Background
Chronic obstructive pulmonary disease is associated with a variety of comorbidities [
1,
2], that are associated with hospital admissions and mortality [
3]. One of them is depression [
4] which is also linked to the clinical state and course of COPD [
5,
6]. A further common factor in both COPD and depression are deteriorations in quality of life [
7‐
10].
One of the screening tools for depression is the Patient Health Questionnaire Depression Scale 9, a 9-item self-report module containing the 9 signs and symptoms of major depression as delineated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) [
11]; a detailed description of the PHQ-9 questionnaire is given in the Additional file
1. Although the questions were constructed to refer to the same psychometric dimension “depression”, they are not synonymous, and some of them appear to be susceptible to impairments common in somatic diseases.
A relationship between biomedical disease conditions and depression scores has been assessed for a number of chronic diseases [
12‐
14]. In COPD, many studies evaluated the sum score, and some studies selected single items, such as suicide ideation [
15]. The spectrum of alterations common in COPD raises the question whether other items of the PHQ-9 and its sum score are related to different COPD characteristics.
To our knowledge, there is no study addressing this question and quantifying the impact of specific COPD characteristics on depression. This impact could also explain the wide range of prevalence estimates of depression in different COPD populations [
16,
17]. Based on these considerations, we analysed the relationship between COPD characteristics and the results of the PHQ-9 using data from the baseline visit of the large German COPD cohort COSYCONET (German
COPD and
Systemic
Consequences - Comorbidities
Network) [
18]. To elucidate the impact of COPD, we also demonstrated the associations between the single PHQ-9 items with anthropometric data, gender, age, smoking status, comorbidities and COPD characteristics.
Discussion
In the present study, we analysed the impact of COPD on the PHQ-9 depression score to reveal whether specific COPD characteristics were associated with changes in the score. The characteristics identified as relevant for the PHQ-9 comprised symptoms and exacerbation risk according to GOLD groups A to D, and the comorbidities asthma, sleep apnoea, gastrointestinal disorders, osteoporosis and arthritis. The GOLD groups were related to all single PHQ-9 items in a parallel manner, whereas the spirometric GOLD grades 1–4 were only related to some questions. The different role of the single items was underlined by their associations with anthropometric data and comorbidities. Our observations suggest that on average the chronic disease COPD was associated with PHQ-9 scores elevations by 1–2 score points. Conversely, when hypothetically assuming patients being in GOLD group A, or without the comorbidities analysed, the PHQ-9 sum score was reduced by this amount.
In all analyses age, gender, BMI, smoking status and pack years were carried as covariates to adjust for their influences. Females, younger subjects and active smokers showed higher scores of depression [
25], which is in line with previous data [
26‐
28]. We additionally found pack years to be related to the sum score, as well as BMI [
29]. The associations with age, gender, BMI and smoking were robust throughout all analyses, thereby underlining the validity of the analyses regarding COPD characteristics.
Both categorisations according to GOLD [
19] were related to the PHQ-9 sum score but the relationship to groups A-D was much more consistent and stronger than that to grades 1–4. Symptoms and exacerbation risk had completely additive effects not only on the sum score, but on all single items. Overall, in GOLD D compared to A, the PHQ-9 sum score was higher by more than 4 points. The strong effect observed for symptoms is in accordance with published data, despite the fact that these were obtained using previous GOLD definitions [
30] or the CAT instead of mMRC score [
6]. The average PHQ-9 sum score in our population was about 6.3 points and not far from the cut-off value of ≥10 considered as indicative for depression [
11]. In view of this, the magnitude of the effects of COPD on the PHQ-9 score indicate a significant impact on the diagnosis of depression, in accordance with elevated prevalence values in the literature [
5].
The mean influence of COPD, based on either symptoms/exacerbations or comorbidities, on the mean PHQ-9 sum score could be quantified as difference between 6.3 versus 4.5 or 5.2 points, respectively (Fig.
4). Formal adjustment of the mean PHQ-9 score for COPD severity or comorbidities led to values that are similar to values reported for the general population [
31]. Correspondingly, the prevalence of score values ≥10 decreased from 22.0 to 11.6% or 14.6%, respectively, again being closer to the range of the general population [
32,
33]. The effect attributable to COPD was similar in patients with or without the diagnosis of mental disorder or intake of antidepressants, although their baseline values were different. This suggests that COPD severity and comorbidities are associated with a systematic additive effect on the PHQ-9, and the relationship of COPD to the PHQ-9 was not limited to patients with premorbid depressive symptoms. The numerical estimates provided by us (Figs.
