5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects

Antonio Cerasa, Aldo Quattrone, Fabrizio Piras, Graziella Mangone, Angela Magariello, Sabrina Fagioli, Paolo Girardi, Maria Muglia, Carlo Caltagirone, Gianfranco Spalletta

Research output: Contribution to journalArticle


Genetic variants within the serotonin transporter gene (5-HTTLPR) impact the neurobiology and risk for anxiety-related behaviours. There are also gender differences in the prevalence of anxiety-related behaviours. Although numerous studies have investigated the influence of 5-HTTLPR genotype on the neural systems involved in emotional regulation, none have investigated how these effects are modulated by gender and anxiety. We investigated this issue using two complementary region of interest-based structural neuroimaging approaches (voxel-based morphometry and Freesurfer) in 138 healthy individuals categorized into 'no anxiety' and 'subclinical anxiety' groups based on the Hamilton Rating Scale for Anxiety (HAM-A). Preliminarily, using anxiety as a continuous variable, we found a significant interaction effect of genotype by gender on anxiety. Females homozygous for the Short allele showed the highest HAM-A scores and males the lowest. In addition, a three-way significant interaction among genotype, gender and anxiety category was found for the right amygdala volume. Post hoc tests revealed that homozygous females carrying the Short variant with a subclinical anxiety condition had larger volume. The reported interaction effects demonstrate that gender strongly modulates the relationship between 5-HTTLPR genotype and subclinical expression of anxiety acting on amygdala, one region of the emotional neural network specifically involved in the anxiety-like behaviours.

Original languageEnglish
Article numbernst144
Pages (from-to)1537-1545
Number of pages9
JournalSocial Cognitive and Affective Neuroscience
Issue number10
Publication statusPublished - 2013


  • 5-HTTLPR genotype
  • Amygdala
  • Anterior cingulate cortex
  • Anxiety
  • Cortical thickness
  • Gender

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Experimental and Cognitive Psychology

Fingerprint Dive into the research topics of '5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects'. Together they form a unique fingerprint.

  • Cite this