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There is increasing evidence that depression may be associated with structural brain pathology. Magnetic resonance imaging (MRI) has revealed decreased volume in cortical regions, particularly the frontal cortex, but also in subcortical structures, such as the hippocampus, amygdala, caudate, and putamen (see Sheline & Minyun, 2002, for review). These findings are supported by post-mortem studies. Furthermore, some of these neuroanatomical changes may relate to some of the cognitive features of depression; thus, hippocampal volume loss has been associated with changes in functions such as memory performance.

It has been known for some time that elderly depressives have features of cerebral atrophy (sulcal widening and ventricular enlargement) midway between that in depression and dementia. Patients with pseudo-dementia have more abnormalities than those without. More recently, a model of 'vascular depression' occurring later in life has emerged, suggesting that some individuals with depression in old age have underlying cerebrovascular disease affecting areas of the brain important in the control of mood. While perhaps more obvious in the case of post-stroke depression, microvascular disease seems also to be associated with depression. For example, MRI scans and measures of depression were taken in 1077 non-demented, elderly adults (Cees de Groot et al., 2000). Virtually all subjects had white-matter lesions; the 5% of patients without them had lower depression scores than the rest. When adjusted for other relevant variables, those with more severe white-matter lesions were up to five times more likely to have depressive symptoms than those with only mild white-matter lesions. Of those with a depressive disorder, those with an onset after age 60 had more severe white-matter lesions than those with an onset before age 60.

The implications of such vascular contributions to depression include the question of whether it can be prevented by early monitoring and intervention with respect to the cardiovascular risk factors thought to underlie white-matter lesions. Clinically, depression associated with vascular disease appears to be more resistant to treatment.

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