Sleep Deprivation in Depressed Adolescents and Psychiatric Controls

Sleep Deprivation in Depressed Adolescents and Psychiatric Controls

Sleep Deprivation in Depressed Adolescents and Psychiatric Controls MICHAEL W. NAYLOR, M.D., CHERYL A. KING, PH.D., KATHLEEN A. LINDSAY, B.A., TAMLYNN...

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Sleep Deprivation in Depressed Adolescents and Psychiatric Controls MICHAEL W. NAYLOR, M.D., CHERYL A. KING, PH.D., KATHLEEN A. LINDSAY, B.A., TAMLYNN EVANS, M.S., R.N., JOHN ARMELAGOS, R.N.C., BENJAMIN N. SHAIN, M.D., PH.D., AND JOHN F. GREDEN, M.D.

Abstract. Up to 70% of depressed adults have an antidepressant response to sleep deprivation. To study the effects of sleep deprivation on depression severity and level of arousal in psychiatrically disturbed adolescents, we deprived 17 patients of sleep for 36 hours. Severity of depression and subjective arousal were assessed at baseline, during sleep deprivation, and after 1 night's recovery sleep. We found that severely depressed adolescents showed a significant decrease in depression severity, whereas depressed patients in remission and psychiatric controls worsened after sleep deprivation. Patients with depression in remission showed a significant decrease in subjective arousal after sleep deprivation. In contrast to findings in depressed adults, the effects of sleep deprivation persisted after 1 night of recovery sleep, and diurnal variation of mood did not predict response to sleep deprivation. These findings are consistent with those reported in the adult literature, and suggest a common psychophysiology between adult and adolescent depression. J. Am. Acad. Child Adolesc. Psychiatry, 1993,32,4:753-759. Key Words: sleep deprivation, adolescence, depression, mood, arousal. , Sleep deprivation has been reported to result in a transient improvement of mood in 30% to 70% of depressed adults (Gillin et al., 1984). Clinical improvement, often dramatic, is usually short-lived, generally lasting only until recovery sleep (Roy-Byrne et aI., 1984). Nevertheless, sustained responses have been reported, and the effects can be so profound as to switch depressed bipolar patients into mania (Cole and Mueller, 1976). Sleep deprivation is most likely to have an antidepressant effect in patients with the endogenous subtype of depression (Larsen etaI., 1976) and those with diurnal variation of mood (Reinink et ai., 1990). In c~mtrast, normal controls and nondepressed psychiatric patients typically either experience no change or become dysphoric and irritable after sleep deprivation (Gerner et ai., 1979; Pflug, 1976). : Virtually all sleep deprivation research has been done with depressed adults, and the literature in this age range is extensive. In contrast, only two groups have studied the effects of sleep deprivation on mood in depressed children

,Accepted August 18, 1992. Drs. Naylor and King, and Mr. Armelagos are with the University of Michigan Adolescent Psychiatry Inpatient Program; Ms. Lindsay is: with the University of Kentucky Department of Psychology; Ms. Evans is with Munson Hospital (Traverse City, MI); Dr. Shain is with St. Charles Hospital (Toledo, OH); and Dr. Greden is with the University of Michigan Department of Psychiatry. Dr. Naylor is also with the University of Michigan Sleep Diagnostic and Research Unit in Psychiatry. Presented in part at the 37th Annual Meeting of the American Academy ofChild and Adolescent Psychiatry; Chicago, lIIinois; October 1990. iSupported in part by a Young Investigator's Award (MWN) sponsored by the National Alliance for Research in Schizophrenia and Depression (NARSAD) and by a Departmental Grantfrom the University of Michigan Department of Psychiatry. The authors thank the staff of the Adolescent Psychiatry Inpatient Unit, without whom this study would not have been possible. .Reprint requests to Dr. Naylor, Department of Psychiatry, Box 0290, 200 East Hospital Drive, Ann Arbor, MI48109-0290 0890-8567/93/3204-0753$03.00/0© 1993 by the American Academy of Child and Adolescent Psychiatry. J. Am. Acad. Child Adolesc. Psychiatry, 32:4, July 1993

or adolescents. King et ai. (1987) studied the effects of combined partial sleep deprivation and medication on mood in a 12-year-old child. The patient experienced mild beneficial effects; however, because of confounding variables such as antidepressant medications and inconsistent ratings, the results cannot be easily generalized. Detrinis et ai. (1990) investigated the effects of sleep deprivation in adolescents. Their four depressed subjects (ages unspecified) experienced improved mood and psychomotor activity similar to that reported in adults. In contrast to the findings in adults, however, the beneficial effects lasted for as long as 3 days after sleep deprivation. Three types of sleep deprivation have been studied. In total sleep deprivation, subjects remain awake from early one morning until late the next evening, thus losing one complete night's sleep. In partial sleep deprivation, subjects are limited to half their normal night's sleep either during the first half or the last half of the night (Schilgen and Tolle, 1980). Depriving patients of sleep during the last half of the night is more effective in eliciting an antidepressant response in depressed patients than sleep deprivation during the first half (Sack et ai., 1988). Partial sleep deprivation and total sleep deprivation are equally effective in terms of the frequency and magnitude of the antidepressant effect of sleep deprivation (Schilgen et ai., 1976). In rapid eye movement (REM) sleep deprivation, subjects are awakened at the onset of electroencephalographically determined REM sleep, then permitted to return to sleep. REM sleep deprivation is usually administered nightly during a period of several weeks. The antidepressant effects of REM sleep deprivation may take longer to appear, but they typically last much longer than total or partial sleep deprivation effects (Vogel et ai., 1975, 1980). The psychophysiology of the antidepressant effect of sleep deprivation is unknown. Three mechanisms have been proposed to explain the effect of sleep deprivation in depressed patients: (1) deficiency of a sleep-inducing neurochemical, (2) circadian rhythm disturbance (phase advance or amplitude reduction), and (3) the depressogenic effect of

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sleep. Borbely and Wirz-Justice (1982) proposed a mathematical two-process model of sleep regulation, the Process S deficiency model, which attempts to explain both the abnormal sleep pattern observed in depression and the antidepressant effect of sleep deprivation in major depression. According to this model, a sleep dependent factor and a sleep independent factor (Process S and Process C, respectively) interact to determine onset and duration of sleep. Process C refers to the diurnal variation of sleep propensity. Process S (purported to be a sleep-inducing neurochemical) accumulates during wakefulness and dissipates during sleep. The "intensity" of sleep as measured by the EEG slow wave sleep power density reflects the activity of Process S. According to Borbely's hypothesis, depression results from deficient Process S. Sleep deprivation is assumed to result in the build-up of Process S with a resultant improvement in mood and sleep abnormalities found in depression. Several lines of evidence offer support for the Process S deficiency model. Polysomnographic studies have shown that depressed adults have longer sleep latency, less efficient sleep, less slow wave sleep, and shorter REM sleep latency than do age-matched normal controls (Kupfer et aI., 1978). The prolonged sleep onset, impaired sleep maintenance, and reduction of slow wave sleep in depression are attributed to the deficiency of Process S-mediated sleep induction and maintenance. Process S also is presumed to inhibit REM sleep; thus, REM sleep is "disinhibited" and appears earlier in the night. Reynolds et ai. (1987) tested the Process S deficiency model by depriving elderly depressed patients of one night's sleep and comparing baseline EEG sleep with recovery EEG sleep. Patients whose mood improved with sleep deprivation (responders) demonstrated electrophysiological evidence of improved sleep from baseline to recovery sleep, including a significant decrease in sleep latency, increase in sleep efficiency, and elevated slow wave sleep. The sleep of nonresponders, in contrast, remained significantly impaired. The authors concluded that the data showed an interaction between sleep regulation and depression as predicted by Borbely's model. In another study designed to test Borbely's theory, Campbell and Gillin (1987) confined normal volunteers to bed for 60 consecutive hours and allowed them to sleep ad libitum to prevent the build-up of Process S. They found that their subjects developed sleep abnormalities reminiscent of those seen in major depression including reductions in slow wave sleep, decreased sleep efficiency, and shorter REM latency compared with baseline. A second theory suggests that depression is caused by the disruption of circadian rhythms that regulate the sleep-wake, neuroendocrine, and body temperature cycles. Functions such as the propensity for REM sleep, body temperature regulation, and cortisol secretion are controlled by a "strong" central pacemaker, whereas growth hormone release and slow wave sleep. These pacemakers are located in the suprachiasmatic nuclei of the hypothalamus. Circadian rhythms typically exhibit a "day length" in excess of 24hours when free running; however, individual rhythms are entrained (or synchronized) into 24-hour periods by environmental time cues. Several time cues, or zeitgebers, have

