Clozapine-induced weight gain:: a study in monozygotic twins and same-sex sib pairs

To assess the relative contribution of genetic factors in antipsychotic-induced weight gain, we explored the similarity in body mass index (BMI) (kg/m(2)) change under clozapine only (clozapine Delta BMI) and upon additional inclusion of BMI change under prior antipsychotic medication (total Delta BMI) of five monozygotic twins in comparison with seven same-sex sibs. Twin and sib pairs were identified by a telephone screening of 786 office-based psychiatrists. Measured data on weight and other clinical variables were obtained cross-sectionally and retrospectively from medical records. We found greater similarity in total Delta BMI in monozygotic twins (intrapair difference 2.78 +/- 3.41 kg/m(2)) than in same-sex sibs (5.55 +/- 4.35 kg/m(2)), resulting in heritability estimates of h(2)=0.8 and A=0.45 (ACE twin model). However, intrapair differences in clozapine ABM I were similar between twins (4.18 +/- 4.27 kg/m(2)) and sibs (4.68 +/- 4.88 kg/m(2)) We hypothesize that the weight plateau achieved under clozapine is influenced by genetic factors. The weight gain achieved during pretreatment with other antipsychotics seems to limit clozapine-induced weight gain, thus presumably explaining why heritability/similarity in monozygotic twins in comparison with same-sex sibs is greater for total Delta BMI than for clozapine Delta BML An important caveat is that, owing to the sample size, the heritability estimates have a large standard error and thus have to be interpreted with caution. Psychiatr Genet 15:285-289 (c) 2005 Lippincott Williams & Wilkins.