Interaction of 5-HTT and HTR1A gene polymorphisms in treatment responses to mirtazapine in patients with major depressive disorder

Hun Soo Chang, Hwa Young Lee, Ji Hyun Cha, Eun Soo Won, Byung-Joo Ham, Bohye Kim, Min-Soo Lee

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We tested for the association of HTR1A and 5-HTT genetic polymorphisms with treatment response to mirtazapine and evaluated the interactive effect between the polymorphisms in 283 patients with major depressive disorder. Korean subjects with diagnosis of major depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. Clinical symptoms were evaluated using the 17-item Hamilton Depression Rating (HAMD-17) Scale at baseline and after 1, 2, 4, 8, and 12 weeks of treatment with mirtazapine. The genetic association of 5-HTTLPR and HTR1A+272G>A with treatment response was analyzed. We found a significant association of the 12.12-repeat genotype of 5-HTT various number tandem repeat (VNTR) with a large percentage decline in HAMD-17 Scale score after 4, 8, and 12 weeks of treatment with mirtazapine. We also found that the frequency of the 12.12-repeat genotype was higher in responders than in nonresponders at week 8. The HTR1A+272GG genotype was significantly associated with a large percentage decline in HAMD-17 Scale score at 4, 8, and 12 weeks, although the genotypic frequencies were comparable between responders and nonresponders during the study period. Patients with the 12.12-repeat 5-HTT VNTR and GG of HTR1A+272G>A showed the highest HAMD-17 Scale percentage reduction during the study period and a better treatment response status after 4 weeks. These results suggest that the interaction between HTR1A+272G>A and 5-HTT VNTR is involved in the response to mirtazapine treatment and that a combination of these may be a useful marker for predicting treatment response to mirtazapine.

Original languageEnglish
Pages (from-to)446-454
Number of pages9
JournalJournal of Clinical Psychopharmacology
Volume34
Issue number4
DOIs
Publication statusPublished - 2014 Jan 1

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Major Depressive Disorder
Tandem Repeat Sequences
Genes
Genotype
Therapeutics
Genetic Polymorphisms
mirtazapine
Diagnostic and Statistical Manual of Mental Disorders
Interviews
Depression

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Interaction of 5-HTT and HTR1A gene polymorphisms in treatment responses to mirtazapine in patients with major depressive disorder. / Chang, Hun Soo; Lee, Hwa Young; Cha, Ji Hyun; Won, Eun Soo; Ham, Byung-Joo; Kim, Bohye; Lee, Min-Soo.

In: Journal of Clinical Psychopharmacology, Vol. 34, No. 4, 01.01.2014, p. 446-454.

Research output: Contribution to journalArticle

Chang, Hun Soo ; Lee, Hwa Young ; Cha, Ji Hyun ; Won, Eun Soo ; Ham, Byung-Joo ; Kim, Bohye ; Lee, Min-Soo. / Interaction of 5-HTT and HTR1A gene polymorphisms in treatment responses to mirtazapine in patients with major depressive disorder. In: Journal of Clinical Psychopharmacology. 2014 ; Vol. 34, No. 4. pp. 446-454.
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AU - Lee, Min-Soo

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AB - We tested for the association of HTR1A and 5-HTT genetic polymorphisms with treatment response to mirtazapine and evaluated the interactive effect between the polymorphisms in 283 patients with major depressive disorder. Korean subjects with diagnosis of major depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. Clinical symptoms were evaluated using the 17-item Hamilton Depression Rating (HAMD-17) Scale at baseline and after 1, 2, 4, 8, and 12 weeks of treatment with mirtazapine. The genetic association of 5-HTTLPR and HTR1A+272G>A with treatment response was analyzed. We found a significant association of the 12.12-repeat genotype of 5-HTT various number tandem repeat (VNTR) with a large percentage decline in HAMD-17 Scale score after 4, 8, and 12 weeks of treatment with mirtazapine. We also found that the frequency of the 12.12-repeat genotype was higher in responders than in nonresponders at week 8. The HTR1A+272GG genotype was significantly associated with a large percentage decline in HAMD-17 Scale score at 4, 8, and 12 weeks, although the genotypic frequencies were comparable between responders and nonresponders during the study period. Patients with the 12.12-repeat 5-HTT VNTR and GG of HTR1A+272G>A showed the highest HAMD-17 Scale percentage reduction during the study period and a better treatment response status after 4 weeks. These results suggest that the interaction between HTR1A+272G>A and 5-HTT VNTR is involved in the response to mirtazapine treatment and that a combination of these may be a useful marker for predicting treatment response to mirtazapine.

KW - major depression

KW - mirtazapine

KW - serotonin receptor 1A

KW - serotonin transporter

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