REM Sleep and Schizophrenia

Imagine that REM sleep, a process that occurs in the hippocampus, is like an airline control tower that is trying to organise the landing of airplanes into a busy airport for a short period during the night while you are sleeping. The airplanes represent many scattered emotions and non-concrete information that is spread throughout the perceptual areas of the brain. The landing of the planes is like the collection of random emotional data in the form of impulses , then sorting ,disposing or placing of data into emotional memory banks using previously stored emotional memories to assist the process. Human research supports the function of rapid eye movement (REM) sleep in memory formation. Wagner, Gais, and Born (2001) state “Results are consonant with a supportive function of REM sleep predominating late sleep for the formation of emotional memory in humans.”

Studies with deep electrodes have established that while the EEG of the neocortex is low in voltage during the REM sleep state, “the EEG of the hippocampus is increased in size at a 4-10 Hz (theta) frequency” (Siegel 2000).

Slowing of noradrenergic cells may be responsible for some of the symptoms of sleep deprivation, since norepinephrine release has been shown to increase the “signal to noise ratio” of information processing in a number of brain regions (Hasselmo et al 1997).

I hypothesize that REM sleep helps the brain regulate emotions by altering the sensitivity of D1 and/or D2 receptors. Studies have shown schizophrenics have unusual characteristics of D1 and D2 receptors (Abi-Dargham et al 2002). I suggest that in schizophrenics, REM sleep is unable to successfully carry out it’s task, resulting in an overabundance of emotional- memory-related connections and data. This initially leads to fogginess in higher thinking but ultimately to hallucinations and/or disorganized thoughts. Without proper functioning of REM sleep processes, psychosis occurs. The reason for malfunction would dictate the duration and type of psychosis. i.e. Too much emotional data overloading REM, poor foundation memories needed for sorting. Poor quality fluid and chemical combinations creating difficult pathways for impulses to leave their point of origin and head towards the hippocampus. Perhaps this creates a dream/nightmare state (Psychosis) that exists while awake?

Possible overloading reasons:

• Sleep deprivation resulting in less REM sleep.
• Perhaps the REM data could be too much for the REM mechanism to process during stressful times.
• Ruminations that occur during periods of high anxiety might overload the REM process.
• Double bind parenting could cause increased emotional stress and result in an ineffective REM process.
• In schizophrenia and certain types of severe depression, the hippocampus shrinks.
• Anxiety and depression can lead to psychosis due to an increase or overflow of the REM data sites.
• Anxiety and wakening during sleep decrease the effective clearing of data sites because there is less REM sleep.
• It’s commonly known that sleep deprivation causes psychosis, if the Rem mechanism can’t function due to lack of sleep, it overflows [rewrite]. Overloaded REM in a normal individual will spill out onto daytime wakening and perceptions in these circumstances,possibly in the areas they are waiting to be collected from.
• Poorly functioning REM might result from nightmares which wake the person up and so they never actually continue with an adequate cleansing of the REM sites.

Perhaps hypersomnia during stressful times is an unsuccessful attempt for allowing effective REM sleep in schizophrenics.

Possible reasons for REM mechanism failure:

• Genetic predisposition to a faulty mechanism.
• A poorly functioning REM system could also be caused by dehydration, high fructose junk food, coca cola, coffee, cigarettes, poor vitamin intake, low phosphorus levels. Higher levels of nutrients have been shown to affect REM and are linked to better sleep.
• Some poorly functioning REM mechanisms could be caused by maternal infections during pregnancy, head injury or other illnesses during childhood.
• Schizophrenia might occur after childhood because the REM takes a while to become overloaded. Perhaps in some cases of high chronic stress or low mood or poor sleep REM data never completely clears so it eventually floods certain areas of the brain, polluting perceptions while the individual is awake .
• This could explain why prodromal schizophrenics withdraw and become socially autistic, perhaps the cloudiness they complain about is like a polluted stuffiness from over stuffed REM sites that interfere with the processes necessary for the person to take in external information and separate it from their internal overflowing REM data sites.
• Excessive intake of Junk food, high fructose diets, cola and coffee are common amongst Schizophrenics. Perhaps these diets adversely affect the mechanism or homeostasis required for emptying of the can. It could be as simple as chemical imbalances in the brain resulting in a poorly functioning REM mechanism or flow of impulses.
  • Jin et al, 2005: “Recently, considerable progress has been made in our understanding of the function and regulation of the brain-specific sodium-dependent inorganic phosphate transporter 1 (NPT1), which is found to exist principally in cerebrum and cerebellum. A high phosphate diet caused an increase in serum Pi accompanied by a decrease in calcium, and a decrease in body weight coupled with a decreased relative weight of cerebellum. A study showed the specific radioactivity of the phosphatides was depressed in sleeping as compared with waking animals. These observations suggest that the physiological conditions attributable to environmental, emotional or other determinants can influence shifts in brain metabolism during the sleep-wakefulness cycle.”
• “Regular coffee and caffeine causes REM sleep to shift to the early part of the night and stages 3 and 4 sleep to shift to the later part” (Karakan et al, 1976)
• Infection can lead to psychosis. “Sleep deprivation may enable bacterial growth and that sufficient sleep impedes bacterial growth. What’s even more interesting is that di-muramyl peptides created during infection enhance non-REM sleep (but not REM sleep)” (Hobson 1994). It has been shown that even after an individual has recovered from some bacterial infections the ‘dead’ bodies of the tiny bacterium still remain in the brain. This must sometimes impede certain processes or synapsing.

Other possible connections:

• Siblings of schizophrenics often complain of vivid nightmares.
• Post traumatic Stress disorder clients complain of terrible nightmares.
• Antipsychotics Medications that are sedating have a faster acting effect than non-sedating antipsychotics.
• Some antidepressants can cause psychosis and some antidepressants have been shown to block REM sleep but antidepressants given during the prodromal phase might be beneficial in decrease the workload on the emotional data sorting process.
• Hypersomnia may be the body’s way to try to empty/sort the REM data, as is sometimes seen in mild depression or prodromal schizophrenia. Sleeping late increases REM (Plihal and Born 1997).
• It is rare to find a schizophrenic that doesn’t smoke. “Epidemiological investigations indicate that, compared with never smokers, current smokers experience greater difficulty in initiating and maintaining sleep and are generally more dissatisfied with their sleep quality.” (Zhang et al 2006)
• Could there be a natural steroidal effect that is produced during times of stress that potentiates psychosis by damaging the brain?
• Perhaps individuals who are tested as genetically susceptible to schizophrenia will be able to put preventative strategies into place by altering their lifestyle.

Interesting Facts:

• 95% schizophrenic persons smoke cigarettes.
• Cigarettes interfere with sleep quality.
• Nicotine patches interfere with sleep quality.
• Research in the UK links smoking mothers to be with a 20% increase in offspring with psychosis.
• Anti psychotic medication functions differently when a patient stops smoking.
• Most schizophrenics drink excessive amounts of caffeine, mostly coffee and coke. In certain areas of the brain, caffeine and nicotine enhance the transmission of dopamine, the main neurotransmitter involved in schizophrenia and the site of anti-psychotic medications. When dopamine rages, it can lead to psychosis.
• In a sample of 146 patients with schizophrenia from Pennsylvania, the rates of smoking were more than twice as high than the general United States population (59.6% vs. 23.4%). The study participants also reported smoking more cigarettes (24 vs. 13.5) and ingesting more caffeine (471.6mg vs. 254.2mg) at a rate of about ten more cigarettes and two more cups of coffee each day.
• Caffeine interferes with the sleep process.  One recent study shows that subjects fell asleep more easily when they were not ingesting caffeine, while another other shows that the duration and quality of sleep were improved on non-caffeine days.
• Schizophrenia is associated with increases in Dopamine whereas Parkinsons disease is associated with decreases in Dopamine.
• A reduced risk for Parkinson’s disease (PD) among cigarettesmokers has been observed consistently during the past 30 years.Recent evidence suggests that caffeine may also be protective.
• Poor diets deficient in certain nutrients have been shown to contribute to poor sleep.
• Schizophrenic persons often have low nutrient diets.  Poor nutrition elevates homocysteine levels.
• Research recently showed that Normal sleepers, consumed the highest food variety in their diets, and very short sleepers had the least variation in what they ate. A varied diet tends to be a marker for good health since it includes multiple sources of nutrients.
  Read more: http://healthland.time.com/2013/02/07/does-your-diet-influence-how-well-you-sleep/#ixzz2dYmFwnlW   http://healthland.time.com/2013/02/07/does-your-diet-influence-how-well-you-sleep/
• There has previously been found that there is a marked elevation of plasma homocysteine in young male schizophrenic patients in hospital. Serum homocysteine levels were studied in 184 consecutively admitted schizophrenic patients and 305 control subjects from an employee screening program. Homocysteine levels were markedly increased in this population of newly admitted schizophrenic patients, especially in young males. Newly admitted male schizophrenic patients have elevated homocysteine levels that cannot be explained on the basis of poor hospital nutrition. Smoking may raise homocysteine by 1–2 μM/L but this is not a large enough effect to explain our findings.
• Some researchers have already shown a link between folic acid and schizophrenia.
• Psychosis is usually preceded by high levels of stress.
• Stress interferes with sleep quality.”The prevalence of insomnia may, in fact, be the result of deteriorating sleep mechanisms associated with increased sensitivity to arousal-producing stress hormones, such as CRH and cortisol.

• During times of great stress schizophrenic persons display extremely poor sleep habits.
• The siblings of schizophrenic persons often exhibit strange dreaming phenomena.
• Schizophrenics often liken there symptoms to dreaming while awake.
• Schizophrenia often appears during adolescence.
• Adolescents have marked changes in need for length of sleep and their circadian rhythm changes.
• Schizophrenics have biological body temperature control problems.
• Biological body temperature regulation changes when a person is sleeping.
• Persons abusing barbiturates become psychotic.
• Barbiturates decrease REM sleep.
• Heavy marijuana use is linked to psychosis and schizophrenia.
• During discontinuation of heavy heavy marijuana use, PSG measures of sleep disturbance were detected in heavy marijuana users compared with a drug free control group.
• New mums have lots of sleepless nights but new research suggests that a lack of sleep could place them at greater risk of suffering from postnatal psychosis.
• Schizophrenia could simply be a sleep disorder.
• This is to say there is an underlying belief that the area of the brain which promotes REM sleep, rapid eye movement and dreaming may also be the area that is predominantly supportive of the symptoms that manifest in the schizophrenia patient. In examining dopamine levels at the prefrontal cortex, we find the levels are significantly decreased in individuals who suffer from schizophrenia. Interesting enough, this same decrease in dopamine occurs, temporarily, during our periods of REM sleep and the onset of dreaming phases.  http://voices.yahoo.com/active-rem-sleep-dreaming-schizophrenia-connection-612659.html
• First degree relatives of schizophrenic persons often suffer from recurrent nightmares.
• The contraceptive pill interferes with the absorption of caffeine.
• Interesting fact, I have never known a schizophrenic to have an acute psychotic episode, while taking contraceptive pills.
• Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Disturbed sleep can be found in 30-80% of schizophrenic patients, depending on the degree of psychotic symptomatology. Measured by polysomnography, reduced sleep efficiency and total sleep time, as well as increased sleep latency, are found in most patients with schizophrenia and appear to be an important part of the pathophysiology of this disorder.  http://www.ncbi.nlm.nih.gov/pubmed/18840034
• Sleep disturbance is as much a part of schizophrenic disorder as it is of affective illness. Research is cited indicating that after REM deprivation, remitted schizophrenics show an abnormally large transient increase in REM sleep and that active schizophrenics have dreams that are more bland and not as well confined to REM sleep as those of normals.  http://psycnet.apa.org/psycinfo/1981-26026-001

Sources:

• Wagner, Gais, and Born (2001): Emotional Memory Formation Is Enhanced across Sleep Intervals with High Amounts of Rapid Eye Movement Sleep. Learning and Memory. Vol. 8, No. 2, pp. 112-119, March/April 2001
• Siegel, J. M. Brainstem mechanisms generating REM sleep. In: Principals and Practice of Sleep Medicine, Second Edition. Edited by M. K. Kryger, T. Roth, W. C. Dement. New York: Saunders, 2000.
• Hasselmo, Linster, Patil, Ma, and Cekic. Noradrenergic Suppression of Synaptic Transmission May Influence Cortical Signal-to-Noise Ratio. The Journal of Neurophysiology Vol. 77 No. 6 June 1997, pp. 3326-3339.
• Abi-Dargham, Mawlawi, Lombardo, Gil, Martinez, Huang, Hwang, Keilp, Kochan, Van Heertum, Gorman, Laruelle.
  Prefrontal Dopamine D1 Receptors and Working Memory in Schizophrenia. The Journal of Neuroscience, May 1, 2002, 22(9):3708-3719
• Isaac, and Berridge. Wake-Promoting Actions of Dopamine D1 and D2 Receptor Stimulation. Journal of Pharmacology And Experimental Therapeutics. August 27, 2003;
• Jin, Hwang, Yu, Anderson, Lee, Lee, Prats, Morello, Beck, Jr., Cho. A High Inorganic Phosphate Diet Perturbs Brain Growth, Alters Akt-ERK Signaling, and Results in Changes in Cap-Dependent Translation. December 7, 2005. Toxicological Sciences 2006 90(1):221-229;
• Karacan, Thornby, Anch, Booth, Williams, Salis. Dose-related sleep disturbances induced by coffee and caffeine. Clin Pharmacol Ther. 1976 Dec;20(6):682-9.
• Hobson. “Sleep and the Immune System”. In: The Chemistry of Conscious States: How The Brain Changes. Little, Brown 1994.
• Plihal and Born. Effects of Early and Late Nocturnal Sleep on Declarative and Procedural Memory. The Journal of Cognitive Neuroscience, Vol 9, 534-547, Copyright © 1997 by The MIT Press
• Zhang, Samet, Caffo, Punjabi. Cigarette Smoking and Nocturnal Sleep Architecture. American Journal of Epidemiology 2006.

Glossary:

Acetylcholine (Ach) – the neurotransmitter in all autonomic ganglia. In other words, it is a chemical that allows neurons to communicate with each other.

Aminergic – Relating to nerve cells or fibres.

Dentate gyrus – Part of the hippocampal formation. It contains granule cells, which project to the pyramidal cells, but mostly to the interneurons of the CA3 subfield of the hippocampus.

Dopamine – dopamine functions as a neurotransmitter, activating the five types of dopamine receptor – D1, D2, D3, D4 and D5, and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra.

EEG topography – using a large number of electrodes to triangulate the source of the electrical activity.

Electroencephalography – the neurophysiologic measurement of the electrical activity of the brain by recording from electrodes placed on the scalp or, in special cases, subdurally or in the cerebral cortex.

Electroencephalogram (EEG) – The resulting traces from Electroencephalography, known as an and represent a summation of post-synaptic potentials from a large number of neurons.

Entorhinal cortex (EC) – Important memory center in the brain. The EC forms the main input to the hippocampus and is responsible for the pre-processing (familiarity) of the input signals.

Hippocampus – has an essential role in the formation of new memories about experienced events (episodic or autobiographical memory).

Medulla oblongata – is the lower portion of the brainstem.

Mesencephalon (or midbrain) – is the middle of three vesicles that arise from the neural tube that forms the brain of developing animals.

Nicotinic acetylcholine receptors (nAChRs) – ionotropic receptors that form ligand gated ion channels in cells’ plasma membranes. Like the other type of acetylcholine receptors, muscarinic acetylcholine receptors (mAChRs), their opening is triggered by the neurotransmitter acetylcholine (ACh), but they are also opened by nicotine.

Noradrenergic – liberating, activated by, or involving norepinephrine in the transmission of nerve impulses

Pons – part of the central nervous system, and relays sensory information between the cerebellum and cerebrum.

Ponto-geniculo-occipital (PGO) spikes – periodically generated during the REM sleep, which are considered to be the main stimuli of dreams. Play an important role in triggering and maintaining rapid eye movement sleep. Similar potentials can be elicited in waking by intense auditory stimulation that elicit orienting

Scalp electrodes – picks up the activity of large groups of neurons

Sensory gating – a process by which the brain adjusts its response to stimuli. It is a largely automatic process. When one stimulus is presented, there is a response. But when it is followed by a second stimulus soon after, the response to the second stimulus is blunted. This is an adaptive mechanism to prevent overstimulation. It helps to focus on a stimulus among a host of other distracing stimuli. The mechanism of sensory gating involves feed-forward and feed-back inhibition of the stimulus perceived. It involves GABA-ergic and α7 nicotinergic receptor-mediated inhibition of the pyramidal neurons in the cornu ammonis (CA3) region of the hippocampus.

Theta rhythms – are one of several characteristic electroencephalogram waveforms associated with various sleep and wakefulness states.