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556 Electroencephalography and Clinical Neurophysiology

Elsevier Publishing Company, Amsterdam - Printed in The Netherlands

CLINICAL AND LABORATORY NOTES

SLEEP LABORATORY ADAPTATION IN NORMAL SUBJECTS


A N D DEPRESSED PATIENTS ("FIRST NIGHT EFFECT") 1

JOE MENDELS, M.D. s AND DAVID R. HAWKINS, M.D.


Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill, N.C. (U.S.A.)

(Accepted for publication: November 23, 1966)

It is common practice to exclude the data obtained from ing in the morning), the "actual sleep period" (total sleep
subjects during their first night in the sleep laboratory in period minus the time awake and drowsy), the "actual
studies of the psychophysiology of sleep. It has been sug- sleep period plus drowsy", and the time spent in stages
gested that the subjects' behavior is affected by the nov- awake, drowsy, l, 2, 3, 4 and 1-REM sleep.
elty of the circumstances and that the data will consequent- Table II shows the latency to the onset of sleep and to
ly be modified by this experience. the onset of each stage of sleep from "goodnight". ("First
We have studied the sleep pattern of 21 depressed asleep" usually means the first entry into stage 1. However,
patients and fifteen control subjects (Hawkins and Mendels several subjects went directly into stage 2 sleep.)
1966; Mendels and Hawkins 1967) and herewith report a The latency of onset for each stage of sleep from the
comparison of the sleep for nights 1 and 2 for each group time the subjects first entered stage 1 was reduced. How-
of subjects. ever, only the reduction in time taken by the control sub-
jects to reach stage 3 (night 1, 45.7 min; night 2, 28.6 min;
METHOD P < 0.05) and stage 1-REM (night l, 139.1 min; night 2,
Twenty-one inpatients diagnosed as suffering from a 86.9 min; P < 0.05) were significant. The reduction in the
depressive illness and fifteen paid volunteer control sub- time taken by the depressed patients to reach stage 4
jects were studied in the sleep laboratory for 3-6 nights (night l, 119.3 min; night 2, 67.2 min; P < 0.05) was
each. The depressed patients were studied within a few significant, whereas there was no significant change in
days of admission to the hospital. the time taken to reach stages 1-REM and 3.
The subjects were studied in air conditioned, sound There was an increase (not significant) in the number
attenuated, electrically shielded rooms. The EEG tracings of R E M periods from night 1 to night 2 (controls 0.7,
were from the occipital and frontal regions referred to the depressives 1.0) and a decrease (not significant) in the num-
vertex. E M G monitoring of the submental muscles was ber of spontaneous awakenings per night in both groups.
performed routinely. Eye movements were monitored by
means of a ceramic strain gauge attached over the eyelid. DISCUSSION
Body movements were measured as artifacts appearing on
the EEG and E M G tracings. The records were analyzed as Like Agnew et al. (1966) we have found significant dif-
1 min epochs using the system described by Dement and ferences between the EEG sleep characteristics obtained
Kleitman (1957) for classifying EEG sleep, with one modi- from nights 1 and 2 of the study. On the former there was
fication (i.e., scoring a stage "drowsy" which consists more time awake and drowsy and less time in stage 3; and
essentially of slow alpha activity and is intermediate it took longer to fall asleep and to reach each stage of sleep.
between "awake" and stage I). There were also more frequent awakenings. We did not
The significance of the changes in sleep patterns between find the decrease in the number of stage shifts which they
nights 1 and 2 for each group of subjects was deter- reported.
mined by a Wilcoxon "signed rank T test" for matched Of particular interest is the finding that it took the
samples (Walker and Lev 1953). control subjects 52.2 min longer to reach the first stage 1-
R E M period after "goodnight", and 41.5 min longer to
RESULTS
reach it after first entering stage 1 sleep, on the first night
Table I shows the mean times for nights I and 2 for the as compared with night 2. Also there was a mean of 0.7
"total sleep period" (time from 1st drowsy to last awaken- R E M periods less on the first night than on the second
night, and the subjects slept an average of 15.1 min .~ss in
1 This work was supported by N.I.M.H. Grants num- stage 1-REM sleep on night 1 than on night 2. This indi-
ber MH-06633 and 329-NIH-234. cates that there is a frequent tendency to miss the first
2 Present address: Dept. of Psychiatry, University of R E M period on night 1 in the laboratory. Agnew et al.
Pennsylvania, Piersol Bldg., Spruce St., Philadelphia, Pa. came to a similar conclusion.
Electroenceph. clin. NeurophysioL, 1967, 22:556-558
SLEEP LABORATORY ADAPTATION 557

