Abstract
Schizophrenic patients suffer from more metabolic or sleep problems. Little is known about risk factors. We recruited 17 patients with chronic schizophrenia from the rehabilitation center in a medical center in Taiwan and measured their demographic data, cognitive performance, and physical fitness, metabolic profiles and sleep parameters. They were divided into two groups according to clinical severity, then compared in terms of metabolic and sleep parameters.
Those with more severe symptomatology had more metabolic abnormality and shorter slow wave sleep (SWS). Our findings suggest clinical symptoms as linked with heavier body weight, wider neck circumference, elevated blood pressure, and shorter SWS. Further studies are warranted to confirm the preliminary finding and to elucidate the underlying mechanism
Keywords: Schizophrenia, Metabolic syndrome, Sleep disturbance, Slow wave sleep, Body weight, Neck circumference
1. Introduction
Schizophrenia, a psychiatric disorder causing deterioration of cognitive and daily function, is associated with obesity and metabolic syndrome, rendering patients vulnerable to morbidity and mortality[1].1 Biological factors, lifestyle, and antipsychotics all contribute to obesity of patients[2], [3], which influences their sleep quality[4]. Prevalence of poor sleepers among schizophrenics is around 45%, related to adverse events of medication and accompanying depression and psychological distress [5], [6]. Metabolic abnormality and sleep disturbance seem correlated. Consequently, these patients reportedly have poor life quality; correlation between clinical symptoms and sleep quality remains unclear. We hypothesize patients with severe clinical symptoms as more likely to have metabolic abnormality and sleep disturbance.
2. Methods
Study was approved by China Medical University Hospital Institutional Review Board (IRB). All participants gave written informed consent.
2.1. Participants
We recruited 17 schizophrenic patients from the Rehabilitation Center of the China Medical University Hospital Psychiatric Department. All met criteria of schizophrenia, paranoid type, according to DSM-IV-TR[7]. We rated the subjects by Positive and Negative Syndrome Scale (PANSS) [8], with respective items scored from 1(absent) to 7(extreme severity). We rated their depressive symptoms by Hamilton Depression Rating Scale[9], and quality oflife by Quality ofLife Scale (QLS) [10]. Extrapyramidal symptoms were rated by Abnormal Involuntary Movement (AIMS) [11], Simpson-Angus (SAS) [12], and Barnes Rating Scale (BARS) [13]. Daily antipsychotic doses were recorderd as chlorpromazine equivalents [14],14 and daily benzodiazepine doses as diazepam equivalents [15].
Inclusion criteria included (1) schizophrenic patients stable under current antipsychotics and benzodiazepine for at least three months; (2) engaged in regular rehabilitation program for at least three months; (3) aged between 20 and 50; (4) Han Taiwanese who speak Chinese fluently and understand this study well
Exclusion criteria included histories of (1) cerebrovascular, cardiovascular, and metabolic disorders (stroke, hypertension, diabetes mellitus); (2) neurologic disorders like epilepsy and traumatic brain injury; (3) physical disability (eg, fractures); (4) current DSM-IV-TR diagnosis of substance dependence (such as nicotine); (5) a DSM-IV-TR diagnosis of mental retardation, and (6) acute suicide or aggressive behaviors and (7) regular exercise.
2.2 Cognitive performance testing
Schizophrenic patients show impaired cognitive function [16], [17]. Our study included trail making, semantic association of verbal fluency, maze, verbal and non-verbal working memory, instant word list, delay word list, instant and, delayed visual reproduction, and digit symbol coding, as conducted by well-trained psychologists.
