Andrew Krystal, MD

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Familial Natural Short Sleep: Genetics and Associations with Resilient and Major Depression

Dr. Andrew Krystal is the Ray and Dagmar Dolby Distinguished Professor in the Departments of Psychiatry and Neurology, Vice-Chair for Research in the Department of Psychiatry, Director of the Dolby Family Center for Mood Disorders, Director of the UCSF Interventional Psychiatry Program and Co-Director of the TMS & Neuromodulation Clinic. He is Board Certified in Clinical Neurophysiology by the American Board of Clinical Neurophysiology and the American Board of Psychiatry and Neurology and Board Certified in Psychiatry by the American Board of Psychiatry and Neurology. He is a pioneer in the application of computational modeling to the study of biomarker development using EEG in patients with depression and sleep disorders and application of biomarkers in treatment development clinical trials. He also has extensive experience in clinical and research personalization of therapies for the treatment of patients with mood disorders. He has been the principal investigator of more than 50 single-site and multi-site clinical trials.

Many papers and society guidelines recommend that all adults regularly get 7-9 hours of sleep for optimal health and function. However, such recommendations are not consistent with available data indicating that there is significant variability in the population in the vulnerability to and impact of sleep deprivation. Further, there is human and animal research indicating that there is a significant genetic component to total sleep time and response to sleep deprivation.
Building on these observations our group has identified and studied families that include individuals who consistently sleep less than the general population without any evident negative consequences. We have found that this short sleep phenotype, referred to as familial natural short sleep (FNSS), is inherited with an autosomal dominant pattern and have identified four genes that are associated with this trait both in those families and in mice bred to have these mutations.
This talk reviews these mutations, what is understand regarding the mechanisms by which they mediate the short-sleep phenotype based on mouse studies. In addition, we review the results of our efforts to study the behavior and physiology of these individuals with a focus on evidence that these mutations are associated with increased resilience and less depression.