3D MRI studies of neuroanatomic changes in unipolar major depression: The role of stress and medical comorbidity

Increasing evidence has accumulated for structural brain changes associated with unipolar recurrent major depression. Studies of neuroanatomic structu re in early-onset recurrent depression have only recently found evidence fo r depression-associated structural change. Studies using high-resolution th ree-dimensional magnetic resonance imaging (MRI) are now available to exami ne smaller brain structures with precision. Brain changes associated with e arly-onset major depression have been reported in the hippocampus, amygdala , caudate nucleus, putamen, and frontal cortex, structures that are extensi vely interconnected. They comprise a neuroanatomic circuit that has been te rm ed the limbic-cortical-striatal-pallidal-thalamic tract. Of these struct ures, volume loss in the hippocampus is the only consistently observed chan ge to persist past the resolution of the depression. Possible mechanisms fo r tissue loss include neuronal loss through exposure to repeated episodes o f hypercortisolemia; glial cell loss, resulting in increased vulnerability to glutamate neurotoxicity; stress-induced reduction in neurotrophic factor s; and stress-induced reduction in neurogenesis. Many depressed patients, p articularly those with late-onset depression, have comorbid physical illnes ses producing a high rate of hyperintensities in deep white matter and subc ortical gray matter and brain damage to key structures involved in the modu lation of emotion. Combining MRI studies with functional studies has the po tential to localize abnormalities in blood flow, metabolism, and neurotrans mitter receptors and provide a better integrated model of depression. Biol Psychiatry 2000;48: 791-800 (C) 2000 Society of Biological Psychiatry.