pii: sp-00600-15
http://dx.doi.org/10.5665/sleep.5216
EDITORIAL
Is Sleep Health a Potential Pathway to Global Mental Health? Commentary on Koyanagi and Stickley. The association between sleep problems and psychotic symptoms in the general population: a global perspective. SLEEP 2015;38:1875–1885. Hyong Jin Cho, MD, PhD Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Sleep disturbance represents a major public health burden due to its high prevalence, negative health impact, and economic implications.1 Psychotic symptoms in the healthy general population, also called psychotic-like experiences or subclinical psychotic symptoms, are not uncommon, with the median prevalence estimated to be 5% to 8% according to a systematic review.2 Furthermore, subclinical psychotic symptoms share most risk factors with schizophrenia, including genetic, obstetric, developmental, substance use, psychopathological, social, and environmental risk factors3; and indeed increase the risk of schizophrenia.4 The existing evidence supports the notion of psychosis as a continuum ranging from subclinical psychotic symptoms to full-blown schizophrenia cases rather than a discrete nosological entity.2 In this context, there has been increasing clinical and research interest in the psychosis prodrome (a retrospective perspective because the concept of “prodrome” implies a necessary transition to disease), and in ultra-high-risk individuals for psychosis (prospective perspective).5 Sleep disturbance has been reported to be the most common symptom in the prodrome of psychosis6 and to be an important predictor of psychosis development among help-seeking individuals at ultra-high risk for psychosis.7 Similarly, sleep disturbance has been found associated with subclinical psychotic symptoms in cross-sectional and prospective studies.8–15 Thus, sleep disturbance is a modifiable risk factor for subclinical psychotic symptoms, and the treatment of sleep disturbance could ultimately lead to the prevention of clinical psychotic disorders. Despite the significance and potential practical impact of the associations between sleep disturbance and subclinical psychotic symptoms as described above, most studies on this topic have been conducted in high-income countries.8–15 In fact, the study of Koyanagi and Stickley reported in this issue of SLEEP appears to be not only the first study to address this topic from a global perspective, but also the first to examine it in low- and middle-income coiuntries.16 This study is significant because it is an important replication of previous studies in a global context and especially in low- and middle-income countries, where the resources for mental health research and care are scarce despite the high unmet need. One cannot simply Submitted for publication October, 2015 Accepted for publication October, 2015 Address correspondence to: Hyong Jin Cho, MD, PhD, 300 UCLA Medical Plaza, Suite 3200A, Los Angeles, California 90095; Email: hjcho@ mednet.ucla.edu SLEEP, Vol. 38, No. 12, 2015
transplant and apply the research findings from high-income countries to elsewhere without a proper replication. The study is also significant because there are some important differences and similarities in its findings compared to the previous studies conducted in high-income countries. Although schizophrenia is accepted as a ubiquitous condition across countries, its presentation (i.e., the content and severity of psychotic symptoms) is influenced by sociocultural factors.17 Possibly reflecting this sociocultural influence (although methodological issues cannot be ignored), the overall prevalence of psychotic symptoms in this study (14.0%) was almost triple the median prevalence of psychotic symptoms estimated by a systematic review that only included high-income countries (5.3%).2 Moreover, in Koyanagi and Stickley study, the prevalence of psychotic symptoms varied greatly across countries, ranging from 0.7% to 45.7%.16 However, a more remarkable finding was that the association between sleep problems and psychotic symptoms was consistently significant throughout the world (overall odds ratio [OR] 2.41) with a lesser variation than the prevalence of psychotic symptoms (ORs ranging from 1.27 to 11.45). Of note, the overall OR remained significant after further adjustment for anxiety and depression (OR = 1.59). The robust association between sleep problems and psychotic symptoms consistently observed in the global context is a reasonable justification for future trials of insomnia treatment among individuals experiencing subclinical psychotic symptoms. Although Koyanagi and Stickley16 conducted a cross-sectional study that could not establish temporal or causal relationships between sleep problems and psychotic symptoms, their findings combined with those of longitudinal studies previously conducted in high-income countries9,12 provide a sound rationale for such clinical trials. In fact, as the authors note,16 in addition to an uncontrolled pilot trial,18 there is an ongoing randomized controlled trial of cognitive-behavioral therapy for insomnia (CBT-I) to improve sleep (primary outcome) for patients with distressing delusions or hallucinations in the context of a schizophrenia spectrum diagnosis.19 This ongoing trial will assess psychotic symptoms as secondary outcomes. Future trials should include individuals with subclinical psychotic symptoms and ultimately examine whether the treatment of sleep disturbance in these individuals averts the transition from subclinical symptoms to clinical disorders. Clinical trials that aim to prevent the development of psychotic disorders in the targeted sample of individuals with subclinical psychotic symptoms (who are therefore at high risk) may have a reasonable cost-effectiveness and a major practical
1837
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impact. Furthermore, sleep disturbance is treatable using behavioral treatments such as CBT-I and also a brief intervention named “Brief Behavioral Treatment for Insomnia” (BBTI).20 These behavioral treatments have a comparable efficacy to pharmacologic treatments but without the adverse effects observed in pharmacologic treatments.21 In particular, BBTI overcomes the limitation in implementing CBT-I, which requires clinicians specifically trained in sleep medicine and cognitivebehavioral therapy principles.21 Clinical trials of insomnia treatments targeting depression prevention are currently ongoing: “Promoting Sleep and Healthy Aging Research Study (PROSHARE)” (ClinicalTrials.gov Identifier: NCT01641263) and “Preventing Depression in Late Life: A Model for Low and Middle Income Countries” (NCT02145429). While the former is being conducted in Los Angeles, USA, using CBT-I, the latter is being conducted in Goa, India, using BBTI administered by lay health counselors. Given the example of these ongoing prevention trials for depression, a similar trial of insomnia treatment to prevent psychosis may not be an overly ambitious endeavor even in low- and middle-income countries. Future research should also investigate the potential mechanisms of the association between sleep disturbance and psychotic symptoms. In particular, potential biological mechanisms underlying the contribution of sleep disturbance to the development of psychotic symptoms and disorders warrant further examination. For example, innate immune system and inflammation are a potential target for mechanistic investigation because sleep disturbance is known to increase systemic inflammation,22 and recent research has shown increased systemic and neural inflammation in both ultra-high-risk individuals and schizophrenia patients.23–25 In summary, the report by Koyanagi and Stickley16 provides a valuable piece of evidence on the relationships between sleep problems and psychotic symptoms from a global perspective, with a particular coverage of low- and middle-income countries. Future research should investigate the potential mechanisms underlying these relationships and ultimately test whether the treatment of sleep disturbance in individuals with subclinical psychotic symptoms prevents the development of psychotic disorders. CITATION Cho HJ. Is sleep health a potential pathway to global mental health? SLEEP 2015;38(12):1837–1838. DISCLOSURE STATEMENT Dr. Cho has indicated no financial conflicts of interest. REFERENCES
1. Morin CM, Jarrin DC. Epidemiology of insomnia: prevalence, course, risk factors, and public health burden. Sleep Med Clin 2013;8:281–97. 2. van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L. A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol Med 2009;39:179–95. 3. Kelleher I, Cannon M. Psychotic-like experiences in the general population: characterizing a high-risk group for psychosis. Psychol Med 2011;41:1–6.
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4. Poulton R, Caspi A, Moffitt TE, Cannon M, Murray R, Harrington H. Children’s self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study. Arch Gen Psychiatry 2000;57:1053–8. 5. Phillips LJ, Leicester SB, O’dwyer LE, et al. The PACE Clinic: identification and management of young people at “ultra” high risk of psychosis. J Psychiatr Pract 2002;8:255–69. 6. Yung AR, McGorry PD. The initial prodrome in psychosis: descriptive and qualitative aspects. Aust N Z J Psychiatry 1996;30:587–99. 7. Ruhrmann S, Schultze-Lutter F, Salokangas RK, et al. Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study. Arch Gen Psychiatry 2010;67:241–51. 8. Jeppesen P, Clemmensen L, Munkholm A, et al. Psychotic experiences co-occur with sleep problems, negative affect and mental disorders in preadolescence. J Child Psychol Psychiatry 2015;56:558–65. 9. Thompson A, Lereya ST, Lewis G, Zammit S, Fisher HL, Wolke D. Childhood sleep disturbance and risk of psychotic experiences at 18: UK birth cohort. Br J Psychiatry 2015;207:23–9. 10. Taylor MJ, Gregory AM, Freeman D, Ronald A. Do sleep disturbances and psychotic-like experiences in adolescence share genetic and environmental influences? J Abnorm Psychol 2015;124:674–84. 11. Lee YJ, Cho S-J, Cho IH, Jang JH, Kim SJ. The relationship between psychotic-like experiences and sleep disturbances in adolescents. Sleep Med 2012;13:1021–7. 12. Freeman D, Stahl D, McManus S, et al. Insomnia, worry, anxiety and depression as predictors of the occurrence and persistence of paranoid thinking. Soc Psychiatry Psychiatr Epidemiol 2012;47:1195–203. 13. Freeman D, Brugha T, Meltzer H, Jenkins R, Stahl D, Bebbington P. Persecutory ideation and insomnia: findings from the second British National Survey of Psychiatric Morbidity. J Psychiatr Res 2010;44:1021–6. 