Ellen Ivity, B.A. (Psychology), MSc. Candidate, Department of Medicine, University of Alberta

1. The Effects of Arachidonic Acid and Docosahexaenoic Acid Levels on Children with Attention Deficit/Hyperactivity Disorder Ellen Ivity, B.A. (Psychology), MSc. Candidate, Department of Medicine, University of Alberta Dr. Tom Clandinin, Ph.D. Professor of Nutrition, Departments of Agricultural, Food, and Nutritional Science and Medicine

2. Outline • Description of AD/HD • Description of AA and DHA • Review of the Research • Rationale • Hypotheses

3. Inclusion Criteria • Methods • Analyses • Conclusions

4. Attention Deficit/Hyperactivity Disorder • Most common childhood behavioural disorder • Affects all facets of an individual’s life • 3 to 5 percent of children

5. Diagnosis • Usually made in children by the age of seven • Males are three times more likely to be • diagnosed with the disorder than females • Classified into three subtypes: • Primarily Inattentive (ADHD/I) • Primarily Hyperactive-Impulsive (ADHD/HI) • The Combined Type (ADHD/C)

6. Symptomology Inattention: Difficulties sustaining attention Makes careless mistakes Difficulties planning, monitoring, and completing tasks Is disorganized, loses things, forgetful Avoids tasks that require sustained mental effort

7. Symptomology Hyperactivity: Cannot stay seated Squirms and fidgets Cannot play quietly, talks too much Runs, jumps and climbs at inappropriate times Impulsivity: Acts and speaks without thinking Has difficulties taking turns Cannot wait for things Calls out answers before the question is completed Extreme mood swings

8. Aetiology • Multifactorial • Genetics, imbalances of neurotransmitters, • and diet are a few possible causative factors. • Males require three times more essential fatty • acids than females for normal development. • As Attention Deficit/Hyperactivity Disorder is • associated with low levels of essential fatty acids, • this may account for the higher prevalence of males • in this disorder’s population.

9. Treatment • Methylphenidate is the most popular medication used to treat AD/HD. • Two million children take Ritalin around the world. • The number of prescriptions for the drug doubles every two years.

10. Treatment • The production of Ritalin has increased by almost five hundred percent in the last five years. • In 1996 alone, consumers spent over 373 million dollars on Methylphenidate.

11. Prognosis Approximately half of children notice a considerable decrease in hyperactivity as they grow older. 20% - 60% continue to be afflicted with significant problems of inattention, distractibility, and impulsivity throughout the span of their lives.

12. Arachidonic acid & Docosahexaenoic acid • The Omega 3 (n-3) and Omega 6 (n-6) fatty acids have been implicated in the aetiology of Attention Deficit/Hyperactivity Disorder (AD/HD). • Necessary in ensuring the proper development and functioning of virtually every organ system in the human body. • They cannot be produced by the body, hence, they are considered as essential and must be obtained from the diet.

13. Arachidonic acid & Docosahexaenoic acid More than one third of fatty acids in the brain are of the omega 3 and omega 6 classes. Arachidonic acid (AA), an omega 6 fatty acid, and Docosahexaenoic acid (DHA), an omega 3 fatty acid, are the most prevalent. They are the most abundant in the nervous system, reproductive organs, grey matter of the brain, and the retina.

14. Sources of AA • Animal meats • Liver • Kidney

15. Sources of DHA • Herring • Mackerel • Salmon • Tuna • Sardines

16. Modifying sources of dietary fat alters the composition and metabolism of various tissues in the body, as well as the composition of structural lipids in membranes. Therefore, to ensure healthy brain and body functioning, sufficient dietary intakes of AA and DHA are required. Research suggests that low levels of AA and DHA may contribute to the cognitive, behavioural, and physical symptoms observed in children with Attention Deficit/Hyperactivity Disorder.

17. Research Review • 1966 - Caldwell and Churchill suggested a causal • relationship between essential fatty acid (EFA) • deficiency and negative behaviours. • Low brain levels of essential fatty acids may affect • neural functioning. • EFA deficiency leads to functional and structural • deficits. Impairments in the retina and brain are • observed, specifically in the frontal cortex, striatum, • and dopaminergic system.

18. Monkeys • Drs. Carlson and Neuringer, in 1999, observed • Lower n-3 levels in the brain and retina and abnormal • retinal function • EFA deficiency affects the temperament, motivation, and • sensation of monkeys, which in turn affects cognition. • Increased look duration times in a visual attention test • as compared to healthy controls

19. Research Review In infants, longer look duration correlates positively with poorer performance on later cognitive tests. Look duration may be a measure of information processing speed. Look duration time may be a measure of ability to shift attention or disengage from a stimulus, or a measure of higher reactivity to visual stimuli.

20. Mice In 2000, Carrie and colleagues found that • Phospholipids in the frontal cortex are highly enriched • in fatty acids. • Chronic ALA deficiency leads to significant reductions • of EFA in the frontal regions, as well as in the striatum. • Supplementation of ALA increases EFA to control • levels in the striatum but not in the prefrontal cortex, • suggesting that chronic EFA deficiency can lead to • long-term impairments in prefrontal cortex functioning.

