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Individuals with asthma may be at increased risk of depression, but few studies have identified precursors to depression onset. The study goal was to identify risk factors for depression onset among a community-based sample of adults with asthma.
Data were from 3 telephone interviews of a longitudinal cohort (n=439) conducted at 2-year intervals. The Center for Epidemiologic Studies Depression scale (CESD) measured depressive symptoms. Multiple regression analyses tested associations of sociodemographic and health-related variables with depression prevalence (cross-sectional analyses) and incident depression (longitudinal analyses).
15% of subjects were classified as “depressed” (CESD≥23) at each interview. Individuals depressed at baseline were more likely to drop out (OR=1.76 [95% CI 1.05, 2.96]). Low perceived control of asthma (measured with the Perceived Control of Asthma Questionnaire [PCAQ]) exhibited the most consistent association with depression. Lower PCAQ was cross-sectionally associated with depression (OR=0.51 per 0.5 SD difference in PCAQ [0.35, 0.75]). Depression onset was noted in 38 individuals. Decrease in perceived control at follow-up was associated with depression onset (OR=7.47 [2.15, 26.01]).
Low perceived control of asthma predicted depression onset among adults with asthma. This risk factor may respond to self-management education.
Rates of depression or depressive symptoms are often found to be higher among persons with chronic health conditions1-3. This finding has generally been substantiated among adults with asthma4-9. For example, odds of major depression and dysthymia among adults with asthma have been reported to be 60%-70% higher than among adults without asthma8,9. Kovacs reported that 20.5% of a sample of adults with asthma were at least moderately depressed, compared to 8.3% of controls4. Although not directly compared to referent populations, Lavoie et al found that 19% of a large sample of adults with physician-diagnosed asthma met criteria for either depressive disorders or depressive disorders plus anxiety disorders6, and a similar proportion (18%) was reported by Eisner in a cohort of 743 adults who had been hospitalized for asthma7. These rates are considerably higher than 12-month prevalence rates of approximately 7% that have been identified in the general population10-12. In contrast, Taitel stated that depression was no more prevalent among adult asthma patients than among “healthy” individuals13.
In many chronic health conditions, symptom severity appears to be an important determinant of depression14-22. This also appears to be the case in adult asthma. Among adults with asthma, depression appears to be more frequent among persons who perceive their asthma as severe and life-threatening than among those who perceive their asthma as less severe23. Consistent with this, more frequent and/or severe asthma symptoms have been associated with depression7,24. In studies not limited to persons with asthma, there also appears to be a relationship between respiratory symptoms and depression25.
Although ascertaining rates of depressive symptoms among adults with asthma is important, it is also critical to identify antecedents of changes in depressive symptoms. Despite the importance of this question, there have been no studies identifying precursors to the onset of depressive symptoms among persons with asthma. Among individuals with other chronic conditions studied longitudinally, increases in symptom frequency or severity (e.g., pain or disability among individuals with rheumatoid arthritis) have been correlated with or predictive of an increase in depression7,26-31. Two studies identified functional losses as clearly preceding the onset of new depressive symptoms among a group of women with rheumatoid arthritis27,28. Few studies have been able to identify true precursors to the onset of depressive symptoms in chronic diseases generally, however, because of the requirements for longitudinal follow-up and a sample large enough to provide adequate numbers of incident cases of depression.
The objectives of these analyses were to identify differences among individuals who were and were not depressed at an initial assessment, and to identify predictors of the onset depression over time.
Data were collected during an ongoing longitudinal cohort study of adults with asthma. The principal data source is a recurrent telephone interview. Details of recruitment and initial follow-up of the cohort have been previously reported32-35. Briefly, we initially recruited adults with asthma from a random sample of board-certified pulmonary specialists, allergy/immunology specialists, and family practitioners in Northern California. Later, we recruited additional subjects using random-digit telephone dialing to identify persons reporting a physician’s diagnosis of asthma. In these analyses, we used data from three interview waves conducted approximately two years apart in 2000-2001 (baseline interview for these analyses, when depressive symptoms were first measured; time 1 [T1; n=439]), 2002-2003 (T2; n=347; 77% of those interviewed at T1), and 2004-2005 (T3; n=314; 92% of those interviewed at T2) (See Figure 1). All procedures were approved by the University’s Committee on Human Research, and all subjects gave informed consent to participate.
