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February 1995, Vol 52, No. 2 >
Article | February 1995

In Quest of Identifying Vulnerability Markers for Psychiatric Disorders by All-Night Polysomnography

Christoph J. Lauer, PhD; Wolfgang Schreiber, MD; Florian Holsboer, MD, PhD; Jürgen-Christian Krieg, MD
Arch Gen Psychiatry. 1995;52(2):145-153. doi:10.1001/archpsyc.1995.03950140063009
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Background:  The persistence of a depressionlike sleep pattern in fully remitted depressed patients suggests that the pattern is a trait characteristic of sleep measurements. However, in the past, subjects have undergone investigation only after the onset of the disorder, and, therefore, the altered sleep pattern may merely represent a biological scar.

Methods:  We polysomnographically investigated 54 healthy subjects who had no lifetime or current diagnosis of a psychiatric disorder but had at least one first-degree relative with major depression or a bipolar disorder and at least one further close relative with major depression, a bipolar disorder, or a schizophrenic disorder. Twenty unrelated control probands without a personal and family history of psychiatric disorders and 18 unrelated inpatients with major depression served as reference groups. Prior to investigation, all healthy subjects had been free of any prescription and nonprescription drug for at least 3 months. The depressed patients were free of drugs for at least 1 week. All subjects slept for 2 nights in the sleep research unit. The sleep of the second night was recorded and visually scored.

Results:  Analysis of the individual sleep cycles in these subjects revealed both a reduced amount of slow wave sleep and increased rapid eye movement density in the first sleep cycle. Discriminant analysis showed that 10 subjects (18%) had sleep patterns similar to those of depressed patients.

Conclusions:  According to our observations, one fifth of the healthy subjects with a high genetic load for psychiatric disorders showed a conspicuous (depression-like) sleep pattern. The follow-up will determine whether this sleep pattern indeed represents a trait marker indicating vulnerability.

REFERENCES

1 +
Gillin JC, Sitaram N, Wehr T, Duncan W, Post R, Murphy DL, Mendelson WB, Wyatt RJ, Bunney WE.  Sleep and affective illness . In: Post RM, Ballenger JC, eds. Neurobiology of Mood Disorders . Baltimore, Md: Williams & Wilkins; 1984;:157-189.
2 +
Reynolds CF, Kupfer DJ.  Sleep research in affective illness: state of the art circa 1987 . Sleep . 1987;;10:199-215.
3 +
Lauer CJ, Riemann D, Wiegand M, Berger M.  From early to late adulthood: changes in EEG sleep of depressed patients and healthy volunteers . Biol Psychiatry . 1991;;29:979-993.
4 +
Schulz H.  Sleep in affective disorders: an experimental study in depressed and remitted patients . In: Smirne S, Franceschi M, Ferini-Strambi L, eds. Sleep in Medical and Neuropsychiatric Disorders . New York, NY: Masson Publishing USA Inc; 1988;:75-86.
5 +
Riemann D, Berger M.  EEG sleep in depression and in remission and the REM sleep response to the cholinergic agonist RS-86 . Neuropsychopharmacology . 1989;;2:145-152.
6 +
Rush AJ, Erman MK, Giles DE, Schlesser MA, Carpenter G, Vasavada N, Roffwarg HP.  Polysomnographic findings in recently drug-free and clinically remitted depressed patients . Arch Gen Psychiatry . 1986;;43:878-884.
7 +
Steiger A, von Bardeleben U, Herth T, Holsboer F.  Sleep-EEG and nocturnal secretion of cortisol and human growth hormone in male patients with endogenous depression before treatment and after recovery . J Affect Disord . 1989;;16:189-195.
8 +
Giles DE, Jarrett RB, Roffwarg HP, Rush AJ.  Reduced rapid eye movement latency: a predictor of recurrence in depression . Neuropsychopharmacology . 1987;;1:33-39.
9 +
Sitaram N, Dube S, Keshavan M, Davies A, Reynal P.  The association of supersensitive cholinergic REM-induction and affective illness within pedigrees . J Psychiatry Res . 1987;;21:487-497.
10 +
Giles DE, Kupfer DJ, Roffwarg HP, Rush AJ, Biggs MM, Etzel BA.  Polysomnographic parameters in first-degree relatives of unipolar probands . Psychiatry Res . 1989;;27:127-136.
11 +
Krieg J-C, Lauer CJ, Hermle L, von Bardeleben U, Pollmächer T, Holsboer F.  Psychometric, polysomnographic, and neuroendocrine measures in subjects at high risk for psychiatric disorders: preliminary results . Neuropsychobiology . 1990;;23:57-67.
12 +
Schreiber W, Lauer CJ, Krumrey K, Holsboer F, Krieg J-C.  Cholinergic REM sleep induction test in subjects at high risk for psychiatric disorders . Biol Psychiatry . 1992;;32:79-90.
13 +
Goetz RR, Puig-Antich J, Ryan N, Rabinovich H, Ambrosini PJ, Nelson B, Krawiec V.  Electroencephalographic sleep of adolescents with major depression and normal controls . Arch Gen Psychiatry . 1987;;44:61-68.
14 +
Appelboom-Fondu J, Kerkhofs M, Mendlewicz J.  Depression in adolescents and young adults: polysomnographic and neuroendocrine aspects . J Affect Disord . 1988;;14:35-40.
15 +
Kupfer DJ, Frank E, Ehlers CL.  EEG sleep in young depressives: first and second night effects . Biol Psychiatry . 1989;;25:87-97.
16 +
Lauer CJ, Krieg J-C, Riemann D, Zulley J, Berger M.  A polysomnographic study in young psychiatric inpatients: major depression, anorexia nervosa, bulimia nervosa . J Affect Disord . 1990;;18:235-245.
17 +
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition . Washington, DC: American Psychiatric Association; 1987;.
18 +
Wittchen H-U, Zaudig M, Schramm E, Spengler P, Mombour W, Klug J, Horn R. SKID: Strukturiertes Klinisches Interview für DSM-III-R Weinheim, Germany: Beltz; 1990;.
19 +
Hiller W, Zaudig M, Mombour W.  Development of diagnostic checklists for use in routine clinical care: a guideline designed to assess DSM-III-R diagnoses . Arch Gen Psychiatry . 1990;;47:782-784.
20 +
Cross-National Collaborative Group.  The changing rate of major depression: cross-national comparisons . JAMA . 1992;;268:3098-3105.
21 +
Lauer CJ, Pollmächer T.  On the issue of drug washout prior to polysomnographic studies in depressed patients . Neuropsychopharmacology . 1992;;6:11-16.
22 +
Rechtschaffen A, Kales A. A Manual of Standardized Terminology: Techniques and Scoring System for Sleep Stages of Human Subjects . Washington, DC: National Institute of Health Publications; 1968;.
23 +
Lauer CJ, Krieg J-C, Garcia-Borreguero D, Özdaglar A, Holsboer F.  Panic disorder and major depression: a comparative electroencephalographic sleep study . Psychiatry Res . 1992;;44:41-54.
24 +
Gillin JC, Duncan W, Pettigrew KD, Frankel BL, Snyder F.  Successful separation of depressed, normal, and insomniac subjects by EEG sleep data . Arch Gen Psychiatry . 1979;;36:85-90.
25 +
Feinberg M, Gillin JC, Carroll BJ, Greden JF, Zis AP.  EEG studies of sleep in the diagnosis of depression . Biol Psychiatry . 1982;;17:305-316.
26 +
Kerkhofs M, Hoffmann G, De Martelaere V, Linkowski P, Mendlewicz J.  Sleep EEG recordings in depressive disorders . J Affect Disord . 1985;;9:47-53.
27 +
Lauer CJ, Hermle L, Pollmächer T, Krieg J-C, Holsboer F. A polysomnographic study in subjects at high risk for psychiatric disorders. Presented at the 10th Congress of European Sleep Research Society; March 20, 1990; Strasbourg, France.
28 +
Kupfer DJ, Ulrich RF, Coble PA, Jarrett DB, Grochocinski VJ, Doman J, Matthews G, Borbély AA.  Application of automated REM and slow wave sleep analysis, II: testing the assumption of the two-process model of sleep regulation in normal and depressed patients . Psychiatry Res . 1984;;13:335-343.
29 +
Cashman MA, Coble P, McCann BS, Taska L, Reynolds CF, Kupfer DJ.  Sleep markers of major depressive disorder in adolescent patients . Sleep Res . 1986;;15:91.
30 +
Sitaram N, Gillin JC, Bunney WE.  Cholinergic and catecholaminergic receptor sensitivity in affective illness . In: Post RM, Ballenger JC, eds. Neurobiology of Mood Disorders . Baltimore, Md: Williams & Wilkins; 1984;:629-651.
31 +
Berger M, Riemann D, Höchli D, Spiegel R.  The cholinergic rapid eye movement sleep induction test with RS-86: state or trait marker of depression? Arch Gen Psychiatry . 1989;;46:421-428.
32 +
Gillin JC, Sutton L, Ruiz C, Kelsoe J, Dupont RM, Darko D, Risch SC, Golshan S, Janowsky D.  The cholinergic rapid eye movement induction test with arecoline in depression . Arch Gen Psychiatry . 1991;;48:264-270.
33 +
Weissman MM, Gershon ES, Kidd KK, Prusoff BA, Leckman JF, Dibble E, Hamovit J, Thompson WD, Pauls DL, Guroff J.  Psychiatric disorders in the relatives of probands with affective disorders . Arch Gen Psychiatry . 1984;;41:13-21.
34 +
McGuffin P, Katz R.  Nature, nurture and affective disorders . In: Deakin JFW, ed. The Biology of Affective Disorders . London, England: Gaskell Press; 1986;.
35 +
Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckamn JF, Schery W, Targum SD, Nurnberger JI, Goldin RL, Bunney WE Jr.  A family study of schizoaffective, bipolar I, bipolar II, unipolar and normal control probands . Arch Gen Psychiatry . 1982;;39:1157-1167.
36 +
Rice J, Reich T, Andreasen NC, Endicott J, Van Eerdewegh M, Fishman R, Hirschfeld RMA, Klerman GL.  Familial transmission of bipolar illness . Arch Gen Psychiatry . 1987;;44:441-447.
37 +
Lauer CJ, Wiegand M, Krieg J-C.  All-night electroencephalographic sleep and cranial computed tomography in depression: a study of unipolar and bipolar patients . Eur Arch Psychiatry Clin Neurosci . 1992;;242:59-68.
38 +
Duncan WC, Pettigrew KD, Gillin JC.  REM architecture changes in bipolar and unipolar depression . Am J Psychiatry . 1979;;136:1424-1427.
39 +
Giles DE, Rush AJ, Roffwarg HP.  Sleep parameters in bipolar I, bipolar II, and unipolar depression . Biol Psychiatry . 1986;;21:1340-1343.
40 +
de Maertelaer V, Hoffmann G, Lemaiere M, Mendlewicz J.  Sleep spindle activity changes in patients with affective disorder . Sleep . 1987;;10:443-451.
41 +
Kerkhofs M, Kempenaers C, Linkowski P, de Maertelaer V, Mendlewicz J.  Multivariate study of sleep EEG in depression . Acta Psychiatr Scand . 1988;;77:463-468.
42 +
Webb WB, Campbell SS.  Relationship in sleep characteristics of identical and fraternal twins . Arch Gen Psychiatry . 1983;;40:1093-1095.
43 +
Nurnberger J, Sitaram N, Gershon ES, Gillin JC.  A twin study of cholinergic REM induction . Biol Psychiatry . 1983;;18:1161-1165.
44 +
Hori A.  Sleep characteristics in twins . Jpn J Psychiatry Neurol . 1986;;40:35-46.
45 +
Linkowski P, Kerkhofs M, Hauspie R, Susanne C, Mendlewicz J.  EEG sleep patterns in man: a twin study . Electroencephalogr Clin Neurophysiol . 1989;;73:279-284.
46 +
Linkowski P, Kerkhofs M, Hauspie R, Mendlewicz J.  Genetic determinants of EEG sleep: a study in twins living apart . Electroencephalogr Clin Neurophysiol . 1991;;79:114-118.
47 +
Giles DE, Biggs MM, Rush AJ, Roffwarg HP.  Risk factors in families of unipolar depression, I: incidence of illness and reduced REM latency . J Affect Disord . 1988;;14:51-59.
48 +
Giles DE, Kupfer DJ, Roffwarg RP.  EEG sleep before and after the first episode of depression . Sleep Res . 1990;;19:161.

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1 +
Gillin JC, Sitaram N, Wehr T, Duncan W, Post R, Murphy DL, Mendelson WB, Wyatt RJ, Bunney WE.  Sleep and affective illness . In: Post RM, Ballenger JC, eds. Neurobiology of Mood Disorders . Baltimore, Md: Williams & Wilkins; 1984;:157-189.
2 +
Reynolds CF, Kupfer DJ.  Sleep research in affective illness: state of the art circa 1987 . Sleep . 1987;;10:199-215.
3 +
Lauer CJ, Riemann D, Wiegand M, Berger M.  From early to late adulthood: changes in EEG sleep of depressed patients and healthy volunteers . Biol Psychiatry . 1991;;29:979-993.
4 +
Schulz H.  Sleep in affective disorders: an experimental study in depressed and remitted patients . In: Smirne S, Franceschi M, Ferini-Strambi L, eds. Sleep in Medical and Neuropsychiatric Disorders . New York, NY: Masson Publishing USA Inc; 1988;:75-86.
5 +
Riemann D, Berger M.  EEG sleep in depression and in remission and the REM sleep response to the cholinergic agonist RS-86 . Neuropsychopharmacology . 1989;;2:145-152.
6 +
Rush AJ, Erman MK, Giles DE, Schlesser MA, Carpenter G, Vasavada N, Roffwarg HP.  Polysomnographic findings in recently drug-free and clinically remitted depressed patients . Arch Gen Psychiatry . 1986;;43:878-884.
7 +
Steiger A, von Bardeleben U, Herth T, Holsboer F.  Sleep-EEG and nocturnal secretion of cortisol and human growth hormone in male patients with endogenous depression before treatment and after recovery . J Affect Disord . 1989;;16:189-195.
8 +
Giles DE, Jarrett RB, Roffwarg HP, Rush AJ.  Reduced rapid eye movement latency: a predictor of recurrence in depression . Neuropsychopharmacology . 1987;;1:33-39.
9 +
Sitaram N, Dube S, Keshavan M, Davies A, Reynal P.  The association of supersensitive cholinergic REM-induction and affective illness within pedigrees . J Psychiatry Res . 1987;;21:487-497.
10 +
Giles DE, Kupfer DJ, Roffwarg HP, Rush AJ, Biggs MM, Etzel BA.  Polysomnographic parameters in first-degree relatives of unipolar probands . Psychiatry Res . 1989;;27:127-136.
11 +
Krieg J-C, Lauer CJ, Hermle L, von Bardeleben U, Pollmächer T, Holsboer F.  Psychometric, polysomnographic, and neuroendocrine measures in subjects at high risk for psychiatric disorders: preliminary results . Neuropsychobiology . 1990;;23:57-67.
12 +
Schreiber W, Lauer CJ, Krumrey K, Holsboer F, Krieg J-C.  Cholinergic REM sleep induction test in subjects at high risk for psychiatric disorders . Biol Psychiatry . 1992;;32:79-90.
13 +
Goetz RR, Puig-Antich J, Ryan N, Rabinovich H, Ambrosini PJ, Nelson B, Krawiec V.  Electroencephalographic sleep of adolescents with major depression and normal controls . Arch Gen Psychiatry . 1987;;44:61-68.
14 +
Appelboom-Fondu J, Kerkhofs M, Mendlewicz J.  Depression in adolescents and young adults: polysomnographic and neuroendocrine aspects . J Affect Disord . 1988;;14:35-40.
15 +
Kupfer DJ, Frank E, Ehlers CL.  EEG sleep in young depressives: first and second night effects . Biol Psychiatry . 1989;;25:87-97.
16 +
Lauer CJ, Krieg J-C, Riemann D, Zulley J, Berger M.  A polysomnographic study in young psychiatric inpatients: major depression, anorexia nervosa, bulimia nervosa . J Affect Disord . 1990;;18:235-245.
17 +
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition . Washington, DC: American Psychiatric Association; 1987;.
18 +
Wittchen H-U, Zaudig M, Schramm E, Spengler P, Mombour W, Klug J, Horn R. SKID: Strukturiertes Klinisches Interview für DSM-III-R Weinheim, Germany: Beltz; 1990;.
19 +
Hiller W, Zaudig M, Mombour W.  Development of diagnostic checklists for use in routine clinical care: a guideline designed to assess DSM-III-R diagnoses . Arch Gen Psychiatry . 1990;;47:782-784.
20 +
Cross-National Collaborative Group.  The changing rate of major depression: cross-national comparisons . JAMA . 1992;;268:3098-3105.
21 +
Lauer CJ, Pollmächer T.  On the issue of drug washout prior to polysomnographic studies in depressed patients . Neuropsychopharmacology . 1992;;6:11-16.
22 +
Rechtschaffen A, Kales A. A Manual of Standardized Terminology: Techniques and Scoring System for Sleep Stages of Human Subjects . Washington, DC: National Institute of Health Publications; 1968;.
23 +
Lauer CJ, Krieg J-C, Garcia-Borreguero D, Özdaglar A, Holsboer F.  Panic disorder and major depression: a comparative electroencephalographic sleep study . Psychiatry Res . 1992;;44:41-54.
24 +
Gillin JC, Duncan W, Pettigrew KD, Frankel BL, Snyder F.  Successful separation of depressed, normal, and insomniac subjects by EEG sleep data . Arch Gen Psychiatry . 1979;;36:85-90.
25 +
Feinberg M, Gillin JC, Carroll BJ, Greden JF, Zis AP.  EEG studies of sleep in the diagnosis of depression . Biol Psychiatry . 1982;;17:305-316.
26 +
Kerkhofs M, Hoffmann G, De Martelaere V, Linkowski P, Mendlewicz J.  Sleep EEG recordings in depressive disorders . J Affect Disord . 1985;;9:47-53.
27 +
Lauer CJ, Hermle L, Pollmächer T, Krieg J-C, Holsboer F. A polysomnographic study in subjects at high risk for psychiatric disorders. Presented at the 10th Congress of European Sleep Research Society; March 20, 1990; Strasbourg, France.
28 +
Kupfer DJ, Ulrich RF, Coble PA, Jarrett DB, Grochocinski VJ, Doman J, Matthews G, Borbély AA.  Application of automated REM and slow wave sleep analysis, II: testing the assumption of the two-process model of sleep regulation in normal and depressed patients . Psychiatry Res . 1984;;13:335-343.
29 +
Cashman MA, Coble P, McCann BS, Taska L, Reynolds CF, Kupfer DJ.  Sleep markers of major depressive disorder in adolescent patients . Sleep Res . 1986;;15:91.
30 +
Sitaram N, Gillin JC, Bunney WE.  Cholinergic and catecholaminergic receptor sensitivity in affective illness . In: Post RM, Ballenger JC, eds. Neurobiology of Mood Disorders . Baltimore, Md: Williams & Wilkins; 1984;:629-651.
