Effect of oxidative stress and essential fatty acids on behavior

Attention deficit/hyperactivity disorder (ADHD) is a common neurobiological disorder of childhood that frequently continues into adolescence and adulthood. The origin of the disorder is multifactorial and not well understood. Although pharmaceutical treatments are available, the side effects are considerable and the drugs do not address the root cause of the disorder. Lower proportions of essential fatty acids, especially the n-3 fatty acids, have been found in plasma phospholipids and red blood cell (RBC) membranes of children and adults with ADHD. There have been several trials of dietary supplementation with essential fatty acids with some success in improving behavior. It is not known why these fatty acids are lower in ADHD, or how to maximize the effects of supplementation as an alternative treatment. In this thesis the possible association of oxidative stress with ADHD behavior and essential fatty acid status is addressed. In a case-control study in college-age students essential fatty acid status and markers of oxidative stress are examined. Although n-3 fatty acids in plasma phospholipids and RBC were lower in the ADHD cases compared to the matched controls, no signs of increased oxidative stress were found. Nutritional status of vitamin B6, C, E, iron, magnesium and zinc were equivalent or higher in the ADHD group. F2 isoprostanes in urine and RBC glucose-6-phosphate dehydrogenase activity were not different. There is no evidence of increased oxidative stress in this population of students with ADHD. The lower proportions of n-3 fatty acids found add to an increasing body of data concerning the association of these fatty acids with ADHD. The hypothesis that oxidative stress is associated with essential fatty acid status was also explored in an animal model of ADHD, the juvenile spontaneously hypertensive rat (SHR). The juvenile SHR had much lower vitamin E in plasma and brain compared to the aged-matched Sprague-Dawley (SD) rats on the same diet, accompanied by lower levels of EFA in plasma and brain. The SHR also had impaired learning, impaired extinction and increased impulsivity compared to the SD rats. In an intervention study, a synthetic diet with 3 levels of alpha tocopherol (AT, 0 50 and 250 IU/kg diet)) was fed to weanling groups of SHR and the same diet with 50 IU/kg to weanling SD rats. Only with the highest AT were equivalent tissue levels of AT in the SHR compared to the SD rats attained. The higher AT increased the proportions of DHA and total n-3 fatty acids in blood and brain of the SHR and was associated with normalization of several behavior measures compared to the SD rats. In this animal model of ADHD, supplementation with AT increased EFA status and improved behavior