2.3 Cardiometabolic parameters and physical fitness
Patients’ weight and height, body mass index (BMI), neck circumference (NC), waist circumference, hip circumference, and waist-hip ratio (WHR) were recorded. Body fat was assessed by Omron body fat scale. Physical fitness was gauged according to a profile distributed by Bureau of Health Promotion, Department of Health, Taiwan. First, we checked sit-up frequency in one minute. Second, they underwent three-minute 35-centimeter-ladder climbing. We checked post-exercise heart rate (PEHR) at the end of the first minute (PEHR1), the second minute (PEHR2), and the third minute (PEHR3) while they stopped exercise. PEHR2 and PEHR3 were checked via similar method with total climbing time recorded.
Heart rate, systolic and diastolic blood pressure were measured before blood examination. Blood samples were taken at 8:00 a.m. after a 12-hour overnight fast, with subjects’ blood withdrawn from an antecubital vein to measure plasma levels of glucose, insulin, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, and cortisol. Insulin was quantified by chemiluminescent immunoassay sandwich method, and serum glucose by glucose-oxidase-based assay. We rated insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR), assessed by the formula of fasting insulin (μU/ml) x fasting glucose (mg/dl)/405 [18].
The presence of metabolic syndrome was recorded as defined by National Cholesterol Education Program (NCEP) guidelines: waist circumference ≧102 cm (male) and ≧ 88 cm (female), triglyceride (TG) ≧ 150 mg/dl, HDL-cholesterol < 40 mg/dL (male) and < 50 mg/dL (female), blood pressure ≧130/85 mmHg, and fasting glucose ≧ 110 mg/dl[19]. Metabolic syndrome index was summated by the above criteria.
2.4 Sleep measurement
Sleep rating scales were self-recorded by all subjects preceding polysomnography examination: Pittsburgh Sleep Quality Index (PSQI) [20], Insomnia Severity Index (ISI) [21], Epworth Sleepness Scale (ESS) [22], and Pre-Sleep Arousal Scale (PSAS) [23]. Polysomnography (PSG) followed standardized techniques: digital electroencephalography (EEG), electromyography, and electrooculography signals acquired with Alice 4 system. PSG electrode montage was utilized, composed of EEG sites F3 and C3 (referenced to A2) and F4 and C4 (referenced to A1). PSG data were scored manually on a small monitor, using 30-second epochs for staging and arousal detection, as well as 2- or 5-minute respiratory data. We drew parameters from sleep polysomnography, including time in bed (TIB), total sleep time (TST), sleep latency, awakening time, sleep efficiency (TST/TIB).
Sleep architecture was assessed for each 30-second epoch coded as Wake, Stage 1, Stage 2, Stage 3+4 (slow wave sleep, SWS), and Rapid Eye-Movement (REM) sleep according to criteria made by Rechtschaffen and Kales [24]. Arousals were identified according to criteria of the American Sleep Disorders Association (ASDA) 1992 [25]. We identified apnea and hypopnea as flat air flow lower than 20% and 70% of the baseline, respectively, whose amplitude was measured during the nearest preceding period of regular breathing with stable oxygen saturation. We identified Apnea-hypopnea index as total apnea and hypopnea divided by total sleep time.
3. Data analysis
We divided participants into two groups according to severity of clinical manifestation Cut-off value was median number of the PANSS total scores. Student’-T test compared all variables between the two groups.
4. Results
Age and gender between groups were similar, as was duration of education and age at illness onset. Duration of illness of the H-PANSS group was longer. Clinical Global Impression (CGI) [11] tallied higher and Quality of Life Scale (QLS) lower in the H-PANSS group, depressive symptoms rated by Hamilton Depression Scale similar between groups (Table 1). Current medications calculated by chlorpromazine and Diazepam equivalents were also similar. There were no differences between the two groups in severity of EPS rated by Abnormal Involuntary Movement Scale, Barnes Akathsia Rating Scale, and Simpson-Angus Scale (Table 1).
Table 1.
