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Cerebrovascular disease
Research paper
Serotonin transporter gene polymorphisms may be associated with poststroke neurological recovery after escitalopram use
  1. Eun-Jae Lee1,
  2. Mi-Sun Oh2,
  3. Jong S Kim1,
  4. Dae-Il Chang3,
  5. Jong-Ho Park4,
  6. Jae-Kwan Cha5,
  7. Ji Hoe Heo6,
  8. Sung-Il Sohn7,
  9. Dong-Eog Kim8,
  10. Hahn Young Kim9,
  11. Jei Kim10,
  12. Woo-Keun Seo11,
  13. Jun Lee12,
  14. Sang-Won Park13,
  15. Yun Joong Kim2,
  16. Byung-Chul Lee2
  17. for the EMOTION investigators
  1. 1 Department of Neurology, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea
  2. 2 Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea
  3. 3 Department of Neurology, Kyung Hee University Medical Center, Seoul, Republic of Korea
  4. 4 Department of Neurology, Seonam University, Myongji Hospital, Goyang, Republic of Korea
  5. 5 Department of Neurology, Dong-A University Hospital, Busan, Republic of Korea
  6. 6 Department of Neurology, Yonsei University, Severance Hospital, Seoul, Republic of Korea
  7. 7 Department of Neurology, Keimyung University, Dongsan Medical Center, Daegu, Republic of Korea
  8. 8 Department of Neurology, Dongguk University, Ilsan hospital, Goyang, Republic of Korea
  9. 9 Department of Neurology, Konkuk University School of Medicine, Seul, Republic of Korea
  10. 10 Department of Neurology, Chungnam University Hospital, Daejeon, Republic of Korea
  11. 11 Department of Neurology, Korea University, Guro Hospital, Seoul, Republic of Korea
  12. 12 Department of Neurology, Yeungnam University Hospital, Daegu, Republic of Korea
  13. 13 Department of Neurology, Daegu Fatima Hospital, Daegu, Republic of Korea
  1. Correspondence to Professor Jong S Kim, Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul 138-736, Republic of South Korea; jongskim{at}amc.seoul.kr and Professor Byung-Chul Lee, Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, Republic of South Korea; ssbrain{at}hallym.ac.kr

Abstract

Objective Selective serotonin reuptake inhibitors (SSRIs) putatively improve neurological recovery after stroke. We aimed to investigate whether serotonin transporter (SERT) gene polymorphisms are related to the responsiveness to SSRIs in the poststroke neurological recovery.

Methods This was a post hoc analysis of the EMOTION study (ClinicalTrials.gov NCT01278498), a randomised, placebo-controlled, double-blind trial examining the efficacy of escitalopram on emotional and neurological disturbances after acute stroke. Patients with no/minimal disability initially (modified Rankin Scale (mRS) 0–1) were excluded. Of the participants, 301 underwent genetic studies of the STin2 (a variable number tandem repeat (VNTR) in intron 2) (STin2 12/10 and STin2 12/12 genotypes) and 5-HTTLPR (a variable-length repeat in the promoter region) polymorphisms of SERT. We explored whether neurological function (National Institutes of Health Stroke Scale (NIHSS) score and mRS) at 3 months would differ according to SERT polymorphisms within each treatment arm (escitalopram and placebo).

Results Among the escitalopram users (n=159), neurological function in subjects with STin2 12/10 (n=29) improved significantly more than that in STin2 12/12 carriers (n=130) at 3 months. After adjusting for age, initial NIHSS and depression, STin2 12/10 independently predicted a good clinical outcome (mRS 0–1) (OR 2.99, 95% CI 1.04 to 8.58) at 3 months. However, differences between STin2 polymorphisms were not shown in the placebo group (n=142). 5-HTTLPR polymorphisms were not associated with neurological recovery in any treatment group.

Conclusion STin2 VNTR polymorphisms may be associated with poststroke neurological recovery after SSRI therapy. Further studies are needed to identify the role of serotonin in neurological recovery after stroke.

  • serotonin
  • stroke
  • motor recovery
  • gene
  • depression

https://doi.org/10.1136/jnnp-2017-316882

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    Footnotes

    • E-JL and M-SO contributed equally.

    • Contributors Conception and design of the study, obtaining funds: JSK, B-CL. Acquisition and analysis of data: all authors. Drafting a significant portion of the manuscript or figures: E-JL, M-SO, JSK and B-CL.

    • Funding This study was supported by a grant from the Ministry for Health, Welfare and Family Affairs, Republic of Korea (HI14C1985) and the Ministry of Health and Family Welfare, Republic of Korea (HI16C1078).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval Institutional review boards of all participating local centres.

    • Provenance and peer review Not commissioned; externally peer reviewed.