Effect of morning and afternoon naps on mood after total sleep deprivation in patients with major depression

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Effect of Morning and Afternoon Naps on Mood After Total Sleep Deprivation in Patients with Major Depression Michael Wiegand,* Dieter Riemann, Wolfgang Schreiber, Christoph J. Lauer, and Mathias Berger"

In 30 depressed patients who had responded to total sleep deprivation therapy, morning naps led more frequently to relapses into depression than did afternoon naps. Longer naps were less detrimental than shorter ones, and there was no significant relationship between the effect of a nap on mood and its content of slow-wave-sleep. The amount of the rapid eye-movement sleep, too, was unrelated to clinical nap effects. Thus, some of the current theories on the re!ati~nsh;.p between sleep and depressive symptomatology are not supported by the data. Our results demonstrate the importance of nap timing, suggesting a circadian variation of propensiC¢ to relapae into depression.

Key Words: depression, total sleep deprivation, naps

Introduction Total sleep deprivation (TSD) is an effective treatment for major depression (for review, see Gerner et al 1979; Gillin 1983; Wu and Bunney 1990). According to Wu and Bunney, who reviewed 61 articles on the topic, including over 1700 individual patients, the overall response rate reported in the literature is 59%. In contrast to other antidepressant treatments, the therapeutic effect develops rapidly, but a relapse into depression usually occurs after the following nocturnal sleep; 83% of patients not receiving medication and 59% of patients receiving medication are reported to relapse after the first night of sleep (Wu and Bunney 1990). From the Max Planck Institute of Psychiatry, (MW, WS, CJL) Munich, and Central Institute of Mental Health (DR, MB), Mannheim, Germany. Address reprint requests to M. Wicgand, M.D., Psychia_nicClinic of the Technical University of Munich, Ismaninger Strasse 22, W-8000 Miinchen 80, Germany. *Current address: Psychiatric Clinic, Technical University of Munich, Germany. tCurrent address: Psychiatric Clinic, University of Freiburg, Germany. Received March ! 1, 1992; December 4, 1992. © 1993 Society of Biological Psychiatry

Although limited in its clinical usefulness, TSD has become an important paradigm in research on affective disorders. To elucidate its mechanism of action, previous sPddies have tamed to identify predictors of response to TSD (Gillin 1983; Roy-Byrne et al 1984). Accordiag to Duncan et al (1980), response to TSD is predicted by a baseline sleep electroencephalographic (EEG) pattern with features typical for depression [increased intermittent and early morning awakening, reduced rapid eye-movement (REM) latency, reduced sleep efficiency]. In a study with a larger sample, Riemann et al (1991) confirmed the predictive value of a shortened REM latency for response to TSD. Other reliable neurobiological predictors, especially neurochemical ones, have not yet been identified. Among clinical va_dables, diurnal variation in mood is clearly related to response to sleep deprivation (Reinink et al 1990; Riemann et al 1991). In the present study, an alternative experimental approach to investigate the antidepressant properties of sleep 0006-3223/93/$06.00