Demographic and clinical characteristics
| Demographic characteristics | L-PANSS (n=80) | H-PANSS (n=9) | P value |
|---|---|---|---|
| Age (years) | 35 ± 9.3 | 37 ± 9.6 | 0.801 |
| Male/Female(male percentage) | 2/6 (25%) | 4/5 (44%) | 0.434 |
| Duration of education (years) | 13.0 ± 3.3 | 11.6 ± 3.6 | 0.405 |
| Age at illness onset (years) (years) | 25.1 ± 7.5 | 22.3 ± 7.4 | 0.453 |
| Duration of illness (months) | 101.5 ± 71.8 | 186.7 ± 63.8 | 0.021 * |
| Clinical psychiatric condition rating scales | |||
| Clinical Global Impression (CGI) | 2.9 ± 0.4 | 3.7 ± 0.5 | 0.002 ** |
| Quality of life scale (QLS) | 63.3 ± 11.4 | 35.4 ± 14.0 | < 0.001** |
| Hamilton Depression Rating scale | 8.1 ± 5.2 | 12.7 ± 8.4 | 0.207 |
| Medication amount | |||
| Chlorpromazine equivalents | 212.5 ± 64.1 | 237.2 ± 91.0 | 0.532 |
| Diazepam equivalents | 12.5 ± 16.9 | 5.0 ± 6.1 | 0.232 |
| Extra-pyramidal symptoms rating scales | |||
| Abnormal Involuntary Movement scale | 4.1 ± 6.3 | 5.11 ± 4.5 | 0.712 |
| Barnes Akathisia Rating scale | 0.6 ± 1.2 | 2.1 ± 2.6 | 0.162 |
| Simpson-Angus scale | 5.8 ± 4.7 | 7.3 ± 3.5 | 0.440 |
All data were expressed as mean value ± standard deviation, except gender.
Low-PANSS (L-PANSS) group included schizophrenics with Positive and Negative Syndrome Scale (PANSS) total score below 65 (median of PANSS total scores of all 17 subjects); High-PANSS (H-PANSS) group included those with PANSS total scores 65 or higher.
*:P<0.05 and **:P<0.01, significance between groups.
Cognitive performances between groups were similar. (Table 2)
Table 2.
Cognition tests measured in two groups of patients
| Parameters | L-PANSS (n=8) | H-PANSS (n=9) | P value |
|---|---|---|---|
| Trail making test | 1.6 ± 0.9 | 2.0 ± 1.0 | 0.435 |
| Digit symbol coding | 4.9 ± 2.0 | 4.6 ± 3.1 | 0.807 |
| Semantic association of verbal fluency | 0.6 ± 0.5 | 0.4 ± 0.5 | 0.488 |
| Maze | 3.8 ± 1.6 | 4.2 ± 4.6 | 0.787 |
| Verbal working memory | 7.6 ± 3.9 | 8.7 ± 3.9 | 0.590 |
| Non-verbal working memory | 4.5 ± 3.1 | 5.6 ± 3.1 | 0.491 |
| Instant word list | 5.6 ± 2.8 | 5.1 ± 3.0 | 0.719 |
| Delay word list | 6.5 ± 2.6 | 6.6 ± 2.2 | 0.963 |
| Instant visual reproduction | 4.9 ± 2.2 | 4.8 ± 2.3 | 0.931 |
| Delay visual reproduction | 6.4 ± 2.6 | 5.1 ± 2.2 | 0.291 |
Data were expressed as mean value ± standard deviation.
Low-PANSS (L-PANSS) group included schizophrenics with Positive and Negative Syndrome Scale (PANSS) total score below 65 (median of PANSS total scores of all 17 subjects); High-PANSS (H-PANSS) group comprised those with PANSS total scores 65 or higher. No significance appeared between groups
Body weight and neck circumference (NC) in the H-PANSS group were higher than those in the L-PANSS group. Body height, BMI, waist circumference, hip circumference, WHR and body fat between groups were similar, as was physical fitness measured by sit-up and climbing (Table 3). Both systolic and diastolic blood pressures in the H-PANSS group were higher. Metabolic index, heart rate, fasting sugar, insulin, Homa-IR, cortisol, cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein between groups were similar (Table 3).
