Elbctroencephalography and Clinical Neurophysiology, 1978, 4 4 : 5 1 3 - - 5 1 7
513
© Elsevier/North-Holland Scientific Publishers Ltd.
Clinical note REM SLEEP IN PRIMARY
DEPRESSION:
A COMPUTERIZED
ANALYSIS*
RICHARD J. McPARTLAND, DAVID J. KUPFER, PATRICIA COBLE, DUANE SPIKER and GARY MATTHEWS
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Penn. (U.S.A.) (Accepted for publication: August 10, 1977)
EEG sleep research in affective states has yielded a number of significant findings linking rapid eye movement (REM) sleep changes to nosologic schema For depressive subtypes. In particular, primary depression is characterized by a shortened REM tatency (Kupfer and Foster 1972), which may be indicative of the level of severity (Spiker et al. 1977). Furthermore, baseline REM measures may help to ~4iscriminate between psychotic and non-psychotic depressive subtypes (Kupfer et al. 1977a) and may relate to eventual clinical drug response (Kupfer et al. 1977b). Preliminary findings on children indicate Lhat specific REM abnormalities, similar to those shown by adult depressives, are also characteristic of Childhood depression (Coble et al. 1977). It has also been hypothesized that some unknown stimulus of REM sleep is a naturally occurring endogenous antidepressant; consequently, by increasing REM pressure, whether experimentally or by drug, clinical improvements can be achieved (Vogel et al. 1977). All of these studies support the hypothesis that alterations of REM sleep in depression are prominent and of pronounced clinical and theoretical importance. To date, these findings have been achieved by using manual techniques for scoring REM sleep time and quantitating REM activity. Since manual REM scoring ignores much of the information contained in electrooculographic recordings, automated REM analysis should be used to obtain a more complete understanding of REM sleep and its relation to clinical states. This report uses the automated REM analyzer to investigate, in patients with primary depression, inter-REM period changes along 3 orthogonal dimensions; REM size, REM frequency and REM~ time. Method The EEG sleep of thirty-five depressed inpatients * This research was supported in part by research grant MH 24652 from the National Institute of Mental Health.
who were admitted to the Clinical Research Unit (22 females and 13 males) and had a mean age of 43.5 years _+ 2.5 S.E. was studied for 7 consecutive nights. Diagnosis was determined on the basis of the Research Diagnostic Criteria (RDC), and all patients met the criteria for majordepressive disorder, primary type. All patients were drug-free for a minimum of 14 days prior to the study, and received placebo during the seven study nights. All night Ac recordings of both left and right monocular eleetrooculogram (EOG) potentials were made using a frequency modulated magnetic tape recorder. For the purpose of automated REM analysis, each REM period's EOG potentials were replayed, at 16 times real time, to the REM analyzer. In brief, the REM analyzer is a software routine implemented on a PDP-11 minicomputer to detect REM waveforms and measure their characteristics. A REM is detected when there are simultaneous (within 115 msec) threshold crossings of opposite polarity by the two EOG potentials. Each EOG biopotential has two thresholds set at + 25 pV. After recogmzing a REM waveform, its voltage integral over time, duration and time of occurrence are measured. Subsequent to a night's REM analysis, composite parameters for each REM period are calculated. They are: the number of REMs occurring (C), their total voltage integral over time (I), the sum of their durations (D), and the average REM size (I/C). Each night's REM latency (RL, time asleep until the onset of the first REM period) and each REM period's REM time (RT) and REM activity (RA, a 9 point scale for rating intensity of REMs during a REM period) were calculated using manual methods (Rechtschaffen and Kales 1968). In addition, hybrid REM period measures of REM frequency (C/RT) and REM % phasic activity (D/RT) were calculated. For each patient, mean (average of 7 nights) REM period and whole night measures were determined. Because fewer than half of the study nights contained 5 or more REM periods, only the first 4 REM periods for each night were considered individually.
514
R.J. M C P A R T L A N D ET AL.
TABLE I Correlations b e t w e e n a u t o m a t e d and manual REM measures indicating validity o f a u t o m a t e d REM analysis.
A u t o m a t e d R e i n Measures Manual REM measures
REM time (RT) REM activity (RA) REM density (RA/RT)
Number of REMs (C)
Average REM size (I/C)
REM duration sum (D)
REM frequency (C/RT)
REM % phasic activity (D/RT)
0.64 c
0.10
0.54 c
-0.01
0.03
0.91 c
0.39 a
0.88 c
0.05 b
0.56 c
0.62 c
0.47 b
0.65 c
0.80 c
0.81 c
a p < 0.05. b p < 0.01. c p < 0.001.
Results Validity o f t h e REM analyzer was investigated by correlating total n i g h t a u t o m a t e d and h y b r i d REM p a r a m e t e r s w i t h m a n u a l l y s c o r e d REM variables. The results are t a b u l a t e d in Table I. The m a n u a l l y derived REM d e n s i t y measure ( R A / R T ) c o r r e l a t e s significantly w i t h t h e a u t o m a t e d d e n s i t y m e a s u r e s o f REM f r e q u e n c y (r = 0.80, P < 0.001) and % phasic activity (r = 0.81, P < 0.001). Manual REM activity correlates significantly w i t h the n u m b e r o f R E M s (r = 0.91, P < 0.01) and t h e i r d u r a t i o n s u m (r = 0.88, P < 0.001). Since REM activity is b y d e f i n i t i o n p r o p o r t i o n a l to the n u m b e r o f REMs and their total
d u r a t i o n , this is an e x p e c t e d result. Manual REM time and a u t o m a t e d REM c o u n t are also significantly c o r r e l a t e d (r = 0.64, P < 0.001) reflecting REM t i m e as a t o n i c p e r i o d in w h i c h phasic R E M s occur. Of the t h r e e intuitively i n d e p e n d e n t a u t o m a t e d measures w h i c h r e p r e s e n t t h r e e basic aspects o f REM p e r i o d s , REM f r e q u e n c y , t i m e and size, c o r r e l a t i o n s o f average nightly and REM p e r i o d d a t a s h o w e d REM freq u e n c y and size t o be f u n c t i o n a l l y r e l a t e d (r = 0.38, P < 0.01). Table II lists average values (± S.E.) for t o t a l night and individual REM period measures. Changes across t h e night for each REM p e r i o d d a t a are s h o w n in Fig. 1. Average REM size increased by a significant
T A B L E II Average REM period m e a s u r e s derived f r o m 7 nights o f sleep f r o m e a c h o f 35 p r i m a r y d e p r e s s e d h o s p i t a l i z e d patients. Total n i g h t RT, C and I are s u m s over all R E M periods. Total n i g h t I/C is an average across all R E M s and t o t a l night C / R T is t h e ratio o f total n i g h t C and RT.
REM period
Average REM size (I/C)
REM f r e q u e n c y (C/RT)
REM t i m e (RT)
Number of REMs (C)
REM integral (I)
1 2 3 4 Total n i g h t
10.4 10.2 11.1 12.0 11.6
10.1 8.2 8.0 8.7 9.0
21.3 19.6 22.6 22.1 70.0
209.8 162.8 186.5 201.8 617.7
2639 2055 2425 2729 7939
+ ± ± ± ±
0.6 0.6 0.7 0.9 0.6
± ± ± ± ±
1.1 0.8 0.8 0.9 0.8
± ± ± ± ±
2.5 1.4 1.7 1.7 4.7
± 33.7 ± 19.0 ± 23 -+ 25.3 ± 67.5
+- 511 ± 295 ± 387 ± 517 ± 1101
REM SLEEP IN PRIMARY DEPRESSION
515
12 AVERAGE (I/C)
(~v-sec per REM) I0 I0 ~ REM FREQUENCY 9 ~ (C/RT) (#/min) 8--
25 23 REM TIME
21
(min)
19
(T)
17 I
I
I
2
3
4
REM PERIOD * p< 0.05
* * p< 0.01
Fig. 1. Average orthogonal automated REM period measures vs. the rank of the REM period derived from 7 nights of sleep from each of 35 primary depressed hospitalized patients.
degree from REM periods 2--3 and 3--4 with REM size being significantly greater at the end of the night (REMP4) than at the beginning (REMP1). The opposite is true for REM frequency, which decreased significantly from RLM periods 1--2 and then remained constant. REM time remains relatively constant across REM periods. The global parameters, REM count (C) and integral sum (I), do not vary significantly from REM period to REM period. Correlations of REM latency with automated measures showed a significant correlation with REM frequency only for the first REM period (r = 0.35, P < 0.05).
Discussion This report represents a clinical application of a new software version of the REM analyzer to investigate characteristics of REM sleep in depression. This REM analyzer is unique in its ability to measure fundamental orthogonal characteristics of REM sleep, i.e., REM time, REM frequency and REM size.
Additionally, global variables of REM count (REM time times frequency) and total REM area (REM time times frequency times size) are produced. Validity of this software version is established, as it was earlier for the hardwired model (McPartland et al. 1971, 1974), by high correlations of automated and visually derived REM density measures, of both automated REM count and duration sum, to manually scored REM activity and of REM count to REM time. REM sleep periods can be characterized by the three conceptually independent parameters: REM time, a tonic measure; REM frequency and REM size, both phasic characteristics. Depressed patients have REM sleep period times comparable to normal subjects, and in the depressives, as with normals, REM time does not significantly change across REM periods (Williams et al. 1974). In normals, phasic REM frequency has been shown to increase in each succeeding REM period throughout the night (Aserinsky 1973; Thomas et al. 1970; Benoit et al. 1974). However, in our depressed group the highest phasic REM
516 frequency occurred during the first REM period and was significantly reduced in later REM periods. This high initial REM frequency and short REM latency (Kupfer and Foster 1972) characteristic of depression suggests that depressives have a high phasic REM pressure at sleep onset which is rapidly dissipated by the first REM period leading to lower values of REM frequency and normal REM cycle lengths. That severity of depression is correlated to initial phasic REM pressure is supported by the correlations of REM latency to severity of depression and to the REM frequency of the first REM period. Further studies of these relationships are being conducted in an investigation relating REM measures to drug treatment response. If it were not for the first REM period, REM size would be monotonically increasing across REM periods. The size of the REMs during the first REM period may have been abnormally heightened due to the high initial phasic REM pressure. Apart from the first REM period, REM size-REM period changes may be similar in depressed and normal subjects. Further studies are needed to ascertain patterns of REM size in normals and to establish age dependent norms for both REM size and frequency. REM sleep time is the remaining basic REM measure which, although intensively studied in normals is still controversial with respect to patterning across REM periods. Some studies report an increase in REM time with the rank of the REM period (Aserinsky 1968; Benoit 1974; Dement 1964) while others report consistency of REM time with rank (Williams 1974). Besides the intrinsic value of understanding the mechanisms of sleep, these norms must be established in order to serve as a basis of comparison for clinical sleep data acquired from many diverse but sleep related disorders. Vogel and coworkers also have reported on REM measures manifested by drug-free depressives (Vogel 1977). The measure of REM frequency (the number of 3 sec epochs of REM sleep with at least one REM, divided by the total number o f 3 sec epochs of REM sleep) used in their studies showed constant values across REM periods. Although not in agreement with the patterning o f REM frequency reported here, the REM frequency in Vogel's depressed group was significantly elevated in comparison with control subjects.* What Vogel calls REM frequency may better be described as an approximation of % phasic REM activity, i.e., the ratio of time spent asleep in phasic REM sleep to total REM sleep time. The more exact measure of % phasic activity, which was readily available with our computer analysis program, in-
This work was presented at a symposium on sleep and REM sleep deprivation at the Annual Meeting of the Association for the Psychophysiological Study of Sleep, Houston, Texas, April, 1977.
R.J. MCPARTLAND ET,AL. dicated that in our depressed sample the patterning across REM periods of % phasic activity resembled that for REM frequency, i.e., a high first REM period value followed by a significant decrease in value for the second REM period and constancy for the remainder o f the night. In summary, their findings indicate a high phasic REM pressure persisting throughout the night in contrast to our results of a rapid dissipation of phasic REM pressure during the first REM period. Finally, investigations are currently under way to replicate these results in another group of depressed patients, as well as to investigate treatment (tricyclic antidepressant) drug levels and patterning of REM frequency and other REM variables. Since it is well known that tricyclic antidepressant drug treatment tends to suppress REM sleep, and since there is recent evidence that challenge doses of amitriptyline cause immediate changes in REM (REM latency, time and activity) sleep which may prove to be predictive of drug response, the use of the REM analyzer is important in obtaining a better understanding of these phenomena.