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deprivation is presented. It is based on clinical observations that point to the reversibility of a favorable sleep deprivation effect by a short daytime nap. In an early report by Pflug and T611e (1971), it was mentioned for the first time that in some responders to TSD, a daytime nap after successful sleep deprivation provoked a worsening of mood. In a single case study, Knowles et al ~¢I OTO~,,.,described_ a relapse into depression caused by a short nap (15 min of non-REM sleep) in the early morning (5:00 AM), and RoyByrne et al (1984) observed a severe mood worsening subsequent to as little as 90 sec of polysomnographically recorded sleep at 3:30 PM. In a single case study of 48-hr sleep deprivation, Southmayd et al (1987) observed a relapse in a TSD responder after several very short episodes of sleep during the second deprivation night, with a cumulated total of 11.1 min of stage 2 sleep, revealed by continuous EEG monitoring. The observations from these anecdotal re~ tn~ts and case studies could be confirmed by some systematic investigations. In the first study on this topic (Wiegand et al 1987b), we observed effects ranging from improvement to dramatic worsening in drug-free depressed patients who, after TSD, took a nap at 1:00 PM. In 6 of 12 responders to TSD, the nap led to a clear relapse into depression. The results of this pilot study did not allow definite conclusions as to the respective determinants of relapse but pointed to the role of longer nap sleep duration and the occurrence of REM sleep as crucial factors. In a separate analysis of hourly mood r,:tings before and after the naps, we found a delayed mooa setback in those TSD responders who had not worsened immediately after the nap (Wiegand et al 1987a). Other systematic studies yielded inconsistent results. Kraft et al (1984) described a relapse in one of seven depressed patients after a 10-min afternoon nap following response to sleep deprivation. Gillin et al (1989), however, did not observe such relapses following 10-min naps at 8:30 A M or 3:00 r,M In a ~ h l d v i n n a t i ~ n t e r,~t,,~i,,in,-, ,-~,~d ication, Giedke (1988) observed no consistent effect of naps at 1:30 PM on mood. Wu and Bunney (1990) ment;oned unpublished data from their group showing relapses in five of seven TSD responders after a 60-min nap. The antidepressant effect of sleep deprivation and its v y oa~,,,,l.~ ~ u a y u i u ~ , ii&pS as w r i i d~ liOi.,tl.tilldl

ale(~)

supports the hypothesis that sleep can be depressiogenic in depression. This assumption is further supported by the frequent clinical phenomenon of positive diurnal variation in mood, with a maximal depressed mood in the morning and a gradual improvement during the course of the day (Haug and F/ihndrich 1990). Several hypotheses have been proposed to explain the antidepressant eur.t:t ".... of sleep deprivation and, conversely, the "depressiogenic" properties of sleep in depression. Among these, the following are presently the most dis-

cussed (van der Hoofdakker and Beersma 1988; Wu and Bunney 1990): 1. Several theories emphasize the involvement of circadian processes in these phenomena. Under a chronobiological perspective, major depression can be characterized by an alteration of the "internal clock". Sleep deprivatioa is presumed to exert its antidepressant action by either resynchronizing disturbed rhythms or by preventing sleep during a so-called critical phase in the early morning hours (Wehr and Wirz-Justice 1981; Kripke 1984). In light of these theories, the timing of a daytime nap following sleep deprivation can be expected to be crucial to its effect on mood and depressive symptomatology. 2. The "two-process model" of sleep (Borb61y, 1987; Borb61y and Wirz-Justice, 1982) postulates a deficiency in a homeostatic "process S" (associated with EEG slowwave activity) in depression that may account for the im'~irm,~nt in mood. Sleep depfivatien is pi~umed to increase the level of"process S" by lengthening the duration of wakefulness, thus leading to improvement in mood. This model allows the prediction that the depressiogenic impact of sleep is related to the degree of "process S" reduction. Correspondingly, the EEG slow-wave activity during a nap can be expected to be essential to its "depressiogenic" action. 3. Wu and Bunney (1990) proposed the hypothesis of a sleep-associated depressiogenic process, possibly represented by a substance that is released during sleep and is metabolized during wakefulness. In many respects, this theory resembles the Borb61y and Wirz-Justice model; the latter differs from the former in implying a "euphorogenic" substance released in wakefulness rather than a "depressiogenic" substance released during sleep. Both theories allow the hypothesis that longer naps are more detrimental than shorter ones and that longer prior wakefulness protects against the mood worsening caused by daytime naps. 4. With regard to the antidepressant effect of selective REM sleep deprivation observed by Vogel et al (1980), it has been hypothesized that REM sleep suppression is essential to the beneficial effects of several antidepressant treatment modalities, including sleep deprivation (Berger et al 1990). This view is in line with the cholinergicadrenergic imbalance model of depression (Janowsky et al 19';-'2)and the reciprocal interaction model of REM sleep regulation (McCarley ! 982). In light of this approach, the occurrence of REM sleep during a daytime nap, as a correlate of elevated cholinergic neuronal activity, should be accompanied by a greater propensity of relapse into depression. The induction of depressive symptomatology by short sleep episodes can be regarded as a cmcia! experiment to test these hypotheses. The study presented here was designed to examine this phenomenon systematically to elu-

Naps After Sleep Deprivation in Depression

cidate the nature of the depressiogenic properties of sleep in depression. The main purpose was to examine the relationship between the clinical effects of daytime naps following sleep deprivation and the timing of the nap (morning versus afternoon). Other factors were also considered: the length of a nap as well as the occurrence and the amount of both slow-wave sleep and REM sleep. Special emphasis was placed on the possible interaction of these variables with nap timing.

