This proposal will support the research and further the applicant's training as a clinician-scientist at the nexus of psychiatry and sleep disorders medicine. Dr. Plante's goals are to examine the neurophysiology of hypersomnolence in depression during sleep and wakefulness, to identify biomarkers for excessive sleepiness, and to ultimately translate these findings into targeted neuromodulatory interventions for individuals with mood disorders. To achieve these aims, a didactic plan focused on the development of: 1) a stronger conceptual grounding of advanced high-density electroencephalogram (hdEEG) applications in mood and sleep disorders research, and 2) more sophisticated methodological skills including biostatistics and clinical trials design, will complement Dr. Plante's background n clinical psychiatry and sleep medicine. Training objectives will be accomplished through targeted coursework and multidisciplinary mentorship in the context of the comprehensive scholarly resources available at the University of Wisconsin School of Medicine and Public Health. The research plan will utilize knowledge and new techniques learned to investigate novel hypotheses regarding the nature of cortical oscillations during sleep and wakefulness in depressed patients with hypersomnia, and thereby alter clinical symptomatology. Adults with unipolar major depressive disorder (MDD) and co-morbid hypersomnolence will be evaluated during sleep and wake using hdEEG, and the nature of their slow wave activity during sleep and theta/alpha activity during wake contrasted with healthy controls and MDD participants without co-morbid hypersomnia. Additionally, hypersomnolent MDD participants will undergo overnight slow wave induction, a novel neuromodulatory therapy, to both examine the role of slow waves in excessive sleepiness and evaluate the efficacy of this somatic treatment in these patients. This prospective examination of the physiologic basis of hypersomnolence in mood disorders is designed to set the stage for the applicant to develop, and ultimately test, novel diagnostic and treatment modalities among hypersomnolent mood disordered patients with the potential to meaningfully improve quality of life and illness-related outcomes. Building on didactic training and data generated by these experiments, Dr. Plante will focus the latter stages of the award on obtaining training in the design of clinical trials and developing a randomized controlled trial of the use of slow wave induction as a novel treatment for mood disorders with co-morbid hypersomnia. At the end of the award period, Dr. Plante will be well-poised to extend his research in several novel directions with clear translational relevance as a fully independent investigator in sleep and psychiatric disorders.

Public Health Relevance

The goal of this research is to examine the biological basis of hypersomnia in major depressive disorder (MDD). Objective measures associated with daytime sleepiness and the restorative aspects of sleep, as well as treatments targeted at affecting these measures, will be examined. The research is a critical step in developing safe and effective treatments that will improve quality of life and the course of illness in patients sufferng from MDD, a major public health problem both nationally and internationally.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH099234-05
Application #
9180725
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Chavez, Mark
Project Start
2012-12-01
Project End
2017-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
5
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychiatry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Plante, David T (2018) Nocturnal sleep architecture in idiopathic hypersomnia: a systematic review and meta-analysis. Sleep Med 45:17-24
Plante, David T; Birn, Rasmus M; Walsh, Erin C et al. (2018) Reduced resting-state thalamostriatal functional connectivity is associated with excessive daytime sleepiness in persons with and without depressive disorders. J Affect Disord 227:517-520
Plante, David T; Cook, Jesse D; Goldstein, Michael R (2017) Objective measures of sleep duration and continuity in major depressive disorder with comorbid hypersomnolence: a primary investigation with contiguous systematic review and meta-analysis. J Sleep Res 26:255-265
Plante, David T (2017) Sleep propensity in psychiatric hypersomnolence: A systematic review and meta-analysis of multiple sleep latency test findings. Sleep Med Rev 31:48-57
Cook, Jesse D; Prairie, Michael L; Plante, David T (2017) Utility of the Fitbit Flex to evaluate sleep in major depressive disorder: A comparison against polysomnography and wrist-worn actigraphy. J Affect Disord 217:299-305
Plante, David T; Finn, Laurel A; Hagen, Erika W et al. (2017) Longitudinal associations of hypersomnolence and depression in the Wisconsin Sleep Cohort Study. J Affect Disord 207:197-202
Plante, David T; Finn, Laurel A; Hagen, Erika W et al. (2016) Subjective and Objective Measures of Hypersomnolence Demonstrate Divergent Associations with Depression among Participants in the Wisconsin Sleep Cohort Study. J Clin Sleep Med 12:571-8
Plante, David T; Goldstein, Michael R; Cook, Jesse D et al. (2016) Effects of partial sleep deprivation on slow waves during non-rapid eye movement sleep: A high density EEG investigation. Clin Neurophysiol 127:1436-1444
Goldstein, Michael R; Cook, Jesse D; Plante, David T (2016) The 5?-reductase inhibitor finasteride is not associated with alterations in sleep spindles in men referred for polysomnography. Hum Psychopharmacol 31:70-4
Plante, D T; Goldstein, M R; Cook, J D et al. (2016) Effects of oral temazepam on slow waves during non-rapid eye movement sleep in healthy young adults: A high-density EEG investigation. Int J Psychophysiol 101:25-32

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