14. Freeman D, McManus S, Brugha T, Meltzer H, Jenkins R, Bebbington P. Concomitants of paranoia in the general population. Psychol Med 2011;41:923–36. 15. Freeman D, Pugh K, Vorontsova N, Southgate L. Insomnia and paranoia. Schizophr Res 2009;108:280–4. 16. Koyanagi A, Stickley A. The association between sleep problems and psychotic symptoms in the general population: a global perspective. Sleep 2015;38:1875–85. 17. Kalra G, Bhugra D, Shah N. Cultural aspects of schizophrenia. Int Rev Psychiatry 2012;24:441–9. 18. Myers E, Startup H, Freeman D. Cognitive behavioural treatment of insomnia in individuals with persistent persecutory delusions: a pilot trial. J Behav Ther Exp Psychiatry 2011;42:330–6. 19. Freeman D, Startup H, Myers E, et al. The effects of using cognitive behavioural therapy to improve sleep for patients with delusions and hallucinations (the BEST study): study protocol for a randomized controlled trial. Trials 2013;14:214. 20. Buysse DJ, Germain A, Moul DE, et al. Efficacy of brief behavioral treatment for chronic insomnia in older adults. Arch Intern Med 2011;171:887–95. 21. Troxel WM, Germain A, Buysse DJ. Clinical management of insomnia with brief behavioral treatment (BBTI). Behav Sleep Med 2012;10:266–79. 22. Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry 2015 Jun 1 [Epub ahead of print]. 23. Perkins DO, Jeffries CD, Addington J, et al. Towards a psychosis risk blood diagnostic for persons experiencing high-risk symptoms: preliminary results from the NAPLS project. Schizophr Bull 2015;41:419–28. 24. Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Metaanalysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 2011;70:663–71. 25. Bloomfield PS, Selvaraj S, Veronese M, et al. Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [11C] PBR28 PET brain imaging study. Am J Psychiatry 2015 Oct 16. [Epub ahead of print].
Editorial—Cho
http://dx.doi.org/10.5665/sleep.5216
EDITORIAL
Is Sleep Health a Potential Pathway to Global Mental Health? Commentary on Koyanagi and Stickley. The association between sleep problems and psychotic symptoms in the general population: a global perspective. SLEEP 2015;38:1875–1885. Hyong Jin Cho, MD, PhD Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Sleep disturbance represents a major public health burden due to its high prevalence, negative health impact, and economic implications.1 Psychotic symptoms in the healthy general population, also called psychotic-like experiences or subclinical psychotic symptoms, are not uncommon, with the median prevalence estimated to be 5% to 8% according to a systematic review.2 Furthermore, subclinical psychotic symptoms share most risk factors with schizophrenia, including genetic, obstetric, developmental, substance use, psychopathological, social, and environmental risk factors3; and indeed increase the risk of schizophrenia.4 The existing evidence supports the notion of psychosis as a continuum ranging from subclinical psychotic symptoms to full-blown schizophrenia cases rather than a discrete nosological entity.2 In this context, there has been increasing clinical and research interest in the psychosis prodrome (a retrospective perspective because the concept of “prodrome” implies a necessary transition to disease), and in ultra-high-risk individuals for psychosis (prospective perspective).5 Sleep disturbance has been reported to be the most common symptom in the prodrome of psychosis6 and to be an important predictor of psychosis development among help-seeking individuals at ultra-high risk for psychosis.7 Similarly, sleep disturbance has been found associated with subclinical psychotic symptoms in cross-sectional and prospective studies.8–15 Thus, sleep disturbance is a modifiable risk factor for subclinical psychotic symptoms, and the treatment of sleep disturbance could ultimately lead to the prevention of clinical psychotic disorders. Despite the significance and potential practical impact of the associations between sleep disturbance and subclinical psychotic symptoms as described above, most studies on this topic have been conducted in high-income countries.8–15 In fact, the study of Koyanagi and Stickley reported in this issue of SLEEP appears to be not only the first study to address this topic from a global perspective, but also the first to examine it in low- and middle-income coiuntries.16 This study is significant because it is an important replication of previous studies in a global context and especially in low- and middle-income countries, where the resources for mental health research and care are scarce despite the high unmet need. One cannot simply Submitted for publication October, 2015 Accepted for publication October, 2015 Address correspondence to: Hyong Jin Cho, MD, PhD, 300 UCLA Medical Plaza, Suite 3200A, Los Angeles, California 90095; Email: hjcho@ mednet.ucla.edu SLEEP, Vol. 38, No. 12, 2015
