<qa>  What is the cause of the decrease in focal brain volumes?Late-life MDD is characterized by 1 Neuroanatomical changes in neocortical and subcortical regions of the brain. These principally comprise a decrease in focal brain volumes and an increase in the volume of high intensity lesions in the parenchyma; 2 The increase in high intensity lesions occurs largely, though not exclusively, in the white matter; 3 Preliminary studies suggest that there are abnormalities in white matter regions and tracts even in areas that appear normal in MR images in patients with late-life MDD when compared with controls; 4 Biochemical and biophysical changes in the white matter are likely related to the pathophysiology of major psychiatric disorders independent of the impact of cerebrovascular diseaserisk factors. 