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PurposeTo examine long-term cognitive effects of chemotherapy and identify predictors among women with breast cancer (WBC).Patients and methodsSixty-nine WBC scheduled to receive chemotherapy, and 64 matched-controls with no cancer, participated. Objective and subjective cognition, total sleep time, nap time, circadian activity rhythms (CAR), sleep quality, fatigue, and depression were measured pre-chemotherapy (Baseline), end of cycle 4 (Cycle-4), and one-year post-chemotherapy (1-Year).ResultsWBC showed no change in objective cognitive measures from Baseline to Cycle-4 but significantly improved from both time points to 1-Year. Matched-controls showed an increase in test performance at all time points. WBC had significantly higher self-reported cognitive dysfunction at Cycle-4 and 1-Year compared to baseline and compared to matched-controls. Worse neuropsychological functioning was predicted by less robust CARs (i.e., inconsistent 24 h pattern), worse sleep quality, longer naps, and worse cognitive complaints. Worse subjective cognition was predicted by lower sleep quality and higher fatigue and depressed mood.ConclusionObjective testing showed increases in performance scores from pre- and post-chemotherapy to one year later in WBC, but matched-controls showed an increase in test performance from baseline to Cycle-4 and from Cycle-4 to 1-Year, likely due to a practice effect. The fact that WBC showed no practice effects may reflect a form of learning deficit. Compared with the matched-controls, WBC reported significant worsened cognitive function. In WBC, worse objective and subjective cognitive functioning were predicted by worse sleep and sleep-related behaviors (naps and CAR). Interventions that target sleep, circadian rhythms, and fatigue may benefit cognitive function in WBC.

PurposeThe goal of this study was to examine whether daily increased morning light exposure would maintain or improve sleep and the circadian pattern of relatively more activity in the day and less during the night in women undergoing chemotherapy for breast cancer.Patients and methodsParticipants were 39 women with newly diagnosed breast cancer, randomized to either 30-mins of daily morning bright white light (BWL) or dim red light (DRL). Sleep/wake was measured objectively for 72-h with wrist actigraphy and subjectively with the Pittsburgh Sleep Quality Index (PSQI) prior to and during chemotherapy cycles 1 and 4. The study was registered with the National Institutes of Health ClinicalTrials.gov (Clinical Trials number: NCT00478257).ResultsResults from actigraphy suggested that compared to the DRL group, women in the BWL group had longer night-time sleep, fewer sleep disturbances during the night, and had fewer and shorter daytime naps at the end of cycle 4 of chemotherapy as well as exhibiting less activity at night and more activity during the day by the end of cycle 4. Results from PSQI indicated that components of sleep quality improved but daytime dysfunction deteriorated during cycle 4 treatment in the BWL group; meanwhile the DRL group used more sleep medications in the treatment weeks which might have led to the improved sleep quality during the recovery weeks of both cycles.ConclusionThese results suggest that bright white light therapy administered every morning on awakening may protect women undergoing chemotherapy for breast cancer from nighttime sleep and daytime wake disruption. Randomized clinical trials in larger samples are needed to confirm these findings.

Key pointsExercise elicits circadian phase-shifting effects, but additional information is needed. The phase-response curve describing the magnitude and direction of circadian rhythm phase shifts, depending on the time of the zeigeber (time cue) stimulus, is the most fundamental chronobiological tool for alleviating circadian misalignment and related morbidity. Fifty-one older and 48 young adults followed a circadian rhythms measurement protocol for up to 5.5 days, and performed 1 h of moderate treadmill exercise for 3 consecutive days at one of eight times of the day/night. Temporal changes in the phase of 6-sulphatoxymelatonin (aMT6s) were measured from evening onset, cosine acrophase, morning offset and duration of excretion. Significant phase-response curves were established for aMT6 onset and acrophase with large phase delays from 7:00 pm to 10:00 pm and large phase advances at both 7:00 am and from 1:00 pm to 4:00 pm. Delays or advances would be desired, for example, for adjustment to westward or eastward air travel, respectively. Along with known synergism with bright light, the above PRCs with a second phase advance region (afternoon) could support both practical and clinical applications.AbstractAlthough bright light is regarded as the primary circadian zeitgeber, its limitations support exploring alternative zeitgebers. Exercise elicits significant circadian phase-shifting effects, but fundamental information regarding these effects is needed. The primary aim of the present study was to establish phase-response curves (PRCs) documenting the size and direction of phase shifts in relation to the circadian time of exercise. Aerobically fit older (n = 51; 59-75 years) and young adults (n = 48; 18-30 years) followed a 90 min laboratory ultrashort sleep-wake cycle (60 min wake/30 min sleep) for up to 5½ days. At the same clock time on three consecutive days, each participant performed 60 min of moderate treadmill exercise (65-75% of heart rate reserve) at one of eight times of day/night. To describe PRCs, phase shifts were measured for the cosine-fitted acrophase of urinary 6-sulphatoxymelatonin (aMT6s), as well as for the evening rise, morning decline and change in duration of aMT6s excretion. Significant PRCs were found for aMT6s acrophase, onset and duration, with peak phase advances corresponding to clock times of 7:00 am and from 1:00 pm to 4:00 pm, delays from 7:00 pm to 10:00 pm, and minimal shifts around 4:00 pm and 2:00 am. There were no significant age or sex differences. The amplitudes of the aMT6s onset and acrophase PRCs are comparable to expectations for bright light of equal duration. The phase advance to afternoon exercise and the exercise-induced PRC for change in aMT6s duration are novel findings. The results support further research exploring additive phase-shifting effects of bright light and exercise and health benefits.

