Hippocampal volume in postmenopausal cynomolgus macaques with behavioral depression

Objective: Magnetic resonance imaging (MRI) studies report hippocampal (HC) volume reductions in depression. Despite observations of functional heterogeneity and ovarian steroid influence in the hippocampus, few studies report regional volume alterations or control for menstrual cycle phase. Using in vitro methods, we recently observed reduced anterior HC volume in antidepressant-naive, ovarian-intact, behaviorally depressed adult female monkeys. The purpose of this study was to confirm these findings in vivo and examine whether lack of ovarian steroids affects the relationship between depression and HC volume. Methods: MRI was used to measure whole, anterior, and posterior HC volumes in a matched sample of antidepressant-naive, surgically postmenopausal adult female cynomolgus macaques characterized for behavioral depression (six depressed, six nondepressed). High-resolution structural MRIs were acquired, and HC regions of interest were manually segmented. HC volumes were normalized to whole brain volumes before analysis. Results: Similar to the previous in vitro study, HC volume measured in vivo was associated with depression. In contrast to the previous study of ovarian-intact female monkeys, whole, anterior, and posterior volumes of both the left and right hippocampi were significantly smaller in depressed compared with nondepressed surgically postmenopausal female monkeys. Conclusions: These findings confirm and extend previous observations of smaller HC volumes in behaviorally depressed female monkeys and suggest a possible role for ovarian steroids in HC protection in depression. Further studies of the potential modulating effects of ovarian function on the relationship between depression and HC volume are warranted.