Alternative Medicine for Insomnia Found

Natural Insomnia Program

Natural Insomnia Program is credited to Christian Goodman, who is a health expert, and he is willing to help those people suffering from insomnia for long. Many people end up suffering from the sleepless night, which ends up affecting their following day schedule. For instance, the author sleepless night has destructed his marriage and also career, but with the help of the program, he has been to overcomes this problem. Through the various studies, it shows that most of the people sleep after 45 minutes, but with the help of the program, this would be reduced to 10 to 15 minutes. The most common solution to relaxing the body is through linguistic audio, which would help the brain to relax and thus sleep effectively. Many people have used the program, and they have ended solving the problem entirely. The program is available either in the video series and e-Book and works within the shortest time possible. Read more...

Natural Insomnia Program Summary


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Contents: Ebook, Video Series
Author: Christian Goodman
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My Natural Insomnia Program Review

Highly Recommended

The author presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this book are precise.

When compared to other e-books and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

Measuring Sleep Disorders

Until 2002, there were no specific instruments to clinically assess sleep problems of PD in a comprehensive and holistic fashion. Existing sleep scales for other disorders, such as the Pittsburgh Sleep Quality Index (PSQI), Stanford Sleepiness Scale, or the Karolinska Sleepiness Scale, are not specific for PD and have problems related to scale clinimetrics in relation to complexity and face validity when these are used in PD (66, 71-73). For instance, the PSQI, although quantifiable, does not specifically address sleep disturbances of PD, such as restlessness of legs, painful posturing of arms or legs, tremors, or fidgeting. The Stanford Sleepiness Scale and the Karolinska Sleepiness Scale appear too short for a comprehensive assessment of sleep problems. The gold standards for measurement of physiological aspects of sleep architecture are PSG and MSLT. However, these are tests of sleep structure, need specialized sleep laboratories, and can be expensive. In the United Kingdom, for...

Sleep Benefit and Sleep Hygiene

Sleep benefit is a common phenomenon of variable duration ranging from 30 minutes to 3 hours in PD and implies improvement in mobility and motor state in the morning and after drug intake at night (98). The mechanism of sleep benefit is unknown, and possible causes include (i) recovery of dopaminergic function and storage during sleep, (ii) a circadian rhythm-related phenomenon, or (iii) a pharmacological response to dopaminergic drugs (7,30). Good sleep hygiene is also useful. Activities such as a hot bath a couple of hours before bedtime, maximizing daytime activity, ensuring bright light exposure, having a hot sweet drink or a light snack at bedtime, use of handrails in bed and or satin sheets to enable easier turning in bed, flexible bed times, a reclining armchair for some, and avoiding stimulants such as tea or coffee at bedtime are part of good sleep hygiene (81). Nocturia remains one of the most common causes of sleep disruption in PD and can be reduced by avoiding diuretics,...

Effects of Exogenous GH Administration on Sleep Quality

Early studies in rats and in cats indicated that injections of exogenous GH may stimulate REM sleep (94,95). In humans, the stimulation of REM sleep was confirmed in a study involving an intramuscular GH injection administered 15 min before bedtime (96). In addition, this treatment resulted in a decrease in SW sleep. A more recent study reported no effects on sleep quality when GH levels were elevated either by intravenous infusion or by intramuscular injection given approx 3 h before sleep onset (97). As indicated above, in GH-deficient subjects, prolonged treatment with daily injections of exogenous GH resulted in a marked increase in REM sleep (92).

Effects of GHRH on Sleep Quality

A number of studies have demonstrated effects of GHRH on sleep quality and it has been suggested that GH secretion and sleep may share common regulatory mechanisms (98). In rodents, intracerebral as well as systemic injections of GHRH stimulate non-REM sleep, even in hypophysectomized animals (99-102). Systemic injections of GHRH also stimulate REM sleep in intact, but not in hypophysectomized rodents (101,102). Conversely, inhibition of endogenous GHRH using GHRH antagonists or antibodies to GHRH decreases both non-REM sleep and GH secretion (98,103) .Inhumans, discrepant data have been reported. No effects of GHRH on visually scored sleep stages were found when the peptide was injected during daytime or before sleep onset (104,105), or when it was given as an infusion (97,106). However, delta power during the first 100 min of sleep was significantly enhanced following bedtime injection of GHRH (105). When the intravenous injections were performed during sleep, stimulatory effects on...

Sleep Quality in the Elderly

Sleep is of great importance for health and the quality of life. There is a strong association between sleep disorders on the one hand, and illness and early death on the other. The mortality is higher among elderly persons with sleep disorders than in those who sleep well, and the excess mortality is related to the predominant causes of death, such as heart disease, stroke, cancer, and suicide. Poor sleep also shows a negative interaction with many somatic and psychiatric diseases and symptoms, as well as causing a deterioration in the quality of life. These diseases and symptoms are more important in explaining sleep deterioration than the age and sex of the patients, although there is a tendency toward an increase in sleep problems with increasing age. There are some evident differences in sleep between men and women. Women report more difficulties in initiating and maintaining sleep than men, whereas men display more sleep disturbances at EEG assessments. Men are also more...

Pharmacological Toxicological Effects 51 Insomnia

Donath and colleagues performed a randomized, double-blind, placebo-controlled, cross-over study assessing the short-term (single dose) and long-term (14-day multiple dosage) effects of valerian extract on sleep structure and sleep quality. There were significant differences between valerian and placebo for parameters describing slow-wave sleep (SWS) and shorter sleep latency, with very low adverse events. Leathwood and colleagues demonstrated valerian's effect on sleep quality (11). A freeze-dried aqueous extract of valerian root (Rhizoma Valeriana officinalis L. ) 400 mg was compared to two Hova (valerian 60 mg and hop flower extract 30 mg per tablet) tablets and placebo (finely ground brown sugar) in this crossover study involving 128 volunteers. Study participants took the study medication 1 hour before retiring, and filled out a questionnaire the following morning. This was repeated on nonconsecutive nights, such that each of the three treatments, identified only by a code...

Sleep Quality

2.4.1 Sleep Quality Definitions and Measurement Sleep quality generally refers to subjective perceptions about one's sleep and may be assessed using purely qualitative indicators (e.g., sleep that is restful, sound, restorative, of good quality ) or a combination of qualitative and quantitative indicators. Sleep diaries often include one or more qualitative indicators about the previous night's sleep, which are assessed using visual analog or Likert-type scales (Monk et al, 1994). The Pittsburgh Sleep Quality Index (PSQI), which is the most widely used self-report sleep instrument and has been translated into over 30 languages, is an example of a multiple-indicator measure of sleep quality (Buysse et al, 1989). The PSQI includes 19 retrospective questions about one's sleep over the past month. These questions are used to derive seven subscales (sleep duration, sleep latency, sleep efficiency, sleep disturbance, daytime dysfunction, use of medications for sleep, overall sleep quality),...

Posttraumatic Stress Disorder

Although there are many forms of psychological injury that can be the focus of a compensation claim (including chronic pain, cognitive impairment, postconcussive syndrome, depression), this review will focus onposttraumatic stress disorder (PTSD). This condition is diagnosed when the individual has (a) suffered a traumatic experience, and subsequently suffers (b) re-experiencing (e.g. flashbacks, nightmares), (c) avoidance (e.g. effortful avoidance of trauma-related thoughts, emotional numbing), and (d) hyperarousal (e.g. insomnia, irritability) symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV American Psychiatric Association, 1994), PTSD has the distinctive feature of including a precipitating stressor as part of the disorder's definition. This establishes a straightforward connection between a triggering traumatic event and a variety of observed symptoms (Freckelton, 1997). Such a relationship enables PTSD to be susceptible to...

Epidemiology And Symptoms

Sleep dysfunction in PD is multifactorial, and as many as 98 of patients with PD may suffer at some time from nocturnal symptoms that can disturb their sleep (2). Overall prevalence figures range from 25 to 98 (2-4). A community-based study reported 60 of PD patients with sleep problems, compared with 33 of age- and sex-matched healthy controls (4). The NMSQuest study in 123 PD patients across all age groups and 96 age-matched controls, using a validated nonmotor symptom questionnaire in an international multicenter setting, identified high rates for a range of sleep-related disorders (14). Although some complaints such as nocturia (67 ) were common in controls, other complaints such as insomnia (41 ), intense vivid dreams (31 ), acting out during dreams (33 ), restless legs (37 ), and daytime sleepiness (28 ) were more prevalent in PD and may reflect more fundamental dysfunction of sleep-related mechanisms. In another observational study, Hely et al. (15) evaluated PD patients for a...

Rapid Eye Movement Behavior Disorder and Restless Legs Syndrome

The treatment of choice for RBD is clonazepam, a benzodiazepine, although the mechanism is unknown and there are no controlled trials (13). Other drugs thought to be helpful for RBD include pramipexole, levodopa, carbamazepine, donepezil, and melatonin (64,89-91). Caution needs to be exercised with the use of clonazepam, as in some cases, RBD may be confused with sleep apnea, which can be worsened by clonazepam. Nighttime dosing with drugs such as selegiline may aggravate RBD. Others have reported a paradoxical worsening of RBD with deep brain stimulation (DBS) of the subthalamic nucleus (STN) (92).

Lesley R Brown and David A Harris

The prion disorders include Creutzfeldt-Jakob disease (CJD), kuru, Gerstmann-Straussler syndrome, and fatal familial insomnia in man, as well as scrapie and bovine spongiform encephalopathy ( mad cow disease ) in animals. In man, these diseases are characterized clinically by dementia and motor dysfunction and neuropathologically by neuronal loss, spongiosis, and amyloid deposition. Infectious, inherited, and sporadic forms of prion diseases have been described. Prion diseases are of now of enormous concern from a public health standpoint because of an epidemic of bovine spongiform encephalopathy in Britain and other European countries and recent evidence that this disease has already been transmitted to human beings by consumption of contaminated beef (1,2).

Chronic Diseases and Neurocognition

Negative cognitive outcomes are also associated with type I and type II diabetes mellitus, pulmonary diseases such as chronic obstructive pulmonary disease and asthma, hepatic diseases such as cirrhosis, kidney diseases, autoimmune diseases such as systemic lupus erythematosus, various cancers, sleep disorders such as obstructive sleep apnea, and the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS) (see Bellia et al, 2007 Biessels et al, 2008 Borson et al, 2008 Kurella et al, 2005 Tarter et al, 2001 Zhang et al, 2007).

Patients Description Of Pain And Meaning

The location, temporal nature, description by the patient (e.g., whether it is sharp, dull, aching, stabbing, pulsating, buzzing, numb, burning, tingling, cramping), and activities that might be the cause of the pain can provide valuable clues that might eventually lead to the correct therapeutic regimen. Also, listen for key descriptions associated with depression, such as insomnia, loss of appetite, loss of hope, irritability, and short-tempered actions with loved ones.

Vaccination Against Typhoid Fever A Century of Research End of the Beginning or Beginning of the

As its name implies, typhoid fever is a septicemic illness associated with alteration in consciousness (the Greek word typhos means stupor ). It is cause by the Gram-negative bacillus Salmonella typhi which belongs to the enterobacteriaceae family. In its untreated form, the disease is marked by increasing fever, headache, insomnia, and general malaise. More serious complications include intestinal perforations and bleeding, severe alteration in consciousness, and possibly shock, which can be fatal. Similar but usually less severe cases, called paratyphoid fever, are caused by Salmonella paratyphi A, B, and C. Together, S. typhi and S. paratyphi infections are referred to as enteric fevers.

Tryptophan 5hydroxylase

This reaction is a key step in the formation of the neurotransmitter serotonin, as well as the hormone melatonin, which responds to light and dark periods and is associated with the biological clock in vertebrates. Rat brain stem enzyme, which is stimulated by Fe2 + , is composed of two isozymes, one of which has a molecular weight of 300 000. Despite a monomeric molecular weight of 59 000 it is also claimed to be a tetramer. l-Phenylalanine is a substrate, but not l-tyrosine C113 . Influences in vivo that reduce brain tryptophan concentration cause the enzyme activity to increase, apparently by an increase in Vmax A1920 , an effect that should sustain brain serotonin levels in face of alterations in tryptophan availability. Liver enzyme (that also acts on phenylalanine) is stimulated by 5-fluorotryptophan and 7-azatryptophan by up to 20-fold, and at higher cofactor concentrations by phenylalanine and thienylalanine A791 . Pineal enzyme shows a diurnal rhythm with raised activities at...

Selective Serotonin Reuptake Inhibitors

The SSRIs are relatively well tolerated, although acute, treatment-emergent side effects such as agitation, diarrhea loose stools, insomnia, nausea, and sedation may occur. Occasionally, SSRIs may worsen tremor, and chronic use is associated with an increased risk of developing endocrinologic and metabolic adverse effects, such as hyponatremia, sexual dysfunction, and weight gain (Table 1) (50-52). The concomitant use of amantadine has been reported to reduce the risk of SSRI-induced sexual dysfunction (53). Reversible SSRI-induced worsening of parkinsonism has also been reported, but data are conflicting regarding the magnitude of this risk (54-56). Pharmacodynamic studies have not detected any significant reduction of motor function in patients with PD treated with SSRIs (57-58). Patients on a concomitant monoamine oxidase-B (MAO-B) inhibitor (e.g., rasagiline, selegiline) may be at increased risk of developing 5-HT syndrome however, the overall risk appears to be minimal. In one...

Detection and Assessment

The DSM-IV diagnostic criteria for major depression includes the persistent presence of five of the following nine symptoms anhedonia, depressed mood, diminished ability to think or concentrate, fatigue or loss of energy, feelings of worth-lessness or inappropriate guilt, insomnia or hypersomnia, psychomotor agitation or retardation, recurrent thoughts of death, and significant weight gain or loss (36). However, because several of these symptoms overlap with features of PD, the assessment of depression in patients with PD is not always straightforward. This is highlighted by a study demonstrating that anergy, early morning awakening, and psychomotor retardation are common and similarly frequent in both depressed and nondepressed patients with PD (105).

Measures of Brain Dynamics Effective Connectivity

The experimental application of measures of effective connectivity presents a number of difficult problems. Structural equation modeling and dynamic causal modeling are sensitive to choices made about the underlying structural model, while causal measures based time series analysis are prone to issues surrounding sample sizes or systematic sampling biases. Effective information, as defined above, shares some of these problems, in addition to issues related to its use of systematic perturbations, which are likely to be difficult to estimate in real neuronal systems. These difficulties notwithstanding, some promising avenues towards extracting effective connectivity from brain data have recently been pursued. The combination of transcranial magnetic stimulation (TMS) with functional neuroimaging, for the first time, allows the quantification of effects of localized perturbations on extended brain networks engaged in the performance of specific tasks (Paus, 1999 Pascual-Leone et al.,...

Jimo Borjigin Xing Sun and Michael M Wang

Circadian rhythms are found in virtually all organisms and are tightly coupled to environmental lighting conditions. These rhythms dictate our daily sleep schedule and hormonal fluctuations (1) and even influence our susceptibility to disease such as heart attacks (2), strokes (3), and seizures (4). One of the best studied circadian rhythms is the activity of the pineal gland, an organ situated deep within the brain. The pineal exhibits dramatic diurnal fluctuations in secretion of the hormone mela-tonin, which is best known for its soporific effects in humans. Melatonin is the only vertebrate hormone that is known to universally link environmental light information to the body's physiological responses, including clock resetting, seasonal reproduction, and sleep (5). To understand the molecular basis of the circadian regulation of the pineal gland, we identified a set of genes expressed exclusively in the nighttime pineal. One of these genes, the pineal night-specific ATPase (PINA)...

Polypeptides as Neurotransmitters

Spinal motor neurons that innervate skeletal muscles, the intravenous infusion of benzodiazepines acts to inhibit the muscular spasms in epileptic seizures and seizures resulting from drug overdose and poisons. Probably as a result of its general inhibitory effects on the brain, GABA also functions as a neurotransmitter involved in mood and emotion. Benzodiazepines such as Valium are thus given orally to treat anxiety and sleeplessness.

Regulatory Status

The German E Commission has approved St. John's wort for internal consumption for psychogenic disturbances, depressive states, sleep disorders, and anxiety and nervous excitement, particularly that associated with menopause. Oily Hypericum preparations are approved for stomach and gastrointestinal complaints, including diarrhea. Oily Hypericum preparations are also approved by the Commission E for external use for the treatment of incised and contused wounds, muscle aches, and first degree burns (96).

