title: Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs.
abstract: 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 DeltaBMI) and upon additional inclusion of BMI change under prior antipsychotic medication (total DeltaBMI) 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 DeltaBMI 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 DeltaBMI 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 DeltaBMI than for clozapine DeltaBMI. 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.
authors.affiliation: Clinical Research Group, Department of Child and Adolescent Psychiatry, University of Marburg, Hans-Sachs-Str. 6, D - 35039 Marburg, Germany. frank.theisen@med.uni-marburg.de
authors.forename: Frank M
authors.initials: FM
authors.lastname: Theisen
authors.forename: Stefan
authors.initials: S
authors.lastname: Gebhardt
authors.forename: Michael
authors.initials: M
authors.lastname: Haberhausen
authors.forename: Monika
authors.initials: M
authors.lastname: Heinzel-Gutenbrunner
authors.forename: Peter M
authors.initials: PM
authors.lastname: Wehmeier
authors.forename: Jürgen-Christian
authors.initials: JC
authors.lastname: Krieg
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kühnau
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmidtke
authors.forename: Helmut
authors.initials: H
authors.lastname: Remschmidt
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D003024:Clozapine / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D012727:Sex Characteristics; D035781:Siblings; D014430:Twins, Monozygotic; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*
chemical_list: D003024:Clozapine