Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics.
TL;DR: It appears possible that the high-potency drugs exert their effects on sleep in schizophrenic patients, for the most part, in an indirect way by suppressing stressful psychotic symptomatology.
Abstract: Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Disturbed sleep can be found in 30–80% of schizophrenic patients, depending on the degree of psychotic symptomatology. Measured by polysomnography, reduced sleep efficiency and total sleep time, as well as increased sleep latency, are found in most patients with schizophrenia and appear to be an important part of the pathophysiology of this disorder. Some studies also reported alterations of stage 2 sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep variables, i.e. reduced REM latency and REM density. A number of sleep parameters, such as the amount of SWS and the REM latency, are significantly correlated to clinical variables, including severity of illness, positive symptoms, negative symptoms, outcome, neurocognitive impairment and brain structure. Concerning specific sleep disorders, there is some evidence that schizophrenic patients carry a higher risk of experiencing a sleep-related breathing disorder, especially those demonstrating the known risk factors, including being overweight but also long-term use of antipsychotics. However, it is still unclear whether periodic leg movements in sleep or restless legs syndrome (RLS) are found with a higher or lower prevalence in schizophrenic patients than in healthy controls. There are no consistent effects of first-generation antipsychotics on measuresof sleep continuity and sleep structure, including the percentage of sleep stages or sleep and REM latency in healthy controls. In contrast to first-generation antipsychotics, the studied atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, ziprasidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity, with an increase in either total sleep time (TST) or sleep efficiency, and individually varying effects on other sleep parameters, such as an increase in REM latency observed for olanzapine, quetiapine and ziprasidone, and an increase in SWS documented for olanzapine and ziprasidone in healthy subjects. The treatment of schizophrenic patients with first-generation antipsychotics is consistently associated with an increase in TST and sleep efficiency, and mostly an increase in REM latency, whereas the influence on specific sleep stages is more variable. On the other hand, withdrawal of such treatment is followed by a change in sleep structure mainly in the opposite direction, indicating a deterioration of sleep quality. On the background of the rather inconsistent effects of first-generation antipsychotics observed in healthy subjects, it appears possible that the high-potency drugs exert their effects on sleep in schizophrenic patients, for the most part, in an indirect way by suppressing stressful psychotic symptomatology. In contrast, the available data concerning second-generation antipsychotics (clozapine, olanzapine, risperidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity in patients and healthy subjects, with an increase in TST and sleep efficiency or a decrease in wakefulness. Additionally, clozapine and olanzapine demonstrate comparable influences on other sleep variables, such as SWS or REM density, in controls and schizophrenic patients. Possibly, the effects of second-generation antipsychotics observed on sleep in healthy subjects and schizophrenic patients might involve the action of these drugs on symptomatology, such as depression, cognitive impairment, and negative and positive symptoms. Specific sleep disorders, such as RLS, sleep-related breathing disorders, night-eating syndrome, somnambulism and rhythm disorders have been described as possible adverse effects of antipsychotics and should be considered in the differential diagnosis of disturbed or unrestful sleep in this population.
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TL;DR: It is indicated that STOP null mice sleep less overall, and their sleep and wake periods are more fragmented than those of WT mice, which are consistent with the sleep patterns observed in patients with schizophrenia.
Abstract: Disruption of sleep/wake cycles is common in patients with schizophrenia and correlates with cognitive and affective abnormalities. Mice deficient in stable tubule only polypeptide (STOP) show cognitive, behavioral, and neurobiological deficits that resemble those seen in patients with schizophrenia, but little is known about their sleep phenotype. We characterized baseline sleep/wake patterns and recovery sleep following sleep deprivation in STOP null mice. Polysomnography was conducted in adult male STOP null and wild-type (WT) mice under a 12:12 hours light:dark cycle before, during, and after 6 hours of sleep deprivation during the light phase. At baseline, STOP null mice spent more time awake and less time in non-rapid eye movement sleep (NREMS) over a 24-hour period, with more frequent transitions between wake and NREMS, compared to WT mice, especially during the dark phase. The distributions of wake, NREMS and REMS across the light and the dark phases differed by genotype, and so did features of the electroencephalogram (EEG). Following sleep deprivation, both genotypes showed homeostatic increases in sleep duration, with no significant genotype differences in the initial compensatory increase in sleep intensity (EEG delta power). These results indicate that STOP null mice sleep less overall, and their sleep and wake periods are more fragmented than those of WT mice. These features in STOP null mice are consistent with the sleep patterns observed in patients with schizophrenia.
10 citations
08 May 2015
10 citations
TL;DR: Despite the prevalence of sleep disruption in psychiatric illness, the precise mechanism(s) of the interaction remains unclear and recent evidence suggests that this comorbidity may in part be due to common pathways and mechanisms.
Abstract: The above quote of Hippocrates dates back more than 2,000 years and demonstrates that a connection between sleep and health has long been recognized. Psychiatric disorders are no exception, with abnormal sleep patterns manifesting in nearly all mental disorders. The importance of sleep in psychiatric disorders can be seen in the incorporation of sleep in the diagnostic criteria for many disorders (classified according to the DSM 5 [1] and ICD-10) and applicable not only to adults, but also children and adolescents. More recently, the NIMH based research domain criteria (RDoC) initiative, which hopes to develop ‘‘... new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures’’, has named sleep (within arousal/regulatory systems) as one of five research domains, further highlighting the importance of sleep in future research and intervention in psychiatry [2]. Altered sleep patterns in psychiatric illness take varying forms, but are outwardly apparent to patients and clinicians under the umbrella term ‘‘disrupted sleep’’, which includes difficulty falling asleep, staying asleep, waking too early, ill-timed sleep, interrupted or non-restorative sleep and daytime sleepiness. Subjective complaints of troubled sleep by patients have been confirmed using objective and physiological measures of sleep. In a meta-analysis of sleep in adults with psychiatric disorders, Benca and colleagues [3] found that individuals in most psychiatric diagnostic categories, ranging from mood disorders to schizophrenia, showed signs of disrupted sleep. For example, over 80 % of depressed patients complain of difficulties falling or staying asleep. Furthermore, the magnitude of sleep problems is often linked to disease severity and, importantly, quality of life [4], making sleep an important therapeutic target for improving overall well-being. Despite the prevalence of sleep disruption in psychiatric illness, the precise mechanism(s) of the interaction remains unclear. Recent evidence suggests that this comorbidity may in part be due to common pathways and mechanisms. For example, several genes, intimately involved in the generation and regulation of circadian rhythms and sleep, have been linked to mental illness and vice versa [5–8]. Furthermore, psychiatric disorders are often associated with abnormal brain functioning—from neurotransmitter signaling to cortical network connectivity. As sleep is a complex state, dependent on efficacious brain functioning on multiple levels (e.g., neurotransmitters to networks), the fact that many psychiatric disorders are accompanied by a sleep phenotype is to be expected [9]. Thus, the aberrations in cortical functioning underlying psychiatric illness may also manifest as disrupted or irregular sleep. Much of the work regarding sleep in psychiatric populations has focused on adults; however, psychiatric disorders in childhood and adolescence are just as, if not more, important. For one, many psychiatric disorders have their peak onset during adolescence [10]. Some have speculated that this may be due to the neurobiological changes that occur during adolescence. The most striking among these is a significant cortical restructuring during which cortical grey matter volume plummets concurrent with an increase in white matter volume [11]. Furthermore, symptom persistence in mental disorders is higher during adolescence than during adulthood, and early onset of psychiatric illness seems to be L. Tarokh (&) C. Hamann B. G. Schimmelmann University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bolligenstr. 111, Haus A, 3000 Bern 60, Switzerland e-mail: leila.tarokh@kjp.unibe.ch
10 citations
TL;DR: Findings indicate that sleep markers can distinguish unaffected siblings of schizophrenia from healthy controls and serve as an endophenotype for schizophrenia.
Abstract: BACKGROUND Sleep disturbances in schizophrenia are common throughout its course including in the prodrome, and have been mainly attributed to severity of symptoms and antipsychotic use. We aimed to investigate whether early course patients with schizophrenia and young non-psychotic siblings of patients with schizophrenia also show sleep disturbances and whether sleep correlates with symptoms and functioning. METHODS Three study groups, that is, adults newly diagnosed with schizophrenia (n = 54), young non-psychotic siblings of schizophrenia patients (n = 56) and a sample of healthy controls matched to the patients and siblings (n = 61) were evaluated on Horne and Ostberg Morningness-Eveningness Questionnaire, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. Severity of symptoms and functioning are assessed using the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale, respectively. Age, gender, occupation and marital status were regarded as covariates, and differences between the three groups were evaluated using analysis of covariance. RESULTS Early course schizophrenia patients and non-psychotic siblings of schizophrenia patients showed significantly reduced sleep quality relative to healthy controls (P < .001). Schizophrenia patients had significantly higher daytime sleepiness compared to controls (P < .001). Chronotypes in schizophrenia patients and unaffected siblings did not significantly differ from those of the healthy controls. CONCLUSIONS Like chronic medicated schizophrenia patients, early course schizophrenia patients and young non-psychotic siblings of individuals with schizophrenia have sleep disturbances. These findings indicate that sleep markers can distinguish unaffected siblings of schizophrenia from healthy controls and serve as an endophenotype for schizophrenia.
10 citations
Cites background from "Sleep disturbances in patients with..."
...Sleep disturbances occur in 30% to 80% of schizophrenic patients, with variations depending on the severity of the disease (Cohrs, 2008)....
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TL;DR: This scenario suggests that the synthesis of neuroactive steroids during acute SD may be enacted as a neuroprotective response in the PFC; however, such compensation may in turn set off neurobehavioural complications by interfering with the corticolimbic connections responsible for executive functions and emotional regulation.
Abstract: Sleep deprivation (SD) is associated with a broad spectrum of cognitive and behavioural complications, including emotional lability and enhanced stress reactivity, as well as deficits in executive functions, decision making and impulse control. These impairments, which have profound negative consequences on the health and productivity of many individuals, reflect alterations of the prefrontal cortex (PFC) and its connectivity with subcortical regions. However, the molecular underpinnings of these alterations remain elusive. Our group and others have begun examining how the neurobehavioural outcomes of SD may be influenced by neuroactive steroids, a family of molecules deeply implicated in sleep regulation and the stress response. These studies have revealed that, similar to other stressors, acute SD leads to increased synthesis of the neurosteroid allopregnanolone in the PFC. Whereas this up-regulation is likely aimed at counterbalancing the detrimental impact of oxidative stress induced by SD, the increase in prefrontal allopregnanolone levels contributes to deficits in sensorimotor gating and impulse control, signalling a functional impairment of PFC. This scenario suggests that the synthesis of neuroactive steroids during acute SD may be enacted as a neuroprotective response in the PFC; however, such compensation may in turn set off neurobehavioural complications by interfering with the corticolimbic connections responsible for executive functions and emotional regulation.
9 citations
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TL;DR: Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
Abstract: The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
18,358 citations
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01 Jan 1968
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TL;DR: The Brief Psychiatric Rating Scale (BRS) as mentioned in this paper was developed to provide a rapid assessment technique particularly suited to the evaluation of patient change, and it is recommended for use where efficiency, speed, and economy are important considerations.
Abstract: The Brief Psychiatric Rating Scale was developed to provide a rapid assessment technique particularly suited to the evaluation of patient change. Sixteen symptom constructs which have resulted from factor analyses of several larger sets of items, principally Lorr's Multidimensional Scale for Rating Psychiatric Patients (MSRPP) (1953) and Inpatient Multidimensional Psychiatric Scale (IMPS) (1960), have been included for rating on 7-point ordered category rating scales. The attempt has been to include a single scale to record degree of symptomacology in each of the relatively independent symptom areas which have been identified. Some of the preliminary work which has led to the identification of primary symptom constructs has been published (Gorham & Overall, 1960, 1961, Overall, Gorharn, & Shawver, 1961). While other reports are in preparation, applications of the Brief Scale in both pure and applied research suggest the importance of presenting the basic instrument to the wider scientific audience at this time, together with recommendations for its standard use. The primary purpose in developing the Brief Scale has been the development of a highly efficient, rapid evaluation procedure for use in assessing treatment change in psychiatric patients while at the same time yielding a rather comprehensive description of major symptom characteristics. It is recommended for use where efficiency, speed, and economy are important considerations, while more detailed evaluation procedures, such as those developed by Lorr (1953, 1961) should perhaps be wed in other cases. In order to achieve the maximum effectiveness in use of the Brief Scale, a standard interview procedure and more detailed description of rating concepts are included in this report. In addition, each symptom concept is defined briefly in the rating scale statements themselves. Raters using the scale should become thoroughly familiar with the scale definitions presented herein, after which the rating scale statements should be sufficient to provide recall of the nature and delineation of each symptom area. , To increase the reliability of ratings, it is recommended that patients be interviewed jointly by a team of two clinicians, with the two raters making independent ratings at the completion of the interview. An alternative procedure which has been recommended by some is to have raters discuss and arrive at a
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TL;DR: Among the newer antipsychotic agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least, and the differences among newer agents may affect compliance with medication and health risk.
Abstract: OBJECTIVE: The purpose of this study was to estimate and compare the effects of antipsychotics—both the newer ones and the conventional ones—on body weight. METHOD: A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. RESULTS: Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg....
2,271 citations
TL;DR: A method of gravimetric planimetry by standard photographs offers a means to study the course of surface wounds more accurately than by clinical observation or by the pictorial record alone.
Abstract: obtain their surface in square centimeters. This simple method provides a means by objective measurements to make evident changes in the surface of wounds that are not apparent to the naked eye. Figure 1 shows the observations recorded with this method in a man of 42 years of age with hemiplegia and a decubital ulcer over the right buttock. The clinicians who had observed this wound daily had not noticed any remarkable change; however, it is quite obvious that the wound grew larger each time the treatment was changed, and that the use of an antibiotic was followed by a particularly striking enlargement of the lesion. In this instance the procedure of projection and gravimetric planimetry was repeated by different operators and a variation of ±5% was found (indicated by a cross-hatched area on Fig. 1). Figure 2 shows the same type of observation in a woman with hemiplegia and a decubital ulcer. This patient died from septicemia, and the decubital ulcer worsened with the general condition of the patient. A method of gravimetric planimetry by standard photographs offers a means to study the course of surface wounds more accurately than by clinical observation or by the pictorial record alone. References
2,201 citations