The is an application for an ADAMHA Research Scientist Award (Level II). The candidate will use the award to devote his full professional energies to research projects at the interface of psychiatry, sleep disorders medicine and circadian rhythms. He will focus particularly on the development of melatonin as a treatment for disorders of circadian phase. Melatonin is a hormone produced by the pineal gland at night that may be involved in the natural regulation of circadian rhythms. Animal studies have shown that exogenous melatonin administration can synchronize """"""""free- running"""""""" circadian rhythms and can accelerate the rate of adaptation to a new rest/activity cycle. In this project, the constraining effects of the light-dark cycle will be evaluated by giving melatonin to both blind and sighted subjects. The parameters that produce the maximal phase-advancing effects in both groups will be defined by varying the timing, dose and duration of melatonin administration. An attempt to enhance the phase-advancing effects of exogenous melatonin will be made by the co-administration of melatonin with atenolol, a drug that suppresses endogenous melatonin production by blocking pineal beta adrenergic receptors. After defining the optimal treatment parameters, the effects of melatonin in sighted subjects who are adapting to an abrupt advance of their sleep-wake cycle (a laboratory model of shift work adaptation) will be tested. The phase-advancing effects of exogenous melatonin administration will be evaluated by measuring its effect on the timing (phase) of endogenous melatonin production by the pineal gland. Phase will be assessed by obtaining serial blood samples and measuring plasma melatonin concentrations to determine the precise """"""""onset"""""""" of active production. These studies may lead to the use of melatonin as a way to treat both blind and sighted patients with abnormal circadian rhythms.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research (K02)
Project #
Application #
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Schools of Medicine
United States
Zip Code
Koch, Hannah; McCormack, Kai; Sanchez, Mar M et al. (2014) The development of the hypothalamic-pituitary-adrenal axis in rhesus monkeys: effects of age, sex, and early experience. Dev Psychobiol 56:86-95
Sanchez, Mar M; McCormack, Kai; Grand, Alison P et al. (2010) Effects of sex and early maternal abuse on adrenocorticotropin hormone and cortisol responses to the corticotropin-releasing hormone challenge during the first 3 years of life in group-living rhesus monkeys. Dev Psychopathol 22:45-53
Maestripieri, Dario; McCormack, Kai; Lindell, Stephen G et al. (2006) Influence of parenting style on the offspring's behaviour and CSF monoamine metabolite levels in crossfostered and noncrossfostered female rhesus macaques. Behav Brain Res 175:90-5
Maestripieri, Dario; Higley, J Dee; Lindell, Stephen G et al. (2006) Early maternal rejection affects the development of monoaminergic systems and adult abusive parenting in rhesus macaques (Macaca mulatta). Behav Neurosci 120:1017-24
Sanchez, Mar M; Noble, Pamela M; Lyon, Casie K et al. (2005) Alterations in diurnal cortisol rhythm and acoustic startle response in nonhuman primates with adverse rearing. Biol Psychiatry 57:373-81
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
Blood, M L; Sack, R L; Percy, D C et al. (1997) A comparison of sleep detection by wrist actigraphy, behavioral response, and polysomnography. Sleep 20:388-95
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