Methods

Subjects The study was performed simultaneously at the Max Planck Institute of Psychiatry, Munich, and the Central Institute of Mental Health, Mannheim, Germany (part of the data have been published previously by Wiegand et al 1989). Thirty inpatients [10 male, 20 female, 9 single episode, 21 recurrent episodes; mean age 48.7 ___ 11.5 (SD) years] suffering from a major depression according to DSM-IIIR (296.2 x , 296.3 x , 296.5 x , rated by experienced psychiatrist), with a mean baseline depression score ( _ SD) on the Hamilton Depression Rating Scale, 2 l-item version (HAMD-21) of 26.9 +__ 5.3 (minimum 18 points) were included in the study. Informed, written consent was obtained from all patients.

Design After a drug washout period of at least 7 days and an adaptation night in the sleep laboratory, followed by one night of polysomnography, patients were subjected to a TSD. On the following day, patients took a nap in the sleep laboratory (with polysomnographic recording) either at 9:00 AM or 3:00 PM, they were assigned randomly to the morning versus afternoon nap condition. Sleep recordings were terminated when the patient woke up spontaneously without falling asleep again within 5 min. In the morning nap group, two patients did not fall asleep at the scheduled nap ume and were excluded from the present analysis. Gender ratio, mean age, and baseline psychopathology of the resuhmg sample are characterized in Table 1. With regard to these variables, there were no significant differences between the morning and afternoon nap groups nor between responders and nonresponders to TSD.

Polysomnography The recordings were performed using a 17-channel Nihon Kohden 4417 EEG machine that measured the following parameters: EEG (C3-A2/C4-AI), electro-ocuaog~am ~norizontai), and electromyogram (submental). The sleep polygraphs were rated visually according to standard criteria

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409

(Rechtschaffen and Kales 1968). The following definitions of sleep parameters were used:

1. Total sleep time: time spent asleep less any awake time.

2. Sleep onset latency: time from lights out until the appearance of stage 2 sleep. 3. Sleep efficiency: ratio of total sleep time to time in bed. 4. REM latency: time from sleep onset until the first occurrence of REM sleep. 5. REM density: number of 3-sec "miniepochs" of REM sleep containing eye movements as a percentage of the total number of "miniepochs" of REM sleep.

Depression Ratings Depressive symptomatology was observer rated by means of the six-item version of the Hamilton Depression Scale (HAMD-6) (Bech et al 1975) covering depressed mood, guilt feelings, woik and haterest, psychomotor retardation, anxiety (psychic), and physical symptoms (maximum score 22); ratings took place on the day before TSD at approximately 9:00 AM and 3:00 PM and on the day following TSD approximately 9:00 AM and 11:00 AM (or 30 min after termination of a morning nap, respectively) and 3:00 PM and 5:00 PM (or 30 min after termination of an afternoon nap, respectively). Raters were unaware of the experimental conditions. Response to total sle~:p deprivation was defined as a reduction of at least 30% in the HAMD-6 score, based on both 9:00 AM ratings. A nap effect (difference in HAMD-6 ratings after versus before the nap) of four points or more was defined as a relapse; changes between one and three points were termed a slight worsening. The difference in HAMD-6 ratings between 9:00 AM and 3:00 PM on the day before TSD is referred to as

morning/afternoon variation of mood. Statistical Analyses Comparisons between subgroups were mainly performed by means of two-way analyses of variance, with "nap timing" and "response to TSD" as factors. The variations in HAMD-6 scores were analyzed by means of Wilcoxon's test. Correlational analyses were performed by computing product-moment correlation coefficients. The level of significance was set at p < 0.05 (two-tailed).