Table 3.
Cardiometabolic parameters and physical fitness
| Physical parameters | L-PANSS (n=8) | H-PANSS (n=9) | P value |
|---|---|---|---|
| Body weight (BW) (kg) | 65.4 ± 9.6 | 78.3 ± 9.2 | 0.013* |
| Body height (BH) (cm) | 144.9 ± 12.5 | 161.1 ± 15.3 | 0.031* |
| Body mass index (BMI) (kg/m2) | 31.5 ± 5.5 | 30.5 ± 4.1 | 0.653 |
| Neck circumference (NC) (cm) | 35.0 ± 2.6 | 38.6 ± 2.1 | 0.007** |
| Waist circumference (cm) | 91.5 ± 10.5 | 95.8 ± 9.2 | 0.386 |
| Hip circumference (cm) | 104.4 ± 9.1 | 106.8 ± 6.5 | 0.537 |
| Waist-hip ratio (WHR) | 0.89 ± 0.07 | 0.87 ± 0.05 | 0.652 |
| Body fat (%) | 33.8 ± 5.1 | 32.1 ± 6.7 | 0.564 |
| Physical fitness | |||
| Sit-up (/min) | 14.5 ± 12.7 | 14.2 ± 9.4 | 0.959 |
| Stair-climbing PEHR 1 (/min) | 52.9 ± 10.4 | 53.1 ± 8.7 | 0.960 |
| PEHR 2 (/min) | 48.4 ± 9.6 | 47.9 ± 8.5 | 0.913 |
| PEHR 3 (/min) | 47.0 ± 8.2 | 45.8 ± 8.3 | 0.765 |
| Climbing time (s) | 114.8 ± 57.4 | 133.3 ± 39.2 | 0.443 |
| Cardiometabolic parameters | |||
| Heart rate (/minute) | 83.3 ± 16.8 | 85.9 ± 6.9 | 0.671 |
| Systolic blood pressure (mmHg) | 107.8 ± 8.2 | 122.7 ± 6.3 | < 0.001** |
| Diastolic blood pressure (mmHg) | 65.8 ± 7.1 | 77.8 ± 10.2 | 0.014* |
| Fasting sugar (mg/dL) | 91.1 ± 9.6 | 100.7 ± 17.7 | 0.196 |
| Insulin (uIU/mL) | 9.62 ± 4.04 | 29.30 ± 54.06 | 0.322 |
| Homa-IR | 2.21 ± 1.01 | 8.48 ± 17.04 | 0.316 |
| Cortisol (ug/dL) | 13.4 ± 2.4 | 11.4 ± 4.9 | 0.309 |
| Total cholesterol (mg/dL) | 202.6 ± 35.0 | 215.1 ± 44.3 | 0.532 |
| Triglyceride (mg/dL) | 228.5 ± 164.3 | 144.6 ± 77.5 | 0.190 |
| High-density lipoprotein (mg/dL) | 43.9 ± 16.0 | 41.2 ± 7.2 | 0.661 |
| Low-density lipoprotein (mg/dL) | 115.0 ± 27.9 | 142.4 ± 37.4 | 0.111 |
| Metabolic syndrome index | 1.4 ± 1.1 | 1.8 ± 1.6 | 0.549: |
All data were expressed as mean value ± standard deviation.
Low-PANSS (L-PANSS) group included schizophrenics with Positive and Negative Syndrome Scale (PANSS) total score below 65 (median of PANSS total scores of all 17 subjects); High-PANSS (H-PANSS) group included those with PANSS total score 65 or higher. PEHR1, 2, 3: post-exercise heart rate in the first, second and third minute, Homa-IR: homeostasis model assessment of insulin resistance
*:P<0.05 and **:P<0.01, significance between groups.
