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Three different annual cycles in House Sparrows are described: temperate resident, subtropical resident, and temerpate migratory annual cycles. Photoperiodic control of the annual cycle is described, with the role of photoperiod in stimulating gonadal development discussed, along with photorefractoriness. The role of the circadian rhythm in mediating photoperiodic information is also discussed, along with the interaction of melatonin secretion by the pineal gland and the suprachiasmatic nuclei (SCN) of the hypothalamus in regulating this endogenous rhythm.

This chapter considers the challenge of accounting for the mechanisms behind seasonal photoperiodic timing in mammals for two well-defined seasonal responses: reproductive activation and the molting cycle. Topics discussed include neuroanatomical basis to the seasonal control of breeding and the molt; organization of the mammalian “photoperiodic axis”; the control of melatonin synthesis; and the link between melatonin signal transduction and deiodinase-expressing cells.

A basic understanding of how endocrine dysfunction affects the central nervous system is important for a majority of cases referred for assessment by clinical neuropsychologists. Beyond playing a role in assessment and management in more obvious scenarios, such as pituitary adenoma and Graves' disease, increasing attention is being paid to the role of neuropsychology in assessment and management of cognitive dysfunction due to illnesses with direct or indirect effects on the endocrine system and, secondarily, the central nervous system. This chapter discusses principal syndromes of the neuroendocrine system, disorders involving the thyroid hormones, diabetes mellitus, disorders involving the reproductive hormones, disorders involving the adrenal hormones, and melatonin.

Given the expanding number of associations emerging between sleep behaviour and health, measurement of sleep will become increasingly important, if not obligatory, in population-based public health research. This chapter provides the epidemiologist with a basic understanding of the physiological principles underlying sleep-wake regulation and how they might be considered when measuring sleep in epidemiological studies. Sleep is an active, rhythmic process with periodicities on multiple time scales, including homeostatic, ultradian, and circadian cycles. Measurement of sleep first of all requires a definition of what sleep is and estimates of sleep behaviour can be captured using a range of different methods. The chapter highlights possible confounding factors that might be considered when interpreting sleep data, and discusses the potential for sleep to affect the accurate measurement of other biomarkers in health research.

Like all living things, plants or animals, humans are governed by time, specifically by idiosyncratic biological clocks. They measure both daily and yearly activities in essentially all living things. These clocks regulate sleep, eating, mating, and many other life-associated behaviors. But where are biological clocks to be found? How do they work? Clocks are at the heart of modern-day phenomena such as jet lag. How did the evolutionary history of clocks cause this? We now know that clocks are centered in the brain, and they are constantly being set and adjusted in response to external light. But even single-cell organisms without eyes or brains can measure time. An analysis of organisms as diverse as mold, fruit flies, mice, and humans has allowed us to dissect biological clocks in great detail, and to define the genes responsible for this important regulator of human behavior.

Monoamine oxidase (MAO) inhibitors were introduced as antidepressants about thirty years ago. The pharmacological mechanism of their antidepressant effect was related to the inhibition of MAO activity and limitation of the catabolism of the monoamines, serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline. Both monoamines play an important role in the regulation of melatonin biosynthesis from serotonin. This process involves the N-acetylation of serotonin to form N-acetylserotonin (NAS), which is catalysed by N-acetyltransferase (NAT). The synthesis of NAS is triggered by noradrenaline stimulation of the pinealocyte adrenoceptors (mainly β  ₁ receptors). The next step is methylation of NAS to form melatonin, which is catalysed by hydroxyindole-O-methyltransferase. The inhibition of MAO by MAO inhibitors is acute: it occurs within hours of the administration of a single dose. Both tricyclic and heterocyclic antidepressants increase the levels of melatonin in human plasma after administration of a single dose. A single electroconvulsive shock almost doubled rat pineal TV-acetyltransferase activity and the concentrations of melatonin and serotonin. This chapter concentrates on studies of the acute effect of MAO inhibitors on melatonin biosynthesis.

