Response to “Does Sleep Play a Role in the Relationship Among Depression, Anxiety, and Mortality in Lung Transplanted Patients?”

Abstract

We read with interest Guti errez et al's recent letter regarding our recent publication, in which we reported that depression after lung transplantation was associated with increased all-cause mortality (1). Guti errez et al (1) suggested that sleep disturbance could be an important confounder in our analysis and that sleep quality could explain the association of depression and increased mortality. There are a number of health behaviors that may affect the relationship of depression and increased mortality, and we agree that sleep disturbance is often an important aspect of depression. We therefore re-examined our data using measures of disrupted sleep obtained from select items from the Beck Depression Inventory-II (BDI-II) (2) and the Health Practices Index (HPI) (3), which were administered 6 months posttransplantation.Our analysis revealed an inconsistent pattern of results. Examination of responses to the single item of sleep disturbance on the BDI-II revealed that only 11 participants (8%) reported that their sleep was very disturbed (e.g. "sleep a lot more" or "a lot less than usual"), and seven participants (5%) reported more severe sleep problems (e.g. "sleep most of the day" or "wake up 1-2 h early and can't get back to sleep"). The prevalence of sleep disturbance was less than expected and was not associated with survival (hazard ratio [HR] = 1.24 [0.94, 1.65], p = 0.125). In contrast, a post hoc exploratory analysis of the HPI revealed that self-reported sleep disturbance (either hypersomnia or insomnia) was associated with greater depressive symptoms (B = À0.29, p = 0.002) and was predictive of all-cause mortality (HR = 1.70 [1.06, 2.72], p = 0.027). This relationship was attenuated after controlling for depression (HR = 1.63 [0.98, 2.72], p = 0.062), while depression tended to remain predictive of subsequent all-cause mortality (HR = 1.28 [0.99, 2.72], p = 0.052). Although we do not have a ready explanation for the discrepant results from the BDI-II and HPI, the latter findings suggest that the observed relationship between depression 6 months posttransplantation and increased risk of mortality is not fully explained by the presence of sleep disturbance.We also note that physical inactivity, which is common among depressed patients, has also been suggested as a potential mechanism that may contribute to worse outcomes among depressed patients (4). In an exploratory analysis, we observed that higher levels of physical activity assessed by a single item from the HPI were associated with lower depression (B = À0.27, p = 0.004) and a reduced likelihood of mortality (HR = 0.60 [0.45, 0.80], p < 0.001), even after controlling for depressive symptoms (HR = 0.64 [0.47, 0.87], p = 0.004). Further research utilizing more precise assessments of sleep quality, physical activity and other health behaviors (e.g. diet, medication adherence) could provide important insights into potential mechanisms responsible for the observed relationship between depression and mortality in post-lung transplant patients.

A Scoping Review of the Literature on Sleep Quality in Adult Lung Transplant Recipients

“…29 Several investigators found an inverse relationship between poor sleep quality or insomnia scores and the mental health domains of health related quality of life such as anxiety and depression. 28,29,33,34,38 This was consistent with Reilly-Spong et al 24 who found moderately strong correlations between self-reports of sleep on the PSQI and symptoms of depression, anxiety, fatigue, and pain across all organ transplant recipients in their sample. Furthermore, patients with persistently poor sleep quality over time experienced lower mean global quality of life in a study by Burkhalter et al 28…”

“…30–33,35,36 Additional subjective measures of sleep quality included questions from the Wisconsin Sleep Cohort study to assess the frequency of sleep complaints as they related to insomnia, 32 single item question from the Kidney Disease Quality of Life Short Form instrument, 28 and a single item of sleep disturbance on the Beck Depression Inventory-II. 34…”

“…28 Conflicting with these reports were findings from the post hoc analysis on the single item of sleep of the Beck Depression Inventory-II revealing that only 8% of recipients reported that their sleep was disturbed and 5% reported more severe sleep problems. 34…”

“…Table 3 summarizes descriptive characteristics and key findings of the included sources. 24,[28][29][30][31][32][33][34][35][36][37][38]…”

Depressive symptoms and early mortality following lung transplantation: A pilot study

“…It is also possible that individuals with greater depression are less physically active following transplantation . Although no studies have examined this issue in lung transplant recipients, we recently demonstrated that objectively measured physical activity mediates the relationship between depression and clinical events (hospitalization and death) among individuals with end‐stage COPD and have also found that self‐reported physical activity among lung transplant recipients remained associated with mortality after accounting for comorbid depressive symptoms . Third, it is possible that depression may be associated with compromised immune function, which may increase vulnerability to adverse events (eg, pneumonia, graft failure) in this population.…”