Hippocampal Changes Associated with Early-Life Adversity and Vulnerability to Depression

Uma Rao, Li Ann Chen, Anup S. Bidesi, Mujeeb U. Shad, M. Albert Thomas, Constance L. Hammen

Research output: Contribution to journalArticlepeer-review

286 Scopus citations


Background: Smaller hippocampal volume has been reported in some adult and pediatric studies of unipolar major depressive disorder. It is not clear whether the smaller hippocampal volume precedes or is a consequence of the illness. Early-life adversity is associated with both smaller hippocampal volume and increased vulnerability to depressive disorder. Hippocampal changes may mediate the relationship between early-life adversity and depressive illness in a subset of patients. However, there are no reports of longitudinal clinical studies that have examined this issue. Methods: Thirty adolescents with unipolar major depressive disorder, 22 adolescent volunteers with no personal history of a psychiatric illness including depression but who were at high risk for developing depression by virtue of parental depression (high-risk group), and 35 adolescent volunteers with no personal or family history of a psychiatric disorder (control subjects) underwent volumetric magnetic resonance imaging studies. Information was also gathered on early and recent adverse experiences with standard interviews. The participants were followed for up to 5 years to assess the onset and clinical course of depression. Results: Depressed and high-risk groups had significantly smaller left and right hippocampal volumes than control subjects. Higher levels of early-life adversity were associated with smaller hippocampal volumes. Smaller hippocampal volume partially mediated the effect of early-life adversity on depression during longitudinal follow-up. Conclusions: Smaller hippocampal volume in adolescents at high risk for depression suggests that it may be a vulnerability marker for the illness. Early-life adversity may interact with genetic vulnerability to induce hippocampal changes, potentially increasing the risk for depressive disorder.

Original languageEnglish (US)
Pages (from-to)357-364
Number of pages8
JournalBiological Psychiatry
Issue number4
StatePublished - Feb 15 2010
Externally publishedYes


  • Abuse
  • adolescent
  • depression
  • high-risk
  • hippocampus
  • stress

ASJC Scopus subject areas

  • Biological Psychiatry


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