Risk of major depressive disorder in spouses of cancer patients in Japan: A cohort study using health insurance‐based claims data

A cancer diagnosis is a highly stressful event that can lead to psychological disorders, including depression, in the patient. Depressive symptoms occur in 6% to 40% of cancer patients, and up to 15% of cancer patients are diagnosed with major depressive disorder (MDD). However, cancer also affects family members, especially spouses, who share a close personal relationship with the patient and are often the primary caregiver. A recent meta-analysis reported that the prevalence of depression or depressive symptoms (determined by a range of psychometric tools) in caregivers of cancer patients was 42.3%. Although many studies have documented a high level of psychological distress in spouses or caregivers of cancer patients, sometimes surpassing that of the patients themselves, few studies have examined whether spouses are actually diagnosed with MDD or meet Diagnostic and Statistical Manual of Mental Disorders criteria for MDD. Further, no previous study has determined the hazard ratio (HR) of an MDD diagnosis in spouses relative to cancer patients or relative to spouses of cancer-free individuals. We recently conducted a matched cohort study of Japanese workers and their families enrolled in an insured medical services database, in which the risk of MDD in cancer patients in the year after a cancer diagnosis was 2.96-fold greater than in cancer-free individuals. This exploratory analysis aimed to identify the risk of MDD in spouses of cancer patients compared with spouses of a cancer-free group, and compared with cancer patients. We hypothesized that the risk of MDD in spouses of cancer patients is comparable to that of a cancer patient, but higher than the risk in spouses of cancer-free people.


| BACKGROUND
A cancer diagnosis is a highly stressful event that can lead to psychological disorders, including depression, in the patient. Depressive symptoms occur in 6% to 40% of cancer patients, and up to 15% of cancer patients are diagnosed with major depressive disorder (MDD). 1 However, cancer also affects family members, especially spouses, who share a close personal relationship with the patient and are often the primary caregiver. 1 A recent meta-analysis reported that the prevalence of depression or depressive symptoms (determined by a range of psychometric tools) in caregivers of cancer patients was 42.3%. 2 Although many studies have documented a high level of psychological distress in spouses or caregivers of cancer patients, sometimes surpassing that of the patients themselves, few studies have examined whether spouses are actually diagnosed with MDD or meet Diagnostic and Statistical Manual of Mental Disorders criteria for MDD. [3][4][5][6][7] Further, no previous study has determined the hazard ratio (HR) of an MDD diagnosis in spouses relative to cancer patients or relative to spouses of cancer-free individuals.
We recently conducted a matched cohort study of Japanese workers and their families enrolled in an insured medical services database, in which the risk of MDD in cancer patients in the year after a cancer diagnosis was 2.96-fold greater than in cancer-free individuals. 8 This exploratory analysis aimed to identify the risk of MDD in spouses of cancer patients compared with spouses of a cancer-free group, and compared with cancer patients. We hypothesized that the risk of MDD in spouses of cancer patients is comparable to that of a cancer patient, but higher than the risk in spouses of cancer-free people.

| METHODS
This was an exploratory analysis of a previously described matched cohort study 8 using data on individuals enrolled in the JMDC Inc.
(Tokyo, Japan) insured medical services database between January 2011 and September 2018. Because the study used anonymized information, institutional ethics approval and informed consent were not required, in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan.
As described, 8 adult cancer patients who were newly diagnosed with cancer were matched 1:10 to cancer-free individuals according to age, sex, insurance membership category, and index month. Both cancer and cancer-free groups had no MDD diagnosis between 6 and 12 months before the index month (full inclusion criteria are listed in Table S1). This analysis included spouses of individuals in the matched cohort who did not have MDD diagnosis between 6 and 12 months before the index month. As same-sex marriages are not legally recog-

| RESULTS
This analysis included 16,936 married couples from the cancer group and 168,831 married couples from the cancer-free group (Table 1).
Slightly more than half of spouses were men (51.8% and 51.5% in the cancer and cancer-free spouse groups, respectively); the same percentages (51.8%, 51.5%) of spouses were insured workers. The mean age was 53.2 years in both spouse groups and 53. 6

| Study limitations
The effect of other factors, such as cancer type, stage, and prognosis, spousal physical health problems, caregiver status, absences from work, familiarity with mood disorders/MDD, or the quality of the couple's relationship were not evaluated. In addition, there were few female workers among the couples that were included in the analysis.
Finally, the diagnosis criterion for this study was an actual clinical diagnosis of MDD; however, we could not determine from the database how the diagnosis was made (ie, clinical evaluation, structured interview) or whether it was made by a mental health professional or other physician.

| Clinical implications
Greater mental health support, including appropriate diagnosis and treatment of MDD, is required not only for cancer patients, but also for their spouses. Limited.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from JMDC Inc. but were used under licence for the current study; therefore, restrictions apply and the data are not publicly available. For inquiries about access to the data set used in this study, please contact JMDC (https://www.jmdc.co.jp).

SUPPORTING INFORMATION
Additional supporting information may be found online in the Supporting Information section at the end of this article.