N L Cutler

Oregon Health and Science University, Portland, OR, United States

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Publications (6)24.03 Total impact

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    ABSTRACT: Measuring the dim light melatonin onset (DLMO) is a useful and practical way to assess circadian phase position in humans. As a marker for the phase and period of the endogenous circadian pacemaker, the DLMO has been shown to advance with exposure to bright light in the morning and to delay with exposure to bright light in the evening. This ‘phase response curve’ (PRC) to light has been applied in the treatment of winter depression, jet lag and shift work, as well as circadian phase sleep disorders. Exogenous melatonin has phase-shifting effects described by a PRC that is about 12 h out of phase with the PRC to light. That is, melatonin administration in the morning causes phase delays and in the afternoon causes phase advances. All of the circadian phase disorders that have been successfully treated with appropriately timed exposure to bright light can be treated with appropriately scheduled melatonin administration. Melatonin administration is more convenient and therefore may be the preferred treatment.
    Ciba Foundation Symposium 183 - Circadian Clocks and their Adjustment, 09/2007: pages 303 - 326; , ISBN: 9780470514597
  • A J Lewy, N L Cutler, R L Sack
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    ABSTRACT: Several circadian rhythms have been used to assess the phase of the endogenous circadian pacemaker (ECP). However, when more than one marker rhythm is measured, results do not always agree. Questions then inevitably arise. Are there multiple oscillators? Are some markers more reliable than others? Masking is a problem for all marker rhythms. Masking of melatonin is minimized by sampling under dim light. The dim-light melatonin onset (DLMO) is particularly convenient since it can usually be obtained before sleep. However, assessing the DLMO in low melatonin producers may be problematic, particularly with the commonly used operationally defined threshold of 10 pg/ml. This study evaluates various circadian phase markers provided by the plasma melatonin profile in 14 individuals, several of whom are low melatonin producers. The amount (amplitude) of melatonin production appears to influence the phase of many points on the melatonin profile. Accordingly, when low producers are in a data set, we now prefer a lower DLMO threshold than the one previously recommended (10 pg/ml). Indeed, there are some low producers who never exceed this threshold at any time. Radioimmunoassays are now available that have the requisite sensitivity and specificity to support the use of a lower threshold. Nevertheless, the dim-light melatonin offset (DLMOff), even when operationally defined at thresholds less than 10 pg/ml, appears to be confounded by amplitude in this study; in such cases, it may be preferable to use the melatonin synthesis offset (SynOff) because it is not confounded by amplitude and because, theoretically, it is temporally closer to the endogenous mechanism signaling the offset of production. The question of whether the termination mechanism of melatonin synthesis is related to an interval timer or to a second oscillator loosely coupled to the onset oscillator is probably best answered using the SynOff rather than the DLMOff. It is hoped that these findings will make a useful contribution to the debate on the best ways to use points on the melatonin profile to assess circadian phase position in humans.
    Journal of Biological Rhythms 07/1999; 14(3):227-36. · 3.23 Impact Factor
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    ABSTRACT: According to the phase-shift hypothesis for winter depression, morning light (which causes a circadian phase advance) should be more antidepressant than evening light (which causes a delay). Although no studies have shown evening light to be more antidepressant than morning light, investigations have shown either no difference or morning light to be superior. The present study assesses these light-exposure schedules in both crossover and parallel-group comparisons. Fifty-one patients and 49 matched controls were studied for 6 weeks. After a prebaseline assessment and a light/dark and sleep/wake adaptation baseline week, subjects were exposed to bright light at either 6 to 8 AM or 7 to 9 PM for 2 weeks. After a week of withdrawal from light treatment, they were crossed over to the other light schedule. Dim-light melatonin onsets were obtained 7 times during the study to assess circadian phase position. Morning light phase-advanced the dim-light melatonin onset and was more antidepressant than evening light, which phase-delayed it. These findings were statistically significant for both crossover and parallel-group comparisons. Dim-light melatonin onsets were generally delayed in the patients compared with the controls. These results should help establish the importance of circadian (morning or evening) time of light exposure in the treatment of winter depression. We recommend that bright-light exposure be scheduled immediately on awakening in the treatment of most patients with seasonal affective disorder.
    Archives of General Psychiatry 11/1998; 55(10):890-6. · 13.77 Impact Factor
  • A J Lewy, V K Bauer, N L Cutler, R L Sack
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    ABSTRACT: Five patients with winter depression received low doses of melatonin in the afternoon, and five patients received placebo capsules. Melatonin treatment significantly decreased depression ratings compared to placebo. If these findings are replicated in a larger sample with documentation of expected phase shifts, the phase shift hypothesis will be substantially supported.
    Psychiatry Research 02/1998; 77(1):57-61. · 2.68 Impact Factor
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    ABSTRACT: Melatonin's timekeeping function is undoubtedly related to the fact that it is primarily produced during nighttime darkness; that is, melatonin and light occur at opposite times. The human phase response curve (PRC) to melatonin appears to be about 12h out of phase with the PRC to light. These striking complementarities, together with light's acute suppressant effect on melatonin production, suggest that a function for endogenous melatonin is to augment entrainment of the circadian pacemaker by the light-dark cycle. The melatonin PRC also indicates correct administration times for using exogenous melatonin to treat circadian phase disorders.
    Chronobiology International 02/1998; 15(1):71-83. · 4.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Measuring the dim light melatonin onset (DLMO) is a useful and practical way to assess circadian phase position in humans. As a marker for the phase and period of the endogenous circadian pacemaker, the DLMO has been shown to advance with exposure to bright light in the morning and to delay with exposure to bright light in the evening. This 'phase response curve' (PRC) to light has been applied in the treatment of winter depression, jet lag and shift work, as well as circadian phase sleep disorders. Exogenous melatonin has phase-shifting effects described by a PRC that is about 12 h out of phase with the PRC to light. That is, melatonin administration in the morning causes phase delays and in the afternoon causes phase advances. All of the circadian phase disorders that have been successfully treated with appropriately timed exposure to bright light can be treated with appropriately scheduled melatonin administration. Melatonin administration is more convenient and therefore may be the preferred treatment.
    Ciba Foundation symposium 02/1995; 183:303-17; discussion 317-21.