Depression in late life is closely linked with senescence at a very basic level. Before discussing medical illness and disease processes, however, it will be helpful to review some more basic processes that may trigger, or at the very least exacerbate, depression through biochemical or neuroanatomical mechanisms. A noticeable omission in the following discussion is the role of genetic factors in late-life depression. Although evidence is scant, there does seem to be a familial risk for late-onset depression. However, genetic risk factors appear to play a lesser role here than in early-onset disease and probably act through their association with other disease processes.
Cerebrovascular Factors
As previous discussion of vascular depression implies, changes in brain structure and function related to vascular pathologies are a strong risk factor for incident depression. Interestingly, there is little empirical support for a direct link of late-onset depression with general vascular risk factors such as hypertension. This may, however, be due to the very small number of tightly controlled research studies examining this phenomenon. There is nonetheless strong evidence that subcortical hyperintensities are strongly linked with late-onset MDD and that depressive symptoms are well predicted by the site and size of observed lesions. A number of structures and processes related to frontal lobe function appear to be involved in vascular depression. In addition to white matter hyperintensities, identified structural markers include decreased volume of limbic and basal ganglia structures, including the hippocampus, amygdala, anterior cingulate gyrus, caudate, and the putamen; increased metabolism in areas of the limbic system; and decreased metabolic activity in dorsal neocortical areas and the basal ganglia.
Whereas the lesions responsible for vascular depression tend to be relatively small and diffuse, other, more specific neurological dysfunctions may produce diagnosing depression as well. Perhaps the most obvious and most heavily studied is stroke. Of persons in acute hospitals or in-patient rehabilitation for stroke, almost 20% meet criteria for MDD and an equal number experience minor depressive symptoms. Although functional deficits contribute to depression among stroke patients, there is now good evidence that structural damage to the brain is a causal factor, particularly in the months immediately preceding the stroke itself. Studies seeking to identify specific sites that are most closely associated with poststroke depression have yielded mixed findings, but the bulk of evidence implicates left anterior cortical and basal ganglial lesions. Poststroke depression is especially insidious because, unless aggressively treated, it impairs both the pace and final outcome of rehabilitation.
Endocrine Function It is well documented that depression is associated with abnormalities of hypothalamic–pituitary–adrenal (HPA) axis activity across the life span. This is most easily observed in high rates of hypercortisolemia, reflecting hypersecretion of corticotrophin releasing factor (CRF), among depressed individuals. Although research directly linking HPA axis function with depression in older adults is limited, they may be especially vulnerable to this dynamic because of increased sensitivity of adrenocorticotropin to the effects of CRF. Levels of dehydroepiandrosterone (DHEA) are lower in older than in younger adults; this pattern is associated with depressive symptomatology as well. Normal age changes in sleep patterns and sex hormones are also linked with HPA axis activity and may dispose some older adults to treatment depression in late life. There has as yet been little integration of these kinds of findings into a comprehensive model of stress response in late-life depression. However, this is a promising avenue for future study.