Summary REM sleep in 35 inpatients with primary depression was automatically analyzed for 7 consecutive nights during placebo administration. For the total night of sleep, as well as each individual REM period, the number of REMs, their total voltage integral over time, the sum of their durations and the average REM size were automatically calculated. Validity of these automated REM measures was established by significant correlations with manually scored REM measures. Changes in REM sleep across the night were also investigated. Similar to findings in normal subjects, REM time did not change from REM period to REM period. Average REM size increased significantly from REM period 2--3 and 3--4. Contrary to what is seen in normal subjects, REM frequency was high during the first REM period, significantly decreased from the first to second REM period and then remained constant. Finally, a significant inverse correlation between REM frequency for the first REM period and REM latency was noted. This pattern of REM sleep is interpreted as indicating a high pressure for phasic REM at the beginning of the night which is dissipated by the first REM period.
Rdsumd S o m m e i l R E M au cours de depressions primaires: analyse par o r d i n a l e u r
Le sommeil REM a dtd analysd de faqon automatique chez 35 patients internals pour d4pression prim-
REM SLEEP IN PRIMARY DEPRESSION
517 k
aire et examinds pendant 7 nuits cons~cutives avec administration de placebo. Pour le sommeil total de nuit et pour chaque pdriode individuelle de sommeil REM, le hombre de mouvements oculaires rapides (REMs), leur voltage total int~gr~ au cours du temps, la somme de leur durde et leur amplitude moyenne ont dt4 calculds automatiquement. La validit~ de ces mesures automatiques a dtd dtablie par des relations significatives avec les mesures de REMs scor~s manuellement. Les modifications du sommeil REM d'une nuit ~ l'autre ont dtd dgalement ~tudi~es. De m ~ m e que chez les sujets normaux, le temps de R E M s ne change pas d'une pdriode R E M ~ l'autre, l'amplitude m o y e n n e des R E M s augmente significativement de la 2dine pdriode R E M ~ la 3dine et de la 3dme ~tla 4dine. Contrairement fice qui s'observe chez le sujet normal, la fr4quence des R E M s est dlevde au cours de la premidre pdriode de sommeil R E M , diminue de fa
513
© Elsevier/North-Holland Scientific Publishers Ltd.
Clinical note REM SLEEP IN PRIMARY
DEPRESSION:
A COMPUTERIZED
ANALYSIS*
RICHARD J. McPARTLAND, DAVID J. KUPFER, PATRICIA COBLE, DUANE SPIKER and GARY MATTHEWS
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Penn. (U.S.A.) (Accepted for publication: August 10, 1977)
EEG sleep research in affective states has yielded a number of significant findings linking rapid eye movement (REM) sleep changes to nosologic schema For depressive subtypes. In particular, primary depression is characterized by a shortened REM tatency (Kupfer and Foster 1972), which may be indicative of the level of severity (Spiker et al. 1977). Furthermore, baseline REM measures may help to ~4iscriminate between psychotic and non-psychotic depressive subtypes (Kupfer et al. 1977a) and may relate to eventual clinical drug response (Kupfer et al. 1977b). Preliminary findings on children indicate Lhat specific REM abnormalities, similar to those shown by adult depressives, are also characteristic of Childhood depression (Coble et al. 1977). It has also been hypothesized that some unknown stimulus of REM sleep is a naturally occurring endogenous antidepressant; consequently, by increasing REM pressure, whether experimentally or by drug, clinical improvements can be achieved (Vogel et al. 1977). All of these studies support the hypothesis that alterations of REM sleep in depression are prominent and of pronounced clinical and theoretical importance. To date, these findings have been achieved by using manual techniques for scoring REM sleep time and quantitating REM activity. Since manual REM scoring ignores much of the information contained in electrooculographic recordings, automated REM analysis should be used to obtain a more complete understanding of REM sleep and its relation to clinical states. This report uses the automated REM analyzer to investigate, in patients with primary depression, inter-REM period changes along 3 orthogonal dimensions; REM size, REM frequency and REM~ time. Method The EEG sleep of thirty-five depressed inpatients * This research was supported in part by research grant MH 24652 from the National Institute of Mental Health.