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been identified including social interactions, periodic availability of food, and arousal state; however, the most powerful zeitgeber is the light-dark cycle. In healthy subjects, circadian rhythms tend to remain synchronized in relation to one another. (For a review of the anatomy, physiology, and function of the circadian timing system and its proposed involvement in the pathophysiology of affective disorders, see Hallonquist et aI., 1986; Moore-Ede et aI., 1983a, 1983b.) Several investigators propose that a pervasive characteristic of affective illness involves a desynchronization of these internal rhythms (e.g., Pflug and Tolle, 1971; Wehr and Wirz-Justice, 1982). Proposed abnormalities include a phase advance of circadian rhythms (occurring earlier than normal relative to the clock) or decreased amplitude of various biological rhythms. Wehr and Wirz-Justice (1981) hypothesize that the strong oscillator responsible for body temperature rhythm, cortisol secretion, and REM sleep is advanced relative to the weak oscillator that governs the sleep/wake cycle in depressed patients. Depressed patients "sleep too late" in relationship to the strong oscillator, thereby sleeping through a "critical period" characterized by the ascension of body temperature, cortisol secretion, and REM sleep propensity. It has been hypothesized that total sleep deprivation and partial sleep deprivation are effective because the patient remains awake through the critical period and the normal phase relationship between the oscillators is reestablished. Wehr et al. (1979) tested the phase advance hypothesis by acutely advancing the sleep of four depressed bipolar patients by 6 hours. Two patients showed a complete remission for 2 weeks and two partially remitted, offering tentative support for the phase advance theory. Data supporting normalization of phase advanced circadian rhythms after sleep deprivation in depressed patients are scant. Sleep deprivation is reported to prolong REM latency in total sleep deprivation responders (Duncan et aI., 1980), which is taken as evidence that the strong oscillator governing the propensity to enter REM sleep is delayed by sleep deprivation (Joffe and Brown, 1984). This observation is also consistent with the Process S deficiency theory, however. Process S activity, accentuated by sleep deprivation, enhances deep sleep at the expense of REM sleep, thereby prolonging REM latency. Supportive of the theory that the psychophysiological findings in depression are due to a weakening of circadian rhythmicity, Souetre et al. (1989) found decreased amplitudes of circadian cortisol, temperature, thyroid-stimulating hormone, norepinephrine, and melatonin rhythms in depressed adults. After recovery, the amplitudes returned to normal. Available data suggest that sleep deprivation can accentuate the amplitude of disturbed circadian rhythms in depressed patients (for a review see Joffe and Brown, 1984). For example, several investigators have found that depressed patients whose mood improved with sleep deprivation demonstrated an increased amplitude of the circadian cortisol rhythm after total sleep deprivation (Baumgartner et aI., 1990; Gerner et aI., 1979; Yamaguchi et aI., 1978). A third mechanism was proposed by Wu and Bunney (1990) who hypothesized that sleep may be depressogenic. J. Am. Acad. Child Adolesc. Psychiatry, 32:4,July 1993

SLEEP DEPRIVATION IN DEPRESSED ADOLESCENTS

Based on the finding that recovery sleep leads to a complete relapse in 83% of patients who had an antidepressant response to sleep deprivation, the authors suggested that wakefulness inhibited a sleep-related depressongenic process. They hypothesized that the process is mediated by a neurochemical that is metabolized or sequestered during wakefulness and released during sleep. As yet, no studies have been done to test this hypothesis (Wu and Bunney, 1990). It is surprising that sleep deprivation in depressed adolescents has received so little research attention. Effective pharmacological interventions have yet to be identified in appropriately controlled clinical research protocols. In addition, the sleep deprivation procedure is safe and relatively noninvasive. What research has been conducted in nondepressed patients shows that younger adult patients are more sensitive than older patients to the antidepressant effects of sleep deprivation (Pflug, 1976). This possibly is related to the fact that young adults have more efficient recovery sleep after sleep deprivation than do older adults (Webb, 1981). By extension, one could expect that sleep deprivation in depressed adolescents may be even more effective than it is in adults. , The general objective of this study is to conduct the first standardized assessment of the effects oftotal sleep deprivation on clinical and psychophysiological parameters in depressed adolescents. Specifically, these hypotheses are tested: (1) sleep deprivation has an antidepressant effect in severely depressed adolescents, and (2) psychiatric controls and depressed adolescents in partial remission show no benefit or a worsening of symptoms of depression after sleep deprivation.