Depressive symptoms were assessed with the 20-item Center for Epidemiologic Studies Depression scale (CESD)36, which was developed for use as a screening instrument to identify persons at risk for clinical depression. It has been shown to be reliable and valid in a wide range of samples37. CESD scores range from 05–60. Scores ≥16 are considered indicative of possible depression, and scores ≥23 of probable major depressive disorder37. In these analyses, we use a CESD score ≥23 as the study definition of depression to increase the specificity of the classification. Although CESD scores ≥23 are not equivalent to a clinical diagnosis of depression, for simplicity of discussion, individuals with CESD scores ≥ 23 are referred to as “depressed.”
Potential risk factors for depression were selected a priori. Sociodemographic variables examined were: age, sex, educational attainment (less than college degree versus college degree or higher), marital status (married or living with a partner versus other), and race/ethnicity (white, non-Hispanic versus other).
Health-related covariates included smoking status (current, former, or never), comorbid health conditions (assessed based on self-reports of a physician’s diagnosis of the following: high blood pressure, heart disease, diabetes, stomach or intestinal ulcers, arthritis, or osteoporosis), asthma severity, perceived control of asthma, and physical functioning.
Asthma severity was quantified using a previously validated scoring system developed for the assessment of longer-term severity (as opposed to acute symptoms only) and based on asthma symptom frequency over the past two weeks, prior asthma hospitalization and mechanical ventilatory support for asthma, past and current use of systemic corticosteroids, and use of asthma medications other than systemic steroids32,34,38. Asthma severity scores range from 0-28, with higher scores representing more severe asthma, and have been shown to be correlated with pulmonary function and to predict emergency department utilization, hospitalization, restricted activity days, work disability, mortality34,35,39-41.
Perceived control of asthma, or individuals’ perceptions of their ability to deal with asthma and its exacerbations, was measured with the 11-item Perceived Control of Asthma Questionnaire (PCAQ)42. Sample items include, “If I do all the right things, I can successfully manage my asthma,” and “It seems as though fate and other factors beyond my control affect my asthma.” Items are rated on a 5-point Likert scale, with total scores ranging from 11-55. For this study, scores were rescaled to range from 0 to 100 for simplicity of interpretation. Four individuals had missing data for 1 item of the PCAQ in the T2 administration; their scores were calculated without the missing item without extrapolation.
Physical functioning was defined as valued life activity (VLA) disability using a previously validated scale43-45. VLAs are defined as a broad spectrum of life activities deemed to be important by the individual44. VLA disability has been found to be more closely linked to quality of life than is general physical functioning among adults with asthma, and more closely associated with depression and satisfaction with function in other conditions43,44,46. VLA disability was assessed by querying the degree to which asthma had affected 16 activity domains, such as household work, hobbies, and social activities. Activities not performed for reasons other than asthma or that are not important to individuals are not included when summary scores are created. VLA disability was scored as the proportion of rated items that were affected by asthma; scores range from 0-100. VLA disability was assessed only at T1.
Characteristics of individuals who participated through T3 were compared to those who dropped out of the study using chi-square analyses or t-tests.
To identify cross-sectional correlates of T1 depression, bivariate analyses were first conducted. A multivariate logistic regression analysis was then performed to identify independent correlates of depression at T1. These analyses included the sociodemographic and health-related variables described above.
Chi-square analyses and t-tests were initially used to identify associations between baseline and change variables with the onset of depression. Individuals who were depressed at T1 were excluded from these analyses. Baseline factors considered as predictors of incident depression were sociodemographic and health-related factors from T1. Changes in asthma severity and perceived control from T1 to T2 or T2 to T3 were also considered, depending on time of depression onset. For individuals with depression onset at T2, changes from T1 to T2 were examined, while for individuals with depression onset at T3, changes were from T2 to T3 were considered. Change in severity or perceived control was defined as at least a 0.5 standard deviation (SD) worsening (increase for asthma severity; decrease for perceived control scores) from one time period to the next. This degree of change has been shown to approximate a minimum clinically important difference47,48. Multiple logistic regression analysis was then performed to determine independent predictors of depression onset. Among subjects not lost to follow-up, key variables pertinent to the analysis were missing for two individuals; they were excluded from the analysis. Goodness of fit of the logistic models was assessed with the Hosmer and Lemeshow goodness-of-fit test.