who were admitted to the Clinical Research Unit (22 females and 13 males) and had a mean age of 43.5 years _+ 2.5 S.E. was studied for 7 consecutive nights. Diagnosis was determined on the basis of the Research Diagnostic Criteria (RDC), and all patients met the criteria for majordepressive disorder, primary type. All patients were drug-free for a minimum of 14 days prior to the study, and received placebo during the seven study nights. All night Ac recordings of both left and right monocular eleetrooculogram (EOG) potentials were made using a frequency modulated magnetic tape recorder. For the purpose of automated REM analysis, each REM period's EOG potentials were replayed, at 16 times real time, to the REM analyzer. In brief, the REM analyzer is a software routine implemented on a PDP-11 minicomputer to detect REM waveforms and measure their characteristics. A REM is detected when there are simultaneous (within 115 msec) threshold crossings of opposite polarity by the two EOG potentials. Each EOG biopotential has two thresholds set at + 25 pV. After recogmzing a REM waveform, its voltage integral over time, duration and time of occurrence are measured. Subsequent to a night's REM analysis, composite parameters for each REM period are calculated. They are: the number of REMs occurring (C), their total voltage integral over time (I), the sum of their durations (D), and the average REM size (I/C). Each night's REM latency (RL, time asleep until the onset of the first REM period) and each REM period's REM time (RT) and REM activity (RA, a 9 point scale for rating intensity of REMs during a REM period) were calculated using manual methods (Rechtschaffen and Kales 1968). In addition, hybrid REM period measures of REM frequency (C/RT) and REM % phasic activity (D/RT) were calculated. For each patient, mean (average of 7 nights) REM period and whole night measures were determined. Because fewer than half of the study nights contained 5 or more REM periods, only the first 4 REM periods for each night were considered individually.
514
R.J. M C P A R T L A N D ET AL.
TABLE I Correlations b e t w e e n a u t o m a t e d and manual REM measures indicating validity o f a u t o m a t e d REM analysis.
A u t o m a t e d R e i n Measures Manual REM measures
REM time (RT) REM activity (RA) REM density (RA/RT)
Number of REMs (C)
Average REM size (I/C)
REM duration sum (D)
REM frequency (C/RT)
REM % phasic activity (D/RT)
0.64 c
0.10
0.54 c
-0.01
0.03
0.91 c
0.39 a
0.88 c
0.05 b
0.56 c
0.62 c
0.47 b
0.65 c
0.80 c
0.81 c
a p < 0.05. b p < 0.01. c p < 0.001.
Results Validity o f t h e REM analyzer was investigated by correlating total n i g h t a u t o m a t e d and h y b r i d REM p a r a m e t e r s w i t h m a n u a l l y s c o r e d REM variables. The results are t a b u l a t e d in Table I. The m a n u a l l y derived REM d e n s i t y measure ( R A / R T ) c o r r e l a t e s significantly w i t h t h e a u t o m a t e d d e n s i t y m e a s u r e s o f REM f r e q u e n c y (r = 0.80, P < 0.001) and % phasic activity (r = 0.81, P < 0.001). Manual REM activity correlates significantly w i t h the n u m b e r o f R E M s (r = 0.91, P < 0.01) and t h e i r d u r a t i o n s u m (r = 0.88, P < 0.001). Since REM activity is b y d e f i n i t i o n p r o p o r t i o n a l to the n u m b e r o f REMs and their total
d u r a t i o n , this is an e x p e c t e d result. Manual REM time and a u t o m a t e d REM c o u n t are also significantly c o r r e l a t e d (r = 0.64, P < 0.001) reflecting REM t i m e as a t o n i c p e r i o d in w h i c h phasic R E M s occur. Of the t h r e e intuitively i n d e p e n d e n t a u t o m a t e d measures w h i c h r e p r e s e n t t h r e e basic aspects o f REM p e r i o d s , REM f r e q u e n c y , t i m e and size, c o r r e l a t i o n s o f average nightly and REM p e r i o d d a t a s h o w e d REM freq u e n c y and size t o be f u n c t i o n a l l y r e l a t e d (r = 0.38, P < 0.01). Table II lists average values (± S.E.) for t o t a l night and individual REM period measures. Changes across t h e night for each REM p e r i o d d a t a are s h o w n in Fig. 1. Average REM size increased by a significant
T A B L E II Average REM period m e a s u r e s derived f r o m 7 nights o f sleep f r o m e a c h o f 35 p r i m a r y d e p r e s s e d h o s p i t a l i z e d patients. Total n i g h t RT, C and I are s u m s over all R E M periods. Total n i g h t I/C is an average across all R E M s and t o t a l night C / R T is t h e ratio o f total n i g h t C and RT.
