Monthly Research Review December 2016

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


Academic Achievement in Adults with a History of Childhood Attention–Deficit/ Hyperactivity Disorder: A Population-Based Prospective Study.This is the first prospective, population-based study of adult academic outcomes of childhood ADHD. Our data provide evidence that childhood onset ADHD is associated with long-term underachievement in reading and math that may negatively impact ultimate educational attainment and occupational functioning in adulthood.”

Nutritional status and feeding problems of children with attention deficit hyperactivity disorder.Almost half of the ADHD children had suboptimal nutrition compared to 11.1% TD children. It is imperative to screen ADHD children for nutritional status and feeding problems to prevent negative health impacts later on. About 5.6% of the ADHD children were stunted as compared to 3.7% of the TD children, while none of the TD children were severely stunted compared to 3.7% of the ADHD children.”

Impact of attention deficit hyperactivity disorder therapy on fracture risk in children treated in German pediatric practices.Patients receiving attention deficit hyperactivity disorder (ADHD) medications were at a lower risk of fractures than patients without ADHD medications.” However this does NOT give the full picture of long-term ADHD medication usage and bone density in patients. ADHD Medication Use Tied to Reduced Bone Density in Children.

Dyskinesia in Treatment-Naive and Stimulant-Treated Children With ADHD.Before methylphenidate administration, the treated ADHD group showed significantly higher Abnormal Involuntary Movement Scale (AIMS) total score than the control group and the treatment-naive ADHD group. These results call attention that clinicians should take special care for the possible development of dyskinesia during the treatment of their ADHD patients with methylphenidate.” In another study that looked at involuntary movements in ASD children treated with methylphenidate, found that these involuntary movements persisted even after discontinuing the medication.

Chondrocyte proliferation, viability and differentiation is declined following administration of methylphenidate utilized for the treatment of attention–deficit/hyperactivity disorder. This study looks at methylphenidate (MPH) derivative drugs and their effect on cartilage tissue in bones. “It was emphasized that clinicians should not disregard the fact that this drug might suppress chondrocyte cell proliferation and chondrogenic differentiation.”

Comparison of the effects of methylphenidate and the combination of methylphenidate and risperidone in preschool children with attention-deficit hyperactivity disorder. Full text. “Forty-seven children with ADHD aged 3–6 years were enrolled in a 6-week, single-blind clinical trial and administered with methylphenidate (5–30 mg/dl) or the combination of methylphenidate and risperidone (0.25–2 mg/dl). Two parents in combination group decided to discontinue the medication before week 3 due to severely increased appetite (one patient) and sleepiness (one patient). The most common adverse effects in this group were anorexia (21.7%) and sedation (17.4%). Three parents in risperidone group discontinued medication due to decreased appetite (one patient), agitation (one patient), and nervousness and aggression (one patient). The most common adverse effects in this group were insomnia (33.3%) and anorexia (25%).” For such a small study, side effects were high for both groups over 6-weeks. Long-term effects – unknown.

Mood Disorders

Probiotics and Subclinical Psychological Symptoms in Healthy Participants: A Systematic Review and Meta-Analysis.These results show that probiotic consumption may have a positive effect on psychological symptoms of depression, anxiety, and perceived stress in healthy human volunteers.”

Magnesium and depression.It [magnesium] plays a vital modulatory role in brain biochemistry, influencing several neurotransmission pathways associated with the development of depression. Personality changes, including apathy, depression, agitation, confusion, anxiety, and delirium are observed when there is a deficiency of this element. Since the extracellular concentration of magnesium ions may not reflect their intracellular level, none of the current methods of evaluating magnesium status is regarded as satisfactory. The mood-improving potential of magnesium compounds have been confirmed by the results of numerous pre-clinical and clinical studies. It seems that magnesium supplementation is well-tolerated and enhances the efficacy of conventional antidepressant treatments, and as such could be a valuable addition to the standard treatments for depression.”

The effects of magnesium supplementation on subjective anxiety.The efficacy of Mg in the treatment of anxiety in the mildly anxious and those reporting premenstrual syndrome-related anxiety is suggestive of a beneficial effect of Mg intake.”

Relationship between Toxoplasma gondii Seropositivity and Acoustic Startle Response in an Inner-City Population.Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1 million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (Scz), and has been correlated with modestly impaired cognition.”

Neurobehavioural evaluation of resveratrol in murine models of anxiety and schizophrenia.Administration of resveratrol at doses used in this study [200 and 400 mg/kg] produced anxiolysis and anti-psychotic effects in mice.”

The brain-gut axis dysfunctions and hypersensitivity to food antigens in the etiopathogenesis of schizophrenia. Full text. “This paper is a review of the literature on this subject which presents factors both involved in the functioning of brain-gut axis and important for the development of schizophrenia, i.e. 1. intestinal microbiome (intestinal microbiota), 2. permeable intestine (leaky gut syndrome), 3. hypersensitivity to food antigens, including gluten and casein of cow’s milk. Research results seem to be very promising and indicate the possibility of improved clinical outcomes in some patients with schizophrenia by modifying diet, use of probiotics, and the implementation of antibiotic therapy of specific treatment groups.”

Probiotic normalization of Candida albicans in schizophrenia: a randomized, placebo-controlled, longitudinal pilot study.Results from this pilot study hint at an association of C. albicans seropositivity with worse positive psychiatric symptoms, which was confirmed in a larger cohort of 384 males with schizophrenia.”


Autism Spectrum Disorder

Gestational vitamin D deficiency and autism-related traits: the Generation R Study.Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny.”

Bone Accrual in Males with Autism Spectrum Disorder.Boys with ASD had lower spine, hip, and whole body BMD z-scores compared with controls. Although pubertal bone accrual was similar to that in controls, BMD in children with ASD remained low over a 4-year follow-up period, suggesting that low BMD is a consequence of prepubertal factors, such as low physical activity.”

Epilepsy surgery in patients with autism.Aggression and other aberrant behaviors observed in the clinical setting improved in 24 patients. According to caregivers, most patients also experienced some degree of improvement in daily social and cognitive function. Three patients had no functional or behavioral changes associated with seizure reduction, and 2 patients experienced worsening of seizures and behavioral symptoms. The reduction in aberrant behaviors observed in this series suggests that some behaviors previously attributed to autism may be associated with intractable epilepsy, and further highlights the need for systematic evaluation of the relationship between the symptoms of autism and refractory seizures.”

Gut Microbiota and Autism: Key Concepts and Findings.There is an emerging body of evidence linking the intestinal microbiota with autism spectrum disorders (ASD). Studies have demonstrated differences in the composition of gut bacteria between children with ASD and controls. Certain intestinal bacteria have been observed in abundance and may be involved in the pathogenesis of ASD; including members of the Clostridium and Sutterella genus. Evidence from animal models suggest that certain microbial shifts in the gut may produce changes consistent with the clinical picture of autism, with proposed mechanisms including toxin production, aberrations in fermentation processes/products, and immunological and metabolic abnormalities.”

Prescription Drug Use and Polypharmacy Among Medicaid-Enrolled Adults with Autism: A Retrospective Cross-Sectional Analysis.Around 85% of adults with ASD used at least one psychotropic drug class compared with 42% of adults without ASD. Highly common psychotropics were antipsychotics (66%ASD vs 20%noASD), anticonvulsants (59%ASD vs 20%noASD), and anxiolytics/hypnotics/sedatives (21%ASD vs 11%noASD). Other than psychotropics, many adults with ASD used medical prescription drugs such as antimicrobials (47%), dermatologic agents (48%), respiratory agents (38%), gastrointestinal agents (31%), alternative medications (25%), antiparkinsonian agents (22.6%), antihyperlipidemics/statins (7.3%), and immunologics (2.0%). Rates of general (48%ASD vs 32%noASD) and psychotropic polypharmacy (19%ASD vs 6%noASD) were significantly higher in the ASD group.”

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD.” There is a New Zealand study currently underway, investigating the effect of vitamin D and omega-3 supplementation in ASD.

What Happens to Children Who Move off the Autism Spectrum? A Clinical Follow-Up Study.None of the participants met criteria for an autism diagnosis. Ninety-two percent had a lifetime diagnosis and 81% had a present psychiatric disorder based on the K-SADS. ADHD, specific phobia and Obsessive Compulsive Disorder (OCD) were the most common disorders.” Parents need to be aware that even though their children may be doing well (and may possibly lose their ASD diagnosis), they are not in the clear as they enter adulthood. Many psychiatric disorders are evident at an early age. They need to be addressed at this early age so that they are able to function well as they become mature adults.

Defining the hidden evidence in autism research. Forty per cent of rigorously designed clinical trials remain unpublished – a cross-sectional analysis.Publication bias presents a major problem in current clinical research. This study was designed to quantify publication bias in rigorously designed ASD research. The search delivered N = 30 (60%) trials were published, N = 20 (40%) remained unpublished. The majority of trials investigated drugs. The results emphasize the serious issue of publication bias. The large proportion of unpublished results precludes valuable information and has the potential to distort evidence for treatment approaches in ASD.

