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Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication
SCHRES-06669; No of Pages 5 Schizophrenia Research xxx (2016) xxx–xxx
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Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication Hans Y. Oh a,b,⁎, Fiza Singh c, Ai Koyanagi d, Nicole Jameson e, Jason Schiffman e, Jordan DeVylder e a
University of California, Berkeley, School of Public Health, 50 University Hall #7360, Berkeley, CA 94720-7360, USA Pacific Institute for Research and Evaluation, 180 Grand Avenue Suite #1200, Oakland, CA 94612, USA University of California, San Diego, Department of Psychiatry, 9500 Gilman Drive, La Jolla, CA 92093-0810, USA d Parc Sanitari Sant Joan de Déu/CIBERSAM, Research and Development Unit, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, 08830, Spain e University of Maryland, Baltimore, School of Social Work, 525 West Redwood Street, Baltimore, MD 21201, USA b c
a r t i c l e
i n f o
Article history: Received 30 November 2015 Received in revised form 7 January 2016 Accepted 10 January 2016 Available online xxxx Keywords: Sleep Insomnia Psychotic experiences NCS-R
a b s t r a c t Sleep disturbances have been linked to psychotic experiences in the general adult populations of multiple countries, but this association has yet to be confirmed in the United States using robust diagnostic measures. We analyzed a subsample (n = 2304) of the National Comorbidity Survey Replication, and found that when compared with those who did not report any sleep problems, individuals with sleep disturbances lasting two weeks or longer over the past 12 months were significantly more likely to report at least one psychotic experience during that same time frame. Specifically, difficulty falling asleep, waking up during the night, early morning awakenings, and feeling sleepy during the day were each associated with greater odds of reporting psychotic experiences over the past year after controlling for socio-demographic variables. However, only difficulty falling asleep and early morning awakenings were still significant after adjusting for DSM comorbid disorders. Reporting three or four types of sleep disturbances was especially predictive of psychotic experiences. Our findings underscore the importance of detecting and reducing sleep problems among individuals who report PE. © 2016 Elsevier B.V. All rights reserved.
1. Introduction Psychotic Experiences (PE) occur in approximately 7.2% of the general population (Linscott and van Os, 2013), and have been associated with perceived need for help (DeVylder et al. 2014b), poor functioning and distress (Kelleher et al., 2015), co-occurring psychiatric disorders (DeVylder et al., 2015), and suicidality (DeVylder et al., 2015; Kelleher et al., 2012, 2013). While most PE are transitory, they might also signal the onset of psychotic disorder in some individuals (Fisher et al., 2013; Werbeloff et al., 2012). Sleep dysfunction has been correlated with the entire psychosis continuum – from sub-threshold PE to full psychotic disorders – and this relation has been replicated using different methodologies, measures, and samples (Reeve et al., 2015). However, there have only been a few large epidemiological studies of general adult populations that examined the association between sleep disturbance and PE. Freeman et al. (2010) analyzed a national epidemiological survey of households in England, Wales, and Scotland (British National Survey of Psychiatric Morbidity) and examined the extent to which sleep
⁎ Corresponding author at: University of California, Berkeley, School of Public Health, 50 University Hall #7360, Berkeley, CA 94720-7360, USA. E-mail addresses: [email protected] (H.Y. Oh), [email protected] (F. Singh), [email protected] (A. Koyanagi), [email protected] (J. Schiffman), [email protected] (J. DeVylder).
problems as defined by the Clinical Interview Schedule Revised (CISR; Lewis et al., 1992) were associated with persecutory ideation as defined by the Psychosis Screening Questionnaire (Bebbington and Nayani, 1995). The authors found that sleep dysfunction at three different levels of severity (sleep difficulties, moderately severe insomnia, and chronic insomnia) were all associated with increased risk for paranoia, with the more persistent and severe sleep disturbances having larger effects. A subsample of participants were assessed 18 months later, and a longitudinal analysis showed that insomnia predicted the persistence and new inception of paranoia after adjusting for sociodemographic variables (Freeman et al., 2012). Freeman et al. (2011) found similar effect sizes in another survey of households in England (Adult Psychiatric Morbidity Survey), which also used the CIS-R, but only used one definition of insomnia (problems getting or trying to stay asleep in the past week, where it took at least a quarter of an hour to get to sleep, and the problem occurred for at least 6 months). A limitation of these studies is that they did not control for cooccurring psychiatric disorders, though Freeman et al. (2010) did conduct a mediation analysis and found that the association between insomnia and paranoia was partially explained by anxiety, worry, depression, irritability, and to a lesser extent, cannabis use. However, the authors only used symptoms and not clinical diagnoses, and only examined cannabis use instead of substance or alcohol dependence. The most recent and largest analysis of non-clinical adult populations was conducted by Koyanagi and Stickley (2015), who analyzed
http://dx.doi.org/10.1016/j.schres.2016.01.018 0920-9964/© 2016 Elsevier B.V. All rights reserved.
