Norepinephrine and serotonin transporter genes: impact on treatment response in depression

Baffa, Anna, Hohoff, Christa, Baune, Bernhard, Muller-Tidow, Carsten, Tidow, Nicola, Freitag, Christine, Zwanzger, Peter, Deckert, Jurgen, Arolt, Volker, and Domschke, Katharina (2010) Norepinephrine and serotonin transporter genes: impact on treatment response in depression. Neuropsychobiology, 62 (2). pp. 121-131.

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Background/Aims: 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.

Conclusion: 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.

Item ID: 11660
Item Type: Article (Research - C1)
ISSN: 1423-0224
Keywords: pharmacogenetics; norepinephrine transporter; serotonin transporter; antidepressants; anxious depression
Additional Information:

We gratefully acknowledge the skillful technical support of Ms. Kathrin Schwarte, Ms. Beate Lindner and Ms. Lena Sünke Mortensen. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB-TRR-58, C2 and Z2).

Date Deposited: 13 Aug 2010 04:45
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920410 Mental Health @ 100%
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