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Original Article
March 2010

Decreased Hippocampal Volume in Healthy Girls at Risk of Depression

Author Affiliations

Author Affiliations: Department of Psychology, Stanford University, Stanford, California.

Arch Gen Psychiatry. 2010;67(3):270-276. doi:10.1001/archgenpsychiatry.2009.202

Context  Researchers have documented that the hippocampus is smaller in individuals with depression than in those without. The temporal or causal association of this reduction in hippocampal volume in depression, however, is not known.

Objective  To test the hypothesis that reduced hippocampal volume precedes and therefore may be implicated in the onset of depression.

Design  We used magnetic resonance imaging to examine brain structure volume in individuals at high and low familial risk of depression. Anatomic images from magnetic resonance imaging were analyzed using both whole-brain voxel-based morphometry and manual tracing of the bilateral hippocampus.

Setting  A research university.

Participants  Fifty-five girls aged between 9 and 15 years: 23 daughters of mothers with recurrent episodes of depression in the daughter's lifetime (high risk) and 32 age-matched daughters of mothers with no history of psychopathology (low risk). None of the girls had any past or current Axis I psychopathology.

Main Outcome Measures  Group differences in voxel-based morphometry brain matter density estimates and traced hippocampal volume.

Results  Voxel-based morphometry analyses indicated that individuals at high risk of depression had significantly less gray matter density in clusters in the bilateral hippocampus (P < .001) than low-risk participants. Tracing yielded a volumetric reduction in the left hippocampus in the high-risk participants (P < .05).

Conclusions  Compared with individuals at low familial risk of the development of depression, high-risk individuals have reduced hippocampal volume, indicating that neuroanatomic anomalies associated with depression may precede the onset of a depressive episode and influence the development and course of this disorder.