Circadian phase position of normal subjects will be assessed by measuring their plasma melatonin levels in the evening under dim light to determine the nighttime onset of melatonin production by the pineal gland (the dim light melatonin onset, or DLMO). As a marker for circadian phase position, the DLMO appears to accurately reflect the phase-shifting effects of light. These phase-shifting effects will be evaluated in normals and compared to patients suspected of having chronobiologic sleep and mood disorders. Normal subjects will be studied on repeated occasions in order to evaluate inter- and intrasubject variability, as well as time of year effects. There will also be studies to define the phase response curve in normals. Five types of patients will be studied: advanced sleep phase syndrome, delayed sleep phase syndrome, winter depression, unipolar depression and bipolar depression. We propose to test four hypotheses: 1) intraindividual variability in the DLMO can be decreased by a week of standardized light-dark conditions; 2) human circadian rhythms are regulated by bright light according to a phase response curve similar to those described for other animals; 3) bright light is more important than social cures in synchronizing human circadian rhythms; and 4) phase advanced sleep and mood disorders will respond to bright light in the evening and phase delayed disorders will respond to bright light in the morning. We propose to do seven experiments: 1) melatonin production and response to light in normal subjects; 2) effect of social cues on circadian rhythms in normal subjects; 3) effect of light pulses on circadian rhythms in normal subjects; 4) - 6) treatment of putatively chronobiologic sleep and mood disorders with appropriately timed bright light; and 7) effect of shifting sleep on circadian rhythms in normal subjects. These investigations should help us decide how to optimally treat patients with bright light and to identify patients with abnormally advanced and delayed circadian rhythms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH000703-02
Application #
3070110
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Lewy, A J; Bauer, V K; Cutler, N L et al. (1998) Morning vs evening light treatment of patients with winter depression. Arch Gen Psychiatry 55:890-6
Lewy, A J; Bauer, V K; Cutler, N L et al. (1998) Melatonin treatment of winter depression: a pilot study. Psychiatry Res 77:57-61
Lewy, A J; Bauer, V K; Ahmed, S et al. (1998) The human phase response curve (PRC) to melatonin is about 12 hours out of phase with the PRC to light. Chronobiol Int 15:71-83
Sack, R L; Lewy, A J (1997) Melatonin as a chronobiotic: treatment of circadian desynchrony in night workers and the blind. J Biol Rhythms 12:595-603
Lewy, A J; Sack, R L (1997) Exogenous melatonin's phase-shifting effects on the endogenous melatonin profile in sighted humans: a brief review and critique of the literature. J Biol Rhythms 12:588-94
Lewy, A J; Ahmed, S; Sack, R L (1996) Phase shifting the human circadian clock using melatonin. Behav Brain Res 73:131-4
Lewy, A J; Sack, R L (1996) The role of melatonin and light in the human circadian system. Prog Brain Res 111:205-16
Lewy, A J; Sack, R L; Blood, M L et al. (1995) Melatonin marks circadian phase position and resets the endogenous circadian pacemaker in humans. Ciba Found Symp 183:303-17;discussion 317-21
Lewy, A J; Ahmed, S; Jackson, J M et al. (1992) Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int 9:380-92
Sack, R L; Lewy, A J; White, D M et al. (1990) Morning vs evening light treatment for winter depression. Evidence that the therapeutic effects of light are mediated by circadian phase shifts. Arch Gen Psychiatry 47:343-51

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