Please cite this article as: Oh, H.Y., et al., Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.018
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H.Y. Oh et al. / Schizophrenia Research xxx (2016) xxx–xxx
data from the World Health Organization's World Health Survey (WHS). In this survey, respondents were asked one question to assess the severity of their sleep problems over the past 30 days in terms of falling asleep, waking up frequently during the night, and waking up too early in the morning, to which respondents could answer: none, mild, moderate, severe, or extreme. Respondents who answered severe and extreme were coded as having sleep problems, and were almost two and a half times more likely to report at least one psychotic symptom when compared with those who did not have sleep problems [odds ratio (OR): 2.41; 95% confidence interval (CI): 2.18–2.65]. This effect diminished after controlling for anxiety and depression, but remained significant (OR: 1.59; 95% CI: 1.40–1.81). Koyanagi and Stickley's study confirmed the relation between sleep disturbance and PE across 56 mostly middle- and low-income countries; however, their results should be interpreted bearing in mind certain limitations. First, the study did not examine whether specific types of sleep disturbances had variable associations with PE. Second, the 30day assessment of sleep problems left considerable room for the possibility that the sleep problems occurred after the onset of PE. Third, the PE measure excluded events that occurred within the context of sleep, alcohol, and drugs for hallucinations only, and not for delusional ideation; therefore, the PE measure was inherently confounding. Finally, the authors could not control for comorbid conditions using strong diagnostic measures. To our knowledge, there are no studies that examine the relation between sleep disturbance and PE in the general US adult population, and so in this paper, we aim to fill this gap in the literature. We will also address the limitations of previous studies by examining four different types of sleep disturbances that lasted two weeks over the past 12 months (difficulty initiating sleep, difficulty maintaining sleep, early morning awakenings, and feeling sleepy during the day), and by using a measure of PE that excludes sleep-related and substanceinduced experiences. Further, we will control for several comorbid conditions using DSM diagnoses, including several mood, anxiety, and substance use disorders. We hypothesize that all four kinds of sleep disturbances will be associated with PE after controlling for comorbid psychiatric disorders.
2. Methods 2.1. Sample We analyzed data from the National Comorbidity Survey Replication (NCS-R). The sample designs and sampling methods have been described in detail elsewhere (Kessler and Merikangas, 2004). In brief, the NCS-R is a nationally representative survey of 9282 adults residing in households within the 48 contiguous states, selected through a multi-stage sampling design. Most respondents were White (73%), reflecting the general population of the US. The survey investigators provided survey weighting, stratification, and cluster sampling variables to account for the complex sampling techniques used in the NCS-R. The survey consisted of an expanded version of the World Health Organization's Composite International Diagnostic Interview (WHO CIDI), which draws from DSM-IV diagnostic criteria, and uses organic exclusions and diagnostic hierarchy rules. All respondents completed a ‘Part I’ diagnostic interview, and a probability subsample of 5692 respondents completed an additional ‘Part II’ interview that elicited more diagnostic and background information. A random subsample of Part II respondents (n = 2322) completed the psychosis screen. Respondents who were missing any of the variables of interest were excluded from the analysis (n = 18), resulting in a final analytic sample of 2304. Five respondents in our analytic sample self-reported that at some point in their lives they had talked to a doctor or mental health professional about receiving help in dealing with schizophrenia/psychosis. We re-ran our analyses after excluding these individuals, but
since results did not vary significantly, we decided to retain these individuals in our sample. 2.2. Psychotic experiences (past 12 months) PE were assessed using the WHO-CIDI 3.0 Psychosis Screen (Kessler and Ustun, 2004), which has been used to measure PE across the globe (McGrath et al., 2015) and has been validated through associations with hospital admissions and the development of full psychotic disorder in a dose–response fashion (Kaymaz et al., 2012). The WHO-CIDI psychosis screen can be found in the supplemental materials. Respondents were asked to report the lifetime presence of six specific PE, including: (1) visual hallucinations, (2) auditory hallucinations, (3) thought insertion, (4) thought control, (5) telepathy, and (6) delusions of persecution. Endorsing at least one of these experiences during one's lifetime constituted a positive endorsement of lifetime PE. Responses were not considered PE if the experience took place in the context of falling asleep, dreaming, or substance use. Respondents who endorsed lifetime PE were asked whether any of these experiences occurred within the past 12 months. We only used PE over the past year to be consistent with the sleep variables. 2.3. Sleep disturbance (past 12 months) Sleep disturbance items were derived from DSM-IV criteria, but were asked outside of the context of psychiatric diagnoses. Respondents were asked whether or not (yes/no) they had sleep problems that lasted at least two weeks over the past year. Sleep problems were measured using four separate variables, including: getting to sleep when nearly every night it took the respondent 2 h or longer to fall asleep (difficulty initiating sleep); staying asleep when the respondent woke up nearly every night and took an hour or more to get back to sleep (difficulty maintaining sleep); waking too early when the respondent woke up nearly every morning at least 2 h earlier than desired (early morning awakening); and feeling sleepy during the day. 2.4. Control variables Self-reported socio-demographic variables that had the potential to confound the analyses were included as covariates. These variables included race (White, Black, Asian, Latino, Other), sex, age (18–29, 30– 44, 45–59, 60 +), marital status (married, previously married, never married), education level (less than high school, high school, some college, college and beyond), income-poverty ratio (0 = poor, 1–2 near poor, 3 + nonpoor), and work status (employed, unemployed, out of workforce). Since psychiatric disorders can co-vary with sleep and psychosis (Reeve et al., 2015; DeVylder et al., 2015; Schierenbeck et al., 2008), we created a dummy variable to indicate the presence of any one or more of the following co-occurring disorders that occurred within the past 12 months: mood disorders (major depressive, dysthymia, bipolar), anxiety disorders (general anxiety, panic, social phobia, agoraphobia with and without panic attacks), post-traumatic stress disorder, and substance use disorder (alcohol dependence, drug dependence). 