TABLE I
Differences between nights 1 and 2 for sleep periods and stages

Controls Depressives

Night 1 Night 2 Difference P Night 1 Night 2 Difference


(min) (min) (mill) (min) (min) (min)
(%)* (%) (%) (%) (%) (%)
Total sleep
period 431.3 431.1 - - 0.2 ns 388.2 398.3 10.1 ns
Actual sleep
period +
drowsy 395.8 425.0 29.2 ns 319.5 357.5 38.0 ns
Actual sleep
period 278.9 414.4 35.5 ns 301.9 327.6 25.7 ns
Awake 35.5 6.1 --29.4 0.01 49.7 40.8 - - 8.9 ns
8.2* 1.3 - - 6.9 0.05 13.5 10.9 - - 2.6 ns
Drowsy 16.9 10.6 - - 6.3 0.02 50.7 29.9 ---20.8 ns
3.9 2.4 - - 1.5 0.02 •7.6 7.1 --10.5 ns
Stage 1 6.7 4.4 - - 2.3 ns 15.3 11.8 - - 3.5 ns
1.6 1.0 - - 0.06 ns 3.9 3.0 - - 0.9 ns
Stage 2 161.4 160.3 - - 1.1 ns 132.8 160.5 27.7 0.05
37.4 36.6 - - 0.8 ns 34.8 40.1 5.3 ns
Stage 3 41.6 62.3 20.7 0.01 48.7 58.9 10.2 ns
9.6 14.4 4.8 0.01 13.7 15.0 1.3 ns
Stage 4 77.7 80.8 3.1 ns 22.4 20.0 - - 2.4 ns
18.0 19.7 1.7 ns 5.6 4.7 - - 0.9 ns
Stage 1-REM 91.5 106.6 15.1 ns 61.2 76.4 15.2 ns
21.2 24.6 3.4 ns 10.8 19.1 8.3 its

* Each stage is expressed as a percentage of the total sleep period.

The findings from our depressed subjects are essen- The over-all results are in line with the concept of an
tially in the same direction as for the controls, but with less increased state of vigilance or arousal on the first labor-
significant changes from night 1 to night 2. Either adapta- atory night, with the control subjects adapting more rapidly
tion to the experimental situation takes place more slowly to the laboratory than the depressives.
because of the illness, or the pathological nature of the
sleep pattern itself limits any change. Our impression is SUMMARY
that the latter is more likely to be correct as we have studied The sleep EEG patterns of 21 depressed patients and
a small group of depressives who spent 3 or more consec- 15 control subjects are reported in terms of the changes
utive nights in the laboratory and who did show further from night 1 to night 2 in the sleep laboratory.
improvements in their sleep patterns on the third and On night 2 there were several significant changes for
fourth nights. the control subjects: (i) a decrease in the time spent in

TABLE II
Time (in minutes) required to reach each stage of sleep from "goodnight"

Controls Depressives
Night 1 Night 2 Difference P Night 1 Night 2 Difference P

"Goodnight"
to 1st asleep 23.6 13.0 --10.6 ns 50.5 31.9 --18.6 ns
Drowsy 20.0 8.9 --11.1 ns 25.8 25.0 - - 0.8 ns
Stage 2 25.4 14.6 --10.8 ns 60.8 34.7 --26.1 ns
Stage 3 45.7 28.6 --17.1 0.05 94.0 50.4 --43.6 ns
Stage 4 88.4 43.9 --44.5 ns 119.3 67.2 --52.1 0.05
Stage 1-REM 139.1 86.9 --52.2 0.05 143.8 101.5 ---42.3 ns

