Depression, antidepressants, and the shrinking hippocampusBoth the tragic components and the intellectual challenge of depression have deepened in the last decade with a series of high-visibility reports that indicate prolonged, major depression is associated with atrophy within the central nervous system. A report in this issue of PNAS by Czéh et al. (1) adds support to a possible route for reversing these morphological changes. Such atrophy is centered in a brain region called the hippocampus. This structure plays a critical role in learning and memory, and the magnitude of the hippocampal volume loss (nearly 20% in some reports; refs. 2–4) helps explain some well-documented cognitive deficits that accompany major depression. These were careful and well-controlled studies, in that the atrophy was demonstrable after controlling for total cerebral volume and could be dissociated from variables such as history of antidepressant treatment, electroconvulsive therapy, or alcohol use. Moreover, more prolonged depressions were associated with more severe atrophy. These findings of hippocampal atrophy raise immediate questions. First, is it permanent? Tentatively, this appears to be the case, as the atrophy persisted for up to decades after the depressions were in remission. In addition, the extent of atrophy did not lessen with increasing duration of remission (2–4).