REM period
Average REM size (I/C)
REM f r e q u e n c y (C/RT)
REM t i m e (RT)
Number of REMs (C)
REM integral (I)
1 2 3 4 Total n i g h t
10.4 10.2 11.1 12.0 11.6
10.1 8.2 8.0 8.7 9.0
21.3 19.6 22.6 22.1 70.0
209.8 162.8 186.5 201.8 617.7
2639 2055 2425 2729 7939
+ ± ± ± ±
0.6 0.6 0.7 0.9 0.6
± ± ± ± ±
1.1 0.8 0.8 0.9 0.8
± ± ± ± ±
2.5 1.4 1.7 1.7 4.7
± 33.7 ± 19.0 ± 23 -+ 25.3 ± 67.5
+- 511 ± 295 ± 387 ± 517 ± 1101
REM SLEEP IN PRIMARY DEPRESSION
515
12 AVERAGE (I/C)
(~v-sec per REM) I0 I0 ~ REM FREQUENCY 9 ~ (C/RT) (#/min) 8--
25 23 REM TIME
21
(min)
19
(T)
17 I
I
I
2
3
4
REM PERIOD * p< 0.05
* * p< 0.01
Fig. 1. Average orthogonal automated REM period measures vs. the rank of the REM period derived from 7 nights of sleep from each of 35 primary depressed hospitalized patients.
degree from REM periods 2--3 and 3--4 with REM size being significantly greater at the end of the night (REMP4) than at the beginning (REMP1). The opposite is true for REM frequency, which decreased significantly from RLM periods 1--2 and then remained constant. REM time remains relatively constant across REM periods. The global parameters, REM count (C) and integral sum (I), do not vary significantly from REM period to REM period. Correlations of REM latency with automated measures showed a significant correlation with REM frequency only for the first REM period (r = 0.35, P < 0.05).
Discussion This report represents a clinical application of a new software version of the REM analyzer to investigate characteristics of REM sleep in depression. This REM analyzer is unique in its ability to measure fundamental orthogonal characteristics of REM sleep, i.e., REM time, REM frequency and REM size.
Additionally, global variables of REM count (REM time times frequency) and total REM area (REM time times frequency times size) are produced. Validity of this software version is established, as it was earlier for the hardwired model (McPartland et al. 1971, 1974), by high correlations of automated and visually derived REM density measures, of both automated REM count and duration sum, to manually scored REM activity and of REM count to REM time. REM sleep periods can be characterized by the three conceptually independent parameters: REM time, a tonic measure; REM frequency and REM size, both phasic characteristics. Depressed patients have REM sleep period times comparable to normal subjects, and in the depressives, as with normals, REM time does not significantly change across REM periods (Williams et al. 1974). In normals, phasic REM frequency has been shown to increase in each succeeding REM period throughout the night (Aserinsky 1973; Thomas et al. 1970; Benoit et al. 1974). However, in our depressed group the highest phasic REM
516 frequency occurred during the first REM period and was significantly reduced in later REM periods. This high initial REM frequency and short REM latency (Kupfer and Foster 1972) characteristic of depression suggests that depressives have a high phasic REM pressure at sleep onset which is rapidly dissipated by the first REM period leading to lower values of REM frequency and normal REM cycle lengths. That severity of depression is correlated to initial phasic REM pressure is supported by the correlations of REM latency to severity of depression and to the REM frequency of the first REM period. Further studies of these relationships are being conducted in an investigation relating REM measures to drug treatment response. If it were not for the first REM period, REM size would be monotonically increasing across REM periods. The size of the REMs during the first REM period may have been abnormally heightened due to the high initial phasic REM pressure. Apart from the first REM period, REM size-REM period changes may be similar in depressed and normal subjects. Further studies are needed to ascertain patterns of REM size in normals and to establish age dependent norms for both REM size and frequency. REM sleep time is the remaining basic REM measure which, although intensively studied in normals is still controversial with respect to patterning across REM periods. Some studies report an increase in REM time with the rank of the REM period (Aserinsky 1968; Benoit 1974; Dement 1964) while others report consistency of REM time with rank (Williams 1974). Besides the intrinsic value of understanding the mechanisms of sleep, these norms must be established in order to serve as a basis of comparison for clinical sleep data acquired from many diverse but sleep related disorders. Vogel and coworkers also have reported on REM measures manifested by drug-free depressives (Vogel 1977). The measure of REM frequency (the number of 3 sec epochs of REM sleep with at least one REM, divided by the total number o f 3 sec epochs of REM sleep) used in their studies showed constant values across REM periods. Although not in agreement with the patterning o f REM frequency reported here, the REM frequency in Vogel's depressed group was significantly elevated in comparison with control subjects.* What Vogel calls REM frequency may better be described as an approximation of % phasic REM activity, i.e., the ratio of time spent asleep in phasic REM sleep to total REM sleep time. The more exact measure of % phasic activity, which was readily available with our computer analysis program, in-
This work was presented at a symposium on sleep and REM sleep deprivation at the Annual Meeting of the Association for the Psychophysiological Study of Sleep, Houston, Texas, April, 1977.