Electroenceph. clin. NeurophysioL, 1967, 22:556-558


558 J. MENDELS AND D. R. HAWKINS

"awake" and "drowsy"; (ii) an increase in time spent in Les variations pr6sent6es par les malades d6prim6s
stage 3; and (iii) a reduction in the latency to the first vont dans le m~me sens mais sont moins marqu6es que
R E M period and first stage 3. There was an increase in pour les sujets de contr61e.
the number of rapid eye movement periods on the second Ces donn6es confirment la notion d'une augmentation
night, which was just short of statistical significance. de l'6tat de veille ou d'activit6 pendant la premiere nuit
The changes manifested by the depressed patients were pass6e au laboratoire. Elles indiquent aussi que la premiere
in the same direction, though they were less marked than PMO air tendance b. manquer lors de la premiere nuit
in the controls. d'6tude.
The findings support the concept of an increased state
of vigilance or arousal on the first laboratory night. They C. Cochrane, Ph.D., advised on statistical procedures.
also indicate a frequent tendency to miss the first R E M Drs. G. Thrasher, R. Knapp and J. Scott participated in
period on the first study night. various aspects of these studies. We wish to thank Mrs. J.
Benson, Mrs. M. Graves and Mrs. S. Kelly for their tech-
R~SUM~ nical assistance.
REFERENCES
ADAPTATION AU LABORATOIRE D'I~TUDE DU SOM-
MEIL CHEZ DES SUJETS NORMAUX ET DES MALADES AGNEW, H. W., WEaa, W. B. and WILLIAMS,.R.L. The
first night effect: an EEG study of sleep. Psycho-
DEPR1MI~S ("ErFET DE LA PREMIERE NUIT")
physiology, 1966, 2: 263-266.
Les auteurs analysent les variations de I'EEG du som- DEMENT,W. and KLEITMAN,N. Cyclic variations of EEG
meil entre la premiere et la deuxi~me nuit pass6es dans le during sleep and their relation to eye movements, body
laboratoire d'6tude du sommeil chez 21 malades d6prim6s, motility and dreaming. Electroenceph. clin. Neuro-
compar6s /115 sujets de contr61e. physiol., 1957, 9: 673-690.
La deuxi/~me nuit, plusieurs variations significatives HAWKINS, D. and MENDELS, J. Sleep disturbance in
s'observent chez les sujets de contrfle: (i) diminution du depressive syndromes. Amer. J. Psychiat., 1966, 123:
temps d'6veil et de somnolence; (ii) augmentation de la 682-690.
dur6e de stade 3 ; et (iii) r6duction de la latence de la pre- MENDELS, J. and HAWKINS, D. Sleep and depression: a
mi6re p6riode de PMO et du premier stade 3. L'augmen- controlled EEG study. Arch. gen. Psychiat. (Chic.),
tation du hombre de p6riodes de mouvements oculaires 1967 (in press).
rapides au cours de la seconde nuit n'a qu'une signification WALKER, H. M. and LEv, J. Statistical inference. Holt,
statistique r6duite. New York, 1953: 432-434.
Reference: MENDELS,J. and HAWKINS,D. R. Sleep laboratory adaptation in normal subjects and depressed patients
("first night effect"). Electroenceph. clin. Neurophysiol., 1967, 22: 556-558.

E F F E C T OF B U T Y R O L A C T O N E A N D G A M M A - H Y D R O X Y B U T Y R A T E
ON T H E EEG A N D SLEEP CYCLE IN MAN

Y. YAMADA, M . D . , J. YAMAMOTO, M . D . , A. FUJIKI, M . D . , Y. HISHIKAWA, M . D .


AND Z. KANEKO, M . D .

Department of Neuropsychiatry, Osaka University Medical School, Fukushima-ku, Osaka (Japan)

(Accepted for publication: December 12, 1966)

It has been reported that short chain fatty acids induce (Jouvet et aL 1961; Matsuzaki et al. 1964). However,
in animals a "sleep-like" state indistinguishable from Winters and Spooner (1965) have reported that no sig-
natural sleep and that at higher doses they induce an nificant change could be found in the sleep cycle of cats
anesthetic state (Samson et al. 1956; Holmquist and following the injection of'y-hydroxybutyrate. Metcalf et
Ingvar 1957; Laborit et al. 1960). There have been reports al. (1966) have recently reported that the oral administra-
that sodium butyrate and its related compounds, when tion of sodium y-hydroxybutyrate in man does not induce
administered i.v., induce in cats a sleep state with low the REM period of sleep.
voltage fast EEG and rapid eye movements (REM period) The present experiments were undertaken to compare
Electroenceph. clin. Neurophysiol., 1967, 22:558-562

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