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Associations between sleep duration and suicidality in adolescents: A systematic review and dose–response meta-analysis
Accepted Manuscript Associations Between Sleep Duration and Suicidality in Adolescents: A Systematic Review and Dose–Response Meta-Analysis Hsiao-Yean Chiu, Hsin-Chien Lee, Pin-Yuan Chen, Ying-Fan Lai, Yu-Kang Tu PII:
S1087-0792(17)30167-3
DOI:
10.1016/j.smrv.2018.07.003
Reference:
YSMRV 1116
To appear in:
Sleep Medicine Reviews
Received Date: 28 August 2017 Revised Date:
4 July 2018
Accepted Date: 5 July 2018
Please cite this article as: Chiu H-Y, Lee H-C, Chen P-Y, Lai Y-F, Tu Y-K, Associations Between Sleep Duration and Suicidality in Adolescents: A Systematic Review and Dose–Response Meta-Analysis, Sleep Medicine Reviews (2018), doi: 10.1016/j.smrv.2018.07.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Associations Between Sleep Duration and Suicidality in Adolescents: A Systematic Review and Dose–Response Meta-Analysis Running Heading: Sleep Duration and Suicidality Hsiao-Yean Chiu a,b, Hsin-Chien Lee b,c, Pin-Yuan Chen d,e, Ying-Fan Lai a, Yu-Kang Tu f
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AFFILIATIONS: a
School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan.
b
Research Center of Sleep Medicine, School of Medicine, Taipei Medical University, Taipei,
c
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Taiwan.
Department of Psychiatry, Taipei Medical University Shuang Ho Hospital, New Taipei City,
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Taiwan. d
Department of Neurosurgery, Chang Gung Memorial Hospital, Keelung, Taiwan
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School of Medicine, Chang Gung University, Taoyuan, Taiwan.
f
Department of Public Health, Institute of Epidemiology and Preventive Medicine, College of
Corresponding author Yu-Kang Tu
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Public Health, National Taiwan University, Taipei, Taiwan.
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Address: 17, Xu-Zhou Road, Taipei, Taiwan E-mail: [email protected]
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Tel.: +886 2 33668039 Fax: +886 2 23511955 Acknowledgment
The authors declare no potential conflicts of interest regarding the authorship and publication of this article. This meta-analysis was supported by grants from the Ministry of Science and Technology, Taiwan (MOST 106-2314-B-038 -058 -MY3 and MOST 106-2314-B-002 -098 -MY3).
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ACCEPTED MANUSCRIPT Summary
Sleep duration has received considerable attention as a potential risk factor of suicidality in youths; however, evidence on the dose–response association between sleep duration and
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suicidality has not been synthesized. This meta-analysis examined linear and nonlinear dose– response relationships between sleep duration and the risk of suicidality in adolescents and explored potential moderators of the associations. Electronic databases, namely EMBASE,
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PubMed, PsycINFO, Wanfang Data (Chinese database), and the China Knowledge Resource
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Integrated Database, were searched from their inception to April 18, 2017. Studies examining the association between sleep duration and suicidality in adolescents were included. A random-effects dose–response model was used to estimate the linear and nonlinear dose–
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response relationships. We identified 13 reports that included a total of 598,281 participants for a systematic review, and 12 reports were further used for a dose–response meta-analysis. Strong curvilinear dose–response associations were obtained for both suicidal ideation and
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attempts, with the lowest suicidal ideation and attempt risks at sleep durations of 8 h and 8–9
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h per day (all Pnonlinearity < .001). A linear dose–response relationship between sleep duration and suicide plans (pooled OR = 0.89, 95% confidence interval [CI] = 0.88–0.90) was obtained, indicating that the risk of suicide plans statistically decreased by 11% for every 1-h increase in sleep duration. Depression did not moderate the association between sleep duration and suicidality in youths. Our findings suggest curvilinear dose–response associations between sleep duration and the risks of suicidal ideation and attempts and a linear dose–response 2
ACCEPTED MANUSCRIPT relationship between sleep duration and suicide plan risk. Additional longitudinal studies are warranted to establish causality.
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Keywords: Dose–response meta-analysis, sleep duration, suicidality, adolescents
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ACCEPTED MANUSCRIPT INTRODUCTION Suicide in youth is a major public health concern. It has a global rate of 7.4 per 100 000 persons [1] and thus is the third leading cause of death in young boys and the second leading
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cause of death in young girls [2]. Suicidality is defined as suicidal ideation, plans, attempts, and suicide itself [3, 4]. The estimated worldwide lifetime prevalence for suicidal ideation
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ranged from 12.1% to 31.5% and that for suicide attempts ranged from 4.1% to 23.5% [5–8]. Identifying potentially modifiable risk factors of suicidality in adolescents is clinically
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relevant for reducing youth suicide rates.
Although several risk factors for youth suicidality have been identified, namely the female sex [9, 10], psychiatric or mental disorders [11], exposure to bullying and violence [12,
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13], substance abuse [14], weak family functioning [15]and low acceptance from peer groups [16], sleep duration has recently received considerable attention. The National Sleep
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Foundation recommends that the appropriate sleep duration for adolescents is between 8 and
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10 h [17]; however, because of social factors (eg, academic requirements or electronic media) [18] and biological characteristics (e.g., the tendency towards delayed sleep phase coupled with fixed wake up times) (19, 20), more than half of adolescents (53.6%) sleep fewer than 8 h [21].
Over the past decade, several large-scale cross-sectional studies [22–34] have reported inconsistent findings on the association between sleep duration and the risk of youth suicidality. Some studies have suggested a negative association [23, 24]), whereas some have 4
ACCEPTED MANUSCRIPT reported that both shorter and longer sleep durations increased the risk of youth suicidality [25, 34]. Two previous meta-analyses that investigated the associations between sleep disturbances and suicidality in the general population [35] and in patients with psychiatric diagnoses [36]
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revealed that sleep disturbance (e.g., insomnia, nightmares, parasomnia, and sleep-related breathing disorder) substantially increased the risk of suicidality (relative risk = 1.95 to 2.95,
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and odds ratio [OR] = 1.99, respectively). At present, there is no systematic review and
meta-analysis that investigates the relevance of sleep duration to suicidality in adolescents.
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Because suicide is a major concern for adolescent health, the association between sleep duration and youth suicidality may be crucial for detecting, treating, and potentially preventing youth suicide. We therefore conducted a systematic review and dose–response
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meta-analysis to investigate the association between sleep duration and the risks of suicidal ideation, plans, and attempts in adolescents. In addition, we examined the moderating effects
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of the participants’ characteristics and methodological features on the relationship between
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sleep duration and suicidality. Methods
Search strategies and selection criteria This dose–response meta-analysis was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses [37]. A systematic literature search was performed in all fields in EMBASE, PubMed, PsycINFO, ProQuest Dissertations & Theses A&I, Wanfang Data (Chinese database), and the China Knowledge Resource Integrated 5
ACCEPTED MANUSCRIPT Database from their inception to April 18, 2017. The combinations of keywords used are listed as follows: (sleep duration OR sleep time) AND (suicidal ideation OR suicidal plan OR suicidal attempt) AND (adolescent). An example of a search string is provided in Table S1.
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We also manually searched the reference lists of included studies and relevant published reports and contacted study authors.
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We included studies with a cross-sectional, case–control, or cohort study design that evaluated the association between sleep duration and suicidal ideation, plans, or attempts in
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adolescents. No language restriction was applied. If the data of the included studies were incomplete for the analyses, the authors would be contacted to obtain additional information. Two investigators (HYC and YFL) independently searched, screened, and evaluated all
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relevant studies according to the eligibility criteria. Any disagreement was resolved through discussion with a third researcher (PYC).
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Data extraction and assessment of the study quality
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Two investigators (HYC and YFL) independently extracted data from included studies by using a predesigned data extraction form, including the author names, publication year, country where the study was conducted, average age of the study population, percentage of female participants, sample size, outcome variables, and adjusted covariates. Disagreements were resolved through discussion. The Critical Appraisal Checklist recommended by the Joanna Briggs Institute was used to assess the methodological quality of the included studies [38]. The checklist comprises 8 6
ACCEPTED MANUSCRIPT items, and each item is rated as “yes,” “no,” or “unclear.” The included studies were independently evaluated by two researchers (HYC and YFL). Any disagreement was resolved by consensus through face-to-face discussion.
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Data synthesis and analysis The odds ratio (OR) with a 95% confidence interval (CI) was used as a measurement of
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the association between sleep duration and the risks of suicidal ideation, plans, and attempts. For the dose-response meta-analysis, the reported mean of each sleep duration category was
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used. When the ranges of sleep duration categories were reported, we used the average value of the lower and upper bounds of each category. When the lowest category was open ended, the average value of the upper bound and 0 was used. When the highest category was open
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ended, the average value was assumed to be 1.2 times the lower boundary [39]. The highest versus the lowest category of sleep duration in the included studies was first
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analyzed using a random-effects meta-analysis (high versus low meta-analysis) [40]. In the
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dose–response meta-analysis, only studies with at least 3 exposure categories were included (41). We first examined the linear trends of the association between exposure and outcomes by using the method described by Greenland and Longnecker [42, 43]. The estimated linear trends were then pooled using random-effects meta-analysis [40]. For the nonlinear dose– response trends, we used the restricted cubic splines with 4 knots (percentiles of 5%, 35%, 65%, and 95%) [42, 44], and the results from each study were then pooled using random-effects multivariate meta-analysis [45, 46]. A likelihood ratio test was performed to 7
ACCEPTED MANUSCRIPT compare the difference between the linear and nonlinear models [44]. When the lowest category was not the reference category,, we used the method described by Hamling et al [47]. to convert the reported odds ratios to those with the lowest category of sleep duration as the
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reference category. Heterogeneity between studies was assessed using the Q test and I2 statistics, which
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quantify the total variation explained by between-study variation. Subgroup analyses were performed to explain the observed heterogeneity among studies. In the current study, we did
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not give a score to assess study quality; however, we examined indicators of study quality, including sample size and the adjustment for depression, which might have modified our results. Additional factors such as age, the percentage of women, and the country where the
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study was conducted were assessed using subgroup analyses and metaregression. Heterogeneity between subgroups was determined using metaregression. Furthermore, we
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performed a sensitivity analysis to examine the robustness of our findings by excluding 1
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study at a time and recalculating the pooled estimates. RESULTS
Search results and study characteristics We initially identified 640 articles and screened their titles and abstracts (Figure 1). After duplicates and irrelevant articles were excluded, 10 cross-sectional studies [22-25, 27, 29-31, 34, 48] met the inclusion criteria and were thus included for our systematic review and meta-analysis. Because one study [34] reported rate ratios in two adolescent populations in 8
ACCEPTED MANUSCRIPT 2007 and 2009 and two [31, 48] exclusively reported sex-specific rate ratios, 13 reports were included for the final analyses. For the dose–response meta-analysis, we excluded one study [22] with only two sleep duration categories, because at least three exposure categories were
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required to estimate the study-specific trend. Twelve reports were then included for the dose– response meta-analysis. A list of studies excluded after a full-text review is presented in Table
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S2.
Overall, 598,281 adolescents with a mean age of 15.5 years (ranging from 14.6 to 16.3
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years) were included. The average percentage of female adolescents was 48.8%. Only one report was published in Chinese. Of the reports, seven were conducted in South Korea, three in China, and three in the United States. Sleep duration was measured using a self-reported
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sleep duration frequency question in all of the included studies except one, which used the Pittsburgh Sleep Quality Index [22]. Of which, six reports [25, 30, 31, 48] focused on the
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weekday average sleep duration (Monday–Friday) and others investigated the mean sleep
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duration on weekdays and weekends. Several reference categories of exposure were used in the included studies. Four reports used ≥8 h/d as the reference category, three used 8 h/d, two used 6–7 h/d, one used 7–8 h/d, one used 7 h/d, and one used ≥9 h/d. Most reports assessed suicidal ideation, plans, or attempts during the past 12 months using one question; one study [29] focused on the past 6 months. All studies adjusted for potential covariates (Table S3 and S4). Quality of Studies 9
ACCEPTED MANUSCRIPT The results of the Critical Appraisal Checklist assessment of the included studies are presented in Table S5. No article met all eight criteria for a high methodological quality. None of the studies applied the valid and reliable tools in measuring sleep duration and suicidality.
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High vs low metaanalysis In terms of the risk of suicidal ideation, 13 reports [22-25, 27, 29-31, 34, 48] were
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included in the high versus low meta-analysis. The pooled OR was 0.55 (95% CI = 0.47–0.65),
for those with greater sleep duration.
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with evidence of heterogeneity (P < .001, I2 = 92.5%, Figure S1A), suggesting a lower risk
With regards to the risk of suicidal plans, we included six reports [22, 27, 31, 34] in the analysis of high versus low meta-analysis (Figure S1B). The pooled OR was 0.50 (95% CI =
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0.44–0.56) for those with the longest sleep duration compared with those with the shortest sleep duration, with no evidence of heterogeneity (P = .57, I2 = 0.0%).
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For the risk of youth suicide attempts, we included 11 reports (Figure S1C) [22, 25, 27,
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29-31, 34, 48]. The pooled OR was 0.52 (95% CI = 0.41–0.66), with evidence of heterogeneity (P < .0001, I2 = 78.5%). Dose-response association between sleep duration and the risk of suicidal ideation, plans, and attempts
Figure 2A shows the results of the linear and nonlinear dose–response relationship between sleep duration and suicidal ideation. The likelihood ratio test suggested nonlinearity (P = .00003), indicating that there was a nonlinear relationship between sleep duration and 10
ACCEPTED MANUSCRIPT suicidal ideation (Pheterogeneity < .001, I2 = 95.4%), with a U-shaped dose–response curve. The lowest risk of suicidal ideation was observed with a sleep duration of 9 h. Figure 2B presents the results of the linear and nonlinear dose-response relationship
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between sleep duration and suicide plans. The likelihood ratio test suggested linearity (P = .15), and the pooled OR of suicide plans for a 1-h increase in sleep duration was 0.89 (95%
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CI = 0.88–0.90) (i.e., the risk of suicide plans decreased by 11% for every 1-h increase in sleep duration, with no heterogeneity across the included studies (P = .16, I2 = 39.7%).
