Cancer has a considerable impact on physical, emotional, and practical parts of the lives of patients and their family members (1). Especially in palliative phase, the role of family caregiver (FC) is crucial because they are responsible for care to severely ill patients for a long time. Under the great responsibility for the care burden and the confrontation with an instant separation, family members of cancer patients have a high emotional burden (2).

Depressive disorder is more common among FCs of terminal cancer patients than among patients in other phase of cancer (3). Several studies have been conducted to identify the asso-ciated factors with depression of FCs, but few studies have investigated the impact of the patient’s characteristics on the FCs’ depression (4,5). Cancer patients suffer various symptoms (e.g., pain, weakness, anorexia, dry mouth and constipation) in terminal stage of their disease (6), and the symptoms of the patients can influence the FCs’ psychological distress (7).

There has been very little study on the associations bet-ween patients’ symptoms themselves and FCs’ depression in the palliative phase. A recent small studies reported that FCs’ depression was associated with a patient’s trouble sleeping (8) or a discrepancy in the evaluation of constipation between them (9). Thus, this study aimed to investigate the relation-ship between various symptom features of terminally ill cancer patients and their FC’s depression.

A cross-sectional survey was conducted at seven medical centers in Korea during 2014, and 332 consecutive terminally ill cancer patients were recruited. Eligible patients were given information regarding the purpose of study and they were required to identify their primary FC, defined as the person who provided the most informal care and who was =20 years old, able to complete the questionnaire and communi-cate with the interviewer, and willing to participate. Twenty- nine FCs were excluded because they declined to participate. The FCs completed the self-administered questionnaire with the assistance of an interviewer, when necessary. Data from 293 patient-FC pairs were included in the final analysis. This study complied with the Declaration of Helsinki. Study approval was obtained from the institutional review board at each center and all participants signed written informed consent.

FCs’ depression was assessed using the Hospital Anxiety and Depression Scale-Depression (HADS-D), which has been extensively validated in Korean populations (10). HADS-D is composed of seven items and is scored from 0 to 21, with higher scores indicating more severe depression. In the original version, scores are graded in three groups (normal [0~7], borderline abnormal [8~10], and abnormal [11~21]). We categorized subjects into two groups: ‘non-depressed (HADS-D, 0~7)’ or ‘depressed (HADS-D, 8~21).’

Patients’ symptoms were measured by the Korean version of the M.D. Anderson symptom inventory (MDASI) (11). The severity of each symptom in the previous 24 h was rated from 0 (“symptom not present”) to 10 (“as bad as you can imagine”). We divided into two groups by MDASI scores (12): ‘absent (0)’ vs. ‘present (1~10)’ or ‘not severe (0~6)’ vs. ‘severe (7~10).’

Patients’ demographic characteristics and functional status (assessed using the European Cooperative Oncology Group Performance Status (ECOG) were obtained. ECOG 3~4 was considered as poor performance status. The FC survey con-tained demographic characteristics, relationship to the patient and medical comorbidities. Questionnaires also queried household income and objective burden of care, and these factors were categorized into two groups based on the distribution in the current sample: low income (=2 million Korean Won), fre-quent visits for caregiving (>5 d per week), more time spent caregiving (>8 h per day), and long duration of caregiving (>3 months). To assess the FCs’ quality of life (QOL), we used the Korean version of the Caregiver QOL Index-Cancer (CQOLC). CQOLC consists of 35 items (0=not at all to 4= very much). The total score was 140, with higher scores re-flecting a better QOL. The Korean version of the Medical Outcome Study Social Support Survey (MOS-SSS) was used to assess social support systems. MOS-SSS consists of 19 items rated on a 5-point Likert. These variables were classified into two groups, by the median value of the current sample.

Between the two groups according to the FCs’ depression, we compared the differences in the characteristics of patient- FC pairs using a χ² test or independent t test. To identify the relevant factors associated with FC depression, we used a stepwise multivariate regression analysis. Adjusted depression score of FCs according to the symptom features of their pa-tients were calculated using a multivariate regression model. The data were analyzed using STATA SE 9 (STATA Corp., TX, USA). For all analyses, we considered P values of less than 0.05 generated in two-sided tests to indicate statistical significance.

