Panic disorder and serotonergic genes (SLC6A4, HTR1A and HTR2A): Association and interaction with childhood trauma and parenting

Neurosci Lett. 2010 Nov 12;485(1):11-5. doi: 10.1016/j.neulet.2010.08.042. Epub 2010 Sep 15.


Objective: The aim of this study is to evaluate the association between HTR1A, HTR2A and the 5-HTTLPR in panic disorder (PD) patients and controls. In addition, this study also aims to evaluate the interaction between these genes and two environmental factors previously associated with PD: childhood trauma and parental bonding.

Methods: This is a case-control candidate gene association study (107 PD patients and 125 controls). Genes were analyzed using a gene-based test in PLINK followed by single marker association tests and haplotype test only for genes that reached experiment-wide significance in the gene-based test in order to minimize multiple testing. Logistic regression was used to test the relationships between genotype in the additive model, trauma, optimal paternal parenting and optimal maternal parenting and their interactions.

Results: Only HTR1A was associated with PD in gene-based test after correction for multiple tests (p(corrected)=0.027) and one HTR1A haplotype comprising four SNPs was associated with PD (p(corrected)=0.032). In the interaction analysis, no significant gene-environment interaction was found with the genes evaluated.

Conclusion: This study reinforces the association between HTR1A and PD. No major evidence of gene-environment interaction in PD with parenting or trauma was found. Further studies are necessary in order to confirm these findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Child
  • Child Abuse*
  • Child Abuse, Sexual
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Male
  • Panic Disorder / genetics*
  • Panic Disorder / psychology*
  • Parenting*
  • Polymorphism, Genetic
  • Receptor, Serotonin, 5-HT1A / genetics*
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • Receptor, Serotonin, 5-HT2A
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Receptor, Serotonin, 5-HT1A