Showing posts with label sleep. Show all posts
Showing posts with label sleep. Show all posts

Sunday, February 14, 2010

Conclusions about sleep in CPPS

The following is speculative, but sleep deprivation caused by nocturia and sleep disturbances due to CPPS effects on the enteric nervous system (and thus in the end on the HPA axis and on sickness behaviour) is probably an important cause of the severe discomfort and psychological effects seen in CPPS. Especially in non-retired individuals who cannot recover lost sleep during daytime because of work duties. The exact directionality of effects is likely complicated. Are the problem driven by HPA axis disturbances or enteric effects, mediated by the vagus nerve, or by the sleep disturbance caused by nocturia. Regardless of the ultimate cause it is well worth finding strategies for getting a good nights sleep. Strategies such as avoiding caffeinated products, chocolate, alcohol, strawberries and other products know to be diuretic. Especially in the evening and late afternoon.

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The importance of sleep

While this may seem an off topic it is not. Disrupted sleep is a common feature in CPPS and other disease. Why is sleep important? Because regular and normal sleep is important for immunocomptence. In an elegant study it was shown that: “Species that have evolved longer sleep durations appear to be able to increase investment in their immune system an be better protected from parasites” and “suggest that sleep has a much wider role in disease resistance than is currently appreciated”.(1)

So undisturbed sleep is important for psychological, urological (2) and immunological health. This is also why elite athletes pay much attention to get regular and adequate (about 8 hours) sleep to keep at the top. You should take the same care.

While studies on sleep and immunity etc on humans are somewhat contradictory due to methodological differences and the complexity of the studies, some general associations have been shown.

Mild sleep deprivation is associated with increased activity of e.g the HPA axis and the autonomic sympatho-adrenal system. The first signs of alterations are changes in emotional perception. And there is a connection between disturbed sleep (i.e. apnoea) and psychiatric illness (e.g. ADHD, depression, schizophrenia). And conversely certain disease, notably chronic inflammatory diseases, is associated with sleep disturbances.(3-8)

Well known cytokines in sleep and health are IL-1 and IL-6. Sleep deprivation increases diurnal levels of IL-6, IL-1 and TNF-alfa and decreases cortisol levels thus causing daytime sleepiness, fatigue, disrupted concentration and other problems. IL-6 peaks during normal sleep (and promotes slow wave sleep, aka stage 3 and 4 sleep). (9-10) But too much will cause bad sleep.

As aspirin decreases IL-6 (11) it may both improve sleep during infection and likely worsen sleep in healthy individuals if taken in the evening. (IL-6 peaks around 1900 and 0500, and is at its lowest around 0800 and 2100.) Other cytokines do also affect sleep.

Vagus nerve signaling is important for activation of the immune system, and insults to vagus nerve afferents may activate the immune system in the absence of verifiable infection / pathogens and cause sleep disruption. Severing of the nerve diminishes this response. (12-13)

Obesity, metabolic syndrome and diabetes are associated with increased risk of sleep disturbances and obstructive sleep apnea.

Effects of sleep disruption differ depending on amount of disruption and if it occurs during deep sleep (also called restorative sleep, slow wave sleep, stage 3 and 4) or during REM sleep. A few days of sleep deprivation has been shown to increase viable bacteria in blood and lymphatic systems. Early (14) and slow wave sleep (SWS) is correlated with a shift towards Th1 immunity and late and REM sleep with a Th2 / immunosuppressive shift. Frequent arousals are correlated with increased cortisol, epinephrine (adrenaline) and norepinephrine (noradr…) levels. (15)

During infection time in SWS is increased, while duration of REM slep is decreased in “severe inflammatory states” (chronic fatigue, cancer and auto-immune disease). Shift work is associated with increased infection and prolonged sleep loss in military is associated with changes in “hormonal patterns”.(16)

(See by the way the site www.cfs-recovery.org, if it is still on line, where a chronic fatigue sufferer tells his tale of years of failed attempts to get a diagnosis (wow he must have been a hypochondriac… [this is a sarcasm]) and appropriate treatment, before finally testing himself for sleep apnoea, despite no snoring!! After which he fast recovered… Especially notice the many odd symptoms and problems he got!)

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(1) Preston BT, Capellini I, McNamara P, Barton RA, Nunn CL. Parasite resistance and the adaptive significance of sleep. BMC Evol Biol 9:7, 2009 jan 9
(2) Nolan TE, Metheny WP, Smith RP. Unrecognized association of sleep disorders and depression with chronic pelvic pain. South Med J. 1992 Dec;85(12):1181-3.
(3) Chang PP, Ford DE, Mead LA, Cooper-Patrick L, Klag MJ. Insomnia in young men and subsequent depression. The Johns Hopkins Precursors Study. Am J Epidemiol. 146(2):105-14, 1997.
(4) Plante DT, Winkelman JW. Sleep disturbance in bipolar disorder: therapeutic implications. Am J Psychiatry. 165(7):830-43, 2008.
(5) Peppard PE, Szklo-Coxe M, Hla KM, Young T. Longitudinal association of sleep-related breathing disorder and depression. Arch Intern Med. 166(16):1709-15, 2006.
(6) Ellenbogen JM, Hulbert JC, Jiang Y, Stickgold R. The sleeping brain's influence on verbal memory: boosting resistance to interference. PLoS ONE. 2009;4(1):e4117. Epub 2009 Jan 7.
(7) Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep Med Rev 12(3):197-210, 2008.
(8) Schroder CM, O'Hara R. Depression and Obstructive Sleep Apnea (OSA). Ann Gen Psychiatry. 2005 Jun 27;4:13.
(9) Opp MR. Cytokines and sleep. Sleep Med Rev 9:355-364, 2005.
(10) Kapsimalis F, Basta M, Varouchakis G, Gourgoulianis K, Vgontzas A, Kryger M. Cytokines and pathological sleep. Sleep Med 9(6):603-614, 2008.
(11) von Känel R, Kudielka BM, Metzenthin P, Helfricht S, Preckel D, Haeberli A, Stutz M, Fischer JE. Aspirin, but not propranolol, attenuates the acute stress-induced increase in circulating levels of interleukin-6: a randomized, double-blind, placebo-controlled study. Brain Behav Immun. 22(2):150-157, 2008.
(12) Johnston GR, Webster NR. Cytokines and the immunomodulatory function of the vagus nerve. Br J Anaesth. 102(4):453-462, 2009
(13) Van Der Zanden EP, Boeckxstaens GE, de Jonge WJ. The vagus nerve as a modulator of intestinal inflammation. Neurogastroenterol Motil. 21(1):6-17, 2009.
(14) Refers to the first 1-3 hours of sleep, while late refers to the following 3-5 hours.
(15) Lorton D, Lubahn CL, Estus C, Millar BA, Carter JL, Wood CA, Bellinger DL. Bidirectional communication between the brain and the immune system: implications for physiological sleep and disorders with disrupted sleep. Neuroimmunomodulation 13:357-374, 2006.
(16) Majde JA, Krueger JM. Links between the innate immune system and sleep. J Allergy Clin Immunol 116:1188-1198, 2005.

Friday, November 27, 2009

Testosterone and sleep

This is very interesting for CPPS sufferers. As sleep is very important for health and for feeling well. And sleep disturbance is common in CPPS due to the need to void once or twice at night. Which can affect testosterone levels deeply.

Sleep is very important for testosterone levels. This is regardless of when you sleep as long as it is a good undisturbed period of about eight hours.(1) Shorter sleep in old age may be a cause of lower testosterone levels. Bad sleep, especially loss of REM sleep, will depress testosterone levels, but paradoxically high testosterone levels may cause bad sleep too by inducing apnea.(2) A vicious circle!

Individuals with obstructive sleep apnea (OSA) are an extreme example.(3) Sleep disruption will disturb all sleep-controlled endocrine rhythms, not only testosterone. "In conclusion, testosterone increased during sleep and fell during waking, whereas circadian effects seemed marginal. Individual differences were pronounced."(4) "During fragmented sleep, nocturnal testosterone rise was observed only in subjects who showed REM episodes. Our findings indicate that the sleep-related rise in serum testosterone levels is linked with the appearance of first REM sleep. Fragmented sleep disrupted the testosterone rhythm with a considerable attenuation of the nocturnal rise only in subjects who did not show REM sleep."(5)

As nocturia is a common cause of disrupted sleep addressing nocturia in CPPS patients is an important issue. The figure below shows normal sleep (no nightly awakenings) and disrupted sleep (nightly awakenings indicated by blue bars).





The following diagram shows normal nightly testosterone rise (left: A,C) and absence with disrupted rem sleep (right: B, D). Time zero is from onset of melatonin (upper: A,B) and start of sleep (lower: C,D). (Luboshitzky et al, 2001.)



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(1) Axelsson J, Ingre M, Åkerstedt T, Holmbäck U. Effects of acutely displaced sleep on testosterone. J Clin Endocrinol Metab 90:4530-4535, 2005.
(2) Saaresranta T, Polo M. Sleep-disordered breathing and hormones. Eur Respir J 22:161-172, 2003.
(3) Luboshitzky R, Aviv A, Hefetz A, Herer P, Shen-Orr Z, Lavie L, Lavie P. Decreased pituitary-gonadal secretion in men with obstructive sleep apnea. J Clin Endocrin Metab 87(7):3394-3398, 2002.
(4) Axelsson J, Ingre M, Åkerstedt T, Holmbäck U. Effects of Acutely Displaced Sleep on Testosterone. J Clin Endocrin Metab 90(8):4530-4535, 2005.
(5) Luboshitzky R, Zabari Z, Shen-Orr Z, Herer P, Lavie P. Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men. J Clin Endocrin Metab 86(3):1134-1139, 2001.