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Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response

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Abstract

Rationale

Serotonin transporter (5-HTT) and norepinephrine transporter (NET) are the primary targets of many antidepressants. We aimed to determine the potential correlations of 5-HTT/NET gene polymorphisms with the susceptibility to depression and the antidepressant response to selective serotonin reuptake inhibitors (SSRIs) or dual selective serotonin/norepinephrine reuptake inhibitors (SNRIs).

Methods

A total of 579 depressed patients and 437 healthy controls, all of Chinese Han region, were collected and genotyped by polymerase chain reactions (PCR). All patients were under treatment of SSRI or SNRI for 6 weeks, and were evaluated using a 17-item Hamilton Depression Rating Scale (HAMD).

Results

Five hundred sixty-seven of 579 patients completed the total treatment, of which 362 were in SSRI and 205 in SNRI group. It was shown that the NET-T182C, interacting with 5-HTTLPR, was associated with the susceptibility to depression. Patients with both NET-T182C C/C and 5-HTTLPR S/S genotypes had lower baseline HAMD scores. Patients with 5-HTTLPR L/L or STin2 12/12 genotype experienced better clinical response to the SSRI treatment. Besides, the STin2 12/12 carriers showed a superior reduction to HAMD scores over treatment period. No correlation between NET T182C/G1287A polymorphisms and antidepressant response was observed.

Conclusions

Our study revealed a positive association of the NET-T182C polymorphism with susceptibility to and severity of depression, and a positive association between the 5-HTT polymorphisms and the antidepressant response to SSRI. Combinations of these polymorphisms provided some potential gene–gene interaction effects. These findings might be of some clinical values in optimization of depression treatment.

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Acknowledgement

This study was supported by the grant awarded to Dr. Xueli Sun by the Key Technologies R&D Program (# 2004BA720A21-01).

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Authors and Affiliations

  1. Mental Health Center, West China Hospital, Sichuan University, and Chengdu Fourth People’s Hospital, Chengdu, 610041, People’s Republic of China

    Wenjiao Min

  2. Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Tao Li, Xiaohong Ma, Tao Yu, Dong Gao, Bo Zhang, Yang Yun & Xueli Sun

  3. The Division of Psychological Medicine, the Medical Research Centre Social, Genetic and Developmental Psychiatry (MRC SGDP) Centre, Institute of Psychiatry, London, UK

    Tao Li

  4. Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Zhengyu Li

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  1. Wenjiao Min
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  2. Tao Li
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  3. Xiaohong Ma
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Correspondence to Xueli Sun.

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Supplemental Table 1

Primer sequences of PCR (DOC 28 kb)

Supplemental Table 2

Genotype and allele distributions of monoamine transporter gene polymorphisms in responders and non-responders/remissioners and non-remissioners to SNRI. *χ 2 test. a, b Analysis was performed between 12/12 and 12/10 plus 10/10 (GIF 132 kb)

High resolution image (TIFF 219 kb)

Supplemental Figure 1

HAMD scores during the course of SNRI treatment in three a 5-HTTLPR, b STin2, c NET-T182C, and d NET-G1287A groups. All data analyses were performed using repeated-measures ANOVA. No significant difference was found among the three groups in a (F = 1.190, df = 2, p = 0.306); b (F = 0.799, df = 1, p = 0.372); c (F = 0.899, df = 2, p = 0.409); d (F = 0.125, df = 2, p = 0.833) (GIF 51 kb)

High resolution image (TIFF 597 kb)

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Min, W., Li, T., Ma, X. et al. Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response. Psychopharmacology 205, 409–417 (2009). https://doi.org/10.1007/s00213-009-1550-3

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