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Sleep parameters in bipolar I, bipolar II, and unipolar depressions
Sleep Parameters in Bipolar I, Bipolar II, and Unipolar Depressions Donna E. Giles, A. John Rush, and Howard P. Roffwarg
Introduction Dunner et al. (1970) introduced the term “bipolar 11” disorder to designate patients with major depressive and hypomanic episodes. Subsequent research has provided support for the continued clinical discrimination of these subtypes. Endicott et al. ( 1985) compared multiple clinical features of bipolar 11 disorder with bipolar 1 and unipolar depression. Age of onset, suicide attempts, childhood hyperactivity (males), and familial aggregation of bipolar disorder were equivalent between the two bipolar subtypes. Bipolar I1 disorder was similar to unipolar depression in chronicity of affective symptoms. proportion with primary depression. and prevalence of concurrent personality disorders. Compared to both bipolar I and unipolar disorders, bipolar 11 disorder was associated more often with alcoholism, antisocial personality disorder, premenstrual syndrome in the index patient. as well as with phobic and obsessivecompulsive disorders in first-degree relatives. The polysomnogram of unipolar depression has been extensively investigated [see Kupfer and Thase (1983) for a review]; less is known about sleep parameters in bipolar depression. From the Affective Disorders Unit. Department of Psychiatry, Urw versity of Texas Health Science Center at Dallas. Dallas. TX. Supported in part by NIMH Grant MH-3S370 K4.J.R.) and the Upjohn Company Presented in pan at the annual meeting of the Soarty ot Biological Psychiatry, Toronto, Canada, May 1982. Address reprint requests to Dr. Donna E. Gilea. Department 01 Psychiatry, Affective Disorders Unit, University of Texas Health Science Center at Dallas. 5323 Harry Hines Blvd , Dallas, TX 75235. Received Apnl 5. 1986. revised June 3, 1986
0 1986 Swiety of Biolopul
Paychlatry
Bipolar patients have been reported to have greater rapid eye movement (REM) fragmentation (Duncan et al. 1979) and reduced REM latency (Gillin et al. 1975) compared to normals. Whether these patients were bipolar 1 or 11 is unclear. Bipolar II patients were reported to have lower sleep efficiency than bipolar 1 patients and were similar to unipolar subjects (Chemik and Mendels 1974). Diagnosis of bipolar 11 disorder has lower interrater reliability than other categories (Spitzer et al. 1978). Polysomnographic measures may contribute to the discriminability among unipolar, bipolar I, and bipolar II patients, with the benefit of improved diagnosis and treatment selection. This study compared polysomnographic findings in bipolar 1, bipolar 11, and unipolar depressed patients. As it is unclear whether bipolar and unipolar depressions are pathophysiologitally distinct, no specific hypotheses regarding the polysomnographic variables are proposed.
Methods Consecutive bipolar I (n = 10) and bipolar II (n = 12) depressed subjects were matched by age, 17-item Hamilton Rating Scale (HRS-D) scores (Hamilton 1960), and sex with unipolar endogenous depressed patients (n = 22). Subjects were required to have been medicationfree for a minimum of 14 days. All subjects were diagnosed by Research Diagnostic Criteria (RDC) (Spitzer et al. 1978) using the Schedule for Affective Disorders and Schizophrenia-Life-
lltK)h-3223/86/$03,io
1341
BIOL PSYCHIATRY 1986:21:134&1343
Brief Reports
Table 1. Clinical and Descriptive Findings Female
Hypersomnia
Age
(%)
HRS-D
Number of episodes
Episode length (range, months)
Bipolar I
32.0 k 10.0
50
25.9 + 5.2
7.6 2 6.7
30.8 2 11.3
50
26.3 k 4.3
1.6 2 0.7
comparison (n = IO) Bipolar II
5.0 (0.5-12) 17.6 (1.5-120)
30
(n = 10) Unipolar
38.4 t
11.2
17
22.1 2 5.0
5.9 k 6.0
37.3 r
12.9
17
24.4 ‘- 4.8
2.0 + 1.2
6.5 (I-17) 11.7 (0.5-60)
17
(n = 12) Unipolar
Groups
comparison (n = 12)
Time Version (SADS-L) (Endicott and Spitzer 1978). Endogenous depressions were “definite” endogenous . Polysomnograph (PSG) recordings were scored according to criteria of Rechtschaffen and Kales (1968). The mean of two consecutive recording nights for each variable was used for data analysis. Parameters evaluated included: (1) REM measures: REM latency, REM density,’ total REM time. (2) Continuity measures: sleep latency, total time in bed, total sleep time, Stages l-4 time (%), number of arousals, total REM time. REM latency is defined as the number of minutes between sleep onset and the first halfminute epoch of REM sleep. Sleep onset is defined as any half-minute of polygraphic sleep leading the first lo-min period of sleep, with no more than 2 min of awake or movement time. Although not uniformly used (Knowles et al. 1982), this definition has provided maximum discrimination of endogenous from nonendogenous depression in our laboratory (unpublished data).
Results Table 1 presents age, sex, HRS-D scores, and clinical features for this sample. Student’s r-tests were used to compare groups unless otherwise indicated. Subjects in the matched comparison ‘Only the first three REM periods were used because of the rapid decrement in number of REM periods after REM Period 3.
(%)
0
0
groups [bipolar I versus unipolar (Group I); bipolar II versus unipolar (Group II)] were equivalent in age (p < 0.80 for both groups) and HRS-D scores (p < 0.31 for both groups). Both bipolar groups reported more episodes of affective disorder than their unipolar comparison groups (Group I: Welch’s t = 2.7, df = 8.2, p < 0.03; Group II: Welch’s t = 2.1, df = 10.7,~ < 0.057). Bipolar I and II groups were similar in number of episodes (p = 0.57) and current episode length (p = 0.45). Report of hypersomnia was the same in both bipolar groups (Fisher’s exact test: p -=c0. I I). None of the unipolars reported hypersomnia. Table 2 presents data on the polysomnographic parameters. The bipolar II group had significantly higher REM latency (t = -2.1, df = 22, p < 0.05) and greater total sleep time (Welch’s t = -2.2, df = 16.6, p < 0.04) than their matched unipolar group; total non-REM time accounted for the increased sleep time (Welch’s t = -2.3, df = 16.0, p < 0.04). Organization of sleep, as reflected in percent time in each sleep stage, did not discriminate among the groups. No PSG measure, including REM latency, discriminated bipolar I and II patients. The bipolar I and unipolar endogenous groups did not differ on any PSG measure.
Discussion Bipolar II depressed patients were similar to bipolar I patients on all polysomnographic mea-
Table 7. Comparison
of Selected Polyholnnographic
Finding\
REM latency REM density 7 3 Total REM time Total in bed time Total sleep time Sleep efficiency(%) Total non-REM time Stages (%J
I 7 3 4 Arousals
16.1 47.x 7.0 13.2 3.0
-c t2 i 2
15.4 14.0 5 I 12.4 3.1
12.7 42.6 6.4 16.9 4.6
sures and differed in this sample from their age-, sex-, and severity-matched unipolar endogenous depressed controls. Bipolar II patients had more hypersomnia, higher REM latencies. and more non-REM time. Our findings differ from those of Gillin et al. ( 1979), who found lower REM latencies in the bipolar group. It may be that the unipolar depressed subjects of their investigation were more heterogeneous (i.e., endogenous and nonendogenous) or that their severity covered a broader range of the spectrum. Both severity and type of unipolar depression have contributed to polysomnographic differences (Rush et al. 1982) and were controlled in this study. Hypersomnia was found in both bipolar groups, although the incidence was not statistically different from the unipolars. Three bipolar I patients endorsed hypersomnia, whereas two bipolar II patients reported hypersomnia interspersed with insomnia. Consistent with other reports (Mendels and Chernik 1972; Chemik and Mendels 1974; Gillin et al. 1973, total sleep time was higher in the bipolar II than in the unipolar group. Clinically, our sample is representative of patients presenting with bipolar depression, inasmuch as they report mul-
? -e I+ i t_
-
4.1 9.3 4.0 12.1 2.1
12.9 53.3 6.4 6.0
f + t +
4.8 9 I 3.x 8.7
5.6 Ifr 5.3
15.6 + 7 :: 48.1 t lb.4 6.5 z!z 5 3 8.5 c
1O.l
5.6 + 3.5
._
tiple and relatively short episodes with some hypersomnia, but possibly less than is typically seen. These data provide some support to the nosological comparability of bipolar I and II depressions and suggest that the sleep physiology of bipolar II disorder is somewhat different from that of unipolar endogenous depression when age and severity are controlled. Complicating this interpretation, however, is the finding that the bipolar 1 group was similar to both its unipolar control and the bipolar II group. Perhaps there is a common pathophysiology, at least as expressed via polysomnographic variables. The complexity of these findings underlines the necessity of carefully controlled studies to evaluate the pathological processes implicated in affective disorders.