The mean scores of respective sleep questionnaires, including ESS, ISI, PAS, and PSQI, were similar between L-PANSS and H-PANSS groups (Table 4). Parameters of sleep continuity measured by PSG, including awakening time, bed time, sleep efficiency, sleep latency, and total sleep time between groups were all similar. Marginal difference between the two groups were noted in the ratio of stage 3 and 4 sleep (slow wave sleep) and oxygen saturation rates.
Table 4.
Sleep parameter measurement
| Sleep continuity | L-PANSS (n=8) | H-PANSS (n=9) | P value |
|---|---|---|---|
| Awakening time | 7.0 ± 0.9 | 7.2 ± 0.4 | 0.673 |
| Bed time | 22.7 ± 1.8 | 20.9 ± 1.6 | 0.052 |
| Sleep efficiency (%) | 84.0 ± 12.0 | 63.0 ± 28.3 | 0.071 |
| Sleep latency | 30.9 ± 20.2 | 24.3 ± 19.4 | 0.505 |
| Total sleep time | 7.5 ± 0.7 | 8.4 ± 1.1 | 0.067 |
| Sleep questionnaires | |||
| Epworth Sleepness Scale | 9.0 ± 5.2 | 8.0 ± 4.0 | 0.663 |
| Insomnia Severity Index | 9.1 ± 3.7 | 8.3 ± 3.2 | 0.646 |
| Pre-Sleep Arousal Scale | 32.9 ± 16.6 | 26.4 ± 11.5 | 0.363 |
| Pittsburgh Sleep Quality Index | 13.8 ± 7.1 | 14.3 ± 7.5 | 0.872 |
| Sleep architecture | |||
| NREM S1 (%) | 12.5 ± 14.6 | 29.3 ± 3.5 | 0.190 |
| NREM S2 (%) | 62.8 ± 19.0 | 47.0 ± 21.3 | 0.129 |
| NREM S3 + 4 (%) | 8.0 ± 9.1 | 1.1 ± 2.9 | 0.047* |
| REM sleep (%) | 16.6 ± 5.5 | 22.7 ± 16.6 | 0.337 |
| Sleep obstruction parameters | |||
| Apnea-hypopnea index | 6.2 ± 8.8 | 8.8 ± 9.4 | 0.560 |
| Mean SpO2 (%) | 96.6 ± 1.5 | 95.0 ± 1.5 | 0.046* |
| ALM (events/hour) | 8.8 ± 8.1 | 19.4 ± 19.0 | 0.164 |
| Leg movement | 53.1 ± 109.2 | 11.6 ± 34.7 | 0.295 |
All data were expressed as mean value ± standard deviation.
Low-PANSS (L-PANSS) group included schizophrenics with Positive and Negative Syndrome Scale (PANSS) total score below 65 (median of PANSS total scores of all 17 subjects); High-PANSS (H-PANSS) group included those with PANSS total scores 65 or higher. NREM: non-rapid eye movement, REM: rapid eye movement, SpO2: saturation of peripheral oxygen, ALM: arousal and limb movement. NREM S3 + 4 (SWS) in the H-PANSS group was lower. Intergroup NREM S1, S2 and REM sleep were similar (Table 4). Mean SpO2 in the H-PANSS group was lower. Apnea-hypopnea index, Arousal and Limb Movement, and leg movement between groups were similar (Table 4).
*:P<0.05 and **:P<0.01, significance between groups.
