The Depressed Frail Phenotype: The Clinical Manifestation of Increased Biological Aging

Abstract

Depression in later life is a severe public health problem, associated with higher rates of mortality, suicide, and dementia. Effectiveness of treatment is limited by the failure to deconstruct the heterogeneity of the illness and because diagnostic criteria, pathophysiological models, and treatment algorithms for depression are primarily based on studies of younger adults even though symptoms of the illness and physiology of the patient change with age. Thus, understanding how aging interacts with depressive illness may elucidate endophenotypes of late life depression with different clinical manifestations and underlying mechanisms that can then be targeted with more personalized approaches to treatment. This paper proposes a model for the critical confluence between depression and frailty, a high-risk morbidity and mortality syndrome of later life. This model hypothesizes that characteristics of frailty in adults with late life depression represent the clinical manifestation of greater biological aging and their presence in the context of a depressive illness exposes elders to deleterious trajectories. Potential common biological substrates that may result in the manifestation of the depressed frail phenotype including mitochondrial functioning, dopaminergic neurotransmission, and inflammatory processes and implications for the assessment and treatment of adults with late life depression are discussed. As society continues to live longer, the preservation of the quality of these added years becomes paramount, and the combined impact of depression and frailty on the preservation of this quality warrants the attention of clinical researchers and physicians.

Multicomponent Frailty Assessment Tools for Older People with Psychiatric Disorders: A Systematic Review

“…Given the established high level of comorbidity of frailty with psychiatric disorders and evidenced associations between psychiatric disorders and frailty, inaccurate assessment of frailty in psychiatric populations holds substantial clinical risks. If frailty is not recognized and treated within this high‐risk population, the potential for adverse outcomes including worsening of psychiatric symptoms and delayed psychiatric remission increases . Similarly, if an individual is inaccurately assessed as frail or pre‐frail based on psychiatric symptoms alone, this could inappropriately or unnecessarily inform treatment planning and provisions.…”

“…Furthermore, physical frailty was shown to adversely affect the course of late‐life depression, with increased odds of nonremission associated with increased physical frailty . Brown and colleagues proposed a depressed frail phenotype as a high‐risk profile for late‐life frailty. Given that psychiatric disorders are also pervasive late‐life issues with increased risks for many of the same adverse outcomes as frailty including dementia and morality, frailty in the context of a psychiatric disorder warrants specialist clinical detection and intervention.…”

Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline

“…In addition, several studies have reported that older adults with significant hearing loss report lower physical activity levels, perform worse on the Short Physical Performance Battery, and have slowed gait speeds (42). Frailty characteristics such as slowed gait speed exhibit significant reciprocal relationships with both cognition (43) and mood (44) and thus may represent an intermediate step in the progression of some older adults from hearing loss to cognitive decline and late-life depression.…”

Late life depression: nursing actions that can help

“…Although some slowing is not unexpected in normal aging, psychomotor retardation, such as disturbances in speech, facial expression, fine motor behavior, and gross locomotor activity (especially a decreased walking speed ) are more apparent in people with LLD . Fatigue is often experienced as a physical tiring and lack of energy rather than as a mental fatigue . It is important to note that symptoms of frailty (including loss of interest, weight loss, psychomotor slowing, and physical tiring) overlap with symptoms of LLD and are frequently associated with comorbid medical concerns …”