Method Twenty-one adolescents hospitalized on the Adolescent Psychiatry Inpatient Unit at the University of Michigan Medical Center were recruited for the study. Four subjects, all boys, were excluded from the study; three failed to complete the protocol, and one presented unreliable data. The ~ubjects included four boys (ages 12.9 to 17.3 years, X ± SD = 15.8 ± 1.9) and 13 girls (ages 12.5 to 16.7 years, X ± SD = 14.9 ± 1.3 years). All were pubertal (Tanner stage 3 or later). Exclusion criteria were a sleep disorder, a medical or neurological condition that could affect mood or sleep, or the use of psychoactive medications or drugs within 2 y.reeks before the study. Inclusion criteria included a fullscale IQ :2: 80 and a reading level :2: grade 5. All were c;:affeine-free for the duration of the study. Written informed consent was obtained from the subject and his or her parents before inclusion in the study. Subjects and their parents were blind to the hypotheses of the study. Participants were paid (or their participation in the study. . Subjects were diagnosed according to DSM-III-R criteria (American Psychiatric Association, 1987) using information from a semistructured interview, the Schedule for Affective I?isorders and Schizophrenia for School-Aged ChildrenPresent Episode (K-SADS-P Puig-Antich et aI., 1986) with K = 0.83 for affective disorders, clinical interviews of the patients and their parents, psychological testing, and milieu observations. Diagnoses were made by consensus of the J.Am. Acad. Child Adolesc. Psychiatry, 32:4, July 1993

attending child psychiatrist and the primary clinician using all available diagnostic information. Primary diagnoses were defined as those whose symptoms necessitated hospitalization. Depression severity was measured using the Hamilton Rating Scale for Depression (HRSD) (Hamilton, 1960), which was administered at the time of the K-SADS-P inter~ view. The interrater reliability for the HRSD was r = 0.91 (intraclass correlation coefficient). Patients were divided into four study groups; the severely depressed group (SDG, currently depressed, HRSD > IS, n = 4), the mildly depressed group (MD, currently depressed, HRSD::; 15, n = 4), the depressed in partial remission group (DIR, previously met criteria for major depressive episode, currently euthymic, HRSD < 10, n = 6), and psychiatric controls (PC, nondepressed, HRSD < 10, n = 3). The HRSD cutoff of 15 to determine group assignment was decided a priori. Primary diagnoses for the SDG patients were major depressive episode (MDE, n = 3, one with psychotic features) and bipolar disorder not otherwise specified (NOS), depressed (type II, n = 1). Primary diagnoses for the mildly depressed group were MDE (n = 2) and dysthymia (n = 2). All six subjects in the DIR group had MDE in partial remission. Diagnoses for the psychiatric control group included separation anxiety disorder (n = 1), bulimia nervosa (n = 1), and anorexia nervosa (n = 1). Concurrent diagnoses included disruptive behavior disorder (n = 5), eating disorder (n = 6), anxiety disorder (n = 6), personality disorder (n = 3), developmental reading disability (n = 2), alcohol dependence (n = 1), dysthymia (n = 1), brief reactive psychosis (n = I), and identity disturbance (n = I). Severity of the patients' depression was assessed at time points 0800 and 2000 hours on day I (baseline day, BL) using a modified 12-item HDRS (mHRSD). The mHRSD is based on the standard 17-item HRSD with the insight, sleep, and weight items omitted. The mHRSD interviews were conducted by three of the authors (M.W.N., T.E., and I.A.). The interrater reliability was 0.96 (intraclass correlation coefficient). Patients were kept awake from time 0800 on day 1 until time 2000 on day 2 (sleep deprivation day, SDD) of the study (36 hours of total sleep deprivation). Subjects generally were sleep deprived in pairs so they could help keep each other awake. Staff observed the subjects closely, always keeping them within eyesight. The adolescents were allowed to play games such as ping-pong, talk quietly, and watch movies to maintain wakefulness. The mHRSD was repeated at times 0800 and 2000 on both days 2 and 3 (postrecovery sleep day, PRS). Subjective arousal was measured concurrently with mood using the Al (energetic arousal) subscale of Thayer's ActivationlDeactivation Adjective Checklist-Short Form (ADACL; Thayer, 1967). The ADACL is a self-administered four-point rating scale that measures energetic and tense arousal. Subjects are presented with an adjective describing various states of arousal and asked to rate whether they definitely feel that way or definitely do not. Adjectives describing energetic arousal include "active," "energetic," "vigorous," "lively," and "full of pep." The psychometric properties of the ADACL are well established (Thayer, 1967). For a summary of the research design, see Table 1. 755

NAYLOR ET AL. TABLE

0200 Day 1 (baseline day) mHRSD ADACL Day 2 (sleep deprivation day) mHRSD ADACL Day 3 (postrecovery sleep day) mHRSD ADACL

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Note: mHRSD-modified Hamilton Rating Scale for Depression; ADACL = ActivationlDeactivation Adjective Checklist.

Data were analyzed using a one-factor repeated measures analysis of variance ANOVA comparing OSOO and 2000 hours ADACL-Al and mHRSD values for each experimental group. Planned post hoc comparisons of BL values of depression and arousal with SOD and PRS values were made using Fisher's Protected Least Significant Difference (PLSD). Group (mildly versus severely depressed adolescents) X treatment (sleep deprivation condition) interactions on depression and arousal were analyzed using a two-factor repeated measures ANOVA. The association between severity of depression and level of arousal was assessed using Spearman's correlation coefficient. A p value < 0.05 was considered significant.

decrease in depression severity from BL to SOD and BL to PRS at both OSOO and 2000 hours (Table 2, Fig. 1). Patients with mild depression showed no significant change in depression after sleep deprivation (Table 2, Fig. 2). There was a treatment effect at time OSOO for sleep

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The findings offer support for our hypothesis that sleep deprivation leads to decreased severity of depression in severely depressed adolescents. Severely depressed adolescents showed a significant treatment effect at the OSOO, F(3,S) = S.9, p < 0.02 and the 2000, F(3,S) = 20.S, P < 0.002 time points. Post hoc analyses showed a significant

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FIG. 1. The effect of sleep deprivation on measures or'depression and arousal in severely depressed adolescents (N = 4).

2. The Effect of Sleep Deprivation on Measures of Depression and Subjective Arousal in Depressed and Psychiatric Comparison Adolescents

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Note: mHRSD = modified Hamilton Rating Scale for Depression; ADACL = ActivationlDeactivation Checklist; BL = baseline day; SDD = sleep deprivation day; PRS = pOStrecovery sleep day. F(3,8) = 8.9, p ::; 0.016; BL vs. SDD and BL vs. PRS significant at the 95% confidence level, Fisher's PLSD. F(3,8) = 20.8, p ::; 0.002; BL vs. SDD and BL vs. PRS significant at the 95% confidence level, Fisher's PLSD. < F(5,12) = 3.4, p ::; 0.08; BL vs. PRS significant at the 95% confidence level, Fisher's PLSD.

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F(4,1O) = 5.8, p ::; 0.03; BL vs. SDD and BL vs. PRS significant at the 95% confidence level, Fisher's PLSD. F(2,6) = 7.7, P ::; 0.05; BL vs. SDD significant at the 95% confidence level, Fisher's PLSD.

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J. Am. Acad. Child Adolesc. Psychiatry, 32:4, July 1993

SLEEP DEPRIVAnON IN DEPRESSED ADOLESCENTS

deprivation in adolescents with remitted depression that approached significance, F(5,12) = 3.4, p < 0.08. Post hoc analysis revealed that depression severity in the DIR group increased significantly from BL to PRS (Table 2, Fig. 3). Psychiatric controls also worsened with sleep deprivation, F(2,6) = 7.7, p ::; 0.05, at time 2000, with significant worsen~ng of depression from BL to SDD (Table 2, Fig. 4). . Consistent with the different patterns of response for each group, we found a significant group X treatment interaction for depression severity between severely depressed adoles¢ents at both the 0800, F(2,12) = 9.4, P ::; 0.004, and the 2000, F(2,12) = 6.9, p ::; 0.01, times. Severely depressed adolescents showed a decrease in severity of depression after sleep deprivation, whereas mildly depressed patients worsened. i Subjective level of arousal (ADACL-Al) and severity of qepression (mHRSD) were negatively correlated. Higher ratings of depression severity were mildly correlated with l~wer levels of arousal at time 0800 (p = -0.58; z = -2.3, p::; 0.03) and strongly associated with lower levels of arousal at time 2000 p (= -0.76; z = -2.0, P ::; 0.004). Severely depressed, mildly depressed, and psychiatric control patients showed no significant change in level of ~ubjective arousal after sleep deprivation (Figs. 1, 2, and 4). There was a significant treatment effect for arousal in patients with remitted depression at time 0800, F(2,6) = 5.8,

