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BACKGROUND: Reduced hippocampal volume has been associated with clinical depression. However, it remains unclear whether these changes are a biological vulnerability marker or a consequence of this disorder. METHODS AND RESULTS (STUDY 1): We first compared hippocampal volumes between (i) never-depressed individuals with elevated risk for depression by virtue of high neuroticism (ii) recovered depressed individuals with matched levels of neuroticism; and (iii) individuals with low neuroticism and no history of depression. We replicated the finding of reduced hippocampal volume in the recovered group; unexpectedly however, the never-depressed high-risk group showed an increase in volume. One hypothesis is that this group had a mean age above the typical onset age for depression; hence, these participants who have remained euthymic despite their personality risk might in fact possess some resilience. METHODS AND RESULTS (STUDY 2): A subsequent study was therefore carried out to compare hippocampal volume between high-neurotic vs. low-neurotic volunteers in a younger sample. No group difference was found. LIMITATIONS: The present findings are limited by a small sample size; the cross-sectional design precluded us from makineg definitive conclusions about causal effect. CONCLUSION: Our overall results suggest that reduced hippocampal volumes is a neural marker for the scar effect of depression, although this structural impairment could also be seen as a vulnerability marker for the development of future recurrent episodes. By contrast, larger hippocampal volumes could be a biological marker of resilience. These findings have clinical implications regarding treatment development for the prevention of illness onset and recurrent depressive episodes.

Original publication




Journal article


J Affect Disord

Publication Date





199 - 202


Depression, Hippocampus, Neuroticism, Resilience, Risk, Vulnerability, Adolescent, Adult, Anxiety Disorders, Atrophy, Case-Control Studies, Cross-Sectional Studies, Depression, Female, Hippocampus, Humans, Hypertrophy, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Neuroticism, Resilience, Psychological, Risk Factors, Young Adult