31 +
Berger M, Riemann D, Höchli D, Spiegel R.  The cholinergic rapid eye movement sleep induction test with RS-86: state or trait marker of depression? Arch Gen Psychiatry . 1989;;46:421-428.
32 +
Gillin JC, Sutton L, Ruiz C, Kelsoe J, Dupont RM, Darko D, Risch SC, Golshan S, Janowsky D.  The cholinergic rapid eye movement induction test with arecoline in depression . Arch Gen Psychiatry . 1991;;48:264-270.
33 +
Weissman MM, Gershon ES, Kidd KK, Prusoff BA, Leckman JF, Dibble E, Hamovit J, Thompson WD, Pauls DL, Guroff J.  Psychiatric disorders in the relatives of probands with affective disorders . Arch Gen Psychiatry . 1984;;41:13-21.
34 +
McGuffin P, Katz R.  Nature, nurture and affective disorders . In: Deakin JFW, ed. The Biology of Affective Disorders . London, England: Gaskell Press; 1986;.
35 +
Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckamn JF, Schery W, Targum SD, Nurnberger JI, Goldin RL, Bunney WE Jr.  A family study of schizoaffective, bipolar I, bipolar II, unipolar and normal control probands . Arch Gen Psychiatry . 1982;;39:1157-1167.
36 +
Rice J, Reich T, Andreasen NC, Endicott J, Van Eerdewegh M, Fishman R, Hirschfeld RMA, Klerman GL.  Familial transmission of bipolar illness . Arch Gen Psychiatry . 1987;;44:441-447.
37 +
Lauer CJ, Wiegand M, Krieg J-C.  All-night electroencephalographic sleep and cranial computed tomography in depression: a study of unipolar and bipolar patients . Eur Arch Psychiatry Clin Neurosci . 1992;;242:59-68.
38 +
Duncan WC, Pettigrew KD, Gillin JC.  REM architecture changes in bipolar and unipolar depression . Am J Psychiatry . 1979;;136:1424-1427.
39 +
Giles DE, Rush AJ, Roffwarg HP.  Sleep parameters in bipolar I, bipolar II, and unipolar depression . Biol Psychiatry . 1986;;21:1340-1343.
40 +
de Maertelaer V, Hoffmann G, Lemaiere M, Mendlewicz J.  Sleep spindle activity changes in patients with affective disorder . Sleep . 1987;;10:443-451.
41 +
Kerkhofs M, Kempenaers C, Linkowski P, de Maertelaer V, Mendlewicz J.  Multivariate study of sleep EEG in depression . Acta Psychiatr Scand . 1988;;77:463-468.
42 +
Webb WB, Campbell SS.  Relationship in sleep characteristics of identical and fraternal twins . Arch Gen Psychiatry . 1983;;40:1093-1095.
43 +
Nurnberger J, Sitaram N, Gershon ES, Gillin JC.  A twin study of cholinergic REM induction . Biol Psychiatry . 1983;;18:1161-1165.
44 +
Hori A.  Sleep characteristics in twins . Jpn J Psychiatry Neurol . 1986;;40:35-46.
45 +
Linkowski P, Kerkhofs M, Hauspie R, Susanne C, Mendlewicz J.  EEG sleep patterns in man: a twin study . Electroencephalogr Clin Neurophysiol . 1989;;73:279-284.
46 +
Linkowski P, Kerkhofs M, Hauspie R, Mendlewicz J.  Genetic determinants of EEG sleep: a study in twins living apart . Electroencephalogr Clin Neurophysiol . 1991;;79:114-118.
47 +
Giles DE, Biggs MM, Rush AJ, Roffwarg HP.  Risk factors in families of unipolar depression, I: incidence of illness and reduced REM latency . J Affect Disord . 1988;;14:51-59.
48 +
Giles DE, Kupfer DJ, Roffwarg RP.  EEG sleep before and after the first episode of depression . Sleep Res . 1990;;19:161.

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