Beta-carotene and Oxidative Stress in Pediatric Second Generation Antipsychotic Use

Overview

Weight gain, hypertension, high cholesterol and sugar abnormalities in childhood are strongly linked and predict the risk of further complications and early death in adulthood. The newer antipsychotics, called the second generation antipsychotics are commonly used to treat mood disorders in adult and pediatric populations. Their use has substantially increased (up to 5-fold) in the past 15 years in children due to their approved use by the Food and Drug Administration and higher acceptance in the general medical community. However, second generation antipsychotics are known to have very damaging side effects that cause children to gain substantial amounts of weight, have high cholesterol, high blood pressure and high sugar levels. Despite the known risks their use is still needed and may be contributing to the high rates of obesity-related diseases in childhood and ultimately shorter life-spans in adulthood. How second generation antipsychotics cause these side effects is still not well known. Preliminary evidence has identified a novel pathway that may be associated with second generation antipsychotic side effects. This pathway has not been studied, is involved in vitamin A metabolism and is called the beta-carotene pathway. Beta-carotene is an important part of our diet because it acts as an anti-oxidant (fights harmful oxidative stress in the body) and it produces the active form of vitamin A which is essential for several processes in our body. The investigator's work has identified a backup in this pathway which the investigators hypothesize is due to genetic variation of the enzymes found within this pathway. The investigators hypothesize that genetic variation in the beta-carotene pathway is responsible for the side effects associated with second generation antipsychotics. The investigators want to complete a cross-sectional, pilot study in the pediatric population that will be used for future prospective, extramural applications. The investigators propose two aims for this study: Aim 1: Determine how second generation antipsychotics change beta-carotene metabolism. For this aim, the investigators hypothesize that high beta-carotene:retinoic acid ratios will be due to genetic varition in the beta-carotene pathway. Aim 2: Define the relationship between beta-carotene metabolism, oxidative stress and second generation antipsychotic induced insulin resistance. For this aim the investigators hypothesize that low beta-carotene levels will be associated with high oxidative stress levels and insulin resistance.