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Idea Lab

Posted 12 October 2007

Is Psychosis a State of Waking Dreams?

Editor's note: Since we first went online, we have received e-mails from readers pointing out the resemblance between dreaming and the positive symptoms of schizophrenia. Most recently, Petrina Ryan wondered whether the REM sleep period might not serve as a way to sort through the day's mental activity, and might be malfunctioning in schizophrenia. We asked Claude Gottesmann of the UniversitÚ de Nice-Sophia Antipolis, Nice, France, to briefly review what is known about the relationship between sleep and schizophrenia.

Reply by Claude Gottesmann

Schizophrenia: a conjectured daytime psychobiological invasion by rapid eye movement (REM) sleep
The cognitive function of the rapid eye movement (REM) dreaming sleep stage is still an open question. The main hypothesis (Hennevin et al., 1995; Smith, 1995), still disputed (Vertes and Siegel, 2005), is that REM sleep is the period of processing and integration of daytime experienced data in definitive memory. The second one (not far from the question of Petrina Ryan) is that REM sleep washes out daytime accumulated data by a reverse learning mechanism for an efficient working brain the next day: "we dream in order to forget" (Crick and Mitchison, 1983) . However, in relation to the present topic, the first clearly established linkage of REM sleep with madness was made by the philosopher Kant, who predicted, "The madman is a waking dreamer," and more recently by Hughings Jackson, who stated, "Find out all about dreams and you will find out about insanity."

Today, although the central processes responsible for the late occurrence of schizophrenia, after childhood, are not clearly established (like the still later occurrence of Huntington disease), it has long been shown that it is a polygenic syndrome (Gottesman and Shields, 1967), the neurobiological disturbances of which are now better known. Available data about the schizophrenia-REM sleep relationship show that there are not only psychological but also strong neurobiological similarities (Gottesmann, 2005; Gottesmann, 2006; Gottesmann, 2004; Gottesmann, 2002; Gottesmann, 1999; Gottesmann and Gottesman, 2007). Indeed, these observations have been made about REM sleep (Gottesmann, 2006):

1. The classical EEG (0.5-25 c/s) is nearly without alpha rhythm, exactly as in schizophrenia during waking. It reflects a deficit of habituation processes, well established in this disease.

2. The more recently discovered gamma rhythm (centered on 50 c/s) is no longer synchronized over cortical areas, an index of intracerebral disconnections. Schizophrenia is characterized by such abnormalities.

3. Cortical neuron spontaneous firing (Figure 1 top left) in animals, as well as event-related potentials—prepulse inhibition—in animals (Figure 1 bottom left) and in humans, shows a profound disinhibition process, as in schizophrenia.

View larger image

Figure 1
Left top. The pyramidal neurons recorded by Evarts (Evarts, 1964) in monkeys fire regularly at a high rate during waking. The high-frequency irregular bursts during REM sleep are the index of disappearance of cortical inhibitory control processes. Left bottom. A cortical disinhibition during REM sleep was also already shown by Demetrescu et al. (Demetrescu et al., 1966) in cats by help of the prepulse inhibition method. Open circles = cortical activating influences. Black circles = inhibitory influences. Center top and middle. The noradrenergic (Aston-Jones and Bloom, 1981) and serotonergic (McGinty and. Harper, 1976) neurons become silent during REM sleep, as shown in rats and cats, respectively. Bottom. Both neuromodulators mainly inhibit cortical neurons, which is another criterion of cortical disinhibition during REM sleep (Reader et al., 1979). NA = noradrenaline. 5-HT = serotonin. Right top and bottom. The variation of neurotransmitters is exactly the same as in schizophrenia (LÚna et al., 2005) DA = dopamine. Glu = glutamate. Ach = acetylcholine.

4. On emerging from dreaming there is lack of differentiation between self- and hetero-sensory stimulation (tickle), as in the schizophrenia waking state.

5. There is deactivation of the dorsolateral prefrontal cortex, as in schizophrenia, which can explain the decrease or loss of self-conscious awareness in both states.

6. The primary visual cortex is deactivated and there is presynaptic inhibition of thalamic sensory afferents. The deficit of sensory constraints favors occurrence of hallucinations. This sensory deafferentation also explains the increased threshold for pain often reported during psychotic episodes.

7. Gamma and hippocampal theta rhythms are abundant in rats. They become overabundant during waking under dopamine agonists, which induce in humans psychotic symptoms as well as vivid dreaming.

8. Noradrenergic and serotonergic neurons become silent (Figure 1, center top and middle). Both neuromodulators mainly inhibit cortical neurons (Figure 1, center bottom) and are in deficit in schizophrenia. This is another criterion of disturbance of cortical inhibitory control processes.

