Influence of 5-HTTLPR and TPH variants on illness time course in mood disorders

The aim of our study was to investigate gene variants in the long-term outcome of mood disorders. We retrospectively studied a sample of inpatients affected by recurrent and rapid cycling mood disorders. The serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) and the A218C tryptophan hydroxylase (TPH) gene variant were determined using a PCR-based technique. For 5-HTTLPR polymorphism we genotyped 435 inpatients affected by major depressive (n = 153), bipolar (n = 213) and rapid cycling (n = 69) mood disorders and 456 controls; for TPH we genotyped 399 inpatients (MD, n = 132; BP, n = 203; rapid cycling n = 64) and 259 controls. Random Regression Model analysis was used to investigate the longitudinal time course of the illness. 5-HTTLPR and TPH polymorphisms were not associated with mood disorders time course. However we observed an excess of 5-HTTLPR*long alleles among rapid cycling subjects compared to both controls (P = 0.018) and remitting mood disorders (P = 0.006). TPH frequencies did not differ between mood disorders subtypes. Our results suggest that 5-HTTLPR variants may confer a susceptibility toward rapid cycling mood disorders. (C) 2001 Elsevier Science Ltd. All rights reserved.