All analyses were conducted using SAS 9.2 (SAS, Cary, NC).
Subject characteristics are shown in Table 1. Mean age of subjects at baseline was approximately 44 years, 70% were female, 44% had at least a college education, and 8% were current smokers.
One hundred twenty-five individuals were lost from the cohort (declined participation or were lost to follow-up) between T1 and T3. Cohort members who dropped out were younger (42.5 vs. 45.0 years, p=.005), had lower education (32.8% vs. 49.0% with college education, p=.002), and more commonly were current smokers (17.6% vs. 4.5%, p<.0001). Individuals who dropped out also had lower perceived control of their asthma at baseline (66.1 vs. 70.0, p=.003). Odds of dropping out were significantly elevated among individuals depressed at baseline (OR 1.76 [1.05, 2.96]). Omission of subjects who were depressed at baseline, however, did not substantively change the results of the comparisons between those who were retained and those who were lost from the cohort for the other variables noted above (i.e., demographics, smoking, and perceived control of asthma).
Approximately 15% of the cohort was depressed (CESD ≥ 23) at each assessment: 17.1% at T1 (n = 75), 14.4% at T2 (n = 49), and 15.0% at T3 (n = 47). Fifteen individuals (3.4%) were depressed at all three interviews.
In bivariate analyses, current smokers and individuals with lower education, greater asthma severity, greater disability, and lower perceived control of asthma were more likely to be depressed (Table 2).
A multivariate logistic regression analysis was performed to identify independent correlates of depression at baseline (Table 2). Four factors were identified: current smoking (OR 2.87 [95% CI 1.14, 7.21]), former smoking (2.23 [1.17, 4.22]), lower perceived control (PCAQ) score (OR per .5 SD difference in PCAQ 0.51 [0.35, 0.75]), and greater proportion of VLAs affected (OR per .5 standard deviation difference 1.58 [1.33, 1.87]). Higher PCAQ scores reflect perceptions of greater asthma control, so greater perceived control was protective; current and former smoking and disability were associated with increased risk. In a secondary analysis excluding PCAQ and VLA disability as potential mediators of disease severity, asthma severity score was significantly associated with depression (OR 1.08 [1.03, 1.13]).
Thirty-eight individuals (10.4% of 364 not depressed at T1) became depressed at one of the follow-up interviews (26 at T2 and 12 at T3. See Figure 1). Among individuals who became depressed, the mean (±SD) increase in CESD score was 17.6 (±8.8) points. All scores increased by at least 3 points.
In bivariate analyses, individuals who became depressed were more likely to have lower education (34.2% with college education vs. 54.9%, p= .02), to have ≥1 comorbid condition at baseline (71.1% vs. 39.9%, p=.0004), to be current smokers at baseline (10.5% vs. 3.4%, p=.04), and had lower baseline PCAQ scores, indicating poorer perceived control (42.7 vs. 39.1, p=.0002) (Table 3). In a multiple logistic regression including all variables, decrease in PCAQ score ≥0.5 SD from the preceding interview (OR 7.47 [2.15, 26.01], consistent with worsening perceived control, was associated with onset of depression. Presence of a comorbid condition at baseline (OR 2.75 [1.21, 6.24]), past smoking (OR 4.73 [1.49, 15.06]), and higher baseline CESD score (OR per CESD point 1.22 [1.11, 1.35]) were also each associated with depression onset.
In this study of adults with asthma in the community, depression was approximately twice as common (~15%) as in the general population (~7%). Lower perceived control of asthma, as measured by a validated instrument (PCAQ), was associated with a greater likelihood of depression at T1, and a decrease in perceived control coincided with depression onset at follow-up, even after controlling for asthma severity and changes in asthma severity. Low perceived control of asthma has previously been linked with lower quality of life, lower asthma-specific health status, greater health care utilization, and mortality41,42,49,50. Our findings are consistent with these observations in suggesting a role of perceived control in depression prevalence and incidence in asthma, and with findings in other chronic conditions26,51,52.