2.5. Analysis We estimated standard errors through design-based analyses that used the Taylor series linearization method to account for the complex multistage clustered design, with US metropolitan statistical areas or counties as the primary sampling units. We used sampling weights for all statistical analyses to account for individual-level sampling factors (i.e. non-response and unequal probabilities of selection). We used STATA SE to compute Wald χ2 tests, comparing sleep disturbance variables between those who reported PE and those who did not. We then examined the relation between sleep disturbance and PE adjusting for potential socio-demographic confounders in the first block, and
Please cite this article as: Oh, H.Y., et al., Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.018
H.Y. Oh et al. / Schizophrenia Research xxx (2016) xxx–xxx
controlling for co-occurring disorders in the second block. We performed analyses separately using each of the four types of sleep disturbances. We then created a count variable of the different sleep problems (0–4), and examined its relation to PE. We present our findings as odds ratios (ORs) with confidence intervals (CI), and we established significance at the α = .05 level. 3. Results Prior studies have reported the descriptive statistics for the NCS-R in detail (DeVylder et al., 2015). We reported descriptive statistics of the main sleep disturbance and psychosis variables in Table 1. Approximately 2.91% of the sample reported psychotic experiences over the past 12 months. With respect to sleep disturbance, 41.89% of the total sample reported at least one type of sleep disturbance over the past year. Specifically, 16.77% of the sample reported difficulty falling asleep, 19.80% reported difficulty staying asleep, 16.64% reported waking up too early, and 30.54% reported feeling sleepy during the day. When compared with people without PE, those with PE had higher rates of all the sleep disturbances except for difficulty staying asleep, and had higher rates of having three to four types of sleep disturbances. We found that reporting sleep problems lasting a period of at least two weeks over the past year was associated with increased risk for PE. Specifically, problems falling asleep and waking up too early were associated with more than a two-fold increased likelihood of reporting PE after adjusting for demographic covariates, and these effects persisted after controlling for co-occurring disorders. Waking up in the middle of the night and feeling sleepy during the day were associated with an increased risk for PE after adjusting for demographic covariates, but these large effect sizes were no longer significant after controlling for co-occurring disorders, possibly reflecting limited statistical power due to the low prevalence of PE over the past year (Table 2). The number of sleep disturbance types was associated with increased risk for PE in a dose–response fashion. Reporting all four types of sleep disturbances was significantly associated with more than a three-fold increased risk for reporting PE (OR: 3.04, p = 0.001) when compared with those who reported none of the sleep disturbances, even after adjusting for demographic covariates and co-occurring disorders. 4. Discussion Overall, our study contributed to the literature by replicating the association between sleep disturbance and PE in the US general adult population. Given the limitations of prior studies, we conducted our analyses using (1) a sleep measure that specified four different sleep disturbances that lasted two weeks over the past year, (2) a PE measure that excluded sleep-related and substance-induced experiences, and (3) DSM psychiatric disorders as control variables. Individuals who reported at least two weeks of persistent sleep problems in the prior year were more likely to report PE than those who did not report
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Table 2 Associations between sleep disturbance and psychotic experiences in the past 12 months (n = 2304). PE adjusted for demographic variables OR (95% CI) Did you have a period lasting two weeks or longer in the past 12 months when you had any of the following problems with your sleep: Difficulty initiating asleep
2.25 (1.46–3.47)** Difficulty maintaining asleep 1.76 (1.02–3.02)* Early morning awakening 2.47 (1.34–4.53)** Feeling sleepy during the 1.79 (1.07–2.98)* day Count of types of sleep disturbances 0 1.0 1 1.21 (0.52–2.85) 2 1.44 (0.63–3.30) 3 2.33 (0.97–5.62) 4 3.31 (1.69–6.48)**
PE adjusted for demographic variables and co-morbid disorders OR (95% CI)
2.06 (1.26–3.35)** 1.56 (0.94–2.61) 2.28 (1.29–4.04)** 1.63 (0.94–2.86)
1.0 1.19 (0.50–2.84) 1.38 (0.59–3.25) 2.18 (0.85–5.54) 3.04 (1.61–5.76)**
Demographic variables: race, sex, age, marital status, income, education, employment status. Co-morbid disorders occurred within the past year and included: mood disorders (major depressive, dysthymia, bipolar); anxiety disorders (general anxiety, panic, social phobia, agoraphobia with and without panic attacks); post-traumatic stress disorder; substance use disorder (alcohol dependence, drug dependence). ⁎ p b 0.05. ⁎⁎ p b 0.01.
these sleep problems after controlling for demographic variables. This was true for each of the four types of sleep disturbances. After controlling for several DSM co-morbid disorders, only difficulty initiating sleep and early morning awakenings were significantly associated with increased odds of reporting PE. Extant literature on sleep and psychosis paints a hazy picture of how specific types of sleep disturbances might be connected to specific types of PE (e.g. auditory hallucinations, visual hallucinations, paranoid ideation). We were unable to examine this because the WHO CIDI psychosis screen only allowed us to disaggregate the PE subtypes over the lifetime, not over the past year. Future research should explore the unique effects of specific sleep disturbances on specific psychotic symptoms. While each individual sleep disturbance was related to PE, having three or four of the sleep disturbances conferred an especially large risk. The dose–response relationship between the number of sleep disturbances and PE (i.e. the more kinds of disturbances a person has, the more he or she is likely report PE) is a notable finding, but could be attributable to the sleep variables being related to one another (a = 0.75), resulting in increased power and overall effect.
