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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Major depressive disorder has become a prominent cause of disability, as lifetime prevalence has increased to similar 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 (Delta HAM-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 Delta HAM-D 17 with independent factors including: age, gender, depression diagnosis, antidepressant treatment and selected 5-HTR SNPs. We found improved increment HAM-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
Number of pages8
JournalFrontiers in Pharmacology
Volume10
DOIs
Publication statusPublished - 19-Dec-2019

Keywords

  • 5-HT receptor genes
  • treatment response
  • polymorphism
  • antidepressant
  • treatment-free depression
  • PSYCHIATRY WFSBP GUIDELINES
  • BIOLOGICAL TREATMENT
  • WORLD FEDERATION
  • DISORDERS
  • SOCIETIES
  • OBESITY
  • WOMEN

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