4. Discussion
To our knowledge, this is the first study to suggest that severer clinical symptoms are associated with metabolic and sleep disturbance in patients with schizophrenia. In more detail, this study demonstrates that schizophrenia patients with severe symptomatology may have more metabolic abnormalities including heavier body weight, wider neck circumference, and elevated systolic/diastolic blood pressure. We found no intergroup statistical significance in terms of blood sugar, insulin, cortisol, and lipid profiles. This is the first study to suggest that schizophrenic patients with more severe symptoms might have decreased oxygen saturation. It also demonstrated that patients with more severe symptoms had reduced SWS when their sleep efficiency and total sleep time were similar to the low PANSS group. Results concurred with prior studies: positive symptoms of schizophrenia increased REM sleep eye movement density, short REM latency, reduced sleep efficiency and prolonged sleep latency [26], [27], [28], [29]. Conversely, negative symptoms relate to short REM latency and SWS deficit [30], [31]. cognitive symptoms to SWS deficit [28], [29]. Sarkar et al. [32] found significant difference in SWS parameters (including increased Stage 3 and decreased Stage 4 latency between patients and controls.
The strength of this study is control over two groups of patients similar in basic demographic data, cognitive function performance, and physical fitness. Limitations of the study included small sample size and cross-section design. In sum, this study suggests clinical symptoms as linked with heavier body weight, wider neck circumference, elevated blood pressure, and shorter SWS in schizophrenic pateints. Further studies must confirm preliminary findings and elucidate the underlying mechanism.
Acknowledgments
This study is supported in part by Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH103-TD-B-111-004).
References
- [1].McEvoy JP, Meyer JM, Goff DC, Nasrallah HA, Davis SM, Sullivan L. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res. 2005;80:19–32. doi: 10.1016/j.schres.2005.07.014. [DOI] [PubMed] [Google Scholar]
- [2].Green AI, Patel JK, Goisman RM, Allison DB, Blackburn G. Weight gain from novel antipsychotic drugs: need for action. Gen Hosp Psychiatry. 2000;22:224–35. doi: 10.1016/S0163-8343(00)00081-5. [DOI] [PubMed] [Google Scholar]
- [3].Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS drugs. 2005;19(1):1–93. doi: 10.2165/00023210-200519010-00001. [DOI] [PubMed] [Google Scholar]
- [4].Palmese LB, DeGeorge PC, Ratliff JC, Srihari VH, Wexler BE, Krystal AD. Insomnia is frequent in schizophrenia and associated with night eating and obesity. Schizophr Res. 2011;133:238–43. doi: 10.1016/j.schres.2011.07.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Ritsner M, Kurs R, Ponizovsky A, Hadjez J. Perceived quality of life in schizophrenia: relationships to sleep quality. Qual Life Res. 2004;13:783–91. doi: 10.1023/B:QURE.0000021687.18783.d6. [DOI] [PubMed] [Google Scholar]
- [6].Ritsner M, Modai I, Ponizovsky A. Assessing psychological distress in psychiatric patients: validation of the Talbieh Brief Distress Inventory. Compr Psychiatry. 2002;43:229–34. doi: 10.1053/comp.2002.30800. [DOI] [PubMed] [Google Scholar]
- [7].Association AP. Diagnostic and Statistical Manual of Mental Disorders. 4. Washington, DC: American Psychiatric Association; 1994. [Google Scholar]
- [8].Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76. doi: 10.1093/schbul/13.2.261. [DOI] [PubMed] [Google Scholar]
- [9].Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62. doi: 10.1136/jnnp.23.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Heinrichs DW, Hanlon TE, Carpenter WT. Jr. The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome. Schizophr Bull. 1984;10:388–98. doi: 10.1093/schbul/10.3.388. [DOI] [PubMed] [Google Scholar]
- [11].Rockville M. Guy W. ECDEU Assessment Manual for Psychopharmacology: Revised (DHEW publication number ADM 76-338). US: Department of Health, Education and Welfare, Public Health Service, Alcohol, Drug Abuse and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976.
