Molecular study of weight gain related to atypical antipsychotics: clinical implications of the CYP2D6 genotype

Atypical antipsychotics, especially some of them, influence cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of atypical antipsychotics in children and adolescents, their metabolic and endocrine adverse effects are of particular concern especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on atypical antipsychotics adverse effects include CYP2D6 polymorphisms. Our study, performed in 2009-2014, with a two-year enrolment period during which we recruited children and adolescents with a diagnosis of schizophrenia or bipolar disorder on treatment with the antipsychotics (Risperidone, Aripiprazole or Olanzapine), included 81 patients, aged between 9 and 20 years, median age being 15.74 years. The gender percentage was 54% girls/46% boys. The CYP2D6 genotyping was performed after enrolment of the last patient. Based on the CYP2D6 genotype, three activity groups were identified and compared and we found that the patients with wt/*4 genotype, intermediary metabolizer (carrier of one functional and one non-functional allele) have significantly higher weight gain values than the patients who did not exhibit allele *4. The CYP2D6 genotype in children and adolescents with schizophrenia and bipolar disorder, proved to be a good predictor for the response to atypical antipsychotics and the side effects registered. The significant correlations between the CYP2D6 polymorphisms and the weight gain/BMI (body mass index) increase, as major side effects induced by antipsychotics proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk individuals.