Sleep Disturbances in Various Nonaffective Psychiatric Disorders

Sleep Disturbances in Various Nonaffective Psychiatric Disorders

0193-953x/87 $0.00 + .20 Skep Disorders Sleep Disturbances in Various Nonaffective Psychiatric Disorders Monika Gierz, M.D.,* Scott S. Campbell, Ph...

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0193-953x/87 $0.00 + .20

Skep Disorders

Sleep Disturbances in Various Nonaffective Psychiatric Disorders Monika Gierz, M.D.,* Scott S. Campbell, Ph.D .,t and ] . Christian Gillin, M .D .:f:

"Troubled minds have troubled sleep and troubled sleep causes troubled minds." With these words, Frederic Snyder helped establish the field of clinical psychiatric sleep disorders in the mid 1960s. The discovery of REM sleep and its close association with dreaming spurred the early research on electroencephalogram (EEG) sleep in psychiatry, particularly in schizophrenia, where it was hoped that hallucinations might be pathophysiologically related to REM sleep. During the past 15 years or so, however, much of the focus has been on sleep disorders in affective illness, stimulated by the association of short REM latency with major depression. Nevertheless, it should not be forgotten that disturbed sleep is frequently mentioned by either patients with other psychiatric disorders or by formal diagnostic criteria for other disorders, for example, "trouble falling asleep or staying asleep" in post-traumatic stress disorder, generalized anxiety disorder, or psychoactive substance use disorder (DSM-111-R). In this article, we shall briefly review EEG sleep studies in schizophrenia, obsessive-compulsive disorder, eating disorders, panic disorder, borderline personality disorder, Alzheimer's disease, and certain instances of substance abuse.

SCHIZOPHRENIA Although schizophrenia has not been a major object of sleep research in recent years, EEG sleep abnormalities remain among the best docu*UCSD Fellow in Clinical Psychopharmacology and Psychobiology t Assistant Research Psychobiologist, UCSD :f:Professor of Psychiatry; Director, UCSD Mental Health Clinical Research Center; Director, UCSD Fellowship in Clinical Psychopharmacology and Psychobiology Department of Psychiatry, Veterans Administration Medical Center, San Diego, California and University of California, San Diego, La Jolla, California Supported in part by Veterans Administration Medical Center, the UCSD Fellowship in Clinical Psychopharmacology and Psychobiology_MH18399 (M_G)_,_MH.381'38,_and.AGOSl.31

Psychiatric Clinics of North America-Vol. 10, No. 4, December 1987






mented biologic findings in schizophrenia. These abnormal measures include loss of D elta (stage 3 + 4) sleep, apparent short RE M latency in a high percentage of patients, and inadequate REM rebound following experimental REM deprivation in some schizophrenic patients. The lack of interest may reflect the fact that some of these abnormalities are diagnostically nonspecific. Nevertheless, this comment is applicable to most biologic markers in clinical psychiatric research (such as hypothalamic-pituitary-adrenal activation and low CSF 5-hydroxy-indole-acetic acid concentration) and, in any case, should not necessarily detract from attempts to understand the clinical and pathophysiologic significance of any well established biologic abnormality in medicine. REM Sleep in Schizophrenic Patients In the first all-night polygraphic study of schizophrenic patients, Dement 18 compared 17 chronic schizophrenics with 13 medical students. His findings suggested that total REM sleep was the same in both groups, although some schizophrenic patients seemed to show a shorter REM latency than the controls. Subsequent research has failed to describe a consistent or unique pattern of REM sleep abnormalities that could serve as a state or trait marker of schizophrenia. No consistent difference in REM percentage during sleep has been found in studies comparing chronic schizophrenic patients with normals. 11 · 12• 21 • 22 • 38 The sleep of psychotic or autistic children studied by Ornitz and associates 62 a showed no difference in sleep pattern when compared with normal controls. When hallucinating and nonhallucinating patients were compared, Koresko and coworkers 46A as well as Feinberg and colleagues 22 found no difference in REM percentage. A third study, however, described low normal REM percentage in hallucinating, and very low REM percentage in nonhallucinating, patients. 64 Amounts of REM sleep were also discrepant in their findings. Feinberg and coworkers 21 reported high levels of REM sleep in four recovered schizophrenics. Gulevich and associates 34 described increased REM sleep, REM "storms" and short REM latencies comparing chronic unmedicated schizophrenics in remission with nonpsychotic controls. On the other hand, Azumi 1 found less RE M sleep in a group of 35 chronic schizophrenics than in 33 normals. To explain this discrepancy, Feinberg and colleagues 21 postulated that short-term-schizophrenics (ill less than 1 year) have lower REM sleep than long-term-schizophrenics (ill more than 1 year). During acute phases of illness, psychotic patients not only have decreased total sleep time but also show very little REM sleep. 49 • 92 Later studies confirmed Feinberg' s postulate that REM sleep time tends to be reduced in acute schizophrenia102 and increased in chronic patients near remission. 34 Kupfer and coworkers 47 conducted an often-cited longitudinal study of six acute schizophrenic patients with nightly polygraphic sleep recordings during psychotic episodes. Three of the patients did not receive medication at any time. During the "waxing" phase of the psychotic episode, patients suffered insomnia and a disproportionate loss of REM sleep. As the psychotic episode waned, both REM and NREM gradually returned to normal values. During the postpsychotic and remission periods, the schizophrenics slept relatively well and did not show evidence of REM rebound during



recovery phase. Similar findings were present in two acutely ill patients studied longitudinally by Gillin and Wyatt. 32 Other studies suggested reduced REM sleep in acute phases of illness with normal REM sleep in recovery and remission. 86 REM latency is defined as the time period from falling asleep to the onset of the first REM period. In normals, this interval is approximately 70 to 90 minutes. Short REM latency is consistently reported in narcolepsy and affective disorders, especially in depression. 31 REM latency in schizophrenia is highly variable. Dement's original study 18 suggested that REM latency might be short in some schizophrenic patients. Feinberg22 was the first to systemically investigate this parameter, which he found to be significantly more variable in actively ill schizophrenics than in controls. As mentioned previously, Gulevich et al. 34 suggested that REM latency was short in some remitted schizophrenics. Likewise, both Stern and colleagues, 86 studying young acute schizophrenics, and Jus et al. 44 , studying elderly schizophrenics, reported short REM latency compared with agematched controls. Reich et al. 72 suggested that REM latency might be abbreviated in schizophrenic patients with affective features. Moreover, baseline REM latency was shorter in patients who later required antidepressant medications. The most recent papers on REM latency in schizophrenia reflect the controversy and diversity of earlier findings. In a study of five chronic schizophrenic patients, undergoing an acute psychotic exacerbation, Hiatt et al. 39 reported a significant reduction of REM latency when compared with normal controls. These patients met RDC criteria for schizophrenia and were drug free for at least 2 months at the time of the study. More recently, Zarcone et al. 104 compared the REM latencies in patients with the diagnoses of schizophrenia, schizoaffective disorder, and major depressive disorder. The authors found low REM latencies in all three patient groups as well as "consistently decreased slow wave sleep in all three patient groups compared with normal controls." Their conclusion points to the fact that short REM latency still might be connected with affective symptomatology, "cutting across the diagnostic lines." In another recently published study, however, Ganguli and coworkers 28 investigated EEG sleep abnormalities in a carefully screened group of young, never medicated, nonschizoaffective schizophrenics and compared this group with delusional depressives, nondelusional depressives, and normal controls. They found in the schizophrenic group normal REM latencies, a normal first REM period duration and decreased delta wave count during non-REM sleep. Delta sleep per cent and temporal distribution of delta sleep across the night was similar to that seen in normal controls. REM Sleep Deprivation After REM sleep deprivation, normal subjects experience REM rebound during recovery nights defined as an increase of REM sleep above the individual's normal levels. REM sleep deprivation in schizophrenic patients, however, has variable and controversial effects. Two studies showed _normal REM sleep reboun.d-aft~~J"i¥at:.iGn-in-the-seh~ephFeme--patiett~ as compared with controls. Several of the patients were receiving phenothiazines during the study. 17• 96 Three different investigation groups found a





significant lack of REM rebound in schizophrenic patients on recovery nights when compared with nonpsychotic patients. 7• 30· 103 The decreased or defective response to REM deprivation in actively symptomatic schizophrenics led to the formulation of the phasic event intrusion hypothesis by Dement, 19 which implied that psychosis might result from the breakthrough of pontine-geniculate-occipital (PGO) waves into waking and into NREM sleep. Reflecting this theory, Benson and Zarcone9 tried to evaluate the phasic events of REM sleep, namely through middle ear muscle activity (MEMA) and periorbital integrated potentials (PIPs). Both phenomena have been postulated as possible peripheral PGO equivalents in humans. The authors examined schizophrenic, schizoaffective, and depressed patients but failed to find increased phase events in wakefulness or NREM sleep. NREM Sleep Abnormalities in Schizophrenia NREM sleep disturbances, particularly reduced stage-4 sleep, have been consistently described in schizophrenic patients. 11 • 24 • 39 The diagnostic specificity of low stage-4 sleep in schizophrenic patients, however, is poor, as this finding is common in many other pathologic conditions. More recently, a group in Italy reported an abnormal distribution of sleep spindles and short-REM latency in depressed patients that was perfectly parallel to that in the schizophrenic group reported by Hiatt. 35 Chronobiologic Observations in Schizophrenic Patients The literature describing circadian rhythms in schizophrenic patients is scarce. Morgan and Cheadle60 noticed that schizophrenic patients tended to retire to bed early and get up early. In addition, the temperature curve of the schizophrenic patients was phase shifted to the left; that is, they were phase advanced and their temperature peak occurred earlier. The patients also showed lower mean temperatures throughout the recordings. Peak temperature was not associated with age, sex, dosage of major tranquilizers, social withdrawal score, or paranoid ideation. A second paper by Mills and associates 58 described two schizophrenic patients observed under fre e-running conditions for 21 days in an isolation unit. They showed an abnormally fast circadian period. This finding is consistent with the phase advance of the temperature rhythm described by Morgan and Cheadle. 60

SLEEP IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER Obsessive-compulsive disorder (OCD) is a rather rare, usually chronic disorder with generally moderate to severe impairment in functioning. Typical features are obsessions, which are ego-dystonic thoughts, ideas, or images, and compulsions that are "repetitive and seemingly purposeful behaviors performed according to certain rules and in a stereotyped fashion." 4 Common associated features are depression and anxiety. In fact, antidepressants have proved to be effective in these patients. 43 For these



reasons, it is interesting that the EEG sleep is similar in depressives and patients with OCD. Insel and coworkers 42 studied the sleep of 14 obsessional patients with all-night EEG recordings . Nine of these patients complained of sleep disturbances including difficulties falling asleep and staying asleep. Two patients reported hypersomnia. Most of the sleep difficulties were subjectively connected with compulsive activities (like checking or hand washing at night). When compared with normal controls, both depressed patients and patients with OCD showed short REM latency, decreased total sleep time, decreased stage-4 sleep, increased awakenings, and decreased sleep efficiency (the ratio of sleep time to time spent in bed). The groups differed in two measures: The patients with OCD had a tendency toward lower REM density and they had more stage-1 and 3 sleep than the depressed patients. Neither the presence nor the severity of depressive symptoms accounted for the short REM latency in OCD.

SLEEP CHANGES IN PATIENTS WITH EATING DISORDERS So far, only a few articles have reported EEG sleep measures in patients with eating disorders. Again, the high prevalence of depressed mood in these patients prompted researchers to investigate the possibility of an overlap or coexistence of a mood disorder in patients with eating disorders. 15• 45• 89 Reports of endocrine disturbance, 29· 36• 40 positive family history for affective illness, 101 and the favorable response to antidepressant medication43· 89 supported the association between depression and eating disorders. Nevertheless, most studies have reported basically normal sleep EEG patterns in the majority of nondepressed patients with anorexia or bulimia. 41 · 51 • 98 Hudson et al. 41 found no basic difference in sleep architecture between bulimics with and without concomitant depression, although patients with major depression showed typical abnormalities. Levy et al. 51 also found no significant REM differences between patients with eating disorder and controls, but the low weight anorectics in their sample appeared to have decreased delta sleep. In a study of two bulimic normal weight, euthymic women, Weilburg and associates99 found long, rather than short REM latencies, as well as the absence of the typical EEG pattern during a REM period. In another study, Walsh and coworkers98 compared eight anorectics, 16 bilimics, and 14 normal controls. The anorectic patients showed a decrease in total sleep time and a trend toward a decrease in total rest. The bulimic women displayed no major differences when compared with the normal control group. In the only study that differs, Neil and colleagues62 compared EEG sleep patterns in anorectic patients with and without abnormal waking clinical EEGs. Patients with normal waking EEGs showed significantly shorter REM latency and less delta sleep compared with both patients with abnormal EEGs and normal controls. Patients were not characterized according to affective illness. Finally, in a longitudinal study of 10 patients with anorexia nervosa,





Lacey and coworkers~3 found that sieep was particularly fragmeni.e J J u1 ir"1g the last 4 hours of the night in low-weight patients . After returning to normal weight, patients slept longer, had less awakening time, and more REM sleep.

SLEEP IN PATIENTS WITH GENERALIZED ANXIETY DISORDER AND PANIC DISORDER Disorders of initiating and maintaining sleep (DIMS) are frequently associated with anxiety states according to both DSM -III and the Association of Sleep Disorder Centers (ASDC). Nevertheless, only recently have investigators studied the sleep EEG characteristics of patients with various types of anxiety disorders. Reynolds and associates 73 compared the sleep pattern of patients with generalized anxiety disorder (GAD), primary depression, and normal controls. Both patient groups had prolonged sleep latency, increased intermittent wakefulness, and diminished sleep efficiency. Depressed as well as anxious patients had reduced amounts of delta sleep. Short REM latency was only observed in the depressed patients. Patients with panic disorder also report sleep disturbances, characterized by difficulties falling asleep and multiple nocturnal awakenings. Uhde and colleagues91 published preliminary results from an ongoing study of nine patients. Patients showed significantly increased overall movement time, but the total time awake was not found to be different when compared with controls. Panic patients also had a mild shortening of REM latency and decreased REM density, although the significance of these findings was unclear. One of their subjects experienced a panic attack shortly after an awakening at 2 A.M . , apparently during sleep. Unfortunately, the patient did not immediately report his incident to staff, so a possible EEG relationship to staging could not be determined. We mention this case report because Lesser and associates 50 described the occurrence of a panic attack during EEG recorded delta sleep in a patient with panic d isorder. The patient awoke , was alert, felt frightened, and experienced symptoms typical for her daytime panic attacks (palpitations, tachycardia, shortness of breath, abdominal discomfort). Gundhaus and colleagues33 compared depressed patients and individuals who suffered from depression as well as panic disorder. In the panicdepressed cohort, the authors found decreased sleep efficiency, but sleep latencies approximated normal values. Roy-Byrne et al. 78 investigated the sleep of patients with panic disorder from a different point of view. Because sleep deprivation has been reported to have antidepressant effects in many depressed patients, they compared 12 panic patients with 10 depressives and 10 controls to determine the effect of one-night sleep deprivation on mood and behavior of patients with panic disorder. They found the well-known improvement of symptoms in the depressed cohort. As a group, the patients with panic disorder did not differ in their response from the controls "although a subgroup did experience noticeable worsening in their symptoms of anxiety



with 40 per cent experiencing an increase in panic attacks on the day following sleep deprivation."


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Borderline personality disorder (BPD) has been described as a condition of "stable instability," the stable character structure with its typical propensity to unstable mood and behavior. DSM-III descriptively emphasizes emotional lability, impulsivity, and behavioral dyscontrol together with prominent affective elements such as chronic dysphoria, depression, rage, and anxiety. Several authors investigating the affective disturbance in borderline patients, suggested a significant overlap between subgroups in both conditions. 1· 87 In 1981, Akiskal challenged the DSM-III characterologic description of borderlines, pointing out that BPD could be viewed as manifestations of atypical affective disorders. Carroll 16 argued that borderline psychopathology represents both a personality disorder as well as affective disorder. In a pilot study, Reynolds 73 investigated the EEG sleep of borderlines and primary depressives. Both groups had increased sleep latencies and increased REM activity and density, especially during the first REM period. The findings in the borderline patients were independent of the level of their depressive symptoms. This report confirms earlier findings by Bell and coworkers, 8 who reported similar sleep abnormalities in borderline patients with and without major depression. In a later report, Akiskal et al. 2 found that the mean REM latency of 24 nondepressed, nonschizotypal borderline outpatients was in the range of the 30 depressed patients and differed from the normal controls and the nonborderline personality disorders. Akiskal again focused on the diversity of affective spectrum disorders in his sample of borderline patients as being responsible for the REM latency results. Similar results were reported by McNamara et al., 55 who studied 10 depressed borderline patients and compared this group with 10 nondelusional depressed patients and 10 controls. Although the borderline patients showed diverse admitting diagnoses (substance abuse, dysphoria, suicidal ideation, eating disorder) the authors found close similarities in Hamilton ratings and sleep architecture when comparing the depressed borderlines with the patients with major depression. Both groups had sleep continuity disturbance, reduced delta sleep, short REM latencies and increased REM density, especially during the first REM period. The authors rightly point out that longitudinal studies of borderline patients would be desirable to clarify a possible underlying subtype of unrecognized mood disorder. SLEEP CHANGES IN ALZHEIMER'S DISEASE Senile dementia of the Alzheimer's type (SDAT) is the most prevalent form of dementia among older individuals, afflicti~ to l~r cent of the population over 65 years of age. 46 • 61 · 80 One of the earliest and, ulti-






mateiy, most disruptive symptoms associated \Vith SDAT i11v0lves chaugcs in the organization of the sleep/waking system. Though sleep disturbances are also frequently associated with the normal aging process, 20· 26 • 57· 66 they appear to be more pronounced in many patients with Alzheimer's disease. These changes in the sleep/waking system are reflected in both behavioral and physiologic indices. Until recently, data on the behavioral changes have been limited primarily to subjective studies and anecdotal reports. However, with the increasing use of ambulatory monitoring systems that reliably and effectively record behavioral indices, more quantitative data are emerging. Objective studies of physiologic variables (such as sleep EEG) have been hampered by the difficulties inherent in obtaining 24hour, or even night-time, laboratory recordings in these patients. SDAT patients often become easily disoriented, agitated, and irritable under such circumstances. Nevertheless, in recent years, a fairly detailed and more or less coherent picture of the deterioration in the sleep/waking process of patients with Alzheimer's disease has begun to emerge.

Behavioral Changes The behavioral alterations that accompany sleep disturbance in SDAT are expressed most dramatically in two related phenomena: "sundowning" and "night wandering." Both of these conditions underscore the considerable daily variation in cognitive state which characterizes SDAT, and they represent a substantial problem in the management of demented patients, whether institutionalized or living at home. Sundowning refers to a state in demented patients characterized by episodes of general nocturnal confusion, as well as by any, or all, of the following: autonomic overactivity, paranoid ideas, oneiroid experiences and confusion of people, time, and place. 52 Although few systematic studies have adddressed the causes of sundowning, there is suggestive evidence that loss of visual environmental cues may be a contributing factor. 13 · 52 Feinberg and coworkers 23 also reported similar states of confusion in some demented patients in association with the transition from REM sleep to waking. Based on these findings, the authors suggested that both sundowning and night wandering may result from "an inability of an impaired cerebrum to distinguish dream from reality or from pathological persistence into waking of REM phenomena." Night wandering is a related behavioral disturbance in which the demented patient awakens and roams the immediate surroundings, typically in a confused state, often unable to find his or her way back to bed. Night wandering is not only hazardous to the patient (because of falls and other accidents), but is also one of the primary symptoms leading to institutionalization of SDAT patients. In a survey of family members whose elderly dependents were institutionalized, Sanford79 found that sleep disturbance (night wandering, in particular) was the most common problem encountered in managing dependents at home. Eighty-four per cent of the respondents considered this problem intolerable and, thus, cause for institutionalization of the dependent. In a similar study, 59 per cent of primary care givers of demented patients cited "night waking" as a serious behavioral problem in home management. 70



Less dramatic changes in sleep/wake behavior have also been identified, in the form of more variable bedtimes and nocturnal sleep durations, 23 · 71 as well as an increased incidence of daytime napping, among Alzheimer's populations. 67-69 . 84 All of these findings reflect a fundamental deterioration in the brain mechanisms controlling the timing of sleep and wakefulness. 5 · 53 · 88 Physiologic Changes

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The breakdown in the sleep/wake timing system is also evident in the polysomnographic recordings of SDAT patients. Perhaps the most consistent finding across laboratory sleep studies is a substantial fragmentation of nocturnal sleep, as reflected in decreased sleep efficiency measures and increased number and duration of awakenings within sleep. 68· 75 · 85 The increased nocturnal sleep fragmentation is accompanied by increased daytime sleepiness in demented patients. Prinz and coworkers 68 found that demented subjects exhibited multiple sleep episodes during the daytime, averaging 78. 7 minutes of sleep per day. In contrast, healthy age-matched controls napped "infrequently or not al all," averaging only 6.6 minutes of sleep during the same interval. The nocturnal sleep fragmentation associated with SDAT is probably related, at least in part, to the fact that sleep also appears to be "shallower" in SDAT patients. This is reflected in reduced amounts and proportions of slow wave sleep. 10• 52• 54 · 68 Declines in SWS are so extreme that visually scored stage-4 is often virtually absent from the sleep records of these patients. Because of such shallowing, SDAT patients may be more susceptible to environmental disturbances such as noise or changes in ambient temperature. Changes in the structure of other aspects of NREM sleep have also been reported. There is a substantial reduction in the incidence of sleep spindles (12 to 15 Hz) and K-complexes, as well as a slowing in the frequency of spindling activity. This makes the scoring of stage-2 sleep in the records of demented patients difficult or impossible 3· 56 and has led some investigators to label the state, "indeterminant sleep. " 75 . 85 The deterioration in stage-2 sleep appears to parallel the cognitive deterioration in demented patients. 75 In addition, as spindles may play an important role in maintenance of sleep, 81 the observed reductions in this parameter may be related to the reduced capacity of patients with SDAT to maintain prolonged sleep episodes. Findings are less consistent with regard to changes in REM sleep parameters in demented patients. Some investigators have found reductions in the absolute amount and in the percentage of REM within a night's sleep, 23 • 67 · 68 whereas others have not. 10· 52• 54 · 75 Lengthened REM sleep latencies in demented subjects have also been reported, 10· 67 • 68 · 93 although this held only when intervening wakefulness between initial sleep onset and the first REM period was included. This again suggests a sleep maintenance problem rather than a specific alteration in the REM sleep system. The inconsistency of results with regard to REM measures probably reflects differences in___patient SJlmpl~osition in terms of age,-se¥.edt*of dementia, and length of time of illness. For example, Vitiello and co-








workers 93 found no difference in REM measures between controls and patients with mild SDAT. However, patients with moderate to severe SDAT showed less REM sleep and longer average REM latencies than the control group. In summary, the earliest indication of deterioration in the sleep process in SDAT is a substantial fragmentation of nocturnal sleep and a redistribution of sleep across the 24-hour day. This is followed by reductions in slow wave sleep amounts and by alterations in the structure of stage-2 sleep. Only in the latter stages of the disease do alterations in the REM sleep system become apparent. It should be noted that this profile is based on the results of several cross-sectional studies. No longitudinal studies of sleep changes in SDAT have been undertaken. Prinz and coworkers68 did examine the sleep of ten SDAT patients "in the late stages of the disease" on two occasions, spaced a year apart. Sleep, like mental function, showed a "general pattern of decline," but no single measure showed a significant change. Sleep Apnea Respiratory function during sleep may also be affected in SDAT. It has been hypothesized that the neuronal degeneration associated with SDAT "might exacerbate sleep apnea by disrupting neural control of brain centers associated with regulation of sleep/wakefulness and respiration. "82 Thus, several studies have compared the incidence of apnea in SDAT with that in age-matched control subjects. Smallwood and coworkers failed to confirm their hypothesis, finding no greater incidence of apnea in a group of mild-to-moderate SDAT patients than in healthy, age- and gender-matched control subjects. Other investigators, however, have reported increased proportions of female patients with SDAT with elevated apnea indices (AI > 5) compared with healthy controls. 27 • 77 • 95 Such increases are primarily due to higher numbers of obstructive, as opposed to central or mixed, apneas. Several laboratories have found a relationship between apnea index 77 or oxygen desaturation 10• 59 and cognitive impairment in demented patients. Smirne and coworkers, 83 on the other hand, d id not observe this relationship . Implications Taken together, the behavioral and physiologic changes described here may be viewed in terms of a fundamental breakdown in the biologic timing system mediating the sleep/wake process. The most notable alteration- a markedly reduced capacity for the maintenance of nocturnal sleep and of daytime alertness- reflects the virtual disappearance of normal circadian rhythmicity in sleep and wakefulness. Age-related changes in circadian organization are also evident in body temperature and neuroendocrine function. zo, 37• 94 • 100 · 105 Few studies have examined such variables in Alzheimer's disease, with conflicting results. 14• 69 Thus, the extent to which such circadian changes may be further pronounced in SDAT awaits further study. Nevertheless, owing to the overall cognitive decline associated with SDAT, it seems quite likely that these patients may have a reduced capac-



ity to respond to the usual periodic cues that allow us to adjust our internal rhythms to the external world. By increasing the strength of such social and environmental synchronizers (for example, timed exposure to bright light, regular exercise, well-defined daily schedules) re-establishment of more manageable sleep/wake patterns may be possible. Can the changes in the sleep system of SDAT patients be of use in diagnosis? Results of studies using discriminant analysis indicate that certain sleep parameters are almost as effective as mental function indices in discriminating SDAT patients from controls. 67 Likewise, REM latency, first REM period duration, and sleep maintenance index all were effective in classifying demented versus elderly depressed patients. 75 Because many of the early symptoms of SDAT (forgetfulness, irritability, agitation) are also major symptoms of depression, such differential diagnosis would be of considerable importance. However, these authors caution against premature application of such diagnostic techniques. They emphasize that further study is required to determine if such measures are effective in accurately discriminating patients with the "dementia syndrome of depression" from those with Alzheimer's dementia.

SLEEP DURING WITHDRAWAL FROM STIMULANTS Cocaine and amphetamines are commonly abused stimulants that apparently potentiate central aminergic neurotransmission, although they differ somewhat in their physiologic and clinical effects. The effect of cocaine on human sleep has apparently been examined in only one study. As part of a comprehensive research program on the effects of cocaine on depression, Post et al. 65 administered cocaine (starting at 30 to 60 mg per day, reaching 65 to 200 mg per day, in divided doses at 9:00 A.M. and 10:00 P.M.) to five moderately depressed patients for an average of 6 days. Cocaine significantly suppressed REM sleep (from 89 minues per night at baseline to 74 minutes on drug and 104 minutes on recovery) and total sleep time (from 351 minutes on baseline to 317 minutes on drug and 379 minutes on recovery). The effects appeared to be dose dependent, and did not appear to be related to changes in mood or autonomic function. No studies have been reported of sleep in cocaine addicts. The sleep effects of amphetamine have been studied extensively, in normal subjects, in patients with narcolepsy, in depression, and to a lesser extent, in stimulant addicts. It is well known that acute administration of amphetamine reduces total sleep time and REM sleep but that partial tolerance develops over time. Upon withdrawal, REM sleep "rebounds." In two studies, sleep was recorded polygraphically as addicted patients were withdrawn. In the first, Oswald and Thacore 63 showed that REM sleep remained elevated for several weeks. Although the patients appeared depressed and listless, no attempt was made to correlate their clinical symptoms with their altered sleep patterns. In a more detailed study of withdrawal in individuals who had regularly used fairl}!...-high_doses of amphetamine for at leas.L5-mo.nths,-Watwnet al. 97 reported on four subjects who were admitted as voluntary research






subjects to a psychiatric hospital, where they took the last dose of amphetamine on the first day of hospitalization but received no medication thereafter. All of the patients became depressed during withdrawal. Depression peaked about 48 to 72 hours after the last dose and was mostly over after approximately 4 days, although some subjects showed persisting depression and fatigue for weeks to months. During the first days of withdrawal, three subjects, who were apparently sleep deprived upon entering the study, slept for unusually long periods, including two who spent more than 16 hours asleep each 24 hours. These three patients also showed unusually high levels of Stages 3 and 4 sleep during the acute recovery period. During the second through fourth nights of withdrawal, all patients showed unusually high amounts of REM sleep (141 to 357 minutes compared with a normal mean of 90 minutes) and REM per cent (31.9 to 36.5 per cent compared with 22 per cent). Two subjects showed short REM latency (about 11 minutes compared with 80 minutes). Although REM latency did not correlate to a statistically significant extent with ratings of depression, total sleep time, REM sleep time, and total REMs (a measure of number of eye movements during REM sleep over the night) it correlated positively and significantly with depressive ratings.

CONCLUSIONS Altered sleep must be understood in the context of the 24-hour day. In the clinical situation, it must be viewed as one part of the entire syndrome, varying with individual patient characteristics, severity of symptoms, phase of the natural history of the disorder, treatment, and so forth. Although no sleep measure has yet been found to be specific and sensitive enough to be pathognomonic for a specific clinical psychiatric syndrome, disturbed sleep is a common feature of many psychiatric disorders. Insomnia is common, at least at times, in all of the disorders reviewed here, although hypersomnia seems to be a transient phenomena during withdrawal from amphetamine in some abusers. Reduced stage-4 sleep is a common but diagnostically nonspecific finding in most of the disorders reviewed here. Does reduced stage-4 have any clinical use? Further research is needed to address this question , but the preliminary evidence from Ganguli and associates 28 suggests that negative symptoms of schizophrenia may be inversely related to amounts of stage 4. In addition, Loewenstein and colleagues 52 suggested that loss of stage-4 sleep might be an early correlate of cognitive decline in patients with Alzheimer's disease, above and beyond the normal age-related reduction in stage 4. 23 Tamura and Karacan 90 have shown that stage-4 sleep is reduced in many neurologic disorders. Thus, stage 4 may reflect, in part, some anatomic or functional cortical abnormality in some syndromes. Interestingly, patients with amphetamine withdrawal did not appear to show a reduction in stage-4 sleep. As this review makes clear, short REM latency is by no means found only in depression. It has been reported in many, but not all, studies of schizophrenia, in the only published study of obsessive-compulsive disor-



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