REVIEW: Biological risk factors for late life depression

Depression in late life is a recognised public health problem. After establishing socio-demographic and psychological risk factors for depression, epidemiological research has focused on biological factors. This review summarises the evidence on the associations of cerebrovascular pathology, inflammation, and endocrine and nutritional status with depression in the elderly. The most consistent finding in biological psychiatry is the disturbance of the hypothalamic–pituary–adrenal axis in depressed persons. About half of the patients with severe depression have a disturbed glucocorticoid feedback mechanism and many exhibit hypercortisolism. Longitudinal studies show that this endocrine dysfunction increases the risk of relapse. More recently, silent brain infarcts and cerebral white matter lesions on MRI were found to be more frequent in the depressed elderly than in controls. Cerebral small vessel disease has been rediscovered as a potential cause of depression. Furthermore, there is evidence of immune activation in depressed persons. However, it remains unclear as to whether inflammation contributes to the pathological process as longitudinal studies are lacking. Clinical studies have also related many nutrients to psychological symptoms, but the evidence in elderly persons is consistent only for some vitamin deficiencies. In conclusion, despite a substantial body of literature on biological correlates of late life depression, little is known about causal relations. Prospective population-based studies are warranted.