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OBJECTIVE: An important current hypothesis suggests that the relationship between severe depression and the hippocampus is essentially toxic. The purpose of this study was to assess the generalizability of the impact of depression on hippocampal function. METHOD: Participants were 8,229 outpatients who 1) fulfilled DSM-IV criteria for major depressive disorder based on clinical assessment and 2) were tested for delayed recall, a memory function that is particularly related to hippocampal integrity in humans, during two visits several weeks apart. RESULTS: As expected, at presentation with depression, the subjects' current illness severity was the major determinant of performance, as opposed to the intensity of their previous depressive history (the number and length of past episodes). However, following clinical response at the second visit, the length of previous depressive history became more significant than current symptoms. The following factors had significant, independent impact: age, education level, and profession. CONCLUSIONS: Previous studies of small samples assessed for memory function, more or less specific to the hippocampus, have shown great variability in age, gender, education level, and the length and intensity of depressive episode. Hence, a very large sample was required to disentangle the central effect of previous depressive history. As demonstrated in a general practice sample in this study, the hypothesis that the length of past depression impairs memory performance is supported, suggesting that there is a toxic link between the burden of depression and cognition. This finding has important implications for public health.

Original publication




Journal article


Am J Psychiatry

Publication Date





731 - 739


Adolescent, Adult, Aged, Aged, 80 and over, Antidepressive Agents, Benzodiazepines, Depressive Disorder, Major, Drug Therapy, Combination, Female, Follow-Up Studies, France, Hippocampus, Humans, Male, Memory, Short-Term, Middle Aged, Neuropsychological Tests, Psychometrics, Recurrence, Retention (Psychology)