Depression and the hippocampus: cause or effect?

摘要

Research examining the relationship between major depressive disorder (MDD) and hippocampal volume has long wrestled with the chicken and egg question. From the time the first report was published finding smaller hippocampal volumes in patients with MDD compared with healthy control subjects (1), there have been hundreds of studies in the literature, with the majority, but not all, finding smaller hippocampal volumes in MDD (2). The direction of a potential causal arrow, however, remains unresolved. Studies supporting a role for episodes of MDD leading to smaller hippocampal volumes have found that longer cumulative duration of lifetime depression, total number of recurrent episodes, and earlier age of onset of depression are associated with hippocampal volume loss (2,3). On the other hand, evidence also supports the causality arrow pointing in the opposite direction. Studies supporting the role of hippocampal structural impairment in the etiology of depression have found that a smaller hippocampus predicts worse clinical outcome, and genetic influences on brain structures, including the hippocampus, have been identified in twin studies (4).