Schizophrenia Research Forum - A Catalyst for Creative Thinking


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

Comments on News and Primary Papers


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?

View all comments by Arun Sasi

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.

References
Abi-Dargham A, Moore H (2003) Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia. Neuroscientist 9:404-416. Abstract

Allison T (1968) Recovery cycles of primary evoked potentials in cats sensorimotor cortex. Experentia 24:240-241. Abstract

Behrendt RP, Young C (2004) Hallucinations in schizophrenia, sensori impairment and brain disease: an unified model. Behav Brain Sci 27:771-787. Abstract

Blagrove M, Blakemore SJ, Thayer BRJ (2006) The ability to self-tickle following rapid eye movement sleep dreaming. Conscious Cogn 15:285-294. Abstract

Braun AR, Balkin TJ, Wesensten NJ, Carson RE, Varga M, Baldwin P, Selbie S, Belenky G, Herscovitch P (1997) Regional cerebral blood flow throughout the sleep-wake cycle: An 150 PET study. Brain 120:1173-1197. Abstract

Braun AR, Balkin TJ, Wesensten NJ, Gwardry f, Carson RE, Varga M, Baldwin P, Belenky G, Herscovitch P (1998) Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep. Science 279:91-95. Abstract

Buchsbaum MS, Ingvar DH, Kessler R, Waters RN, Cappelletti J, Van Kammen DP, King AC, Johnson JL, Manning RG, Flynn RW, Bunney WEJ, Sokoloff L (1982) Cerebral glucography with positron tomography, use in normal subjects and in patients with schizophrenia. Arch Gen Psychiat 39:251-259. Abstract

Cantero JL, Atienza M, Madsen JR, Stickgold R (2004) Gamma EEG dynamics in neocortex and hippocampus during human wakefulness and sleep. Neuroimage 22:1271-1280. Abstract

Collerton D, Perry E, McKeith I (2005) Why people see things that are not there: A novel perception and attention deficit model for recurrent visual hallucinations. Brain Behav Sci 28:737-757. Abstract

Corsi-Cabrera M, Miro E, del Rio Portilla Y, Perez-Garci E, Villanueva Y, Guevera M (2003) Rapid eye movement sleep dreaming is characterized by uncoupled EEG activity netween frontal abd perceptual cortical regions. Brain Cogn 51:337-345. Abstract

Dagnino N, Favale E, Loeb C, Manfredi M, Seitun A (1969) Presynaptic and postsynaptic changes in specific thalamic nuclei during deep sleep. Arch Ital Biol 107:668-684.

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

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

Fletcher PC, McKenna PJ, Frith CD, Grasby PM, Friston KJ, Dolan RJ (1998) Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging. Arch Gen Psychiat 55:1001-1008. Abstract

Friedman JI, Adler DN, Davis KL (1999) The role of norepinephrine in the physiopathology of cognitive disorders: potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer's disease. Biol Psychiat 46:1243-1252. Abstract

Gandolfo G, Arnaud C, Gottesmann C (1980) Transmission in the ventrobasal complex of rat during the sleep-waking cycle. Brain Res Bull 5:921-927. Abstract

Ghelarducci B, Pisa M, Pompeiano M (1970) Transformation of somatic afferent volleys across the prethalamic and thalamic components of the lemniscal sytem during the rapid eye movements of sleep. Electroenceph Clin Neurophysiol 29:348-357. Abstract

Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41:1-24. Abstract

Griffin J, Tyrrell I (2003) Human Givens: A new approach to emotional health and clear thinking. New York: HG Publishing.

Hobson, J. A., Stickgold, R. and Pace-Schott, E. F., 1998. The neuropsychology of REM sleep dreaming. NeuroReport. 9, R1-R14. Abstract

Hong CCH, Harris JC, Pearlson GD, Kim J-S, Calhoun VC, Fallon JH, Golay X, Gillen JS, Simmonds DJ, van Zijl PCM, Zee DS, Pekar JJ (2009) fMRI evidence for multisensory recruitment associated with rapid eye movements during sleep. Hum Brain Map 30:1705-1722. Abstract

Kisley MA, Olincy A., Robbins E., Polk S.D., Adler L.E., Waldo M.C., Freedman R (2003) Sensory gating impairment associated with schizophrenia persists into REM sleep;. Psychophysiology 40:29-38. Abstract

Kubicki M, Styner M, Gerig G, Markant D, Smith K, MacCarley RW, Shenton ME (2008) Reduced interhemispheric connectivity in schizophrenic-tractography based segmentation of the corpus callosum. Schizophr Res 106:125-131. Abstract

Lauriat TL, Dracheva S, Chin B, Schmeidler J, McInnes LA, Haroutunian V (2006) Quantitative analysis of glutamate transporter mRNA expression in prefrontal and primary visual cortex in normal and schizophrenic brain. Neuroscience 137:843-851. Abstract

LÚna I, Parrot S, Deschaux O, Muffat S, Sauvinet V, Renaud B, Suaud-Chagny MF, Gottesmann C (2005) 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 81:891-899. Abstract

Linner L, Wiker C, Wadenberg ML, Schalling M, Svensson TH (2002) Noradrenaline reuptake inhibition enhances the antipsychotic-like effect of raclopride and potentiates D2-blockade-induced dopamine release in the medial prefrontal cortex of the rat. Neuropsychpharmacology 27:691-698. Abstract

Llinas R, Ribary U (1993) Coherent 40 Hz oscillation characterizes dream state in humans. Proc Nat Acad Sci USA, 90:2078-2081. Abstract

Mackay AV, Iversen LL, Rossor M, Spokes E, Bird E, Arregui A, Snyder S (1982) Increased brain dopamine and dopamine receptors in schizophrenia. Arch Gen Psychiat 39:991-997. Abstract

Maquet P, Peters JM, Aerts J, Delfiore G, Degueldre C, Luxen A, Franck, G., (1996) Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature 383:163-166. Abstract

Marrosu F, Portas C, Mascia MF, Casu MA, Fa M, Giagheddu M, Imperato A, Gessa GL (1995) Microdialysis measurement of cortical and hippocampal acetylcholine release during sleep-wake cycle in freely moving cats. Brain Res 671:329-332. Abstract

Meyer-Lindenberg A, Poline JB, Kohn PD, Holt JL, Egan MF, Weinberger DR, Berman KF (2001) Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. Am J Psychiat 158:1809-1817. Abstract

Meyer-Lindenberg A, Olsen RK, Kohn PD, Brown T, Egan MF, Weinberber DR, Berman KF (2005) Regionally specific disturbance of dorsolateral prefrontal-hippocampal function connectivity in schizophrenia. Arch Gen Psychiat 62:379-386. Abstract

Montgomery SM, Sirota A, Buzsaki G (2008) Theta and gamma coordination of hippocampal networks during waking and rapid eye movement sleep. J Neurosci 28:6731-6741. Abstract

Parsons LM, Sergent J, Hodges DA, Fox PT (2005) The brain basis of piano performance. Neuropsychologia 43:199-215. Abstract

Peled A, Geva AB, Kremen WS, Blankfeld HM, Esfandiarfard R, Nordahl TE (2001) Functional connectivity and working memory in schizophrenia: an EEG study. Int J Neurosci 106:47-61. Abstract

Rossi GF, Palestini M, Pisano M, Rosadini G (1965) An experimental study of the cortical reactivity during sleep and wakefulness. In : Aspects anatomo-fonctionnels de la physiologie du sommeil CNRS, Paris:509-532.

Reeves, M., Lindholm, D. E., Myles, P. S., Fletcher, H., and Hunt, J. O. (2001). Adding ketamine to morphine for patient-controlled analgesia after major abdominal surgery: a double-blind, randomized trial. Anesth. Analg. 93, 116-120. Abstract

Silver H, Barash I, Aharon N, Kaplan A, Poyurovsky M (2000) Fluvoxamine augmentation of antipsychotics improves negative symptoms in psychotic chronic schizophrenic patients: a placebo-controlled study. Int Clin Psychopharmacol 15:257-261. Abstract

Stassen HH, Coppola R, Gottesman II, Torrey EF, Kuny S, Rickler KC, Hell D (1999) EEG differences in monozygotic twins discordant and concordant for schizophrenia. Psychophysiology 36:109-117. Abstract

Thompson DF, Pierce DR (1999) Drug-induced nightmares. Ann pharmacother 33:93-98. Abstract

Tononi G, Edelman GM (2000) Schizophrenia and the mechanism of conscious integration. Brain Res Rev 31:391-400. Abstract

Van Hes R, Smid P, Stroomer CN, Tipker K, Tulp MT, Van der Heyden JA, McCreary AC, Hesselink MB, Kruse CG (2003) SLV310, a novel, potential antipsychotic, combining potent dopamine d2 receptor antagonism with serotonin reuptake inhibition. Bioorg Med Chem Lett 13:405-408. Abstract

Weinberger DR, Berman KF, Zec, R.F., (1986) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. 1. Regional cerebral blood flow evidence. Arch Gen Psychiat 43:114-124. Abstract

Young CE, Beach TG, Falkai P, Honer WG (1998) SNAP-25 deficit and hippocampal connectivity in schizophrenia. Cer Cort 8:261-268. Abstract

View all comments by Claude Gottesmann