The authors wish to express their appreciation to David Savage, Marie Marks, and Anita Roman for their secretarial support; to George Carpenter, M.A., Roger Martinez, B.A and Dan Shea, B.A.. who provided technical assistance in the polysomnographic studies; to Kenneth Z. Altshuler, M.D.. Stanton Sharp Professor and Chairman. who provided administrative support; and to the anonymous reviewers for their clarifying comments. --
Brief Reports
References Chemik DA, Mendels J (1974): Sleep in bipolar and unipolar depressed patients. Sleep Res 3: 123. Duncan WC Jr, Pettigrew KD, Gillin JC (1979): REM architecture changes in bipolar and unipolar depression. Am J Psychiatry 136:1424-1427. Dunner DL, Gershon ES, Goodwin FK (1970): Heritable factors in the severity of affective disorders. Sci Proc Am Psychiatr Assoc 123: 187-188. Endicott J, Spitzer RL (1978): A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia-Life-Time Version. Arch Gen Psychiatry 35:837-844. Endicott J, Nee J, Andreason N, Clayton PJ, Keller M, Coryell W (1985): Bipolar II: Combine or keep separate? J Affect Dis 8: 17-28. Foster FG, Kupfer DJ, Coble P, McPartland RJ ( 1976): Rapid eye movement sleep density. An objective indicator in severe medical-depressive syndromes. Arch Gen Psychiutr?, 33:1119-l 123. Gillin JC, Bunney WE Jr, Buchbinder R (1975): Sleep changes in unipolar and bipolar depressed patients as compared with normals. Presented at the Second International Sleep Research Congress and 15th Annual Meeting of the Association for the Psychophysiological Study of Sleep, Edinburgh, Scotland. Gillin JC, Duncan W, Pettigrew KD, Frankel BL, Snyder F (1979): Successful separation of depressed, normal and insomniac subjects by EEG sleep data. Arch Gen Psychiatry 36:85-90.
BIOL PSYCHIATRY 1986:21:1340-1343
1343
Hamilton M (1960): A rating scale for depression. Neural Neurosurg Psychiatry 12~56-62.
J
Knowles JB, MacLean AW, Cairns J (1982): Definitions of REM latency: Some comparisons with particular reference to depression. Biol Psychiatry 17:993-1002. Kupfer DJ, Foster FG, Cable P, McPartland RJ, Ulrich RF (1978): The application of EEG sleep for the differential diagnosis of affective disorders. Am J Psychiutv 135169-74. Kupfer DJ, Thase ME (1983): The use of the sleep laboratory in the diagnosis of affective disorders. Psychiutr Clin North Am 6:3. Mendels J, Chemik DA (1972): Sleep of manic-depressives and recurrent depressives. Sleep Res 1:142. Rechtschaffen A, Kales A (I 968): A Manual of Stundurdized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. National Institute of Health Publication 204. Washington, DC: US Government Printing Office. Rush AJ, Giles DE, Roffwarg HP, Parker CR (1982): Sleep EEG and Dexamethasone Suppression Test findings in outpatients with unipolar major depressive disorders. Biol Psychiatry 17:327-341. Spitzer RL, Endicott J, Robins E (1978): Research Diagnostic Criteria: Rationale and reliability. Arch Gen Psychiatry 36:773-782.
