Skip to main content Accessibility help

Sleep and circadian rhythm disruption in schizophrenia

  • Katharina Wulff (a1), Derk-Jan Dijk (a2), Benita Middleton (a2), Russell G. Foster (a1) and Eileen M. Joyce (a3)...



Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions.


A systematic exploration of circadian time patterns in individuals with schizophrenia with recurrent sleep disruption.


We examined the relationship between sleep–wake activity, recorded actigraphically over 6 weeks, along with ambient light exposure and simultaneous circadian clock timing, by collecting weekly 48 h profiles of a urinary metabolite of melatonin in 20 out-patients with schizophrenia and 21 healthy control individuals matched for age, gender and being unemployed.


Significant sleep/circadian disruption occurred in all the participants with schizophrenia. Half these individuals showed severe circadian misalignment ranging from phase-advance/delay to non-24 h periods in sleep–wake and melatonin cycles, and the other half showed patterns from excessive sleep to highly irregular and fragmented sleep epochs but with normally timed melatonin production.


Severe circadian sleep/wake disruptions exist despite stability in mood, mental state and newer antipsychotic treatment. They cannot be explained by the individuals' level of everyday function.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Sleep and circadian rhythm disruption in schizophrenia
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Sleep and circadian rhythm disruption in schizophrenia
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Sleep and circadian rhythm disruption in schizophrenia
      Available formats


Royal College of Psychiatrists, This paper accords with the Wellcome Trust Open Access policy and is governed by the licence available at

Corresponding author

Russell G. Foster, University of Oxford, Level 6, West Wing, The John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK. Email:


Hide All

See editorial, pp. 273–274, this issue.

