Serotonin transporter gene polymorphism and response to lithium augmentation in patients with treatment-refractory depression

The promoter region of the serotonin transporter gene (5HTTLPR) displays a polymorphism, which consists in the presence or absence of a 44 base-pair segment producing either a long (l), or short (s) allele. Previous studies have suggested a superior response of l-allele carriers to selective serotonin reuptake inhibitors (1). We examined the association of the 5HTTLPR polymorphism with the response to lithium augmentation, which is thought to enhance serotoninergic activity (2). Posthoc genotyping was performed in 46 patients with treatment-resistant depression who had undergone a 4-week lithium augmentation treatment. One subgroup was treated according to a stepwise treatment algorithm (SSTR) [n=28], the other was treated as usual (TAU) [n=18]. Survival analysis revealed a significantly more rapid response and a higher probability of response in carriers of the ss-genotype, but only in TAU patients (p<0,01). Ss-carriers might more than others profit by early lithium augmentation. The absence of this difference in SSTR patients may be due to factors selecting a higher degree of refractoriness throughout the highly standardized treatment procedure before reaching the lithium augmentation step.

(1) Yu YW, et al. Mol Psychiatry 7 (2002) 1115–9

(2) Wegener G, et al. Psychopharmacology (Berl) 1666 (2003) 188–94