Almandil, NBA; (2013) Factors Influencing Weight Gain in Young People Treated with Antipsychotics. Doctoral thesis , UCL (University College London).

Abstract

Atypical antipsychotic treatment in both children and adults carries significant risk for excessive weight gain that varies widely across individuals. This variation suggests genetic and/or environmental factors are involved in antipsychotic-induced weight gain. This thesis aimed to: 1) provide a systematic review and meta-analysis of the effects of atypical antipsychotics in children and adolescents on weight gain; 2) genotype three specific genes (HTR2C receptors, LEP and LEPR) which are thought to be likely candidates for association between risperidone and weight gain in young people; 3) assess the association between the genotypes of each gene and weight gain. A genetic study was conducted in outpatient mental health clinics/hospitals in the UK and the Kingdom of Saudi Arabia. In this study we investigated the association of 5 single nucleotide polymorphisms (SNPs) with weight gain in a cohort composed of 200 children and adolescents undergoing first treatment with the antipsychotic risperidone over 36 weeks. Of the 200 patients, DNA samples were successfully collected from 197 patients. For all genes we found no significant association with risperidone–induced weight gain after controlling for baseline weight, age, gender, diagnosis and ethnicity. A significant association was found between baseline body mass index (BMI)-standardised z scores (BMIz) and age at the onset of risperidone treatment and weight gain, patients with a lower baseline BMI gained more weight, (p<0.001), and younger patients tended to gain more weight (p<0.001) for all 5 SNPs tested. There was a significant association between weight gain and ethnicity, with individuals of Arab origin being more likely to gain weight than young British for all SNPs. No association between weight gain and gender was found. In this sample no significant association between risperidone-induced weight gain and any of the genotypes tested was found. The novel aspects of this study are the ethnicity of the sample and the age group. Future directions will include genotyping of other relevant variants, such as in MC4R and FTO. The goal of such work includes identifying segments of patient groups for appropriate targeted clinical interventions.

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