Initial conditions of psychotropic drug response: Studies of serotonin transporter long promoter region (5-HTTLPR), serotonin transporter efficiency, cytokine and kinase gene expression relevant to depression and antidepressant outcome

Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice

“…There is evidence that humans carrying the s allele of the 5-HTTLPR, who presumably have lower 5-HTT expression, are more prone to psychiatric disorders and are often resistant to treatment with SSRIs compared with individuals homozygous for the l allele (6,46). Our data, together with that of others (47), suggest that OCT3 may serve to buffer the increase in 5-HT that follows antidepressant treatment.…”

“…Carriers of this short gene variant (s) are more prone to psychiatric disorders than noncarriers and are often more resistant to conventional treatment with selective 5-HT reuptake inhibitors (SSRIs) than individuals homozygous for the long allele (l) (2)(3)(4)(5). The mechanistic basis for this relationship has come under close scrutiny in recent years (6), but remains to be fully elucidated. Here we tested the hypothesis that upregulation of an alternate 5-HT uptake mechanism might contribute to reduced clinical efficacy of SSRIs in carriers of the s allele.…”

The interaction of serotonin transporter gene polymorphisms and early adverse life events on vulnerability for major depression

“…Space constraints preclude a detailed review of this burgeoning literature, but taken together, the results have been mixed [18][19][20][21][22][23][24], with some studies describing failure to attain remission in a trial of citalopram in patients with the s/s genotype [18], and another study reporting no association between the SERT genotype and clinical response to sertraline [19]. Moreover, in two studies, superior clinical responses to paroxetine and fluvoxamine were observed in patients with the l/l genotype [20,21]. In contrast, a superior response to SSRIs also was reported in patients with the s/s genotype [22,23].…”

Fluoxetine response in impulsive–aggressive behavior and serotonin transporter polymorphism in personality disorder

“…It consists of a 44-base pair deletion (short or s variant) or insertion (long or l variant) endowed with functional consequences. The s form is associated with lower transcriptional activity and reduced 5HT re-uptake efficiency (Rausch, 2005). In 1998, Smeraldi et al (Smeraldi et al, 1998) first showed an association between antidepressant fluvoxamine response and the 5-HTTLPR polymorphism, with a better response to fluvoxamine showed for l-allele carriers compared with s-variant homozygotes.…”