Late-life depression: structural brain abnormalities, treatment and risk factors

Abstract

Major depression is a prevalent disease among the elderly, significantly decreasing the quality of life. The age of first onset of depression can be early in life, so called early-onset depression (EOD), as well as first occur in old age, i.e. late-onset depression (LOD). Some previous studies have suggested aetiological differences between EOD and LOD in the elderly. However, the number of these studies investigating elderly EOD and LOD patients is small. Therefore the importance of age of onset in the aetiology of late-life depression remains unclear. We used Magnetic Resonance Imaging (MRI) to examine hippocampal volume and subcortical white matter lesions in elderly patients with EOD and LOD and healthy elderly subjects. Both the hippocampus and subcortical white matter lesions have been implicated in the aetiology and treatment outcome of late-life depression. Hippocampal volume decrease and increased prevalence of subcortical white matter lesions in depressed patients might point to underlying disease pathology and have been related to the outcome of antidepressive treatment. In addition, different brain changes in elderly patients with EOD and LOD may suggest different neural underlying mechanisms. First we tested whether late-life depression was associated with structural brain abnormalities. We compared elderly patients with late-life depression and age-matched healthy elderly and found the volume of the hippocampus to be decreased in the patients. Secondly, we examined if this hippocampal volume decrease was general or specific for EOD or LOD by comparing hippocampal volume and white matter lesions in EOD, LOD, and healthy subjects. We found hippocampal volume to be decreased only in EOD patients. White matter lesions were increased only in LOD subjects. Finally, the presence of white matter lesions was not related to the decrease in hippocampal volume. The hippocampus is an important neural structure in the aetiology of late-life depression. Previous research has suggested that multiple, chronic depressive episodes lead to hippocampal damage. Our finding fitted with this observation. Hippocampal volume decrease was observed in late-life depressed patients, particularly in those with a long history of depressive symptomatology. Previous research implies that the neurotoxic effects on the hippocampus by glucocorticoids, known to be overtly released during depressive episodes, explain the hippocampal volume decrease in major depression. Subcortical white matter lesions were more present in LOD patients. These lesions are due to vascular pathology. Therefore, the increased presence of white matter lesions may suggest vascular pathology to play an important role in the aetiology of LOD. We conclude from these findings that different neural mechanisms play a role in late-life depression and that age of onset may be a valuable marker of these mechanisms. We also wanted to know whether the structural brain abnormalities influence the outcome of short-term antidepressive treatment. We therefore compared structural brain abnormalities of responders and non-responders to short-term antidepressant therapy. We did not find any differences in structural brain abnormalities between responders and non-responders. This could suggest that for short-term therapy, treatment protocols should not be modified due to the presence of structural brain abnormalities.