Impact of the HTR3A gene with early life trauma on emotional brain networks and depressed mood

Justine M. Gatt, Leanne M. Williams, Peter R. Schofield, Carol Dobson-Stone, Robert H. Paul, Stuart M. Grieve, Richard Clark, Evian Gordon, Charles B. Nemeroff

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Background: The risk for mental illnesses such as depression is increasingly conceptualized as the product of gene-environment interactions and their impact on brain structure and function. The role of serotonin 3A receptor gene (HTR3A -42C>T polymorphism) and its interaction with early life stress (ELS) was investigated in view of the receptor's localization to brain regions central to emotion processing. Methods: Fronto-limbic grey matter (GM) loss was measured using magnetic resonance imaging and assessed using voxelbased morphometry analysis in 397 nonclinical individuals from the Brain Resource International Database. Negative mood symptoms were also assessed. Results: The HTR3A CC genotype group, compared to the T carriers, demonstrated comparative loss to GM in hippocampal structures, which extended to the frontal cortices for those CC genotype individuals also exposed to ELS. Elevations in depressed mood were also evident. Conclusions: These findings suggest that the HTR3A CC genotype may be associated with alterations in brain structures central to emotion processing, particularly when exposed to stress, and further highlight the potential role of the serotonin system in the pathophysiology of affective disorders. In contrast, those individuals with the T allele, in particular the TT genotype, may be more protected from such alterations combined with minimal exposure to ELS events. Depression and Anxiety 27:752-759, 2010.

Original languageEnglish (US)
Pages (from-to)752-759
Number of pages8
JournalDepression and anxiety
Issue number8
StatePublished - Aug 2010


  • Brain Research and Integrative Neuroscience Network (BRAINnet)
  • Brain Resource International Database
  • Depression
  • Emotional brain imaging
  • HTR3A
  • Stress

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology


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