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Gottesmann C, Gottesman I. The neurobiological characteristics of rapid eye movement (REM) sleep are candidate endophenotypes of depression, schizophrenia, mental retardation and dementia. Prog Neurobiol. 2007 Mar 1 ; 81(4):237-50. Pubmed Abstract

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Primary Papers: The neurobiological characteristics of rapid eye movement (REM) sleep are candidate endophenotypes of depression, schizophrenia, mental retardation and dementia.

Comment by:  Arun Sasi
Submitted 18 October 2010
Posted 18 October 2010
  I recommend this paper

It is a wonderful concept. But I wonder whether REM in schizophrenia patients matches their waking EEG?

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Primary Papers: The neurobiological characteristics of rapid eye movement (REM) sleep are candidate endophenotypes of depression, schizophrenia, mental retardation and dementia.

Comment by:  Claude Gottesmann
Submitted 21 October 2010
Posted 21 October 2010

In reply to Dr. Sasi: From the psychological standpoint, there are strong similarities between dreaming and schizophrenia. Indeed, dreaming is characterized by "sensory hallucinations, bizarre imagery, diminished reflective awareness, orientational instability, intensification of emotion and instinctual behaviors" (Hobson et al., 1998), which strongly resemble schizophrenic symptoms.

From the neurobiological standpoint, there are now 14 similarities between dreaming and schizophrenia:

1. During REM sleep there is no alpha rhythm. In schizophrenia, during waking there is a strong deficit of alpha rhythm (Stassen et al., 1999). In a relaxing-chair situated in a soundproof room, the schizophrenic patient shows nearly no alpha rhythm contrary to normals. This is an index of decrease of habituation processes related to central inhibition deficit.

2. The gate control is disturbed during REM sleep. The recovery cycle of the auditory N100 component of the evoked potential is disinhibited, like in schizophrenia during waking: there is the same forebrain disinhibition in both states (Kisley et al., 2003).

This cortical disinhibition during REM sleep was already shown in cats by pyramidal neuron discharges (Evarts, 1964) and recovery cycle of evoked potentials (Rossi et al., 1965; Demetrescu et al., 1966; Allison, 1968).

3. The gamma rhythm centered on 40 Hz becomes uncoupled in the cortical areas (Corsi-Cabrera et al., 2003), between hippocampus and cortex (Cantero et al., 2004), and the intra-hippocampal gamma coherence is decreased (Montgomery et al., 2008). This intracerebral disconnection is one of the main hypotheses of schizophrenia (Young et al., 1998; Peled et al., 2001; Tononi and Edelman, 2000; Meyer-Lindenberg et al., 2001; Meyer-Lindenberg et al., 2005; Kubicki et al., 2008).

4. There is no reset of gamma rhythm by sensory stimulation during REM sleep (Llinas and Ribary, 1993). This is a characteristic of sensory de-afferentation which favors, like the lowering of gate control, the appearance of schizophrenic hallucinations (Behrendt and Young, 2004).

5. The dorsolateral prefrontal cortex is deactivated during REM sleep (Maquet et al., 1996; Braun et al., 1997), as is the case in schizophrenia, particularly when the cognitive functions are disturbed (Buchsbaum et al., 1982; Weinberger et al., 1986; Fletcher et al., 1998).

6. There is one documented occasion when the dorsolateral prefrontal cortex and the posterior cingulate cortex (which is not part of the limbic system) are together deactivated, like in REM sleep: it is when pianists are so involved in their playing, that they lose contact with the environment, like in schizophrenia (Parsons et al., 2005).

7. The deactivation of the primary visual cortex during REM sleep (Braun et al., 1998) is now open to discussion (Hong et al., 2009). However, the disconnection from sensory input which favors hallucinations (Behrendt and Young, 2004) is reinforced by thalamic presynaptic inhibition during the REM sleep eye movements (Dagnino et al., 1969; Ghelarducci et al., 1970; Gandolfo et al., 1980).

8. This functional de-afferentation during REM sleep could also explain the increased pain threshold observed during schizophrenic acute episodes (Griffin and Tyrrell, 2003).

9. On emerging from dreaming, there is lack of differentiation between self- and hetero-sensory stimulation (tickle), as in the schizophrenia waking state (Blagrove et al., 2006).

10. Noradrenergic and serotonergic neurons become silent during REM sleep. Both neuromodulators are in deficit in schizophrenia (Friedman et al., 1999; Silver et al., 2000; Linner et al., 2002; Van Hes et al., 2003).

11. Prefrontal dopamine concentration is decreased when compared to waking, while glutamate is unchanged (LÚna et al., 2005), both as in schizophrenia (glutamate unchanged transporters) (Abi-Dargham and Moore, 2003; Lauriat et al., 2006).

12. The nucleus accumbens level of dopamine is maximal in rats, while glutamate is minimal (LÚna et al., 2005), both as in schizophrenia (Mackay et al., 1982; Grace, 1991).

13. Cortical acetylcholine concentration in cats is decreased when compared to active waking (Marrosu et al., 1995). Such a decrease is known to favor hallucinations and cognitive deficit, both observed in schizophrenia (Collerton et al., 2005).

14. Central pharmacological increase of dopamine, and glutamate decrease, induce both psychotic symptoms and vivid dreaming (Thompson and Pierce, 1999; Reeves, 2001).

I attentively looked for results in opposition with my hypothesis, but have found none.

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View all comments by Claude Gottesmann