Norepinephrine and serotonin transporter genes: impact on treatment response in depression.
OBJECTIVE
The norepinephrine transporter (NET) and serotonin transporter (5-HTT) genes constitute promising candidate genes in major depression. Seven polymorphisms in the promoter, intronic and exonic region of the NET gene, as well as serotonin-transporter-linked promoter region (5-HTTLPR) and 5-HTT rs25531 polymorphisms were analyzed with respect to antidepressant treatment response with particular attention to gender effects and subtypes of melancholic or anxious depression.


METHODS
252 unrelated Caucasian patients (f = 142; m = 110) with major depression were genotyped for NET and 5-HTT polymorphisms. Genotype effects on Hamilton Depression Rating Scale score changes over 6 weeks of antidepressant treatment were analyzed using analysis of covariance with repeated measures.


RESULTS
There was no effect of any of the 7 investigated NET, or the two 5-HTT polymorphisms, on the overall treatment response. An additional -/CT insertion/deletion (ins/del) polymorphism (rs58532686), however, was significantly associated with melancholic depression, with a better response in 12 patients carrying the deletion. Stratification for anxious versus nonanxious depression revealed a significantly detrimental effect of the less active 5-HTTLPR S allele (p = 0.007) and 5-HTTLPR/5-HTT rs25531 haplotypes on treatment response in patients with anxious depression.


CONCLUSIONS
The present findings do not support a major impact of the NET and 5-HTT genes on antidepressant treatment response in major depression per se. However, there might be an impact of a -/CT ins/del polymorphism in the enhancer domain of the NET gene on treatment response in melancholic depression, which remains to be functionally investigated in future studies. The observed significant influence of the 5-HTT gene variation on antidepressant treatment in anxious depression points to anxious depression as a potential diagnostic entity of its own, requiring specific diagnostic and therapeutic attention.
Baffa
Anna
A
Department of Psychiatry, University of Münster, Münster, Germany.
Hohoff
Christa
C
Baune
Bernhard T
BT
Müller-Tidow
Carsten
C
Tidow
Nicola
N
Freitag
Christine
C
Zwanzger
Peter
P
Deckert
Jürgen
J
Arolt
Volker
V
Domschke
Katharina
K
D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis / Q000379:methods; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People
D000928:Antidepressive Agents; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins