Sleep in neuropsychiatric disorders

Sleep disorders have been recognized for millennia as a common complication of medical and neurologic disease. Virtually all neuropsychiatric disorders carry with them the potential for disturbances of sleep. When such complications do exist, they are typically associated with decreased quality of life, increased morbidity, and, in some cases, increased mortality rates. The prevalence of major sleep disorders among neurologic patients is high, but the rate of detection and treatment is quite low. The major sleep-related problems in this population can be divided into six areas: insomnia, circadian rhythm (sleep-wake schedule) disorders, hypersomnia, sleep-related breathing disorders, motor disturbances in sleep, and parasomnias. In this brief review, general clinical principles, diagnostic assessment and management guidelines for each of these areas are considered and their specific manifestations in neuropsychiatric disorders identified.     

Effects of comorbid diagnoses on sleep disturbance in PTSD

Objective: Patients with post-traumatic stress disorder (PTSD) are frequently diagnosed with other psychiatric comorbid conditions. This study tested the hypothesis that PTSD patients suffer a greater proportion of sleep problems according to comorbid diagnoses. Method: National Comorbidity Survey (NCS) data from 591 individuals diagnosed with PTSD were analyzed. Revised versions of the Diagnostic Interview Schedule and Composite International Diagnostic Interview were administered to a representative sample of males and females. Groups consisted of patients diagnosed with lifetime PTSD and with current comorbid panic disorder, major depressive disorder, generalized anxiety disorder, and alcohol dependence. Results: Patients diagnosed with PTSD/panic disorder reported a significantly greater proportion of nightmare complaints (96%) and insomnia (100%) compared with the other comorbid groups. Conclusions: A greater proportion of PTSD patients with comorbid panic disorder complain of sleep-related problems than other comorbid groups. This effect appears unique to panic, rather than other general anxiety disorder or depression. Prospective sleep studies are needed to differentiate the role of sleep in PTSD and PD, as well as to examine the role of psychiatric comorbidity in worsening sleep in PTSD patients.     

Nocturnal choking episodes: under-recognized and misdiagnosed

Causes of nocturnal paroxysmal events include a variety of disorders such as epileptic seizures, parasomnias, sleep-related movement disorders, and psychiatric disturbances. Timing and semiology of the events, simultaneous video-electroencephalographic observation, presence of any daytime events, and relevant psychiatric and medical history may help in sorting out various possibilities considered in the differential diagnosis of such events. Timely diagnosis of these events is crucial for appropriate management; under-recognition and misdiagnosis of nonepileptic events is not uncommon. Described here are two cases within the spectrum of nocturnal paroxysmal events, one with nocturnal panic attacks and the other with frontal lobe epilepsy, each presenting with choking episodes.     

Actigraphic sleep monitoring in posttraumatic stress disorder (PTSD) patients

Posttraumatic stress disorder (PTSD) patients frequently complain that they suffer from sleep disturbances. To date, the polysomnographic studies that have attempted to study PTSD patients' subjective complaints of sleep difficulties have produced conflicting results. The objective of the present study was to compare PTSD patients' subjective complaints of poor sleep and objective actigraphic recordings of their sleep over a period of several consecutive nights. The results indicate that PTSD patients do not suffer from poorer sleep than a control group, based on actigraphic measures, and that their subjective sleep evaluation is inconsistent with objective sleep measures. These patients fail to correctly estimate their sleep.     

Sleep in Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is often associated with sleep disturbances. In this review, we focus on the published literature on subjective and objective findings of sleep in patients with PTSD. Insomnia and nightmares are most commonly reported subjective sleep disturbances. Polysomnographic investigations have frequently reported rapid eye movement (REM) sleep abnormalities in PTSD. However, studies have not been consistent about the type of REM sleep dysfunction in PTSD patients. Antidepressants such as nefazodone, trazodone, fluvoxamine, and imagery rehearsal therapy are found to be beneficial in the treatment of PTSD associated sleep disturbances as well as core symptoms of this anxiety disorder. We propose use of such modalities of treatment in PTSD patients with predominant sleep disturbances. Further studies are required to clarify polysomnographic sleep changes especially role of REM sleep dysregulation and treatment of sleep disturbances in PTSD.     

Post-traumatic stress disorder and sleep-what a nightmare!

According to DSM IV criteria, sleep disturbances are incorporated in the definition of post-traumatic stress disorder (PTSD). These include the re-experiencing symptoms (nightmares, criteria B) and a hyperarousal state (difficulty initiating and maintaining sleep, criteria D). PTSD patients commonly complain of sleep disturbances. Moreover, insomnia, restless sleep and trauma-related dreams might be the primary complaint of some patients. However, although subjective sleep disturbances are considered characteristic of PTSD, sleep laboratory studies have provided inconsistent evidence of objective sleep disorders. A variety of sleep architectures and sleep patterns has been reported in PTSD. However, only a few studies have controlled for comorbidities. Thus, uncertainty exists to what extent the sustained complaints of sleep disturbances in chronic PTSD are specifically related to the impact of exposure to traumatic stress, or rather are a consequence of comorbid disorders. Specific changes in REM sleep suggest a pathophysiologic role of REM sleep abnormality in PTSD (e.g. anxiety dreams, increased REM density, exaggerated startle response, decreased dream recall and elevated awakening thresholds from REM sleep). However, again, studies have failed to show consistent changes in percentage of REM sleep or in REM latency. There might be a coexistence of pressure to REM along with inhibitory forces of REM that result in high variability of REM parameters across patients. Alternatively, changes in REM sleep might reflect the effect of comorbid psychiatric disorders that results in inconsistent findings between patients. The current review tries to address these issues based on recent studies carried out in this field.     

Sleep and Suicide in Psychiatric Patients

Suicidal patients often report problems with their sleep. Although sleep-related complaints and EEG (electroencephalographic) changes have been seen widely across the spectrum of psychiatric disorders, sleep complaints such as insomnia, hypersomnia, nightmares, and sleep panic attacks are more common in suicidal patients. The subjective quality of sleep as measured by self-rated questionnaires also appears to be more disturbed in suicidal depressive patients. Sleep studies have reported various polysomnographic findings including increased REM (rapid eye movement) time and REM activity in suicidal patients with depression, schizoaffective disorder, and schizophrenia. One mechanism responsible for this possible association between suicide and sleep could be the role of serotonin (5HT). Serotonergic function has been found to be low in patients who attempted and/or completed suicide, particularly those who used violent methods. Aggression dyscontrol appears to be an intervening factor between serotonin and suicide. Additionally, agents that enhance serotonergic transmission decrease suicidal behavior. Serotonin has also been documented to play an important role in onset and maintenance of slow wave sleep and in REM sleep. CSF 5-HIAA levels have been correlated with slow wave sleep in patients with depression as well as schizophrenia. Moreover, 5HT2 receptor antagonists have improved slow wave sleep. Further studies are needed to investigate the possible role of sleep disturbance in suicidal behavior.     

Sleep disturbances in patients with Parkinson disease

Sleep disturbances are among the most common disabling nonmotor symptoms of Parkinson disease (PD). Recently, awareness of sleep disorders related to PD has increased, reflecting their significant negative impact on the quality of life of the patient. However, sleep disturbances are still often under-recognized. In PD, multiple factors are associated with sleep disturbances; impaired arousal systems and sleep structure as disease-related changes, nocturnal motor symptoms, hallucinations and psychosis, pain, nocturia, depressive symptoms and dopaminergic medication can all cause insomnia. Further, these factors can coexist and influence each other during the course of the disease. In addition, sleep-related breathing disorder, restless legs syndrome (RLS) and rapid eye movement sleep behavior disorder (RBD) can also lead to impaired sleep. Some idiopathic RBD patients have been associated with a risk for developing neurodegenerative diseases, including PD. Therefore, early diagnosis of RBD may have significant clinical implications for neuroprotective strategies. Several studies have revealed an increased incidence of RLS in PD patients compared to the general population. The favorable responses to dopaminergic medications in treating both RLS and PD suggest shared pathophysiologies between the two diseases; however, neuroimaging studies of dopaminergic systems remain inconclusive. In this review, we discuss the current understanding of sleep disturbances in PD and the existing treatments.     

Nocturnal and daytime panic attacks--comparison of sleep architecture, heart rate variability, and response to sodium lactate challenge.

BACKGROUND: The purpose of this study was to determine if nocturnal panic patients have greater autonomic dysregulation than patients with daytime panic. METHODS: Three groups were studied: patients who suffer from panic attacks during sleep (n = 12), those who suffer from daytime panic attacks only (n = 12), and control subjects (n = 12). Each subject underwent 24-hour holter monitoring for heart rate variability (HRV), an overnight sleep recording, and sodium lactate challenge during wakefulness. RESULTS: There was a marked subjective response to the sodium lactate challenge in the panic disorder (PD) patients but not in control subjects. Each group showed changes in HRV in response to sodium lactate challenge. The decrease in HRV measures was more marked in PD patients as a whole than in control subjects. During non-rapid eye movement (REM) sleep the value for total power (TP) was significantly higher in the nocturnal panic patients. The PD patients as a whole had higher values for TP and low-frequency (LF) power during REM sleep than control subjects. There were no significant differences between the two PD groups in sleep architecture. The PD patients as a whole had lower sleep efficiency and less stage 4 sleep than control subjects. CONCLUSIONS: These findings indicate that there are substantial differences between PD and control subjects in autonomic regulation and that there are small differences between patients with daytime panic attacks and those with sleep-related panic attacks.     

Epidemiology and clinical features of sleep disorders in extrapyramidal disease

Sleep disturbances are common in extrapyramidal diseases, including not only insomnia but excessive daytime sleepiness and parasomnias. In particular, complaints related to sleep are extremely common among patients affected by Parkinson's disease (PD). The underlying causes may include: patient age, associated illnesses, cognitive impairment, motor dysfunction caused by disease, neurochemical changes related to the disease, drugs, and secondary psychological responses to the disease. The exact prevalence of sleep disorders in PD is difficult to ascertain, due to the heterogeneity of patients as well as to the different criteria and methods used to diagnose and classify sleep disturbances. In this study, we will attempt to review the epidemiological data and to describe the various sleep disorders, which have been identified in extrapyramidal diseases, with particular reference to PD. There are no data available at present as to the role of gender in sleep disturbances. Finally, the benefit of sleep on extrapyramidal diseases will be addressed, taking into account that the above causes may modify the effects of sleep.     

Sleep and psychiatry

Psychiatric disorders constitute 15.4% of the disease burden in established market economies. Many psychiatric disorders are associated with sleep disturbances, and the relationship is often bidirectional. This paper reviews the prevalence of various psychiatric disorders, their clinical presentation, and their association with sleep disorders. Among the psychiatric disorders reviewed are affective disorders, psychosis, anxiety disorders (including posttraumatic stress disorder), substance abuse disorders, eating disorders, and attention deficit/hyperactivity disorders. The spectrum of associated sleep disorders includes insomnia, hypersomnia, nocturnal panic, sleep paralysis, hypnagogic hallucinations, restless legs/periodic limb movements of sleep, obstructive sleep apnea, and parasomnias. The effects on sleep of various psychotropic medications utilized to treat the above psychiatric disorders are summarized.     

A Neurodegenerative Disease Sleep Questionnaire: Principal component analysis in Parkinson's disease

Sleep disturbances are common in many neurodegenerative diseases and may include altered sleep duration, fragmented sleep, nocturia, excessive daytime sleepiness, and vivid dreaming experiences, with occasional parasomnias. Although representing the “gold standard,” polysomnography is not always cost-effective or available for measuring sleep disturbance, particularly for screening. Although numerous sleep-related questionnaires exist, many focus on a specific sleep disturbance (e.g., restless legs, REM Behavior Disorder) and do not capture efficiently the variety of sleep issues experienced by such patients. We administered the 12-item Neurodegenerative Disease Sleep Questionnaire (NDSQ) and the Epworth Sleepiness Scale to 145 idiopathic Parkinson's disease patients. Principal component analysis using eigenvalues greater than 1 suggested five separate components: sleep quality (e.g., sleep fragmentation), nocturia, vivid dreams/nightmares, restless legs symptoms, and sleep-disordered breathing. These results demonstrate construct validity of our sleep questionnaire and suggest that the NDSQ may be a useful screening tool for sleep disturbances in at least some types of neurodegenerative disorders.     

