Stress and hippocampal plasticity: implications for the pathophysiology ofaffective disorders

The hippocampal formation, a structure involved in declarative, spatial and contextual memory, is a particularly sensitive and vulnerable brain region to stress and stress hormones. The hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesi s of dentate gyrus granule neurons, and repeated stress causes atrophy of d endrites in the CA3 region. In addition, ovarian steroids regulate synapse formation during the estrous cycle of female rats. All three forms of struc tural remodeling of the hippocampus are mediated by hormones working in con cert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) rece ptors. EAA and NMDA receptors are also involved in neuronal death that is c aused in pyramidal neurons by seizures and by ischemia and prolonged psycho social stress. In the human hippocampus, magnetic resonance imaging studies have shown that there is a selective atrophy in recurrent depressive illne ss, accompanied by deficits in memory performance. Hippocampal atrophy may be a feature of affective disorders that is not treated by all medications. From a therapeutic standpoint, it is essential to distinguish between perm anent damage and reversible atrophy in order to develop treatment strategie s to either prevent or reverse deficits. In addition, remodeling of brain c ells may occur in other brain regions. Possible treatments are discussed. C opyright (C) 2001 John Wiley & Sons, Ltd.