Sexual Differentiation Of Vocal Control Areas In Adulthood

In adulthood, next to androgen and estrogen receptors, vocal neurons express receptors for non-gonadal hormones, in particular the pineal hormone melatonin (Gahr and Kosar, 1996 Jansen et al., 2005), and are sensitive for modulatory action of monoaminergic systems (Appeltants et al., 2001, 2002 Sakaguchi et al., 2000). These neurochemical phenotypes suggest that vocal phenotypes are under the control of multiple environmental signals that directly act on vocal neurons, bypassing in part the gonadal system. Such mechanisms might explain the impact of the sociosexual and physical environment on the differentiation of vocal areas and on song development and performance that appears independent of gonadal hormones (Bentley et al., 1999 Deviche and Gulledge, 2000 Gulledge and Deviche, 1998 Tramontin et al., 1999). The most direct evidence suggesting non-gonadal plasticity of vocalization comes from works on adult male zebra finches melatonin affects their song pattern and the...

Aging Markers Based On Behavior And Circadian Rhythms

It has been reported that zebrafish is a diurnal vertebrate with a clear circadian pattern of daytime activity and nighttime rest (Cahill, 1996 Cahill, 2002 Dekens et al., 2003 Delaunay et al., 2000 Hurd et al., 1998 Kazimi and Cahill, 1999). Zhdanova has been studying the sleep-like state in zebrafish, using a high-throughput image-analysis system (Zhdanova et al., 2001). Previous studies have shown that the sleep-like state in zebrafish has fundamental similarities with sleep in mammals, including characteristic postures, elevated arousal threshold to sensory stimulation and a compensatory rest rebound following rest deprivation (Zhdanova et al., 2001). ''Sleep'' in zebrafish can be induced by conventional hypnotics, diazepam and sodium pentobarbital, and the circadian hormone melatonin (Zhdanova et al., 2001). While the age-related decline in human sleep is a well-known phenomenon, it is not yet established whether this is true in lower vertebrates. In order to determine whether...

Lithium Salts As Medication

As mentioned, lithium represents a common treatment for bipolar disorder. Lithium salts were first used therapeutically in the nineteenth century as remedies for sleeplessness and gout. Since the report of their efficacy in the treatment of bipolar disorder in the late 1940s by John Cade, lithium has been widely used in the treatment of acute manic symptoms and mood episode prophylaxis 21 . As mentioned, a number of double-blind studies have confirmed lithium's efficacy both in the acute treatment of mania, and for mania prophylaxis 14 . Further, multiple studies have suggested that lithium may be useful for both the acute and prophylactic treatment of depression (see 22 and 23 for meta-analysis and review). Unfortunately, many of the studies addressing monotherapy antidepressant effects had with some methodological shortcomings in particular, low sample sizes and the use of crossover study designs. In clinical experience, lithium's antidepressant effects as monotherapy may be modest,...

Prion proteins and prion diseases

CREUTZFELDT-jAKOB-disease (CJD), GERSTMANN-STRAUSSLER-SOHEINKER-disease (GSS) and fatal familial insomnia (FFI) are rare inherited diseases in humans. CREUTZFELDT-JAKOB-disease (CJD) for example starts with neurological symptoms (difficulties with coordination, tremor), patients loose speech, then the control over body and mind. Death occurs within 6 month of outbreak. Most victims are more than 60 years old.

Conservation status

In migration the birds made a great impression on watchers. The classic report of this spectacle is from famed American observer, John James Audubon I spotted a flock of passenger pigeons, and I realized that the number of pigeons in the flock was greater than I had ever seen before, and I decided to count them. I got off my horse, sat down and began to pencil a dot on a piece of paper for each bird that I saw. Soon I discovered that it was impossible to continue, for the birds were coming in huge groups. In 21 minutes I had made 163 dots. As I departed, the flocks grew still denser, and the air was literally filled with pigeons they darkened the sun as in an eclipse, and their droppings fell like snowflakes. The whistling of their beating wings could practically make one fall asleep. During the entire time I waited for my lunch in Young's Inn, and I saw legion after legion fly by the width

Confounding Factors in Neuroendocrine Research

Factors are age, sex, pubertal stage (in adolescents), phase of the menstrual cycle intake of oral contraceptives menopause (in women), ethnicity, weight, smoking, caffeine alcohol or drug intake, strenuous exercise, and history of endocrine immune hepatic or psychiatric disorders. In terms of the study setting, one may want to standardize time of day, food intake, and in case of multiple blood collections, allow for enough time between first venipuncture and subsequent hormone analysis, as an endocrine stress response may occur. Sleep disorders and shift working may distort circadian endocrine rhythms (for an overview, see Heim and Ehlert, 1999 Kudielka et al, 2007).

Effects of Manipulations of the Sleep Wake Cycle

Upper panel Mean (+SEM) profiles of plasma GH in 8 normal young men studied during a 53-h period including 8 h of nocturnal sleep, 28 h of sleep deprivation and 8 h of daytime sleep. The black bar represents the nocturnal sleep period. The open bar represents the period of nocturnal sleep deprivation. The dashed bar represents the period of daytime sleep. Lower panel, Individual plasma GH profile from one representative subject. Symbols are as in upper panel. Fig. 2. Upper panel Mean (+SEM) profiles of plasma GH in 8 normal young men studied during a 53-h period including 8 h of nocturnal sleep, 28 h of sleep deprivation and 8 h of daytime sleep. The black bar represents the nocturnal sleep period. The open bar represents the period of nocturnal sleep deprivation. The dashed bar represents the period of daytime sleep. Lower panel, Individual plasma GH profile from one representative subject. Symbols are as in upper panel.

Increased GH Release During Slow Wave Sleep

Sleep does not involve a constant state of reduced brain activity but instead an approximate 90-min oscillation between non-REM (rapid eye movement) stages and REM stages, which is normally repeated 4-6 times per night. Polygraphic sleep recordings include electroencephalograph (EEG), electromyographic (EMG), and electrooculographic (EOG) recordings. The so-called polysomnogram is visually scored in 20- or 30-s epochs in stages I, II, III, IV, REM, and Wake using standardized criteria (30). In the normal sequence, waking is followed by the lighter stages of non-REM sleep (i.e., stages I and II) and then within 10-20 min by so-called slow wave sleep (SWS stages III and IV), which is maintained for nearly one hour in normal young subjects. Lighter stages of non-REM sleep then reappear and the first REM period is initiated. As the night progresses, non-REM sleep becomes more shallow, the duration of REM episodes becomes longer and the number and the duration of awakenings increase....

Behavioral Medicine and Sleep Future Directions

The development of valid and reliable measures will play a critical role in our ability to evaluate relationships among sleep and health, including the translation of this knowledge to clinical applications. Epidemiologic studies, which play a key role in developing and refining conceptual models, are in need of validated and reliable, low-burden measures that assess traditional and emerging dimensions of sleep, including habitual sleep duration, daytime naps, fatigue, and sleep debt, as well as primary sleep disorders such as insomnia and sleep apnea. These measures may also prove important for reducing participant burden in studies that conduct multiple repeated assessments such as randomized clinical trials and experimental studies designed to probe mechanisms. Wrist actigra-phy holds great promise for decreasing subjective bias associated with self-report measures and for providing high-dimensional data that may be used to probe temporal characteristics of dynamic relationships...

Pharmacological Stimulation of Slow Wave Sleep

GHB is a metabolite of gamma-aminobutyric acid (GABA) that is normally present in the mammalian brain and is thought to be acting as a neurotransmitter (56-58). GHB readily crosses the blood-brain barrier but has a short duration of action, which limits its use for the treatment of insomnia. A recent study showed that bedtime administration of GHB, even at a very low dose, results in a twofold increase in the amount of GH secreted during sleep (59). This effect of GHB on nocturnal GH secretion resulted from an increase in the amplitude and the duration of the normal secretory pulse associated with sleep

Relationship Between Gh Secretion And Sleep In Pathological States

A few studies have examined nocturnal GH secretion in patients with obstructive apnea before and after treatment (82-84). As expected, nocturnal GH release is decreased in untreated apneic subjects. Because adult patients with this pathology are frequently obese, the low overnight GH levels could reflect the hyposomatotropism of obesity, rather than result from the shallow and fragmented nature of their sleep. However, two studies that have examined the nocturnal GH profile before and after treatment with continuous positive airway pressure (CPAP) have demonstrated that treatment of the sleep disorder resulted in a clear increase in the amount of GH secreted during the first few hours of sleep (83,84). An example is illustrated in Fig. 7. In children, surgical correction of obstructive sleep apnea may restore GH secretion and normal growth rate (82). daytime recovery sleep after sleep deprivation but, as expected, the amount of GH secreted in the sleep onset pulse is markedly...

