Frailty and Depression: Comorbidity in the Context of Imperfect Measurement

To the Editor: We read with great interest the recent article by Lakey and colleagues regarding associations between antidepressant use, depressive symptoms, and incident frailty in older women. We believe that the clarification of connections between frailty and depression is an important topic for research and clinical attention. Their finding that antidepressant use is associated with higher incidence of frailty (as defined by Fried and colleagues) independent of depression status may have significant implications for treatment of depression and anxiety in older adults, but the general association between frailty and depression should be interpreted in light of evidence suggesting that the criteria used in their measurement may determine the strong correlation between the two constructs, to a large extent. Although the authors recognize this possibility and use a depression screening instrument that does not include items about fatigue and energy, this may not be sufficient to avoid what they call operational confounding. A recent study found that, even when corrected for chance agreement, Fried frailty criteria, and the Diagnostic Interview Schedule, a fully structured instrument that has been extensively validated against psychiatric interview, for major depression agreed in the study’s categorization of older adults to a much greater extent than would be expected by the operational overlap of fatigue items alone. The concordance as indicated by the chance-corrected kappa coefficients was in the “moderate” range, which is particularly notable because kappa is generally used to indicate the amount of agreement between two raters of the same construct. These findings suggest that currently available measures of frailty and depression are poor at discriminating between the two distinct constructs or that they identify the same underlying condition. The former possibility has important implications for studies such as the one by Lakey and colleagues that examine associations between frailty and depression. If, as the authors suggest, antidepressant users have a more-severe form of depression than nonusers, they may also have a higher subclinical baseline level of frailty by virtue of the measurement instruments used to identify frailty and depression. Antidepressant users would then have a lower threshold for manifesting frailty, which would explain the finding that antidepressant users have a higher risk of developing frailty even when not meeting criteria for depression. If, alternatively, frailty and depression are congruent conditions in later life, the search for differentiation and association between the constructs would be largely unnecessary. Although analytical evidence does not support this scenario of a single underlying condition, it is easy to see why it is difficult to distinguish them. For instance, apart from the aforementioned definitional overlaps, endorsement of more vegetative symptoms (e.g., sleep difficulty, fatigue) rather than cognitive or mood symptoms often marks depression in later life. For this reason, it has been suggested that, in late life, mood disturbances can be conceptualized as “depression without sadness. ” It is necessary for future work to reconcile the conceptual differences between frailty and depression with the apparent lack of operational differentiation. Resolving these questions of operational and conceptual overlap will help improve measurement of both conditions and will help researchers and clinicians better understand the reasons for their comorbidity. Interdisciplinary research that is informed by psychiatry, gerontology, and epidemiology will be particularly important for translating findings regarding frailty into effective clinical care.