Based on previous research, we expected asthma severity to be significantly associated with depression, and this was the case in bivariate analyses, but not in multivariate analyses. Previous studies have shown that lower perceived control is associated with more severe asthma49, and in a secondary analysis excluding PCAQ and VLA disability from the regression model, asthma severity was significantly associated with baseline depression, suggesting that one or both of the latter variables was mediating the effects of disease severity. Thus, while asthma severity may have played a role in depression, it may have been mediated through and overshadowed by perceived control of disease.
Previous studies have shown relationships between disability and depression27,28,55-58. In this study, however, there was a strong cross-sectional relationship between VLA disability and depression, but no significant associations between VLA disability and depression onset. VLA disability scores were not available at follow-up, so that we could not test whether an increase in disability was associated with depression onset, as has been found in studies of other conditions27,28.
Individuals who were depressed were more likely to be lost to follow-up. Such bias through attrition has important implications for future longitudinal studies, particularly those dealing with psychological well-being and distress, and suggest the need for extra vigilance in follow-up or use of data management or analytic approaches to handling such attrition. Because we excluded those with baseline depression from our analysis of depression onset, the effect of such loss to follow-up was minimized in that modeling.
Depression has considerable economic and health costs and exerts a negative influence on health in diverse ways, including increasing the risk of physical decline and the risk of mortality, and is associated with poor treatment adherence, which may adversely affect treatment and health status18,59,61,62, 63. Although we do not have information regarding treatment adherence in this sample, these general findings have been supported in asthma-specific research, with depression being linked to poor asthma control6,24,64 and risk of hospitalization7. Thus, finding methods to avoid or ameliorate psychological distress among individuals with asthma could play an important role in improving both the health outcomes and quality of life of individuals with asthma, as well as decreasing societal costs.
This study has important limitations. Our measure of depressive symptoms, the CESD, was designed as a screening tool, and is not a diagnostic measure. It is possible that use of a diagnostic measure of depression would affect the analysis of risk factors. Nonetheless, patients with depressive symptoms warrant further evaluation in clinical practice, and treatment for depressive symptoms may be appropriate even in the absence of a diagnosis of major depression66. The overall study was powered to look at a variety of physical, social, and environmental factors in asthma. Nonetheless, for the relatively infrequent event of incident depression, the confidence intervals were moderately large for some predictors, even though the observed point estimates were unlikely to be due to chance, based on the exclusion of 1 from these confidence intervals.
The sample may be biased in ways that make it unrepresentative of all adults with asthma. However, the sample was recruited from a random sample of community allergists, pulmonologists, and family practice physicians, and then further supplemented with a population sample, a heterogeneous approach that probably increases the generalizablity of the results. The attrition between T1 and T3 (28% over 3 interviews) could bias the results. Although there were relatively few differences between individuals who remained in the study compared to those who dropped out, those who dropped out were more likely to be depressed. It is also possible that factors not included in these analyses, such as neighborhood characteristics67, could affect the occurrence of depression.
In summary, we found that rates of depression were approximately twice as high in this community-based sample of adults with asthma than among the general population. Low perceived control of asthma emerged as the most consistent predictor of depression. Previous studies suggest that perceived control may improve with self-management education. For example, receiving instruction on metered-dose inhaler use was associated with increased perceived control49, and perceived control has increased following asthma self-management education50,53,54. Because of the implications of depression for medication adherence and asthma control, general physical health, and health services use, as well as quality of life, identifying the precursors of depression concomitant with asthma is critical. These findings provide a basis for future work examining the role of perceived disease control in development of depression among adults with asthma.
Difficulties encountered: Individuals who were depressed were more likely to be lost to follow-up
Alternative methodologies that would have been helpful: Diagnostic clinical interview to assess depression. Verification of asthma diagnosis by medical providers.
New lessons arising from study: Low perceived control of asthma is a consistent predictor of depression.
Lessons for clinical practice as a result of the study: Low perceived control is a strong predictor of depression among adults with asthma. Depression is associated with poor medication adherence and poor outcomes among adults with asthma. There is evidence that perceived control can be improved through self-management education.
Supported by R01 ES 10906 (NIH-NIEHS)