Serotonin transporter gene and response to lithium augmentation in depression

• Published in: Psychiatric genetics Vol. 18; no. 2; pp. 92 - 97
• Main Authors: Stamm, Thomas J, Adli, Mazda, Kirchheiner, Julia, Smolka, Michael N, Kaiser, Rolf, Tremblay, Pierre Benoit, Bauer, Michael
• Format: Journal Article
• Language: English
• Published: England 01-04-2008
• Subjects: Adult; Alleles; Antidepressive Agents - therapeutic use; Antipsychotic Agents - therapeutic use; Chromosomes, Human, Pair 17 - genetics; Depressive Disorder - complications; Depressive Disorder - drug therapy; Depressive Disorder - genetics; Drug Therapy, Combination; Female; Genotype; Humans; Lithium Carbonate - therapeutic use; Male; Middle Aged; Minisatellite Repeats; Proportional Hazards Models; Prospective Studies; Psychotic Disorders - complications; Serotonin Plasma Membrane Transport Proteins - genetics; Treatment Outcome
• ISSN: 0955-8829; 1473-5873
• DOI: 10.1097/YPG.0b013e3282f08a19

The serotonin (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) is associated with better response to selective serotonin reuptake inhibitors in Caucasian patients carrying the long (l)-allele. In contrast, augmentation of antidepressant drugs with pindolol has been shown to improve responsiveness to antidepressants in short (s)-allele carriers. Lithium augmentation is a well-established strategy for overcoming treatment resistance. In this study, the 5-HTTLPR allele variant's effect on lithium augmentation was analyzed in antidepressant-nonresponsive patients.
We measured remission rates during lithium augmentation in 50 depressed patients genotyped for the 5-HTTLPR. All patients took part in phase II of the German Algorithm Project, a prospective study for the evaluation of a standardized stepwise drug treatment regimen. For statistical analysis, the Cox regression model including several clinical factors besides the 5-HTTLPR was used.
Only the genotype of the 5-HTTLPR (P<0.006) showed a signficant influence on remission. Patients homozygous for the s-allele had a more favorable response compared with those heterozygous (hazard ratio=6.9; P=0.005) or homozygous for the l allele (hazard ratio=4.5; P=0.003).
The findings support a differential effect of the 5-HTTLPR gene on primary treatment with antidepressants and treatment augmentation. Similar to the observations with pindolol, s/s-allele patients showed a higher benefit from lithium augmentation than did patients carrying other 5-HTTLPR genotypes. Thus, the s/s genotype might predict an individual's risk of antidepressant nonresponsiveness and sensitivity to augmentative drugs such as lithium.