Elsevier

Biological Psychiatry

Volume 67, Issue 4, 15 February 2010, Pages 357-364
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2009.10.017Get rights and content

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.

Section snippets

Methods and Materials

These data are part of a larger ongoing study on the development and course of depression in adolescents, as well as the relationship between depression and substance use disorders. The studies were performed at two sites, Harbor-University of California at Los Angeles Medical Center and University of Texas Southwestern Medical Center. Because of space limitations, the methods are described briefly, and additional information is provided in Supplement 1.

Demographic and Clinical Characteristics of the Sample

Magnetic resonance scans were aborted in one control and one depressed participant when they reported anxiety. Data from two control subjects had significant motion artifacts. Therefore, results are presented for 32 control, 22 high-risk, and 29 depressed participants. Demographic and clinical features of the sample are outlined in Table 1. The groups did not differ significantly with respect to age, sex, ethnicity/race, or pubertal status. The depressed and high-risk groups had lower SES and a

Discussion

The findings of this study replicate and extend prior work (19, 20, 21). Smaller hippocampal volume was observed in depressed adolescents (20, 21). The results also indicated that morphologic changes in the hippocampus might be evident before clinical manifestation of the illness in individuals at high risk for the disorder (27). Higher levels of adversity during childhood increased the likelihood of smaller hippocampal volume in at-risk youth even after controlling for chronic stress during

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