Psychobiology and Treatment Response in Primary Insomnia

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

Insomnia is a widely prevalent problem with serious consequences for mental and physical health, including risk for the development of major depressive and anxiety disorders. Fundamental questions persist regarding how affective disturbance is related to sleep disturbances; focusing on primary insomnia is a key to addressing these questions. The broad aim of this study is to better define the psychobiology of insomnia based on clues from its clinical phenomenology, responses to pharmacological treatment probes, and functional neuroimaging studies of sleep and wake states. Our model of primary insomnia emphasizes two major dimensions of dysfunction, affective disturbance and heightened central nervous system arousal. We propose that individuals with primary insomnia vary in their degree of affective disturbance and heightened arousal, leading to different individual profiles of sleep-wake behaviors. These different profiles may require pharmacotherapy specifically tailored to the individual's symptom constellation. In order to test our model, we will use innovative methods of clinical assessment (including mood and anxiety "spectrum" assessments and ecological momentary assessment of mood and arousal), pharmacological treatment problems, and [18F]-FDG positron emission tomography (PET) studies during wakefulness, NREM sleep to identify functional neuoanatomic correlates to affective disturbance and heightened arousal. We will address the following specific aims: Aim 1: To characterize the dimensions of affective disturbance and heightened arousal among patients with primary insomnia; the relationship of these dimensions to each other; and their relationships to insomnia symptoms. Aim 2: To determine the differential effects of treatment with an anti-depressant (nefazodone), a benzodiazepine receptor agonist (zolpidem), and placebo on the dimensions of affective disturbance and heightened arousal in patients with primary insomnia. Aim 3: To examine the functional neuroanatomy of primary insomnia during waking, NREM sleep, and REM sleep as related to the dimensions of affective disturbance and heightened arousal. Results from this study will lead to improved understanding of the psychobiology of primary insomnia and its relationship to mood and anxiety disorders; better recognition of relevant insomnia subgroups for future classifications; and the development of more targeted and effective treatments for primary insomnia.