Sleep and the gastrointestinal tract

In this review, an integration of GI functioning is attempted with regard to its relationship to sleep, how this interaction may lead to complaints of sleep disorders, and the pathogenesis of some GI disorders. Data are presented to support the notion that sleep-related GER is an important factor not only in the development of esophagitis but also in the respiratory complications of GER. Although sensory functioning is altered markedly during sleep with regard to most standard sensory functions (eg, auditory), there seems to be an enhancement of some visceral sensation during sleep that seems to protect the tracheobronchial tree from aspiration of gastric contents reflux during sleep. Patients who have functional bowel disorders reveal an increase in sleep complaints compared with normal volunteers. The actual mechanisms of these disturbances remain somewhat obscure and studies do not demonstrate any consistent abnormalities in sleep patterns of these patients. Some studies show that autonomic functioning during sleep, particularly REM sleep, can distinguish patients who have IBS. Thus, the continued study of sleep and GI functioning promises to create a new dimension in the understanding of the pathophysiology of a variety of GI disorders.     

Sleep related eating disorder

Nighttime eating is categorized as either sleep-related eating disorder (SRED) or night eating syndrome (NES). Critical reviews of the literature on both disorders have suggested that they are situated at opposite poles of a disordered eating spectrum. The feeding behavior in SRED is characterized by recurrent episodes of eating after an arousal from nighttime sleep with amnesia. Conversely, NES could be considered as an abnormality in the circadian rhythm of meal timing with a normal circadian timing of sleep onset. Both conditions clearly concentrate to occur during young adulthood, and are often relentless and chronic. Misunderstanding and low awareness of SRED and NES have limited our ability to determine the exact prevalence of the two disorders. SRED is frequently associated with other sleep disorders, in particular parasomnias such as sleep walking. Cognitive-behavioral therapy is ineffective, but pharmacotherapy is very effective in controlling SRED. Especially, studies have shown that the anti-seizure medication topiramate may be an effective treatment for SRED.     

Psychiatric Illness and Parasomnias: a Systematic Review

Purpose of Review

Little is known about the presence of parasomnias such as nightmare disorder, sleep paralysis, REM sleep behavior disorder (RBD), and sleep-related eating disorders (SRED) in people with mental illness. A predominant view suggests that psychotropic medications might be contributing to parasomnias. This article summarizes knowledge regarding the relationships between psychiatric disorders and parasomnias, and possible confounds. A systematic search of the literature in the past 10 years identified 19 articles.

Recent Findings

There were significantly elevated rates of parasomnias in psychiatric disorders (average prevalence of nightmares was 38.9%, sleep paralysis 22.3%, SRED 9.9%, sleepwalking 8.5%, and RBD 3.8%). Medication usage was only one of many risk factors (other sleep disorders, medical comorbidities, and substance abuse) which were associated with parasomnias.

Summary

A strong association exists between mental illness and parasomnias which is not fully explained by medications. Prospective longitudinal studies are needed to develop a better understanding of the unique and shared variance from multiple risk factors.

     

Subjective sleep complaints in pediatric depression: a controlled study and comparison with EEG measures of sleep and waking