- [12].Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl. 1970;212:11–19. doi: 10.1111/j.1600-0447.1970.tb02066.x. [DOI] [PubMed] [Google Scholar]
- [13].Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatry. 1989;154:672–76. doi: 10.1192/bjp.154.5.672. [DOI] [PubMed] [Google Scholar]
- [14].Woods SW. Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry. 2003;64:663–67. doi: 10.4088/JCP.v64n0607. [DOI] [PubMed] [Google Scholar]
- [15].Ashton H. The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatry. 2005;18:249–55. doi: 10.1097/01.yco.0000165594.60434.84. [DOI] [PubMed] [Google Scholar]
- [16].Kern RS, Nuechterlein KH, Green MF, Baade LE, Fenton WS, Gold JM. The MATRICS Consensus Cognitive Battery, part 2: co-norming and standardization. Am J Psychiatry. 2008;165:214–20. doi: 10.1176/appi.ajp.2007.07010043. [DOI] [PubMed] [Google Scholar]
- [17].Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD. The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry. 2008;165:203–13. doi: 10.1176/appi.ajp.2007.07010042. [DOI] [PubMed] [Google Scholar]
- [18].Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–19. doi: 10.1007/BF00280883. [DOI] [PubMed] [Google Scholar]
- [19].Expert Panel on Detection E Treatment of High Blood Cholesterol in A. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III) JAMA. 2001;285:2486–97. doi: 10.1001/jama.285.19.2486. [DOI] [PubMed] [Google Scholar]
- [20].Buysse DJ, Reynolds CF, 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213. doi: 10.1016/0165-1781(89)90047-4. [DOI] [PubMed] [Google Scholar]
- [21].Insomnia CM. M. psychological assessment and management. New York: Guilford Press; 1993. [Google Scholar]
- [22].Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540–45. doi: 10.1093/sleep/14.6.540. [DOI] [PubMed] [Google Scholar]
- [23].Nicassio PM, Mendlowitz DR, Fussell JJ, Petras L. The phenomenology of the pre-sleep state: the development of the pre-sleep arousal scale. Behav Res Ther. 1985;23:263–71. doi: 10.1016/0005-7967(85)90004-X. [DOI] [PubMed] [Google Scholar]
- [24].Rechtschaffen A, Kales A.A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Washington, DC: Government Printing Office: NIH Publication; 1968. [Google Scholar]
- [25].arousals EEG. scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep. 1992;15:173–84. [PubMed] [Google Scholar]
- [26].Zarcone VP, Benson KL. BPRS symptom factors and sleep variables in schizophrenia. Psychiatry Res. 1997;66:111–20. doi: 10.1016/S0165-1781(96)02857-0. [DOI] [PubMed] [Google Scholar]
- [27].Poulin J, Daoust AM, Forest G, Stip E, Godbout R. Sleep architecture and its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia. Schizophr Res. 2003;62:147–53. doi: 10.1016/S0920-9964(02)00346-8. [DOI] [PubMed] [Google Scholar]
- [28].Monti JM, Monti D. Sleep in schizophrenia patients and the effects of antipsychotic drugs. Sleep Med Rev. 2004;8:133–48. doi: 10.1016/S1087-0792(02)00158-2. [DOI] [PubMed] [Google Scholar]
- [29].Yang C, Winkelman JW. Clinical significance of sleep EEG abnormalities in chronic schizophrenia. Schizophr Res. 2006;82:251–60. doi: 10.1016/j.schres.2005.10.021. [DOI] [PubMed] [Google Scholar]
- [30].Tandon R, Shipley JE, Eiser AS, Greden JF. Association between abnormal REM sleep and negative symptoms in schizophrenia. Psychiatry Res. 1989;27:359–61. doi: 10.1016/0165-1781(89)90151-0. [DOI] [PubMed] [Google Scholar]
- [31].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. doi: 10.1016/0022-3956(95)00023-X. [DOI] [PubMed] [Google Scholar]
- [32].Sarkar S, Katshu MZ, Nizamie SH, Praharaj SK. Slow wave sleep deficits as a trait marker in patients with schizophrenia. Schizophr Res. 2010;124:127–33. doi: 10.1016/j.schres.2010.08.013. [DOI] [PubMed] [Google Scholar]