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Figure 2C shows the results of the linear and nonlinear dose-response relationship between sleep duration and suicide attempts. The likelihood ratio test suggested nonlinearity (P = .0006), indicating a significant nonlinear dose–response relationship (P heterogeneity < .001,
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I2 = 94.1%) with a U-shaped dose–response curve. The lowest risk of suicide attempts was observed with a sleep duration of 8–9 h.
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Subgroup analysis, metaregression, and sensitivity analyses
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Subgroup analyses and metaregression analyses for the high versus low analyses are presented in Table 1. No significant factor explaining the observed heterogeneity was identified for suicidal ideation, plans, or attempts. Notably, the studies that adjusted for depression had an OR comparable with that of studies that did not. Sensitivity analyses demonstrated similar results (Table S6), indicating that the overall results were not significantly influenced by any single study, with ORs and 95% CIs ranging from 0.54 (0.46–0.63) to 0.57 (0.48–0.67) for suicidal ideation, 0.44 (0.36–0.55) to 0.51 11
ACCEPTED MANUSCRIPT (0.45–0.57) for suicide plans, and 0.49 (0.38–0.62) to 0.55 (0.43–0.70) for suicide attempts. DISCUSSION In this dose–response meta-analysis, we found a U-shaped association between sleep
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duration and youth suicidal ideation and attempts incidence. We also found a negative linear dose-response association in youth suicidal plans. Every 1-h increase in sleep duration led to a
factor for the development of youth suicidality.
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decreased risk of 11% of suicide plans in adolescents. Sleep duration is an independent risk
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Suicide is a multifactorial behavior, and our findings suggest that adequate sleep may be a protective factor that reduces the suicide rate in adolescents. Mechanisms linking sleep to suicidality may differ between short and long sleep durations. One possibility is that being
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awake at night creates a window of vulnerability with respect to suicidality. That is, both sleep deprivation and circadian effects compromise daytime and nighttime frontal lobe
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function/executive function. Hypoactivation of the frontal lobe could diminish
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problem-solving abilities and increase impulsive behavior, both of which may increase suicide risk [49]. The serotonergic system has been proposed to mediate the association between short sleep duration and suicide [50]. A previous study reported that the prefrontal cortex exhibited low serotonin synthesis in suicide attempters compared with healthy controls [51]. Lower neuron density and deficient serotonin input in the prefrontal cortex, which controls executive function, may contribute to impulsive aggressive traits that cause suicidality [52, 53]. Serotonin and its receptors in the brain also play a critical role in sleep– 12
ACCEPTED MANUSCRIPT wake regulation. Serotonin secretion is highest during wakefulness and decreases during sleep [54]. Increasing evidence suggests that restricted sleep results in loss of sensitivity or desensitization of postsynaptic serotonin receptors (55, 56). Under these scenarios, reduced
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sleep duration might lead to a loss of serotonin function and thus adversely affect impulse control and judgment, which in turn increases the likelihood of suicide.
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Explanations for the relationship between long sleep duration and increased suicidality are currently speculative. The relevant literature demonstrates that depressive symptoms play
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a moderating role in the linkage between a long sleep duration and suicidality, as evidenced by the relationship disappearing after adjustment for depressive mood [57]. Nonetheless, our results from subgroup analyses indicated no moderating role, which is consistent with
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previous meta-analyses [35, 36], showing that depression did not moderate the association between sleep disturbances and suicidality. Collectively, studies have suggested that the
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maintenance of sleep may be involved in suicidality independent of depression. The elevation
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of serotonergic activity caused by increased sleep duration might be a possible explanation [50]. Because the underlying mechanisms are still not well understood, further investigations are warranted.
Our meta-analysis has several limitations. First, because of the cross-sectional design of the included studies, we need to be cautious when making causal inferences about the relationship between sleep duration and youth suicidality. Second, most of the included studies used self-reported questionnaires with a single item measuring sleep duration and 13
ACCEPTED MANUSCRIPT suicidality; thus, recall bias could not be excluded. Third, our study participants were mostly from schools, and adolescents who dropped out of school or were not present at school were not included, which might limit the generalizability of the current dose–response
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meta-analysis. Fourth, because of only a few studies included, a publication bias test was not utilized in the current study. The potential for publication bias could not be excluded.
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Nevertheless, we employed a robust search strategy and included a large-scale sample, which greatly increased the statistical power for detecting the dose–response associations between
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sleep duration and youth suicidal ideation, plans, and attempts. Moreover, the sensitivity analyses provided solid evidence of the robustness of our findings. In addition, the inclusion of studies from various geographic areas substantially increased the generalizability of our
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findings.
In summary, our meta-analysis provides evidence to support that sleep duration plays an
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important role in the development of youth suicidal behaviours. Our findings suggests that
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both long and short sleep duration are significantly associated with an increased incident risk of suicidal ideation and attempts, with the lowest risks of suicidal ideation and attempt at sleep durations of 8–9 h per day. In addition, we noted an 11% reduction in the risk of suicide plans for every 1-h increase in sleep duration. These findings have substantial public health implications and suggest increasing the sleep duration for the prevention of youth suicidal ideation, plans, and attempts. Prospective longitudinal studies with longer follow-up times are required to establish causality and to elucidate the underlying mechanisms. Prospective 14
ACCEPTED MANUSCRIPT studies investigating the relationships between sleep deprivation and suicidal ideation in
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healthy and clinical subjects are required.
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ACCEPTED MANUSCRIPT Practice points 1.
U-shaped associations of sleep duration with the risk of suicidal ideation and attempts are observed, with lowest suicidal ideation and attempts risks at sleep durations of 8–9 h per day. A linear relationship between sleep duration and suicidal plan is found, with an 11%
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2.
reduction in suicide plans risk for every 1-h increase in sleep duration. 3.
Appropriate sleep duration should be considered as one of influencing factors in
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developing preventive strategies of youth suicidal ideation, plans, and attempts.
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Research agenda Future studies should:
1. Adopt a longitudinal study design to investigate the causality of sleep duration and suicidality and its underlying mechanisms.
2. Conduct prospective studies to examine the association between sleep deprivation and
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suicidal ideation in healthy and clinical subjects. 3. Employ objective instruments such as actigraphs to assess sleep duration to allow more precise estimations of sleep duration.
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4. Develop interventions for targeting the issues of sleep duration in adolescents.
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[44] Desquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 2010;29:1037-57.
[45] White IR. Multivariate random-effects meta-analysis. STAT J 2009;9:40-56.
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[46] Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose-response data. STAT J 2006;6:40-57.
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[47] Hamling J, Lee P, Weitkunat R, Ambuhl M. Facilitating meta-analyses by deriving
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relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category. Stat Med 2008;27:954-70. [48] Jang SI, Lee KS, Park EC. Relationship between current sleep duration and past suicidal ideation or attempt among korean adolescents. J Prev Med Public Health 2013;46:329-35. *[49]Perlis ML, Grandner MA, Chakravorty S, Bernert RA, Brown GK, Thase ME. Suicide and sleep: is it a bad thing to be awake when reason sleeps? Sleep Med Rev 2016;29:101-7. 22
ACCEPTED MANUSCRIPT *[50]Kohyama J. Sleep, serotonin, and suicide in Japan. J Physiol Anthropol 2011;30:1-8. [51] Leyton M, Paquette V, Gravel P, Rosa-Neto P, Weston F, Diksic M, et al. alpha-[11C]Methyl-L-tryptophan trapping in the orbital and ventral medial prefrontal
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cortex of suicide attempters. Eur Neuropsychopharmacol 2006;16:220-3. *[52]Mann JJ. The serotonergic system in mood disorders and suicidal behaviour. Philos
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Trans R Soc Lond B Biol Sci 2013;368:20120537.
[53] Underwood MD, Kassir SA, Bakalian MJ, Galfalvy H, Mann JJ, Arango V. Neuron
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Density and Serotonin Receptor Binding in Prefrontal Cortex in Suicide. Int J Neuropsychopharmacol 2012;15:435-47.
[54] Portas CM, Bjorvatn B, Ursin R. Serotonin and the sleep/wake cycle: special emphasis on
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microdialysis studies. Progress in neurobiology. 2000;60(1):13-35. [55] Roman V, Walstra I, Luiten PG, Meerlo P. Too little sleep gradually desensitizes the
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serotonin 1A receptor system. Sleep 2005;28:1505-10.
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[56] Novati A, Roman V, Cetin T, Hagewoud R, den Boer JA, Luiten PG, et al. Chronically restricted sleep leads to depression-like changes in neurotransmitter receptor sensitivity and neuroendocrine stress reactivity in rats. Sleep 2008;31:1579-85. [57] Kim JH, Park EC, Cho WH, Park CY, Choi WJ, Chang HS. Association between total sleep duration and suicidal ideation among the Korean general adult population. Sleep 2013;36:1563-72.
23
Table 1 Metaregression and subgroup analyses ACCEPTED Factors
MANUSCRIPT
I2 (%)
Point (95% CI)
n
P for heterogeneity*
estimate Suicidal ideation (n = 13) Metaregression Mean age
8
-0.29 (-0.59 to 0.003)
85.6
Female percentage
13
0.0002 (-0.005 to 0.006)
92.8
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Subgroup analyses Sample size
0.19
≥20,000
8
0.52 (0.42 to 0.63)
94.9
<20,000
5
0.64 (0.53 to 0.78)
55.4
Study region
0.33
3
0.58 (0.40 to 0.84)
85.2
South Korea
7
0.53 (0.43 to 0.66)
95.5
USA
3
0.59 (0.40 to 0.87)
76.3
Yes
6
No
7
Statistical adjusted for depression 8
No
5
Statistical adjusted for smoking Yes No
Yes No
0.76
0.57 (0.49 to 0.66)
85.4
0.54 (0.43 to 0.69)
91.0 0.14
0.60 (0.51 to 0.70)
88.1
0.48 (0.37 to 0.62)
89.3 0.71
7
0.54 (0.45 to 0.64)
90.5
6
0.58 (0.43 to 0.78)
92.1
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Statistical adjusted for drinking
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Yes
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Weekday sleep duration
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China
0.71
7
0.54 (0.45 to 0.64)
90.5
6
0.58 (0.43 to 0.78)
92.1
Yes No
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Statistical adjusted for drug use
0.36
3
0.49 (0.38 to 0.63)
85.7
10
0.58 (0.48 to 0.70)
93.5
Statistical adjusted for other sleep variables†
0.13
Yes
6
0.62 (0.51 to 0.76)
89.7
No
7
0.50 (0.41 to 0.61)
88.5
Mean age
5
0.016 (-0.52 to 0.54)
0
Female percentage
6
0.001 (-0.008 to 0.011)
0
Suicidal plan(n = 6) Metaregression
Subgroup analyses Sample size
0.19
3 0.41 (0.32 to 0.53) ACCEPTED MANUSCRIPT
≥20,000 <20,000
3
0.52 (0.46 to 0.59)
0 0
Study region
0.64
China and South Korea
4
0.49 (0.43 to 0.56)
2.4
America
2
0.54 (0.35 to 0.81)
0
Weekday sleep duration
0.46 2
0.50 (0.44 to 0.60)
0
No
4
0.51 (0.45 to 0.57)
0
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Yes
0.19
Statistical adjusted for depression Yes
3
0.41 (0.32 to 0.53)
0
No
3
0.52 (0.46 to 0.59)
0
Statistical adjusted for smoking
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0.19
3
0.41 (0.32 to 0.53)
0
No
3
0.52 (0.46 to 0.59)
0
Statistical adjusted for drinking Yes
3
No
3
Statistical adjusted for other sleep †
variables
3
No Suicidal attempt (n = 11) Metaregression
Female percentage Subgroup analyses
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Sample size
0.41 (0.32 to 0.53)
0
0.52 (0.46 to 0.59)
0 0.19 0
3
0.52 (0.46 to 0.59)
0
7
0.38 (-0.097 to 0.852)
47.2
11
0.003 (-0.007 to 0.012)
80.6
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Mean age
0.19
0.41 (0.32 to 0.53)
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Yes
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Yes
0.82
≥20,000
7
0.53 (0.38 to 0.73)
85.4
<20,000
4
0.50 (0.41 to 0.61)
0
Study regions China
0.80 3
0.58 (0.39 to 0.87)
77.2
South Korea
6
0.49 (0.32 to 0.74)
86.3
America
2
0.56 (0.32 to 0.96)
5.4
Weekday sleep duration
0.65
Yes
6
0.49 (0.34 to 0.70)
87.3
No
5
0.55 (0.42to 0.73)
21.6 0.44
Adjusted for depression Yes
7
0.47 (0.32 to 0.70)
83.9
No
4
0.60 (0.44 to 0.83)
66.2
ACCEPTED MANUSCRIPT
Statistical adjusted for smoking
0.82
Yes
7
0.50 (0.41 to 0.61)
85.4
No
4
0.53 (0.38 to 0.73)
78.5
Statistical adjusted for drinking
0.65
Yes
6
0.49 (0.34 to 0.70)
87.3
No
5
0.55 (0.42 to 0.73)
21.6
Statistical adjusted for drug use
0.95 3
0.51 (0.31 to 0.84)
71.1
No
8
0.52 (0.39 to 0.70)
81.0
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Yes
Statistical adjusted for other sleep
0.97
†
variables
5
0.51 (0.30 to 0.86)
No
6
0.53 (0.40 to 0.69)
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Yes
68.5 86.4
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CI = confidence interval. * Between subgroups with metaregression analysis. † perception of getting enough sleep, awakening time and bedtime, nightmares and insomnia, restorative sleep,
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and chronotype.
ACCEPTED MANUSCRIPT
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Potentially relevant articles identified (n = 640) 33 EMBASE 34 PubMed 1 PsycINFO 567 ProQuest Dissertations & Theses A&I 4 Wanfang Data Chinese database 0 China Knowledge Resource Integrated Database 1 Hand searching by checking the reference lists of included studies
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Articles excluded after screening of title and abstract (n = 627) - Did not report the sleep duration - Did not mention suicidality
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Full text articles extracted for detailed evaluation (n = 13) Excluded (n = 3) -Did not report sleep duration category
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10 eligible articles were included and 1 article had rate ratios in different years (i.e., 2007 and 2009) and 2 exclusively involved gender specific rate ratios, resulting in 13 eligible reports for systematic review
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Articles included in systematic review (n = 13) Suicidal ideations (n = 13) Suicidal plans (n = 6) Suicidal attempts (n = 11)
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Articles with only 2 sleep duration categories (n = 1) was excluded from dose-response metaanalysis
Articles included in dose-response metaanalysis (n = 12) Suicidal ideations (n = 12) Suicidal plans (n = 5) Suicidal attempts (n = 10)
Figure 1 Flow chart of literatures search for studies investigating association between sleep duration and the risks of suicidal ideations, plans, and attempts.
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(B)
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Figure 2 the linear and non-linear associations of sleep duration with (A) suicidal ideation, (B) suicidal plan, (C) suicidal attempt.
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(C)
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(A)
S1087-0792(17)30167-3
DOI:
10.1016/j.smrv.2018.07.003
Reference:
YSMRV 1116
To appear in:
Sleep Medicine Reviews
Received Date: 28 August 2017 Revised Date:
4 July 2018
Accepted Date: 5 July 2018
Please cite this article as: Chiu H-Y, Lee H-C, Chen P-Y, Lai Y-F, Tu Y-K, Associations Between Sleep Duration and Suicidality in Adolescents: A Systematic Review and Dose–Response Meta-Analysis, Sleep Medicine Reviews (2018), doi: 10.1016/j.smrv.2018.07.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Associations Between Sleep Duration and Suicidality in Adolescents: A Systematic Review and Dose–Response Meta-Analysis Running Heading: Sleep Duration and Suicidality Hsiao-Yean Chiu a,b, Hsin-Chien Lee b,c, Pin-Yuan Chen d,e, Ying-Fan Lai a, Yu-Kang Tu f
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AFFILIATIONS: a
School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan.
b
Research Center of Sleep Medicine, School of Medicine, Taipei Medical University, Taipei,
c
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Taiwan.
Department of Psychiatry, Taipei Medical University Shuang Ho Hospital, New Taipei City,
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Taiwan. d
Department of Neurosurgery, Chang Gung Memorial Hospital, Keelung, Taiwan
e
School of Medicine, Chang Gung University, Taoyuan, Taiwan.
f
Department of Public Health, Institute of Epidemiology and Preventive Medicine, College of
Corresponding author Yu-Kang Tu
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Public Health, National Taiwan University, Taipei, Taiwan.
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Address: 17, Xu-Zhou Road, Taipei, Taiwan E-mail: [email protected]
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Tel.: +886 2 33668039 Fax: +886 2 23511955 Acknowledgment
The authors declare no potential conflicts of interest regarding the authorship and publication of this article. This meta-analysis was supported by grants from the Ministry of Science and Technology, Taiwan (MOST 106-2314-B-038 -058 -MY3 and MOST 106-2314-B-002 -098 -MY3).
1
ACCEPTED MANUSCRIPT Summary
Sleep duration has received considerable attention as a potential risk factor of suicidality in youths; however, evidence on the dose–response association between sleep duration and
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suicidality has not been synthesized. This meta-analysis examined linear and nonlinear dose– response relationships between sleep duration and the risk of suicidality in adolescents and explored potential moderators of the associations. Electronic databases, namely EMBASE,
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PubMed, PsycINFO, Wanfang Data (Chinese database), and the China Knowledge Resource
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Integrated Database, were searched from their inception to April 18, 2017. Studies examining the association between sleep duration and suicidality in adolescents were included. A random-effects dose–response model was used to estimate the linear and nonlinear dose–
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response relationships. We identified 13 reports that included a total of 598,281 participants for a systematic review, and 12 reports were further used for a dose–response meta-analysis. Strong curvilinear dose–response associations were obtained for both suicidal ideation and
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attempts, with the lowest suicidal ideation and attempt risks at sleep durations of 8 h and 8–9
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h per day (all Pnonlinearity < .001). A linear dose–response relationship between sleep duration and suicide plans (pooled OR = 0.89, 95% confidence interval [CI] = 0.88–0.90) was obtained, indicating that the risk of suicide plans statistically decreased by 11% for every 1-h increase in sleep duration. Depression did not moderate the association between sleep duration and suicidality in youths. Our findings suggest curvilinear dose–response associations between sleep duration and the risks of suicidal ideation and attempts and a linear dose–response 2
ACCEPTED MANUSCRIPT relationship between sleep duration and suicide plan risk. Additional longitudinal studies are warranted to establish causality.
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Keywords: Dose–response meta-analysis, sleep duration, suicidality, adolescents
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ACCEPTED MANUSCRIPT INTRODUCTION Suicide in youth is a major public health concern. It has a global rate of 7.4 per 100 000 persons [1] and thus is the third leading cause of death in young boys and the second leading
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cause of death in young girls [2]. Suicidality is defined as suicidal ideation, plans, attempts, and suicide itself [3, 4]. The estimated worldwide lifetime prevalence for suicidal ideation
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ranged from 12.1% to 31.5% and that for suicide attempts ranged from 4.1% to 23.5% [5–8]. Identifying potentially modifiable risk factors of suicidality in adolescents is clinically
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relevant for reducing youth suicide rates.
Although several risk factors for youth suicidality have been identified, namely the female sex [9, 10], psychiatric or mental disorders [11], exposure to bullying and violence [12,
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13], substance abuse [14], weak family functioning [15]and low acceptance from peer groups [16], sleep duration has recently received considerable attention. The National Sleep
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Foundation recommends that the appropriate sleep duration for adolescents is between 8 and
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10 h [17]; however, because of social factors (eg, academic requirements or electronic media) [18] and biological characteristics (e.g., the tendency towards delayed sleep phase coupled with fixed wake up times) (19, 20), more than half of adolescents (53.6%) sleep fewer than 8 h [21].
Over the past decade, several large-scale cross-sectional studies [22–34] have reported inconsistent findings on the association between sleep duration and the risk of youth suicidality. Some studies have suggested a negative association [23, 24]), whereas some have 4
ACCEPTED MANUSCRIPT reported that both shorter and longer sleep durations increased the risk of youth suicidality [25, 34]. Two previous meta-analyses that investigated the associations between sleep disturbances and suicidality in the general population [35] and in patients with psychiatric diagnoses [36]
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revealed that sleep disturbance (e.g., insomnia, nightmares, parasomnia, and sleep-related breathing disorder) substantially increased the risk of suicidality (relative risk = 1.95 to 2.95,
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and odds ratio [OR] = 1.99, respectively). At present, there is no systematic review and
meta-analysis that investigates the relevance of sleep duration to suicidality in adolescents.
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Because suicide is a major concern for adolescent health, the association between sleep duration and youth suicidality may be crucial for detecting, treating, and potentially preventing youth suicide. We therefore conducted a systematic review and dose–response
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meta-analysis to investigate the association between sleep duration and the risks of suicidal ideation, plans, and attempts in adolescents. In addition, we examined the moderating effects
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of the participants’ characteristics and methodological features on the relationship between
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sleep duration and suicidality. Methods
Search strategies and selection criteria This dose–response meta-analysis was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses [37]. A systematic literature search was performed in all fields in EMBASE, PubMed, PsycINFO, ProQuest Dissertations & Theses A&I, Wanfang Data (Chinese database), and the China Knowledge Resource Integrated 5
ACCEPTED MANUSCRIPT Database from their inception to April 18, 2017. The combinations of keywords used are listed as follows: (sleep duration OR sleep time) AND (suicidal ideation OR suicidal plan OR suicidal attempt) AND (adolescent). An example of a search string is provided in Table S1.
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We also manually searched the reference lists of included studies and relevant published reports and contacted study authors.
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We included studies with a cross-sectional, case–control, or cohort study design that evaluated the association between sleep duration and suicidal ideation, plans, or attempts in
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adolescents. No language restriction was applied. If the data of the included studies were incomplete for the analyses, the authors would be contacted to obtain additional information. Two investigators (HYC and YFL) independently searched, screened, and evaluated all
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relevant studies according to the eligibility criteria. Any disagreement was resolved through discussion with a third researcher (PYC).
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Data extraction and assessment of the study quality
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Two investigators (HYC and YFL) independently extracted data from included studies by using a predesigned data extraction form, including the author names, publication year, country where the study was conducted, average age of the study population, percentage of female participants, sample size, outcome variables, and adjusted covariates. Disagreements were resolved through discussion. The Critical Appraisal Checklist recommended by the Joanna Briggs Institute was used to assess the methodological quality of the included studies [38]. The checklist comprises 8 6
ACCEPTED MANUSCRIPT items, and each item is rated as “yes,” “no,” or “unclear.” The included studies were independently evaluated by two researchers (HYC and YFL). Any disagreement was resolved by consensus through face-to-face discussion.
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Data synthesis and analysis The odds ratio (OR) with a 95% confidence interval (CI) was used as a measurement of
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the association between sleep duration and the risks of suicidal ideation, plans, and attempts. For the dose-response meta-analysis, the reported mean of each sleep duration category was
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used. When the ranges of sleep duration categories were reported, we used the average value of the lower and upper bounds of each category. When the lowest category was open ended, the average value of the upper bound and 0 was used. When the highest category was open
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ended, the average value was assumed to be 1.2 times the lower boundary [39]. The highest versus the lowest category of sleep duration in the included studies was first
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analyzed using a random-effects meta-analysis (high versus low meta-analysis) [40]. In the
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dose–response meta-analysis, only studies with at least 3 exposure categories were included (41). We first examined the linear trends of the association between exposure and outcomes by using the method described by Greenland and Longnecker [42, 43]. The estimated linear trends were then pooled using random-effects meta-analysis [40]. For the nonlinear dose– response trends, we used the restricted cubic splines with 4 knots (percentiles of 5%, 35%, 65%, and 95%) [42, 44], and the results from each study were then pooled using random-effects multivariate meta-analysis [45, 46]. A likelihood ratio test was performed to 7
ACCEPTED MANUSCRIPT compare the difference between the linear and nonlinear models [44]. When the lowest category was not the reference category,, we used the method described by Hamling et al [47]. to convert the reported odds ratios to those with the lowest category of sleep duration as the
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reference category. Heterogeneity between studies was assessed using the Q test and I2 statistics, which
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quantify the total variation explained by between-study variation. Subgroup analyses were performed to explain the observed heterogeneity among studies. In the current study, we did
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not give a score to assess study quality; however, we examined indicators of study quality, including sample size and the adjustment for depression, which might have modified our results. Additional factors such as age, the percentage of women, and the country where the
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study was conducted were assessed using subgroup analyses and metaregression. Heterogeneity between subgroups was determined using metaregression. Furthermore, we
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performed a sensitivity analysis to examine the robustness of our findings by excluding 1
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study at a time and recalculating the pooled estimates. RESULTS
Search results and study characteristics We initially identified 640 articles and screened their titles and abstracts (Figure 1). After duplicates and irrelevant articles were excluded, 10 cross-sectional studies [22-25, 27, 29-31, 34, 48] met the inclusion criteria and were thus included for our systematic review and meta-analysis. Because one study [34] reported rate ratios in two adolescent populations in 8
ACCEPTED MANUSCRIPT 2007 and 2009 and two [31, 48] exclusively reported sex-specific rate ratios, 13 reports were included for the final analyses. For the dose–response meta-analysis, we excluded one study [22] with only two sleep duration categories, because at least three exposure categories were
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required to estimate the study-specific trend. Twelve reports were then included for the dose– response meta-analysis. A list of studies excluded after a full-text review is presented in Table
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S2.
Overall, 598,281 adolescents with a mean age of 15.5 years (ranging from 14.6 to 16.3
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years) were included. The average percentage of female adolescents was 48.8%. Only one report was published in Chinese. Of the reports, seven were conducted in South Korea, three in China, and three in the United States. Sleep duration was measured using a self-reported
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sleep duration frequency question in all of the included studies except one, which used the Pittsburgh Sleep Quality Index [22]. Of which, six reports [25, 30, 31, 48] focused on the
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weekday average sleep duration (Monday–Friday) and others investigated the mean sleep
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duration on weekdays and weekends. Several reference categories of exposure were used in the included studies. Four reports used ≥8 h/d as the reference category, three used 8 h/d, two used 6–7 h/d, one used 7–8 h/d, one used 7 h/d, and one used ≥9 h/d. Most reports assessed suicidal ideation, plans, or attempts during the past 12 months using one question; one study [29] focused on the past 6 months. All studies adjusted for potential covariates (Table S3 and S4). Quality of Studies 9
ACCEPTED MANUSCRIPT The results of the Critical Appraisal Checklist assessment of the included studies are presented in Table S5. No article met all eight criteria for a high methodological quality. None of the studies applied the valid and reliable tools in measuring sleep duration and suicidality.
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High vs low metaanalysis In terms of the risk of suicidal ideation, 13 reports [22-25, 27, 29-31, 34, 48] were
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included in the high versus low meta-analysis. The pooled OR was 0.55 (95% CI = 0.47–0.65),
for those with greater sleep duration.
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with evidence of heterogeneity (P < .001, I2 = 92.5%, Figure S1A), suggesting a lower risk
With regards to the risk of suicidal plans, we included six reports [22, 27, 31, 34] in the analysis of high versus low meta-analysis (Figure S1B). The pooled OR was 0.50 (95% CI =
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0.44–0.56) for those with the longest sleep duration compared with those with the shortest sleep duration, with no evidence of heterogeneity (P = .57, I2 = 0.0%).
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For the risk of youth suicide attempts, we included 11 reports (Figure S1C) [22, 25, 27,
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29-31, 34, 48]. The pooled OR was 0.52 (95% CI = 0.41–0.66), with evidence of heterogeneity (P < .0001, I2 = 78.5%). Dose-response association between sleep duration and the risk of suicidal ideation, plans, and attempts
Figure 2A shows the results of the linear and nonlinear dose–response relationship between sleep duration and suicidal ideation. The likelihood ratio test suggested nonlinearity (P = .00003), indicating that there was a nonlinear relationship between sleep duration and 10
ACCEPTED MANUSCRIPT suicidal ideation (Pheterogeneity < .001, I2 = 95.4%), with a U-shaped dose–response curve. The lowest risk of suicidal ideation was observed with a sleep duration of 9 h. Figure 2B presents the results of the linear and nonlinear dose-response relationship
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between sleep duration and suicide plans. The likelihood ratio test suggested linearity (P = .15), and the pooled OR of suicide plans for a 1-h increase in sleep duration was 0.89 (95%
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CI = 0.88–0.90) (i.e., the risk of suicide plans decreased by 11% for every 1-h increase in sleep duration, with no heterogeneity across the included studies (P = .16, I2 = 39.7%).
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Figure 2C shows the results of the linear and nonlinear dose-response relationship between sleep duration and suicide attempts. The likelihood ratio test suggested nonlinearity (P = .0006), indicating a significant nonlinear dose–response relationship (P heterogeneity < .001,
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I2 = 94.1%) with a U-shaped dose–response curve. The lowest risk of suicide attempts was observed with a sleep duration of 8–9 h.
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Subgroup analysis, metaregression, and sensitivity analyses
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Subgroup analyses and metaregression analyses for the high versus low analyses are presented in Table 1. No significant factor explaining the observed heterogeneity was identified for suicidal ideation, plans, or attempts. Notably, the studies that adjusted for depression had an OR comparable with that of studies that did not. Sensitivity analyses demonstrated similar results (Table S6), indicating that the overall results were not significantly influenced by any single study, with ORs and 95% CIs ranging from 0.54 (0.46–0.63) to 0.57 (0.48–0.67) for suicidal ideation, 0.44 (0.36–0.55) to 0.51 11
ACCEPTED MANUSCRIPT (0.45–0.57) for suicide plans, and 0.49 (0.38–0.62) to 0.55 (0.43–0.70) for suicide attempts. DISCUSSION In this dose–response meta-analysis, we found a U-shaped association between sleep
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duration and youth suicidal ideation and attempts incidence. We also found a negative linear dose-response association in youth suicidal plans. Every 1-h increase in sleep duration led to a
factor for the development of youth suicidality.
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decreased risk of 11% of suicide plans in adolescents. Sleep duration is an independent risk
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Suicide is a multifactorial behavior, and our findings suggest that adequate sleep may be a protective factor that reduces the suicide rate in adolescents. Mechanisms linking sleep to suicidality may differ between short and long sleep durations. One possibility is that being
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awake at night creates a window of vulnerability with respect to suicidality. That is, both sleep deprivation and circadian effects compromise daytime and nighttime frontal lobe
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function/executive function. Hypoactivation of the frontal lobe could diminish
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problem-solving abilities and increase impulsive behavior, both of which may increase suicide risk [49]. The serotonergic system has been proposed to mediate the association between short sleep duration and suicide [50]. A previous study reported that the prefrontal cortex exhibited low serotonin synthesis in suicide attempters compared with healthy controls [51]. Lower neuron density and deficient serotonin input in the prefrontal cortex, which controls executive function, may contribute to impulsive aggressive traits that cause suicidality [52, 53]. Serotonin and its receptors in the brain also play a critical role in sleep– 12
ACCEPTED MANUSCRIPT wake regulation. Serotonin secretion is highest during wakefulness and decreases during sleep [54]. Increasing evidence suggests that restricted sleep results in loss of sensitivity or desensitization of postsynaptic serotonin receptors (55, 56). Under these scenarios, reduced
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sleep duration might lead to a loss of serotonin function and thus adversely affect impulse control and judgment, which in turn increases the likelihood of suicide.
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Explanations for the relationship between long sleep duration and increased suicidality are currently speculative. The relevant literature demonstrates that depressive symptoms play
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a moderating role in the linkage between a long sleep duration and suicidality, as evidenced by the relationship disappearing after adjustment for depressive mood [57]. Nonetheless, our results from subgroup analyses indicated no moderating role, which is consistent with
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previous meta-analyses [35, 36], showing that depression did not moderate the association between sleep disturbances and suicidality. Collectively, studies have suggested that the
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maintenance of sleep may be involved in suicidality independent of depression. The elevation
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of serotonergic activity caused by increased sleep duration might be a possible explanation [50]. Because the underlying mechanisms are still not well understood, further investigations are warranted.
Our meta-analysis has several limitations. First, because of the cross-sectional design of the included studies, we need to be cautious when making causal inferences about the relationship between sleep duration and youth suicidality. Second, most of the included studies used self-reported questionnaires with a single item measuring sleep duration and 13
ACCEPTED MANUSCRIPT suicidality; thus, recall bias could not be excluded. Third, our study participants were mostly from schools, and adolescents who dropped out of school or were not present at school were not included, which might limit the generalizability of the current dose–response
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meta-analysis. Fourth, because of only a few studies included, a publication bias test was not utilized in the current study. The potential for publication bias could not be excluded.
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Nevertheless, we employed a robust search strategy and included a large-scale sample, which greatly increased the statistical power for detecting the dose–response associations between
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sleep duration and youth suicidal ideation, plans, and attempts. Moreover, the sensitivity analyses provided solid evidence of the robustness of our findings. In addition, the inclusion of studies from various geographic areas substantially increased the generalizability of our
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findings.
In summary, our meta-analysis provides evidence to support that sleep duration plays an
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important role in the development of youth suicidal behaviours. Our findings suggests that
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both long and short sleep duration are significantly associated with an increased incident risk of suicidal ideation and attempts, with the lowest risks of suicidal ideation and attempt at sleep durations of 8–9 h per day. In addition, we noted an 11% reduction in the risk of suicide plans for every 1-h increase in sleep duration. These findings have substantial public health implications and suggest increasing the sleep duration for the prevention of youth suicidal ideation, plans, and attempts. Prospective longitudinal studies with longer follow-up times are required to establish causality and to elucidate the underlying mechanisms. Prospective 14
ACCEPTED MANUSCRIPT studies investigating the relationships between sleep deprivation and suicidal ideation in
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healthy and clinical subjects are required.
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ACCEPTED MANUSCRIPT Practice points 1.
