Recent in-vitro studies show that antipsychotic drugs increase lipid biosynthesis through changes in gene expression. Based on these finding we compared the expression of two central lipid biosynthesis genes, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD), in whole blood of olanzapine-treated and unmedicated patients. Patients with psychotic disorders were consecutively selected from an ongoing, naturalistic study, and divided into two groups according to the following criteria: (1) strict monotherapy with olanzapine (n=19) or (2) no current medication (n=19). The groups were matched on gender, race and body mass index. Blood lipid levels were examined, and gene expression in whole blood was assessed with quantitative real-time PCR. Expression of FASN (p=0.003) and SCD (p=0.002) was significantly up-regulated in olanzapine-treated compared to unmedicated patients. Transcriptional activation of lipid biosynthesis genes in peripheral blood cells of olanzapine-treated patients suggests a direct lipogenic action of antipsychotic drugs, which may be related to metabolic adverse effects.