Introduction Dunner et al. (1970) introduced the term “bipolar 11” disorder to designate patients with major depressive and hypomanic episodes. Subsequent research has provided support for the continued clinical discrimination of these subtypes. Endicott et al. ( 1985) compared multiple clinical features of bipolar 11 disorder with bipolar 1 and unipolar depression. Age of onset, suicide attempts, childhood hyperactivity (males), and familial aggregation of bipolar disorder were equivalent between the two bipolar subtypes. Bipolar I1 disorder was similar to unipolar depression in chronicity of affective symptoms. proportion with primary depression. and prevalence of concurrent personality disorders. Compared to both bipolar I and unipolar disorders, bipolar 11 disorder was associated more often with alcoholism, antisocial personality disorder, premenstrual syndrome in the index patient. as well as with phobic and obsessivecompulsive disorders in first-degree relatives. The polysomnogram of unipolar depression has been extensively investigated [see Kupfer and Thase (1983) for a review]; less is known about sleep parameters in bipolar depression. From the Affective Disorders Unit. Department of Psychiatry, Urw versity of Texas Health Science Center at Dallas. Dallas. TX. Supported in part by NIMH Grant MH-3S370 K4.J.R.) and the Upjohn Company Presented in pan at the annual meeting of the Soarty ot Biological Psychiatry, Toronto, Canada, May 1982. Address reprint requests to Dr. Donna E. Gilea. Department 01 Psychiatry, Affective Disorders Unit, University of Texas Health Science Center at Dallas. 5323 Harry Hines Blvd , Dallas, TX 75235. Received Apnl 5. 1986. revised June 3, 1986
0 1986 Swiety of Biolopul
Paychlatry
Bipolar patients have been reported to have greater rapid eye movement (REM) fragmentation (Duncan et al. 1979) and reduced REM latency (Gillin et al. 1975) compared to normals. Whether these patients were bipolar 1 or 11 is unclear. Bipolar II patients were reported to have lower sleep efficiency than bipolar 1 patients and were similar to unipolar subjects (Chemik and Mendels 1974). Diagnosis of bipolar 11 disorder has lower interrater reliability than other categories (Spitzer et al. 1978). Polysomnographic measures may contribute to the discriminability among unipolar, bipolar I, and bipolar II patients, with the benefit of improved diagnosis and treatment selection. This study compared polysomnographic findings in bipolar 1, bipolar 11, and unipolar depressed patients. As it is unclear whether bipolar and unipolar depressions are pathophysiologitally distinct, no specific hypotheses regarding the polysomnographic variables are proposed.
Methods Consecutive bipolar I (n = 10) and bipolar II (n = 12) depressed subjects were matched by age, 17-item Hamilton Rating Scale (HRS-D) scores (Hamilton 1960), and sex with unipolar endogenous depressed patients (n = 22). Subjects were required to have been medicationfree for a minimum of 14 days. All subjects were diagnosed by Research Diagnostic Criteria (RDC) (Spitzer et al. 1978) using the Schedule for Affective Disorders and Schizophrenia-Life-
lltK)h-3223/86/$03,io
1341
BIOL PSYCHIATRY 1986:21:134&1343
Brief Reports
Table 1. Clinical and Descriptive Findings Female
Hypersomnia
Age
(%)
HRS-D
Number of episodes
Episode length (range, months)
Bipolar I
32.0 k 10.0
50
25.9 + 5.2
7.6 2 6.7
30.8 2 11.3
50
26.3 k 4.3
1.6 2 0.7
comparison (n = IO) Bipolar II
5.0 (0.5-12) 17.6 (1.5-120)
30
(n = 10) Unipolar
38.4 t
11.2
17
22.1 2 5.0
5.9 k 6.0
37.3 r
12.9
17
24.4 ‘- 4.8
2.0 + 1.2
6.5 (I-17) 11.7 (0.5-60)
17
(n = 12) Unipolar
Groups
comparison (n = 12)
Time Version (SADS-L) (Endicott and Spitzer 1978). Endogenous depressions were “definite” endogenous . Polysomnograph (PSG) recordings were scored according to criteria of Rechtschaffen and Kales (1968). The mean of two consecutive recording nights for each variable was used for data analysis. Parameters evaluated included: (1) REM measures: REM latency, REM density,’ total REM time. (2) Continuity measures: sleep latency, total time in bed, total sleep time, Stages l-4 time (%), number of arousals, total REM time. REM latency is defined as the number of minutes between sleep onset and the first halfminute epoch of REM sleep. Sleep onset is defined as any half-minute of polygraphic sleep leading the first lo-min period of sleep, with no more than 2 min of awake or movement time. Although not uniformly used (Knowles et al. 1982), this definition has provided maximum discrimination of endogenous from nonendogenous depression in our laboratory (unpublished data).