Table 1 Descriptive data for sleep disturbance variables in the past 12 months.
Type of sleep disturbance Difficulty falling asleep Difficulty staying asleep Waking up too early Feeling sleepy during the day Count of sleep disturbance types 0 1 2 3 4
Total % (SE)
No PE % (SE)
12-month PE % (SE)
F-statistic (p-value)
16.77 (1.17) 19.80 (1.05) 16.64 (1.14) 30.88 (1.51)
16.33 (1.16) 19.58 (1.09) 16.21 (1.18) 30.54 (1.52)
31.23 (4.93) 27.17 (4.8) 30.99 (5.72) 42.06 (5.72)
14.56 (0.00) 2.72 (0.11) 8.87 (0.00) 4.33 (0.04)
58.11 (1.72) 18.69 (1.06) 9.81 (0.96) 7.77 (0.65) 5.62 (0.47)
58.46 (1.77) 18.73 (1.12) 9.82 (1.00) 7.67 (0.65) 5.33 (0.49)
46.55 (6.92) 17.29 (5.18) 9.64 (2.79) 11.19 (3.56) 15.33 (4.01)
3.51 (0.01)
Weighted percentage (standard error).
Please cite this article as: Oh, H.Y., et al., Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.018
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Interpretation of our findings should be made bearing in mind that our study was cross-sectional and did not allow us to establish the temporal order of events; thus, sleep disturbance may cause PE, and the reverse can also be true. It is also possible that sleep disturbance and PE may work cyclically and contribute to each other. Any causal claims based on our study should acknowledge this potential limitation. Multiple theories have been suggested to explain the association between sleep disturbance and PE, ranging from circadian rhythm abnormalities to biological models such as aberrant development of brain regions that support sleep (Reeve et al. 2015). Studies have also proposed that loss of sleep leads to inadequate synaptic pruning and abnormal neuronal synchronization (Sprecher et al., 2015), which may underlie PE. An additional theory arises from studies that suggest sleep deprivation is associated with neuroinflammation (Motivala, 2011), and alterations in the immune system lead to brain changes that precipitate the onset and progression of schizophrenia (Watkins and Andrews, 2015). However, there is some evidence to suggest that inflammation may also contribute to poor sleep, which would indicate bi-directionality. Future studies can test these theories and increase our understanding of the mechanisms that underlie the relation between sleep and PE. Our findings have clinical implications. PE are often fleeting and innocuous, and so providers have struggled to find the most prudent yet minimally invasive treatment for those who report distress from these experiences (Oh et al., 2014). Most of the participants in our sample are not likely to develop psychotic disorder, and placing these individuals in unnecessary treatment could potentially inflict harm. But if PE can help identify other clinically relevant issues that might be worth screening (e.g., sleep problems, suicidality), then PE may play a key role in clinical formulation and treatment planning (DeVylder et al., 2014a). In light of our findings, providers may consider screening for sleep problems among those who report PE. Additionally, given the literature that suggests that sleep dysfunction is a contributory factor for paranoia and hallucinations, researchers are now conducting clinical trials to determine whether treating sleep problems through Cognitive Behavioral Therapy (CBT) can reduce PE in the general population (see Freeman et al., 2015b). A recent study found that CBT might be highly effective for improving sleep in patients with schizophrenia spectrum diagnosis, although the effect of CBT on delusions and hallucinations were small and mixed with wide confidence intervals and some negative correlations (Freeman et al., 2015a). A brief CBT intervention to reduce worry has been shown to reduce persistent delusions (Freeman et al., 2015a), and sleep might play a mediating role, as worrying can often result in difficulty falling asleep (Harvey, 2002). Treatment for sleep is rarely stigmatized since sleep disturbance appears to be a common human experience, and so interventions targeting sleep may provide an easier and/or complementary inroad towards working directly with psychotic symptoms. Interventions to address PE may focus on improving quality of sleep through various treatment modalities, which can prevent the onset of other neuropsychiatric problems beyond psychosis, and can enhance general cognitive and emotional functioning.
Conflict of interest The authors have no affiliations with industrial or commercial entities and have not received financial support from commercial entities for their work.
Contributors Hans Oh conducted the literature review and all statistical analyses. Fiza Singh edited the manuscript and contributed to the discussion section. Ai Koyanagi provided recommendations improve the literature review and analyses. Nicole Jameson revised the manuscript. Jason Schiffman edited the manuscript. Jordan DeVylder guided the analysis and revised the manuscript.
Funding body agreements This project was not supported through external funding.
Acknowledgments The authors would like to thank those involved with the Collaborative Psychiatric Epidemiology Surveys for making their data publicly available to the research community.
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Please cite this article as: Oh, H.Y., et al., Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.018
Contents lists available at ScienceDirect
Schizophrenia Research journal homepage: www.elsevier.com/locate/schres
Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication Hans Y. Oh a,b,⁎, Fiza Singh c, Ai Koyanagi d, Nicole Jameson e, Jason Schiffman e, Jordan DeVylder e a
University of California, Berkeley, School of Public Health, 50 University Hall #7360, Berkeley, CA 94720-7360, USA Pacific Institute for Research and Evaluation, 180 Grand Avenue Suite #1200, Oakland, CA 94612, USA University of California, San Diego, Department of Psychiatry, 9500 Gilman Drive, La Jolla, CA 92093-0810, USA d Parc Sanitari Sant Joan de Déu/CIBERSAM, Research and Development Unit, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, 08830, Spain e University of Maryland, Baltimore, School of Social Work, 525 West Redwood Street, Baltimore, MD 21201, USA b c
a r t i c l e
i n f o
Article history: Received 30 November 2015 Received in revised form 7 January 2016 Accepted 10 January 2016 Available online xxxx Keywords: Sleep Insomnia Psychotic experiences NCS-R
a b s t r a c t Sleep disturbances have been linked to psychotic experiences in the general adult populations of multiple countries, but this association has yet to be confirmed in the United States using robust diagnostic measures. We analyzed a subsample (n = 2304) of the National Comorbidity Survey Replication, and found that when compared with those who did not report any sleep problems, individuals with sleep disturbances lasting two weeks or longer over the past 12 months were significantly more likely to report at least one psychotic experience during that same time frame. Specifically, difficulty falling asleep, waking up during the night, early morning awakenings, and feeling sleepy during the day were each associated with greater odds of reporting psychotic experiences over the past year after controlling for socio-demographic variables. However, only difficulty falling asleep and early morning awakenings were still significant after adjusting for DSM comorbid disorders. Reporting three or four types of sleep disturbances was especially predictive of psychotic experiences. Our findings underscore the importance of detecting and reducing sleep problems among individuals who report PE. © 2016 Elsevier B.V. All rights reserved.
1. Introduction Psychotic Experiences (PE) occur in approximately 7.2% of the general population (Linscott and van Os, 2013), and have been associated with perceived need for help (DeVylder et al. 2014b), poor functioning and distress (Kelleher et al., 2015), co-occurring psychiatric disorders (DeVylder et al., 2015), and suicidality (DeVylder et al., 2015; Kelleher et al., 2012, 2013). While most PE are transitory, they might also signal the onset of psychotic disorder in some individuals (Fisher et al., 2013; Werbeloff et al., 2012). Sleep dysfunction has been correlated with the entire psychosis continuum – from sub-threshold PE to full psychotic disorders – and this relation has been replicated using different methodologies, measures, and samples (Reeve et al., 2015). However, there have only been a few large epidemiological studies of general adult populations that examined the association between sleep disturbance and PE. Freeman et al. (2010) analyzed a national epidemiological survey of households in England, Wales, and Scotland (British National Survey of Psychiatric Morbidity) and examined the extent to which sleep
⁎ Corresponding author at: University of California, Berkeley, School of Public Health, 50 University Hall #7360, Berkeley, CA 94720-7360, USA. E-mail addresses: [email protected] (H.Y. Oh), [email protected] (F. Singh), [email protected] (A. Koyanagi), [email protected] (J. Schiffman), [email protected] (J. DeVylder).
problems as defined by the Clinical Interview Schedule Revised (CISR; Lewis et al., 1992) were associated with persecutory ideation as defined by the Psychosis Screening Questionnaire (Bebbington and Nayani, 1995). The authors found that sleep dysfunction at three different levels of severity (sleep difficulties, moderately severe insomnia, and chronic insomnia) were all associated with increased risk for paranoia, with the more persistent and severe sleep disturbances having larger effects. A subsample of participants were assessed 18 months later, and a longitudinal analysis showed that insomnia predicted the persistence and new inception of paranoia after adjusting for sociodemographic variables (Freeman et al., 2012). Freeman et al. (2011) found similar effect sizes in another survey of households in England (Adult Psychiatric Morbidity Survey), which also used the CIS-R, but only used one definition of insomnia (problems getting or trying to stay asleep in the past week, where it took at least a quarter of an hour to get to sleep, and the problem occurred for at least 6 months). A limitation of these studies is that they did not control for cooccurring psychiatric disorders, though Freeman et al. (2010) did conduct a mediation analysis and found that the association between insomnia and paranoia was partially explained by anxiety, worry, depression, irritability, and to a lesser extent, cannabis use. However, the authors only used symptoms and not clinical diagnoses, and only examined cannabis use instead of substance or alcohol dependence. The most recent and largest analysis of non-clinical adult populations was conducted by Koyanagi and Stickley (2015), who analyzed
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Please cite this article as: Oh, H.Y., et al., Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.018
