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Autism Spectrum Disorder and Child Behavior

Introduction:

Autism is a developmental disorder of the brain characterized by poor social and communication skills usually occurring in the first 3 years of life without remission. Attention Deficit Hyperactivity Disorder (ADHD) is a behavioral problem that is often characterized by inattentiveness, over-activity, and impulsivity (8). Autism spectrum disorder is characterized by repetitive behavior, limited interest in activities, poor emotional expression, lack of imaginative play, and different eating behaviors. The Centers of Disease Control has reported an increasing number of cases in recent years possibly related to a change in diagnostic methods. Unfortunately, prevention of autism completely is not possible, although a reduction of risk factors may be pursued by the mother prior to and during pregnancy through education of risk factors. Even if all measures of prevention are pursued through education, genetic and other factors beyond one’s control can predispose a child to develop autism. Research has produced several potential prevention interventions with some evidence for the improvement of autism, but there has not been any specific treatments to date resulting in complete resolution of the condition. Additionally, a direct link to any particular etiology has not yet been identified.

Cause of Autism:

Autism has been linked to genetic factors, environmental exposure, parent age, diseases such as diabetes in the parent, prenatal viral infections in the mother, mercury poisoning, diet, and gastrointestinal tract disease. Vaccines with thimerosal have been implicated as a cause in the past but this substance was determined not to be responsible. Due to parental concern, there are vaccines without thimerosal produced.

Certain conditions may put a child at higher risk of developing autism:

40 studies were included in a meta-analysis by Gardener H et al which looked into possible causes of autism. There were 50 potential prenatal triggers of autism reviewed. The conditions which showed a connection to autism included use of medications in pregnancy, mothers born in a foreign country, advanced age of the parent, being a first born child, and diabetes. The strongest association of autism was seen in mothers with prior fetal loss, hypertension, proteinuria, pre-eclampsia and swelling. (10)

Gluten and/or dairy free diet and autism:

The theory using a diet free in gluten and casein stems from the belief that these 2 substances may cause production of opiate like products such as casomorphin in the gut resulting in a sedating affect upon the brain. This same sedative effect has also been implicated in the cause of sudden infant death syndrome by enhancing sedation. Diets free of gluten and casein have some evidence of benefit in autism.

Additional links to autism:

According to Potts, M et al, the cause of autism has been in public debate for decades. Latest studies by the School of public Health, University of California, Berkeley, USA, show links between stomach and intestinal diseases and autism. In the study, children with autism displayed unusual eating patterns such as lower appetites, being picky eaters, and having digestive problems. Links between diet and autism are thought to be a possible cause, warranting additional investigation. (1)

Dietary modification and autism:

A review by Mulloy A et al reported the effects of gluten-free and/or casein-free (GFCF) diets in the treatment of autism spectrum disorder (ASD). Fourteen studies (n=188) were included in the review. Seven studies, discussed in further detail below, reported positive results, 4 reported negative results, 2 reported mixed results and in one study the effect of the intervention could not be determined. In one study of two 3-year old patients (1 male, 1 female) with autism on a megavitamin (B6 complexes+ magnesium + others not stated) plus a GFCF diet for 24 months reported improvements after 2 weeks of intervention. A second study included 28 males and 22 females aged 3.5–16 years old on a 12-month GFCF diet. At the end of the study significant changes from baseline on ratings of social isolation, eye contact, speech, learning skills, hyperactivity, stereotypical activity, panic attacks, and self-mutilation were reported. A separate study of 10 male children aged 7.5 years old on a 12-month GFCF diet found improvements in total autistic trait score (measured by the Diagnosis of Psychotic Behavior in Children [DIPAB]), and statistically significant changes in the other standardized assessments. A fourth study of a 7 year old girl with autism on a GFCF diet for 24 months resulted in improvements in nonverbal communication, stereotypy, and social interactions and claim the girl’s behavior was ’’normalized’’. A fifth study of 8 boys and 7 girls aged 6-14 years old on a 48-month GFCF diet reported improved averages in language skills after 1 year, language skills, after 4 years, social interaction, play based creativity, motor abilities, statistically significant decrease in urine peptide levels (UPL). A sixth study of 9 males and 1 female aged 5-8 years old on a GFCF diet reported a statistically significant decrease in urinary metal concentrations and behavioral improvements from parents. A final study prescribed 10 males and 5 females aged 2-16 years old specific diets based on their UPL pattern. Diets included: GFCF, gluten-restricted, casein-free, and gluten-free, casein-restricted. Each diet was implemented for 12 months. Results included statistically significant decrease in UPL and improvements in antibodies and behavior. (2)

The efficacy of a gluten-free and dairy-free diet:

In a test for the efficacy of a gluten-free and dairy-free diet in autism, autistic symptoms and urinary peptide levels were monitored at the subjects home over a 12-week study. The study included a sample of 15 autistic children between the ages of 2-16 years. There were no statistically significant findings linking an association despite that several parents noted improvement in the symptoms of their children on this diet. (3)