Results Table 1 presents age, sex, HRS-D scores, and clinical features for this sample. Student’s r-tests were used to compare groups unless otherwise indicated. Subjects in the matched comparison ‘Only the first three REM periods were used because of the rapid decrement in number of REM periods after REM Period 3.
(%)
0
0
groups [bipolar I versus unipolar (Group I); bipolar II versus unipolar (Group II)] were equivalent in age (p < 0.80 for both groups) and HRS-D scores (p < 0.31 for both groups). Both bipolar groups reported more episodes of affective disorder than their unipolar comparison groups (Group I: Welch’s t = 2.7, df = 8.2, p < 0.03; Group II: Welch’s t = 2.1, df = 10.7,~ < 0.057). Bipolar I and II groups were similar in number of episodes (p = 0.57) and current episode length (p = 0.45). Report of hypersomnia was the same in both bipolar groups (Fisher’s exact test: p -=c0. I I). None of the unipolars reported hypersomnia. Table 2 presents data on the polysomnographic parameters. The bipolar II group had significantly higher REM latency (t = -2.1, df = 22, p < 0.05) and greater total sleep time (Welch’s t = -2.2, df = 16.6, p < 0.04) than their matched unipolar group; total non-REM time accounted for the increased sleep time (Welch’s t = -2.3, df = 16.0, p < 0.04). Organization of sleep, as reflected in percent time in each sleep stage, did not discriminate among the groups. No PSG measure, including REM latency, discriminated bipolar I and II patients. The bipolar I and unipolar endogenous groups did not differ on any PSG measure.
Discussion Bipolar II depressed patients were similar to bipolar I patients on all polysomnographic mea-
Table 7. Comparison
of Selected Polyholnnographic
Finding\
REM latency REM density 7 3 Total REM time Total in bed time Total sleep time Sleep efficiency(%) Total non-REM time Stages (%J
I 7 3 4 Arousals
16.1 47.x 7.0 13.2 3.0
-c t2 i 2
15.4 14.0 5 I 12.4 3.1
12.7 42.6 6.4 16.9 4.6
sures and differed in this sample from their age-, sex-, and severity-matched unipolar endogenous depressed controls. Bipolar II patients had more hypersomnia, higher REM latencies. and more non-REM time. Our findings differ from those of Gillin et al. ( 1979), who found lower REM latencies in the bipolar group. It may be that the unipolar depressed subjects of their investigation were more heterogeneous (i.e., endogenous and nonendogenous) or that their severity covered a broader range of the spectrum. Both severity and type of unipolar depression have contributed to polysomnographic differences (Rush et al. 1982) and were controlled in this study. Hypersomnia was found in both bipolar groups, although the incidence was not statistically different from the unipolars. Three bipolar I patients endorsed hypersomnia, whereas two bipolar II patients reported hypersomnia interspersed with insomnia. Consistent with other reports (Mendels and Chernik 1972; Chemik and Mendels 1974; Gillin et al. 1973, total sleep time was higher in the bipolar II than in the unipolar group. Clinically, our sample is representative of patients presenting with bipolar depression, inasmuch as they report mul-
? -e I+ i t_
-
4.1 9.3 4.0 12.1 2.1
12.9 53.3 6.4 6.0
f + t +
4.8 9 I 3.x 8.7
5.6 Ifr 5.3
15.6 + 7 :: 48.1 t lb.4 6.5 z!z 5 3 8.5 c
1O.l
5.6 + 3.5
._
tiple and relatively short episodes with some hypersomnia, but possibly less than is typically seen. These data provide some support to the nosological comparability of bipolar I and II depressions and suggest that the sleep physiology of bipolar II disorder is somewhat different from that of unipolar endogenous depression when age and severity are controlled. Complicating this interpretation, however, is the finding that the bipolar 1 group was similar to both its unipolar control and the bipolar II group. Perhaps there is a common pathophysiology, at least as expressed via polysomnographic variables. The complexity of these findings underlines the necessity of carefully controlled studies to evaluate the pathological processes implicated in affective disorders.