Results

Characteristics of Nap Sleep aot~ 2 u~,.,,u~.s morning and afternoon nap sleep. Naps at 9:00 AM and 3:00 PM did not differ in any of the sleep parameters. Responders to TSD exhibited significantly less

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Table I. Clinical Description of the Study Samplea Total

Male/female ratio Meanage(_+SD)(yr) Mean HAMD-21 baseline score ( ± SD)

Respoaders to TSD

Nonresponders to TSD

Naps at 9:00 AM (n = 13)

Naps at 3:00 PM (n = 15)

Naps at 9:00 AM (n = 8)

Naps at 3:00 PM (n = 11)

Naps ai 9:00 AM (n = 5)

Naps at 3:00 PM (n = 4)

ANOVA b

2/I ! 51.1 ± 10.6 28.5 ± 5.6

8/7 46.5 __ 12.9 25.7 +- 5.3

1/7 52.5 -- 12.3 28.5 -- 4.8

4/7 48.5 -+ 11.8 26.5 -- 5.6

I/4 48.8 _+ 7.9 28.6 +- 7.3

4/0 4 1 . 0 - + t5.9 23.8 -- 4.3

NS NS

~TSD. total sleep deprivation; HAMD-21, Hamilton Depression Scale, 21-item version. bANOVA, analysis of variation results (with factors "nap timing" and "response to TSD"); NS, not significant.

REM sleep and a lower REM density than nonresponders. Results did not change when analyzing the relative instead of the absolute amounts of sleep stages.

Influence of Nap Timing and Preceding Response to TSD on Mood Changes Figure 1 describes the distribution of nap effects in the morning and afternoon nap groups, separately for responders and nonresponders to TSD. Five of the responders who took a nap at 9:00 AM exhibited severe relapse into depression. In contrast, afternoon naps induced only slight (if any) worsening in re,ponders to TSD, with the exception of one patient who showed a dramatic deterioration in mood. A significant difference in the relapse rate between morning and afternoon naps occurred in responders to TSD [Fisher's exact test comparing rate of r~'lapse (nap effect ->4) with rate of nonrelapse (nap effect <4; p = 0.041, two-tailed]. An analysis of variance (Table 2, bottom) reflected the same trend for the nap effect, yet did not yield significant differences with regard to the factors "nap timing" and "response to T'SD." R e l a t i o n x h i n A m n n o0 M o n r l C h a n o a ~ .............

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Duration, Content of Slow-Wave Sleep, and Content oJ REM Sleep Figure 2 demonstrates the relationship between nap sleep duration (total sleep time) and the effect on mood. The two parameters are negatively correlated; the coefficient is significant for the total sample, indicating that longer naps had less effect on mood. A separate analysis for morning and afternoon naps (Table 3) showed that this relationship was (nonsignificantly) more pronounced in afternoon naps. Neither the amount of REM sleep during a nap nor the content of slow-wave sleep was related significantly to its clinical impact. A separate analysis was dedicated to the question of whether the occurrence versus absence of REM sleep, irrespective of its duration, might influence the clinical

impact of a daytime nap. Naps containing REM sleep (n = 11 in the total sample) led to virtually no mood changes (AHAMD-6, 0.6 __. 3.6 points), whereas naps without REM sleep (n = 17) induced a mood worsening (AHAMD-6, 3.2 ___ 4.1 points); however, the difference did not reach levels of significance. The trend was more pronounced in afternoon naps, which induced a mean mood improvement when REM sleep was present (AHAMD-6, 0.5 _+ 2.6 points) in contrast to naps without REM sleep (AHAMD-6, 3.1 _+ 4.7 points). Naps containing REM sleep were significantly longer than naps without REM sleep (85. l _+ 47.2 min versus 29.0 +_ 22.1 min, respectively; p < 0.001, Wilcoxon's test, two-tailed).

