms, seven studies assessed anxiety symptoms, and three studies assessed cognition. The majority of the studies found positive results on all measures of depressive symptoms.”

Vitamin D

Vitamin D status in pediatric irritable bowel Syndrome. Full pdf. “Pediatric patients with IBS had significantly lower 25(OH)D concentration compared to controls despite having similar mean BMI values as controls. Only 7% of the children and adolescents with IBS were vitamin D sufficient, and >50% of the subjects with IBS had vitamin D deficiency. This is a much higher prevalence of vitamin D deficiency compared to IBD and other malabsorption syndromes. Monitoring for vitamin D deficiency should be part of the routine care for patients with IBS.”

Autism Spectrum Disorder

Noise and autism spectrum disorder in children: An exploratory survey.Most teachers found noise control to be an important issue for students with autism and many observed children using ear defenders. In terms of managing issues related to noise, most teachers agreed that thick or soundproof walls and carpet in the classroom were the most important issues for children with ASD.”

Effects of ω-3 fatty acids on stereotypical behavior and social interactions in Wistar rats prenatally exposed to lipopolysaccarides.Prenatal exposure to LPS [lipopolysaccharides] significantly increased the episodes of stereotyped movements and decreased social interaction in the offspring, after ω-3 PUFA supplementation these parameters reversed. Supplementation with ω-3 PUFA reversed animal behaviors that often are observed in autism and other mental disorders in rats prenatally exposed to LPS, and also exerted neuroprotective effects in marker levels of neuronal damage and expression of TGF-β.”

Pediatric Hypovitaminosis D: Molecular Perspectives and Clinical Implications. Full text. An excellent review of the importance of adequate vitamin D in paediatrics.Vitamin D plays an important role in repairing DNA damage; thus, its deficiency would result in impaired DNA repair and higher de novo genetic mutation rates linked to an increased risk of autism. There is evidence that vitamin D influences fetal brain growth and neuronal differentiation, and there is an inverse correlation between the serum level of calcidiol concentration and autism rating scale, and a higher level of calcidiol may reduce the risk of autism. There are now speculations that problematic social behaviors in autistic children may also be linked to vitamin D deficiency and abnormal level of serotonin. Higher levels of serotonin have been linked to a gene activated by vitamin D, which in turn produces an enzyme, tryptophan hydroxylase 2 (TPH-2), that converts tryptophan to 5-hydroxytryptamine (serotonin) that leads to a higher level of serotonin production, and another gene that makes the enzyme tryptophan hydroxylase 1 (TPH-1) to be inhibited by vitamin D to halt serotonin production.”

Vitamin D and autism, what’s new?An increasing amount of evidence points to the possibility that gestational and early childhood vitamin D deficiency [25(OH)D < 40 ng/ml] cause some cases of autism. Vitamin D is metabolized into a seco-steroid hormone that regulates about 3% of the 26,000 genes in the coding human genome. It is also a neurosteroid that is active in brain development, having effects on cellular proliferation, differentiation, calcium signaling, neurotrophic and neuroprotective actions; it also appears to have an effect on neurotransmission and synaptic plasticity. Children who are, or who are destined to become, autistic have lower 25(OH)D levels at 3 months of gestation, at birth and at age 8 compared to their unaffected siblings. Two open label trials found high dose vitamin D improves the core symptoms of autism in about 75% of autistic children. A few of the improvements were remarkable.  In terms of prevention, a recent small study showed vitamin D supplementation during pregnancy (5000 IU/day) and during infancy and early childhood (1000 IU/day) significantly reduced the expected incidence of autism in mothers who already had one autistic child from 20% to 5%. Vitamin D is safe; for example, over the last 15 years, Poison Control reports there have been approximately 15,000 cases of vitamin D overdose. However only three of these 15,000 people developed clinical toxicity and no one died. Given those facts, practitioners might consider treating autism with 300 IU/kg/day, and seek to prevent autism by supplementing pregnant and lactating women (5000 IU/day) and infants and young children (150 IU/kg/day) checking 25(OH)D levels every 3 months.”

Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials. Full text. “Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders). Compared with placebo, n-3 LCPUFA improved social interaction and repetitive and restricted interests and behaviours. Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA.”

Elevated Urinary Glyphosate and Clostridia Metabolites With Altered Dopamine Metabolism in Triplets With Autistic Spectrum Disorder or Suspected Seizure Disorder: A Case Study. Full text. “The pattern of metabolites in the urine samples of the males with autism are consistent with a recent theory of autism that connects widespread glyphosate use with alteration of animal and human gastrointestinal flora. That theory is that the normally beneficial bacteria species that are sensitive to glyphosate are diminished and harmful bacteria species, such as Clostridia, that are insensitive to glyphosate, are increased following exposure to glyphosate. Excessive dopamine, caused by inhibition of dopamine-beta-hydroxylase by Clostridia metabolites, in turn, produces oxidative species that damage neuronal Krebs cycle enzymes, neuronal mitochondria, and neuronal structural elements such as the neurofibrils.”

Detection of Clostridium perfringens toxin genes in the gut microbiota of autistic children.We studied stool specimens from 33 autistic children aged 2-9 years with gastrointestinal (GI) abnormalities and 13 control children without autism and without GI symptoms. Our results indicate that autistic subjects with gastrointestinal disease harbor statistically significantly higher counts of C. perfringens in their gut compared to control children. Autistic subjects also harbor statistically significantly higher counts of beta2-toxin gene-producing C. perfringens in their gut compared to control children, and the incidence of beta2-toxin gene-producing C. perfringens is significantly higher in autistic subjects compared to control children.”

The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder. Full text. “Recent studies suggest that ASD is linked to mitochondrial dysfunction, although the exact nature of mitochondrial abnormalities in ASD appears to be complicated. For example, classic mitochondrial disease is found in 5% of children with ASD, yet up to 50% of children with ASD may have biomarkers of mitochondrial dysfunction. This study provides empirical support for common mitochondrial treatments and demonstrates that the relationship between activities of mitochondrial components might be a marker to follow in addition to absolute activities. Measurements of mitochondrial activity that can be practically repeated over time may be very useful to monitor the biochemical effects of treatments.

Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor alpha autoimmune disorder.Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in Autism Spectrum Disorder (ASD). FRAAs disrupt folate transport across the blood-brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. The thyroid showed significant FRα expression during the early prenatal period but expression decreased significantly in later gestation and postnatal thyroid tissue. This study suggests that thyroid dysfunction in ASD may be related to the blocking FRAA. The high expression of FRα in the early fetal thyroid suggests that fetal and neonatal exposure to maternal FRAAs could affect the development of the thyroid and may contribute to the pathology in ASD.”

Elimination diets’ efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. Full text. ” This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, glutenfree/casein-free diet and oligoantigenic diet. The GFCF diet might be beneficial for children with ASD and food intolerance/allergy or underlying gastrointestinal disease. However, the evidence for the effectiveness of GFCF diets in children with ASD is weak and thus these diets cannot be generally recommended as a treatment for children with ASD. With regard to oligoantigenic diets, if applied under close supervision, these interventions could be valuable instruments to assess whether ADHD is triggered by food. Furthermore, we have observed large individual differences in terms of time that is needed for any positive effects of the diet to surface during the elimination phase. Some children appear to be ‘fastresponders’, who show a positive reaction after a few days, whereas other children are ‘slow-responders’, who show a positive reaction after a couple of weeks.” Clinically we see huge differences in behaviour in ASD and ADHD children when reactive foods are eliminated from their diet. Designing a rigorus dietary elimination study, is extremley difficult to do. Unfortunately, when such elimination diet  studies are done, those children that respond get lost when the data gets “massaged” statistically.

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!