U-shaped associations of sleep duration with the risk of suicidal ideation and attempts are observed, with lowest suicidal ideation and attempts risks at sleep durations of 8–9 h per day. A linear relationship between sleep duration and suicidal plan is found, with an 11%
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2.
reduction in suicide plans risk for every 1-h increase in sleep duration. 3.
Appropriate sleep duration should be considered as one of influencing factors in
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developing preventive strategies of youth suicidal ideation, plans, and attempts.
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Research agenda Future studies should:
1. Adopt a longitudinal study design to investigate the causality of sleep duration and suicidality and its underlying mechanisms.
2. Conduct prospective studies to examine the association between sleep deprivation and
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suicidal ideation in healthy and clinical subjects. 3. Employ objective instruments such as actigraphs to assess sleep duration to allow more precise estimations of sleep duration.
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4. Develop interventions for targeting the issues of sleep duration in adolescents.
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23
Table 1 Metaregression and subgroup analyses ACCEPTED Factors
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I2 (%)
Point (95% CI)
n
P for heterogeneity*
estimate Suicidal ideation (n = 13) Metaregression Mean age
8
-0.29 (-0.59 to 0.003)
85.6
Female percentage
13
0.0002 (-0.005 to 0.006)
92.8
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Subgroup analyses Sample size
0.19
≥20,000
8
0.52 (0.42 to 0.63)
94.9
<20,000
5
0.64 (0.53 to 0.78)
55.4
Study region
0.33
3
0.58 (0.40 to 0.84)
85.2
South Korea
7
0.53 (0.43 to 0.66)
95.5
USA
3
0.59 (0.40 to 0.87)
76.3
Yes
6
No
7
Statistical adjusted for depression 8
No
5
Statistical adjusted for smoking Yes No
Yes No
0.76
0.57 (0.49 to 0.66)
85.4
0.54 (0.43 to 0.69)
91.0 0.14
0.60 (0.51 to 0.70)
88.1
0.48 (0.37 to 0.62)
89.3 0.71
7
0.54 (0.45 to 0.64)
90.5
6
0.58 (0.43 to 0.78)
92.1
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Statistical adjusted for drinking
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Yes
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Weekday sleep duration
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China
0.71
7
0.54 (0.45 to 0.64)
90.5
6
0.58 (0.43 to 0.78)
92.1
Yes No
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Statistical adjusted for drug use
0.36
3
0.49 (0.38 to 0.63)
85.7
10
0.58 (0.48 to 0.70)
93.5
Statistical adjusted for other sleep variables†
0.13
Yes
6
0.62 (0.51 to 0.76)
89.7
No
7
0.50 (0.41 to 0.61)
88.5
Mean age
5
0.016 (-0.52 to 0.54)
0
Female percentage
6
0.001 (-0.008 to 0.011)
0
Suicidal plan(n = 6) Metaregression
Subgroup analyses Sample size
0.19
3 0.41 (0.32 to 0.53) ACCEPTED MANUSCRIPT
≥20,000 <20,000
3
0.52 (0.46 to 0.59)
0 0
Study region
0.64
China and South Korea
4
0.49 (0.43 to 0.56)
2.4
America
2
0.54 (0.35 to 0.81)
0
Weekday sleep duration
0.46 2
0.50 (0.44 to 0.60)
0
No
4
0.51 (0.45 to 0.57)
0
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Yes
0.19
Statistical adjusted for depression Yes
3
0.41 (0.32 to 0.53)
0
No
3
0.52 (0.46 to 0.59)
0
Statistical adjusted for smoking
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0.19
3
0.41 (0.32 to 0.53)
0
No
3
0.52 (0.46 to 0.59)
0
Statistical adjusted for drinking Yes
3
No
3
Statistical adjusted for other sleep †
variables
3
No Suicidal attempt (n = 11) Metaregression
Female percentage Subgroup analyses
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Sample size
0.41 (0.32 to 0.53)
0
0.52 (0.46 to 0.59)
0 0.19 0
3
0.52 (0.46 to 0.59)
0
7
0.38 (-0.097 to 0.852)
47.2
11
0.003 (-0.007 to 0.012)
80.6
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Mean age
0.19
0.41 (0.32 to 0.53)
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Yes
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Yes
0.82
≥20,000
7
0.53 (0.38 to 0.73)
85.4
<20,000
4
0.50 (0.41 to 0.61)
0
Study regions China
0.80 3
0.58 (0.39 to 0.87)
77.2
South Korea
6
0.49 (0.32 to 0.74)
86.3
America
2
0.56 (0.32 to 0.96)
5.4
Weekday sleep duration
0.65
Yes
6
0.49 (0.34 to 0.70)
87.3
No
5
0.55 (0.42to 0.73)
21.6 0.44
Adjusted for depression Yes
7
0.47 (0.32 to 0.70)
83.9
No
4
0.60 (0.44 to 0.83)
66.2
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Statistical adjusted for smoking
0.82
Yes
7
0.50 (0.41 to 0.61)
85.4
No
4
0.53 (0.38 to 0.73)
78.5
Statistical adjusted for drinking
0.65
Yes
6
0.49 (0.34 to 0.70)
87.3
No
5
0.55 (0.42 to 0.73)
21.6
Statistical adjusted for drug use
0.95 3
0.51 (0.31 to 0.84)
71.1
No
8
0.52 (0.39 to 0.70)
81.0
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Yes
Statistical adjusted for other sleep
0.97
†
variables
5
0.51 (0.30 to 0.86)
No
6
0.53 (0.40 to 0.69)
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Yes
68.5 86.4
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CI = confidence interval. * Between subgroups with metaregression analysis. † perception of getting enough sleep, awakening time and bedtime, nightmares and insomnia, restorative sleep,
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and chronotype.
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Potentially relevant articles identified (n = 640) 33 EMBASE 34 PubMed 1 PsycINFO 567 ProQuest Dissertations & Theses A&I 4 Wanfang Data Chinese database 0 China Knowledge Resource Integrated Database 1 Hand searching by checking the reference lists of included studies
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Articles excluded after screening of title and abstract (n = 627) - Did not report the sleep duration - Did not mention suicidality
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Full text articles extracted for detailed evaluation (n = 13) Excluded (n = 3) -Did not report sleep duration category
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10 eligible articles were included and 1 article had rate ratios in different years (i.e., 2007 and 2009) and 2 exclusively involved gender specific rate ratios, resulting in 13 eligible reports for systematic review
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Articles included in systematic review (n = 13) Suicidal ideations (n = 13) Suicidal plans (n = 6) Suicidal attempts (n = 11)
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Articles with only 2 sleep duration categories (n = 1) was excluded from dose-response metaanalysis
Articles included in dose-response metaanalysis (n = 12) Suicidal ideations (n = 12) Suicidal plans (n = 5) Suicidal attempts (n = 10)
Figure 1 Flow chart of literatures search for studies investigating association between sleep duration and the risks of suicidal ideations, plans, and attempts.
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(B)
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Figure 2 the linear and non-linear associations of sleep duration with (A) suicidal ideation, (B) suicidal plan, (C) suicidal attempt.
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(C)
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(A)