SERT and NET polymorphisms, temperament and antidepressant response.

BACKGROUND

The genetic variations in norepinephrine transporter (NET) and serotonin transporter (SERT) genes have been associated with personality traits, several psychiatric disorders and the efficacy of antidepressant treatment.

AIMS: We investigated the separate effects and possible interactions between NET T-182C (rs2242446) and SERT 5-HTTLPR (rs4795541) polymorphisms on selective serotonin reuptake inhibitors (SSRI) treatment response and temperamental traits assessed by the Temperament and Character Inventory (TCI) in a clinical sample of subjects with major depressive disorder (MDD).

METHODS

Our sample of 97 patients with major depression completed the 107-item TCI temperament questionnaire (version IX) at the initial assessment of the study and after 6 weeks of follow-up. All subjects received selective SSRI medications. Temperament dimension scores at baseline ( 1 ) and endpoint ( 2 ) during antidepressant treatment were analyzed between NET and SERT genotypes.

RESULTS

SS-genotype of 5-HTTLPR was associated with higher baseline Persistence scores than SL- or LL-genotype. A corresponding but weaker association was found at endpoint. No differences were found between 5-HTTLPR genotypes and other temperament dimensions and 5-HTTLPR genotypes had no effect on treatment response.

CONCLUSIONS

Our results suggest that the SS-genotype of 5-HTTLPR is associated with Persistence scores in patients with MDD. Higher Persistence could be viewed as a negative trait when recovering from stress and its association with short and "weaker" S-allele may be related to less efficient serotonin neurotransmission, possibly resulting in less effective coping strategies on a behavioral level.