Electroconvulsive therapy is considered to be the most effective treatment for endogenous depression, but despite vigorous research there is no consensus on the mechanism of the antidepressant effect. One attempt to explain the mechanism uses a neuroendocrine hypothesis. Because it is generally accepted that the therapeutic effect of electroconvulsive shock (ECS) occurs after chronic (but not single) administration. In the past decade, evidence accumulated that depression might result from desynchronization of circadian rhythms. Such normalization is achieved simply by a single administration of the pineal gland hormone melatonin in rats. Also, administration of a single dose of melatonin has been reported to change circadian rhythms in humans. Elevation of human plasma melatonin levels was observed after a single dose of the heterocyclic antidepressants, desipramine and fluvoxamine, and of monoamine oxidase (MAO) inhibitors. If the stimulation of melatonin synthesis with consequent normalization of disrupted circadian rhythms is, indeed, the common denominator of the antidepressant effect, it is interesting to study the effect of ECS on melatonin synthesis.

Steroid hormones, including estrogens, play an important role in regulating aggressive behaviors in many vertebrate species. Recent studies have demonstrated that the effects of estrogens on aggressive behaviors are dependent on experience. Studies in the rodent genus Peromyscus indicate that estrogens affect aggressive behavior through different mechanisms under different photoperiod schedules. Under winter-like short days, estrogens were found to act rapidly to increase aggression whereas these rapid effects were absent under long days. In contrast estrogens were found to decrease aggression in mice in long days. Our working hypothesis for these results is that rapid effects of estrogens under short days are mediated by nongenomic pathways whereas the longer term effects of estrogens under long days are mediated by the transcriptional effects of estrogens. These data suggest the molecular pathways downstream of estrogen receptors may be subject to regulation by salient environmental cues such as photoperiod.

This chapter describes the blue moon phenomenon, the effect of anomalous aerosol light scattering, and the red tide and dead fish event caused by dinoflagellate and Gymnodinium brevis. Various studies on rhythmic leaf movements, circadian rhythm, and their control by the endogenous biological clock are presented. The chapter also discusses the incidence of bioluminescence in Gonyaulax polyedra, its mechanism, what causes it, and clock control. The role of melatonin in rhythms, biological rhythm research, and the circadian clock of Gonyaulax and its knowledge and usefulness are emphasized.

Normal dreaming occurs during the deepest sleep states. Obviously, if experiencing a frightening dream, sleeping people could be injured if they jumped out of bed and started to run. Fortunately, the brain has a natural protective mechanism during dreaming: body paralysis. During the primary sleep stage in which dreaming occurs, the body’s muscle tone is shut off and muscles become limp. Only the eye muscles are spared, still able to move during a dream. This state in which dreaming takes place is rapid eye movement (REM) sleep. Restated, during REM sleep, a switch is thrown in the brain stem that shuts off body movement during dreaming. People with Lewy disorders of all types often lose this switch function. In other words, they can still move during the dreams of REM sleep. In the midst of a dream, they may act out by yelling, kicking, or hitting the air. This behavior is termed dream enactment behavior. When it is a recurring event it is termed REM sleep behavior disorder. REM sleep behavior disorder occurs in people with Lewy disorders—Parkinson’s disease, DLB, or PDD. It also occurs in another disorder in which alpha-synuclein is abnormally deposited in the nervous system, multiple system atrophy (MSA). Recall from Chapter 2 that alpha-synuclein is present in Lewy bodies and is thought to be a causative factor in all of these conditions. REM sleep behavior disorder may be present years or even decades before the occurrence of DLB, PDD, Parkinson’s disease, or multiple system atrophy. It is often one of the first signs of these disorders, predating most other manifestations. That does not mean that everyone who acts out their dreams will eventually develop Parkinson’s disease, DLB, or MSA. However, it does confer an increased risk. It should be noted that certain medications may provoke REM sleep behavior disorder, such as the commonly used antidepressants. Also, sleepwalking in children should not be confused with this disorder. Sleepwalking occurs in a different sleep stage and is not thought to be a forerunner of Lewy body conditions.

This chapter presents an overview of potential maternal effects on behavioral development, including pre- and postnatal effects of social experiences, stress, and seasonality on the expression of developing phenotypes. It suggests that maternal effects will have a selective advantage when they increase the survival and reproductive success of offspring. This chapter also discusses effects of maternal physiology including gonadal hormones, glucocorticoids and melatonin on offspring phenotype.

There are about 400,000 species of plants in this world. Only a small fraction, perhaps 100 in number, contain hallucinogenic chemicals. Nearly a century ago, Lewis Lewin, professor of pharmacology at the University of Berlin, in speaking of drugs he called phantasticants, said “The passionate desire which … leads man to flee from the monotony of daily life … has made him discover strange substances (which) have been integral to human evolution both societal and cultural for thousands of years.” An unusual problem presents itself to me in writing about these drugs: They straddle the worlds of science and mysticism. The Encyclopedia Britannica defines mysticism as the practice of religious ecstasies (religious experiences during alternate states of consciousness), together with whatever ideologies, ethics, rites, myths, legends, and magic may be related to them. Science I am comfortable with; mysticism not so much. Yet in our exploration of the agents found in this chapter, we will encounter many persons speaking of drug-induced mystical experiences. I have attempted to get around my unease by first providing the history and the pharmacology of these agents and then touching only lightly on mysticism, allowing readers to draw their own conclusions. What shall we call these chemicals? Hallucinogen, a substance that induces perception of objects with no reality, is the term most commonly encountered and the one that I have settled on for the title of this chapter. However, it comes with a caveat. Albert Hofmann, the discoverer of LSD, our prototypic hallucinogen, has pointed out that a true hallucination has the force of reality, but the effects of LSD only rarely include this feature. Two additional terms that we will find useful are psychotomimetic and psychedelic. We have already considered the former, an ability to mimic psychosis, in our discussion of amphetamine-induced paranoid psychosis in chapter 4 and the effects of phencyclidine in chapter 6. A psychedelic was defined in 1957 by Humphrey Osmond, inventor of the word, as a drug like LSD “which enriches the mind and enlarges the vision.”

The term sleep disorder (somnipathy) simply means a disturbance of an individual’s normal sleep pat­tern. Doctors typically see patients in whom the dis­turbance is having a negative effect upon physical, mental, or emotional functioning, but subclinical dis­turbances of sleep are common and something almost everyone will suffer at some point in their life. Sleep disorders are a heterogeneous group, ranging from the frequently experienced insomnia to the extremely rare hypersomnias such as Kleine– Levin syndrome. However, there are many shared characteristics and this chapter will concentrate mainly on providing a framework for assessment, diagnosis, and manage­ment in the generic sense, with some guidance on spe­cific disorders in the latter sections. A good working knowledge of basic sleep disorders is essential in all specialties of clinical medicine. As a general rule, sleep disorders within the general hos­pital environment tend to be poorly managed, with great detriment to the patient. There are a variety of reasons why it is important to be able to diagnose and treat sleep disorders: … ● Epidemiology: sleep disorders are very common and affect all ages. ● Co- morbidities: sleep disturbances may be a primary disorder or secondary to a mental or physical disorder. They are often prodromal symptoms of psychiatric conditions. ● Impact upon physical health: poor sleep is linked to increased mortality and morbidity from many pathologies (see ‘Consequences of inadequate sleep’, p. 405). ● Medications (not just psychotropics) often affect sleep. ● Sleep disturbance is an important part of many primary psychiatric conditions (e.g. mood disorders, psychosis, anxiety disorders); further information on these can be found in the chapter relating to each disorder. … Sleep is a natural state of bodily rest seen in humans and many animals and is essential for survival. It is different from wakefulness in that the organism has a decreased ability to react to stimuli, but this is more easily reversible than in hibernation or coma. Sleep is poorly understood, but it is likely that it has several functions relating to restoration of body equilibrium and energy stores. There are a variety of theories re­garding the function of sleep, which are outlined in Box 28.1.