Omega-3 supplementation in autism spectrum disorders: A still open question? Full text. “Various attempts to suspend the omega-3 supplementation during the 22 months of follow-up failed because of significant symptom worsening (restlessness, agitation, decrease of responsiveness to teaching), which then disappeared after the resumption of the treatment. Considering anecdotal experiences, including that of our patient, and nonrandomized trials,[10],[11] the presence of a subgroup of ASD patients who are really responders to omega-3 cannot be excluded. These responders might not appear when evaluating the omega-3 effects in a sample taken as a whole.[12] Further, considering the high heterogeneity of ASD phenotypes and etiologies, it seems to be very unlikely that a given treatment produces the same results in all affected individuals.[13]

Serological screening for Celiac Disease in 382 pre-schoolers with Autism Spectrum Disorder. Full text. “Among the GI symptoms reported by parents of children with ASD and CD in our sample there were diarrhea and inappetence. The former is one of the most frequently reported GI symptoms in ASD children in several studies [5, 40] while the latter has been recently detected as one of the most common GI symptoms in a large sample of pre-schoolers with ASD [41]. Besides, half of the ASD children with CD were asymptomatic at the time of the serological screening: this prevalence could be ascribed not only to the presence of true asymptomatic forms of CD but also to the severe communication difficulties of non-verbal preschool children with ASD, making them unable to express GI and systemic symptoms suggestive of CD (e.g. recurrent abdominal pain, abdominal distension, chronic fatigue) [4, 42]. Otherwise, pre-schoolers with ASD could show their GI-related distress in alternative ways through a greater severity of problem behaviors such as irritability [43], anxiety and affective problems [44, 45], or externalizing behaviors (oppositional defiant behaviors and tantrums) [46]. These clinical data contributed to highlight the importance of a serological screening for CD in young children with ASD, even in absence of clear GI or systemic symptoms or other risk factors related to CD.”

A Profile on Emergency Department Utilization in Adolescents and Young Adults with Autism Spectrum Disorders.The current study examined the rates of ED utilization between 2005 and 2013 in ASD youth 12- to 21-years-old. Adolescents with ASD accessed ED services four times as often as adolescents without ASD.”

The Relationship between Zinc Levels and Autism: A Systematic Review and Meta-analysis.There was significant statistical difference between plasma Zn concentration and autistic patients besides healthy controls. Based on sensitivity analysis, zinc supplements can be used for the nutritional therapy for autistic patients.”

Ketogenic diet and childhood neurological disorders other than epilepsy: an overview.In the last years, ketogenic diet (KD) has been experimentally utilized in various childhood neurologic disorders such as mitochondriopathies, alternating hemiplegia of childhood (AHC), brain tumors, migraine, and autism spectrum disorder (ASD). KD could improve cognitive and social skills in a subset of children with ASD.

Psychotropic Medication Use among Insured Children with Autism Spectrum Disorder. Nearly half (48.5 %) of children with ASD received psychotropics in the year observed; the most common classes were stimulants, alpha-agonists, or atomoxetine (30.2 %), antipsychotics (20.5 %), and antidepressants (17.8 %). The widespread use of psychotropics we observed, particularly given weak evidence supporting the effectiveness of these medications for most children with ASD, highlights challenges in ASD treatment.”

Effect of gluten free diet [GFD] on gastrointestinal and behavioral indices for children with autism spectrum disorders: a randomized clinical trial.Of the 80 children, 53.9% had gastrointestinal abnormalities. In the GFD group, the prevalence of gastrointestinal symptoms decreased significantly after intake of GFD (40.57% vs. 17.10%) but increased insignificantly in the RD group (42.45% vs. 44.05%). GFD intervention resulted in a significant decrease in behavioral disorders (80.03±14.07 vs. 75.82±15.37) but an insignificant increase in the RD group (79.92±15.49 vs. 80.92±16.24).”

The relationship between screen time, nighttime sleep duration, and behavioural problems in preschool children in China. This study was done in 3-6 year old children. “After adjusting for potential confounders, children with ST [Screen Time] ≥2 h/day had a significantly increased risk of having total difficulties, emotional symptoms, conduct problems, hyperactivity, peer problems, and prosocial problems, as well as behavioural symptoms of autism spectrum disorder.”

Autism Spectrum Disorder and Avoidant/Restrictive Food Intake Disorder. A very interesting case study. I will leave the reader to make up their own mind if parents are going about this in the right way. More importantly, common sense is telling us that nutritionally this child is starving. Compare this case to this documentary The Girl Who Never Ate.

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse.Ketogenic diet feeding improved multiple measures of sociability and reduced repetitive behavior in female mice; effects in males were more limited. Additional experiments in female mice showed that a less strict, more clinically-relevant diet formula was equally effective in improving sociability and reducing repetitive behavior. Taken together these results add to the growing number of studies suggesting that ketogenic and related diets may provide significant relief from the core symptoms of autism spectrum disorder, and suggest that in some cases there may be increased efficacy in females.”


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!