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
