Article ID: CJ-17-0197
Background: The present comparative study with healthy volunteers was conducted to investigate the depressive status and temperament in patients with chronic thromboembolic pulmonary hypertension (CTEPH).
Methods and Results: The results of the temperament and personality scale test, and the Quick Inventory of Depressive Symptomatology-Self Report revealed that CTEPH patients have a significantly higher depressive status than healthy volunteers.
Conclusions: It may be that CTEPH patients are more likely to have a depressive temperament in origin. It is expected that the relationship between the biological traits of CTEPH (e.g., genetics) and patients’ depressive temperament will be elucidated in the future.
Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as a progressive disease of increasing pulmonary vascular resistance due to chronic thromboembolism in the pulmonary arteries that leads to pulmonary hypertension and right-sided heart failure.1,2 The etiology of CTEPH, including genetic abnormalities, has not been elucidated as yet. Interestingly, in the clinical setting, we often feel that most CTEPH patients may have depressive tendencies. However, the possibility of such a link has not been investigated thus far. It has been reported that depression is highly correlated in patients with chronic heart failure, and that depression predicts a significantly worse prognosis for these patients.3 Importantly, we often feel that CTEPH patients may have a depressive temperament even at the early stages, without heart failure. Therefore, the present comparative study with healthy volunteers was conducted to investigate the depressive status and temperament in patients with CTEPH.
The present study was performed on 40 consecutive CTEPH patients who had been diagnosed on the basis of pulmonary angiography and lung perfusion scintigraphy. The baseline characteristics of the CTEPH patients are described in Table 1. As a control group, 45 age- and gender-matched healthy volunteers were recruited to the study. All participants provided informed consent. The study protocol and analyses of the data obtained were approved by the Institutional Review Board. All patients and healthy volunteers completed a temperament and personality scale test.4,5 In addition, they completed the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), a 16-item symptom severity rating scale that reflects the severity of depressive symptoms.6,7
| All CTEPH patients |
QIDS ≤5 (n=25) |
QIDS ≥6 (n=15) |
P-value between patients with QIDS ≤5 and those with QIDS ≥6 |
|
|---|---|---|---|---|
| Age (years) | 61 [47–70] | 62 [53–71] | 52 [39–64] | 0.158 |
| Gender (male) | 11 (27.5) | 5 (20.0) | 6 (40.0) | 0.273 |
| NYHA | 0.152 | |||
| I | 0 (0) | 0 (0) | 0 (0) | |
| II | 28 (70) | 20 (80) | 8 (53) | |
| III | 12 (30) | 5 (20) | 7 (47) | |
| IV | 0 (0) | 0 (0) | 0 (0) | |
| Mean RAP (mmHg) | 6.0 [3.0–7.25] | 5.0 [3.0–7.5] | 6.0 [4.0–8.0] | 0.400 |
| Mean PAP (mmHg) | 42.0 [37.5–46.3] | 42.0 [33.5–46.5] | 42.0 [40.0–53.0] | 0.613 |
| PVR (Wood units) | 8.17 [6.6–11.4] | 8.1 [6.2–10.9] | 8.6 [7.2–11.7] | 0.746 |
| Cardiac output (L/min) | 4.10 [3.45–4.77] | 4.08 [3.45–4.88] | 4.20 [3.30–4.84] | 0.767 |
| 6MWD (m) | 380 [326–444] (n=31) | 393 [299–446] (n=20) | 380 [352–450] (n=11) | 0.831 |
| BNP (pg/mL) | 54.4 [31.5–131.8] | 67.1 [37.6–181.4] | 49.5 [21.7–125.1] | 0.230 |
Data are given as the number of patients in each group, with percentages in parentheses, or as median values with the interquartile range in brackets. *P<0.05. Significant differences between patients with QIDS ≤5 and those with QIDS ≥6 were determined using the Mann-Whitney U-test or Fisher’s exact test, as appropriate. BNP, B-type natriuretic peptide; CTEPH, chronic thromboembolic pulmonary hypertension; NYHA, New York Heart Association; PAP, pulmonary arterial pressure; PVR, pulmonary vascular resistance; QIDS, Quick Inventory of Depressive Symptomatology; RAP, right atrial pressure; 6MWD, 6-min walk distance.
The results of the temperament and personality scale test and the QIDS-SR are summarized in Table 2. Of note, of the parameters evaluated in the temperament and personality scale test, only depressive temperament differed significantly between the CTEPH patients and healthy volunteers (70.0 vs. 33.3%, respectively; P=0.001); there were no significant differences in any other parameters evaluated, including cyclothymia, hyperthymic temperament, irritable temperament, anxiety temperament, schizoid temperament, and melancholic temperament.
