Neuroanatomical changes associated with unipolar major depression

There is increasing evidence for structural brain changes associated with unipolar recurrent major depression. Many depressed patients have comorbid physical illnesses, producing a high rate of subcortical white matter changes and brain damage to key structures involved in the modulation of emotion. This is especially true in the case of late-onset depression, which typically occurs in the setting of age-related illnesses, such as Parkinson's disease, Alzheimer's disease, poststroke syndromes, and myocardial infarction. In addition, there is now evidence for brain changes associated with early-onset major depression. Volume decreases have been reported in the hippocampus, amygdala, caudate, putamen, and frontal cortex. These structures are extensively interconnected and are part of a neuroanatomical circuit that has been termed the limbic-cortical-striatal-pallidal-thalamic tract. Possible mechanisms for tissue loss include neuronal loss through exposure to repeated episodes of hypercortisolemia or glial cell loss, resulting in increased vulnerability to glutamate neurotoxicity. Studies combining the anatomical and morphological information of MRI studies with functional studies have the potential to localize abnormalities in blood flow, metabolism, and neurotransmitter receptors and provide a better integrated model of depression.