Association of Serotonin Transporter Gene (5-HTTLPR/rs25531) Polymorphism with Comorbidities of Panic Disorder

Neuropsychobiology. 2021;80(4):333-341. doi: 10.1159/000512699. Epub 2020 Dec 17.

Abstract

Introduction: Panic disorder (PD) has many comorbidities such as depression, bipolar disorder (BPD), and agoraphobia (AG). PD is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Recently, a tri-allelic serotonin transporter (5-HTTLPR/rs25531) polymorphism was reported to be more sensitive to personality traits compared to the bi-allelic 5-HTTLPR polymorphism. We hypothesized that the 5-HTTLPR/rs25531 polymorphism may lead to a pathological anxious state depending on the presence or absence of a comorbidity in PD.

Methods: In this study, we investigated the relationship between comorbidities in PD and tri-allelic 5-HTTLPR polymorphisms. A total of 515 patients with PD (148 males, 367 females) were genotyped, and the Revised NEO Personality Inventory as well as anxiety-related psychological tests were administered. Depression, BPD, and AG were diagnosed as comorbidities.

Results: For the tri-allele 5-HTTLPR genotype, a significant interaction effect was found between openness to experience and comorbid depression. Examination of the interaction between AG and the tri-allelic 5-HTTLPR genotype revealed that L' allele carriers are associated with higher trait anxiety than the S'S' genotype group in PD without AG.

Conclusion: Some anxiety and personality traits can be characterized by the tri-allelic gene effect of 5-HTTLPR. These results suggest that tri-allelic 5-HTTLPR genotypes have genetic effects on the presence of comorbidities of PD.

Keywords: 5-HTTLPR; Agoraphobia; Comorbidity; Depression; Panic disorder.

MeSH terms

  • Comorbidity
  • Female
  • Genotype
  • Humans
  • Male
  • Panic Disorder* / epidemiology
  • Panic Disorder* / genetics
  • Polymorphism, Genetic
  • Serotonin Plasma Membrane Transport Proteins* / genetics

Substances

  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins