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Biomedical subjects

Jeffrey A Elliott

Publications and source records attributed to Jeffrey A Elliott.

At least 19 recordsLinked to original sources

Daily illumination exposure and melatonin: influence of ophthalmic dysfunction and sleep duration.

BACKGROUND: Ocular pathology lessens light's efficacy to maintain optimal circadian entrainment. We examined whether ophthalmic dysfunction explains unique variance in melatonin excretion of older adults over and above the variance explained by daily illumination, medical, and sociodemographic factors. We also examined whether ophthalmic dysfunction influences relationships between ambient illumination and melatonin. METHODS: Thirty older adults (mean age = 69 years; Blacks = 42% and Whites = 58%) of both genders participated in the study. Demographic and health data were collected at baseline. Participants underwent eye exams at SUNY Downstate Medical Center, wore an actigraph to monitor illumination and sleep, and collected urine specimens to estimate aMT6s concentrations. RESULTS: Hierarchical regression analysis showed that illumination factors explained 29% of the variance in aMT6s mesor. The proportion of variance explained by ophthalmic factors, sleep duration, and race was 10%, 2%, and 2%, respectively. Illumination factors explained 19% of the variance in aMT6s acrophase. The proportion of variance explained by ophthalmic factors, sleep duration, and race was 11%; 17%; and 2%, respectively. Controlling for sleep duration and race reduced the correlations between illumination and melatonin, whereas controlling for ophthalmic factors did not. CONCLUSION: Ophthalmic exams showed that elevated intraocular pressure and large cup-to-disk ratios were independently associated with earlier melatonin timing. Lower illumination exposure also had independent associations with earlier melatonin timing. Conceivably, ophthalmic and illumination factors might have an additive effect on the timing of melatonin excretion, which in turn might predispose individuals to experience early morning awakenings.

Journal Article↗

Bright light treatment of depression for older adults [ISRCTN55452501].

BACKGROUND: The incidence of insomnia and depression in the elder population is significant. It is hoped that use of light treatment for this group could provide safe, economic, and effective rapid recovery. METHODS: In this home-based trial we treated depressed elderly subjects with bright white (8,500 Lux) and dim red (<10 Lux) light for one hour a day at three different times (morning, mid-wake and evening). A placebo response washout was used for the first week. Wake treatment was conducted prior to the initiation of treatment, to explore antidepressant response and the interaction with light treatment. Urine and saliva samples were collected during a 24-hour period both before and after treatment and assayed for aMT6s and melatonin respectively to observe any change in circadian timing. Subjects wore a wrist monitor to record light exposure and wrist activity. Daily log sheets and weekly mood (GDS) and physical symptom (SAFTEE) scales were administered. Each subject was given a SCID interview and each completed a mood questionnaire (SIGH-SAD-SR) before and after treatment. Also, Hamilton Depression Rating (SIGH-SAD version) interviews were conducted by a researcher who was blind to the treatment condition. A control group of healthy, age-matched, volunteers was studied for one day to obtain baseline data for comparison of actigraphy and hormone levels. RESULTS: Eighty-one volunteers, between 60 and 79 years old, completed the study. Both treatment and placebo groups experienced mood improvement. Average GDS scores improved 5 points, the Hamilton Depression Rating Scale (HDRS) 17 scores (extracted from the self-rated SIGH-SAD-SR) improved 6 points. There were no significant treatment effects or time-by-treatment interactions. No significant adverse reactions were observed in either treatment group. The assays of urine and saliva showed no significant differences between the treatment and placebo groups. The healthy control group was active earlier and slept earlier but received less light than the depressed group at baseline. CONCLUSION: Antidepressant response to bright light treatment in this age group was not statistically superior to placebo. Both treatment and placebo groups experienced a clinically significant overall improvement of 16%.

Age Factors↗

Circadian phase-shifting effects of a laboratory environment: a clinical trial with bright and dim light.

BACKGROUND: Our aims were to examine the influence of different bright light schedules on mood, sleep, and circadian organization in older adults (n = 60, ages 60-79 years) with insomnia and/or depression, contrasting with responses of young, healthy controls (n = 30, ages 20-40 years). METHODS: Volunteers were assessed for one week in their home environments. Urine was collected over two 24-hour periods to establish baseline acrophase of 6-sulphatoxymelatonin (aMT6s) excretion. Immediately following home recording, volunteers spent five nights and four days in the laboratory. Sleep periods were fixed at eight hours in darkness, consistent with the volunteers' usual sleep periods. Volunteers were randomly assigned to one of three light treatments (four hours per day) within the wake period: (A) two hours of 3,000 lux at 1-3 hours and 13-15 hours after arising; (B) four hours of 3,000 lux at 6-10 hours after arising; (C) four hours of dim placebo light at 6-10 hours after arising. Lighting was 50 lux during the remainder of wakefulness. The resulting aMT6s acrophase was determined during the final 30 hours in the laboratory. RESULTS: Neither mood nor total melatonin excretion differed significantly by treatment. For the three light treatments, significant and similar phase-response plots were found, indicating that the shift in aMT6s acrophase was dependent upon the circadian time of treatment. The changes in circadian timing were not significantly correlated to changes in sleep or mood. CONCLUSION: The trial failed to demonstrate photoperiodic effects. The results suggest that even low levels of illumination and/or fixed timing of behavior had significant phase-shifting effects.

Journal Article↗

Influence of photoperiod and running wheel access on the entrainment of split circadian rhythms in hamsters.

BACKGROUND: In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion) and for the day (e.g., rest and low melatonin secretion). Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition. RESULTS: Rhythm splitting was observed in wheel-running and general locomotion of Siberian and Syrian hamsters. The latter also manifest split rhythms in body temperature. Access to a running wheel was necessary neither for the induction nor maintenance of this entrainment pattern. While rhythms were only transiently split in many animals with two 5 h nights, the incidence of splitting was greater with twice daily nights of shorter duration. Removal of running wheels altered the body temperature rhythm but did not eliminate its clear bimodality. CONCLUSION: The expression of entrained, split circadian rhythms exhibits no strict dependence on access to a running wheel, but can be facilitated by manipulation of ambient lighting conditions. These circadian entrainment patterns may be of therapeutic value to human shift-workers and others facing chronobiological challenges.

Animals↗

Circadian entrainment and phase resetting differ markedly under dimly illuminated versus completely dark nights.

An endogenous circadian pacemaker uses photic input to synchronize mammalian physiological and behavioral rhythms to the 24 h day. Sunlight during dusk and dawn is thought to entrain the pacemaker of nocturnal rodents, whereas moonlight and starlight are presumed to exert little influence. We show that, to the contrary, dim illumination (<0.005 lux), similar in intensity to starlight and dim moonlight, markedly alters entrainment of hamster activity rhythms. Under 24 h light:dark:light:dark cycles (LDLD), for example, activity rhythms can disassociate, or split, into two distinct components, and the incidence of split entrainment is increased when daily scotophases are dimly lit rather than completely dark. The three present studies examine whether dim illumination promotes LDLD-induced splitting (1) by increasing nonphotic feedback during novelty-induced activity bouts, (2) by potentiating nonphotic and/or photic resetting, or (3) by influencing phase jumping responses under skeleton photoperiods simulating increases in day length. Experiment 1 illustrates that dim-exposed animals display split rhythms, while animals without dim light do not, despite equivalent activity levels. In Experiments 2 and 3, dim illumination potentiated both nonphotic and photic resetting, and the specific nature of these interactions suggests mechanisms through which dim illumination may alter entrainment under LDLD. Dim light likely promotes LDLD-induced splitting by facilitating both nonphotic resetting and bright light-induced phase jumping in animals entrained to short nights. The actions of dim illumination may be distinct from canonical responses to bright light, and potentially influence the interactions between oscillators comprising the circadian pacemaker.

Activity Cycles↗

Scotopic illumination enhances entrainment of circadian rhythms to lengthening light:dark cycles.

Endogenously generated circadian rhythms are synchronized with the environment through phase-resetting actions of light. Starlight and dim moonlight are of insufficient intensity to reset the phase of the clock directly, but recent studies have indicated that dim nocturnal illumination may otherwise substantially alter entrainment to bright lighting regimes. In this article, the authors demonstrate that, compared to total darkness, dim illumination at night (< 0.010 lux) alters the entrainment of male Syrian hamsters to bright-light T cycles, gradually increasing in cycle length (T) from 24 h to 30 h. Only 1 of 18 hamsters exposed to complete darkness at night entrained to cycles of T > 26 h. In the presence of dim nocturnal illumination, however, a majority of hamsters entrained to Ts of 28 h or longer. The presence or absence of a running wheel had only minor effects on entrainment to lengthening light cycles. The results further establish the potent effects of scotopic illumination on circadian entrainment and suggest that naturalistic ambient lighting at night may enhance the plasticity of the circadian pacemaker.

Animals↗

Ethnicity, sleep, mood, and illumination in postmenopausal women.

BACKGROUND: This study examined how ethnic differences in sleep and depression were related to environmental illumination and circadian rhythms. METHODS: In an ancillary study to the Women's Health Initiative, 459 postmenopausal women were recorded for one week in their homes, using wrist monitors. Sleep and illumination experience were estimated. Depression was self-rated with a brief adjective check list. Affective diagnoses were made using the SCID interview. Sleep disordered breathing was monitored with home pulse oximetry. RESULTS: Hispanic and African-American women slept less than European-American women, according to both objective recordings and their own sleep logs. Non-European-American women had more blood oxygen desaturations during sleep, which accounted for 26% of sleep duration variance associated with ethnicity. Hispanic women were much more depressed. Hispanic, African-American and Native-American women experienced less daily illumination. Less daily illumination experience was associated with poorer global functioning, longer but more disturbed sleep, and more depression. CONCLUSIONS: Curtailed sleep and poor mood were related to ethnicity. Sleep disordered breathing was a factor in the curtailed sleep of minority women. Less illumination was experienced by non-European-American women, but illumination accounted for little of the contrasts between ethnic groups in sleep and mood. Social factors may be involved.

Black or African American↗

Naps and circadian rhythms in postmenopausal women.

BACKGROUND: Napping patterns and relationships among naps, circadian rhythms, and nocturnal sleep were evaluated in postmenopausal women. Naps and nocturnal sleep were compared between depressed women and healthy volunteers. METHODS: The study included 436 postmenopausal women between the ages of 50 and 81 years. Psychiatric interviews were conducted using the Structured Clinical Interview for DSM-IV Axis I Disorders. Each participant wore a wrist-activity monitor and kept a daily sleep log at home for 1 week. The major urinary melatonin metabolite (6-sulfatoxymelatonin [aMT6s]) was measured for two 24-hour periods at home. RESULTS: There was no significant difference in naps and nocturnal sleep patterns between depressed participants (n = 30) and those with no history of mental disorder (n = 222). Three peaks occurred in the timing of napping: approximately 1 hour before bedtime, 8 to 9 hours after wake-up time, and 2 hours after waking, in descending order of magnitude. Significant inverse correlations were observed between evening nap duration and both wake-up time and aMT6s acrophase. The onset time of aMT6s excretion was advanced by 32 minutes in evening nappers. CONCLUSIONS: Evening napping, a characteristic of these postmenopausal women, may be related to an advance of circadian rhythms in this age group. Relationships between evening napping and earlier wake-up time may be a common manifestation of advanced circadian rhythms or may be a homeostatic effect.

Aged↗

Melatonin excretion with affect disorders over age 60.

Numerous studies have reported low melatonin secretion in depression, but other studies have suggested no deficit or an increase. Alterations of circadian phase or duration of melatonin secretion have also been described. Since melatonin secretion decreases as we age, it seemed interesting to examine melatonin and depression in an aging sample. Volunteers who complained of mood or sleep problems were recruited for studies in which fractional urine specimens were collected for 24 h, both at home and in the laboratory. The major metabolite, 6-sulfatoxymelatonin (aMT6s), was determined by radioimmunoassay. Of 72 volunteers aged 60-78 years, seven had current major depression and 55% had a lifetime history of an affective disorder. A 55-fold range of home aMT6s excretion rates was observed. A lifetime history of any affective disorder was significantly associated with greater log(10)[mesor] aMT6s excretion in home collections and laboratory collections, but current affective disorders were neither significantly related to melatonin excretion nor to aMT6s acrophase timing, onset, offset or duration. These results are only weakly consistent with a photoperiodic hypothesis of depression.

Aged↗

Luteinizing hormone following light exposure in healthy young men.

Urinary luteinizing hormone (LH) and the melatonin metabolite (6-sulfatoxymelatonin; aMT6s) were measured in normal young men following early morning light exposure. Eleven young healthy men ages 19-30 years participated in this study. During separate weeks in counterbalanced order, each subject received both 5 days of bright light treatment (BL) and 5 days of placebo light treatment (PL) for 1 h (05:00-06:00). LH excretion was increased 69.5% after bright light exposure, but was not changed by placebo light exposure. The acrophases and offsets of aMT6s were advanced, but the duration of aMT6s excretion was not changed after BL. Light stimulation of LH could have interesting applications in psychiatry and reproductive endocrinology.

Adult↗

Actigraphy suggests age-related differences in napping and nocturnal sleep.

The aim of this study was to contrast the time distribution of out-of-bed napping in young and older adults through recordings of wrist activity, and to evaluate the correlates of napping with nocturnal sleep. Seventy-three young adults between 18 and 32 years and 60 older adults between 60 and 75 years of age participated in the study. Subjects were selected for good general health and had few sleep complaints. They wore wrist-activity monitors and kept daily sleep logs for 1 week. Automatic sleep scoring was edited by the authors, supplemented by sleep logs and illumination data as well as activity data. Napping episodes were modestly increased in older adults, but there was no difference in the daily duration of napping. Older adults napped more in the evening (especially within 2 h before bedtime), whereas young adults napped more in the afternoon. The older adults with evening naps (n = 31) showed earlier nocturnal wake-up times and decreased nocturnal sleep duration compared with the older adults without evening naps (n = 29). There was no difference in nocturnal sleep between young adults with afternoon naps (n = 32) and without afternoon naps (n = 41). In determining the effects of napping on nocturnal sleep, timing of napping and age are important. Maintaining alertness during the evening (e.g. by bright light exposure or moderate exercise) would be a possible approach to delay wake-up times in older adults.

Adolescent↗

Age-related changes of circadian rhythms and sleep-wake cycles.

OBJECTIVES: To compare relationships between the sleep-wake cycle and endogenous circadian rhythms in young and older adults and to examine correlates between evening naps and circadian rhythms in older adults. DESIGN: For 1 week of home recording, subjects wore wrist-activity monitors and kept daily sleep logs. After the home monitoring, subjects entered the laboratory on a 90-minute sleep-wake schedule and were monitored on this schedule for at least 30 hours. SETTING: Community living and laboratory. PARTICIPANTS: Sixty-seven young adults, aged 18 to 32, and 56 older adults, aged 60 to 75, who were healthy and had few sleep complaints. MEASUREMENTS: Times of nocturnal sleep, out-of-bed napping, and illumination were obtained at home. Sleep propensity and oral body temperature (OBT) were measured in the laboratory, along with circadian rhythms of cortisol and 6-sulfatoxymelatonin (aMT6s, assayed from urine samples collected every 90 minutes). RESULTS: Home sleep times and illumination acrophases (fitted peak times) were advanced in older adults. The phase angles (time intervals) between onset of aMT6s and sleep onset were not changed in older adults, but sleep offset was more advanced than acrophase and offset of aMT6s with aging. Acrophases of cortisol and sleep propensity were advanced in older adults to the same extent as sleep times, but OBT was less advanced than sleep times. Older adults who took evening naps showed more advanced sleep offset and circadian rhythms of aMT6s, but there were no differences in the phase angles of sleep onset and circadian rhythms of aMT6s and cortisol compared with older adults who did not take evening naps. CONCLUSION: Measuring different circadian markers suggested different phase relationships between the sleep-wake cycle and endogenous circadian rhythms in aging. Early awakening in older adults cannot be explained simply by a relative phase advance of the circadian system. Evening naps and advanced illumination may play a role in the advance of the circadian system in aging.

Adolescent↗

Plasticity of hamster circadian entrainment patterns depends on light intensity.

The multiple oscillatory basis of the mammalian circadian pacemaker is adduced by, among other phenomena, the occurrence of split locomotor activity rhythms in rodents after prolonged exposure to constant light. More recently, split rhythms entrained to a 24h light:dark:light:dark cycle have been documented following scheduled access of hamsters to a novel running wheel or by photoperiod manipulations alone. Because the incidence of constant light-induced splitting depends on light intensity, the role of this variable was assessed in this new splitting paradigm. Male Syrian hamsters, entrained to a 14h light:10h dark cycle, were transferred to individual running wheel cages 7h after light onset. Transfer coincided with the beginning of the scotophase of a new photocycle alternating between 5h of relative dark and 7h of light. For four weeks bright photophases (approximately 350 lux) were alternated with either dim (< 0.1 lux) or completely dark (0 lux) scotophases. An additional group received moderate intensity photophases (approximately 45 lux) paired with dim scotophase illumination. For an additional four weeks, all hamsters were exposed to the same bright:dim light:dark cycle. Dim light in the scotophase significantly increased the incidence of split activity rhythms relative to that observed with completely dark scotophases. Overall wheel-running rates and activity induced by a cage change were also increased in dim light-exposed animals. Group differences largely disappeared four weeks later when hamsters previously maintained in completely dark scotophases were exposed to dim scotophases. Photophase light intensity did not affect the overall incidence of splitting, but influenced the timing of activity in the afternoon scotophase. The effects of dim illumination may be mediated in part via enhanced locomotor responses to transfer to a new cage or by changes in coupling interactions between component oscillators.

Animals↗

Entrainment of circadian programs.

Of the three defining properties of circadian rhythmicity--persisting free-running rhythm, temperature compensation, and entrainment--the last is often poorly understood by many chronobiologists. This paper gives an overview of entrainment. Where have we been? Where are we now? Whence should we be going? Particular emphasis is given to a discussion of the Discrete vs. Continuous models for entrainment. We provide an integrated mechanism for entrainment from a limit-cycle perspective.

Animals↗

PRC bisection tests.

This communication presents a new method for evaluating phase response curves (PRCs). A PRC describes the phase shifts produced in an oscillator by stimuli applied at different initial phase-states of that oscillator. In the PRC bisection tests, we repeatedly cut in half the circular distribution of the initial phase-states of the oscillator when stimuli are given. Empirically, we locate that optimal diameter which best bisects the circular distribution of phase responses into arcs of relative phase advance and phase delay. We compute a D score reflecting the success of the best bisection. The null hypothesis of a random distribution of phase responses by initial phase is tested with a Monte Carlo procedure, which computes Dr scores from random combinations of phase shifts with initial phases, thus determining the probability, given the null hypothesis, that the observed D score was from a random distribution. The bisection procedure can be extended to examine whether stronger phase shifts are produced in one phase response curve than in contrasting curves. Also, the bisection procedure yields an estimate of the inflection point of the phase response curve. A method is given to estimate the power of the PRC bisection test.

Animals↗

Entrainment of 2 subjective nights by daily light:dark:light:dark cycles in 3 rodent species.

Recent work with exotic 24-h light:dark:light:dark (LDLD) cycles indicates surprising flexibility in the entrainment patterns of Syrian hamsters. Following exposure to an LDLD cycle, hamsters may adopt a form of rhythm splitting in which markers of subjective night (e.g., activity, melatonin) are expressed in each of the twice daily scotophases. This pattern contrasts markedly with that of conventionally entrained hamsters in which markers of subjective night are expressed once daily in only 1 of the 2 dark periods. The "split" entrainment pattern was examined further here in Syrian and Siberian hamsters and in mice exposed to LDLD 7:5:7:5, a condition that reliably induces split activity rhythms in all 3 species. The phase angle of entrainment and activity duration were generally similar comparing the 2 daily activity bouts in each species. The stability of this split entrainment state was assessed by deletions of photophases on individual days, by exposure to skeleton photoperiods, and by transfer to constant darkness. As in Syrian hamsters, the one-time substitution of darkness for one 7-h photophase did not grossly alter activity patterns of Siberian hamsters but acutely disrupted the split rhythms of mice. Skeleton light pulses of progressively shorter duration did not significantly alter split entrainment patterns of either Syrian or Siberian hamsters. Both species continued to exhibit stable entrainment with activity expressed in alternate scotophases of an LD 1:5 cycle presented 4 times daily. In contrast, the split activity rhythms of mice were not maintained under skeleton pulses. In constant darkness, rhythms of Siberian hamsters remained distinctly split for a minimum of 2 cycles. Split entrainment to these novel LDLD and 4-pulse skeleton lighting regimes demonstrates a marked degree of plasticity common to the circadian systems of several rodent species and identifies novel entrainment patterns that may be reliably elicited with simple environmental manipulations. Inter- and intraspecific differences in the stability of split activity rhythms likely reflect differences in coupling interactions between the component circadian oscillators, which, adopting separate phase relations to these novel LD cycles, yield a split entrainment pattern.

Animals↗

Efficacy of enhanced evening light for advanced sleep phase syndrome.

This study tested whether a newly designed enhanced evening light therapy was well tolerated and effective in relieving symptoms of Advanced, Sleep Phase Syndrome (ASPS). Participants with self-reported ASPS symptoms were 47 older adults (21 men and 26 women, age 60-86). After baseline, participants underwent 28 consecutive days of either dim or enhanced intensity light treatment for 2-3 hr in the evening. Enhanced evening light (approximately 265 lux) exposure was no more effective than a placebo dim light (approximately 2 lux) at alleviating advanced sleep phase as measured by actigraphically recorded sleep and urinary 6-sulphatoxymelatonin (aMT6s) excretion patterns. Participants receiving the enhanced light reported subjective benefit and a significant delay in sleep onset as compared to the placebo. Although compliance was good and the new enhanced evening light therapy design was well tolerated, the benefits were statistically equivocal.

Aged↗

No association of 6-sulfatoxymelatonin with in-bed 60-Hz magnetic field exposure or illumination level among older adults.

We examined the association of 6-sulfatoxymelatonin (aMT6s) excretion with in-bed 60-Hz magnetic field (MF) exposure and other potential regulators. Adults aged 50-81 years (n=242 years, mean 67.6+/-5.7 years) were monitored for 1 week in their home environments. Mean and maximum MF exposure were assessed with EMDEX Lite instruments. Illumination mesor, amplitude, and acrophase (peak time) were determined from 24-h Actillume wrist monitors. Other regulators of aMT6s assessed were age, usage of melatonin-altering medications, and day length. During two 24-h intervals, all urine voidings were collected. The mesor, amplitude, and acrophase of aMT6s excretion were determined. Multiple regression analyses revealed no association between MF and aMT6s. Medication usage was associated with significantly lower aMT6s mesor and amplitude. Illumination acrophase and amplitude were significantly associated with aMT6s acrophase. These data suggest no influence of nocturnal environmental MF exposure on aMT6s excretion in older adults.

Aged↗