Functional and structural brain alterations in insomnia: implications for pathophysiology.

Insomnia is defined as the complaint of not being able to fall asleep or to maintain sleep, and/or nonrestorative sleep, accompanied by impaired daytime functioning on a social, emotional or professional level. Insomnia per se is a very frequent complaint and can be caused by environmental, medical, mental or psychosocial factors or the intake of drugs. Primary insomnia is an insomnia subtype characterized by the absence of a causative medical or psychiatric factor. From a pathophysiological point of view, persistent hyperarousal on autonomous, emotional, cognitive or neurobiological levels is thought to be the decisive factor for the development and persistence of chronic primary insomnia. This view is supported by studies confirming that patients with primary insomnia display heightened levels of fast frequencies of the sleep EEG, show increased production of cortisol and interleukin-6, and demonstrate increased metabolism in several brain areas during sleep (as measured by positron emission tomography). Furthermore, primary insomnia is coupled with cognitive deficits during waking and with impairments of nocturnal memory consolidation. Just recently, reductions in hippocampal volume size have been reported in patients suffering from primary insomnia. In the light of neurobiological theories of sleep-wake regulation, primary insomnia may be conceptualised as the final common pathway of the interaction of a genetic vulnerability to an imbalance between arousing and sleep-inducing brain centres (which is triggered by psychosocial and/or medical stressors) with perpetuating mechanisms such as maladaptive behaviours, learned sleep-preventing associations and cognitive factors.