Relationship Between Nap Effect and the Preceding Course of Mood Figure 3 describes the course of depression ratings for each responder to TSD during the days before and after TSD, separately for the morning (upper part) and afternoon (lower part) nap group. Again, the induction of clear mood worsening by morning naps in the majority of TSD responders is evident (p < 0.01; Wilcoxon's test, two-tailed). Afternoon naps, in contrast, led to slight changes in mood (nonsignificant). In one case only was a release induced. Although the patients had been randomly assigned to the 9:00 AM versus 3:00 PM nap condition, the afternoon nap group exhibited more pronounced morning/afternoon variation in mood on the preceding day than the morning nap group; however, the difference did not reach levels of significance (see Table 2). There was no overall correlation between morning/afternoon variation in mood on the preceding day and the nap effect (Table 3); however, in the afternoon nap group, the correlation was nonsignificantly negative. Baseline HAMD-2i scores, as well as age, turned out to be uncorrelated with the nap effect. Patients with recurrent depression did not differ from those with a single episode with regard to the frequency of relapses.

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471

BIOL PSYCHIATRY 1993;33:467-.476

Table 2. Nap Sleep, Nap Effect, and MominodAfternoon Variation in Mood: Comparison of Morning Versus Afternoon Naps and Responders Versus Nonresponders to Total Sleep Deprivation (TSD) Total Naps at 9:00 AM Nap sleep Total sleep time (rain) Sleep onset latency (min) Sleep efficiency (%) Stage 0 (rain) Stage 1 (min) Stage 2 (rain) Slow-wave sleep (min~ REM sleep (min~ Naps w i t h R E M sleep (n = 11) REM sleep (min) REM latency (min) REM density Nap effect and variation of mood Nap effecff Morning/afternoon variation of m o o d :

Responders to T S D Naps at 3:00 PM

Naps at 9:00 art

Nonresponders to T S D

Naps at 3:00 .*M

Naps at 9:00 AM

Naps at 3:00 PM

ANOVA"

