Serotonin transporter gene polymorphisms and depressive symptoms in patients with chronic obstructive pulmonary disease

ABSTRACT

Background: We examined the relationship between polymorphisms in the promoter region of the serotonin transport (SERT) gene (5-HTTLPR, short ‘S’ and long ‘L’ alleles) and in intron 2 variable number tandem repeat (STin2VNTR, 9, 10, or 12-repeat alleles) with depression or anxiety in patients with COPD.

Methods: 302 patients with moderate to severe COPD participated in SERT study. History and number of prior depressive episodes were measured using the Structured Clinical Interview for Depression; Hospital Anxiety Depression Scale (HAD) depression ≥8 or a Patient Health Questionnaire-9 (PHQ-9) >,10.

Results: 240 (80%) male sample had a mean age of 68.0 years. Current depression was 22% (HAD) or 21% (PHQ-9), anxiety was 25% (HAD), and suicidal ideation (6%). 5-HTTLPR or STin2 VNTR genotypes were not associated with current depressive or anxiety symptoms. The mean number of prior depressive episodes was higher for patients with the 5-HTTLPR genotype S/S or S/L compared with L/L (4.4 ± 6.1; 5.3 ± 6.8; 4.0 ± 6.1, p < 0.001) and with STin2VNTR high-risk genotype (9/12 or 12/12), medium risk (9/10 or 10/12) compared to low risk (10/10) genotypes (5.1 ± 6.8; 4.9 ± 6.7; 2.7 ± 4.5, p < 0.001).

Conclusions: SERT 5-HTTLPR and STin2-VNTR polymorphisms were not associated with current depressive and anxiety symptoms, but the high-risk STin2-VNTR genotypes and S/L were associated with the number of prior depressive episodes.

KEYWORDS:

• COPD
• depression
• SERT polymorphisms
• anxiety

Article highlights

• The serotonin transporter (SERT) gene 5-HTTLPR S/L allele was associated with the number of prior depressive episodes.

• The high-risk STin2 VNTR genotypes was related with the number of prior depressive episodes.

• The 5-HTTLPR L/L allele polymorphism was associated with chronic obstructive pulmonary disease (COPD) severity.

• SERT 5-HTTLPR and STin2 VNTR polymorphisms were not associated with current depressive and anxiety symptoms.

• Further work is needed to pursue the potential value of SERT genotyping as a predictor of recurrent depression in COPD.

Declaration of interest

A. Yohannes has declared receiving consultation fees from AstraZeneca. All other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer declaration

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

1. M. Yohannes contributed to the data analysis and writing up the paper. R. Kohen contributed to the design, recruitment of subjects and writing up of the paper. H. Q. Nguyen contributed to the design, recruitment of subject data analysis and writing up of the paper. K. C. Pike contributed to the data analysis and writing up of the paper. S. Borson contributed to the data analysis writing up of the paper. V. Fan contributed to the design, recruitment of subjects, data analysis and writing up of the paper. V. Fan is the guarantor of the paper and takes responsibility for the integrity of the work as a whole. All authors have provided writing up of the paper and final approval of the manuscript for submission.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This research was funded by National Institutes of Health [R01HL093146].