The impact of an omega-3 enriched diet on hyperactivity and biochemistry in an animal model of attentiondeficit/ hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is the most diagnosed behavioral disorder in children. It affects around 5% of children worldwide and 11% of children in the United States, with rates increasing. Pharmaceutical treatments, such as amphetamines and methylphenidates, are not effective for everyone and are known to have unwanted side effects. While the etiology of the disorder is not yet fully understood, there are clear genetic and environmental components. Nutritional insufficiencies have recently become a popular environmental risk factor under investigation. Essential fatty acids (EFA), omega-3 polyunsaturated fatty acids (PUFA) in particular, are needed for proper brain development and function. Our lab has found lower proportions of omega-3 PUFA in the phospholipids and red blood cell membranes of about 40% of the children and adults with ADHD. Other research groups have subsequently confirmed similar findings. It is not yet known why a subgroup of the ADHD population seem to display EFA insufficiency, or if supplementation can reliably prevent or alleviate symptoms of the disorder. However, multiple human and animal studies have reported a reduction in ADHD-symptoms with omega-3 PUFA supplementation. Thus, we hypothesized that an omega-3 PUFA enriched diet would reduce the ADHD symptom of hyperactivity, modulate dopamine and serotonin turnover, and increase omega-3 PUFA proportion in plasma and brain phospholipids in the Spontaneously Hypertensive Rat (SHR) animal model for ADHD. Additionally, we explored the relationship between oxidative stress, EFA status, and ADHD behavior with the prediction that SHR will display greater oxidative stress than the control strain, Wistar Kyota Rat (WKY). In order to develop a protocol that elucidates the behavioral differences between the two rat strains, we conducted a pilot study on various behavioral tests on the WKY and SHR while on standard rat chow. Results from our preliminary data led us to use the open field test as a measure of hyperactivity. In our intervention study, the omega-3 enriched diet (omega-3 diet) had no impact on measures of hyperactivity. However, our intervention successfully increased omega-3 PUFA proportions in plasma and brain phospholipid membranes. WKY had a higher proportion of eicosapentaenoic acid (EPA) in both plasma and brain than SHR, and SHR had a higher proportion of docosahexaenoic acid in plasma for both diets. Results of the liver total glutathione (GSH) analysis suggested that the omega-3 diet reduced oxidative stress, but that the SHR had lower oxidative stress than the WKY. SHR on the omega-3 diet had a lower concentration of dopamine in the neostriatum than SHR on the omega-6 dominant diet, and both rat strains on the omega-3 diet had lower serotonin concentration. Consistent with the lack of impact on behavior, dopamine and serotonin turnover were not modulated by diet. However, dopamine turnover in the SHR was lower than that in the WKY. In summary, our dietary intervention did not impact behavior, which was consistent with the lack of impact on neurotransmission, despite the alteration in phospholipid proportions. Future studies should focus on determining the most effective dose, EPA/DHA ratio, and time period for an omega-3 PUFA intervention