Immunity, Aging, and Geriatric Depression

Abstract

Despite pioneering findings on immune functions in various depressive syndromes, few recent studies focus on the role of inflammation and its potential in generating novel antidepressant therapies. We suggest that geriatric depression is the behavioral syndrome par excellence in which inflammatory processes are likely to play an etiological role. We base this assertion on the following observations: Geriatric depression occurs in the context of medical and neurological illnesses in which inflammatory processes are part of their pathogenesis. Both aging and depression are associated with pronounced and prolonged immune responses. Brain areas related to mood processing, have increased inflammatory responses during aging. Moreover, the connectivity among mood regulating structures may be modulated by inflammatory responses. Geriatric depression exacerbates the pathology of its comorbid medical and neurological disorders raising the question whether depression-related inflammatory changes mediate the worsening of their outcomes. Finally, geriatric depression often occurs in persons exposed to chronic stress, a state precipitating geriatric depression and triggering pro-inflammatory responses. The clinical lesson derived from the available information is that depressed older adults should be examined for inflammatory disorders or risk factors of inflammation. It is premature to use anti-inflammatory agents in the treatment of geriatric depression. However, treatment of co-morbid conditions increasing CNS inflammatory responses can have general health benefits and should be part of clinical practice. Neuroimaging may identify microstructural abnormalities and dysfunction of neural networks associated with inflammatory processes accompanying geriatric depression. Transgenic animal models may help to identify candidate anti-inflammatory agents that later may be tested in clinical trials of geriatric depression.

The association of late-life depression with all-cause and cardiovascular mortality among community-dwelling older adults: systematic review and meta-analysis

“…In addition, depression may result in higher risk of comorbidities through delayed immune responses and the triggering of pro-inflammatory responses, which in turn may influence mortality from various causes. 25,26 The results of our study may have clinical and public health implications. Given the high prevalence of late-life depression and its association with mortality, interventions aimed at prevention of depression among older adults should also help with reducing mortality.…”

“…In addition, depression may result in higher risk of comorbidities through delayed immune responses and the triggering of pro-inflammatory responses, which in turn may influence mortality from various causes. 25,26…”

A review of the relationship between proinflammatory cytokines and major depressive disorder

“…The peripheral immune system is characterized by the processing of immunogenic pathogens and activation of neutrophils and macrophages resulting in the release of cytokines that signals the microglia-dominated central immune system. The central immune system then responds to the peripheral cytokines through upregulation of proinflammatory proteins, receptors, and hormones within the CNS (Morimoto and Alexopoulos, 2011). Dysregulation of this system is thought to lead to the structural and biochemical changes associated with MDD development.…”

Cognitive Deficits in Geriatric Depression

“…In addition, inflammatory processes may promote both depression and Alzheimer’s disease. Some pro-inflammatory cytokines have been linked to depression, vascular disease, and cognitive compromise (92, 93) and the same cytokines may have direct effects on cognitive status particularly in verbal encoding and memory functions (94). Antidepressants may modify the levels of inflammatory cytokines (95), but it remains unclear whether antidepressants reduce the risk of Alzheimer’s disease.…”