9. Prefrontal dopamine concentration is decreased when compared to waking, while glutamate is unchanged, both as in schizophrenia (Figure 1, right top).

10. The nucleus accumbens level of dopamine is maximal in rats while glutamate is minimal, both as in schizophrenia (Figure 1, right bottom). Both features induce psychotic symptoms as well as vivid dreaming in humans.

11. Cortical acetylcholine concentration in cats is decreased when compared to active waking. Such a decrease is known to favor hallucinations and cognitive deficit, both observed in schizophrenia (Figure 1, right top).

The above-listed characteristics of REM sleep are candidate endophenotypes (Gottesman and Gould, 2003) of schizophrenia, and identification of their genetic underpinnings by research on animal models (Gould and Gottesman, 2006) offers a highly promising avenue of research into prevention and early treatment of this disease (Gottesmann and Gottesman, 2007).

References
G. Aston-Jones, F.E. Bloom, Activity of norepinephrine-containing neurons in behaving rats anticipates fluctuations in the sleep-waking cycle., J. Neurosci. 1 (1981) 876-886. Abstract

F. Crick, G. Mitchison, The function of dream sleep., Nature 304 (1983) 111-114. Abstract

M. Demetrescu, M. Demetrescu, G. Iosif, Diffuse regulation of visual thalamo-cortical responsiveness during sleep and wakefulness., Electroenceph. Clin. Neurophysiol. 20 (1966) 450-469. Abstract

E.V. Evarts, Temporal patterns of discharge of pyramidal tract neurons during sleep and waking in the monkey., J. Neurophysiol. 27 (1964) 152-171. Abstract

I.I. Gottesman, T.D. Gould, The endophenotype concept in psychiatry: Etymology and strategic intentions., Amer. J. Psychiat. 160 (2003) 636-645. Abstract

I.I. Gottesman, J. Shields, A polygenic theory of schizophrenia, Proc Nat Acad Sci (USA) 58 (1967) 199-205. Abstract

C. Gottesmann, Dreaming and schizophrenia. A common neurobiological background, Sleep Biol. Rhyt. 3 (2005) 64-74.

C. Gottesmann, The dreaming sleep stage: a new neurobiological model of schizophrenia?, Neuroscience 140 (2006) 1105-1115. Abstract

C. Gottesmann, Find out about dreams and you will find out about insanity (Hughlings Jackson). In: J.E. Pletson (Ed.), Progress in Schizophrenia Research, Nova Science Publications Inc, Hauppage, 2004, pp. 23-43.

C. Gottesmann, The neurochemistry of waking and sleeping mental activity. The disinhibition-dopamine hypothesis., Psychiat. Clin. Neurosci. 56 (2002) 345-354. Abstract

C. Gottesmann, Neurophysiological support of consciousness during waking and sleep., Prog. Neurobiol. 59 (1999) 469-508. Abstract

C. Gottesmann, I.I. Gottesman, The neurobiological characteristics of the rapid eye movement (REM) dreaming sleep stage are candidate endophenotypes of mental diseases., Prog. Neurobiol. 81 (2007) 237-250. Abstract

T.D. Gould, I.I. Gottesman, Psychiatric endophenotypes and the development of valid animal models, Genes, Brain and Behavior 5 (2006) 113-119. Abstract

E. Hennevin, B. Hars, C. Maho, V. Bloch, Processing of learned information in paradoxical sleep: relevance for memory., Behav. Brain Res. 69 (1995) 125-135. Abstract

I. LÚna, S. Parrot, O. Deschaux, S. Muffat, V. Sauvinet, B. Renaud, M.F. Suaud-Chagny, C. Gottesmann, Variations in the extracellular levels of dopamine, noradrenaline, glutamate and aspartate across the sleep-wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats, J. Neurosci. Res. 81 (2005) 891-899. Abstract

D.J. McGinty, R.M. Harper, Dorsal raphe neurons: depression of firing during sleep in cats., Brain Res. 101 (1976) 569-575. Abstract

T.A. Reader, A. Ferron, L. Descarries, H.H. Jasper, Modulatory role for biogenic amines in the cerebral cortex. Microiontophoretic studies. Brain Res. 1979 Jan 12;160(2):217-29. Abstract

C. Smith, Sleep states and memory processes., Behav. Brain Res. 69 (1995) 137-145. Abstract

R. Vertes, J. Siegel, Time for the sleep community to take a critical look at the purported role of sleep in memory processing, Sleep 28 (2005) 1228-1229. Abstract


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