Sleep EEG in Depression

Clinical improvement of depression is frequently accompanied by a normalization of sleep continuity disturbance. Difficulties in falling asleep, maintaining sleep, and problems with early morning awakening are going down [38], while disturbance of sleep architecture (reduced SWS and REM latency) may persist even in successfully treated patients [39, 40]. 

Some parameters of sleep architecture and REM sleep seem to be related to the response of the patients to therapeutic treatments and the long-term course of the disease [41-44]. Predominantly, the increase of delta ratio in the initial treatment phase seems to discriminate treatment responder from nonresponder [45]. Recent data from Hatzinger et al. [46] show that patients with a still increased REM density and reduced SWS after a successful antidepressant therapy are more likely to develop recurrence than patients who do not show these features. 

It is not yet clear whether persistent alterations of sleep architecture like reduced SWS and REM latency and increased REM density reflect an increased vulnerability for the development of depression or a neurobiological scar acquired during the course of the disease [39, 46-48]. Nevertheless, it is evident that depression and sleep EEG alterations are closely linked and that the EEG can provide information about the intensity of the disease (state aspect) and about the vulnerability for developing further episodes, i.e. the stability of the long-term course (trait-like aspect). 

Neurotransmitters and Hormones Controlling Sleep Pattern and Mood 

An explanation for sleep EEG alterations in depression is provided by the well established monaminergic-cholinergic imbalance model [49] which includes monoaminergic dysfunction in depression. The result is a disturbance of the mutual interactions between the diverse nuclei which control the transitions between REM and nonREM states (see Fig. 7.5, right part). This concept was developed in close relation to the monamionergic-cholinergic imbalance model of depression [50] which is based on observations that inhibition of the aminergic system by re- 

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Armitage R Microarchitectural findings in sleep EEG in depression diagnostic implications. Biol Psychiatry 37 72-84, 1995... 

Armitage R, Roffwarg HP, Rush AJ, et al Digital period analysis of sleep EEG in depression. Biol Psychiatry 31 52-68, 1992b... 

Armitage R, Emslie GJ, Hoffmann RF, Rintelmann J, Rush AJ (2001) Delta sleep EEG in depressed adolescent females and healthy controls. J Affect Disord 63 139-148... 

Mendelson WB, Sack DA, James SP, Martin JV, Wagner R, Garnett D, Milton J, Wehr TA (1987) Frequency analysis of sleep EEG in depression. Psychiatry Res 21 89-94... 

Staner, L., Luthringer, R. Macher, J. P. (1999). Effects of antidepressant drugs on sleep EEG in patients with major depression. Central Nerv. Syst. Drugs 11,... 

Armitage, R., Emslie, G., and Rintelmann, J. (1997) The effect of fluoxetine on sleep EEG in childhood depression a preliminary report. Neuropsychopharmacology 17 241-245. 

Kupfer DJ, Ehlers CL, Frank E, et al Persistent effects of antidepressants EEG sleep studies in depressed patients during maintenance treatment. Biol Psychiatry 35 781-793, 1994... 

Soldatos CR Computerized sleep EEG (CSEEG) in psychiatry and psychopharmacology, in Biological Psychiatry Today. Edited by Obiolo J, Ballus C, Monclus EG, et al. Amsterdam, Elsevier, 1979 Soldatos CR Insomnia in relation to depression and anxiety epidemiologic considerations. J Psychosom Res 38 [suppl l 3-8, 1994 Soldatos CR, Paparrigopoulos TJ Sleep patterns in depression, in WPA Teaching Bulletin on Depression. November [issue 11), 1995 Soldatos CR, Vela-Bueno A, Kales A Sleep in psychiatric disorders. Psychiatric Medicine 4[2) 119-132, 1987... 

Moeller FG, Gillin JC, Irwin M, Golshan S, Kripke DF, Schuckit M (1993) A comparison of sleep EEGs in patients with primary major depression and major depression secondary to alcoholism. J Affect Disord 27 39-42... 

Borbely AA, Tobler I, Loepfe M, Kupfer DJ, Ulrich RF, Grochocinski V, Doman J, Matthews G (1984) All-night spectral analysis of the sleep EEG in untreated depressives and normal controls. Psychiatry Res 12 27-33... 

Held K, Kunzel H, Ising M, Schmid DA, Zobel A, Murck H, Holsboer F, Steiger A (2004) Treatment with the CRH1 receptor antagonist R121919 improves sleep-EEG in patients with depression../ Psychiatry Res 38 129-136... 

Sleep-EEG studies have documented abnormal sleep patterns in depressed patients, especially a tendency to rapidly enter the first stage of REM early in the sleep cycle and decreased time in deep sleep. 

Electroencephalogram (EEG) sleep studies on the use of antidepressants in depressed patients have not produced clear evidence of the involvement of REM or non-REM sleep in the mechanisms underlying clinical change. Furthermore, the role of the physiological mechanisms of sleep during treatment with antidepressants is still unclear. Further basic sleep research is necessary (Gillin 1983) to interpret the effects of antidepressants on EEG sleep in terms of the physiological processes of sleep. 

Landolt H. P, Gillin J. C. (2002). Different effects of phenelzine treatment on EEG topography in waking and sleep in depressed patients. Neuropsychopharmacology 27, 462-9. 

