Sleep in Psychiatric Disorders

Rev. Bras. Psiquiatr. vol.27  suppl.1 São Paulo May 2005
doi: 10.1590/S1516-44462005000500006

ABSTRACT

Altered sleep patterns are prominent in the majority of psychiatric disorders. This article examines the psychiatric disorders that are most often associated to sleep dysfunction as it is related in clinical practice and describes the polysomnographic findings. Patient's main complaints are related to difficulty in initiating and maintaining sleep (initial or middle insomnia, respectively) and poor quality of sleep. Early awakening or terminal insomnia is most described in the depressive conditions. Hypersomnia may be the main symptom in some depressive disorders, as seasonal depression, depression with atypical features or depressive episodes in bipolar disorder. Polysomnographic evaluation shows, in general, a significative reduction in the efficiency and total time of sleep, in detriment to the amount of slow wave sleep. The reduction of rapid eye movement (REM) sleep latency is mainly described for the depression, but has also been reported in other psychiatric disorders.

Introduction

Sleep dysfunction is prominent in most psychiatricdisorders.1 In a survey carried out in variousAmerican cities, 40% of interviewees reporting insomnia and 46.5%of those reporting hypersomnia met the criteria for mentaldisease according to the DSM-III-R.2

In the international classification of sleep disorders(ICSD),3 the third division refers to sleepdysfunction related to clinical and psychiatric disorders. Suchmental disorders are subdivided into: psychoses, mood disorders,anxiety disorders, panic disorders and alcoholism. There is adiscrepancy regarding the classification of mentaldisorders4 in which panic disorder is part of ananxiety disorder. The justification for this separation in theICSD is that some panic disorders may only present episodicmanifestations during sleep.3,5 Therefore, alteredsleep patterns are used as diagnostic criteria for variouspsychiatric profiles, such as major depression, post-traumaticstress disorder and generalized anxiety disorder.4

This article addresses psychiatric disorders that mostfrequently present sleep dysfunction in clinical practice and themain polysomnographic findings described. Some studies evaluatingthe physiopathology of such alterations in certain sleepdisorders and of those caused by the most common drug therapieswill also be discussed. Sleep patterns and changes related tospecific disorders of childhood and adolescence will be presentedseparately.

Mood disorders

1. Depression

Approximately 80% of patients with depression complain ofchanges in sleep patterns. Of these 80%, most present terminalinsomnia, waking up hours before necessary (earlyawakening).6 In cases of accompanying anxietysymptoms, initial insomnia, in which the patient presentsdifficulty in initiating sleep, is also common.6 Inlongitudinal epidemiological studies, insomnia has been found tobe an important predictor of increased risk of depression in oneto three years of follow up.7 In addition, persistentinsomnia has been correlated with the onset of a new depressiveepisode.8

Specific complaints may include frequent nighttime awakenings,poor quality sleep, reduction in total sleep time, andnightmares.9 Although complaints of excessive daytimesleepiness are rare in major depression, some patients withinsomnia relate increased fatigue and try to compensate for theirsleep loss with daytime naps.10

A small percentage of patients with major depression, themajority of whom are young adults,10 complain ofexcessive sleepiness. Most patients with bipolar disorder alsorelate insomnia when in depression, but a significant percentageof patients relate hypersomnia symptoms with prolonged nighttimesleep, difficulty in awakening and excessive daytimesleepiness.9 Patients with seasonal affective disorderand atypical depression also reporthypersomnia.4,9

1) Polysomnographic findings

In patients with depression, polysomnographic findings can bedivided into three main categories: sleep continuity, slow-wavesleep and rapid eye movement (REM) sleep. In the sleep continuitycategory, increased sleep latency, more frequent nighttimeawakenings and early awakening are observed, resulting in sleepfragmentation and decreased sleep efficiency.11Studies comparing depressed patients to age-matched controls haveconfirmed these results.1,9

Slow-wave sleep deficit has been reported by various authors,although not all studies have shown this reduction.1,9Reduced slow-wave sleep seems to be more pronounced in the firstnon-rapid eye movement (NREM) period, which alters itsdistribution throughout the night.12 Decrease in deltapower has also been observed in quantitativeelectroencephalography studies carried out duringsleep.12

The first finding regarding REM sleep was the reduction in REMlatency (period of time from sleep onset to REMonset).1,9-10 Over the years, this has been proven tobe the most frequently described factor in patients with majordepression, although it is as yet unknown whether REM latency isa specific indicator of current or past depression, perhapslinked to cholinergic hyperactivity.9 Other findingsrefer to the increase in the first REM sleep period, in REMdensity (increase in the rate of rapid eye movements) and in REMpercentage.1,9-11

In a study attempting to relate subjective sleep complaints topolysomnographic data in patients with depression, the patientswere incapable of accurately estimating the number of awakeningsduring the night.13 The subjective evaluation of sleepquality seemed to be associated with sleep continuity and theamount of slow-wave sleep.13

2. Mania

During episodes of mania, patients relate reduced total sleeptime, with a subjective sensation of a decreased need for sleep.In various cases, the transition to the mania stage is precededby periods of sleeplessness. It has also been suggested that thetransition from euthymia or depression to the maniac stage occursduring sleep.10

1) Polysomnographic findings

The main characteristic of mania seems to be reduced total sleep time, since the maniac patient appears to have difficulty in falling asleep.1,9-10 Two or three hours after falling asleep, the patient awakes, totally reinvigorated. As in depression, the duration of stages 3 and 4 may be curtailed, although the findings regarding REM sleep were less consistent.1,9-10

Anxiety disorders

1. Generalized anxiety disorder

Patients with generalized anxiety disorder (GAD) frequentlycomplain they cannot relax or stop worrying about their problemswhen they are in bed.5 The sleep dysfunctions mostfrequently associated with GAD profiles are sleep maintenanceinsomnia14 and difficulty in initiating sleep (initialinsomnia).5,10,15 Poor quality sleep and interruptedsleep have also been reported.5,10,14

1) Polysomnographic findings

Patients with GAD present increased sleep latency (frequentlymore than one hour15), increased duration of thelightest sleep stages, lower percentages of REM sleep and, exceptfor isolated cases, increased or normal REM sleeplatency.1,5,10

2. Panic disorder

The most common sleep-related complaints of patients withpanic disorder are initial or maintenance insomnia (approximately70% of the patients) and poor quality or fragmentedsleep.5,10,16 Panic attacks may occur during sleep. Inpatients with nocturnal panic attacks, levels of anxiety seem tobe higher and the duration of the attacks longer. In addition,there is increased presence of somatic symptoms and morecomorbidity with other psychiatric disorders, especiallydepression.17 Symptoms similar to those associatedwith panic attacks during sleep may be found in patients witharrhythmia, gastroesophageal reflux, sleep apnea, night terrorsor REM sleep behavioral disorders.10 All of thesefactors have to be taken into consideration in the differentialdiagnostic evaluation.

Maybe the most important complication of nocturnal panicattacks is chronic sleep deprivation.5,16 In fact,patients with this complication develop anticipation anxiety andavoidance behavior, as seen in daytime attacks. In the specificcase of sleep panic attacks, many patients develop a fear ofsleep and are reluctant to sleep.

1) Polysomnographic findings

When compared with control individuals, patients with panicdisorder present slightly increased sleep latency and reducedsleep efficiency.5,16 There is an increase in time ofmovement during sleep, but there is no temporal relationshipbetween moving and nocturnal panic attacks.18 Sleeppanic attacks generally take place at the end of stage 2 or onsetof stage 3 of REM sleep.5,10,16

3. Post-traumatic stress disorder

The main sleep-related complaints in patients withpost-traumatic stress disorder are insomnia and awakening due toanxiety or nightmares. It is common to find a state of autonomichyperactivity, characterized by hypervigilance andinsomnia.5,10,16 Frequent nightmares are reported by59% to 68% of patients and are a marker for this disease,involving relived experiences as well as imaginary scenarios withfrightening or life-threatening content.5,10,16Awakening due to anxiety seems, in turn, to be more related toREM sleep.5,16

1) Polysomnographic findings

Post-traumatic stress disorder has been associated withincreased sleep latency, decreased sleep efficiency, increase intime awake after sleep onset, reduction in total sleep time,decreased stage 2 sleep and increased stage 1 NREM sleep (sleepthat is more superficial).5,10,16 There isconsiderable controversy regarding the effects of post-traumaticstress disorder on REM sleep. Some authors report normal REMparameters, whereas others relate decreased latency of REM sleepand increased REM density.1,10,16

Schizophrenia

Although sleep disorders in schizophrenia are sufficientlysevere to warrant clinical attention, they are seldom thepredominant complaint.19 In a state of psychoticagitation, there are prolonged periods of total sleeplessness;and when agitation subsides, expressive insomnia takes itsplace.20 There are reports of near total inversion ofthe wake-sleep cycle, a situation in which the patient sleepsduring the day and remains awake at night.20 Severeinsomnia is also described in exacerbations of the schizophrenicprofile and might precede the onset of other symptoms duringrelapse.19,20 Schizophrenic patients may experienceterrifying hypnagogic hallucinations and nightmares.20These may be accompanied by several primary sleep disorders, suchas poor sleep hygiene and increased periodic lower limbmovements.20 When present, sleep apnea comorbidity mayaggravate schizophrenic symptoms.10

Various studies have related schizophrenia to specificpolysomnographic findings, as we shall discuss herein. Slow-wavesleep, as well as sleep maintenance, seems to be inverselyrelated to the size of the cerebral ventricles. It is suggestedthat decreased slow-wave sleep and increased schizophrenicnegative symptoms may be related to reduced brain metabolism andaccelerated ageing or brain atrophy.21

The first attempt to establish a connection between REM sleepabnormalities and schizophrenia was related by Dement, in1955.22 The study was carried out before the advent ofthe neuroleptics, and the author found decreased REM sleeplatency but did not observe any difference in its density inschizophrenics.22 Several studies followed, withdistinct findings in REM parameters.1,10,20 Thisvariation may be explained by the different stages of thedisease, by the imbalance of neurotransmitters and by the use ofshort- and long-term medication.10 Despite theseconflicts, the similarity between the hallucinatory activity thatnormally occurs in REM sleep and the hallucinations found inschizophrenia continue to intrigue researchers, and severaltheories have been suggested in the attempt to explain thissimilarity.10,20

1) Polysomnographic findings

Sleep continuity disturbance, decreased slow-wave sleep,decreased REM latency, increased REM percentage and decreasedamount of time in NREM sleep (in minutes) have beenobserved.1,10,19-20 Atypical antipsychotics such asolanzapine, risperidone and clozapine significantly increasetotal sleep time and stage 2 sleep. In addition, olanzapine andrisperidone increase slow-wave sleep.19 Typicalantipsychotics such as haloperidol, thiothixene and flupentixolsignificantly decrease stage 2 sleep and increase sleepefficiency.19

Alcoholism

Among the general population, alcohol is probably the mostcommonly used sleep-inducing substance.23 Acuteadministration of alcohol to normal volunteers before bedtimetends to curtail sleep latency, increase NREM sleep and decreaseREM sleep within the first hours after intake.23However, alcohol is quickly metabolized. Within four to fivehours after intake there is a decrease in concentration in theblood and the individual may present sleep interrupted by gastricirritation, headache, nightmares, tachycardia and profusesweating. There may also be REM sleep rebound.23

Alcoholic patients generally report insomnia, hypersomnia,disruption of circadian rhythms and parasomnias. Alcoholwithdrawal symptoms may be confused with those related to panicattacks, and the differential diagnosis must be carriedout.24

Alcohol increases the probability of snoring, respiratoryresistance and the occurrence of apneic episodes, even in theindividuals with no history of sleep apnea orsnoring.23

1) Polysomnographic findings

Polysomnographic findings include increased sleep latency anddecreased sleep efficiency, as well as a reduction in total sleeptime, slow-wave sleep and REM sleep.23 Alcoholinhibits REM sleep in a dose-dependent way, even in the presenceof physiological REM sleep debt, such as sleepdeprivation.25

Dementias

Dementias are not homogeneous regarding sleep. However, indementia with Lewy bodies and frontotemporal dementia there isalso a deficit in cholinergic transmission, with a consequentreduction in the percentage of REM sleep, similar to that seen inAlzheimer's disease.26 A peculiarity of dementia withLewy bodies is that it presents a higher frequency of REM sleepbehavior disorder. This occurs because, in this dementia, thereis an early onset of the loss of cholinergic neurons in themagnocellular part of the pontine reticular nucleus, damaging theexcitatory connection between this nucleus and the locuscoeruleus, which is responsible for the atony in REMsleep.26

In vascular dementia, sleep alterations are quiteheterogeneous, depending on the distribution of the cortical andsubcortical lesions, but there is an important reduction in thepercentage of slow-wave sleep.27 However, morein-depth studies of sleep in dementias other than Alzheimer's areneeded.

1. Alzheimer's disease

Alzheimer's disease is the most studied of all dementias. Manyof the sleep dysfunctions present in normal ageing also occur inthe patient with this disease, but with more intensity. In viewof this, there is a reduction in total sleep time and in sleepefficiency,28 as well as advanced sleep phase(trending toward early sleep onset and earlyawakening),29 lower amplitude of circadian cycles(such as hormonal secretion, activity andtemperature),30-31 reduction in slow-wave sleep(stages 3 and 4), reduction in REM sleep and increased stage 1sleep.28,32 In addition, patients with Alzheimer'spresent episodes of nighttime agitation, hypnagogichallucinations and aimless sleepwalking.33

Some of the dysfunctions present in Alzheimer's disease may beattributed to the growing disruption of circadian cycles,possibly accompanied by atrophy of the suprachiasmaticnucleus.34 This disruption increases in parallel withdisease severity.35 It has also been observed that thelack of a rhythmic pattern in the secretion of melatonin affectsthe sleep of these patients, and that the administration ofexogenous melatonin, or the stimulation of its production throughmorning phototherapy, help correct it partially.36 InAlzheimer's disease, dysfunctions that affect REM sleep areespecially important due to their physiopathology since one ofthe most affected structures at the onset of Alzheimer's isprecisely a cholinergic nucleus involved in cortical activityduring this stage, the basal nucleus of Meynert.37Therefore, it has been speculated that the relationship betweenREM sleep and Alzheimer's is functional since REM sleep isrelated to learning processes, severely impaired by thisdisease.37 In fact, when patients are given drugs thatenhance cholinergic conduction, there is an increase in thepercentage of REM sleep, as well as an improvement incognition.38

1) Polysomnographic findings

As previously discussed, polysomnographic findings include asignificant reduction in the percentage of REM sleep, lowerfrequency of rapid eye movements during REM sleep (decreased REMdensity) and decreased sleep efficiency due to the increase inthe number of awakenings after sleep onset.28 Adecrease in the basal rhythm has been observed in the spectralanalysis of electroencephalogram during REM sleep.39According to some authors, the decrease in the basal rhythm ofREM sleep in the spectral analysis is a sensitive marker fordifferentiating Alzheimer's disease from normalaging.40 The presence of diffuse delta and thetarhythms is also noticed, in both sleep and wake, with generalslowing on electroencephalogram in frontal and temporalabnormalities.28,38

In the elderly, depression can simulate Alzheimer's disease.However, in depression, the polysomnographic profile indicatescholinergic hyperactivity, with increase in percentage andreduction of latency of REM sleep.41

Sleep in children and adolescents and sleep dysfunctions in the most frequent psychiatric disorders

Sleep, seen in its various aspects, suffers modifications overthe individual's life and these are more significant in the firstyears of life. A baby, right after birth, sleeps approximately 16to 20 hours a day, whereas a two-year-old child sleepsapproximately 12 hours.42 In pre-adolescence, thewaking period is at a maximum, and the need for a daily nap isvery rare. The lack of daily sleepiness may disguise primarysleep dysfunctions such as sleep apnea and narcolepsy. Duringpuberty, there is an increase in daily sleepiness, as assessedthrough the multiple sleep latency test, possibly accompanied byan increased need for sleep. Whether there is alteration of thebiological (circadian) clock has been questioned, although someauthors suggest that there is a trend toward a delay in itsphase.43-46

The most frequent psychiatric disorders that may affect sleepin children and adolescents are depression, anxiety, andattention deficit hyperactivity disorder (ADHD). The anxietyprofiles present sleep complaints and polysomnographic findingssimilar to those of adults. However, the occurrence of multipleawakenings during the night is relevant, when the patient reportsa sensation of fear and imminent danger.47

1. Childhood depression

The symptoms of childhood depression are similar to thoseobserved in the adult population, although with somepeculiarities such as exaggerated fears and refusal to go toschool.48 It has been shown that, among childrenpresenting altered sleep patterns, 75% complain of insomnia, and25% report excessive sleepiness.45 Those with insomniamainly complain of difficulty in initiating sleep and have theimpression that their sleep is superficial and of poor quality,consequently experiencing difficulty in waking up early to go toschool, together with daytime tiredness.45

1) Polysomnographic findings

Findings have been inconsistent and hardly specific: inchildhood (Tanner stages 1 and 2), there is increased sleeplatency and decreased latency for the first episode of REM sleep.In adolescents (Tanner stages 3, 4 and 5), in addition to thesefindings, there is increased REM density.47

2. Attention deficit hyperactivity disorder

Children with ADHD complain of difficulty in waking up in themorning (perhaps due to sleeping too little), fragmented sleep,poor quality sleep and increased movement during sleep. It hasbeen observed that children with obstructive sleep apneasyndrome, with periodic limb movements or narcolepsy, presentmore ADHD-related symptoms.49

1) Polysomnographic findings

In ADHD, increased physical activity during sleep, increasedfrequency of periodic limb movements and reduction in REM sleephave been observed.49

The treatment of ADHD, combined with careful orientationregarding appropriate sleep rhythm, has proven effective.Patients, when untreated, can present increased daytimesleepiness (observed in the multiple sleep latency test).Nevertheless, re-assessment of the treatment with stimulants -better scheduling, reduction of total dosage, etc - when carriedout, propitiates better quality sleep and a consequentimprovement in daytime behavior.49

Final considerations

The sleep alterations most frequently observed in mostpsychiatric disorders refer to difficulty in initiating sleep(initial insomnia), difficulty in maintaining sleep (middleinsomnia), poor quality sleep and interrupted sleep. Terminalinsomnia or early awakening is more often related to depressiveprofiles.

In describing polysomnographic findings in psychiatricpatients, we principally observe significant reductions in sleepefficiency and total sleep time, which are consequences of thereduction of NREM sleep. In affective disorders, the percentageof REM sleep is increased. Reduction of REM sleep latency isprincipally described for depression but may occur in otherpathologies. Although no specific finding is pathognomonic,patterns of sleep dysfunction have been observed in certainpsychiatric disorders. Even though a specific psychiatricdiagnosis cannot be made based on polysomnographic data alone,sleep studies can help answer specific questions such as how todifferentiate depression from dementia in the elderly.

There may still be a strong correlation between psychiatricdisorders and primary sleep disorders. Therefore, patients withsleep apnea or narcolepsy seem to present high levels of anxiety,depression and alcoholism. More relevant still is the directrelation between poor sleep hygiene and various other psychiatricprofiles. This relationship must be taken into consideration bypsychiatrists in clinical practice since instructing patients insleep hygiene can reduce the amount of medication administered,improving symptomatology and patient quality of life.

References

1. Benca RM, Obermayer WH, Thisted RA, Gillin JC. Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry. 1992;49(6):651-68; discussion 669-70.       

2. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA. 1989;262(11):1479-84.       

3. American Sleep Disorders Association. The International classification of sleep disorders, revised: diagnostic and coding manual. Rochester: American Sleep Disorders Association; 1997.        [ Links ]

4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994.       

5. Uhde TW. Anxiety disorders. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 3rd ed. Philadelphia: WB Saunders; 2000. p. 1123-39.       Links ]

6. Guerra ABG, Calil HM. Depressão. In: Hetem LAB, Graeff FG, editores. Transtornos de ansiedade. São Paulo: Atheneu; 2004. p. 371-88.       

7. Riemann D, Voderholzer U. Primary insomnia: a risk factor to develop depression? J Affect Disord. 2003;76(1-3):255-9.      

8. Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002;6(2):97-111.      

9. Benca RM. Mood disorders. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 3rd ed. Philadelphia: WB Saunders; 2000. p. 1140-57.       

10. Wooten VD, Buysse DJ. Sleep in psychiatric disorders. In: Chokroverty S. Sleep disorders medicine: basic science, technical considerations and clinical aspects. 2nd ed. New York: Butterworth-Heinemann; 1999. p. 573-86.      

11. Gann H, van Calker D, Feige B, Cloot O, Bruck R, Berger M, et al. Polysomnographic comparison between patients with primary alcohol dependency during subacute withdrawal and patients with a major depression. Eur Arch Psychiatry Clin Neurosci. 2004;254(4):263-71.   

12. Kupfer DJ, Reynolds CF 3rd, Ulrich RF, Grochocinski VJ. Comparison of automated REM and slow-wave sleep analysis in young and middle-aged depressed subjects. Biol Psychiatry. 1986;21(2):189-200.       

13. Argyropoulos SV, Hicks JA, Nash JR, Bell CJ, Rich AS, Nutt DJ, et al. Correlation of subjective and objective sleep measurements at different stages of the treatment of depression. Psychiatry Res. 2003;120(2):179-90.       

14. Monti JM, Monti D. Sleep disturbance in generalized anxiety disorder and its treatment. Sleep Med Rev. 2000;4(3):263-76.     

15. Culpepper L. Generalized anxiety disorder in primary care: emerging issues in management and treatment. J Clin Psychiatry. 2002:63(Suppl 8):35-42.      

16. Sheikh JI, Woodward SH, Leskin GA. Sleep in post-traumatic stress disorder and panic: convergence and divergence. Depress Anxiety. 2003;18(4):187-97.      

17. O'Mahony JF, Ward BG. Differences between those who panic by day and those who also panic by night. J Behav Ther Exp Psychiatry. 2003;34(3-4):239-49.       

18. Brown TM, Uhde TW. Sleep panic attacks: a micro-movement analysis. Depress Anxiety. 2003;18(4):214-20.       

19. Monti JM, Monti D. Sleep in schizophrenia patients and the effects of antipsychotic drugs. Sleep Med Rev. 2004;8(2):133-48.     

20. Benson KL, Zarcone Jr VP. Schizophrenia. In: Kryger MH, Roth T, Dement WC. Principles and practice of sleep medicine. 3rd ed. Philadelphia: WB Saunders; 2000. p. 1159-67.       

21. Keshavan MS, Petteggrew JW, Reynolds CF 3rd, Panchalingam KS, Montrose D, Miewald J, et al. Biological correlates of slow wave sleep deficits in functional psychoses: 31P-magnetic resonance spectroscopy. Psychiatry Res. 1995;57(2):91-100.       

22. Dement WC. Dream recall and eye movements during sleep in schizophrenics and normals. J Nerv Ment Dis. 1955;122(3):263-9.      

23. Castaneda R, Sussman N, Levy R, O'Malley M, Westreich L. A review of the effects of moderate alcohol intake on psychiatric and sleep disorders. In: Galanter M, editor. Recent developments in alcoholism. New York: Plenum Press; 1998. v. 14, p. 197-226.     

24. Lotufo-Neto F, Gentil V. Alcoholism and phobic anxiety - a clinical demographic comparison. Addiction. 1994;89(4):447-53.       

25. Lobo LL, Tufik S. Effects of alcohol on sleep parameters of sleep-deprived healthy volunteers. Sleep. 1997;20(1):52-9.      

26. Ferman TJ, Boeve BF, Smith GE, Silber MH, Kokmen E, Petersen RC, et al. REM sleep behavior disorder and dementia: cognitive differences when compared with AD. Neurology. 1999;52(5):951-7.      

27. Autret A, Lucas B, Mondon K, Hommet C, Corcia P, Saudeau D, et al. Sleep and brain lesions: a critical review of the literature and additional new cases. Neurophysiol Clin. 2001;31(6):356-75.       

28. Montplaisir J, Petit D, Lorrain D, Gauthier S, Nielsen T. Sleep in Alzheimer's disease: further considerations on the role of brainstem and forebrain cholinergic populations in sleep-wake mechanisms. Sleep. 1995;18(3):145-8.      

29. Richardson GS, Carskadon MA, Orav EJ, Dement WC. Circadian variation of sleep tendency in elderly and young adult subjects. Sleep. 1982;5(Suppl 2):S82-94.      

30. Sakai K, El Mansari M, Lin JS, Zhang JG, Vanni-Mercier G. The posterior hypothalamus in the regulation of wakefulness and paradoxical sleep. In: Mancia M, Marini G, editors. The diencephalon and sleep. New York: Raven Press; 1990. p. 171-98       

31. Witting W, Kwa IH, Eikelenboom P, Mirmiran M, Swaab DF. Alterations in the circadian rest-activity rhythm in aging and Alzheimer's disease. Biol Psychiatry. 1990;27(6):563-72.      

32. Vitiello MV, Bliwise DL, Prinz PN. Sleep in Alzheimer's disease and the sundown syndrome. Neurology. 1992;42(7 suppl 6):83-93.     

33. Johnson J. Delirium in the elderly: incidence, diagnosis, management, and functional status in general medical patients [abstract]. Gerontologist. 1987;27:243A. [Presented in 40th annual scientific meeting of the Gerontological Society of America. November 18-November 22, 1987, Washington, DC].      

34. Swaab DF, Fliers E, Partiman TS. The suprachiasmatic nucleus of the human brain in relation to sex, age, and senile dementia. Brain Res. 1985;342(1):37-44.       

35. Aharon-Peretz J, Masiah A, Pillar T, Epstein R, Tzischinsky O, Lavie P. Sleep-wake cycles in multi-infarct dementia and dementia of the Alzheimer type. Neurology. 1991;41(10):1616-19.      

36. Jean-Louis G, Zizi F, von Gizycki H, Taub H. Effects of melatonin in two individuals with Alzheimer's disease. Percept Mot Skills. 1998;87(1):331-9.       

37. Christos GA. Is Alzheimer's disease related to a deficit or malfunction of rapid eye movement (REM) sleep? Med Hypotheses. 1993;41(5):435-9.       

38. Moraes WAS, Poyares DL, Ramos LR, Bertolucci PH, Tufik S. Anticholinesterase drug donepezil increases REM sleep duration in Alzheimer's disease patients: preliminary data [abstract]. Sleep. 2001;24:A369.         [ Links ] [Presented in Associated Professional Sleep Societies 15th Annual Meeting. June 5-10, 2001. Chicago, Illinois, USA].

39. Petit D, Montplaisir J, Lorrain D, Gauthier S. Spectral analysis of the rapid eye movement sleep electroencephalogram in right and left temporal regions: a biological marker of Alzheimer's disease. Ann Neurol. 1992;32(2):172-6.        [ Links ]

40. Hassainia F, Petit D, Nielsen T, Gauthier S, Montplaisir J. Quantitative EEG and statistical mapping of wakefulness and REM sleep in the evaluation of mild to moderate Alzheimer's disease. Eur Neurol. 1997;37(4):219-24.      

41. Bahro M, Riemann D, Stadtmüller G, Berger M, Gattaz WF. REM sleep parameters in the discrimination of probable Alzheimer's disease from old-age depression. Biol Psychiatry. 1993;34(7):482-6.      

42. Anders TF, Sadeh A, Appareddy V. Normal sleep in neonates and children. In: Ferber R, Kryger M, editors. Principles and practice of sleep medicine in the child. 3rd ed. Philadelphia: W B Saunders; 1995. p. 7-18.   

43. Carskadon MA, Keenan S, Dement WC. Night time sleep and daytime sleep tendency in preadolescents. In: Guilleminault C, editor. Sleep and its disorders in children. New York: Raven Press; 1987. p. 43-52.       

44. Carskadon MA, Dement WC. Sleepiness in the normal adolescents. In: Guilleminault C, editor. Sleep and its disorders in children. New York: Raven Press; 1987. p. 53-66.       

45. Dahl RE, Carskadon MA. Sleep and its disorders in adolescence. In: Ferber R, Kryger M, editors. Principles and practice of sleep medicine in the child. Philadelphia: W B Saunders; 1995. p. 19-27.    

46. Willians RL, Karacan I, Hursch CJ. The normal sleep in early adulthood. In: Williams RL. Electroencephalography of human sleep: clinical applications (A Wiley biomedical-health publication). New York: John Wiley & Sons; 1974. p. 26-68.      

47. Wolfson AR, Trentacoste SV, Dahl RE. Sleep in children with behavioral and psychiatric disorders. In: Loughlin GM, Carrol JL, Marcus CL, editors. Sleep and breathing in children: a developmental approach. New York: Marcel Dekker; 2000. p. 385-95.      

48. Institute of Medicine Report of Research on Child and Adolescents with mental, behavioral and developmental disorders. Bethesda: National Institute of Mental Health, U.S. Department of Health and Human Services; 1990.      

49. Cohen-Zion M, Ancoli-Israel S. Sleep in children with Attention-Deficit Hyperactivity Disorder (ADHD): a review of naturalistic and stimulant intervention studies. Sleep Med Rev. 2004;8(5):379-402.