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In this study, we found that (1) severely depressed adolescents demonstrated an antidepressant response to sleep deprivation, (2) the antidepressant response to sleep deprivation persisted for at least 1 day after recovery sleep, and (3) the presence of diurnal variation did not differentiate responders and nonresponders. Our finding that more severely depressed patients had an antidepressant response to sleep deprivation is in agreement with findings from the adult literature that reports a positive correlation between subjects' antidepressant response to sleep deprivation and severity of depression (Joffe and Brown, 1984; Post et aI., 1976; Rudolf and Tolle, 1978). In contrast with the adult literature, however, diurnal variation of mood did not predict response to total sleep deprivation in our population. Although both severely and mildly depressed adolescents demonstrated a diurnal variation in mood, only severely depressed subjects responded to total sleep deprivation. This suggests that severity of depression 10

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p:S; 0.03. Post hoc analysis revealed a significant decrease in energetic arousal between BL and SDD and BL and PRS (Fig. 3). There was no significant group X treatment interaction for measures of subjective arousal at either 0800 hours, F(2,12) = 2.7, NS, or 2000 hours F(2,12) = 2.2, NS. Diurnal variation of mood as determined by BL mHRSD scores did not predict an antidepressant response to sleep deprivation. All four of the severely depressed adolescents had an antidepressant response to sleep deprivation, whereas . none of the mildly depressed patients improved. In each group, three adolescents had a notable diurnal variation of mood (worse in the morning) and one had no diurnal variation. None had a reverse diurnal variation. In general, the sleep deprivation procedure was well tolerated. Fatigue was the most common complaint, and accounted for two of the three dropouts. Gastrointestinal upset accounted for one dropout. One patient in the severely depressed group (diagnosed with bipolar disorder NOS) became hypomanic after sleep deprivation with mild euphoria, decreased need for sleep, increased energy, intiusiveness, rapid speech, and hyperactivity. The hypomania lasted for 5 days after sleep deprivation; however, subsequently the patient returned to her baseline state of depression.

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FIG. 3. The effect of sleep deprivation on measures of depression and arousal in depressed adolescents in remission (N = 6). J:Am.Acad. Child Adolesc. Psychiatry, 32:4, July 1993

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NAYLOR ET AL.

is a better predictor of an antidepressant response to total sleep deprivation in depressed adolescents than is diurnal variation of mood. Our findings also differ from those reported in the adult literature in that the antidepressant response in responders persisted for at least 1 day following recovery sleep. The vast majority of reports in the adult literature indicate a relapse following recovery sleep, regardless how brief the sleep. Several investigators have reported that adult patients who have had an antidepressant response to sleep deprivation have a complete relapse after naps as brief as 10 minutes (Knowles et aI., 1979; Kraft et aI., 1984; Roy-Byrne et aI., 1984; Wiegand et aI., 1987). Wu and Bunney (1990) estimate that 83% of unmedicated patients who had an antidepressant response to sleep deprivation relapse after 1 night of recovery sleep. Southmayd et ai. (1990) measured mood every 2 hours during recovery sleep in nine patients who responded to total sleep deprivation. They found that all subjects showed a precipitous decline in mood during recovery sleep commencing approximately 4 hours after onset of recovery sleep. Relapse was unrelated to the amount of preceding slow wave sleep or the presence or absence of REM sleep. No critical period, during which time the detrimental effect of recovery sleep is confined, was documented. Our findings are in agreement with those reported by Detrinis et ai. (1990), however, who found that depressed adolescents classified as responders continued to show beneficial effects of sleep deprivation after 3 to 5 days of recovery sleep. Given the small number of subjects in each cell, it is not possible to comment definitively on the roles of maturation and age in determining response to sleep deprivation. Although the literature supports the contention that younger depressed adults have a more dramatic antidepressant response to sleep deprivation than do older patients (Pflug, 1976), it does not necessarily follow that the same holds for adolescents. The age range in adolescents is considerably smaller than in adults, making it less likely to see an age effect. Adolescence is a time of rapid growth and sexual maturation, and it is possible that degree of sexual maturation plays a larger role in determining response to sleep deprivation than age in depressed adolescents. The contributions of age and sexual maturation clearly deserve more research. One must be cautious in trying to make generalizations based on these data. First, the sample size is quite small. Second, the sample is largely female; a reflection of the higher incidence of depression in adolescent females, a higher dropout rate for males in this study, and the greater incidence of substance abuse among the males in our population. Third, neither the patients nor the raters were blind to the experimental conditions, and raters were not blind to the hypotheses of the study. Though this could conceivably introduce bias into the protocol, several precautions were taken to eliminate these threats. Patients were kept blind to the hypotheses of the study. In addition, multiple interviewers were used to lessen the likelihood of rater bias. Frequent 758