The common assumption that population sleep duration has declined in the past few decades has not been supported by recent reviews, which have been limited to self-reported data. The aim of this review was to assess whether there has been a reduction in objectively recorded sleep duration over the last 50+ years. The literature was searched for studies published from 1960 to 2013, which assessed objective sleep duration (total sleep time (TST)) in healthy normal-sleeping adults. The search found 168 studies that met inclusion criteria, with 257 data points representing 6052 individuals ages 18-88 y. Data were assessed by comparing the regression lines of age vs. TST in studies conducted between 1960 and 1989 vs. 1990-2013. Weighted regression analyses assessed the association of year of study with age-adjusted TST across all data points. Regression analyses also assessed the association of year of study with TST separately for 10-y age categories (e.g., ages 18-27 y), and separately for polysomnographic and actigraphic data, and for studies involving a fixed sleep schedule and participants' customary sleep schedules. Analyses revealed no significant association of sleep duration with study year. The results are consistent with recent reviews of subjective data, which have challenged the notion of a modern epidemic of insufficient sleep.

Seasonal effects on mood have been observed throughout much of human history.  Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight).  We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of melatonin secretion.  The timing of melatonin secretion interacts with gene transcription in the pituitary pars tuberalis to modulate production of TSH (thyrotropin), hypothalamic T3 (triiodothyronine), and tuberalin peptides which modulate pituitary production of regulatory gonadotropins and other hormones.  Pituitary hormones largely mediate seasonal physiologic and behavioral variations.  As a result of long winter nights or inadequate illumination, we propose that delayed morning offset of nocturnal melatonin secretion, suppressing pars tuberalis function, could be the main cause for winter depression and even cause depressions at other times of year.  Irregularities of circadian sleep timing and thyroid homeostasis contribute to depression.  Bright light and sleep restriction are antidepressant and conversely, sometimes trigger mania.  We propose that internal desynchronization or bifurcation of SCN circadian rhythms may underlie rapid-cycling manic-depressive disorders and perhaps most mania.  Much further research will be needed to add substance to these theories.

Epidemiologic studies have consistently shown that sleeping

Abstract Background Most mammals are seasonal breeders whose gonads grow to anticipate reproduction in the spring and summer. As day length increases, secretion increases for two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This response is largely controlled by light. Light effects on gonadotropins are mediated through effects on the suprachiasmatic nucleus and responses of the circadian system. There is some evidence that seasonal breeding in humans is regulated by similar mechanisms, and that light stimulates LH secretion, but primate responses seem complex. Methods To gain further information on effects of bright light on LH and FSH secretion in humans, we analyzed urine samples collected in three experiments conducted for other goals. First, volunteers ages 18-30 years and 60-75 commenced an ultra-short 90-min sleep-wake cycle, during which they were exposed to 3000 lux light for 3 hours at balanced times of day, repeated for 3 days. Urine samples were assayed to explore any LH phase response curve. Second, depressed participants 60-79 years of age were treated with bright light or dim placebo light for 28 days, with measurements of urinary LH and FSH before and after treatment. Third, women of ages 20-45 years with premenstrual dysphoric disorder (PMDD) were treated to one 3-hour exposure of morning light, measuring LH and FSH in urine before and after the treatments. Results Two of the three studies showed significant increases in LH after light treatment, and FSH also tended to increase, but there were no significant contrasts with parallel placebo treatments and no significant time-of-day treatment effects. Conclusions These results gave some support for the hypothesis that bright light may augment LH secretion. Longer-duration studies may be needed to clarify the effects of light on human LH and FSH.

This manuscript presents a new method and computer program for evaluating phase response curves (PRCs). A phase response curve describes those phase shifts produced in an oscillator by stimuli applied at different initial phase-states of that oscillator. Analysis of variance (ANOVA) has often been used to evaluate the null hypothesis that resultant phase shifts are randomly related to the initial phase-state of the oscillator at which stimuli are given, but the PRC bisection tests presented here have several advantages. 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. We locate an optimal diameter which best bisects the circular distribution of phase responses into arcs of phase advance and phase delay. A D score reflecting the success of the best bisection is computed. The null hypothesis of a random distribution of phase responses by initial phase is tested with a Monte Carlo procedure, which bisects random combinations of phase shifts with initial phases, thus determining the probability of the null hypothesis that the observed D score was from a random distribution. The bisection procedure can also be used to examine whether stronger phase shifts are produced in one phase response curve than in a contrasting curve. Further, the bisection procedure yields an estimate of the inflection point of the phase response curve. Finally, a method is given to estimate the power of the PRC bisection procedure.