The amygdala primarily regulates extrahypothalamic release of CRH, which may explain the findings of elevations of CRH in CSF in depression, although that would not explain hypercortisolemia per se. We found no pattern of relationship between amygdala volume and plasma cortisol level, although there was a modest but nonsignificant relationship between a higher cortisol level and a smaller left hippocampal volume (r=–0.31, df=9, p=0.38). However, our patients had treated depression, and hypercortisolemia has been reported only with current episodes of depression. Future studies should look at cortisol-amygdala relationships in untreated depression. The amygdala and hippocampus also have important interconnections, as suggested by Dr. Tebartz van Elst et al., and we found a modest but nonsignificant relationship between a greater right amygdala volume and a smaller right hippocampal volume in patients (r=–0.35, df=15, p=0.19) but no pattern of relationship in comparison subjects. Future studies are indicated to replicate and extend the finding of greater amygdala volume in depression and the relationship between amygdala volume and number of depressive episodes.