Sleep-disordered breathing and periodic limb movements in sleep in older patients with schizophrenia

Sleep-Disordered Breathing and Periodic Limb Movements in Sleep in Older Patients with Schizophrenia Sonia Ancoli-Israel, Jennifer Martin, Denise W. Jones, Michael Caligiuri, Thomas Patterson, M. Jackuelyn Harris, and Dilip V. Jeste Background: Since the prevalence of both sleep-disordered breathing (SDB) and periodic limb movements in sleep (PLMS) increase with age, we explored whether older schizophrenia patients would have a high incidence of SDB and PLMS. Correlations between sleep and clinical variables were also examined. Methods: Fifty-two patients (mean age 5 59.6 years, SD 5 8.9) had their sleep/wake, respiration, and leg movements recorded using a modified Medilog/Respitrace portable recording system plus oximetry. A battery of clinical, psychosocial, and motor disturbance variables were collected by research center staff. Results: Forty-eight percent of these patients had at least 10 respiratory events per hour of sleep. These patients reported more symptoms of daytime sleepiness than patients with fewer than 10 events per hour. The relatively high prevalence of SDB in this group may contribute to overall sleep disturbances, and does not appear to be a result of high body mass index. Only 14% of the patients had at least five limb movements per hour of sleep, suggesting the prevalence of PLMS is much lower than expected in this age group. The number of leg jerks was inversely related to symptoms of tardive dyskinesia. Conclusions: The disturbance of sleep in these patients may be due, in part, to SDB, but is unlikely due to PLMS. Biol Psychiatry 1999;45:1426 –1432 © 1999 Society of Biological Psychiatry Key Words: Sleep-disordered breathing, periodic limb movements in sleep, dopamine, schizophrenia, sleep, aging

From the Department of Psychiatry, University of California, San Diego and the San Diego Veterans Affairs Healthcare System (SA-I, DWJ, MC, TP, MJH, DVJ) and San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology (JM), San Diego, California. Address reprint requests to Ancoli-Israel, PhD, Department of Psychiatry 116A, San Diego Veterans Affairs Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161. Received January 6, 1998; revised April 6, 1998; accepted April 17, 1998.

© 1999 Society of Biological Psychiatry

Introduction

M

any schizophrenia patients have difficulty falling asleep and/or staying asleep, while others exhibit daytime sleepiness (Kempenaers et al 1988; Sweetwood et al 1976, 1980; Benca et al 1992; van Kammen et al 1986). These symptoms are suggestive of certain sleep disorders such as sleep-disordered breathing (SDB) or periodic limb movements in sleep (PLMS). Kripke and Gherini (1977) reported an association between schizophrenia symptoms and apnea symptoms in a 47-year-old schizophrenia patient with both the daytime sleepiness and the stertorous breathing improving with thioridazine treatment. One study examined the prevalence of periodic limb movements in sleep in a group of younger schizophrenia patients and found that 12.9% had PLMS compared to 4.7% of their nonpsychiatric controls (Neeper et al 1992). Benson and Zarcone (1994) noted that 15% of the schizophrenia patients screened in their laboratory had SDB, 11% had PLMS, and 2% had both. The prevalence of sleep disorders in older schizophrenia patients specifically has never been reported. It is known that sleep of the healthy elderly is disturbed, in part due to the high prevalence of SDB and PLMS (Ancoli-Israel et al 1991a, 1991b). SDB is a disorder in which respiration ceases (apnea) or is reduced (hypopnea) multiple times during sleep (Guilleminault 1989). Hundreds of episodes can occur during the night, each followed by an awakening during which breathing resumes. As a result, the patient experiences both hypoxemia and disrupted sleep. Clinical diagnoses are often made when the apnea index (AI, i.e., the number of apneas per hour of sleep) is greater than five or when the respiratory disturbance index (RDI, i.e., the number of apneas plus hypopneas per hour of sleep) is greater than 10. Consequences of untreated SDB can include daytime sleepiness and complaints of insomnia, cardiac arrhythmias, hypertension, confusion, memory loss, and cognitive impairment (Guilleminault 1989). The prevalence rate of SDB (defined as RDI . 10) in 0006-3223/99/$20.00 PII S0006-3223(98)00166-8

Sleep in Older Schizophrenia Patients

middle-aged, healthy individuals has been estimated to be approximately 11% for men and 5% for women (Young et al 1993; Kripke et al 1997). In the normal elderly, this disorder is much more common. Ancoli-Israel et al (1991b) studied psychiatrically normal adults aged 65 years and older and found that 62% had 10 or more apneas per hour of sleep. Covert sleep apnea was both common in the elderly, and almost impossible to diagnose based on history alone. A detailed discussion of the different studies on the prevalence of these disorders in the elderly can be found in Ancoli-Israel (1989). PLMS is a disorder in which people kick or jerk their legs every 20 – 40 sec, in sleep, for periods throughout the night, causing arousals that disrupt sleep (Coleman et al 1980; Montplaisir and Godbout 1989). A myoclonus index (MI; i.e., the number of leg jerks causing arousals per hour of sleep) of five is required for a diagnosis to be made. Patients with PLMS often complain of insomnia and sometimes excessive daytime sleepiness. They may also complain of restless legs and leg twitches, motor restlessness resembling akathisia, and cold feet (Montplaisir and Godbout 1989; Ancoli-Israel et al 1986). Although PLMS is difficult to treat, benzodiazepines, opiates, or derivatives of levodopa have been recommended (Kaplan et al 1993; Mitler et al 1986; Hening et al 1986; Kavey et al 1988). Ancoli-Israel et al (1991a) found that 45% of elderly had an MI of five or greater. When comparing those with and without PLMS, elderly with PLMS were less satisfied with their sleep. Restless legs syndrome (RLS) is a separate disorder in which people complain of uncomfortable sensations in their legs during the waking state (Coccagna and Lugaresi 1981; Coleman 1982). All patients with restless legs syndrome have PLMS, but the reverse is not true. Although, to our knowledge, the prevalence of RLS has not been established in schizophrenia patients, the symptoms resemble those of neuroleptic-induced akathisia. Schizophrenia patients taking neuroleptic medications often develop symptoms of akathisia and tardive dyskinesia (TD). Some of these symptoms resemble those of PLMS and restless leg syndrome (Blom and Ekbom 1961; Hening et al 1986; Walters et al 1995). Walters et al (1991) showed that in 9 patients with neuroleptic-induced akathisia, all had increased awakenings and decreased sleep efficiency, but their sleep disturbance was not as severe as that in patients with RLS. In addition, 5 of the 9 patients had PLMS, a rate higher than that which would be expected in a normal population. These patients, however, like those of Benson and Zarcone (1994), were fairly young (mean age 5 49 years). In the older psychiatric patients, therefore, as in nonpsychiatric elderly, some of the sleep complaints may be secondary to the presence of SDB and/or PLMS.

BIOL PSYCHIATRY 1999;45:1426 –1432

1427

This study examined the prevalence of SDB and PLMS in a population of older schizophrenia outpatients. The potential interactions between age and psychopathology were examined, and, since the prevalence of both SDB and PLMS increases with advancing age (Ancoli-Israel et al 1991a, 1991b), we explored whether older schizophrenia patients would have a higher incidence of SDB and PLMS.

Methods and Materials Subjects Subjects were 35 men and 17 women enrolled in a larger study of late-life psychosis at the UCSD Geriatric Psychiatry Clinical Research Center. Forty-four of the patients had been diagnosed with schizophrenia, and 8 were diagnosed with schizoaffective disorder as per DSM-III-R (American Psychiatric Association 1987). There were no differences in sleep variables between these two groups, therefore, all data presented are from the combined sample. Eighty-five percent (n 5 44) were taking neuroleptic medications at the time of the study. The most common neuroleptic (17% of the patients taking neuroleptics) was haloperidol, although some were taking clozapine, fluphenazine, chlorpromazine, trifluoperazine, thiothixene, thioridazine, perphenazine, loxapine, or risperidone. Of the 44 patients diagnosed with schizophrenia, 33 were diagnosed with early-onset schizophrenia (EOS; onset before age 45), and 11 were diagnosed with late-onset schizophrenia (LOS; onset after age 45). Demographic and clinical data are presented in Table 1.

Apparatus The modified Medilog/Respitrace portable recording system, in conjunction with portable oximetry, was used to record sleep (Ancoli-Israel et al 1981). The system records four channels of information: thoracic and abdominal respiration, tibialis electromyogram (EMG), and wrist activity (for distinguishing wake from sleep). The data were stored on a small tape recorder and were then played back onto a polygraph. The resulting hard copy recording was scored for total sleep time, total wake time, number, duration and type of apneas, number, duration and type of hypopneas, AI, RDI, number of leg movements during sleep, and MI. The system has previously been validated with traditional polysomnography with apnea index reliability of r 5 .80 (Ancoli-Israel et al 1981). This reliability is no different from that found with two raters scoring the same polysomnogram (Bliwise et al 1984). Wrist activity has been validated for distinguishing wake from sleep in multiple populations, including demented elderly (Cole et al 1992; Ancoli-Israel et al 1997). Oxygen saturation levels were recorded with a portable computer system and finger pulse oximetry (Biox model number 3700). The oximeter sampled blood oxygen saturation levels every 2 sec and stored these data in memory and on disk throughout the recording to minimize data loss.

1428

S. Ancoli-Israel et al

BIOL PSYCHIATRY 1999;45:1426 –1432

Table 1. Clinical Description of Schizophrenia Patients (n 5 52) Mean Age (years) BMIa Duration of illness (years) Current neuroleptic dose (mg cpze)b Duration of neuroleptic use (years) SAPS scorec SANS scored Adjusted QWB scoree MMSEf

SD

59.6 8.9 28.5 7.4 26.7 14.0 532 1244 3.9 7.7 5.6 4.1 8.6 4.5 .57 .12 26.8 2.7

Range 45–76 17.4 –51.8 3–51 0 – 8330 0 –32.1 0 –16 0 –18 .42–.86 17–30

a

BMI, body mass index, (kg/m2). Jeste and Wyatt (1982). cpze, chlorpromazine equivalents. c SAPS, Scale for the Assessment of Positive Symptoms (range 5 0 –20). d SANS, Scale for the Assessment of Negative Symptoms (range 5 0 –25). e QWB, Quality of Well Being Scale (0 5 dead, 1.0 5 optimal health). f MMSE, Mini-Mental Status Exam (range 0 –30). b

Procedure The Structured Clinical Interview for DSM-III-R (SCID) (Spitzer and Williams 1986) was administered to all patients by trained geriatric psychiatry or psychology fellows. Diagnosis of schizophrenia or schizoaffective disorder was made at a research staffing attended by at least two board-certified psychiatrists. These procedures have been previously described (Jeste et al 1995). Each patient was administered a sleep questionnaire previously used by our laboratory (Ancoli-Israel et al 1991b). Questions were asked about sleep satisfaction, complaints of insomnia, trouble falling asleep, mid-sleep awakenings, and symptoms of delayed sleep phase or advanced sleep phase. Questions were also asked about SDB (such as snoring or gasping) and PLMS (such as leg twitches) and daytime sleepiness. Patients were seen at the Clinical Research Center every 6 months, where research assistants administered a battery of rating scales including the Mini-Mental State Examination, (MMSE; higher scores are indicative of better functioning) (Folstein et al 1975), the Quality of Well Being (QWB) scale (higher QWB scores indicate a better quality of life) (Kaplan and Anderson 1990), the Brief Psychiatric Rating Scale (BPRS, with higher scores indicating more severe psychiatric symptoms) (Overall and Gorham 1962), the Scale for the Assessment of Positive Symptoms (SAPS, with higher scores indicating more positive symptoms, e.g., hallucinations, delusions) (Andreasen and Olsen 1982), the Scale for the Assessment of Negative Symptoms (SANS, with higher scores indicating more negative symptoms, e.g., social withdrawal, alogia) (Andreasen and Olsen 1982), the Abnormal Involuntary Movement Scale (AIMS, a measure of dyskinesia) (Guy 1976), and the Simpson & Angus Extrapyramidal Symptoms scale (a clinical rating of Parkinsonism with higher scores indicating greater Parkinsonism) (Simpson and Angus 1970). Weight and height were measured so that body mass index (BMI; kg/cm2) could be computed. Patients’ sleep was recorded in their own beds in their homes. Since both SDB and PLMS vary from night to night (Guilleminault 1987; Mason et al 1989), 2 nights of sleep were recorded

whenever possible (44% of the sample) to obtain a more stable and reliable estimate of sleep disturbance. The mean of the 2 nights was used for data analyses. The equipment was applied in the late afternoon or early evening in the patient’s own home. The oximetry system was placed by the patient’s bed, and the patient was instructed both verbally and in written form on how to place the finger pulse oximetry transducer on a finger at bedtime. For patients who were clinically less stable, a caregiver supervised the procedure and helped the patient get in and out of bed. In the morning, the research assistant returned to the patient’s home to collect all the equipment. Oximetry data were examined and edited to remove artifacts and to verify that the quality and duration of recordings were adequate. The PROFOX computer program was used to estimate the number of oxygen desaturations .4%, mean desaturation level, lowest desaturation level, and time spent at saturation levels less than 90%, less than 80%, and less than 70% (Timms et al 1988). After each record had been scored, patients were notified of the results, and a note was placed in the patient’s medical file.

Data Analysis Sleep variables were nonnormally distributed; therefore Spearman rank-order correlations were used to examine relationships between sleep and clinical variables, and Mann–Whitney nonparametric comparisons were used to compare men to women, patients with RDI . 10 to those with RDI , 10, and patients using neuroleptic medications with patients not using neuroleptic medications. Since these analyses were exploratory in nature, the critical value for alpha was set at .05 for all comparisons and correlations.

Results Demographics Table 1 lists the demographic and clinical information for all patients. There were no significant differences between men and women or between schizophrenia and schizoaffective patients in sleep measures.

Sleep-Disordered Breathing Forty-eight percent of the schizophrenia patients had an RDI . 10, and 20% had RDI . 20. Since 71% of the subjects were under age 65, to compare data to those of normal elderly, prevalence was also computed for those patients over age 65 (n 5 15; see Table 2). Prevalence rates were 54% for RDI . 10 and 31% for RDI . 20. As expected, those with RDI . 10 had significantly higher RDI (mean RDI 5 24.6, SD 5 15.4, range 5 10 –75.8) compared to those with RDI , 10 (mean RDI 5 4.8, SD 5 3.1, range 5 0.6 –9.6), and greater numbers of desaturation events (mean 5 63.8, SD 5 74, range 5 3–311 vs. mean 5 22.4, SD 5 20.8, range 5 3–76,

Sleep in Older Schizophrenia Patients

BIOL PSYCHIATRY 1999;45:1426 –1432

Table 2. Prevalence of Sleep-Disordered Breathing and Periodic Limb Movements in Sleep in Schizophrenia Patients

RDI $ 10 RDI $ 20 MI $ 5

45–76 years (n 5 52)

65–76 years (n 5 15)

48% 20% 14%

54% 31% 8%

respectively). There were no significant differences, however, in the mean SaO2 levels, the lowest SaO2 levels, or the percent time spent at SaO2 . 90%. These data are summarized in Table 3. Additional analyses were done comparing patients with RDI . 10 vs. those with RDI , 10 on clinical variables. Those with RDI . 10 had a significantly lower MMSE scores (mean 5 25.9, SD 5 3.2) than those with RDI , 10 (mean 5 27.7, SD 5 1.9; p 5 .041). There were no significant correlations among MMSE, age, and RDI. Of the patients with RDI . 10, 78% reported symptoms of daytime sleepiness (i.e., falling asleep at inappropriate times and/or trouble staying awake until bedtime one or more days per week), whereas only 27% of patients with RDI , 10 had similar reports of sleepiness (x2 5 15.21, p , .0001). There were no significant differences between these groups in other clinical variables or in age or BMI. Table 3. Mann–Whitney Tests for Respiratory Values of Patients with Respiratory Disturbance Indices $10 (n 5 26) vs. Patients with Respiratory Disturbance Indices ,10 (n 5 24)

RDI Mean SD Range Number of desaturation events .4% Mean SD Range Mean SaO2 level Mean SD Range Lowest SaO2 level Mean SD Range % time at SaO2 ,90% Mean SD Range

Patients with RDI $ 10

Patients with RDI , 10

24.6 15.4 10.0 –75.8

4.8 3.1 0.6 –9.6

,.0005

63.8 74.0 3.0 –311.0

22.4 20.8 3.0 –76.0

.017

94.4 1.6 89.5–96.7

95.1 1.5 92.2–97.1

.273

81.9 10.2 43.0 –90.0

85.4 5.4 69.0 –93.0

.202

3.8 9.1 0 –38

99.0 1.9 92.9 –100.0

.262

p value

Respiratory disturbance indices (RDIs) were unavailable for 2 patients due to insufficient recordings.

1429

Correlations were computed for RDI and clinical variables with no significant results.

Periodic Limb Movements in Sleep Only 14% (7 patients) had an MI . 5. The mean MI for the entire group was 3.9 (SD 5 13.3, range 5 0 – 82.6). The mean MI for those with MI . 5 was 26.40 (SD 5 27.60, range 5 5.09 – 82.64). For those 65 years or older, the prevalence rate of MI . 5 was 8%. There were no significant differences between patients with and without PLMS in mean age, daily neuroleptic use, or duration of neuroleptic use. Correlations were computed between MI and clinical variables. Those with more severe PLMS had lower scores both on the AIMS, indicating less severe dyskinesia (r 5 2.46, p 5 .001), and on the Dementia Rating Scale (DRS), indicating lower cognitive functioning (r 5 2.46, p 5 .001). Five of the 7 patients with PLMS also had RDI . 10.

Sleep Variables On average, data were collected for 16.2 hours. The average bedtime was 21:20 hours (SD 5 2.0 hours; range 17:15– 04:21 hours) and the average final awakening time was 06:55 hours (SD 5 1.0 hours; range 5 0310 –1312 hours). On average, patients were asleep for 7.5 hours (SD 5 2.1 hours; range 5 2.4 –13 hours) and were awake during the night (i.e., number of minutes awake after sleep onset, WASO) for 2.2 hours (SD 5 1.6 hours; range 5 17 min–9.1 hours). Sleep variables were correlated with other clinical variables. Patients who went to bed early had more negative symptoms (higher SANS scores) (r 5 -.34; p 5 .018). Those who woke up later had worse quality of life (lower QWB score) (r 5 -.31, p 5 .032). Those who spent more time awake at night had more extrapyramidal symptoms (higher scores on the Simpson–Angus extrapyramidal symptoms scale) (r 5 .36, p 5 .017).

Neuroleptic Use and Sleep At the time of the recording, 44 patients were taking neuroleptic medications. Those taking neuroleptics went to bed earlier (21:07 hours vs. 22:59 hours; p 5 .030) and slept longer (468 min vs. 359 min; p 5 .016) than those not taking neuroleptics. There were no significant differences between these two groups in any other sleep variables, in respiratory variables, or in number of leg movements.

Discussion It is known that SDB and PLMS are very common in older nonpsychiatric adults. This study examined whether there

1430

S. Ancoli-Israel et al

BIOL PSYCHIATRY 1999;45:1426 –1432

is a high prevalence of SDB and PLMS in older schizophrenia patients relative to older nonpsychiatric adults that might explain the high prevalence of sleep disturbances found in this population. In our previous sample of healthy elderly aged 65 years and older (age range of 65–95 years and recorded with the same unattended sleep recording equipment as the current sample), the prevalence of RDI . 10 was 62%, while for RDI . 20 it was 44% (Ancoli-Israel et al 1991b). When an age-matched subsample of the healthy elderly aged 65–76 years was selected from our previous study, there was no significant difference in prevalence (45% had RDI . 10 compared to 54% in the schizophrenia patients in the current sample); however, there was a significant difference between healthy elderly with RDI . 20 (19%) and the schizophrenia patients with RDI . 20 (31%; x2 5 3.84, p , .050). These older schizophrenia patients, therefore, had a higher prevalence of severe SDB than the subsample of healthy elderly from our previous study. These observed differences were not due to differences in BMI; the average BMI for this group of nonpsychiatric adults was 25.1, and for the schizophrenia patients over 65 was 25.5 (see Table 4). Although MMSE data were not collected for the elderly healthy sample, the volunteers in that study were not cognitively impaired. Since this comparison group was not a matched control group, it remains unknown whether these findings are in fact related to the pathology of schizophrenia or to other differences between the two samples. Nevertheless, the data are suggestive and need to be further explored. The low prevalence of PLMS in this group of schizophrenia patients was surprising. Whereas 45% of nonschizophrenia elderly and 45% of those aged 65–76 years had MI . 5 (Ancoli-Israel et al 1991a), only 14% of the current sample of schizophrenia patients met this criterion, and only 8% (1 out of 13) of those over 65 met the criterion. Since levodopa is often used to treat PLMS (Kaplan et al 1993), it has been suggested that patients with PLMS might be in a hypodopaminergic state. In two recent reports, patients with Parkinson’s disease, a disease of dopamine deficiency, had increased frequency of PLMS (Wetter et al 1997; Dihenia et al 1997). Since dopaminergic levels have been shown to be high in some subcortical areas in schizophrenia patients (Davis et al 1991; Matthysse 1997), this might explain the low prevalence of PLMS. Although neuroleptics decrease dopaminergic activity, it is possible that even with neuroleptic use, the dopaminergic activity was still higher than that found in normals, and thus the low rate of PLMS. The fact that there were no differences in neuroleptic dose between the patients with and without PLMS suggests that the neuroleptics probably had little effect on the PLMS in this

Table 4. Description of Community-Dwelling Healthy Elderly Sample vs. Comparably Aged Schizophrenia Patients

Age (years) Mean SD Range BMIa Mean SD Range RDI Mean SD Range

Healthy elderly (n 5 332)

Schizophrenia patients (n 5 15)

69.9 3.3 65–76

70.4 3.5 65–76

25.1 4.6 14.6 – 44.2

25.5 5.1 18.7–37.4

13.5 17.2 0 –216.5

20.0 21.1 1.6 –75.8

a

BMI, body mass index (kg/m2).

sample of patients. More research in needed to examine this hypothesis. The inverse relationship between PLMS and dyskinesia (as measured by the AIMS) might also fit in with the dopaminergic theory. Those with more leg jerks had less abnormal involuntary movements or less severe TD. TD is a reflection of hyperdopaminergia, therefore, according to the dopaminergic theory, it would not be surprising for those with less severe TD to have more severe PLMS. As one would expect, there were more reports of daytime sleepiness in the schizophrenia patients with SDB (RDI . 10) than those with no SDB (RDI , 10). The relationship between respiratory disturbances and decreased cognitive functioning, as reported by others in clinic and community samples (Bliwise 1993; AncoliIsrael and Coy 1994), was confirmed in our schizophrenia sample. There was also a relationship between leg movements and cognitive impairment, suggesting that either the sleep disturbances caused by the leg movements or the high prevalence of SDB in this subgroup may contribute to their lower scores on the MMSE. Although not every older schizophrenia patient can have his/her sleep recorded, and it is difficult to make the diagnosis of SDB based on history (Ancoli-Israel et al 1991b), future cognition studies of older schizophrenia patients need to keep this relationship between specific sleep disorders and cognitive functioning in mind in designing studies and interpreting results. On average, patients spent over 9 hours in bed, slept for 7.5 hours, and were awake for about 2 hours. There was also great variability in sleep patterns among patients, with one not going to bed until 4:21 in the morning, and not waking until after noon, suggesting that some schizophrenia patients may have been phase-delayed, i.e., their nighttime sleep period began and ended later than normal. Those patients with more negative symptoms had earlier

Sleep in Older Schizophrenia Patients

bedtimes most likely because they were less active and more socially withdrawn and therefore “escaped” by going to bed earlier. Patients taking neuroleptics were significantly sleepier during the night, going to bed earlier and sleeping more. It is unclear from these data whether the increased sleepiness was a side effect of the neuroleptic medications. In a study of young drug-naive schizophrenia patients and normal controls, Lauer et al (1997) found that the patients had shorter sleep periods, less total sleep time, lower sleep efficiency, longer sleep onset latencies, and more wake time than the normal controls. Therefore, in our data, the excessive sleepiness may in fact be secondary to the neuroleptic use rather than secondary to the schizophrenia. Further exploration of the impact of neuroleptic medications on sleep disturbance may yield clinically useful information about the frequent sleep complaints in this population. There were several limitations that need to be mentioned. The sample size of this study was relatively small. In addition, the study was cross-sectional and therefore causal inferences cannot be drawn from these data. Multiple comparisons were made without stringent type I error control. As a result, the findings of the current study should be replicated with a larger sample. A great limitation was that a matched control group was not available at the time of data collection. Future studies should also examine the effect of newer “atypical” antipsychotic medications on sleep. In summary, the high amount of SDB found in this sample suggests that the sleep disturbances seen may be secondary to SDB as well as to medication use and to the schizophrenia process. Those patients who both have SDB and are taking neuroleptics are most likely to be sleepiest of all. Our sample was not large enough to explore this relationship. We hypothesize that in older patients with schizophrenia, the alleged elevated levels of dopamine in subcortical brain areas may be protective against the high amount of leg kicks usually seen in this age group. We continue to explore these questions. Supported by NIMH 49671, NIA AG02711, NIA AG08415, NHLBI HL44915, NIMH MH45131, NIMH MH43693, NIMH MH49671, the Research Service of the Veterans Affairs San Diego Healthcare System, Department of Veterans Affairs VISN22 MIRECC, and the Sam and Rose Stein Institute for Research on Aging. Portions of these data were presented at the annual meetings of the Association of Professional Sleep Societies, Los Angeles, 1993 and in Nashville, 1995.

References American Psychiatric Association (1987): Diagnostic and Statistical Manual of Mental Disorders, 3rd ed rev. Washington, DC: American Psychiatric Press.

BIOL PSYCHIATRY 1999;45:1426 –1432

1431

Ancoli-Israel S (1989): Epidemiology of sleep disorders. In: Roth T, Roehrs TA, editors. Clinics in Geriatric Medicine. Philadelphia: Saunders, pp 347–362. Ancoli-Israel S, Coy TV (1994): Are breathing disturbances in elderly equivalent to sleep apnea syndrome? Sleep 17: 77– 83. Ancoli-Israel S, Kripke DF, Mason W, Messin S (1981): Comparisons of home sleep recordings and polysomnograms in older adults with sleep disorders. Sleep 4:283–291. Ancoli-Israel S, Seifert AR, Lemon M (1986): Thermal biofeedback and periodic movements in sleep: Patients’ subjective reports and a case study. Biofeedback Self Regul 11:177–188. Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O (1991a): Periodic limb movements in sleep in community-dwelling elderly. Sleep 14:496 –500. Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O (1991b): Sleep disordered breathing in communitydwelling elderly. Sleep 14:486 – 495. Ancoli-Israel S, Mason WJ, Clopton P, Fell R, Jones DW, Klauber MR (1997): Use of wrist activity for monitoring sleep/wake in demented nursing home patients. Sleep 20: 24 –27. Andreasen NC, Olsen S (1982): Negative v. positive schizophrenia: Definition and validation. Arch Gen Psychiatry 39:789 – 794. Benca RM, Obermeyer WH, Thisted RA, Gillin JC (1992): Sleep and psychiatric disorders: A meta-analysis. Arch Gen Psychiatry 49:651– 668. Benson KL, Zarcone VP (1994): Sleep abnormalities in schizophrenia and other psychotic disorders. In: Oldham JM, Riba MB, editors. Review of Psychiatry. Washington, DC: American Psychiatric Press, pp 677–705. Bliwise DL (1993): Sleep apnea and cognitive function: Where do we stand? Sleep 16:S72–S73. Bliwise DL, Gourash-Bliwise N, Chmura-Kraemer H, Dement WC (1984): Measurement error in visually scored electrophysiological data: Respiration during sleep. J Neurosci Methods 12:49 –56. Blom S, Ekbom KA (1961): Comparison between akathisia developing on treatment with phenothiazine derivatives and the restless legs syndrome. Acta Med Scand 170:689 – 694. Coccagna G, Lugaresi E (1981): Restless legs syndrome and nocturnal myoclonus. Int J Neurol 15:77– 89. Cole RJ, Kripke DF, Gruen W, Mullaney DJ, Gillin JC (1992): Automatic sleep/wake identification from wrist activity. Sleep 15:461– 469. Coleman RM (1982): Periodic movements in sleep (nocturnal myoclonus) and restless legs syndrome. In: Guilleminault C, editor. Sleeping and Waking Disorders: Indications and Techniques. Menlo Park: Addison-Wesley, pp 265–296. Coleman RM, Pollak CP, Weitzman ED (1980): Periodic movements in sleep (nocturnal myoclonus): Relation to sleep disorders. Ann Neurol 8:416 – 421. Davis KL, Kahn RS, Ko G, Davidson M (1991): Dopamine in schizophrenia: A review and conceptualization. Am J Psychiatry 148:1474 –1486. Dihenia BH, Rye DB, Bliwise DL (1997): Daytime alertness in Parkinson’s disease. Sleep Res 26:550. Folstein MF, Folstein SE, McHugh PR (1975): Mini-mental

1432

BIOL PSYCHIATRY 1999;45:1426 –1432

state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189 –198. Guilleminault C (1987): Obstructive sleep apnea syndrome and its treatment in children: Areas of agreement and controversy. Pediatr Pulmonol 3:429 – 436. Guilleminault C (1989): Clinical features and evaluation of obstructive sleep apnea. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. Philadelphia: Saunders, pp 552–558. Guy W (1976): Abnormal Involuntary Movement Scale (AIMS). In: Psychopharmacology Research Branch N, editor. ECDEU Assessment Manual for Psychopharmacology, rev (Publication ADM 76-338). Rockville, MD: National Institute of Mental Health, pp 534 –537. Hening WA, Walters A, Kavey N, Gidro-Frank S, Cote L, Fahn S (1986): Dyskinesias while awake and periodic movements in sleep in restless legs syndrome: Treatment with opioids. Neurology 36:1363–1366. Jeste DV, Wyatt RJ (1982): Understanding and Treating Tardive Dyskinesia. New York: Guilford Press. Jeste DV, Harris MJ, Krull A, Kuck J, McAdams LA, Heaton R (1995): Clinical and neuropsychological characteristics of patients with late-onset schizophrenia. Am J Psychiatry 152: 722–730. Kaplan RM, Anderson J (1990): The general health policy model: An integrated approach. In: Spilker B, editor. Quality of Life Assessments in Clinical Trails. New York: Raven, pp 131–149. Kaplan PW, Allen RP, Buchholz DW, Walters JK (1993): A double-blind, placebo-controlled study of the treatment of periodic limb movements in sleep using carbidopa/levidopa and propoxyphene. Sleep 16:717–723. Kavey N, Walters AS, Hening W, Gidro-Frank S (1988): Opioid treatment of periodic movements in sleep in patients without restless legs. Neuropeptides 11:181–184. Kempenaers C, Kerkhofs M, Linkowski P, Mendlewicz J (1988): Sleep EEG variables in young schizophrenic and depressive patients. Biol Psychiatry 24:833– 838. Kripke DF, Gherini S (1977): Schizophrenic hallucinations and sleep apnea: A case report. Sleep Res 6:152. Kripke DF, Ancoli-Israel S, Klauber MR, Wingard DL, Mason WJ, Mullaney DJ (1997): Prevalence of sleep disordered breathing in ages 40-64 years: A population-based survey. Sleep 20:65–76. Lauer CJ, Schreiber W, Pollmacher T, Holsboer F, Krieg JC (1997): Sleep in schizophrenia: A polysomnographic study on drug-naive patients. Neuropsychopharmacology. 16:51– 60. Mason WJ, Ancoli-Israel S, Kripke DF (1989): Apnea revisited: A longitudinal follow-up. Sleep 12:423– 429.

S. Ancoli-Israel et al

Matthysse S (1973): Antipsychotic drug actions: A clue to the neuropathology of schizophrenia? Fed Proc 32;200 –205. Mitler MM, Browman CP, Menn SJ, Gujavarty K, Timms RM (1986): Nocturnal myoclonus: Treatment efficacy of clonazepam and temazepam. Sleep 9:385–392. Montplaisir J, Godbout R (1989): Restless legs syndrome and periodic movements during sleep. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. Philadelphia: Saunders, pp 402– 409. Neeper SA, Benson KL, Faull KF, Zarcone VP Jr (1992): Periodic leg movements in schizophrenia: Incidence and correlates. Sleep Res 21:154. Overall JE, Gorham DR (1962): The brief psychiatric rating scale. Psychol Rep 10:799 – 812. Simpson GW, Angus JWS (1970): A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 212(suppl 1):11–19. Spitzer RL, Williams JBW (1986): Structured Clinical Interview for DSM-III-R – Patient Version. New York: New York State Psychiatric Institute, Biometrics Research. Sweetwood HL, Kripke DF, Grant I, Yager J, Gerst MS (1976): Sleep disorder and psychobiological symptomatology in male psychiatric outpatients and male nonpatients. Psychosom Med 38:373–378. Sweetwood H, Grant I, Kripke DF, Gerst MS, Yager J (1980): Sleep disorders over time: Psychiatric correlates among males. Br J Psychiatry 136:456 – 462. Timms RM, Dawson A, Taft R, Erman MK, Mitler MM (1988): Oxygen saturation by oximetry: Analysis by microcomputer. J Polysom Tech Spring:13–21. van Kammen DP, van Kammen WB, Peters JL, Rosen J, Slawsky RC, Neylan T, et al (1986): CSF MHPG, sleep and psychosis in schizophrenia. Clin.Neuropharmacol 9(suppl 4):575–577. Walters AS, Hening W, Rubinstein M, Chokroverty S (1991): A clinical and polysomnographic comparison of neurolepticinduced akathisia and the idiopathic restless legs syndrome. Sleep 14:339 –345. Walters AS, Aldrich MS, Allen R, Ancoli-Israel S, Buchholz DW, Chokroverty S, et al (1995): Toward a better definition of the restless legs syndrome. Mov Disord 10:634 – 642. Wetter TC, Seidel VC, Scheidtmann K, Trenkwalder C (1997): A comparative polysomnographic study of patients with Parkinson’s disease and multiple system atrophy. Sleep Res 26:604. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993): The occurrence of sleep disordered breathing among middle-aged adults. N Engl J Med 328:1230 –1235.