n = 13 41.6 --. 38.1

n = 15 59.3 ± 47.5

n = 18 45.6 ± 46.1

n = !1 59.2 ± 42.2

n = 5 35.1 ± 23.3

n=4 59.5 ~ 67.8

NS

9.7 ± ~ 6

9.1 ± 7.6

8.9 ± 4.9

9.0 ± 8.6

I I . 0 ± 6.9

9.1 - 4.1

NS

63.4 4.0 5.3 19.7 10.9

± ± ± ± ±

19.8 5.5 6.5 19.8 14.5

63.4 4.5 5.8 31.1 13.2

± ± ± ± __

23.1 7.2 7.6 25.6 20.9

64.4 3.8 6.7 22.8 12.7

± ± ± ± ±

22.9 6.0 7.6 24.7 14.7

67.2 3.7 5.6 36.0 14.1

± ± ± ± ±

20.6 6.0 7.3 27.1 21.6

61.9 4.5 3.1 14.9 8.1

± ± ± ± ±

15.9 5.3 4.0 8.3 15.4

± 29.7 ~ 10.4 + 9.4 _ 16.8 "4- 21.8

NS NS NS NS NS

24.? _ 30.8 n=2

b

5.9 ± 9.9 n = 5

9.1 ± 17.9 n = 6

3.8 ± 6.8 n = 3

3.4 ± 5.4 n = 4

15.4 ± 10.6 25.3 ± 29.9

22.8 ± 22.8 37.0 ± 22.2

10.2 ± 7.9 15.7 ± 36.3

9.4 ± 4.9 49.6 ± 10.9

15.5/31.0 46.5/3.0

35.5/63.5 2.0/21.5

NS

37.1 ± 28.7 n = 13

25.1 ± 17.4 n = 15

20.7 ± 10.1 n = 8

15.6 ± 9.4 n = 11

38.4/84.8 n = 5

34.8/53.3

d

1.7 ± 4.4 - 2 . 7 _ 3.8

1.2 ± 1.6 - ! . 2 ± 1.3

1.5 _ 4.7 - 1 . 3 ± 3.2

2.8 ± 3.8 - 1 . 1 ± 3.2

1.7 --- 4.3 - 2 . 3 ± 3.6

3.9 ± 4.5 - 1 . 0 ± 4.1

9.3 ± 13.9 n = 2

53.0 6.9 6.4 17.8 10.9

a=4

NS NS

°ANOVA, analysis of variation results (with factors "nap timing" and "'response to TSD"); NS, net significant. bMain effect for response to TSD (F = 18.7, df = 1, p = 0.003). ~Main effect for response to TSD (F = 18.6, df = 1, p = 0.003). amain effect for response to TSD (F = 12.2, df = I, p = 0.01). "Nap effect: difference of HAMD-6 ratings after vs. before the nap. rMoming2afternoon variation of mood: difference of HAMD-6 ratings between 9:00 AM and 3:00 PM on the day before TSD.

Discussion A daytime nap can reinduce depressive symptomatology in depressed patients who have improved by means of TSD. Thus far, the present results confirm the clinical impressions and ,~ _.4~.. ..o of some of .h.. vnr,=,~in, ,",u,'us~ . . . . . . .i~ . . .~.m. .d i ~ mentioned above, including data from our previous study obtained in naps at 1:00 PM (Wiegand et al 1987b). In responders to TSD, relapse and slight worsening were more frequent than improvement. This clearly differs from observations in healthy subjects, who in general benefit by a nap toiiowing sleep deprivation (Taub et al 1976; Naitoh 1981). It might be objected that mood worsening may mirror "sleep inertia" effects occ.rring immediately after awakening (Naitoh 1981); however, ratings were performed approximately 30 min after wake-up; after such a delay, sleep inertia effects are expected to be marginal (Webb and Agnew 1974). In particular, the severe relapses that we observed exceeded the range of slight, temporary discomfort that may be the expression of sleep inertia.

The timing of a nap appeared to be important to its effect on depressive symptomatology. Morning naps had the most detrimental impact in responders to TSD, whereas afternoon naps were better tolerated. This finding differs from the results of Gillin et al (1989) who found no difference in the (mostly beneficial) clinical effects of morning versus afternoon naps; howevcr, these naps were very short (10 min). The study b:/ Kraft et al (1984) was restricted to seven patients who took afternoon naps; they observed a relapse in only one case, which is in accordance with our findings. The difference between morning and afternoon naps with regard to the impact on depression seems to support those theories that emphasize the: role of circadian factors and suggests that there may be a circadian variation in propensity to relapse into depression. In analogy to the "internal cohacidence model" (We,hr and Wirz-Justice 1981), it may be sFeculated that a nap at 9:00 in the morning interferes with a "vulnerabl(" or "critical phase," during which the occurrence ,ff sleep is depressiogenic. The importance of circadian factors in the effects of sleep dep-

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109:001

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Figure I. Effects of morning and afternoon naps in responders and nonresponders to TSD; Nap effect = AHAMD-6 prenap versus postnap; 09:00, 9:00 AM; 15:00, 3:00 PM

rivation is further underscored by the observation that the presence of a positive diurnal variation in mood is among the few predictors of response to "ISD that have been identified (Reinink et al 1990; Riemann et al 1991); however, the concept of a "critical phase" has recently been questioned by the data of Southmayd et al (1990) who demonstrated that relapses during the recovery night following successful TSD are not confined to a distinct period of time. Moreover, in the present analyses, timing of naps is not independent of the duration of prior wakefulness because the sleep deprivation periods began consistently at 7:00 AM on the preceding day. Thus, the more detrimental impact of morning naps could alternatively be explained by the S-deficiency hypothesis: Following this model, after continuous sleep deprivation, the deficient "process S" will have a higher level in the afternoon than in the morning, and an afternoon nap will be less likely to reduce process S to a degree leading to recurrence of depressive symptoms, compared with a morning nap where even small amounts of sleep may be sufficient to reinduce depression. Thus, our finding that nap timing is crucial to its effect on mood does not necessarily favor circadian models but