interrater reliability sessions were held to protect the integrity of the mHRSD data. Raters were randomly distributed across the various time points and experimental conditions. This is the preliminary report of an ongoing research project looking at the effects of sleep deprivation on severity of depression, mood, arousal, hedonic capacity, and EEG sleep in depressed adolescents. Future goals of the project are to determine whether changes in polysomnographic sleep variables between baseline and recovery nights predict response to total sleep deprivation, to determine whether specific symptoms respond preferentially to sleep deprivation, and to study circadian variations in mood, arousal, and hedonic capacity. Future plans are to videotape the mHRSD interviews and use raters who are blind to the sleep deprivation status of the patient. It will be impossible, given the design of the protocol, to keep the patient blind to the experimental condition, although future investigators may consider comparing total sleep deprivation with sham partial sleep deprivation in which the partial sleep deprivation is completed the first half of the night rather the second. The findings of this preliminary study are consistent with those reported in the adult literature and suggest a common psychophysiology between adult and adolescent depression. By itself, sleep deprivation is too short-lived to be an effective treatment for depression in adolescents. However, recent findings in adults suggest that antidepressants or lithium carbonate may prolong the effects of sleep deprivation, thereby leading to more rapid resolution of symptoms (Baxter et aI., 1986; Elsenga and van den Hoofdakker, 1990; Grube and Hartwich, 1990; Loosen et aI., 1970). Additionally, periodic sleep deprivation may be an effective prophylactic treatment in recurrent depressions (Christodoulou et aI., 1978) and an effective alternative therapy for treatmentresistant depression (Dessaur et aI., 1985). One intriguing possibility warranting future research is that sleep deprivation, either alone or in combination with adjunctive pharmacological agents, may be an effective intervention for suicidal adolescents in whom a brisk antidepressant response is crucial to minimizing suicidal risk during treatment. References American Psychiatric Association (1987), Diagnostic and Statistical Manual of Mental Disorders, 3rd edition-revised (DSM-III-R). Washington, DC: American Psychiatric Association. Baumgartner, A., Riemann, D. & Berger, M. (1990), Neuroendocrinological investigations during sleep deprivation in depression II. Longitudinal measurements of thyrotropin, TH, cortisol, prolactin, GH, and LH during sleep and sleep deprivation. BioI. Psychiatry, 28:569-587. Baxter, L. R., Liston, E. H., Schwartz, J. M. et al. (1986), Prolongation of the antidepressant response to partial sleep deprivation by lithium. Psychiatric Res., 19: 17-23. Borbely, A. A. & Wirz-Justice, A. (1982), Sleep, sleep deprivation, and depression: a hypothesis derived from a model of sleep regulation. Human Neurobiol., 1:205-210. Campbell, S. S. & Gillin, J. C. (1987), Depressing normal sleep: two tests of the process S deficiency hypothesis. Neuropsychobiology, 18:169-174. Christodoulou, G. N., Malliaras, D. E., Lykouras, E. P., Papadimitriou, G. N. & Stefanis, C. N. (1978), Possible prophylactic effect of sleep deprivation. Am. J. Psychiatry, 135:375-376. Cole, M. G. & Mueller, H. F. (1976), Sleep deprivation in the sleep of elderly depressed patients. J. Am. Geriatr. Soc., 24:308-313.

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