Neural signatures of the interaction between the 5-HTTLPR genotype and stressful life events in healthy women

Angela Favaro, Renzo Manara, Michela Pievani, Maurizio Clementi, Monica Forzan, Alice Bruson, Elena Tenconi, Daniela Degortes, Claudia Pinato, Valeria Giannunzio, Giovanni Battista Frisoni, Paolo Santonastaso

Research output: Contribution to journalArticlepeer-review


A change in neural connectivity of brain structures implicated in the memory of negative life events has been hypothesized to explain the enhancement of memory encoding during the processing of negative stimuli in depressed patients. Here, we investigated the effects of the interaction between negative life events and the 5-HTTLPR genotype - a polymorphism of the serotonin transporter gene - on the functional and structural connectivity of the hippocampal area in 34 healthy women. All participants were genotyped for the presence of the 5-HTTLPR short variant and for the A/G single-nucleotide polymorphism; they underwent clinical assessment including structured diagnostic interviews to exclude the presence of psychiatric disorders and to assess the presence of stressful life events. Resting state functional magnetic resonance imaging and diffusion tensor imaging scans were performed. We found significant interactions between stressful events and the 5-HTTLPR genotype in both the functional connectivity of the parahippocampus with the posterior cingulate cortex and the structural connectivity between the hippocampus and both the amygdala and the putamen. In addition, we found several genotype-related differences in the relationship between functional/structural connectivity of the hippocampal area and the ability to update expectations or stress-related phenotypes, such as anxiety symptoms. If confirmed by future studies, these mechanisms may clarify the role of the 5HTTLPR genotype as a risk factor for depression, in interaction with negative events.

Original languageEnglish
Pages (from-to)157-163
Number of pages7
JournalPsychiatry Research - Neuroimaging
Issue number2
Publication statusPublished - Aug 30 2014


  • 5-HTTLPR
  • Depression
  • Diffusion tensor imaging
  • Iowa Gambling Task
  • Memory bias
  • Resting state fMRI

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Radiology Nuclear Medicine and imaging
  • Neuroscience (miscellaneous)
  • Medicine(all)


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