Understanding the Links Between Schizophrenia and Sleep Disorders

Although schizophrenia is estimated to affect less than 1% of the global population, it imposes a substantial individual and societal burden.¹ Along with the positive and negative symptoms and cognitive impairments that comprise the diagnostic criteria for the disease, a growing body of research consistently shows that patients with schizophrenia often suffer from sleep disturbances.

Sleep impairment — most frequently insomnia — is the most commonly reported symptom in individuals who are in the prodromal phase of schizophrenia.² In addition, both self-report and objective sleep measures have demonstrated sleep abnormalities in research participants at high risk for developing psychosis and in patients with an established diagnosis.

Further studies indicate an inverse link between sleep disturbance and symptom severity in patients with schizophrenia, as well as increased rates of sleep disorders.³ However, the evidence regarding these associations and related risks and treatment considerations has yet to be comprehensively examined. To that end, the researchers in a new paper published in Nature of Science and Sleep reviewed the results of 54 studies that investigated these topics.⁴ Selected findings are highlighted below.

• Insomnia. In animal and human experiments, dysfunctional dopamine receptors have been implicated as a mechanism underlying the association between insomnia and schizophrenia. For example, in a study that captured sleep recordings of 20 healthy males, the duration of the first non-REM period was 47% longer compared with baseline in participants who had received the dopamine D1 antagonist NNC-687 vs placebo.⁵ “D1 antagonist increased spindles (total number, incidence, and burst duration) and delta waves activity (reduced peak amplitude but increased their instantaneous frequency),” the present investigators reported.

“Nearly all antipsychotic medications (APs) are, at least in part, D2 receptor antagonists, making them successful in treating positive symptoms by lowering the overactivity of these receptors and preventing the binding of dopamine.” Many patients are nonadherent to APs, and previous results suggest that severe psychotic symptoms are more likely to develop in patients with impaired sleep vs patients without sleep disturbances following discontinuation of APs.⁶

• Restless legs syndrome (RLS). Because APs exert their effects by blocking D2 receptors, they may lead to or worsen RLS and periodic limb movement disorder (PLMD), conditions that respond to treatment with dopamine agonists. One study found a significantly higher incidence of RLS and prevalence of RLS symptoms in patients with schizophrenia compared with controls (21.4% and 47.8% vs 9.3% and 19.4%, respectively), and more severe symptoms were observed in patients with vs without RLS.⁷
• Obstructive sleep apnea (OSA). Various studies have reported a high prevalence of OSA in patients with schizophrenia — 15.4% in one meta-analysis, for example, and 14% in a study of 175 outpatients.^8,9 Obesity may be one factor underlying this connection. “Excessive weight gain is a common side effect of APs, and both genetically determined and medication-induced obesity can lead to OSA,” according to the review.

Limited findings also point to potential links between schizophrenia and circadian rhythm disorders (which may be affected by APs, lifestyle factors, and psychiatric symptoms), night eating syndrome, and narcolepsy.

Schizophrenia and sleep disturbances are both associated with a higher risk for health problems. Compared with patients with either condition alone, patients who have both disorders generally have worse outcomes and quality of life, higher mortality, and more severe symptoms. “Also, sleep disorders affect social and cognitive functioning, and therefore are likely to contribute in a significant way to the daily challenges commonly experienced by patients with schizophrenia,” review co-author Fabio Ferrarelli, MD, PhD, assistant professor of psychiatry at the University of Pennsylvania Medical Center, told Psychiatry Advisor.

Treatment options

There are numerous approaches that may effectively treat insomnia in this population, although adherence may be a challenge, especially with pharmacological strategies. Cognitive behavioral therapy  can be used to target issues such as lack of daytime activity and bedtime routine, intrusive thoughts or hallucinations at bedtime, or preoccupation with being able to fall or stay asleep.

For acute insomnia or problems with falling or staying asleep, research has demonstrated effectiveness for the second-generation APs paliperidone and olanzapine, atypical APs, the hypnotic agents eszopiclone and zopiclone, and melatonin. “Regardless of the specific approach selected, increasing evidence suggests that patients should be actively engaged in the treatment process,” the authors stated.

Dr Ferrarelli offers the following main takeaways for mental health clinicians.

• Ask your patients if they have sleep problems and, when in doubt, refer them for a sleep study to assess for sleep disorders.
• Do not underestimate the role of poor sleep in precipitating or exacerbating a variety of psychiatric symptoms, including hallucinations, paranoia, poor concentration, thought disorganization, and depressed mood.
• If you work on improving the your patients’ quality of sleep, there is a good chance that some of their symptoms will get better as well.

Next steps

Future research in this area should explore whether having schizophrenia predisposes patients to having sleep disorders or vice versa, and how the presence of one condition influences the occurrence of the other. For example, taking “antipsychotic medications, having a sedentary lifestyle, and smoking — which are all common in schizophrenia — facilitate the onset of sleep disorders, including OSA,” said Dr Ferrarelli. “However, baseline screening for this and other sleep disorders are [is] not performed when patients are initially diagnosed.” Researchers should also investigate how treatment to improve sleep may affect various symptoms of schizophrenia.

References

1. Saha S, Chant D, Welham J, et al. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):e141. 
2. Zanini M, Castro J, Coelho FM, et al. Do sleep abnormalities and misaligned sleep/circadian rhythm patterns represent early clinical characteristics for developing psychosis in high risk populations? [published online October 3, 2013]. Neurosci Biobehav Rev. doi:10.1016/j.neubiorev.2013.08.012
3. Yang C, Winkelman JW. Clinical significance of sleep EEG abnormalities in chronic schizophrenia. Schizophr Res. 2006;82(2):251-260.
4. Kaskie RE, Graziano B, Ferrarelli F. Schizophrenia and sleep disorders: links, risks, and management challenges. Nat Sci Sleep. 2017;9:227-239.
5. Eder DN, Zdravkovic M, Wildschiødtz G. Selective alterations of the first NREM sleep cycle in humans by a dopamine D1 receptor antagonist (NNC-687). J Psychiat. Res. 2003; 37(4):305-312.
6. Chemerinski E, Ho BC, Flaum M, Arndt S, Fleming F, Andreasen NC. Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia. Compr Psychiatry. 2002; 43(5):393-396.
7. Kang SG, Lee HJ, Jung SW, et al. Characteristics and clinical correlates of restless legs syndrome in schizophrenia [published online March 27, 2007]. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31(5):1078-1083.
8. Stubbs B, Vancampfort D, Veronese N, et al. The prevalence and predictors of obstructive sleep apnea in major depressive disorder, bipolar disorder and schizophrenia: a systematic review and meta-analysis [published online March 9, 2016]. J Affect Disord. doi:10.1016/j.jad.2016.02.060
9. Annamalai A, Palmese LB, Chwastiak LA, Srihari VH, Tek C. High rates of obstructive sleep apnea symptoms among patients with schizophrenia. Psychosomatics. 2015; 56(1):59-66. doi:10.1016/j.psym.2014.02.009