Sleep Abnormalities in Conditions of Deficient or Excessive GH Secretion

A limited number of human studies, all originating from the same group of investigators, have examined sleep quality in subjects with congenital isolated GH-deficiency and in acromegalic patients before and after treatment (90). In GH-deficient adults, a decrease in duration of SW sleep and a significant suppression in delta power were observed but there were no significant differences in REM sleep (90,91). After six months of daily treatment with 2 IU m2 GH, the relative amount of REM sleep increased and there was a trend for an increased duration of SW sleep (92). In untreated acromegalic patients without sleep apnea, standard polysomnography revealed a reduction in REM sleep as well as a reduction in amount of SW sleep as compared to control subjects (92). However, a more complex picture emerged when power spectral analysis of the EEG was performed (92). Indeed, though the minutes of REM and SW were decreased, the spectral energy per min spent in both REM and SW was increased,...

Effects of Somatostatin on Sleep

Inconsistent data have been reported concerning the action of somatostatin on sleep. In the rodent, REM sleep was inhibited by immunoneutralization of endogenous soma-tostatin (111) and enhanced by intracerebroventricular administration of exogenous somatostatin (112), while non-REM sleep was inhibited by subcutaneous injections of a long-acting somatostatin analog (113). In humans, repeated intravenous injections or infusion of somatostatin did not influence sleep quality in normal young subjects (107,114), but REM sleep was decreased by somatostatin in the elderly (115).

Cardiovascular Disease

Several studies examined the relationship between sleep and cardiovascular disease, using polysomnography (Guilleminault et al, 1996 Lee et al, 2008 Taheri et al, 2007 von Kanel et al, 2007 Zaregarizi et al, 2007). The polysomnogram was used to measure factors relating to respiration during sleep, sleep-disordered breathing (snoring, apneas, hypopneas) (Taheri et al, 2007 Lee et al, 2008), and upper airway resistance syndrome (Guilleminault et al, 1996). The polysomno-gram involves the simultaneous measurement of some or all of the following parameters 2-lead EEG, EOG (electrooculogram), ECG (electrocardiogram), EMG (electromyogram), oxygen saturation, and a respiration belt. Apnea is a complete cessation of breathing for at least 10 s, whereas hypopnea is a partial cessation of breathing as derived from the polysomnogram. A number of studies focused on respiratory components of the polysomnogram and factors relevant to cardiovascular disease. Taheri and colleagues (2007) found no...

Growth Hormone Releasing Peptide GHRP and Related Molecules

Recent studies have indicated that the release of GH is also under the control of an as yet unidentified stimulatory pathway that may be activated by synthetic compounds such as the GH-releasing peptides (GHRPs) and their functional agonists (116,117). These compounds are thought to act as functional somatostatin antagonists (118). It is not known whether this second axis for GH stimulation is also involved in sleep regulation. Indeed, the findings of the only study that has examined the effects of injections of GHRP-6 around bedtime were an enhancement of the amount of stage II sleep without any other significant effect on either SW sleep or REM sleep (119). These data do not exclude the possibility that, as was previously shown for GHRH, GHRP may have a stimulatory effect on SW sleep when given during the later part of the night, at a time when SW sleep is not naturally abundant. However, a recent study indicates that, in contrast with GHRH, single injections of GHRP, at a dosage...

Putative Mechanisms Underlying Interactions Between Somatotropic Axis And Sleep

Indeed, based on rodent data, it has been proposed that the stimulation of GH release and the promotion of non-REM sleep by GHRH are two separate processes that involve GHRH neurons in two distinct areas of the hypothalamus (135-137). The control of pituitary GH release would primarily involve GHRH neurons in the arcuate nucleus (138). The promotion of non-REM sleep by GHRH would implicate another area of the mediobasal hypothalamus where GHRH neurons are concentrated, within and around the ventromedial nucleus (138). The majority of GHRH neurons in this latter region project to various parts of the basal forebrain which are involved in sleep regulation and may therefore be part of the mechanism linking somatotropic activity and sleep (135-137). The association between GH release and SW sleep could represent synchronous activity in these two regions. However, the findings in several studies of a quantitative relationship between amount of GH secreted and various measures of SW...

Chronic Fatigue Syndrome

Joint pain, headaches, un-restorative sleep, and malaise. Very little research has been conducted in this area. One study examined polysomnography recordings in this population (Scheffers et al, 1992). When comparing chronic fatigue patients, individuals with narcolepsy, and control participants, chronic fatigue patients had the highest prevalence of sleep disorders, as diagnosed via polysomnography. One study examined cognitive function in chronic fatigue syndrome patients and control participants (Yoldas et al, 2003). No group differences in the P300 and N2 components of the ERP were observed during an attention and an oddball task. Although both of these studies collected data on cognitive and psychological factors, neither examined how these measures interacted with electrophysiological findings or sample characteristics.

The Physiology Of Sleep And Its Aging

The sleep wake cycle and the 24-hour rhythm of the body temperature are regulated by a circadian periodicity that originates from the suprachiasmatic nucleus in the hypothalamus. In the morning we wake up, our body temperature increases from the nocturnal level, and we are able to be active throughout the day. In the late evening, when it is dark, we normally go to bed, and after a while we fall asleep. Stages 3 and 4 Referred to as deep sleep, delta sleep, or slow-wave sleep (SWS). Waking from these stages is more difficult than from stages 1 and 2. During SWS, growth hormone is released from the hypothalamus. Many restorative processes, such as healing of injuries and immunological processes necessary for defense against infections or malignancies are most active during SWS (Stanley, 2005). Stage 5 During rapid-eye-movement (REM) sleep, dreams are more common than in other sleep stages. REM sleep may occur in four or five periods throughout the night at intervals of 60 to 90 minutes...

Agerelated Development

The sleep pattern changes in parallel with aging. The time spent in deep sleep (slow-wave sleep) is decreased, and in the very elderly it may be absent. The number of awakenings increases with aging and in many elderly falling asleep after such awakenings becomes increasingly difficult. Elderly persons are therefore more troubled by spending time in the waking state in bed than younger adults. This decline in sleep maintenance is to some extent an expression of the age-related disorganization of the circadian sleep wake rhythm. However, sleep quality in the elderly seems to be more attributable to health-related factors than to age per se. In a study of the influence of somatic health, mental health and age on sleep in a group of elderly men and women, it was found that in men, more severe sleep disturbances were associated with poorer somatic health, poorer mental health, and increasing age, in that order of importance, and that in women, they were correspondingly associated with...

Sleep In Different Countries

The prevalence rates of sleep disturbances vary considerably between different countries of the world. In a recent review of the literature based on data collected in 50 community-dwelling populations, prevalence rates of insomnia ranging from less than 5 to 40 were reported (Ohayon, 2002). In a cross-sectional survey in 10 countries (Austria, Belgium, Brazil, China, Germany, Japan, Portugal, Slovakia, South Africa, and Spain), answers to a standardized questionnaire were collected from 35,327 men and women with mean age 39 years (7.9 of ages 65 years or older). In the whole study group ''not sleeping well'' was reported by the least proportion of respondents in Austria (10.4 ) and the highest proportion in Belgium (32.2 ). Correspondingly, the nocturnal sleep duration varied from 413 69 (mean standard deviation, SD) minutes in Japan to 504 89 minutes in Portugal, and the time taken to fall asleep varied from 15.2 18.4 minutes in Austria to 34.4 42.1 minutes in South Africa. Regular...

Somatic Diseases And Symptoms

Heart diseases and sleep disturbances interact with one another in a reciprocal and complicated way. In a classic study of Finnish adult men, Partinen and coworkers found a higher prevalence of coronary heart diseases in men who slept less than six hours per night after adjustment for age, sleep quality, use of sleeping pills and tranquilizers, smoking, alcohol use, Type A score, neuroticism, use of cardiovascular drugs, and history of hypertension. Difficulty in falling asleep at bedtime has been found to be associated with a two-fold increase in the risk of myocardial infarction during a follow-up period of 4.2 years (Appels and Schoulten, 1991). Further, among patients with myocardial infarction in another study, almost half had had sleep disorders during the six months immediately preceding the onset, which is a higher proportion than in a comparable population without myocardial infarction (Carney et al., 1990). Windows open more often -Easier to fall asleep -Fewer awakenings...

Psychiatric Diseases And Symptoms

Alzheimer's disease and other dementias Senile dementia of the Alzheimer's type (AD) is often associated with sleep impairment, and several kinds of disturbances have been described, such as reduction of sleep efficiency and of the total length of sleep. There is also a relationship between the severity of the sleep disturbance and the severity of the dementia. Patients with AD have an increased number and duration of awakenings, an increased percentage of stage 1 sleep, reduced slow-wave (''deep'') sleep, and reduced REM sleep (Petit et al., 2004). in AD differs from that of depression in showing a greater reduction of REM sleep and a lower REM density. The intellectual ability and the daytime performance may also be impaired by central sleep apnea, which is present in 33 to 53 of patients with AD (Asplund, 1999). Sleep problems are common in elderly persons with depressive disorders, and in the Diagnostic Statistical Manual (DSM-IV) of Mental Disorders, sleep deterioration is...

Recommended Resources

Alessi, C.A., and Schnelle, J.F. (2000). Approach to sleep disorders in the nursing home setting. Sleep Med. Rev. 4, 45-56. Montgomery, P. and Dennis, J. (2004). A systematic review of non-pharmacological therapies for sleep problems in later life. Sleep Med. Rev. 8, 47-62. Ohayon, M.M. Relationship between chronic painful physical condition and insomnia. J. Psychosom. Res. 39, 151-159. Schwartz, S., Mcdowell-Anderson, W., Cole, S.R., Cornoni-Huntley, J., Hays, J.C., and Blazer, D. (1999). Insomnia and heart disease A review of epidemiologic studies. J. Psychosom. Res. 47, 313-333.

Effects on Sleep and Psychological Function

The frequency of sleep disorders increases markedly with aging. It has long been known that nocturnal secretion of GH is correlated with episodes of slow-wave (delta) sleep (SWS) but it is not clear whether this means only that SWS stimulates GH secretion, or whether the stimuli to GH secretion, such as GHRH, can also stimulate SWS. Kerkhofs and colleagues reported that GHRH could acutely promote sleep in normal men, with the specific effects depending upon the timing of drug administration (51). This topic is reviewed by Van Cauter and colleagues in this volume (Chapter 15).

Captivity and Posttraumatic Stress Disorder

In reaction to the mistreatment of prisoners of war during the nineteenth century, beginning in 1864 a series of international meetings known as the Geneva Convention was held. The result was a set of rules regarding the humane treatment of prisoners of war, as well as the sick, the wounded, and those who died in battle. Despite some improvements as a result of the Geneva Convention and the rules for the treatment of prisoners of war that were defined at the Second Hague Conference of 1907, the conditions under which prisoners existed continued to be atrocious in many instances. During World War II for example, American soldiers captured by the Japanese were subjected to inhuman treatment and forced to survive on a near-starvation diet. In many ways, however, American soldiers who were taken prisoner by the Viet Cong or North Vietnamese during the Vietnam War suffered an even worse fate. Reminiscent of the treatment of inmates in concentration camps during World War 11, prisoners in...

Reasons For Noncompliance

Plegia have all been cited as reasons for noncompliance.14 Falling asleep prior to bedtime medications or being unable to walk independently to the kitchen to use refrigerated drops can interfere with drug administration. Other physical hindrances to compliance with eye drops include difficulties with positioning the head, aiming the dropper bottle, and squeezing the bottle. Kass et al.23 found that 20 of patients relied on another person to administer their eye drops. Winfield et al.9 evaluated 200 patients who were prescribed eye drops for various reasons, including glaucoma 57 of these patients admitted difficulty administering their drops, and when directly observed, only 20 instilled a drop correctly on the first try. In another study, 27 of patients were unable to put drops into each eye on the initial attempt Uniform teaching of drop administration was correlated with an increase in the patients' ability to instill eye drops properly.8 These studies reinforce the idea that...

Premenstrual Dysphoric Disorder

Premenstrual dysphoric disorder (PMDD) is characterized by markedly depressed mood, anxiety, affective lability, and decreased interest in daily activities during the last week of luteal phase in menstrual cycles of the last year. In 2002, Atmaca et al. conducted an 8-week, randomized, single-blind, rater-blinded, prospective- and parallel-group, flexible-dosing trial to compare the efficacy of fluoxetine with V. agnus-castus for the treatment of PMDD in 42 females. Both fluoxetine and V. agnus-castus had dose ranges from 20 to 40 mg. Outcome measures included the Penn daily symptom report, Hamilton depression rating scale, clinical global impression (CGI)-severity of illness scale, and CGI-improvement scale. Both drugs were well tolerated. No statistically significant differences between groups were found. The authors concluded that fluoxetine was more effective (a decrease of more than 50 in rating symptoms) for psychological symptoms (depression, irritability, insomnia,...

Online Support Groups and Virtual Communities

As stated previously, only a small proportion of Internet users report using online support groups or virtual communities (HINTS, 2009 Stoddard et al, 2008 van Uden-Kraan et al, 2009). Yet, online support groups allow patients a convenient way to provide and receive informational and emotional support (Brennan et al, 1997 Shaw et al, 2000 Tate and Zabinski, 2004 van Uden-Kraan et al, 2009). The 24 7 accessibility to online support is considered a significant advantage to patients who, because of stress, pain, or the treatment itself, have irregular sleeping habits. Patients report frequent use of discussion groups late at night (Shaw et al, 2000). Again, anonymity is a frequently cited benefit of computer-mediated groups. As one person in the latter study states It's a gift to be able to tell people as much or as little as you want about yourself.

Introduction To Mood Disorders And Limitations Of Current Treatments

Bipolar disorder and unipolar depression are classified as mood disorders. They are common, severe, and chronic illnesses. Depression is typified by a depressed mood, anhedonia (inability to experience pleasure), feelings of worthlessness or excessive guilt, impaired sleep (either insomnia or hyper-somnia), cognitive and concentration deficits, psychomotor changes, recurrent thoughts of death or suicide, and a variety of neurovegetative symptoms. In bipolar disorder, patients typically alternate (albeit not in a one-to-one manner) between episodes of depression (mostly indistinguishable from unipolar depression) and episodes of mania, which is characterized by a heightened mood, hyperaroused state, racing thoughts, increased speed and volume of speech, quicker thought, brisker physical and mental activity levels, inflated self-esteem, grandiosity, increased energy (with a corresponding decreased need for sleep), irritability, impaired judgment, heightened sexuality, and sometimes...

Modulatory Effects Of Components Of The Somatotropic Axis On Sleep

Although the association between sleep and GH release has been well documented, there is also good evidence to indicate that components of the somatotropic axis are involved in regulating sleep quality. Although the roles of each hormone could not be identified, the findings of a recent study in transgenic mice with a deficiency in the somatotropic axis have been particularly convincing as a robust loss of non-REM sleep

Health Precautions For Researchers Handling Bats

Symptoms of rabies usually develop 10-14 days after exposure and include pain, burning and numbness at the site of infection, headaches, insomnia, fever, and difficulty swallowing. However, usually by the time the symptoms are apparent, the progression of the disease can no longer be prevented, ultimately resulting in fatal inflammation of the brain and spinal cord. Therefore, it is imperative that a person seek immediate medical attention after any potential exposure. People handling bats should obtain pre-exposure immunization, which is conferred by 3 doses of vaccine, and check their titers regularly. Additionally, they should simply avoid exposure. Bats captured to establish a captive colony should be quarantined for at least 6 months to assess possible sickness. Always wear gloves when handling bats and avoid rapid and unpredictable movements which increase the chance of bites.

Copper And Neurodegenerative Diseases

Some very interesting recent findings have linked copper to various devastating neurological conditions and a common theme that emerges is the possibility of Cu-induced free-radical production leading to neuronal damage. Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurones, leads to progressive muscular weakness, atrophy, and death. An autosomal dominant form of ALS is caused by mutations in Cu Zn superoxide dismutase (SOD). It appears that the disease results from a gain of function of Cu Zn SOD, associated with abnormal forms of the protein in which copper is bound in a manner that allows the generation of reactive oxygen species (155). Alzheimer's disease is a progressive neurodegenerative disease characterized by amyloid plaques and neuronal cell loss. A major constituent of the plaques is the amyloid-P protein (APP). APP is a copper-binding molecule and can reduce Cu(II) to Cu(I) (156) it may be involved in copper transport in neurones, so...

Augmentation And Novel Treatment Strategies

No benefit was seen when total sleep deprivation was added to paroxetine in fact, the two interventions seem to counteract each other (Reynolds et al., 2005). Light therapy significantly improved depressive symptoms in a study in older depressed patients (Tsai et al., 2004). A small randomized trial comparing repetitive transcra-nial magnetic stimulation (rTMS) and sham treatment in older patients with treatment-resistant MDD reported antidepressant effects in both groups, with no significant benefits associated with rTMS (Mosimann et al., 2004). St John's Wort has been shown to have antidepressant

Allergic rhinosinusitis

To decrease congestion, two strategies are available. The one often employed first by patients is the use of vasoconstrictor agents. These may be used topically, with the problem of rhinitis medicamentosa, rebound vasodilatation that is often worse than the presenting problem. Oral use of decongestants may be effective in ameliorating congestion in some patients but their use may be associated with hypertension and sleep disorders.

Pathways Linking Positive Well Being with Health

The second possibility is that positive well-being is a marker of the broader set of psychosocial factors discussed in Section 2, which are themselves related to health, and has no direct functional role. This possibility has not been investigated very thoroughly to date, since although studies of positive well-being and health have controlled for factors such as socioeconomic status, age, and negative affect, they have seldom included the wide range of potential social and psychological mediators. However, in one investigation we studied the associations between sleep problems and both positive affect and eudaimonic well-being in a population of middle-aged men and women (Steptoe et al, 2008c). Poor sleep was related both to low positive affect and impaired eudaimonic well-being, and both effects remained significant after controlling for socioeconomic position, stress factors (financial strain and neighborhood crime), psychological distress, and social factors (social isolation,...

Pathophysiology of Psychosis and Risk Factors

The presence of dementia, advancing age, impaired vision, depression, sleep disorders, and longer disease duration have all been associated with the development of drug-induced psychosis (15,45-48). Although psychosis has been reported to occur with all of the antiparkinsonian medications (22-25), the dopamine agonists are more likely to cause psychosis than levodopa (49,50). The duration or dose of antiparkinsonian drug therapy, however, has not been found to be associated with an increased risk for psychosis (45,51,52).

Collaborative Organization

Plants do not have neurons or muscles, but they are nevertheless capable of limited movement by rotating their leaves towards the light and sending their roots deep into the soil to capture H2O and nitrogen. In multicellu-lar plant organisms, growth and mitosis are modulated by tryptophan-derived molecules, including serotonin. Furthermore, with the increase in organistic complexity, these molecules, in particular auxin, evolved homeo-static functions for effectively capturing and transporting solar energy and integrating plant rhythms and organism physiology. The plants developed effective transport systems for delivering tryptophan-based molecules from one region to another (e.g., leaf to root), depending on need (Mauseth, 2008). These two methods of producing movement, mitosis and maturation of plant cells, are similar to that seen in unicellular organisms and fungi (Eckert et al., 1999). Auxin and other tryptophan regulate the rapid tracking of leaves toward the shifting source of...

Pharmacological Toxicological Effects

14 females were given 300 mg Hypericum three times daily for 4 weeks, given a 2-week washout period, then given placebo for 4 weeks. The continuity of sleep, onset of sleep, intermittent wake-up phases, and total sleep were not improved. There was, however, a significant increase in deep sleep (stage 3 and 4, slow wave) that was shown by analysis of electroencephalogram activities (23). Thus, Hypericum may be able to improve sleep quality.

Concluding Remarks

GSK-3 a and p have a plethora of functions that complicate assessment of these molecules as a target for therapy. There are multiple important pathological conditions in which GSK-3 is dysregulated including neurological disorders such as bipolar disorder, sleep disorders, Alzheimer's disease, and T2DM. In each of these conditions, inhibition of GSK-3 should provide relief of the driving forces of the diseases. The major concern, however, is that chronic inhibition of GSK-3 can also lead to activation of targets that are proliferative such as certain transcription factors and p-catenin, which is a human oncogene. To counter this concern, there are indications that the levels of inhibition required for effects on metabolic or neurological behaviors are much lower than required for stabilization and activation of p-catenin. Only 25 inhibition of total GSK-3 (as achieved in mice heterozygous for GSK-3P) is sufficient to phenocopy behavioral effects of lithium treatment in mice and to...


Sleep disorders related to PD are multifactorial, and the causation is complex and largely unknown. Degeneration of central sleep regulatory neurons either due to a direct or an indirect effect of dopaminergic cell loss in the brainstem and related thalamo-cortical pathways, is implicated (17,19,20). A preclinical pathological staging of PD has been proposed by Braak (21). It has been traditionally believed that the pathological process of degeneration of dopaminergic neurons starts in the sub-stantia nigra however, Braak (21) proposed an alternative, as he has introduced the concept of a six-stage pathological process, beginning at clearly designated induction sites. In Braak stage 1 of PD, there is degeneration of the olfactory bulb and the anterior olfactory nucleus, which may clinically manifest as olfactory dysfunction. Progression of the pathological process to the lower brainstem occurs in Braak stage 2, which are key areas mediating nonmotor symptoms such as olfaction, sleep...

The Parasomnias

REM sleep behavior disorder (RBD) was first reported by Schenck et al. in 1986 and is a parasomnia, which is typically characterized by vivid and usually frightening dreams or nightmares associated with a paradoxical simple or complex movement during REM sleep when muscles are usually atonic (13,23). RBD is thought to have a population prevalence of 0.5 . During REM sleep, patients enact their dreams, which can be vivid or unpleasant, and partners report vocalizations (talking, shouting, vocal threats) and abnormal movements (arm leg jerks, falling out of bed, violent assaults) (35-40). Typical clinical features of RBD are summarized in Table 3. Although clinical history may suggest a diagnosis, in some situations such as when there is a high risk of physical injury or loud snoring suggestive of obstructive sleep apnea, confirmation of diagnosis should be obtained by a single night of polysomnography (PSG) with video telemetry. PSG would show an increased electromyographic (EMG)...


There is a poor evidence base for the treatment of sleep problems in PD, and the issue is complicated by the fact that treatment of sleep problems in PD needs to take into account the multifactorial nature of sleep disturbances in PD. A review by the Movement Disorder Society Task Force reported that there were no robust trials of dopaminergic agents for the treatment of nonmotor symptoms in PD, including sleep (80). Only modafinil (for EDS) and melatonin (for insomnia) have been studied in randomized, double-blind trials in a small number of patients with PD (Table 6). Other published reports consist of case series and open-label trials with limited and inadequate evidence for treatment. Insomnia-related symptoms Fragmented sleep with difficulty in sleep onset and sleep maintenance Nonpharmacologic measures Avoidance of nighttime alcohol, caffeine, tobacco Increase in daytime physical activity and ensuring exposure to daylight Psychological therapies relaxation training, cognitive...


Sleep disorders in patients with PD are common (94). They are a key component of the nonmotor symptom complex of PD and remain under-diagnosed and under-treated. Sleep problems may arise from uncontrolled motor symptoms, degeneration of the neuroanatomical substrates responsible for the sleep-wake cycle or unwanted medication side effects. Routine assessment of patients with PD should include inquiry regarding the quality of sleep and sleep-related symptoms. Use of validated bedside clinical tools such as the PDSS, SCOPA-Sleep, and ESS offer a robust way to assess the presence or absence of sleep disruption. Uncontrolled nocturnal motor symptoms may be ameliorated by long-acting dopaminergic agents, whereas other sleep disruptions such as hallucinations or RBD require a different approach. In resistant cases, patients may need to undergo a formal sleep study with PSG and or MSLT. Targeted nighttime treatment should result in improved sleep for patients with PD.


Alcohol appears to at least add to the hypnotic effect of kava in mice, and was also observed to increase the lethality of kava (37). These findings may be of importance because some Australian Aboriginal populations now frequently consume kava with alcohol. Concomitant use of barbiturates, melatonin, and other psychopharmacological agents might potentiate the effects of kava as well (38). The hepatotoxic potential of kava (27) also raises concerns about concomitant alcohol use.

Brian J Isetts

Valerian is a unique herb with a long history of use through western Europe as a sedative and hypnotic. A variety of pharmacologically active components are likely responsible for its clinical effects including volatile oils, monoterpenes, valepotriates, and sesquiterpenes. Valerenic acid, a sesquiterpene component of valerian, is postulated to produce sedation through inhibition of the breakdown of gamma-amino butyric acid. The herb is well tolerated, and side effects have been mild and self-limiting in most cases. Isolated reports of liver damage have occurred with valerian being a concomitantly consumed agent, yet anecdotal cases of attempted intentional self-poisoning with the herb have not resulted in fatality and long-term follow-up for subsequent hepatotoxicity in a number of these patients has not revealed liver abnormalities. The herb's postitive safety profile and demonstrated effectiveness in treating insomnia contributes to its popularity.


Because the tissue specificity and circadian expression of PINA correlated well with NAT expression and melatonin synthesis, we suspected that PINA was involved in melatonin biosynthesis. Our investigations of PINA ATP7B mutant LEC rats indeed revealed a defect in NAT protein stability, but, unfortunately, this was caused by an independent mutation in the NAT gene and not by the PINA mutation. We have now generated a novel line of rats in which three of the mutant LEC genes encoding NAT, PINA, and coat color have now been segregated LPP (PINA-), LPN (NAT-), and LPW (wild type in all three loci). Using these strains of rats, we were able to address the role of PINA in normal pineal physiology. Using a novel on-line pineal microdialysis protocol, we have measured the circadian production of melatonin and its precursors in animals quantitatively and reproducibly. In normal rats (LPW Fig. 4), we see low melatonin levels during the day and a sharp rise in melatonin synthesis shortly after...


The identification of PINA in the pineal gland and retina suggests that the pineal may carry out novel functions other than rhythmic melatonin synthesis. The functions may depend on copper transport. The highly parsimonious structure of PINA demonstrates that the critical regions required for ATP7B transporter function are clustered in the C-terminus of the ATP7B and indicates that novel protein partners may be required for native PINA function. The role of PINA in Wilson's disease remains to be proven.


Dida but also Pneumocistis carini especially for those also on chemotherapy), thinning of skin, increased bruising, peripheral edema, vascular bone necrosis, insomnia, irritability, acne, cushingoid state, hypertension, and proximal myopathy (45). Many ofthese effects are reversible with steroid reduction but they can cause serious quality of life issues. Because DMS has a long half-life, we generally recommend morning loading when possible to lessen some of the night-time side effects such as insomnia (i.e., for bid dosing we would recommend taking medication at breakfast and lunch instead of 8 am and 8 pm). For steroid weaning we generally decrease DMS by 2 mg every 4 d as tolerated. It is important to emphasize to patients that steroid dosing is a mix of an art and science and that good doctor patient communication will allow the best care.

Stress Syndromes

One of the most dramatic and widely discussed disorders stemming from the Vietnam War is posttraumatic stress disorder (PTSD). Similar conditions were called shell shock in World War I and combat fatigue insomnia or combat neurosis in World War II and the Korean War. PTSD is, of course, not limited to the casualties of war Earthquakes, fires, airplane crashes, and other disasters produce their share of victims. PTSD involves feelings of anxiety, insomnia, nightmares, problems with social relationships, and other emotional responses. In many cases, flashbacks associated with the stressful experience may occur months or even years after the stressful experience (Roberts, 1988).

General conclusion

The endocrine control of human sexual behavior is better understood than that of any other mammal. This is a most surprising conclusion, since a huge amount of experimental work has been dedicated to non-human mammals. Rather than illuminating us, much of this research has increased the confusion. This is not the moment to pursue explanations for this state of affairs. It is amusing, though, that the most complex of all mammalian species turned out to be the one giving the most consistent data. How this is possible can be an excellent subject for speculation during periods of insomnia.

Affective Disorders

Feelings of intense sadness, hopelessness, pessimism, low self-esteem, loss of appetite and interest, insomnia, fatigue, aches and pains, and memory problems that are symptomatic of depression can also occur as a reaction to the loss of a loved one, physical disorders, financial insecurity, social isolation, or any other serious problem. Unlike psychotic depression, in which guilt, self-deprecation, and bodily complaints are extreme and grossly unrealistic, the apathy, inertia, and withdrawal seen in neurotic or reactive depression are less bizarre and more closely associated with external circumstances.

Activity Rhythms

Approximately 40-70 of elderly people suffer from some type of sleep disorder such as increased waking at night or frequent napping during the day (Van Someren, 2000). These effects are exacerbated in subjects with dementia (Satlin et al., 1991). We have assessed the circadian pattern of locomotor activity in dogs with the Actiwatch actigraph monitoring system (Siwak et al., 2003). Dogs exhibit clear activity-rest rhythms in which activity levels are high during the day and low at night. Moreover, circadian patterns of locomotor activity in dogs exhibit age-related alterations, which vary with cognitive status and housing environment.

Efrain C Azmitia

Abstract Serotonin is involved in many of the behaviors and biological systems that are central to human life, extending from early developmental events related to neurogenesis and maturation, to apoptosis and neurodegeneration that underlie dementia and death. How can a single chemical be so powerful in determining the quality and quantity of human life In this chapter, the evolution of serotonin and its biosynthetic pathways from tryptophan are examined. The essential components of the serotonin biosynthetic pathway are highly conserved. Tryptophan-based chemicals, including serotonin, melatonin and auxin, have important action in the differentiation, mitosis and survival of single cell organisms. As the complexity of life evolved into multicellular organisms, especially plants, serotonin levels rose dramatically. The importance of tryptophan, serotonin and auxin is evident in photosynthesis and plant growth. When the animal kingdom began, the ability to synthesize tryptophan was...

Pineal Gland

The principal hormone of the pineal gland is melatonin. Production and secretion of this hormone is stimulated by activity of the suprachiasmatic nucleus (SCN) in the hypothalamus of the brain via activation of sympathetic neurons to the pineal gland (fig. 11.32). The SCN is the primary center for circadian rhythms in the body rhythms of physiological activity that follow a 24hour pattern. The circadian activity of the SCN is automatic, but environmental light dark changes are required to entrain (synchronize) this activity to a day night cycle. Activity of the SCN, and thus secretion of melatonin, begins to increase with darkness and peaks by the middle of the night. During the day, neural pathways from the retina of the eyes to the hypothalamus (fig. 11.32) act to depress the activity of the SCN, reducing sympathetic stimulation of the pineal and thus decreasing melatonin secretion. The pineal gland has been implicated in a variety of physiological processes. One of the most widely...

Prion Diseases

The name prion diseases was given to transmissible pathogens causing scrapie and other transmissible neurodegenerative diseases and distinguish these pathogens from others, including viroids and viruses. Prion diseases are a group of neurodegenerative diseases that affect animals and humans. Examples of prion diseases include scrapie of sheep, transmissible mink encephalopathy (TME), chronic wasting disease (CWD) of mule deer and elk, bovine spongiform encephalopathy (BSE) of cattle, feline spongiform encephalopathy (FSE), exotic ungulate encephalopathy, and the human diseases kuru, Creutzfeld-Jacob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), and fatal familial insomnia of humans (48).

Genome Wide Studies

Besides the genome-wide scans for type 2 diabetes, scans for traits related to type 2 diabetes have also been performed. Two genome-wide association studies independently reported previously unknown genetic loci in association with fasting glucose concentrations. The first study (Prokopenko et al, 2009) showed that the variants in the gene encoding melatonin receptor 1B (MTNRIB) were consistently associated with fasting glucose across all the 10 genome-wide association studies (n 36,610). The risk allele of the MTNRIB locus was associated with an increase of 0.07 (95 CI 0.06-0.08) mmol l in fasting glucose levels (p 3.2 x 10-50) and with reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, p 1.1 x 10-15). The same allele was also associated with an increased risk of type 2 diabetes (odds ratio 1.09 (1.05-1.12), per G allele p 3.3 x 10-7) in a meta-analysis of 13 case-control studies (18,236 cases and 64,453 controls). This study also confirmed the previous...

Adverse Effects

Bleeding is the major adverse effect of bivalirudin and occurs more commonly in patients with renal impairment. Injection site pain has been reported in individuals given sc bivalirudin (Fox et al., 1993). Mild headache, diarrhea, nausea, and abdominal cramps have also been reported (Fox et al., 1993). In the Hirulog Angioplasty Study (HAS) (now known as the Bivalirudin Angioplasty Trial BAT ), the most frequent adverse effects included back pain, nausea, hypotension, pain, and headache. Approximately 5-10 of patients reported insomnia, hypertension, vomiting, anxiety, dyspepsia, bradycardia, abdominal pain, fever, nervousness, pelvic pain, and pain at the injection site (Bittl et al., 1995 Sciulli and Mauro, 2002) (Table 3).