is compatible with "homeostatic" explanations (e.g., as provided by the process S theory). In a similar way, Wu and Bunney's (1990) model can serve to explain the difference between morning and afternoon naps: If a hypothetical "depressiogenic substance" is metabolized during wakefulness in a linear, time-dependent way, longer preceding wakefulness would lead to lower levels of this substance, and relapse would be less likely in the afternoon because the baseline level of the substance should be lower. Future studies in this field should especially attempt to separate the influences of nap timing and duration of prior wakefulness to allow the separation of "circadian" and "homeostatic" influences. We cannot exclude the possibility that the less harmful impact of afternoon naps is due to an accidental difference in the course of depression on the preceding day: The afternoon nap group tended to exhibit a more pronounced morning/afternoon variation in mood that correlated negatively (not reaching levels of statistical significance) with the nap effect; in addition, these patients tended to have lower HAMD-6 scores before the nap. On the other hand, Figure 3 demonstrates that even those patients who had exhibited a less pronounced positive diurnal variation with high depression levels in the preceding afternoon either improved or showed minor worsening following an at,ernoon nap on the next day. Both the S deficiency and the depressiogenic substance model would predict that independent of nap timing, relapses into depression are more likely to occur following longer naps. In the pilot study by our group of naps at 1:00 PM (Wiegand et al 1987b), there was indeed a tendency for longer naps to have a less favorable impact on depressive symptomatology. The present data do not support this finding and even point to the opposite direction: Longer naps were better tolerated, and this result was more p~,~ounced following afternoon naps; however, after very brief naps ( < 10 min duration), we did not observe relapse, which is in agreement with the findings of Gillin et al (1989) but disagrees with the observation by Roy-Byrne et al (1984) of an ultrashort (90 sec) nap followed by a severe relapse, as well as with the report by Southmayd et al (1987). It can be summarized that very long naps do not seem to be more detrimental than shorter ones. The existing evidence contradicts the assumption of a linear relationship in either direction between nap length and clinical effects and thus is not compatible with the respective predictions of the S-deficiency and depressiogenic substance models. In accordance with Gillin et al (1989), we did not find differences in sleep variables between morning and afternoon naps. In particular, there was no indication of increased REM sleep pressure in morning versus afternoon naps, as could be expected from data by Kupfer et al

Naps After Sleep Deprivation in Depression

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1993;33:467--476

-.apt at 09:oo (.='t 3}1

14-

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15:00

(n--15)1

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Figure 2. Nap effect and nap sleep duration; Nap effect = AHAMD-6 prenap versus postnap; 09:00, 9:00 AM; 15:00, 3:00 PM.

Table 3. Correlation of Nap Effect with Age, Psychopathology, and Sleep Variables" C o ~ e ! a t i o n of , u p

Total sample

Responders

effect with

(n = 28)

(n = 19)

Age (yr)

0.08

- 0.08

0.35

Baseline H A M D - 2 !

0.27

0.30

0.14

- 0.20

- 0.12

0.13

M o m i n g , ' a f t e m o o n variation

Naps at 9:00 AM (n =

13)

Responders

Naps at 3:00 PM

R e s l ~ r , ders

(n = 8)

(n = 15)

(n = I1)

0.38

- 0.12

- 0.51

0.30

0.32

0.25

0.17

- 0.49

- 0.47 - 0.24

in mood Total sleep time ( m i n )

- 0.42 b

- 0.30

- 0.27

- 0.32

- 0.47

S l o w - w a v e sleep ( m i n )

- 0.20

- 0.06

- 0.29

- 0.40

- 0.14

R E M sleep (min)

-0.35

-0.11

-0.13

0.06

-0.44

0.11 -0.28

o~od,ct.-moment co__rre_!ationcoefficients: HAMD-21. Hamilton Depression Scale, 21-item version; REM, rapid eye movement. "p < 0.05, two-hailed; all other coefficients not significant.