We examined the differences in characteristics of patient-FC pairs according to the presence of FC depression (Table 1). Multivariate analysis revealed that low FC QOL (adjusted odds ratio [aOR], 3.32; 95% confidence interval [CI], 1.90~5.81), low social support (aOR, 1.76; 95% CI, 1.01~3.07), spouse (aOR, 2.38; 95% CI, 1.33~4.28), and more caregiving time (aOR, 2.40; 95% CI, 1.30~4.42) were associated with caregivers’ depression (data not shown). There were also significant differ-ences in patient’s symptoms by the presence of FC depression (Supplementary Table 1). Patients of non-depressed FCs complained more about fatigue (P=0.003), nausea (P=0.009), loss of appetite (P<0.001), drowsiness (P=0.003) and dry mouth (P=0.005).

Table 1 . Characteristics by Family Caregivers’ Depression..

Characteristics	Non-depressed (n=145)	Depressed* (n=148)	P value
	%
Patient
Young age (<65 yrs)	51.0	57.4	0.272
Male	49.0	64.2	0.009
Poor performance (ECOG 3~4)	72.4	75.0	0.615
Family caregiver
Old age (≥50 yrs)	42.1	63.5	<0.001
Male	28.6	22.1	0.207
Married	79.3	84.4	0.264
Unemployed	54.5	71.0	0.004
Non-professing a religion	37.4	41.0	0.539
Low educational status (≤high school)	52.1	39.7	0.035
Having a comorbidity	55.2	56.1	0.876
Spouse	27.5	53.9	<0.001
Low QOL (CQOLC total <66)	30.1	63.6	<0.001
Low income (≤2 million KW)	50.7	54.3	0.552
Frequent caregiving (>5 days/week)	55.0	69.6	0.011
More spent caregiving (>8 hours/day)	60.3	81.6	<0.001
Long duration of caregiving (>3 months)	45.8	46.6	0.892
Low social support (MOS-SSS total <74)	41.0	59.6	0.002

ECOG: Eastern Cooperation Oncology Group, QOL: quality of life, CQOLC: Caregiver QOL index-Cancer, KW: Korean Won, MOS-SSS: Medical Outcome Study Social Support Survey..

Classifications are based on the distribution of variables in the current sample..

P values are from χ² test..

^*Defined by Hospital Anxiety and Depression Scale-Depression score ≥8.

The scores were adjusted for identified potential con-founders, and the depression scores of FCs by patients’ symp-tom features are depicted in Figure 1. The mean scores of HADS-D was significantly lower in FCs caring for patients who had symptoms such as loss of appetite (P=0.005), drow-siness (P=0.024) and dry mouth (P=0.043) than in FCs caring for patients who had not. In addition, FCs for patients with severe appetite loss had lower depression scores than those with not severe appetite loss (P=0.039).

Figure 1.

Depression score of family caregivers according to the symptom features of their terminally ill cancer patients.

HADS-D: Hospital Anxiety and Depression Scale-Depression. HADS-D scores were adjusted for potential confounders such as caregivers’ quality of life, level of social support, relationship to patients, and spent time for caregiving.

*P<0.01, †P<0.05.

In this study, we found that some specific symptoms among terminal cancer patients were inversely related to FC depres-sion. This paradoxical finding can be explained by effects of negative symptoms on the FC’s burden. Drowsiness can be directly connected with reduced activity of patients, and thus, the physical burden of FC might be alleviated. The symptoms of appetite loss or dry mouth can also be related to poor oral intake, leading to intravenous nutrition. As the high number of caregiving tasks increase the burden of caregiver (13), increments of negative symptoms may reduce the burden on the caregiver, and thus decrease the rates of depression. Moreover, elder or female caregiver make up a large propor-tion of FCs in Korea (14), and caregiving for terminal patients can be physically more demanding works for them. Another explanation is the psychological disconnection. Patients and their FCs are psychologically bonded and interact tightly with each other. Patients’ suffering can increase psychological burden of FCs (7), however negative symptoms may hinder patients from expressing their distress. To clarify our results, well designed qualitative studies are needed.

FCs in this study may have had less psychological deterio-ration than other FCs of terminal cancer patients, because we included patients who were able to consent to the study and the FC was able to complete the survey. This may have underestimated the impact of various factors on depression. Additionally, it should be cautious that HADS-D is not a clinical diagnostic tool for depressive disorder: it was designed to detect depressive mood (15). Although cross-sectional design does not permit definitive statements about causality, our results underscore the consideration of patients’ symptom character-istics when evaluating FC depression. Further researches with a longitudinal design are needed.

The authors thank the participants who bravely shared their experiences. This research received no specific grant from any funding agency in the public, commercial, or not-for- profit sectors.