Sleep Disorders

Improve our understanding of the processes that lead to specific sleep disorders in children and adults. The following disorders are included in this summary due to both their prevalence and their impact on afflicted patients:

Insomnia (difficulty initiating or maintaining sleep): This should include the development of animal models of insomnia, the study of specific insomnia phenotypes and the application of neurophysiologic, neurochemical, neuroanatomic and functional neuroimaging approaches to the study of insomnia in humans. Understanding why women are at higher risk for insomnia should be a goal as well. Finally, genetic, genomic and proteomic studies are also needed.

Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD): Studies should address the role of altered central dopaminergic mechanisms and abnormal iron metabolism in their pathogenesis. Further development, refinement and validation of animal models of RLS and PLMD are also needed. The use of neuropathologic techniques in the evaluation of brains and spinal cords of affected patients are likely to be useful as well.

Sleep-Disordered breathing (sleep apnea) and disorders of ventilatory control: These studies should address the processes that control both upper airway patency and ventilation itself with a particular focus on the influence of sleep on these biologic processes. The neural connections, neuromodulators and molecular events mediating these state-dependent processes affecting respiration during sleep need to be studied.

Primary disorders leading to hypersomnolence: The neural mechanisms leading to hypersomnolence in conditions such as narcolepsy or primary central nervous system hypersomnolence need to be investigated, and the focus these studies should be how the neurobiologic causes of hypersomnolence differ from or resemble the effects of sleep loss.

An assessment of normal human sleep phenotypes and the normal range of variation in this phenotype in adults and children (including racial and ethnic differences) is needed, not only to establish normative standards but also to serve as a model for recommended sleep behaviors. This assessment should include sleep duration, sleep stage distribution, sleep timing, sleep disruption, sleep quality, and other variables by which sleep and sleepiness can be quantitatively evaluated.

Once normal sleep phenotypes are defined, the associated genotypes should be fully evaluated.

Abnormal sleep phenotypes should subsequently be recognizable and genotyping of these individuals should then be pursued to define the genetic underpinning of abnormal sleep or altered circadian rhythm profiles. The impact of single nucleotide polymorphisms (SNPs) on normal sleep phenotypes should be testable as well.

The phenotype of patients with specific sleep disorders should be carefully defined in order to set the stage for subsequent genetic testing.

Methods to define normal and abnormal phenotypes through questionnaires or simple non-invasive testing should be a goal. Population surveillance and assessment of associated morbidities will then be possible on a large scale.