2 and
3) might be useful to quantify the effect of individual COPD characteristics on the PHQ-9 score.
Depression is recognized as a major condition among COPD comorbidities [
34], but there is a wide range of prevalence estimates [
5], suggesting a significant dependence on the study population and possibly the diagnostic tools. The PHQ-9 as a diagnostic screening tool has been validated in the general population [
35], as well as cohorts with specific morbidities [
12,
14], including COPD. Inspection of its single items raises the question, whether they are sensitive to impairments common in COPD, and indeed some of the items have already been analysed in these patients [
15]. There is no study, however, which quantified the effect of COPD characteristics on the PHQ-9 in detail.
For this purpose, we focused on those patients’ characteristics, which are easily available in clinical practice. Lung function was omitted from the final analysis, as the associations were inconsistent and weak compared to the other influencing factors. An important observation was that all effects on the sum score arising from GOLD groups or from comorbidities were additive and that there were no significant interactions. This considerably simplified the estimation of the impact of COPD characteristics (see Figs.
2 and
3). The combination of comorbidities resulted in a slightly lower effect compared to that of symptoms and exacerbation risk (Fig.
4), suggesting additional influencing factors that are covered by GOLD groups, but not the comorbidities chosen. The effect of COPD severity on the PHQ-9 might even be larger as GOLD group A was taken as reference.
The relationship between depression scores and CAT, as a measure of COPD severity, is close, and a cut-off value of 10 for the PHQ-9 corresponds to cut-off values of 19 to 21 for the CAT [
6]. We similarly observed the best correspondence for a cut-off value of 20. Interestingly, this value is similar to the cut-off value of 18 that has been proposed as superior to the conventional cut-off value of 10 regarding the categorisation of COPD severity [
36]. The predictive power of the CAT score regarding depression seems high, but not high enough to replace a proper depression questionnaire such as the PHQ-9. We found similar results for the visual analogue scale (EQ VAS) of the generic quality of life questionnaire EQ-5D [
9,
10]. All of these findings are in line with the expectation that quality of life scores are closely linked to depression.
Based on the patients’ medication and reports we defined several categorical indices of mental disorder, which resulted in prevalence estimates ranging between 10.3 and 24.3% (Table
3). This, however, did not affect our findings regarding the impact of COPD, and the associations found in the total population were also present when excluding patients with antidepressants. The observation that COPD, as common feature of our patients, showed such homogeneous effects, underlines its systematic impact on the PHQ-9 score and the evaluation on depression based on this.
Studies on the effect of antidepressants on the PHQ-9 reported scores of about 17 at baseline and of 5 after treatment [
31]. In our study population, patients with antidepressants showed mean scores of 9.2, and of 6.8 or 7.8 when hypothetically taking into account COPD. The decrease in the PHQ-9 score was similar to that in patients without antidepressants but higher than in the total study population, indicating that the antidepressant therapy did not normalize the PHQ-9 score in COPD patients. Although there are no reasons to assume that antidepressants should be less effective in COPD compared to other patients [
34], this observation suggest that antidepressant therapy is not fully effective in COPD, possibly due to the impact of continuing symptom burden from respiratory disease.
Limitations
In COSYCONET the presence of mental disorders was asked as lifetime prevalence based on the diagnosis by a physician, and depression was not specifically asked for. However, patients with a diagnosis of depression at the time of the study could be identified by specific medication, and our findings regarding the impact of COPD on the PHQ-9 score were not affected by this. In addition, the effect of respiratory symptoms and exacerbation risk were additive throughout all analyses in a very consistent manner. We cannot exclude selection effects that are unavoidable in a cohort study with comprehensive, demanding assessments, but it seems unlikely that these have affected our results.
The questionnaires used for the diagnosis of depression are not necessarily equivalent [
37], and our results strictly apply to the PHQ-9, which refers to the patients’ clinical state in the previous two weeks. This restriction is unlikely to have played a role in our study, as only patients with stable COPD were investigated [
18]. The PHQ-9 could be particularly susceptible to COPD severity, as some of its questions, although targeting depression, address symptoms that are also common in COPD. This was reflected in the correlation between the PHQ-9 and the CAT or EQ VAS, which do specifically target depression, as well as the analysis of single PHQ-9 items. It would be of interest to clarify whether other diagnostic tools for depression also reflect COPD characteristics.