| 1 | Schizophr Bull 2004 -1 30: 957-67 |
|---|---|
| PMID | 15954201 |
| Title | Sleep in untreated patients with schizophrenia: a meta-analysis. |
| Abstract | The present meta-analysis investigated the characteristics of sleep in patients with schizophrenia without neuroleptic treatment at the time of sleep recording. The 20 selected studies included 652 participants (321 patients with schizophrenia and 331 healthy subjects). Effect sizes were evaluated using d values for the following sleep variables: sleep latency (SL), total sleep time (TST), sleep efficiency index (SEI), total awake time (TAT), stage 2 percentage (S2%), stage 4 percentage, slow-wave-sleep percentage, rapid-eye-movement (REM) percentage, and REM latency. The initial meta-analysis revealed that patients with schizophrenia have the following sleep disorders: increased SL, decreased TST, and decreased SEI. A moderator analysis revealed that these sleep disorders were worse for the neuroleptic-withdrawal group relative to the never-treated group. However, only never-treated patients showed significantly increased TAT and diminished S2%. These results confirm that patients with schizophrenia have sleep disorders that are not necessarily a consequence of neuroleptic treatments, suggesting that sleep disorders are an intrinsic feature of schizophrenia. However, it must be noted that some sleep disorders may be amplified by residual effects of neuroleptic withdrawal, while others appear to be dampened by neuroleptic treatment. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | CNS Drugs 2008 -1 22: 939-62 |
| PMID | 18840034 |
| Title | Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics. |
| 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 measures of 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. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | CNS Drugs 2008 -1 22: 939-62 |
| PMID | 18840034 |
| Title | Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics. |
| 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 measures of 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. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | BMC Neurosci 2009 -1 10: 132 |
| PMID | 19912621 |
| Title | Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level. |
| Abstract | Protein kinase C interacting protein (PKCI/HINT1) is a small protein belonging to the histidine triad (HIT) family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO) mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT) littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA) axis function, we assessed the HPA activity through measurement of plasma corticosterone levels. Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST) and the tail suspension (TST) tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT. PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Neuropharmacology 2010 Jan 58: 69-77 |
| PMID | 19615387 |
| Title | Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist. |
| Abstract | The widely reported effects of oxytocin (OT) on CNS function has generated considerable interest in the therapeutic potential for targeting this system for a variety of human psychiatric diseases, including anxiety disorders, autism, schizophrenia, and depression. The utility of synthetic OT, as both a research tool and neurotherapeutic, is limited by the physiochemical properties inherent in most neuropeptides, notably its short half-life and poor blood brain barrier penetration. Subsequently, the discovery and development of non-peptide molecules that act as selective agonists of the oxytocin receptor (OTR) has been an important goal of the field. In this study, we report the receptor and behavioral pharmacology of WAY-267464, a first generation small-molecule OTR agonist. WAY-267464 is a high-affinity, potent, and selective (vs. V1a, V2, V1b) agonist of the OTR. In assays measuring both behavioral (four-plate test, elevated zero maze) and autonomic (stress-induced hyperthermia) parameters of the anxiety response, WAY-267464 exhibits an anxiolytic-like profile similar to OT. We have demonstrated that the anxiolytic-like profile of WAY-267464 is mediated through central sites of action. WAY-267464 also significantly reverses disruption in prepulse inhibition of the acoustic startle reflex induced by either MK-801 or amphetamine, similar to the antipsychotic-like effects previously reported for OT. Interestingly, in the mouse tail suspension test, WAY-267464 failed to produce changes in immobility that are seen with OT, raising the question of whether the antidepressant-like activity of OT may be working independently of the OTR. A selective OTR antagonist also failed to block the effects of OT on immobility in the TST. The significance of these findings for shaping the clinical development of OTR agonists is discussed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | ISRN Psychiatry 2012 -1 2012: 595141 |
| PMID | 23738205 |
| Title | Comparative evaluation of forced swim test and tail suspension test as models of negative symptom of schizophrenia in rodents. |
| Abstract | Previous studies have shown that the administration of NMDA antagonist can induce negative symptoms of schizophrenia which can be tested through the enhanced immobility observed in the forced swim test (FST). In the present study, we have compared the effects of acute as well as chronic administration of a noncompetitive NMDA receptor antagonist, ketamine on FST, and another behaviour despair model, tail suspension test (TST). Our observations suggest that chronic ketamine administration induced a state of enhanced immobility in FST, but such findings were not replicated in the TST model. Further, in FST, treatment with clozapine reverses the ketamine-induced immobility in mice, whereas it enhances the immobility duration in the TST model. However, haloperidol showed no protective effects in both models. The data suggests that although both of these tests show common behavioural measure of feeling despair, however, the underlying pathophysiology seems to be different. Hence, forced swim test but not tail suspension test can be used as a model of negative symptom of psychosis in mice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Compr Psychiatry 2016 May 67: 33-8 |
| PMID | 27095332 |
| Title | Sleep state misperception in schizophrenia: Are negative symptoms at work? |
| Abstract | This study investigates subjective and objective sleep quality to ascertain whether there is a sleep state misperception in schizophrenia patients, as well as analyze potential effect factors. A total of 148 inpatients with schizophrenia admitted to Beijing HuiLongGuan Hospital were enrolled in this study. The quality of objective sleep was assessed by polysomnography (PSG). On the second day after the successful completion of the PSG evaluation, an interview was arranged to collect patients' recorded subjective evaluation on sleep time, sleep latency, and wake times. Demographic information was collected from an interview, medical records were reviewed, and psychiatric symptoms were assessed using the Positive And Negative Symptom Scale (PANSS). The main finding of this study was that schizophrenic patients exhibited sleep state misperception with a pattern of overestimation of total sleep time (TST) as well as sleep efficiency (SE), and an underestimation of sleep onset latency (SOL). Regarding the ±standard deviation of the differences between subjective and objective TST as a clinical acceptable range, the patients were divided into three groups: the overestimate group, the normal group, and the underestimate group. The differences of total PANSS score, especially the PANSS-N score in the overestimate group, the normal group and the underestimate group were significant, and there were significant differences between the overestimate group and the other groups. A comprehensive evaluation of the subjective and objective sleep quality in patients with schizophrenia is needed, especially when negative symptoms are severe. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Compr Psychiatry 2016 May 67: 33-8 |
| PMID | 27095332 |
| Title | Sleep state misperception in schizophrenia: Are negative symptoms at work? |
| Abstract | This study investigates subjective and objective sleep quality to ascertain whether there is a sleep state misperception in schizophrenia patients, as well as analyze potential effect factors. A total of 148 inpatients with schizophrenia admitted to Beijing HuiLongGuan Hospital were enrolled in this study. The quality of objective sleep was assessed by polysomnography (PSG). On the second day after the successful completion of the PSG evaluation, an interview was arranged to collect patients' recorded subjective evaluation on sleep time, sleep latency, and wake times. Demographic information was collected from an interview, medical records were reviewed, and psychiatric symptoms were assessed using the Positive And Negative Symptom Scale (PANSS). The main finding of this study was that schizophrenic patients exhibited sleep state misperception with a pattern of overestimation of total sleep time (TST) as well as sleep efficiency (SE), and an underestimation of sleep onset latency (SOL). Regarding the ±standard deviation of the differences between subjective and objective TST as a clinical acceptable range, the patients were divided into three groups: the overestimate group, the normal group, and the underestimate group. The differences of total PANSS score, especially the PANSS-N score in the overestimate group, the normal group and the underestimate group were significant, and there were significant differences between the overestimate group and the other groups. A comprehensive evaluation of the subjective and objective sleep quality in patients with schizophrenia is needed, especially when negative symptoms are severe. |
| SCZ Keywords | schizophrenia, schizophrenic |