Most travel overseas is by air, although more and more people today, especially the elderly, are taking cruises. Passenger comfort has declined over the past 40 years despite the advances in aeronautics. This is due to the huge increase in the numbers travelling, the existence of cheaper flights, and the lack of staff to cope with the numbers of passengers both in airports and during flights. There is severe stress associated not only with air travel per se but also with all its accompaniments, such as getting through security, checking passports, tickets, and luggage, fear of overweight bags, finding the right gate, delays and cancellation of flights, missing connections, losing baggage, unexpected strikes, queueing interminably on arrival, and paying airport taxes. This list is seemingly endless.

Complementary and alternative medicine (CAM) is the collective term used for treatments or therapies that have not typically been part of Western medicine. The “complementary” part of this term means that the treatment may be used along with more conventional medicine, while the “alternative” component of the term implies that it may be used in place of traditional medi­cine. Most people in the United States choose not to forgo Western medicine and instead combine CAM and conventional medicine, preferring the term “integrative medicine” over “complementary and alternative medicine.” CAM purports to focus on the whole person, including the physical, mental, emotional, and spiritual components of health. A wide variety of treatments can fit under the umbrella of CAM treatments for autism spectrum disorder (ASD). In this chapter, we will discuss many of these treatments and the evidence base for them. According to studies, 50% to 75% of children with ASD are treated with CAM therapies. Even higher percentages of children with more severe ASD or intellectual disability are treated with CAM. Parents are also more likely to use CAM treatments if the child has seizures, gastrointestinal symptoms, or a behavioral disorder. Parents believe that these therapies are more accessible and less invasive. Most parents are more comfortable when they hear that a treatment falls under the CAM category because they believe it is more “natural” or safer (1, 2). CAM therapies have varying degrees of efficacy and safety data. These different CAM therapies fall under the larger categories of nutrition/dietary interventions, immunomodulation, biochemical and metabolic therapies, detoxification, manipulative and body-based practices, music therapy, sensory integration therapy, hippotherapy (horseback riding), dolphin swim therapy, hyperbaric oxygen therapy, and so forth. It is beyond the scope of this book to discuss each therapy in extensive detail, but I will give an introduction to each type of CAM treatment and then discuss the more important and controversial treatments (2).

Though definitions may vary from source to source, the term alkaloid generally refers to members of a large set of naturally occurring, slightly basic (i.e., alkaline) nitrogen-containing organic compounds. Generally excluded from this group are amino acids, peptides, proteins, N-containing carbohydrates, and nitrogenous bases used in the construction of nucleotides. Though a small number are produced by animals or microorganisms, the vast majority of alkaloids are plant-produced compounds possessing a remarkably diverse range of structural features, from simple cycloaliphatic amines to highly complex polycyclic N-heterocycles. Some representative alkaloids are shown in Fig. 7.1. Alkaloid-containing plants and their extracts have been used by humans for thousands of years, mainly on the basis of their stimulant, therapeutic, or poisonous properties. References to plants containing compounds such as morphine (from opium poppies), strychnine (from seeds of the Strychnos nux-vomica tree), ephedrine (from the plant Ephedra chinensis), and coniine (from the poison hemlock plant) may be found in some of our earliest known writings. Today, it has been estimated that the health care of over 5 billion people worldwide benefits from the use of plant-based medicinal agents, many of which are alkaloids. With that in mind, it is worth noting concerns that deforestation, environmental damage, large-scale development, and unregulated harvesting programs may ultimately lead to the extinction of hundreds of known medicinal plants and perhaps even more whose medicinal properties have yet to be discovered, thereby endangering the prospects for future discoveries of new curative agents for the benefit of all humankind. As a scientific field, alkaloid chemistry itself dates back to the early 1800s with the first isolation of pure crystalline morphine from opium. This milestone achievement allowed the delivery of accurate, therapeutic doses of a drug that was immensely valuable for the relief of pain but which could also lead to fatal overdoses when administered from simple extracts of variable composition and strength. The subsequent rapid development of increasingly sophisticated techniques for the isolation and purification of the active components (often alkaloids) from many other medicinal plants essentially spawned the field of organic chemistry.

In medical school, students learn about the human body by organ system. They spend a few weeks on the heart, then the lung, followed by the gastrointestinal tract. Eventually the whole body is covered. One of the fascinating developments in the last decade has been the functional linkage and new connections of seemingly diverse body systems. Fibromyalgia research finally hit its stride when important studies connected the nervous system, the endocrine (hormone) system, and the immune system. This enabled physicians to devise improved strategies to help fibromyalgia patients. Basic background information provided in this chapter will be expanded upon in later parts of the book when we review treatments. Within the brain is a small region known as the hypothalamus. It makes releasing hormones that travel down a short path to the pituitary gland, which makes stimulating hormones. The stimulating hormones send signals to tissues where hormones are manufactured for specialized functions. Table 3 and Figure 9 show how thyroid, cortisol, insulin, breast milk, and growth hormone are made along the hypothalamic-pituitary axis and the hypothalamic-pituitary-adrenal (HPA) axis. We have already mentioned that emotional stress can bring on or aggravate fibromyalgia. At the National Institutes of Health and the University of Michigan, studies have firmly established some of the factors important in this relationship. The role of corticotropin-releasing hormone (CRH), the precursor or ancestor of the steroid known as cortisol, has been the focus of much of this work. Even though CRH levels are normal in fibromyalgia, CRH responses (stress responses) to different forms of stimulation are blunted. CRH has many important interactions other than leading to the production of steroids. Its expression can be increased by stress, serotonin, and estrogen. Endorphins promote the secretion of CRH. Decreased sympathetic nervous system activity in the adrenal glands and substance P, as well as nitric oxide, can turn off CRH production. Rats with abnormally low stress responses develop many of the features we associate with fibromyalgia. How do these interrelationships translate into a fibromyalgia patient’s feeling of being unwell? The answer is not clear. However, these studies suggest that fibromyalgia patients do not respond normally to acute stress and do not release enough adrenalin.

Drowsiness is common in those with DLB and PDD, and can interfere with thinking and memory, as well as quality of life. There are a variety of potential reasons for this, many treatable. Getting a little sleepy during a boring task or napping after lunch on the weekend is not a sign of a medical problem. However, daytime drowsiness should draw attention in certain circumstances: 1. More than one nap most days, or near-daily naps that span 2 to 3 hours 2. Falling asleep during conversations or eating 3. Frequently falling asleep during reading, watching TV, doing computer work or other vigilant tasks 4. Returning to sleep after breakfast These are signs that could indicate that nighttime sleep was not adequate (nonrestorative) but could have other explanations. Daytime drowsiness has limited causes: 1. Insomnia at bedtime 2. Awakening during the night 3. Insufficient time spent in bed at night 4. Poor quality sleep at night (despite adequate time in bed) 5. Daytime medications inducing drowsiness 6. A primary sleep disorder directly causing drowsiness (which may be DLB or PDD related) We will explore each of these possible causes and how they might be diagnosed and treated. If a person with DLB or PDD is excessively drowsy, at least one of these could be the problem. Inability to get to sleep at bedtime can translate into sleepiness during the daytime. Many people with DLB or PDD who experience insomnia benefit from nighttime carbidopa/levodopa doses. The benefits of carbidopa/levodopa dosing at bedtime for Lewy-related insomnia were addressed in Chapter 9. Various other factors, however, may contribute to insomnia. Sometimes medications taken in the evening are alerting. Such drugs include duloxetine (Cymbalta) or venlafaxine (Effexor), used for depression and often dosed twice daily. Elimination of all but the morning dose may allow sleep in such cases. Other drugs for depression from the Prozac class (SSRIs; see the list in Chapter 18) may also cause insomnia if taken at bedtime. A simple strategy is to simply switch to morning dosing on a trial basis. The tricyclic antidepressants, such as nortriptyline, amitriptyline, or protriptyline, should not cause insomnia; they may induce sleep. Occasionally, sleepy people are prescribed stimulants with long-acting properties, such as extended-release methylphenidate (Concerta), modafinil (Provigil), or armodafinil (Nuvigil).