Gluten, casein, and autism:

It is suggested that abnormal levels of peptides by excessive opioid activity caused by the ingestion of gluten and casein may play a role in autism.  Gluten is found in many common foods made from wheat, barley, rye grains or flour from these grains. Casein is a protein found in dairy products. As part of this study, several randomized clinical trials including diets free of gluten and/or casein were reviewed.  One small trial out of several reviewed reported a reduction of autistic traits, but a benefit in cognitive skills, linguistic ability and motor ability was not seen. (4)

Food allergies and autism:

A study on the effects of food allergies and infantile autism shows that there is a possible relationship.  According to a study in Italy entitled “Food allergy and infantile autism” done at the Department of Paediatrics(sic), University of Rome Las Sapienza found that worsening neurological symptoms has been reported in autistic patients after consuming milk and wheat containing foods.  In a study group of 36 autistic patients and 20 healthy controls, antibodies for milk proteins including casein, lactalbumin and beta-lactoglobulin were seen.  After the elimination of these foods for an 8 week period, there was improvement in the behaviors of the autistic patients despite the fact that the milk antibodies were found to be higher in the controls. (5)

Autism and Breastfeeding:

According to Potts, M et al research has suggested that breast feeding may protect against the development of autism. Breast feeding has been linked to lowering the risks of pneumonia and bronchiolitis, two illnesses correlated with autism. Breast milk offers certain protections against these illnesses, and may also lower the risk of autism. (1)

Food additives and child behavior:

Preservatives and autism:

In a double-blind, placebo-controlled crossover trial, investigators randomly assigned 153 children aged 3 years and 144 children aged 8 to 9 to receive two different fruit drinks containing additives (mix A and mix B) or a placebo drink. Both mixes contained sodium benzoate preservative. Hyperactive behavior was based parent and teacher ratings and a computerized test of attention in the older children. Compared with placebo, mix A had a significant negative effect on the behavior of the younger children, and mix A and B had a significant negative effect on the behavior of the older children. Results did not change when analyses were restricted to children who consumed more than 85% of the drinks. (6)

Artificial colors and autism:

A study of 39 children reported that artificial food coloring had a negative impact on daily Conners’ rating of behavior. The Conners Rating Scales are used as a general screening tool for the detection of problematic behaviors, and Attention Deficit Hyperactivity Disorder symptoms. However, the behavioral changes were not detected by most parents. (7)

A negative link between artificial food dyes and symptoms of attention deficit hyperactivity disorder (ADHD) led to a restriction of food dyes by the British government in 2009. (8)

DHA (Docosahexaenoic acid) in 7-9 year old children:

Richardson AJ et al performed a randomized, double blind placebo controlled trial in which a total of 362, 7-9 year-old children were administered 600 mg of DHA or vegetable oil placebo per day. The initial reading ability of 224 children which scored equal to or under the 20th percentile gained a reading age of 0.8 months more in scores with the DHA supplement. Those that were initially in the 10th percentile or under gained 1.9 months in reading age score. There was no significant improvement in the working memory of children taking DHA. This study also evaluated 14 specific measurements of an ADHD (Attention Deficit Hyperactivity Disorder) symptom scale in the children such as restlessness, change in mood, and resistant behavior. There was a significant placebo effect, but a significant amount of improvement in 8 of the 14 ADHD parameters measured over placebo. The parents of the children noted the benefit, but no significant improvement was seen by the teachers. (15)

Autism and acetaminophen:

A preliminary study by Schultz, ST et al published in 2008 analyzed the results of a survey by parents of 83 autistic children and 80 children who served as controls. The study found that acetaminophen use by children ages 5 or less after the measles, mumps and rubella vaccine appeared to be associated with autism. Ibuprofen use was not found to be associated with autism. More studies will need to be done to evaluate this possibility. (9)

Autism and heavy metals:

Adams JB et al studied 55 children with autism between the ages of 5 and 16. They were tested for levels of toxic metals and compared to 44 controls close in age and gender to the autistic group. The study found higher overall levels of toxic metals in children with autism compared with controls. The levels of the toxic metals were tested in red blood cells, whole blood, and urine. The group with autism had higher levels of lead in both the urine (+74 %, p = 0.02) and rbcs (+41 %, p = 0.002). The autism group also had higher levels of urinary tin (+115 %, p = 0.01), tungsten (+44 %, p = 0.00005) and thallium (+77 %, p = 0.0001). Theories for the increase in these heavy metals were reviewed in the study and included increased exposure, increase in absorption, and decrease in excretion. The study also outlined evidence that antibiotic use reduces mercury excretion and that lower glutathione levels which bind the toxic metals correlate with higher toxic metal levels present in autistic patients. (11)

Melatonin and autistic behavior:

Review of melatonin studies:

A review and meta-analysis of 35 studies by Rossignol DA and Frye RE reported that 9 studies of melatonin levels reported at least one sleep abnormality; 4 studies reported a significant link between melatonin levels and autism spectrum disorder (ASD) symptoms; 5 studies reported gene abnormalities associated with decreased melatonin production; and 6 studies of night-time administration led to improvements in daytime behavior. Of 18 trials looking at the effect of melatonin in ASD specifically only 5 randomized, double-blind, placebo-controlled crossover trials were used in the analysis. Within 5 RCTs reviewed by the author, melatonin was associated with increases in sleep duration (44 min compared with placebo) and decreases in time to fall asleep (39 min compared with placebo), but night-time awakenings were unchanged. (12)

Melatonin and autism spectrum disorder:

Twenty-four children with autism spectrum disorder (ASD), free of psychotropic medications, were included in a 14-week study which looked at dose-response, tolerability, safety, and effect of melatonin supplementation. At either 1 or 3 mg dosages of melatonin improved sleep onset in most children. It was effective in week 1 of treatment, maintained effects over several months and was well tolerated and safe. In addition to showing improvement in sleep, melatonin also improved the behavior of the children leading to a significant reduction in the feelings of stress by the parents. (13)

Autism and L-carnitine:

A double-blind, placebo-controlled crossover trial evaluated the possible effectiveness of the supplement L-carnitine for attention-deficit hyperactivity disorder (ADHD) in boys. L-carnitine was given to the boys at an oral dose of 100 mg per kilogram daily or a maximum of 4 grams oral daily for 8 weeks. The parents completed a Child Behavior Checklist (CBCL) after watching the behavior of their children. Carnitine was found to reduce aggressive behavior and led to improvements in attention compared to placebo. (14)

Summary: Autism Spectrum Disorder and Child Behavior

References:

1.M. Potts, B. Bellows, “Autism and Diet”. J Epidemiol Community Health. 2006 May; 60(5): 375. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2563974/

2.Mulloy A, Lang R, O’Reilly M, Sigafoos J, Lancioni G, Rispoli M. Gluten-free and casein-free diets in the treatment of autism spectrum disorders: a systematic review. Research in Autism Spectrum Disorders 2010; 4(3): 328-339. http://www.edb.utexas.edu/education/assets/files/ltc/gfcf_review.pdf

3.“The gluten-free, casein-free diet in autism:  results of a preliminary double blind clinical trial.” College of Nursing, University of Florida, Gainesville, 32610, USA.  http://www.ncbi.nlm.nih.gov/pubmed/16555138

4.“Gluten- and casein-free diets for autistic spectrum disorder.”  Cochrane Database Syst Rev. 2004:92):CD003498.  http://www.ncbi.nlm.nih.gov/pubmed/15106205

5.“Food allergy and infantile autism” Department of Paediatrics(sic), University of Rome Las Sapienza, Itally.  Panminerva Med. 1995 Sep; 37(3): 137-41.  http://www.ncbi.nlm.nih.gov/pubmed/8869369

6.McCann D et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: A randomised, double-blinded, placebo-controlled trial. Lancet. 2007 Nov 3; 370(9598):1560-7. http://www.ncbi.nlm.nih.gov/pubmed/17825405

7.Pollock I, Warner JO. Effect of artificial food colours on childhood behaviour. Arch Dis Child. 1990 Jan;65(1):74-7. http://www.ncbi.nlm.nih.gov/pubmed/2301986

8.Kanarek RB. Artificial food dyes and attention deficit hyperactivity disorder. Nutr Rev. 2011 Jul;69(7):385-91. http://www.ncbi.nlm.nih.gov/pubmed/21729092

9.Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ji M.Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism. 2008 May;12(3):293-307. http://www.ncbi.nlm.nih.gov/pubmed/18445737

10.Gardener H, Spiegelman D, Buka SL. Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry. 2009 Jul;195(1):7-14. http://www.ncbi.nlm.nih.gov/pubmed/19567888

11.Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W. Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biol Trace Elem Res. 2013 Feb;151(2):171-80. http://www.ncbi.nlm.nih.gov/pubmed/23192845

12.Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol. 2011 Sep;53(9):783-92. http://www.ncbi.nlm.nih.gov/pubmed/21518346

13.Malow B, Adkins KW, McGrew SG,  et al. Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. J Autism Dev Disord. 2012 Aug;42(8):1729-37. http://www.ncbi.nlm.nih.gov/pubmed/22160300

14.Van Oudheusden LJ, Scholte HR. Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids. 2002;76:33-8. http://www.ncbi.nlm.nih.gov/pubmed/12213433

15.Richardson AJ, Burton JR, Sewell RP, Spreckelsen TF, Montgomery P. Docosahexaenoic acid for reading, cognition and behavior in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study). PLoS One. 2012;7(9):e43909. Epub 2012 Sep 6. http://www.ncbi.nlm.nih.gov/pubmed/22970149

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