transplant and apply the research findings from high-income countries to elsewhere without a proper replication. The study is also significant because there are some important differences and similarities in its findings compared to the previous studies conducted in high-income countries. Although schizophrenia is accepted as a ubiquitous condition across countries, its presentation (i.e., the content and severity of psychotic symptoms) is influenced by sociocultural factors.17 Possibly reflecting this sociocultural influence (although methodological issues cannot be ignored), the overall prevalence of psychotic symptoms in this study (14.0%) was almost triple the median prevalence of psychotic symptoms estimated by a systematic review that only included high-income countries (5.3%).2 Moreover, in Koyanagi and Stickley study, the prevalence of psychotic symptoms varied greatly across countries, ranging from 0.7% to 45.7%.16 However, a more remarkable finding was that the association between sleep problems and psychotic symptoms was consistently significant throughout the world (overall odds ratio [OR] 2.41) with a lesser variation than the prevalence of psychotic symptoms (ORs ranging from 1.27 to 11.45). Of note, the overall OR remained significant after further adjustment for anxiety and depression (OR = 1.59). The robust association between sleep problems and psychotic symptoms consistently observed in the global context is a reasonable justification for future trials of insomnia treatment among individuals experiencing subclinical psychotic symptoms. Although Koyanagi and Stickley16 conducted a cross-sectional study that could not establish temporal or causal relationships between sleep problems and psychotic symptoms, their findings combined with those of longitudinal studies previously conducted in high-income countries9,12 provide a sound rationale for such clinical trials. In fact, as the authors note,16 in addition to an uncontrolled pilot trial,18 there is an ongoing randomized controlled trial of cognitive-behavioral therapy for insomnia (CBT-I) to improve sleep (primary outcome) for patients with distressing delusions or hallucinations in the context of a schizophrenia spectrum diagnosis.19 This ongoing trial will assess psychotic symptoms as secondary outcomes. Future trials should include individuals with subclinical psychotic symptoms and ultimately examine whether the treatment of sleep disturbance in these individuals averts the transition from subclinical symptoms to clinical disorders. Clinical trials that aim to prevent the development of psychotic disorders in the targeted sample of individuals with subclinical psychotic symptoms (who are therefore at high risk) may have a reasonable cost-effectiveness and a major practical
1837
Editorial—Cho
impact. Furthermore, sleep disturbance is treatable using behavioral treatments such as CBT-I and also a brief intervention named “Brief Behavioral Treatment for Insomnia” (BBTI).20 These behavioral treatments have a comparable efficacy to pharmacologic treatments but without the adverse effects observed in pharmacologic treatments.21 In particular, BBTI overcomes the limitation in implementing CBT-I, which requires clinicians specifically trained in sleep medicine and cognitivebehavioral therapy principles.21 Clinical trials of insomnia treatments targeting depression prevention are currently ongoing: “Promoting Sleep and Healthy Aging Research Study (PROSHARE)” (ClinicalTrials.gov Identifier: NCT01641263) and “Preventing Depression in Late Life: A Model for Low and Middle Income Countries” (NCT02145429). While the former is being conducted in Los Angeles, USA, using CBT-I, the latter is being conducted in Goa, India, using BBTI administered by lay health counselors. Given the example of these ongoing prevention trials for depression, a similar trial of insomnia treatment to prevent psychosis may not be an overly ambitious endeavor even in low- and middle-income countries. Future research should also investigate the potential mechanisms of the association between sleep disturbance and psychotic symptoms. In particular, potential biological mechanisms underlying the contribution of sleep disturbance to the development of psychotic symptoms and disorders warrant further examination. For example, innate immune system and inflammation are a potential target for mechanistic investigation because sleep disturbance is known to increase systemic inflammation,22 and recent research has shown increased systemic and neural inflammation in both ultra-high-risk individuals and schizophrenia patients.23–25 In summary, the report by Koyanagi and Stickley16 provides a valuable piece of evidence on the relationships between sleep problems and psychotic symptoms from a global perspective, with a particular coverage of low- and middle-income countries. Future research should investigate the potential mechanisms underlying these relationships and ultimately test whether the treatment of sleep disturbance in individuals with subclinical psychotic symptoms prevents the development of psychotic disorders. CITATION Cho HJ. Is sleep health a potential pathway to global mental health? SLEEP 2015;38(12):1837–1838. DISCLOSURE STATEMENT Dr. Cho has indicated no financial conflicts of interest. REFERENCES
1. Morin CM, Jarrin DC. Epidemiology of insomnia: prevalence, course, risk factors, and public health burden. Sleep Med Clin 2013;8:281–97. 2. van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L. A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol Med 2009;39:179–95. 3. Kelleher I, Cannon M. Psychotic-like experiences in the general population: characterizing a high-risk group for psychosis. Psychol Med 2011;41:1–6.
