Etiology and Pathophysiology of Insomnia

Of all the sleep disorders, insomnia is perhaps the only one where there has been a substantial amount of top-down theorization. This may be the case because a framework is required to comprehend a disorder that has multiple causes and an insidious and progressive course. In this chapter, four general models of the etiology and pathophysiology of insomnia are summarized and critically evaluated. In particular, we review how each model characterizes the hyperarousal that is thought to be responsible for disturbing sleep continuity. Additional information is provided on how sleep homeostasis and circadian considerations may mediate, moderate, or interact with the hyperarousal. Insomnia is often considered a disorder of hyperarousal; that is, the patient has a level of arousal that is incompatible with the initiation or maintenance of sleep. The concept of hyperarousal is, however, likely to be quite complex. What is meant by arousal? How does it become elevated? Is hyperarousal a tonic phenomenon, and if not, what factors mediate or moderate its occurrence or intensity? Is arousal a singular construct, and are hyperarousal and sleep necessarily mutually exclusive? In this chapter, we review physiologic, cognitive, behavioral, and neurocognitive models of insomnia. Each of these will be summarized as it pertains to primary insomnia and sleep state misperception insomnia (paradoxical insomnia). These models may also be relevant to the extrinsic or secondary insomnias, which, when chronic, have a great deal in common with primary insomnia.1,2 In addition to reviewing the four models, we also summarize how sleep homeostasis and circadian considerations mediate, moderate, or interact with hyperarousal. Finally, we review a recent hypothesis that suggests that hyperarousal may be better conceptualized as a failure of wakefulness inhibition. PHYSIOLOGIC MODEL OF INSOMNIA The physiologic model suggests that chronic insomnia may be understood as a condition in which the patient has a trait level of arousal, or a level of arousal prior to or during the preferred sleep period, that is incompatible with good sleep continuity. This model assumes that physiologic arousal and sleep are mutually exclusive. Studies evaluating physiologic arousal in insomnia have used a variety of techniques, including basic psychophysiologic measures, whole-body metabolic rate, heart rate variability, caffeine-induced insomnia, neuroendocrine measures, and functional neuroimaging. The studies discussed next support the general concept of physiologic hyperarousal but have yet to be integrated into a formal model that explains how insomnia develops and how arousal effects promote sleeplessness (Fig. 60–1). Psychophysiolgic Measures of Arousal Early studies comparing elevated physiologic arousal between poor sleepers and good sleepers were based on electrophysiologic measures of heart rate, respiration rate, skin and core body temperature, muscle tone, skin conductance and resistance, and peripheral blood flow or vasoconstriction.3-8 Overall, these studies showed that poor sleepers exhibit increased physiologic arousal, and in the case of ECG measures of heart rate, this arousal was particularly evident at sleep onset. Several methodologic difficulties limit the interpretation of these studies. First, subjects in these investigations would not necessarily meet current definitions for primary insomnia, and the inclusion of subjects with other types of insomnia (e.g., sleep phase delay disorder or insomnia secondary to major depression) could have influenced the findings. Second, it is not clear whether these studies carefully excluded short episodes of sleep prior to consolidated sleep onset or short awakenings after sleep onset. The failure to do so could account for some of the sleep onset and nocturnal findings regarding hyperarousal. Third, most of the early studies did not distinguish between state and trait hyperarousal. This distinction is important in order to determine whether physiologic hyperarousal is a 24-hour phenomenon or whether it occurs only at night, only during the sleep period, or only in association with sleep-related stimuli. Of the early studies that provided data regarding this last issue, the results varied based on the measures and protocols adopted.6,7 When examining body temperature, Adam and colleagues found persistent effects across the day. 714 Figure 60–1. The physiologic model. THE PHYSIOLOGIC MODEL