OBJECTIVE: Children with major depressive disorder (MDD) often complain of sleep disturbances; however, polysomnographic studies have failed to find objective evidence of these disturbances. This article examines subjective sleep reports of children with MDD and healthy controls focusing on comparing subjective and objective sleep measures. METHOD: Fifty-one subjects with MDD and 42 healthy subjects, 8-17 years old, participated in a comprehensive psychobiologic study including three nights of EEG sleep recording. Each morning, subjects completed a post-sleep form subjectively rating their sleep, which was then compared with their polysomnographic studies. RESULTS: Depressed subjects reported significantly worse sleep on four scales: subjective sleep quality, perceived number of awakenings, estimated minutes awake, and perceived ease of waking. In contrast to these subjective complaints, objective EEG measures indicated no evidence of disturbed sleep in the depressed sample compared to controls. Furthermore, exploratory analyses focusing on the subset of depressed subjects with the greatest subjective sleep disturbance showed, paradoxically, significantly better sleep in terms of the number of EEG awakenings and objective disturbances. CONCLUSIONS: Despite clinical evidence of subjective sleep complaints in depressed children, our EEG measures showed little evidence to indicate an objective basis for these perceptions. These findings raise provocative questions regarding the nature of sleep complaints associated with early-onset depression.     

Sleep problems in children with attention-deficit/hyperactivity disorder: impact of subtype, comorbidity, and stimulant medication.

OBJECTIVE: To determine the relationship of sleep problems to attention-deficit/hyperactivity disorder (ADHD), diagnostic subtype, comorbid disorders, and the effects of stimulant treatment. METHOD: On the basis of clinical diagnostic interviews, children aged 6 to 12 years were assigned to 4 groups: unmedicated ADHD (n = 79), medicated ADHD (n = 22), clinical comparison (n = 35), and healthy nonclinical comparison (n = 36). These groups were compared on 2 sleep questionnaires completed by the parents that assessed current sleep problems and factors associated with sleep difficulties (i.e., sleep routines, sleep practices, child and family sleep history). RESULTS: Factor analysis revealed 3 sleep problem categories: dyssomnias, parasomnias, and sleep-related involuntary movements. Linear regression analyses showed that (1) dyssomnias were related to confounding factors (i.e., comorbid oppositional defiant disorder and stimulant medication) rather than ADHD; (2) parasomnias were similar in clinical and nonclinical children; and (3) the DSM-IV combined subtype of ADHD was associated with sleep-related involuntary movements. However, sleep-related involuntary movements were more highly associated with separation anxiety. CONCLUSIONS: The results suggest that the relationship between sleep problems and ADHD is complex and depends on the type of sleep problem assessed as well as confounding factors such as comorbid clinical disorders and treatment with stimulant medication.     

Non-rapid eye movement sleep parasomnias

Parasomnias are unpleasant or undesirable behavioral or experiential phenomena that occur during sleep. Once believed unitary phenomena related to psychiatric disorders, it is now clear that parasomnias result from several different phenomena and usually are not related to psychiatric conditions. Parasomnias are categorized as primary (disorders of the sleep states) and secondary (disorders of other organ systems that manifest themselves during sleep). Primary sleep parasomnias can be classified according to the sleep state of origin: rapid eye movement sleep, non-rapid eye movement sleep, and miscellaneous (those not respecting sleep state). Secondary sleep parasomnias are classified by the organ system involved.     

Sighs during sleep in multiple system atrophy

Sighs are physiological phenomena and may occasionally occur during sleep in healthy young adults. Although inspiratory sighs are considered a diagnostic red flag for the parkinsonian form of multiple system atrophy (MSA), its frequency and characteristics are unclear. We aimed to define sigh frequency during sleep recordings in patients with MSA compared to Parkinson's disease (PD) patients, as well as evaluate possible associated breathing disorders or autonomic changes. We analyzed 9 polysomnography's from patients with MSA and 9 from matched PD patients. The proportion of MSA patients (both MSA-P and MSA-C) with sleep-related sighs was significantly higher than that of PD patients, and these occurred predominantly in stages N1 and N2. The median sigh index in sleep and wakefulness were also significantly higher in MSA, although with a significant inter-subject variability. Higher sigh indexes were not associated to other breathing disturbances or with longer disease duration. In MSA, 12% of sighs were associated with oxygen desaturation, while none of the events in PD patients presented with significant changes in oxygen saturation. Respiratory events followed 45% of sighs in MSA, predominantly central sleep apneas, and 29% of sighs in PD, predominantly hypopneas. Our data suggests that high sigh frequencies during sleep should also be considered a red flag for MSA, and future studies should aim to determine whether increased sighing frequency during sleep is specific for this disorder.