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data from the World Health Organization's World Health Survey (WHS). In this survey, respondents were asked one question to assess the severity of their sleep problems over the past 30 days in terms of falling asleep, waking up frequently during the night, and waking up too early in the morning, to which respondents could answer: none, mild, moderate, severe, or extreme. Respondents who answered severe and extreme were coded as having sleep problems, and were almost two and a half times more likely to report at least one psychotic symptom when compared with those who did not have sleep problems [odds ratio (OR): 2.41; 95% confidence interval (CI): 2.18–2.65]. This effect diminished after controlling for anxiety and depression, but remained significant (OR: 1.59; 95% CI: 1.40–1.81). Koyanagi and Stickley's study confirmed the relation between sleep disturbance and PE across 56 mostly middle- and low-income countries; however, their results should be interpreted bearing in mind certain limitations. First, the study did not examine whether specific types of sleep disturbances had variable associations with PE. Second, the 30day assessment of sleep problems left considerable room for the possibility that the sleep problems occurred after the onset of PE. Third, the PE measure excluded events that occurred within the context of sleep, alcohol, and drugs for hallucinations only, and not for delusional ideation; therefore, the PE measure was inherently confounding. Finally, the authors could not control for comorbid conditions using strong diagnostic measures. To our knowledge, there are no studies that examine the relation between sleep disturbance and PE in the general US adult population, and so in this paper, we aim to fill this gap in the literature. We will also address the limitations of previous studies by examining four different types of sleep disturbances that lasted two weeks over the past 12 months (difficulty initiating sleep, difficulty maintaining sleep, early morning awakenings, and feeling sleepy during the day), and by using a measure of PE that excludes sleep-related and substanceinduced experiences. Further, we will control for several comorbid conditions using DSM diagnoses, including several mood, anxiety, and substance use disorders. We hypothesize that all four kinds of sleep disturbances will be associated with PE after controlling for comorbid psychiatric disorders.
2. Methods 2.1. Sample We analyzed data from the National Comorbidity Survey Replication (NCS-R). The sample designs and sampling methods have been described in detail elsewhere (Kessler and Merikangas, 2004). In brief, the NCS-R is a nationally representative survey of 9282 adults residing in households within the 48 contiguous states, selected through a multi-stage sampling design. Most respondents were White (73%), reflecting the general population of the US. The survey investigators provided survey weighting, stratification, and cluster sampling variables to account for the complex sampling techniques used in the NCS-R. The survey consisted of an expanded version of the World Health Organization's Composite International Diagnostic Interview (WHO CIDI), which draws from DSM-IV diagnostic criteria, and uses organic exclusions and diagnostic hierarchy rules. All respondents completed a ‘Part I’ diagnostic interview, and a probability subsample of 5692 respondents completed an additional ‘Part II’ interview that elicited more diagnostic and background information. A random subsample of Part II respondents (n = 2322) completed the psychosis screen. Respondents who were missing any of the variables of interest were excluded from the analysis (n = 18), resulting in a final analytic sample of 2304. Five respondents in our analytic sample self-reported that at some point in their lives they had talked to a doctor or mental health professional about receiving help in dealing with schizophrenia/psychosis. We re-ran our analyses after excluding these individuals, but
since results did not vary significantly, we decided to retain these individuals in our sample. 2.2. Psychotic experiences (past 12 months) PE were assessed using the WHO-CIDI 3.0 Psychosis Screen (Kessler and Ustun, 2004), which has been used to measure PE across the globe (McGrath et al., 2015) and has been validated through associations with hospital admissions and the development of full psychotic disorder in a dose–response fashion (Kaymaz et al., 2012). The WHO-CIDI psychosis screen can be found in the supplemental materials. Respondents were asked to report the lifetime presence of six specific PE, including: (1) visual hallucinations, (2) auditory hallucinations, (3) thought insertion, (4) thought control, (5) telepathy, and (6) delusions of persecution. Endorsing at least one of these experiences during one's lifetime constituted a positive endorsement of lifetime PE. Responses were not considered PE if the experience took place in the context of falling asleep, dreaming, or substance use. Respondents who endorsed lifetime PE were asked whether any of these experiences occurred within the past 12 months. We only used PE over the past year to be consistent with the sleep variables. 2.3. Sleep disturbance (past 12 months) Sleep disturbance items were derived from DSM-IV criteria, but were asked outside of the context of psychiatric diagnoses. Respondents were asked whether or not (yes/no) they had sleep problems that lasted at least two weeks over the past year. Sleep problems were measured using four separate variables, including: getting to sleep when nearly every night it took the respondent 2 h or longer to fall asleep (difficulty initiating sleep); staying asleep when the respondent woke up nearly every night and took an hour or more to get back to sleep (difficulty maintaining sleep); waking too early when the respondent woke up nearly every morning at least 2 h earlier than desired (early morning awakening); and feeling sleepy during the day. 2.4. Control variables Self-reported socio-demographic variables that had the potential to confound the analyses were included as covariates. These variables included race (White, Black, Asian, Latino, Other), sex, age (18–29, 30– 44, 45–59, 60 +), marital status (married, previously married, never married), education level (less than high school, high school, some college, college and beyond), income-poverty ratio (0 = poor, 1–2 near poor, 3 + nonpoor), and work status (employed, unemployed, out of workforce). Since psychiatric disorders can co-vary with sleep and psychosis (Reeve et al., 2015; DeVylder et al., 2015; Schierenbeck et al., 2008), we created a dummy variable to indicate the presence of any one or more of the following co-occurring disorders that occurred within the past 12 months: mood disorders (major depressive, dysthymia, bipolar), anxiety disorders (general anxiety, panic, social phobia, agoraphobia with and without panic attacks), post-traumatic stress disorder, and substance use disorder (alcohol dependence, drug dependence). 2.5. Analysis We estimated standard errors through design-based analyses that used the Taylor series linearization method to account for the complex multistage clustered design, with US metropolitan statistical areas or counties as the primary sampling units. We used sampling weights for all statistical analyses to account for individual-level sampling factors (i.e. non-response and unequal probabilities of selection). We used STATA SE to compute Wald χ2 tests, comparing sleep disturbance variables between those who reported PE and those who did not. We then examined the relation between sleep disturbance and PE adjusting for potential socio-demographic confounders in the first block, and
Please cite this article as: Oh, H.Y., et al., Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.018
H.Y. Oh et al. / Schizophrenia Research xxx (2016) xxx–xxx
controlling for co-occurring disorders in the second block. We performed analyses separately using each of the four types of sleep disturbances. We then created a count variable of the different sleep problems (0–4), and examined its relation to PE. We present our findings as odds ratios (ORs) with confidence intervals (CI), and we established significance at the α = .05 level. 3. Results Prior studies have reported the descriptive statistics for the NCS-R in detail (DeVylder et al., 2015). We reported descriptive statistics of the main sleep disturbance and psychosis variables in Table 1. Approximately 2.91% of the sample reported psychotic experiences over the past 12 months. With respect to sleep disturbance, 41.89% of the total sample reported at least one type of sleep disturbance over the past year. Specifically, 16.77% of the sample reported difficulty falling asleep, 19.80% reported difficulty staying asleep, 16.64% reported waking up too early, and 30.54% reported feeling sleepy during the day. When compared with people without PE, those with PE had higher rates of all the sleep disturbances except for difficulty staying asleep, and had higher rates of having three to four types of sleep disturbances. We found that reporting sleep problems lasting a period of at least two weeks over the past year was associated with increased risk for PE. Specifically, problems falling asleep and waking up too early were associated with more than a two-fold increased likelihood of reporting PE after adjusting for demographic covariates, and these effects persisted after controlling for co-occurring disorders. Waking up in the middle of the night and feeling sleepy during the day were associated with an increased risk for PE after adjusting for demographic covariates, but these large effect sizes were no longer significant after controlling for co-occurring disorders, possibly reflecting limited statistical power due to the low prevalence of PE over the past year (Table 2). The number of sleep disturbance types was associated with increased risk for PE in a dose–response fashion. Reporting all four types of sleep disturbances was significantly associated with more than a three-fold increased risk for reporting PE (OR: 3.04, p = 0.001) when compared with those who reported none of the sleep disturbances, even after adjusting for demographic covariates and co-occurring disorders. 4. Discussion Overall, our study contributed to the literature by replicating the association between sleep disturbance and PE in the US general adult population. Given the limitations of prior studies, we conducted our analyses using (1) a sleep measure that specified four different sleep disturbances that lasted two weeks over the past year, (2) a PE measure that excluded sleep-related and substance-induced experiences, and (3) DSM psychiatric disorders as control variables. Individuals who reported at least two weeks of persistent sleep problems in the prior year were more likely to report PE than those who did not report
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Table 2 Associations between sleep disturbance and psychotic experiences in the past 12 months (n = 2304). PE adjusted for demographic variables OR (95% CI) Did you have a period lasting two weeks or longer in the past 12 months when you had any of the following problems with your sleep: Difficulty initiating asleep
2.25 (1.46–3.47)** Difficulty maintaining asleep 1.76 (1.02–3.02)* Early morning awakening 2.47 (1.34–4.53)** Feeling sleepy during the 1.79 (1.07–2.98)* day Count of types of sleep disturbances 0 1.0 1 1.21 (0.52–2.85) 2 1.44 (0.63–3.30) 3 2.33 (0.97–5.62) 4 3.31 (1.69–6.48)**
PE adjusted for demographic variables and co-morbid disorders OR (95% CI)
2.06 (1.26–3.35)** 1.56 (0.94–2.61) 2.28 (1.29–4.04)** 1.63 (0.94–2.86)
1.0 1.19 (0.50–2.84) 1.38 (0.59–3.25) 2.18 (0.85–5.54) 3.04 (1.61–5.76)**
Demographic variables: race, sex, age, marital status, income, education, employment status. Co-morbid disorders occurred within the past year and included: mood disorders (major depressive, dysthymia, bipolar); anxiety disorders (general anxiety, panic, social phobia, agoraphobia with and without panic attacks); post-traumatic stress disorder; substance use disorder (alcohol dependence, drug dependence). ⁎ p b 0.05. ⁎⁎ p b 0.01.
these sleep problems after controlling for demographic variables. This was true for each of the four types of sleep disturbances. After controlling for several DSM co-morbid disorders, only difficulty initiating sleep and early morning awakenings were significantly associated with increased odds of reporting PE. Extant literature on sleep and psychosis paints a hazy picture of how specific types of sleep disturbances might be connected to specific types of PE (e.g. auditory hallucinations, visual hallucinations, paranoid ideation). We were unable to examine this because the WHO CIDI psychosis screen only allowed us to disaggregate the PE subtypes over the lifetime, not over the past year. Future research should explore the unique effects of specific sleep disturbances on specific psychotic symptoms. While each individual sleep disturbance was related to PE, having three or four of the sleep disturbances conferred an especially large risk. The dose–response relationship between the number of sleep disturbances and PE (i.e. the more kinds of disturbances a person has, the more he or she is likely report PE) is a notable finding, but could be attributable to the sleep variables being related to one another (a = 0.75), resulting in increased power and overall effect.
Table 1 Descriptive data for sleep disturbance variables in the past 12 months.
Type of sleep disturbance Difficulty falling asleep Difficulty staying asleep Waking up too early Feeling sleepy during the day Count of sleep disturbance types 0 1 2 3 4
Total % (SE)
No PE % (SE)
12-month PE % (SE)
F-statistic (p-value)
16.77 (1.17) 19.80 (1.05) 16.64 (1.14) 30.88 (1.51)
16.33 (1.16) 19.58 (1.09) 16.21 (1.18) 30.54 (1.52)
31.23 (4.93) 27.17 (4.8) 30.99 (5.72) 42.06 (5.72)
14.56 (0.00) 2.72 (0.11) 8.87 (0.00) 4.33 (0.04)
58.11 (1.72) 18.69 (1.06) 9.81 (0.96) 7.77 (0.65) 5.62 (0.47)
58.46 (1.77) 18.73 (1.12) 9.82 (1.00) 7.67 (0.65) 5.33 (0.49)
46.55 (6.92) 17.29 (5.18) 9.64 (2.79) 11.19 (3.56) 15.33 (4.01)
3.51 (0.01)
Weighted percentage (standard error).
Please cite this article as: Oh, H.Y., et al., Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.018
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Interpretation of our findings should be made bearing in mind that our study was cross-sectional and did not allow us to establish the temporal order of events; thus, sleep disturbance may cause PE, and the reverse can also be true. It is also possible that sleep disturbance and PE may work cyclically and contribute to each other. Any causal claims based on our study should acknowledge this potential limitation. Multiple theories have been suggested to explain the association between sleep disturbance and PE, ranging from circadian rhythm abnormalities to biological models such as aberrant development of brain regions that support sleep (Reeve et al. 2015). Studies have also proposed that loss of sleep leads to inadequate synaptic pruning and abnormal neuronal synchronization (Sprecher et al., 2015), which may underlie PE. An additional theory arises from studies that suggest sleep deprivation is associated with neuroinflammation (Motivala, 2011), and alterations in the immune system lead to brain changes that precipitate the onset and progression of schizophrenia (Watkins and Andrews, 2015). However, there is some evidence to suggest that inflammation may also contribute to poor sleep, which would indicate bi-directionality. Future studies can test these theories and increase our understanding of the mechanisms that underlie the relation between sleep and PE. Our findings have clinical implications. PE are often fleeting and innocuous, and so providers have struggled to find the most prudent yet minimally invasive treatment for those who report distress from these experiences (Oh et al., 2014). Most of the participants in our sample are not likely to develop psychotic disorder, and placing these individuals in unnecessary treatment could potentially inflict harm. But if PE can help identify other clinically relevant issues that might be worth screening (e.g., sleep problems, suicidality), then PE may play a key role in clinical formulation and treatment planning (DeVylder et al., 2014a). In light of our findings, providers may consider screening for sleep problems among those who report PE. Additionally, given the literature that suggests that sleep dysfunction is a contributory factor for paranoia and hallucinations, researchers are now conducting clinical trials to determine whether treating sleep problems through Cognitive Behavioral Therapy (CBT) can reduce PE in the general population (see Freeman et al., 2015b). A recent study found that CBT might be highly effective for improving sleep in patients with schizophrenia spectrum diagnosis, although the effect of CBT on delusions and hallucinations were small and mixed with wide confidence intervals and some negative correlations (Freeman et al., 2015a). A brief CBT intervention to reduce worry has been shown to reduce persistent delusions (Freeman et al., 2015a), and sleep might play a mediating role, as worrying can often result in difficulty falling asleep (Harvey, 2002). Treatment for sleep is rarely stigmatized since sleep disturbance appears to be a common human experience, and so interventions targeting sleep may provide an easier and/or complementary inroad towards working directly with psychotic symptoms. Interventions to address PE may focus on improving quality of sleep through various treatment modalities, which can prevent the onset of other neuropsychiatric problems beyond psychosis, and can enhance general cognitive and emotional functioning.
Conflict of interest The authors have no affiliations with industrial or commercial entities and have not received financial support from commercial entities for their work.
Contributors Hans Oh conducted the literature review and all statistical analyses. Fiza Singh edited the manuscript and contributed to the discussion section. Ai Koyanagi provided recommendations improve the literature review and analyses. Nicole Jameson revised the manuscript. Jason Schiffman edited the manuscript. Jordan DeVylder guided the analysis and revised the manuscript.
Funding body agreements This project was not supported through external funding.
Acknowledgments The authors would like to thank those involved with the Collaborative Psychiatric Epidemiology Surveys for making their data publicly available to the research community.
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Please cite this article as: Oh, H.Y., et al., Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.018