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4. Poulton R, Caspi A, Moffitt TE, Cannon M, Murray R, Harrington H. Children’s self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study. Arch Gen Psychiatry 2000;57:1053–8. 5. Phillips LJ, Leicester SB, O’dwyer LE, et al. The PACE Clinic: identification and management of young people at “ultra” high risk of psychosis. J Psychiatr Pract 2002;8:255–69. 6. Yung AR, McGorry PD. The initial prodrome in psychosis: descriptive and qualitative aspects. Aust N Z J Psychiatry 1996;30:587–99. 7. Ruhrmann S, Schultze-Lutter F, Salokangas RK, et al. Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study. Arch Gen Psychiatry 2010;67:241–51. 8. Jeppesen P, Clemmensen L, Munkholm A, et al. Psychotic experiences co-occur with sleep problems, negative affect and mental disorders in preadolescence. J Child Psychol Psychiatry 2015;56:558–65. 9. Thompson A, Lereya ST, Lewis G, Zammit S, Fisher HL, Wolke D. Childhood sleep disturbance and risk of psychotic experiences at 18: UK birth cohort. Br J Psychiatry 2015;207:23–9. 10. Taylor MJ, Gregory AM, Freeman D, Ronald A. Do sleep disturbances and psychotic-like experiences in adolescence share genetic and environmental influences? J Abnorm Psychol 2015;124:674–84. 11. Lee YJ, Cho S-J, Cho IH, Jang JH, Kim SJ. The relationship between psychotic-like experiences and sleep disturbances in adolescents. Sleep Med 2012;13:1021–7. 12. Freeman D, Stahl D, McManus S, et al. Insomnia, worry, anxiety and depression as predictors of the occurrence and persistence of paranoid thinking. Soc Psychiatry Psychiatr Epidemiol 2012;47:1195–203. 13. Freeman D, Brugha T, Meltzer H, Jenkins R, Stahl D, Bebbington P. Persecutory ideation and insomnia: findings from the second British National Survey of Psychiatric Morbidity. J Psychiatr Res 2010;44:1021–6. 14. Freeman D, McManus S, Brugha T, Meltzer H, Jenkins R, Bebbington P. Concomitants of paranoia in the general population. Psychol Med 2011;41:923–36. 15. Freeman D, Pugh K, Vorontsova N, Southgate L. Insomnia and paranoia. Schizophr Res 2009;108:280–4. 16. Koyanagi A, Stickley A. The association between sleep problems and psychotic symptoms in the general population: a global perspective. Sleep 2015;38:1875–85. 17. Kalra G, Bhugra D, Shah N. Cultural aspects of schizophrenia. Int Rev Psychiatry 2012;24:441–9. 18. Myers E, Startup H, Freeman D. Cognitive behavioural treatment of insomnia in individuals with persistent persecutory delusions: a pilot trial. J Behav Ther Exp Psychiatry 2011;42:330–6. 19. Freeman D, Startup H, Myers E, et al. The effects of using cognitive behavioural therapy to improve sleep for patients with delusions and hallucinations (the BEST study): study protocol for a randomized controlled trial. Trials 2013;14:214. 20. Buysse DJ, Germain A, Moul DE, et al. Efficacy of brief behavioral treatment for chronic insomnia in older adults. Arch Intern Med 2011;171:887–95. 21. Troxel WM, Germain A, Buysse DJ. Clinical management of insomnia with brief behavioral treatment (BBTI). Behav Sleep Med 2012;10:266–79. 22. Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry 2015 Jun 1 [Epub ahead of print]. 23. Perkins DO, Jeffries CD, Addington J, et al. Towards a psychosis risk blood diagnostic for persons experiencing high-risk symptoms: preliminary results from the NAPLS project. Schizophr Bull 2015;41:419–28. 24. Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Metaanalysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 2011;70:663–71. 25. Bloomfield PS, Selvaraj S, Veronese M, et al. Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [11C] PBR28 PET brain imaging study. Am J Psychiatry 2015 Oct 16. [Epub ahead of print].
Editorial—Cho