21. Mice • The same authors observed • Learning impairments, • Reduced exploratory activity, • Increased anxiety in n-3 deficient mice. • EFA supplementation reverses the above deficits. • Hamazaki and colleagues, in 1999, observed that • Mice reared on omega-3 FA deficient diets for two • generations behaved differently and had different side • effects to behaviour-affecting medicines than controls.

22. Rats • A relationship between levels of brain fatty acids and • functioning of the dopaminergic system exists. • Dr. Zimmer and colleagues, in 1999, found • Decreased dopamine levels and Dopamine 2 (D2) • receptor binding in the prefrontal cortex but not in the • striatum. • Causes visual and behavioural problems.

23. Rats Inadequate storage of dopamine has been implicated in the aetiology of these problems. During learning tasks, the dopamine system is stimulated. Inadequate levels of this neurotransmitter may lead to cognitive impairments, as the brain is unable to sustain a satisfactory level of dopamine release.

24. Children • In 1995, Stevens and colleagues observed • significantly lower levels of AA, EPA, and DHA • in the plasma and blood cell lipids. • a higher number of behavioural problems using • the Conner’s Rating Scale. • higher incidences of behaviour problems, temper • tantrums, and sleep deficits.

25. Children • The same year, Mitchell et al. found • lower levels of AA and DHA, • significantly more language, reading, and learning • difficulties, • 3. more visual and auditory deficits. • The above studies offer evidence that deficiencies in • AA and DHA may be associated with some of the • symptoms observed in ADHD.

26. Myelin Drs. Jumpsen and Clandinin stated, in 1995, that • Memory is dependent on proper neuronal function. • Essential fatty acid deficiency may cause problems with • the myelination of neurons. • The myelin sheath insulates nerve impulses. • Amyelination or dysmyelination due to myelin lipid • deficiency or delays in its production have been shown • to lead to neurological disease.

27. Physical Symptoms Many children with Attention Deficit/ Hyperactivity Disorder have low levels of AA and DHA. A significant number of these children exhibit physical symptoms of essential fatty acid deficiency.

28. Physical Symptoms • Bonnie Kaplan and her colleagues, in 1997, found that • halitosis, • rhinitis, • headaches, and • night awakenings • were more common in children with AD/HD . • Sleep latency was also found to be affected in the • children with AD/HD.

29. Physical Symptoms • In 1995, Stevens et al. found that children with AD/HD • urinated more often, • had greater thirst, and • exhibited more dry skin • The above studies suggest that many children • with AD/HD exhibit physical symptoms of essential • fatty acid deficiency.

30. Rationale Deficiencies in AA and DHA may contribute to the impairments observed in children with AD/HD. Many of these symptoms are alleviated with supplementation of AA and DHA. Therefore, identification of children deficient in AA and DHA is important. Lack of research on these two essential fatty acids and their effects on developmental disorders such as AD/HD. This project plans to increase that knowledge.

31. Hypotheses Some children with AD/HD exhibit symptoms of essential fatty acid deficiency. More specifically, 1. These children have low dietary intakes of DHA and AA, as measured by a four-day diet record. 2. These children have low DHA and AA levels in the phospholipid fractions of their cell membranes, as measured by blood and buccal cell samples.

32. Hypotheses 3. These children exhibit physical symptoms of essential fatty acid deficiency, such as frequent urination and dry skin, as measured by a medical symptom questionnaire.

33. Inclusion Criteria • Participants: One hundred boys and girls from • psychology clinics in Edmonton • Age Range: 6 to 8 years of age • Diagnosis: AD/HD according to the DSM-IV, • with an absence of co-morbid disorders requiring • treatment.

34. Inclusion Criteria • Medication: Can be on or off medication • prescribed to treat AD/HD. • Cannot be taking any other prescription medication. • Cannot be on any special diets or taking any regular • supplements.

35. Methods • Four-day diet record of meat and fish intake. • Medical symptom questionnaire 3. Buccal swab 4. Finger prick

36. Analyses The blood samples and buccal swabs will be analysed to determine each child’s endogenous levels of AA and DHA. The fatty acid levels will be compared to data obtained from previous research on typical children of a similar age range.

37. Analyses The results of the present study will be analysed to see if any relationships exist between endogenous fatty acid levels, medical symptom questionnaire results, and/or dietary intakes.

38. Conclusions • Adequate dietary intakes of Arachidonic acid and Docosahexaenoic acid are required for the healthy development and functioning of cognitive systems. • AD/HD is the most prevalent behavioural disorder in children. The disorder affects all facets of an individual’s life. • The cognitive, behavioural, and physical impairments found in AD/HD are associated with low levels of AA and DHA.

39. Conclusions • Identification of children deficient in these two fatty acids is important. • There is a lack of research on both AA and DHA and their effects on developmental disorders such as AD/HD. The goal of this study is to increase that knowledge.

40. Ultimately, the goal is to develop healthier alternatives to medication for the many individuals who suffer from Attention Deficit/Hyperactivity Disorder.