| Variable | CTEPH patients |
Healthy volunteers (n=45) |
P-valueA |
|---|---|---|---|
| All CTEPH patients (n=40) | |||
| Age (years) | 61 [47–70] | 57 [47–65] | 0.286 |
| No. (%) of women/men | 29 (72.5)/11 (27.5) | 25 (55.6)/20 (44.4) | 0.120 |
| QIDS-SR scores | |||
| 0–5, no depression | 25 (62.5) | 41 (91.1) | 0.002* |
| ≥6, more than mild depression | 15 (37.5) | 4 (8.9) | 0.002* |
| 6–10, mild depression | 10 (25) | 4 (8.9) | 0.077 |
| 11–15, moderate depression | 2 (5) | 0 (0) | 0.219 |
| 16–20, severe depression | 1 (2.5) | 0 (0) | 0.471 |
| 21–27, very severe depression | 2 (5) | 0 (0) | 0.219 |
| Temperament and personality scale testC | |||
| Depressive temperament | 28 (70.0) | 15 (33.3) | 0.001* |
| Cyclothymia | 21 (52.5) | 14 (31.1) | 0.051 |
| Hyperthymic temperament | 18 (45.0) | 21 (48.8) | 1.000 |
| Irritable temperament | 16 (40.0) | 16 (35.6) | 0.823 |
| Anxiety temperament | 12 (30.0) | 6 (13.3) | 0.069 |
| Schizoid temperament | 18 (45.0) | 15 (33.3) | 0.373 |
| Melancholic temperament | 25 (62.5) | 22 (48.9) | 0.275 |
| CTEPH patients with QIDS-SR scores 0–5 (n=25) | P-valueB | ||
| Age (years) | 63 [55–70] | – | 0.062 |
| No. (%) of women/men | 20 (80.0)/5 (20.0) | – | 0.067 |
| Temperament and personality scale testC | |||
| Depressive temperament | 16 (64.0) | – | 0.023* |
| Cyclothymia | 10 (40.0) | – | 0.600 |
| Hyperthymic temperament | 12 (48.0) | – | 1.000 |
| Irritable temperament | 5 (20.0) | – | 0.276 |
| Anxiety temperament | 2 (8.0) | – | 0.702 |
| Schizoid temperament | 11 (44.0) | – | 0.443 |
| Melancholic temperament | 14 (56.0) | – | 0.623 |
Data are given as the number of patients in each group, with percentages in parentheses, or as median values with the interquartile range in brackets. *P<0.05. Significant differences between CTEPH patients and healthy volunteers were determined using the Mann-Whitney U-test or Fisher’s exact test, as appropriate. AP-values between all enrolled CTEPH patients (n=40) and healthy volunteers (n=45). BP-values between CTEPH patients with Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) scores of 0–5 (n=25) and healthy volunteers (n=45). CThe data show the number (percentage) of people positive for the trait. Abbreviations as in Table 1.
On the QIDS-SR, scores in the range 0–5 indicate no clinically significant depression, whereas scores ≥6 indicate more than mild depression.8 In the present study, the number of people with a QIDS-SR score ≥6 was significantly higher in the CTEPH group than in the healthy volunteer group (37.5 vs. 8.9%, respectively; P=0.002). Baseline characteristics are added in the revised manuscript as a new Table 1. There were no significant differences in the baseline characteristics and hemodynamics between patients with QIDS scores ≤5 and those with WIDS scores ≥6 (Table 1). As indicated in Table 2, 12.5% of CTEPH patients had QIDS-SR scores ≥11, indicating more than moderate depression; in contrast, none of the healthy volunteers had QIDS-SR scores ≥11. In addition, even for those CTEPH patients with QIDS-SR scores in the range 0–5, meaning no depression, the number with a depressive temperament was significantly higher (64.0%) than in the healthy volunteer group (P=0.023). These findings suggest that CTEPH patients are more likely to have a depressive temperament. In addition, 4 CTEPH patients diagnosed with depression and 1 with schizophrenia had already been treated for these psychiatric disorders, but no healthy volunteers were not diagnosed and not treated. Other than the total 5 treated CTEPH patients, 11 CTEPH patients had QIDS-SR scores ≥6, suggesting a high prevalence of a depressive state, which was still significant compared with the healthy volunteers (P=0.019).
The relationship between depressive status and clinical severity in CTEPH patients was also analyzed. New York Heart Association (NYHA) classification, B-type natriuretic peptide (BNP), a serological marker of heart overload, and hemodynamic parameters, such as mean pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR), and cardiac output, were not significantly correlated with QIDS-SR scores (NYHA, ρ=0.261, P=0.104; BNP, ρ=−0.184, P=0.256; mean PAP, ρ=0.149, P=0.359; PVR, ρ=0.086, P=0.599; cardiac output, ρ=−0.033, P=0.840), as determined by Spearman rank correlation coefficients, suggesting that there is no correlation between depressive status and the clinical severit y of CTEPH.
There are some limitations in this study. This is an observational study, and the number of patients enrolled was not large. Furthermore, a control group with a disease, such as Group I of pulmonary arterial hypertension (PAH), was considered to understand the significance of the association between depression and CTEPH. To exclude the effect of pulmonary hypertension on depressive status, the control group should have been PAH patients. However, the average age of patients with Group I of PAH is much younger than that of CTEPH patients, at least in Japan. Therefore, in this study, age- and gender-matched healthy volunteers were recruited as a control group.
There are several reports suggesting the association of depressive status and CTEPH,9,10 which demonstrated that anxiety and depression are related with the clinical severity and that they influence the quality of lives in patients. Hence, these previous studies suggest the secondary depressive state in patients. Importantly, this study used the temperament and personality scale test and QIDS-SR score, which correlates with the Hamilton Depression Rating Scale as the representative objective scale for diagnostic criteria of depression; these have not been used in previous studies.9,10 Furthermore, there was no correlation between depressive status and the clinical severity of CTEPH in this study. These results are different from those of previous studies.9,10 This discrepancy should be investigated further in large prospective studies in the future. However, the findings in this study may suggest that symptoms such as dyspnea, due to CTEPH, would not be the cause of depressive status in CTEPH. Therefore, the results from this study suggest the depressive traits rather than state in CTEPH patients.
In conclusion, the present study demonstrates that CTEPH patients have a significantly higher depressive status than healthy volunteers. It may be that CTEPH patients are more likely to have a depressive temperament in origin, and it is expected that the mechanisms of the relationship between the biological traits of CTEPH (e.g., genetics) and patients’ depressive traits will be elucidated in detail in the future.
There are no relationships with industry in this study.
