Higher sleep reactivity and insomnia mutually aggravate depressive symptoms: a cross-sectional epidemiological study in Japan

Higher sleep reactivity and insomnia mutually aggravate depressive symptoms: a cross-sectional epidemiological study in Japan

Sleep Medicine 33 (2017) 130e133 Contents lists available at ScienceDirect Sleep Medicine journal homepage: www.elsevier.com/locate/sleep Brief Com...

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Sleep Medicine 33 (2017) 130e133

Contents lists available at ScienceDirect

Sleep Medicine journal homepage: www.elsevier.com/locate/sleep

Brief Communication

Higher sleep reactivity and insomnia mutually aggravate depressive symptoms: a cross-sectional epidemiological study in Japan Shun Nakajima a, b, c, *, Yoko Komada a, Taeko Sasai-Sakuma a, Isa Okajima d, Yutaka Harada e, Kazue Watanabe f, Yuichi Inoue a, b, c a

Department of Somnology, Tokyo Medical University, Tokyo, Japan Yoyogi Sleep Disorder Center, Tokyo, Japan Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan d Faculty of Human Sciences, Waseda University, Saitama, Japan e Health and Medical Care Bureau, Tottori Prefectural Mental Health and Welfare Center, Tottori, Japan f Welfare Benefits Division, Financial Bureau, Tottori Prefecture General Affairs Department, Tottori, Japan b c

a r t i c l e i n f o

a b s t r a c t

Article history: Received 22 December 2015 Received in revised form 8 August 2016 Accepted 17 December 2016 Available online 1 February 2017

Objective: Sleep reactivity assessed using the Ford Insomnia Response to Stress Test (FIRST) is associated with depression. This study clarified stress reactivity and insomnia effects on depressive symptoms. Methods: A cross-sectional questionnaire survey was administered to 2645 participating government employees (35.4% female, mean age 42.8 years) during health checks conducted at Tottori prefecture, Japan, in June 2012. Questionnaire items included: demographic information; the FIRST; the Pittsburgh Sleep Quality Index (PSQI); and a 12-item version of the Center for Epidemiological Studies Depression scale (CES-D). The study defined CES-D scores of 12 points as positive for depression, PSQI scores of 5.5 points as positive for insomnia symptoms, and FIRST scores of 19 points as indicating higher sleep reactivity. Results: Multivariate logistic regression analysis revealed insomnia (adjusted OR ¼ 3.40), higher sleep reactivity (adjusted OR ¼ 1.78), presence of disease currently being treated (adjusted OR ¼ 1.84), and being female (adjusted OR ¼ 1.53) as independently associated with depression. Participants with insomnia and a high FIRST score showed higher CES-D scores than those with insomnia alone and those with high FIRST without insomnia (all p < 0.01). Conclusions: Sleep reactivity might be associated with depression, independent of insomnia. Elevated sleep reactivity and insomnia symptoms are thought to aggravate depressive symptoms. © 2017 Elsevier B.V. All rights reserved.

Keywords: Ford Insomnia Response to Stress Test (FIRST) Transdiagnostic Comorbidity Vulnerability Mood disorder

1. Introduction More than 80% of patients with major depressive disorders have insomnia symptoms [1]. Furthermore, people with chronic insomnia have increased risk of developing depression [2], which presents the possibility that these two disorders share a common pathological basis [3]. One common factor for insomnia and depression is stress; acute and chronic stress are known to cause or aggravate symptoms of insomnia and depression [4,5]. The Ford Insomnia Response to Stress Test (FIRST), a self-rated questionnaire, can assess stress-induced hyperarousal (sleep reactivity), indicating vulnerability to insomnia [6]. Initially, FIRST was

developed to assess vulnerability to insomnia development. Some reports have described sleep reactivity as playing a role in pathological mechanisms related to insomnia [6e9]. Moreover, Drake et al. recently reported that higher FIRST scores are associated not only with development of insomnia but also with depression [10]. Nevertheless, it remains unclear whether higher stress reactivity and insomnia symptoms affect depressive symptoms independently. To clarify this point, a cross-sectional questionnaire survey to assess the association of sleep reactivity and insomnia symptoms with depression was administered to a population of Japanese government employees. 2. Methods

* Corresponding author. Department of Somnology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. Fax: þ81 3 3374 2038. E-mail address: [email protected] (S. Nakajima). http://dx.doi.org/10.1016/j.sleep.2016.12.023 1389-9457/© 2017 Elsevier B.V. All rights reserved.

The Ethics Committee of the Neuropsychiatric Research Institute (Tokyo, Japan) approved this study. The questionnaire survey

S. Nakajima et al. / Sleep Medicine 33 (2017) 130e133

was administered in June 2012 during health checks of prefectural government employees of Tottori prefecture, Japan. Tottori prefecture, located in western Japan, has 588,667 residents, according to census data of October 2010. First, 3722 prefectural government employees were asked to respond to questionnaires delivered through an internet website. Of that target population, 2645 (71.1%) responded; four respondents who did not provide demographic information were excluded from subsequent analyses. Consequently, data of 2641 respondents (71.0%) were used for subsequent analyses [mean age ¼ 42.8 (SD 10.3) years, 1705 male, 936 female]. The research questionnaires elicited demographic information (age, sex, presence or absence of disease currently treated, living with family members or not, and presence or absence of engagement in shift work, smoking habit, and habitual alcohol ingestion). Respondents also gave answers to tests: the FIRST, the Pittsburgh Sleep Quality Index (PSQI), and the Twelve-item version of the Center for Epidemiological Studies Depression scale (CES-D). The FIRST consists of nine items, with responses given on a fourpoint Likert scale. The total score of the FIRST is 9e36 points. The validity and reliability of the original version of the FIRST and the Japanese version of the FIRST have been validated [6,7]. The cut-off point of the Japanese version of the FIRST for discriminating subjects who have high sleep reactivity was set at 18 points (high sleep reactivity, FIRST score 19; low sleep reactivity, FIRST score <18) [7]. The PSQI measure assesses subjective sleep disturbance [11], which includes 19 self-rated items with a four-point Likert scale, and assesses subjective sleep disturbance during the preceding one-month period [11]. The total score of the scale is 0e21. The Japanese version of the PSQI, which was already validated [12], was used for this study. The cut-off point to distinguish healthy individuals from those with subjective sleep disturbance (positive for insomnia symptom) was set at 5.5 points [12]. The CES-D can identify clinically significant depression [13,14]. The Japanese version of CES-D, which has sufficient validity and reliability [15],

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was used for this study. The study defined participants with CES-D scores 12 points as those having depressive symptoms, according to a previous study [16]. Univariate logistic regression analyses was conducted, with the presence of depression (CES-D score 12) as a dependent variable and age (dichotomized at median value), sex, smoking habit (yes/ no), habitual alcohol ingestion (yes/no), living alone (yes/no), disease currently treated (yes/no: diseases include physical and mental disorder), engagement in shift work (yes/no), higher sleep reactivity (FIRST score >18), and the presence of insomnia (PSQI score 5.5) as independent variables. Thereafter, multivariate logistic regression analysis for investigation of associated factors of the presence of depression was conducted with significant variables in the univariate models. To clarify the contributions of insomnia and higher sleep reactivity to the severity of depressive symptoms, the CES-D score was compared, after excluding insomnia items, among the following four groups using analysis of variance (ANOVA): low FIRST subjects without insomnia, high FIRST subjects without insomnia, low FIRST subjects with insomnia, and high FIRST subjects with insomnia. When a significant difference was found using ANOVA, a Bonferroni test was applied for post hoc analysis. 3. Results The sample comprised 1705 men (64.6%) and 936 women (35.4%), with a mean age of 42.8 (SD 10.3) years. The average scores of the FIRST, PSQI, and CES-D in all subjects were, respectively, 20.3 (SD 6.0), 5.0 (SD 2.6), and 5.0 (SD 5.7). Table 1 presents results of logistic regression analyses for ascertaining depression-associated factors. Univariate logistic regression analyses revealed significant associations between the presence of depression and being female (OR ¼ 1.75, p < 0.01), the presence of disease currently treated (OR ¼ 2.02, p < 0.01), high FIRST score (OR ¼ 2.43, p < 0.01), and insomnia (OR ¼ 3.90, p < 0.01). A subsequent multivariate logistic regression analysis revealed significant associations between

Table 1 Logistic regression analyses on the factors associated with depression. Independent variables Age >43 years 43 years Sex Female Male Smoking habit Yes No Habitual alcohol drinking Yes No Living alone Yes No Disease currently treated Yes No Shift work Yes No FIRST score >18 18 PSQI score 5.5 <5.5

Subjects (%)

Unadjusted Odds Ratio (99% CI)

p value

Adjusted Odds Ratio (99% CI)

p value

1282 (48.5) 1357 (51.3)

0.82 (0.62e1.09)

n.s.

936 (35.4) 1707 (64.6)

1.75 (1.31e2.32)

<0.01

1.53 (1.12e2.10)

<0.01

412 (15.6) 2231 (84.4)

0.97 (0.85e1.11)

n.s.

686 (26.0) 1957 (74.0)

0.82 (0.59e1.15)

n.s.

340 (12.9) 2300 (87.0)

1.32 (0.89e1.95)

n.s.

775 (29.3) 1862 (70.5)

2.02 (1.51e2.71)

<0.01

1.84 (1.35e2.51)

<0.01

126 (4.8) 2517 (95.2)

1.66 (0.94e2.94)

n.s.

1504 (56.9) 1129 (42.7)

2.43 (1.78e3.34)

<0.01

1.78 (1.24e2.49)

<0.01

931 (35.2) 1695 (64.1)

3.90 (2.90e5.26)

<0.01

3.40 (2.49e4.66)

<0.01

Abbreviations: FIRST, The Ford Insomnia Response to Stress Test; PSQL, The Pittsburgh Sleep Quality Index; 99% CI, 99% Confidence Interval; n.s., Not Significant. Bold shows significance (p < .01).

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Fig. 1. Total score of the 12-item version of the Center for Epidemiological Studies Depression Scale (CES-D) after excluding insomnia items in the four groups divided by the presence/absence of insomnia (PSQI >5.5) and high FIRST (>18)/low FIRST (18). Abbreviation: *p < 0.01, n.s., not significant.

depression and female sex (OR ¼ 1.53, p < 0.01), presence of disease currently treated (OR ¼ 1.84, p < 0.01), high FIRST score (OR ¼ 1.78, p < 0.01), and insomnia (OR ¼ 3.40, p < 0.01). Fig. 1 presents the results of a comparison of the total CES-D score after excluding insomnia items among the four groups described above. The average scores of the CES-D were 2.3 (SD 3.7) in the group with low FIRST without insomnia, 3.9 (SD 4.2) in the group with high FIRST but without insomnia, 4.6 (SD 4.6) in the group with low FIRST with insomnia, and 8.2 (SD 6.2) in the group with high FIRST with insomnia. The scores were significantly different among the four groups (F [3, 2617] ¼ 209.5, p < 0.01, partial h2 ¼ 0.19). Post hoc analysis revealed a significantly higher score in the group with high FIRST with insomnia than in the group with low FIRST without insomnia (p < 0.01, d ¼ 1.19 [95% CI: 1.09, 1.29]), the group with high FIRST without insomnia (p < 0.01, d ¼ 0.82 [95% CI: 0.72, 0.92]), and the group with low FIRST with insomnia (p < 0.01, d ¼ 0.62 [95% CI: 0.44, 0.80]). The group with low FIRST with insomnia and the group with high FIRST without insomnia also had significantly higher CES-D scores than the group with low FIRST without insomnia (p < 0.01, d ¼ 0.59 [95% CI: 0.49, 0.69] for the group with low FIRST with insomnia vs the group with low FIRST without insomnia; p < 0.01, d ¼ 0.40 [95% CI: 0.31, 0.49] for the group with high FIRST without insomnia vs the group with low FIRST without insomnia). No significant difference was found for CES-D scores between the group with high FIRST without insomnia and the group with low FIRST with insomnia. 4. Discussion The percentage of diseases currently treated (29.3%) was almost equal to that reported from a previous study using the same questionnaire item (35%) [17]. In this study, as in previous studies [2,18,19], female sex, the presence of disease currently treated, and insomnia were found to be associated with depression. Moreover, results showed that higher FIRST was associated with depression, independent of insomnia. Drake et al. [10] emphasized not only the effects of sleep reactivity on depression through contact with insomnia but also the direct effects of sleep reactivity on depression [10]. The present findings support the results of Drake

et al. This finding suggests that higher sleep reactivity has considerable importance for the mechanisms of depression, irrespective of insomnia. It is noteworthy that the depression score of the group with higher sleep reactivity with insomnia was not only higher than that of the group with lower sleep reactivity with insomnia but also higher than that of the group with higher sleep reactivity without insomnia. The reason for this phenomenon remains unclear. However, considering that individuals with higher sleep reactivity react more negatively to stressors than those with lower sleep reactivity [8], individuals with higher sleep reactivity might feel greater stress from insomnia symptoms than individuals with lower sleep reactivity, leading to more severe depressive symptoms. This finding raises the possibility that the coexistence of higher sleep reactivity and insomnia might act additively or synergistically to aggravate depressive symptoms. Some limitations of this study must be noted. First, insomnia and depression symptoms were determined based on self-rated questionnaires without clinical interviews. In addition, PSQI might reflect the state of other sleep disorders because it is not an insomnia disorder-specific scale. Its low specificity might contribute to the lower association of the FIRST to PSQI than to CES-D. Second, no information related to other sleep disorders or psychiatric disorders that might affect insomnia or depression symptoms was obtained. Third, this study, with a cross-sectional design, could not clarify causal relations among sleep reactivity, insomnia, and depression. Fourth, it did not assess other insomniarelated variables, such as locus of control and anxiety level. Future prospective studies must be conducted to assess these variables. In conclusion, sleep reactivity manifested on FIRST might be associated with the development of depression, irrespective of the presence of insomnia. In addition, higher sleep reactivity and insomnia additively or synergistically aggravate depressive symptoms when they coexist. Acknowledgments A Health Labour Sciences Research Grant by the Ministry of Health, Labor, and Welfare of Japan supported this study.

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