Grant: CIHR New Investigator

Schizophrenia is a relatively common disorder with a lifetime prevalence of approximately 1% and typically arising in late adolescence or early adulthood. The discovery of the first antipsychotics in the 1950s has revolutionized treatment. However, antipsychotic drugs are still not effective in treating a broad range of symptoms and treatment with also remains problematic because of their frequent side effects. One major side effects occurring with some classic and modern antipsychotics (particularly with clozapine and olanzapine) is substantial weight gain, which further adds stigmatization to our patient population. Obesity then often leads to diabetes and high blood pressure; a condition known as the metabolic syndrome. The metabolic syndrome is likely a major factor for the significantly reduced life expectancy of patients. However, it has to be kept in mind that while some patients encounter substantial weight gain, others may not develop this side effect. The underlying molecular, cellular or hormonal mechanisms are not well understood thus far, but the observed inter-individual variability is known to be significantly determined by genetic factors. In our efforts to unravel genetic factors associated with antipsychotic induced weight gain, we will 1) collect a large sample of at least 400 schizophrenia patients treated with antipsychotics bearing high risk for weight gain 2) conduct detailed analyses of genes hypothesized to be involved in the crosstalk between the mechanism of action of antipsychotics and body energy regulation using novel sophisticated genetic analyses and 3) establish collaborations with more groups to conduct joint analyses in larger samples allowing to detect also subtle genetic effects. In conclusion, our studies will lead to determine patients at higher risk for weight gain and thus optimize the choice of prescribing drugs. Furthermore, the identified genes will help to find new targets for the development of novel medications.