The authors wish to express their appreciation to David Savage, Marie Marks, and Anita Roman for their secretarial support; to George Carpenter, M.A., Roger Martinez, B.A and Dan Shea, B.A.. who provided technical assistance in the polysomnographic studies; to Kenneth Z. Altshuler, M.D.. Stanton Sharp Professor and Chairman. who provided administrative support; and to the anonymous reviewers for their clarifying comments. --
Brief Reports
References Chemik DA, Mendels J (1974): Sleep in bipolar and unipolar depressed patients. Sleep Res 3: 123. Duncan WC Jr, Pettigrew KD, Gillin JC (1979): REM architecture changes in bipolar and unipolar depression. Am J Psychiatry 136:1424-1427. Dunner DL, Gershon ES, Goodwin FK (1970): Heritable factors in the severity of affective disorders. Sci Proc Am Psychiatr Assoc 123: 187-188. Endicott J, Spitzer RL (1978): A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia-Life-Time Version. Arch Gen Psychiatry 35:837-844. Endicott J, Nee J, Andreason N, Clayton PJ, Keller M, Coryell W (1985): Bipolar II: Combine or keep separate? J Affect Dis 8: 17-28. Foster FG, Kupfer DJ, Coble P, McPartland RJ ( 1976): Rapid eye movement sleep density. An objective indicator in severe medical-depressive syndromes. Arch Gen Psychiutr?, 33:1119-l 123. Gillin JC, Bunney WE Jr, Buchbinder R (1975): Sleep changes in unipolar and bipolar depressed patients as compared with normals. Presented at the Second International Sleep Research Congress and 15th Annual Meeting of the Association for the Psychophysiological Study of Sleep, Edinburgh, Scotland. Gillin JC, Duncan W, Pettigrew KD, Frankel BL, Snyder F (1979): Successful separation of depressed, normal and insomniac subjects by EEG sleep data. Arch Gen Psychiatry 36:85-90.
BIOL PSYCHIATRY 1986:21:1340-1343
1343
Hamilton M (1960): A rating scale for depression. Neural Neurosurg Psychiatry 12~56-62.
J
Knowles JB, MacLean AW, Cairns J (1982): Definitions of REM latency: Some comparisons with particular reference to depression. Biol Psychiatry 17:993-1002. Kupfer DJ, Foster FG, Cable P, McPartland RJ, Ulrich RF (1978): The application of EEG sleep for the differential diagnosis of affective disorders. Am J Psychiutv 135169-74. Kupfer DJ, Thase ME (1983): The use of the sleep laboratory in the diagnosis of affective disorders. Psychiutr Clin North Am 6:3. Mendels J, Chemik DA (1972): Sleep of manic-depressives and recurrent depressives. Sleep Res 1:142. Rechtschaffen A, Kales A (I 968): A Manual of Stundurdized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. National Institute of Health Publication 204. Washington, DC: US Government Printing Office. Rush AJ, Giles DE, Roffwarg HP, Parker CR (1982): Sleep EEG and Dexamethasone Suppression Test findings in outpatients with unipolar major depressive disorders. Biol Psychiatry 17:327-341. Spitzer RL, Endicott J, Robins E (1978): Research Diagnostic Criteria: Rationale and reliability. Arch Gen Psychiatry 36:773-782.