We hypothesized that the ANKK1-DRD2 rs1800497, DRD3 rs6280, COMT rs4633, and OPRM1 rs1799971 polymorphisms, together with the 5-HTTLPR genotype, could be involved in the smoking habits and nicotine dependence in patients with treatment-resistant psychiatric disorders. This evidence concerns the gene COMT and nicotine dependence.