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.


OBJECTIVE
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.
a Kadri Andre M.D., School of Medicine, University of Tampere , Finland.
Kadri
K
Andre
b Olli Kampman M.D., Ph.D., School of Medicine, University of Tampere , Tampere , and Department of Psychiatry , Seinäjoki Hospital District , Seinäjoki , Finland.
Olli
O
Kampman
c Ari Illi M.D., Ph.D., School of Medicine, University of Tampere , Finland.
Ari
A
Illi
d Merja Viikki, M.D., Ph.D., School of Medicine, University of Tampere , Tampere , and Tampere City Mental Health Care Centre , Tampere , Finland.
Merja
M
Viikki
e Eija Setälä-Soikkeli, M.D., School of Medicine, University of Tampere , Tampere , and Department of Psychiatry , Kanta-Häme Hospital District , Hämeenlinna , Finland.
Eija
E
Setälä-Soikkeli
f Nina Mononen, Ph.D., School of Medicine, University of Tampere; Department of Clinical Chemistry , Pirkanmaa Hospital District; and Fimlab Laboratories , Tampere , Finland.
Nina
N
Mononen
g Terho Lehtimäki M.D., Ph.D., School of Medicine, University of Tampere , Tampere , Department of Clinical Chemistry , Pirkanmaa Hospital District, and Fimlab Laboratories , Tampere , Finland.
Terho
T
Lehtimäki
h Susann Haraldsson, Department of Medical Biosciences , Umeå University , Umeå , Sweden.
Susann
S
Haraldsson
i Pasi A. Koivisto, Department of Neurology , Seinäjoki Hospital District , Seinäjoki , Finland.
Pasi A
PA
Koivisto
j Esa Leinonen M.D., Ph.D., School of Medicine, University of Tampere , Tampere , and Department of Psychiatry , Tampere University Hospital , Tampere , Finland.
Esa
E
Leinonen
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D010555:Personality Inventory; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013694:Temperament / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D055815:Young Adult
D000928:Antidepressive Agents; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human
Antidepressant treatment; Depression; NET; SERT; Temperament