( 1981 ). It is remarkable that in naps containing REM sleep, despite the preceding TSD, mean REM :atencies at both nap time points are rather short. This is not in agreement with the expectation derived from the two-process model of sleep regulation that after sleep deprivation, the rebound of slow-wave sleep should prevent an early onset of REM sleep. Responders to TSD differed from nonresponders with regard to REM sleep variables: They exhibited less REM sleep and lower REM density (a prolonged REM latency failed to reach statistical significance). Sleep structure of daytime naps thus seems to reflect the clinical condition, with nonresponders to TSD exhibiting a more "depressive"

sleep paUern; however, with respect to the relatively small number of naps containing REM sleep (n = 11), these findings should be regarded as preliminary. In nocturnal sleep following TSD, Riemann and Berger (1990) failed to find significant differences in REM sleep variables between responders and nonresponders. Similar to our pilot study of naps at 1:00 PM, the total amount of slow-wave sleep during a daytime nap showed no ~lationship with clinical effect. This does not support the respective expectation derived from the Sdeficiency theory. For any critical test of this hypothesis, however, EEG power spectra wotild be required (which were not available in the present study) because

474

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BIOL PSYCHIATRY 1993;33:467-476

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the amount of visually scored slow-wave sleep can be expected to correlate with EEG delta power (Brunet et al 1988). Consequently, some type of relationship should be present between the amount of slow-wave sleep and mood worsening; however, this is not evidenced by our data.

The chollnergic-amincrgic imbalance model should predict the occurrence and amount of REM sleep to be related with clinical effect; this expectation, too, was not confirmed by our data. Moreover, our findings agree with a recent study by Riemann et al__(in,___~-nress', preliminary results published in Riemann et al 1989), which aimed directly at comparing morning naps containing REM sleep with morning naps without REM sleep and found no differential effects on mood. In contrast, in our former pilot study of naps at 1:00 PM, naps containing REM sleep tended to be more detrimental. Thus, the h~T,othesis derived from the cholinergic-aminergic imbalance model of depression that cholinergic overactivity may be involved in relapses into depression caused by a daytime nap is not supported by the data with respect to naps at 9:00 AM and 3:00 PM. An open question remains as to how far, due to circadian variations in cholinergic functioning, REM sleeprelated mo,:,d worsening is restricted to naps taken at approximately l:00 I'M. It must be concluded that the relationship between nap sleep and its impact on depressive symptomatology does

not appe~,r to be linear and univariate. This is i., agreement with llie conclusions by Southmayd et al t1990). Even when considering the clear differences in relapse rates between morning and afternoon naps, the large variety of clinical effects within each experimental subgroup requires explanation. A multifactorial model would probably fit better with the existing evidence. As a trait factor, there may be a differential sensitivity in each individual patient to manipulations of the sleep--wake cycle that may be manifested in the frequency and intensity of diurnal variatlnn~ in mood, in tho nrnh2hil;tw of response :-LSJ TSD, ~-~ N

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in a differential "vulnerability" to the impact of sleep on

depressive symptomatology following successful sleep deprivation. St~cond, some circadian or ultradian factor may manifest itself in one or more "critical phases," during which sleep is more likely to promote depression. This factor may interact closely with "homeostatic" influences, as suggested by the process S model, the depressiogenic substance theory and the cholinergic-aminergic imbalance hypothesis; however, considerably larger samples would be required to study the complex interactions within such a multifactorial model. To summarize, our main findings are essentially compatible with all major hypotheses that undertake to explain the unfavorable impact of sleep on depression, and they do not clearly refute any of them; however, none of these hypotheses appears to sufticie~tly cover every aspect of

Naps After Sleep Deprivation in Depression

the observations. Relapses caused by daytime naps seem to result from complex interactions of several factors; simple and linear relationships between single variables and clinical effects appear to be improbable.

475

BIOL PSYCHIATRY 1993;33:467-4"/6

We gratefullyacknowledgethe help of Mrs. Ursula Hofer(~search n ~ at the Max Planck Institute of Psychiatry), Mrs. Gaby Reim (research nurse at the Central Institute of Mental Health), as well as the assistance of Matthias Junker and Stephan Sto|z.

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