Steiger A, von Bardeleben U, Herth T, Holsboer F. (1989). Sleep EEG and nocturnal secretion of cortisol and growth hormone in male patients with endogenous depression before treatment and after recovery. J Affect Disord. 16(2-3) 189-95. 

An epidemiological study found significant increases in neurasthenia (i.e., fatigue, depressed mood, lack of initiative, dizziness, and sleep disturbances) in workers who were chronically exposed to jet fuels by inhalation, oral, and/or dermal exposure (Knave et al. 1978). Also, attention and sensorimotor speed were impaired, but no effects were found on memory function or manual dexterity. EEG results suggest that the exposed workers may have had instability in the thalamocortical system. The limitations of the study are discussed in detail in Section 2.2.1.2 under Respiratory Effects. 

With the advent of a standardized sleep laboratory recording technique and scoring system [Rechtschaffen and Kales 1968] and the development of the computerized sleep electroencephalogram [EEG] analysis method (Borbely et al. 1984 Feinberg et al. 1980 Ktonas 1987 Kupfer et al. 1984 Mendelson et al. 1987a J. E. Shipley et al. 1988 Soldatos 1979], the study of sleep in depression became one of the major areas of sleep research. The sleep recordings of depressed patients were shown to be distinctly different... 

The purpose of this chapter is to provide an update of research on 1) the sleep laboratory and computerized sleep EEG findings in depression and 2) the effects of antidepressants on sleep efficiency and sleep stages as well as on computerized sleep EEG patterns. Documentation was based on a MEDLINE library search and on references provided in extensive reviews, such as those by C. F. Reynolds and Kupfer (1987), G. W. Vogel et al. (1990), Benca et al. (1992), van Bemmel (1993), M. Berger and Riemann (1993), Armitage (1995), Montero and Berger (1995). 

Regarding EEG frequencies outside the delta band, several micro-architectural sleep EEG characteristics of depression have been sought in both the remitted and the symptomatic state [Armitage 1995]. Based on preliminary data, certain computerized sleep EEG patterns appear to be relatively specific to depression [e.g., an elevated fast frequency activity on the right hemisphere and a reduced beta and theta interhemispheric coherence] [Armitage et al. 1991, 1992c, 1993]. The consistency of all these findings, however, has not yet been established. 

Armitage R, CaUion JS, Siegel DE, et al Interhemispheric EEG coherence in normal controls and unipolar depressed outpatients. Sleep Res 20 356, 1991 Armitage R, GaUioun SJ, Rush J, et al Gomparison of the delta EEG in the first and second non-REM periods in depressed adults and normal controls. Psychiatry Res 41 65-72, 1992a... 

Kupfer DJ, Spiker DG, Coble P, et al Amitriptyline and EEG sleep in depressed patients, 1 drug effects. Sleep 1 149-159, 1978... 

Kupfer DJ, Ehlers CJ, Pollock BG, et al Clomipramine and EEG sleep in depression. Psychiatry Res 30 165-180, 1989a... 

Kupfer DJ, Reynolds CF 111, Ehlers CL Comparison of EEG sleep measures among depressive subtypes and controls in older individuals. Psychiatry Res 27 13-21, 1989b... 

Mendlewicz J, Dunbar GC, Hoffiman G Changes in sleep EEG architecture during the treatment of depressed patients with mianserin. Acta Psychiatr Scand 72 26-29, 1985... 

Mendlewicz J, Kempenaers C, de Maertelaer V Sleep EEG and amitiiptyhne treatment in depressed inpatients. Biol Psychiatry 30 691-702, 1991... 

Papadimitriou GN, Linkowski P, Kerkhofs M, Kempenaers C, Mendlewicz J (1988) Sleep EEG recordings in generalized anxiety disorder with significant depression. J Affect Disord 15 113-118... 

Staner L, Kerkhofs M, Detroux D, Leyman S, Linkowski P, Mendlewicz J (1995) Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline a double-blind randomized trial in major depression. Sleep 18 470-477... 

Moreover, it is worth noting that most of our knowledge on the relationship between mood and sleep comes from patients with major depression, and for the last decade, from patients with moderate forms of depression. Ethical and safety issues in studying patients with a greater severity of symptoms, especially when patients are unmedicated, could explain the paucity of sleep EEG studies in manic disorder and in severe depression [10]. 

Among these different observable sleep EEG disturbances, REM sleep abnormalities were first considered as pathognomonic of major depression [15]. However, many studies in the eighties, and the seminal paper of Benca et al. [16] who meta-analyzed sleep EEG studies performed in different groups of mental disorders, seriously questioned the specificity of this sleep EEG profile for depression. However, Benca et al. [16] mentioned that the most widespread and most severe disturbances are found in patients with depressive disorder. It should also be pointed out that,... 

Some depressed patients, especially if younger, lethargic and/or bipolar, complain of hypersomnia rather than of insomnia [16], Recurrent winter oversleeping is even considered as a key symptom to diagnose seasonal affective disorder (SAD). Several sleep EEG studies were performed in patients with SAD and none could evidence the typical sleep pattern of major depression (see [10]). Polysomnographic studies... 

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