Psychiatry
265
Research, 36:265-271
Elsevier
Sleep, Depression, and Suicide Erin Sabo, Charles F. Reynolds
III, David J. Kupfer, and Susan R. Berman
Received July 24, 1990; revised version received November 1990.
20, 1990; accepted December 22,
Abstract. In a retrospective study of the electroencephalographic
(EEG) sleep of major depressives with and without a history of suicide attempts, suicide attempters had longer sleep latency, lower sleep efficiency, and fewer late-night delta wave counts than normal controls. Nonattempters, compared to attempters, had less rapid eye movement (REM) time and activity in period 2, but more delta wave counts in non-REM period 4. Although both attempters and nonattempters were like controls in regard to REM period 2, patients with suicide attempts had altered intranight temporal distribution of phasic REM activity, with increased REM activity (by both visual and automated scoring) in REM sleep period 2 (significant group X period interaction). These findings, which may be more traitlike or persistent than state-related, are discussed in the context of current theories on the role of serotonin in the regulation of sleep and in suicidal behavior. Key Words. Sleep, suicide, depression.
During the past decade, there has been increasing interest in psychobiological investigations of suicide. In this context, we performed an exploratory study of the relation between sleep and history of suicidal behavior in patients with major depression. A literature search using Medline uncovered no previous studies. We initially conjectured a relation between sleep and suicide on the basis of data implicating serotonin (5-hydroxytryptamine; 5HT) in sleep and recent work suggesting the involvement of 5HT in impulsive behavior. Methods Subjects. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L: Spitzer et al., 1978) was examined for 1,382 subjects who participated in research protocols funded by the National Institute of Mental Health and conducted in the Sleep Evaluation Center of Western Psychiatric Institute and Clinic since 1974. Subjects were included and considered suicidal if they had both a definite level of intent (score > 3 on the SADS-L item measuring suicidal intent) and a moderate degree of lethality at the time of the intent (score 3 4 on the SADS-L item measuring medical threat) (n = 77; 6.5%). From this reduced sample, subjects were excluded if they had any concurrent or past psychiatric disorder
Erin Sabo, M.D., is a Psychiatric Resident; Charles F. Reynolds III, M.D., is Professor; David J. Kupfer, M.D., is Professor and Chairman; and Susan R. Berman, B.A., is Data Manager, Department of Psychiatry, University of Pittsburgh School of Medicine. (Reprint requests to Dr. C.F. Reynolds 111, 3811 O’Hara St., Pittsburgh, PA Western Psychiatric Institute and Clinic, University of Pittsburgh, 15213-2593, USA.) 0165-17gf/91/$03.50
0 1991 Elsevier Scientific
Publishers
Ireland
Ltd.
266 other than major depressive disorder. Psychotic depressives were not included. (Three of the suicide attempters also qualified for a diagnosis of chronic intermittent depression and one for episodic minor depressive disorder.) This “pure” sample of subjects in a depressive episode with at least one prior suicide attempt (n = 35) was then matched with an equally pure sample (no concurrent or past psychiatric disorder other than major depression) of depressed subjects who had never attempted suicide. The subjects were matched on the following variables: age, sex, Hamilton score, polygraphic low filter setting on the electroencephalographic (EEG) channel, and patient status (inpatient vs. outpatient). (Subjects were not matched on age of illness onset, duration of current episode, or number of prior episodes.) However, groups did not differ in duration of current episode at time of sleep studies, with a median of 29.5 weeks for attempters (n = 18) and 33.0 weeks for nonattempters (n = 14; Z= 0.34, NS). In addition, all but two matched pairs were from the same research protocol. This selective matching process yielded the final sample of 21 subject pairs (Table 1). Twenty of the suicide attempters had a diagnosis of unipolar depression, and one had a history of possible bipolar II disorder. In four of the attempters, medical records were not available for review, and therefore the exact date and number of attempts for these patients could not be determined. Degree of suicidality at the time of the sleep study was determined by item 3 on the Hamilton Rating Scale for Depression (HRSD; Hamilton, 1960) being rated as absent (0), doubtful or trivial (I), mild (2) moderate (3), or severe (4). In depressed patients with a history of suicide attempts, the mean number of attempts was 1.8 (SD = 0.8, n = 17), and the mean number of years from the last attempt to the sleep study was 6.0 (SD = 6.7, median = 3.6, range 6 months to 20 years). The mean rating on HRSD item 3 for the attempters was not significantly different for the attempters vs. the nonattempters (attempters: mean = 1.4, SD = 1.0; nonattempters: mean = 1.1, SD = 1.1; t = 0.88, df= 40, p = NS). The distribution of scores on HRSD item 3 also did not differ significantly between the groups k* = 2.6, df = 3, p = NS). Hence, at the time of sleep evaluation, the two groups did not differ in the HRSD measure of acute suicidal potential. The mean SADS-L rating was 4.29 (SD = 1.06; range 3-6) for seriousness of intent and 4.43 (SD = 0.75; range 4.6) for degree of lethality. Information in medical records available for 17 of the subjects indicated that 13 attempts were by overdose, one by slashed wrists, one by motor vehicle “accident,” and two, unknown. Although we did not personally review the medical records of the nonattempters, it is the practice in our research protocols to base completion of the SADS-L upon the sum of all available information, including review of past psychiatric records. A group of healthy control subjects was also (retrospectively) formed to provide a benchmark for assessing any changes seen in the sleep of the two patient groups. Healthy controls were determined by SADS-L interview to lack a personal history of psychiatric disorder. Physical examination and laboratory tests were used to ascertain the absence of current active medical illness. Controls were matched with patients on the basis of age, sex, and low filter settings used during polysomnography. Procedure. All subjects were free of psychotropic drugs for at least 2 weeks before sleep studies. EEG sleep monitoring was conducted in either private bedrooms at the Sleep Evaluation Center (outpatients) or in private bedrooms on the inpatient units (inpatients). A Grass 78B polygraph was used to record EEG (C3-Al + A2 at 50 pV/cm), electrooculographic (right and left outer canthi), and bipolar submental electromyographic activity. Fourteen matched pairs were recorded at a low filter setting of 1.O, and seven matched pairs were recorded at a low filter setting of 0.3. Technicians who were unaware of patient diagnosis scored sleep in 60-set epochs according to the criteria of Rechtschaffen and Kales (1968). Interrater reliability was maintained at or above 85%. EEG recordings were also analyzed by automated (period/amplitude) delta wave (0.5-3 Hz, 75-250 pV> and rapid eye movement (REM) analysis procedures described elsewhere (Kupfer et al., 1984). Data
Analysis.
Two
overall
analytic
strategies
were used:
(1) an analysis
of variance
267 Table 1. Demographic and clinical descriptors Controls (n=21)
NonAttempters attempters (n=21)
(n = 21)
Mean
SD
Mean
SD
Mean
SD
Age at sleep studies’
39.3
(11.4)
39.3
(11.6)
39.4
(12.3)
Sex (male/female)’
5112
Beck Depression
5112
5112
Inventory 0.68
(n = 19) Hamilton Depression
(1.6)
Rating 22.4
Scale-l 7 item’
(4.8)
22.3
(4.2)
Patient status 1219
(inpatient/outpatient)’
1219
Number of suicide attempts (n=
1.8
17)
(0.8)
0
6.0
(6.7)
NA
3.6
(0.7-
Years since last suicide attempt (n = 17) Median (min-max)
19.7) Endogenous l/5/12
(no/probable/definite)
x2 = 3.77, df = 2, NS
111118
Hamilton question 83 (suicide) 1.4
at time of sleep studies (0, absent/l,
(1.0)
1.1
(1.1)
t = 0.88, df = 40, NS
doubtful or trivial/
2, mild/3, moderateI4,
severe)
515/9l2lO
9/4/5/3/0
x2 = 2.60, df = 3, NS
1. Groups matched on these variables.
(ANOVA) of sleep measures in controls, attempters, and nonattempters, followed by pairwise contrasts using Tukey’s test; and (2) pairwise exploration restricted to attempters vs. nonattempters. In the latter analysis, hand-scored and automated EEG sleep variables were analyzed with an analysis of covariance (ANCOVA) with age as the covariate and patient status (inpatient/outpatient) and attempter status as the main factors. Slow wave sleep variables were also covaried for low filter setting. A repeated measures factor (nonREM/REM cycle) was introduced into the ANCOVA to quantify intranight temporal distribution of delta wave and REM activity. Three additional exploratory analyses were performed: (1) A ~2 analysis of % of each group with a dichotomously defined reduced REM latency (< 60 min); (2) forced discriminant function analysis to determine how well attempters and nonattempters could be separated on the basis of significant univariate contrasts; and (3) correlational analysis to explore the relationship between time from attempt and EEG sleep measures noted to be significantly different between attempters and nonattempters.
Results An ANOVA of sleep measures in all three groups showed that suicide attempters had longer sleep latency, lower sleep efficiency, and fewer late-night delta counts than normals. Secondly, nonattempters, compared to attempters, had less REM time and in period 2, but more delta counts in non-REM period 4 (trend). Both attempters and nonattempters were like the controls in regard to REM period 2. In the two patient groups, we observed that automated REM counts/min showed a activity
268
Fig. 1. Automated REM counts/min by REM period in healthy controls, suicide attempters, and nonattempters
‘1
0 ItI% PERIOD xGROUPI_ F=2R.0F=1l4.6.p
265
Research, 36:265-271
Elsevier
Sleep, Depression, and Suicide Erin Sabo, Charles F. Reynolds
III, David J. Kupfer, and Susan R. Berman
Received July 24, 1990; revised version received November 1990.