R.J. MCPARTLAND ET,AL. dicated that in our depressed sample the patterning across REM periods of % phasic activity resembled that for REM frequency, i.e., a high first REM period value followed by a significant decrease in value for the second REM period and constancy for the remainder o f the night. In summary, their findings indicate a high phasic REM pressure persisting throughout the night in contrast to our results of a rapid dissipation of phasic REM pressure during the first REM period. Finally, investigations are currently under way to replicate these results in another group of depressed patients, as well as to investigate treatment (tricyclic antidepressant) drug levels and patterning of REM frequency and other REM variables. Since it is well known that tricyclic antidepressant drug treatment tends to suppress REM sleep, and since there is recent evidence that challenge doses of amitriptyline cause immediate changes in REM (REM latency, time and activity) sleep which may prove to be predictive of drug response, the use of the REM analyzer is important in obtaining a better understanding of these phenomena.
Summary REM sleep in 35 inpatients with primary depression was automatically analyzed for 7 consecutive nights during placebo administration. For the total night of sleep, as well as each individual REM period, the number of REMs, their total voltage integral over time, the sum of their durations and the average REM size were automatically calculated. Validity of these automated REM measures was established by significant correlations with manually scored REM measures. Changes in REM sleep across the night were also investigated. Similar to findings in normal subjects, REM time did not change from REM period to REM period. Average REM size increased significantly from REM period 2--3 and 3--4. Contrary to what is seen in normal subjects, REM frequency was high during the first REM period, significantly decreased from the first to second REM period and then remained constant. Finally, a significant inverse correlation between REM frequency for the first REM period and REM latency was noted. This pattern of REM sleep is interpreted as indicating a high pressure for phasic REM at the beginning of the night which is dissipated by the first REM period.
Rdsumd S o m m e i l R E M au cours de depressions primaires: analyse par o r d i n a l e u r
Le sommeil REM a dtd analysd de faqon automatique chez 35 patients internals pour d4pression prim-
REM SLEEP IN PRIMARY DEPRESSION
517 k
aire et examinds pendant 7 nuits cons~cutives avec administration de placebo. Pour le sommeil total de nuit et pour chaque pdriode individuelle de sommeil REM, le hombre de mouvements oculaires rapides (REMs), leur voltage total int~gr~ au cours du temps, la somme de leur durde et leur amplitude moyenne ont dt4 calculds automatiquement. La validit~ de ces mesures automatiques a dtd dtablie par des relations significatives avec les mesures de REMs scor~s manuellement. Les modifications du sommeil REM d'une nuit ~ l'autre ont dtd dgalement ~tudi~es. De m ~ m e que chez les sujets normaux, le temps de R E M s ne change pas d'une pdriode R E M ~ l'autre, l'amplitude m o y e n n e des R E M s augmente significativement de la 2dine pdriode R E M ~ la 3dine et de la 3dme ~tla 4dine. Contrairement fice qui s'observe chez le sujet normal, la fr4quence des R E M s est dlevde au cours de la premidre pdriode de sommeil R E M , diminue de fa
