Limited associations between 5-HT receptor gene polymorphisms and treatment response in antidepressant treatment-free patients with depression

Taichi Ochi, Natalya M. Vyalova, Innokentiy S. Losenkov, Diana Z. Paderina, Ivan V. Pozhidaev, Anton J.M. Loonen, German G. Simutkin, Nikolay A. Bokhan, Svetlana A. Ivanova, Bob Wilffert

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Major depressive disorder has become a prominent cause of disability, as lifetime prevalence has increased to ~15% in the Western world. Pharmacological effects of serotonin (5-hydroxytryptamine, 5-HT) are mediated through 5-hydroxytryptamine receptor (5-HTR) binding. Serotonin regulation of amygdala activity is attained through activation of three 5-HT2 family receptor subtypes, 5-HT2A, 5-HT2B, and 5-HT2C. Specifically, HT2A and the HT2C receptors have similar gross cerebral distribution and function, with higher constitutive activity found in HT2C than in HT2A. We investigated the possible association of 5-HTR gene polymorphisms to specific and non-specific antidepressant treatment responses in treatment-free patients in Siberia. 156 patients, aged between 18-70 years and clinically diagnosed with depressive disorders, were treated with antidepressants for 4 weeks. Patients were genotyped for a subset of 29 SNPs from the following 5-HT Receptor genes: HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6. Primary outcome was measured by differences in Hamilton Depression Rating Scale (DHAM‐D 17) scores between baseline/week two, week two/week four and baseline/week four. Univariate linear regression was initially conducted to determine the 5-HTR SNPs to be studied within the multiple linear regression. Multiple linear regression analyses over the three time periods were conducted for DHAM‐D 17 with independent factors including: age, gender, depression diagnosis, antidepressant treatment and selected 5-HTR SNPs. We found improved ΔHAM-D 17 in patients taking tricyclic antidepressants (0-4 weeks: B = 4.85, p = 0.0002; 0-2 weeks: B = 3.58, p = 0.002) compared to patients taking SSRIs. Over the course of study, significant associations between 5-HT receptors SNPs and antidepressant response were not identified.

Original languageEnglish
Article number1462
JournalFrontiers in Pharmacology
Volume10
DOIs
Publication statusPublished - 2019

Keywords

  • 5-HT receptor genes
  • Antidepressant
  • Polymorphism
  • Treatment response
  • Treatment-free depression

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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