20, 1990; accepted December 22,
Abstract. In a retrospective study of the electroencephalographic
(EEG) sleep of major depressives with and without a history of suicide attempts, suicide attempters had longer sleep latency, lower sleep efficiency, and fewer late-night delta wave counts than normal controls. Nonattempters, compared to attempters, had less rapid eye movement (REM) time and activity in period 2, but more delta wave counts in non-REM period 4. Although both attempters and nonattempters were like controls in regard to REM period 2, patients with suicide attempts had altered intranight temporal distribution of phasic REM activity, with increased REM activity (by both visual and automated scoring) in REM sleep period 2 (significant group X period interaction). These findings, which may be more traitlike or persistent than state-related, are discussed in the context of current theories on the role of serotonin in the regulation of sleep and in suicidal behavior. Key Words. Sleep, suicide, depression.
During the past decade, there has been increasing interest in psychobiological investigations of suicide. In this context, we performed an exploratory study of the relation between sleep and history of suicidal behavior in patients with major depression. A literature search using Medline uncovered no previous studies. We initially conjectured a relation between sleep and suicide on the basis of data implicating serotonin (5-hydroxytryptamine; 5HT) in sleep and recent work suggesting the involvement of 5HT in impulsive behavior. Methods Subjects. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L: Spitzer et al., 1978) was examined for 1,382 subjects who participated in research protocols funded by the National Institute of Mental Health and conducted in the Sleep Evaluation Center of Western Psychiatric Institute and Clinic since 1974. Subjects were included and considered suicidal if they had both a definite level of intent (score > 3 on the SADS-L item measuring suicidal intent) and a moderate degree of lethality at the time of the intent (score 3 4 on the SADS-L item measuring medical threat) (n = 77; 6.5%). From this reduced sample, subjects were excluded if they had any concurrent or past psychiatric disorder
Erin Sabo, M.D., is a Psychiatric Resident; Charles F. Reynolds III, M.D., is Professor; David J. Kupfer, M.D., is Professor and Chairman; and Susan R. Berman, B.A., is Data Manager, Department of Psychiatry, University of Pittsburgh School of Medicine. (Reprint requests to Dr. C.F. Reynolds 111, 3811 O’Hara St., Pittsburgh, PA Western Psychiatric Institute and Clinic, University of Pittsburgh, 15213-2593, USA.) 0165-17gf/91/$03.50
0 1991 Elsevier Scientific
Publishers
Ireland
Ltd.
266 other than major depressive disorder. Psychotic depressives were not included. (Three of the suicide attempters also qualified for a diagnosis of chronic intermittent depression and one for episodic minor depressive disorder.) This “pure” sample of subjects in a depressive episode with at least one prior suicide attempt (n = 35) was then matched with an equally pure sample (no concurrent or past psychiatric disorder other than major depression) of depressed subjects who had never attempted suicide. The subjects were matched on the following variables: age, sex, Hamilton score, polygraphic low filter setting on the electroencephalographic (EEG) channel, and patient status (inpatient vs. outpatient). (Subjects were not matched on age of illness onset, duration of current episode, or number of prior episodes.) However, groups did not differ in duration of current episode at time of sleep studies, with a median of 29.5 weeks for attempters (n = 18) and 33.0 weeks for nonattempters (n = 14; Z= 0.34, NS). In addition, all but two matched pairs were from the same research protocol. This selective matching process yielded the final sample of 21 subject pairs (Table 1). Twenty of the suicide attempters had a diagnosis of unipolar depression, and one had a history of possible bipolar II disorder. In four of the attempters, medical records were not available for review, and therefore the exact date and number of attempts for these patients could not be determined. Degree of suicidality at the time of the sleep study was determined by item 3 on the Hamilton Rating Scale for Depression (HRSD; Hamilton, 1960) being rated as absent (0), doubtful or trivial (I), mild (2) moderate (3), or severe (4). In depressed patients with a history of suicide attempts, the mean number of attempts was 1.8 (SD = 0.8, n = 17), and the mean number of years from the last attempt to the sleep study was 6.0 (SD = 6.7, median = 3.6, range 6 months to 20 years). The mean rating on HRSD item 3 for the attempters was not significantly different for the attempters vs. the nonattempters (attempters: mean = 1.4, SD = 1.0; nonattempters: mean = 1.1, SD = 1.1; t = 0.88, df= 40, p = NS). The distribution of