Suicide Risk

Suicidal feelings are high among individuals aged 85 years or over with mental disorders, with 30 believing life was not worth living'' and 10 having thought of taking their own life (Skoog et al., 1996). Among women who felt life was not worth living, the three-year mortality rate was three times that of women without these feelings (43 vs. 14 , respectively). Several studies have shown that recognition of depression among the elderly who attempt or complete suicide is inadequate (Duckworth et al., 1996 Suominen et al., 2004). Only 4 of the elderly who had attempted suicide had been diagnosed with a mood disorder before the attempt, despite having physician contact within the previous year (Suominen et al., 2004). Among elderly depression patients who had committed suicide, 80 of patients had no psychiatric referral, and 87 were untreated (Duckworth et al., 1996). Correlates of suicide include poor perceived health, poor sleep quality, and lack of a confidant (Turvey et...

Clock Time

Sleep onset will elicit a pulse in GH secretion whether sleep is advanced, delayed, or interrupted and re-initiated. Figure 2 illustrates the maintenance of this relationship in subjects who underwent a 12-h shift of the sleep-wake cycle. A pulse of GH secretion following sleep onset has been observed in subjects submitted to a variety of manipulations of the sleep-wake cycle, including a 3-h delay (5), a 5-h delay (14), an 8-h delay (15), a 12-h delay (4,16), a 16-h delay (16), daytime recovery sleep following 28 h of continuous wakefulness (17), nocturnal recovery sleep following 40 h of continuous wakefulness (18), a 7-h advance associated with transmeridian travel (19), and a 7-h advance following 33 h of sleep deprivation in the laboratory (19). Daytime naps are more consistently associated with GH release when they occur in the afternoon and the propensity for SW sleep is relatively high, as opposed to the morning when REM sleep predominates (20,21). The relationship between...

Sleep Continuity

Measures of sleep continuity focus on one's ability to initiate and maintain sleep and may be assessed by self-report, wrist actigraphy, or polysomnography (Hall et al, 2007a). Sleep latency refers to the amount of time it takes to fall asleep (e.g., minutes from good night time to onset of sleep), whereas wakefulness after sleep onset (WASO) refers to the total amount of wakefulness during the sleep period (e.g., minutes of wakefulness between sleep onset and good morning time ). Sleep efficiency is a proportional sleep continuity measure which refers to the percent of time in bed spent asleep. Although operational definitions may differ across laboratories, sleep efficiency is commonly calculated as (time spent asleep time in bed) x 100. Using the example discussed above, an individual who spent 7 h in bed (420 min) and obtained a total of 6 h of sleep (360 min) would have a sleep efficiency value of 85.7 . Arousal index, which refers to the number of transient arousals from sleep...

Sleep Architecture

Sleep architecture refers to the pattern or distribution of visually scored NREM and REM sleep stages as well as quantitative measures derived from power spectral analysis of the EEG (Hall et al, 2007a). Within NREM sleep, measures of sleep architecture include stages 1-4, although stages 3 and 4 are often combined into one slow-wave or delta sleep measure. Measures specific to REM sleep including REM latency (minutes of sleep before the first appearance of REM) and REM density (total number of phasic REMs time spent in REM sleep) are generally included in the sleep architecture domain as they, too, are structural measures of sleep these measures are more strongly linked to major mood Visually scored and quantitative indices of sleep architecture may be measured using laboratory-based or in-home PSG studies. Sleep architecture cannot be assessed by self-report or actigraphy. In this context, it is important to remember that actigraphy measures rest activity patterns and from these...

Lh Levels And Aging

LH levels increase slightly with aging (Baker et al., 1976 Morley et al., 1997). Tenover and coworkers studied older men and noted that pituitary secretion of LH was intact, but testicular secretion of T was impaired in some older men (Tenover et al., 1987). They noted that the normal diurnal variation in T levels is blunted in aging men (Tenover et al., 1988). However, the majority of hypogonadal men over age 60 have low or inappropriately normal LH levels (Korenman et al., 1990). Older men with low T levels typically have abnormal LH pulse frequency and reduced pulse amplitude, suggesting hypothalamic dysfunction (Deslypere et al., 1987). Less pulsatile T and more LH were secreted in healthy middle-aged men at night compared to healthy young men. The association between T rhythm and REM sleep also was disrupted. Most investigators have concluded that the decline in T observed with aging results from combined testicular and hypothalamic abnormalities.

Fatigue and Sleep

The prevalence of sleep complaints was three times greater in a group of MS patients than in controls. Sleep complaints were associated with greater levels of depression. In addition, several lesion sites subserving supplementary motor areas were related to the sleep complaints. The authors speculated that such lesions might be related to the production of sleep-disturbing nocturnal spasms (133).


Hall and colleagues (2000) examined the association between quantitative sleep measures using the EEG (spectral analysis), subjective sleep complaints, stress, and depression. Participants were fourteen individuals who were diagnosed with primary insomnia. It was hypothesized that self-reports of stress and depression would be positively correlated with measures of hyper-arousal during sleep. Hyperarousal during sleep was operationalized as subjective sleep quality as well as an increase in alpha and beta power in the EEG and a decrease in delta power. Results showed that subjective stress burden was negatively correlated with delta power and depression was associated with increased alpha power in the EEG. Intrusion tendency was positively correlated with beta power and negatively associated with subjective sleep quality. The authors point out that these results are in contradiction of previous findings suggesting a discrepancy between subjective measures of sleep and indices of sleep...

Hepatitis B and C

And C patients, abnormal EEG activity (e.g., general slowing of the basic rhythm and of the alpha wave) was associated with increased incidence of various psychological symptoms including mania, depression, and sleep disorders (Tanaka et al, 2004). This association appeared to be independent of multiple medical or treatment factors. Amodio et al (2005) confirmed the general slowing of the mean dominant frequency in hepatitis C patients and also observed increases in frontal alpha power and parietal theta power. These results, unlike those of Tanaka et al (2004), were unrelated to cognitive or other psychological factors.


Electrophysiological research on fibromyalgia has examined sleep, pain processing, general health, and cognitive function. The diagnosis of fibromyalgia is based on diffuse pain in four body quadrants with tenderness upon palpation at certain musculoskeletal points (Landis et al, 2004). Patients often complain of sleep problems such as experiencing non-restorative, restless sleep. A small literature suggests that alpha wave sleep enduring throughout the sleep cycle may characterize chronic pain conditions, particularly fibromyalgia (Rains and Penzien, 2003). Instead of falling into a deep sleep, fibromyal-gia patients may remain in a stage predominated by alpha waves, a waveform typically associated with drowsy wakefulness. Recent research has not strongly supported this observation. In a study of patients undergoing polysomnography to diagnose probable sleep disorders, a subset of patients who had abnormal alpha wave activity were identified (Rains and Penzien, 2003). Less than 40 of...

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Sleep disorders in the elderly. Describes the normal sleep and its aging, and common sleep disorders and their treatment. UniversityAlliance. Sleep Disorders of the Elderly American Academy of Family Physicians Management of Sleep Disorders in the Elderly. Veterans

How to tell time

Light-dark rhythm (photoperiod) is known to regulate production of the hormone melatonin that, in turn, regulates circadian (meaning around a day, as in a 24-hour period) rhythms by a feedback mechanism. In surface-dwelling vertebrates (including human), melatonin is produced during dark hours. It can therefore be expected that subterranean mammals living in constant darkness would display high melatonin levels. This does seem to be the case, yet the role of melatonin in regulating activity rhythms in subterranean animals remains obscure. The ability to perceive and recognize the length of the photoperiod is important for seasonal structuring of reproductive behavior. It has also been suggested that melatonin may suppress production of gonadotrophins, hormones which, in turn, control activity of gonads and, thus, the sexual behavior and reproductive biology. Nothing is known about this aspect in subterranean mammals. Also unclear is how circannual (approximately one year) cycles are...

Sleep Duration

The two most commonly assessed indices of sleep duration include time in bed and total sleep time (Hall et al, 2007a). Operationally, time in bed (TIB) may be defined as total hours elapsed between getting into bed to go to sleep at night ( good night time ) and waking up in the morning ( good morning time ). Total sleep time (TST) may be operationalized as time in bed minus the amount of time needed to fall asleep ( sleep latency ) and amount of time spent awake during the night ( wakefulness after sleep onset ). For example, if an individual gets in bed at 11 00 p.m., takes 30 min to fall asleep, is awake for a total of 30 min during the night, and gets out of bed at 6 00 a.m., their TIB and TST would equal 7 and 6 h, respectively. able to recall brief awakenings from sleep and thus may overestimate sleep duration in comparison to actigraphy- or PSG-assessed indices of sleep duration (Hall et al, under review Lauderdale et al, 2008 Owens et al, under review Silva et al, 2007)....

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