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 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.
Theisen
Frank M
FM
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
Gebhardt
Stefan
S
Haberhausen
Michael
M
Heinzel-Gutenbrunner
Monika
M
Wehmeier
Peter M
PM
Krieg
Jürgen-Christian
JC
Kühnau
Wolfgang
W
Schmidtke
Jörg
J
Remschmidt
Helmut
H
Hebebrand
Johannes
J
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*
D003024:Clozapine