scores on HRSD item 3 also did not differ significantly between the groups k* = 2.6, df = 3, p = NS). Hence, at the time of sleep evaluation, the two groups did not differ in the HRSD measure of acute suicidal potential. The mean SADS-L rating was 4.29 (SD = 1.06; range 3-6) for seriousness of intent and 4.43 (SD = 0.75; range 4.6) for degree of lethality. Information in medical records available for 17 of the subjects indicated that 13 attempts were by overdose, one by slashed wrists, one by motor vehicle “accident,” and two, unknown. Although we did not personally review the medical records of the nonattempters, it is the practice in our research protocols to base completion of the SADS-L upon the sum of all available information, including review of past psychiatric records. A group of healthy control subjects was also (retrospectively) formed to provide a benchmark for assessing any changes seen in the sleep of the two patient groups. Healthy controls were determined by SADS-L interview to lack a personal history of psychiatric disorder. Physical examination and laboratory tests were used to ascertain the absence of current active medical illness. Controls were matched with patients on the basis of age, sex, and low filter settings used during polysomnography. Procedure. All subjects were free of psychotropic drugs for at least 2 weeks before sleep studies. EEG sleep monitoring was conducted in either private bedrooms at the Sleep Evaluation Center (outpatients) or in private bedrooms on the inpatient units (inpatients). A Grass 78B polygraph was used to record EEG (C3-Al + A2 at 50 pV/cm), electrooculographic (right and left outer canthi), and bipolar submental electromyographic activity. Fourteen matched pairs were recorded at a low filter setting of 1.O, and seven matched pairs were recorded at a low filter setting of 0.3. Technicians who were unaware of patient diagnosis scored sleep in 60-set epochs according to the criteria of Rechtschaffen and Kales (1968). Interrater reliability was maintained at or above 85%. EEG recordings were also analyzed by automated (period/amplitude) delta wave (0.5-3 Hz, 75-250 pV> and rapid eye movement (REM) analysis procedures described elsewhere (Kupfer et al., 1984). Data
Analysis.
Two
overall
analytic
strategies
were used:
(1) an analysis
of variance
267 Table 1. Demographic and clinical descriptors Controls (n=21)
NonAttempters attempters (n=21)
(n = 21)
Mean
SD
Mean
SD
Mean
SD
Age at sleep studies’
39.3
(11.4)
39.3
(11.6)
39.4
(12.3)
Sex (male/female)’
5112
Beck Depression
5112
5112
Inventory 0.68
(n = 19) Hamilton Depression
(1.6)
Rating 22.4
Scale-l 7 item’
(4.8)
22.3
(4.2)
Patient status 1219
(inpatient/outpatient)’
1219
Number of suicide attempts (n=
1.8
17)
(0.8)
0
6.0
(6.7)
NA
3.6
(0.7-
Years since last suicide attempt (n = 17) Median (min-max)
19.7) Endogenous l/5/12
(no/probable/definite)
x2 = 3.77, df = 2, NS
111118
Hamilton question 83 (suicide) 1.4
at time of sleep studies (0, absent/l,
(1.0)
1.1
(1.1)
t = 0.88, df = 40, NS
doubtful or trivial/
2, mild/3, moderateI4,
severe)
515/9l2lO
9/4/5/3/0
x2 = 2.60, df = 3, NS
1. Groups matched on these variables.
(ANOVA) of sleep measures in controls, attempters, and nonattempters, followed by pairwise contrasts using Tukey’s test; and (2) pairwise exploration restricted to attempters vs. nonattempters. In the latter analysis, hand-scored and automated EEG sleep variables were analyzed with an analysis of covariance (ANCOVA) with age as the covariate and patient status (inpatient/outpatient) and attempter status as the main factors. Slow wave sleep variables were also covaried for low filter setting. A repeated measures factor (nonREM/REM cycle) was introduced into the ANCOVA to quantify intranight temporal distribution of delta wave and REM activity. Three additional exploratory analyses were performed: (1) A ~2 analysis of % of each group with a dichotomously defined reduced REM latency (< 60 min); (2) forced discriminant function analysis to determine how well attempters and nonattempters could be separated on the basis of significant univariate contrasts; and (3) correlational analysis to explore the relationship between time from attempt and EEG sleep measures noted to be significantly different between attempters and nonattempters.
Results An ANOVA of sleep measures in all three groups showed that suicide attempters had longer sleep latency, lower sleep efficiency, and fewer late-night delta counts than normals. Secondly, nonattempters, compared to attempters, had less REM time and in period 2, but more delta counts in non-REM period 4 (trend). Both attempters and nonattempters were like the controls in regard to REM period 2. In the two patient groups, we observed that automated REM counts/min showed a activity
268
Fig. 1. Automated REM counts/min by REM period in healthy controls, suicide attempters, and nonattempters
‘1
0 ItI% PERIOD xGROUPI_ F=2R.0F=1l4.6.p
