Novel histamine H1 gene polymorphism and clozapine-induced weight gain

A drawback to the treatment of schizophrenia with atypical antispsychotics is the occurrence of weight gain. There is considerable variability among individuals with respect to the ability of clozapine to induce weight gain. Genetic predisposition to clozapine-induced weight gain has been suggested. In addition to clozapine, several other atypical antipsychotics induce weight gain and a common factor is that they all exhibit histamine H1 receptor antagonism. It is well established that H1 antagonism causes weight gain and that the degree of weight gained due to treatment is strongly correlated with the drug's affinity for the H1 receptor. Therefore, genetic variation in the histamine H1 receptor gene may predict patient susceptibility to clozapine-induced weight gain. We obtained weight gain data for 77 patients with schizophrenia that had completed a clozapine trial. During clozapine treatment, weight was assessed at baseline, 6 week and 6 months. We genotyped these patients for a novel histamine H1 polymorphism obtained from Dr. Kerwin's group. Preliminary analyses have not shown associations between H1 genotype and change in weight following 6 weeks (F[2,71]=0.60, p=0.55) and 6 months (F[2.39]=0.04, p=0.95) of clozapine treatment. Further analyses in larger samples are warranted and these samples are currently being collected.