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Neural correlates of epigenesis.

The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging (functional, perfusion, and structural), genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, we found support for a model by which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. These interactions may constitute a neural mechanism for epigenetic vulnerability toward, or protection against, depression.

Pubmed ID: 17032778


  • Canli T
  • Qiu M
  • Omura K
  • Congdon E
  • Haas BW
  • Amin Z
  • Herrmann MJ
  • Constable RT
  • Lesch KP


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

October 24, 2006

Associated Grants

  • Agency: NCRR NIH HHS, Id: 5-M01-RR-10710

Mesh Terms

  • Adult
  • Brain
  • Cerebrovascular Circulation
  • Depression
  • Epigenesis, Genetic
  • Humans
  • Male
  • Models, Neurological
  • Neurons
  • Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • Stress, Psychological