Human Sleep and Its Disorders

In this book we trace the development of several major themes in sleep research, from the first formal description of REM sleep in the early 1950s through the present. Chapter 1 provides those less familiar with this area with a perspective on the many possible ways to examine sleep. Chapter 2 describes in detail a major viewpoint of this book: that observations of pharmacological interventions affecting the neurotrans­ mitters may aid in the understanding of sleep regulation. The remain­ der of the book is devoted to endocrine systems related to sleep (chap. 3) and to the contribution of sleep research to the understanding of various pathological states (chaps. 4-7). The areas of investigation open to those who wish to understand sleep are much broader than the traditional problems of insomnia and narcolepsy. Such disorders as depression, schizophrenia, and alcoholism have long been associated with disordered sleep. Our search for an understanding of the latter phenomena may clarify the nature of these conditions.

1 An Introduction to Sleep Studies.- Techniques of Human Sleep Studies.- The Sleep Stages.- Waking.- NonREM Sleep.- Stage 1.- Stage 2.- Stages 3 and 4.- REM Sleep.- The REM-NonREM Cycle.- Sleep Stages and Age.- Effects of Temporal Variables on Sleep.- Physiological Variables Related to the Sleep Stages.- Sleep Deprivation.- Total Sleep Deprivation.- Selective Sleep Stage Deprivation.- Natural Long, Short, and Variable Sleepers.- Regulation of Sleep.- Passive versus Active Regulation.- The Neurotransmitters.- Pharmacologic and Anatomic Approaches.- Neurotransmitters and the REM-NonREM Cycle.- Neurotransmitters and Arousal.- Circulating Humors and Sleep.- Summary.- 2 A Pharmacologic Approach to Sleep Studies.- Serotonergic System.- L-Tryptophan and Sleep.- Effects of Administration on Sleep.- Metabolic Considerations.- 5-Hydroxytryptophan.- Parachlorophenylalanine.- Methysergide.- Lysergic Acid Diethylamide.- Ventricular Fluid 5-HIAA.- Noradrenergic System.- L-Dihydroxyphenylalanine (L-DOPA).- Effects on REM Sleep.- Effects on NonREM Sleep.- Threo-dihydroxyphenylserine (DOPS).- Alpha-Methyl-Paratyrosine (AMPT) and Alpha-Methyl-Phenylalanine (AMPA).- Alpha-Methyl-DOPA.- Pimozide.- Adrenergic Receptor Blockers.- Other Drugs Influencing Amines.- Monoamine Oxidase Inhibitors.- Tricyclic Antidepressants and Blockers of Amine Re-uptake.- Reserpine.- Debrisoquine.- Amphetamines.- Chlorpromazine.- Effect of Diets Deficient in Catecholamine Precursors.- Metabolites of Norepinephrine and Dopamine in the CSF.- Cholinergic System.- Histaminergic System.- Discussion.- Serotonin.- Serotonin or a Metabolite?.- Relation to REM Sleep.- Relation to NonREM Sleep.- Noradrenergic System.- Norepinephrine or a Precursor?.- Effects on REM Sleep.- Cholinergic System.- Histaminergic System.- Interaction between Transmitters.- Summary.- 3 Neuroendocrinology and Sleep.- Basic Concepts in Neuroendocrinology.- Growth Hormone.- Sleep-Related GH Secretion in Disease States.- Effects of Injections of GH on Sleep.- The Pituitary-Adrenal Axis.- Relation to Sleep-Waking Cycle.- Sleep-Related Cortisol Secretion in Disease States.- Effects of ACTH and Cortisol on the Sleep Stages.- Prolactin.- Relation of PRL Secretion to Other Hormones.- Effects of Drugs on Sleep-Related Prolactin Secretion.- Follicle-Stimulating Hormone and Luteinizing Hormone.- Relation of LH and FSH Secretion to Sleep.- Relation of Testosterone Secretion to Sleep.- Effects of Sex Hormones on Sleep.- Sleep-Related Secretion in Disease States.- Thyroid-Stimulating Hormone.- TSH Secretion and Sleep.- Sleep in Hyper- and Hypothyroidism.- CNS Actions of TRH.- Antidiuretic Hormone.- ADH Secretion during Sleep.- Effects of ADH on Sleep.- Melatonin.- Effects of Melatonin on Sleep.- Summary.- 4 Narcolepsy and Diseases of Excessive Sleep.- Definition.- Sleep Attacks.- Cataplexy.- Sleep Paralysis.- Hypnogogic and Hypnopompic Hallucinations.- Natural History.- Epidemiology and Genetics.- Etiology.- Narcolepsy-Cataplexy.- Secondary Narcolepsy.- Other Disorders of Excessive Daytime Sleep.- Independent Narcolepsy or NonREM Narcolepsy.- Obstructive Sleep Apnea Syndrome.- Narcolepsy with Sleep Apnea.- Hypersomnia with Automatic Behavior.- Hypersomnia with Sleep Drunkenness.- Excessive Daytime Sleepiness Associated with Known Organic Disease.- Excessive Daytime Sleepiness in Depression.- Diagnosis.- Pharmacotherapy of Narcolepsy.- Stimulants.- Tricyclic Antidepressants.- Monoamine Oxidase Inhibitors.- Methysergide.- Other Pharmacotherapies.- Summary.- 5 Clinical Studies of Insomnia.- Normal Sleep.- Incidence of Insomnia.- Kinds of Insomnia.- Tentative List of Causes of Insomnia.- Psychogenic.- Situational.- Alterations of Normal Activity—Rest Cycle.- Dream Related.- Sleep Apnea.- Restless Legs Syndrome.- Nocturnal Myoclonus.- Oversleeping.- Drug Related.- Neurological.- Secondary to or Accompanying a Medical Illness.- Sleep Induction.- Alcohol.- Benzodiazepines.- Mebutamate.- Barbiturates.- Chloral Hydrate.- Glutethimide.- Methaqualone.- Diphenhydramine.- L-Tryptophan.- Electrosleep.- An Approach to Patients Who Complain of Insomnia.- 6 Alcohol, Alcoholism, and the Problem of Dependence.- Animal Studies.- Ethanol and the Sleep EEG of Animals.- Ethanol and Behavioral Measures of Sleep.- Ethanol and Possible Neurotransmitters.- Animal Studies of Spontaneous Ethanol Selection.- Ethanol in Normal Human Subjects.- Effects of Ethanol on Chronic Alcoholics.- Sleep in “Dry” Alcoholics.- Response to Ethanol.- Sleep during Acute Withdrawal.- Issues Raised by Observations of the REM Sleep Rebound.- Experimental Therapies.- Summary.- 7 Affective Disorders and Schizophrenia.- Basic Definitions.- Affective Disorders.- Schizophrenia.- Studies of Sleep in Depressed Patients.- Comparative Studies.- Longitudinal Studies of Depressed Patients.- Sleep of Depressed Patients in Remission.- Chemical Correlates of Sleep in Depression.- Further Sleep Studies in Bipolar Illness.- Sleep during the Switch Process in Manic-Depressive Illness.- Experimental Deprivation of Sleep in Depression.- Effects of REM Sleep Deprivation on Depression.- Effects of Antidepressant Medication and Lithium Salts on Human Sleep.- Concluding Comments on Affective Disorders.- Sleep Studies in Schizophrenia.- Cross-Sectional Studies of Schizophrenia.- Longitudinal Studies of Sleep in Schizophrenia.- Experimental REM Deprivation in Schizophrenia.- Experimental Sleep Deprivation in Schizophrenia.- Effects of Neuroleptics on Sleep.- Concluding Remarks about Sleep in Schizophrenia.- Summary.