Effects of adverse experiences for brain structure and function

Studies of the hippocampus as a target of stress and stress hormones have r evealed a considerable degree of structural plasticity in the adult brain. Repeated stress causes shortening and debranching of dendrites in the CA3 l egion of the hippocampus and suppresses neurogenesis of dentate gyrus granu le neurons. Both forms of structural remodeling of the hippocampus appear t o be reversible and are mediated by glucocorticoid hormones working in conc ert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) recep tors, along with transmitters such as serotonin and the GABA-benzodiazepine system. Glucocorticoids, EAA, and NMDA receptors are also involved in neur onal damage and death that is caused in pyramidal neurons by seizures and b y ischemia. A similar mechanism may be involved in hippocampal damage cause d by severe and prolonged psychosocial stress. Studies using magnetic reson ance imaging have shown that there is a selective atrophy of the human hipp ocampus in a number of psychiatric disorders, as well as during aging in so me individuals, accompanied by deficits in declarative, spatial, and contex tual memory performance. It is therefore important to appreciate how hippoc ampal dysfunction may play a role in the symptoms of the psychiatric illnes s and, from a therapeutic standpoint, to distinguish between a permanent lo ss of cells and a reversible remodeling to develop treatment strategies to prevent or reverse deficits. Remodeling of the hippocampus may be only the tip of the iceberg; other brain regions may also be affected Biol Psychiatr y 2000;48: 721-731 (C) 2000 Society of Biological Psychiatry.