Declaration of interest




Hide All
1 Wulff, K, Gatti, S, Wettstein, JG, Foster, RG. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat Rev Neurosci 2010; 11: 589–99.
2 Tandon, R, Shipley, JE, Taylor, S, Greden, JF, Eiser, A, DeQuardo, J, et al. Electroencephalographic sleep abnormalities in schizophrenia. Relationship to positive/negative symptoms and prior neuroleptic treatment. Arch Gen Psychiatry 1992; 49: 185–94.
3 Lauer, CJ, Schreiber, W, Pollmacher, T, Holsboer, F, Krieg, JC. Sleep in schizophrenia: a polysomnographic study on drug-naive patients. Neuropsychopharmacology 1997; 16: 5160.
4 Nofzinger, EA, van Kammen, DP, Gilbertson, MW, Gurklis, JA, Peters, JL. Electroencephalographic sleep in clinically stable schizophrenic patients: two-weeks versus six-weeks neuroleptic-free. Biol Psychiatry 1993; 33: 829–35.
5 Chouinard, S, Poulin, J, Stip, E, Godbout, R. Sleep in untreated patients with schizophrenia: a meta-analysis. Schizophr Bull 2004; 30: 957–67.
6 Keshavan, MS, Reynolds, CF 3rd, Miewald, JM, Montrose, DM. A longitudinal study of EEG sleep in schizophrenia. Psychiatry Res 1996; 59: 203–11.
7 Keshavan, MS, Miewald, J, Haas, G, Sweeney, J, Ganguli, R, Reynolds, CF. Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders. J Psychiatr Res 1995; 29: 303–14.
8 van Kammen, DP, van Kammen, WB, Peters, J, Goetz, K, Neylan, T. Decreased slow-wave sleep and enlarged lateral ventricles in schizophrenia. Neuropsychopharmacology 1988; 1: 265–71.
9 Dijk, DJ, Archer, SN. PERIOD3, circadian phenotypes, and sleep homeostasis. Sleep Med Rev 2010; 14: 151–60.
10 Hampp, G, Ripperger, JA, Houben, T, Schmutz, I, Blex, C, Perreau-Lenz, S, et al. Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood. Curr Biol 2008; 18: 678–83.
11 Fletcher, PC, Frith, CD. Perceiving is believing: a Bayesian approach to explaining the positive symptoms of schizophrenia. Nat Rev Neurosci 2009; 10: 4858.
12 Wulff, K, Porcheret, K, Cussans, E, Foster, RG. Sleep and circadian rhythm disturbances: multiple genes and multiple phenotypes. Curr Opin Genet Dev 2009; 19: 237–46.
13 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). APA, 1994.
14 McGuffin, P, Farmer, A, Harvey, I. A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch Gen Psychiatry 1991; 48: 764–70.
15 Spitzer, RL, Kroenke, K, Williams, JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA 1999; 282: 1737–44.
16 Buysse, DJ, Reynolds, CF III, Monk, TH, Berman, SR, Kupfer, DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28: 193213.
17 Backhaus, J, Junghanns, K, Broocks, A, Riemann, D, Hohagen, F. Test-retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. J Psychosom Res 2002; 53: 737–40.
18 Carpenter, JS, Andrykowski, MA. Psychometric evaluation of the Pittsburgh Sleep Quality Index. J Psychosom Res 1998; 45: 513.
19 Horne, JA, Ostberg, O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol 1976; 4: 97110.
20 McNair, DM, Lorr, M, Droppleman, L. Manual for the Profile of Mood States. Educational and Industrial Testing Service, 1971.
21 Frances, A, Pincus, HA, First, MB. The Global Assessment of Functioning Scale (GAF). American Psychiatric Association, 1994.
22 Wulff, K, Joyce, EM, Middleton, B, Dijk, DJ, Foster, RG. The suitability of actigraphy, diary data, and urinary melatonin profiles for quantitative assessment of sleep disturbances in schizophrenia: a case report. Chronobiol Int 2006; 23: 485–95.
23 Van Someren, EJ, Swaab, DF, Colenda, CC, Cohen, W, McCall, WV, Rosenquist, PB. Bright light therapy: improved sensitivity to its effects on rest-activity rhythms in Alzheimer patients by application of nonparametric methods. Chronobiol Int 1999; 16: 505–18.
24 World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. WHO, 1992.
25 Aldhous, ME, Arendt, J. Radioimmunoassay for 6-sulphatoxymelatonin in urine using an iodinated tracer. Ann Clin Biochem 1988; 25: 298303.
26 Atkins, M, Burgess, A, Bottomley, C, Riccio, M. Chlorpromazine equivalents: a consensus of opinion for both clinical and research applications. Psychiatr Bull 1997; 21: 224–6.
27 Woods, SW. Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 2003; 64: 663–7.
28 Bai, YM, Ting Chen, T, Chen, JY, Chang, WH, Wu, B, Hung, CH, et al. Equivalent switching dose from oral risperidone to risperidone long-acting injection: a 48-week randomized, prospective, single-blind pharmacokinetic study. J Clin Psychiatry 2007; 68: 1218–25.
29 Weitzman, ED, Czeisler, CA, Coleman, RM, Spielman, AJ, Zimmerman, JC, Dement, W, et al. Delayed sleep phase syndrome. A chronobiological disorder with sleep-onset insomnia. Arch Gen Psychiatry 1981; 38: 737–46.
30 Hayakawa, T, Uchiyama, M, Kamei, Y, Shibui, K, Tagaya, H, Asada, T, et al. Clinical analyses of sighted patients with non-24-hour sleep-wake syndrome: a study of 57 consecutively diagnosed cases. Sleep 2005; 28: 945–52.
31 Weber, AL, Cary, MS, Connor, N, Keyes, P. Human non-24-hour sleep-wake cycles in an everyday environment. Sleep 1980; 2: 347–54.
32 Toh, KL, Jones, CR, He, Y, Eide, EJ, Hinz, WA, Virshup, DM, et al. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 2001; 291: 1040–3.
33 Gronfier, C, Wright, KP Jr, Kronauer, RE, Czeisler, CA. Entrainment of the human circadian pacemaker to longer-than-24-h days. Proc Natl Acad Sci USA 2007; 104: 9081–6.
34 Lisman, JE, Coyle, JT, Green, RW, Javitt, DC, Benes, FM, Heckers, S, et al. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 2008; 31: 234–42.
35 Mills, JN, Morgan, R, Minors, DS, Waterhouse, JM. The free-running circadian rhythms of two schizophrenics. Chronobiologia 1977; 4: 353–60.
36 Haug, HJ, Wirz-Justice, A, Rossler, W. Actigraphy to measure day structure as a therapeutic variable in the treatment of schizophrenic patients. Acta Psychiatr Scand Suppl 2000; 102: 91–5.
37 Wirz-Justice, A, Cajochen, C, Nussbaum, P. A schizophrenic patient with an arrhythmic circadian rest-activity cycle. Psychiatry Res 1997; 73: 8390.
38 Wirz-Justice, A, Haug, HJ, Cajochen, C. Disturbed circadian rest-activity cycles in schizophrenia patients: an effect of drugs? Schizophr Bull 2001; 27: 497502.
39 Martin, J, Jeste, DV, Caliguiri, MP, Patterson, T, Heaton, R, Ancoli-Israel, S. Actigraphic estimates of circadian rhythms and sleep/wake in older schizophrenia patients. Schizophr Res 2001; 47: 7786.
40 Martin, JL, Jeste, DV, Ancoli-Israel, S. Older schizophrenia patients have more disrupted sleep and circadian rhythms than age-matched comparison subjects. J Psychiatr Res 2005; 39: 251–9.
41 Krystal, AD, Thakur, M, Roth, T. Sleep disturbance in psychiatric disorders: effects on function and quality of life in mood disorders, alcoholism, and schizophrenia. Ann Clin Psychiatry 2008; 20: 3946.
42 Bromundt, V, Köster, M, Georgiev-Kill, A, Opwis, K, Wirz-Justice, A, Stoppe, G, et al. Sleep–wake cycles and cognitive functioning in schizophrenia. Br J Psychiatry 2011; 198: 269–76.

Related content

Powered by UNSILO
Type Description Title
Supplementary materials

Wulff et al. supplementary material
Supplementary Table S1-S7

 PDF (263 KB)
263 KB

Sleep and circadian rhythm disruption in schizophrenia

  • Katharina Wulff (a1), Derk-Jan Dijk (a2), Benita Middleton (a2), Russell G. Foster (a1) and Eileen M. Joyce (a3)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.

Sleep and circadian rhythm disruption in schizophrenia

  • Katharina Wulff (a1), Derk-Jan Dijk (a2), Benita Middleton (a2), Russell G. Foster (a1) and Eileen M. Joyce (a3)...
Submit a response


No eLetters have been published for this article.


Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *