Photic sensitivity for circadian response to light varies with photoperiod.

The response of the circadian system to light varies markedly depending on photic history. Under short day lengths, hamsters exhibit larger maximal light-induced phase shifts as compared with those under longer photoperiods. However, effects of photoperiod length on sensitivity to subsaturating light remain unknown. Here, Syrian hamsters were entrained to long or short photoperiods and subsequently exposed to a 15-min light pulse across a range of irradiances (0-68.03 µW/cm(2)) to phase shift activity rhythms. Phase advances exhibited a dose response, with increasing irradiances eliciting greater phase resetting in both conditions. Photic sensitivity, as measured by the half-saturation constant, was increased 40-fold in the short photoperiod condition. In addition, irradiances that generated similar phase advances under short and long days produced equivalent phase delays, and equal photon doses produced larger delays in the short photoperiod condition. Mechanistically, equivalent light exposure induced greater pERK, PER1, and cFOS immunoreactivity in the suprachiasmatic nuclei of animals under shorter days. Patterns of immunoreactivity in all 3 proteins were related to the size of the phase shift rather than the intensity of the photic stimulus, suggesting that photoperiod modulation of light sensitivity lies upstream of these events within the signal transduction cascade. This modulation of light sensitivity by photoperiod means that considerably less light is necessary to elicit a circadian response under the relatively shorter days of winter, extending upon the known seasonal changes in sensitivity of sensory systems. Further characterizing the mechanisms by which photoperiod alters photic response may provide a potent tool for optimizing light treatment for circadian and affective disorders in humans.

Reduced phase-advance of plasma melatonin after bright morning light in the luteal, but not follicular, menstrual cycle phase in premenstrual dysphoric disorder: an extended study.

The authors previously observed blunted phase-shift responses to morning bright light in women with premenstrual dysphoric disorder (PMDD). The aim of this study was to determine if these findings could be replicated using a higher-intensity, shorter-duration light pulse and to compare these results with the effects of an evening bright-light pulse. In 17 PMDD patients and 14 normal control (NC) subjects, the authors measured plasma melatonin at 30-min intervals from 18:00 to 10:00 h in dim (<30 lux) or dark conditions the night before (Night 1) and after (Night 3) a bright-light pulse (administered on Night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3000 lux for 6 h or 6000 lux for 3 h) was given either in the morning (AM light), 7 h after the dim light melatonin onset (DLMO) measured the previous month, or in the evening (PM light), 3 h after the DLMO. In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between Night 1 and Night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak, or area under the curve. These findings replicated the authors' previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6000 vs. 3000 lux) light pulse for a shorter duration (3 vs. 6 h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal-phase subsensitivity or an increased resistance to morning bright-light cues that are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD.

Mortality related to actigraphic long and short sleep.

BACKGROUND: The folk belief that we should sleep 8 h seems to be incorrect. Numerous studies have shown that self-reported sleep longer than 7.5 h or shorter than 6.5 h predicts increased mortality risk. This study examined if prospectively-determined objective sleep duration, as estimated by wrist actigraphy, was associated with mortality risks. METHODS: From 1995-1999, women averaging 67.6 years of age provided one-week actigraphic recordings. Survival could be estimated from follow-up continuing until 2009 for 444 of the women, with an average of 10.5 years before censoring. Multivariate age-stratified Cox regression models were controlled for history of hypertension, diabetes, myocardial infarction, cancer, and major depression. RESULTS: Adjusted survival functions estimated 61% survival (54-69%, 95% C.I.) for those with sleep less than 300 min and 78% survival (73-85%, 95% C.I.) for those with actigraphic sleep longer than 390 min, as compared with survival of 90% (85-94%, 95% C.I.) for those with sleep of 300-390 min. Time-in-bed, sleep efficiency and the timing of melatonin metabolite excretion were also significant mortality risk factors. CONCLUSION: This study confirms a U-shaped relationship between survival and actigraphically measured sleep durations, with the optimal objective sleep duration being shorter than the self-report optimums. People who sleep five or six hours may be reassured. Further studies are needed to identify any modifiable factors for this mortality and possible approaches to prevention.

Circadian regulation of locomotor activity and skeletal muscle gene expression in the horse.

Circadian rhythms are innate 24-h cycles in behavioral and biochemical processes that permit physiological anticipation of daily environmental changes. Elucidating the relationship between activity rhythms and circadian patterns of gene expression may contribute to improved human and equine athletic performance. Six healthy, untrained mares were studied to determine whether locomotor activity behavior and skeletal muscle gene expression reflect endogenous circadian regulation. Activity was recorded for three consecutive 48-h periods: as a group at pasture (P), and individually stabled under a light-dark (LD) cycle and in constant darkness (DD). Halter-mounted Actiwatch-L data-loggers recorded light exposure and motor activity. Analysis of mean activity (average counts/min, activity bouts/day, average bout length) and cosinor parameters (acrophase, amplitude, mesor, goodness of fit) revealed a predominantly ultradian (8.9 ± 0.7 bouts/24 h) and weakly circadian pattern of activity in all three conditions (P, LD, DD). A more robust circadian pattern was observed during LD and DD. Muscle biopsies were obtained from the middle gluteal muscles every 4 h for 24 h under DD. One-way qRT-PCR results confirmed the circadian expression (P < 0.05) of six core clock genes (Arntl, Per1, Per2, Nr1d1, Nr1d2, Dbp) and the muscle-specific transcript, Myf6. Additional genes, Ucp3, Nrip1, and Vegfa, demonstrated P values approaching significance. These findings demonstrate circadian regulation of muscle function and imply that human management regimes may strengthen, or unmask, equine circadian behavioral outputs. As exercise synchronizes circadian rhythms, our findings provide a basis for future work determining peak times for training and competing horses, to reduce injury and to achieve optimal performance.

Increased sensitivity to light-induced melatonin suppression in premenstrual dysphoric disorder.

Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test the hypothesis that patients with premenstrual dysphoric disorder (PMDD), categorized as a depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), have altered sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL) menstrual cycle phases compared with normal control (NC) women. As an extension of a pilot study in which the authors administered 500 lux to 8 PMDD and 5 NC subjects, in the present study the authors administered 200 lux to 10 PMDD and 13 NC subjects during MF and LL menstrual cycle phases. Subjects were admitted to the General Clinical Research Center (GCRC) in dim light (<50 lux) to dark (during sleep) conditions at 16:00 h where nurses inserted an intravenous catheter at 17:00 h and collected plasma samples for melatonin at 30-min intervals from 18:00 to 10:00 h, including between 00:00 and 01:00 h for baseline values, between 01:30 and 03:00 h during the 200 lux light exposure administered from 01:00 to 03:00 h, and at 03:30 and 04:00 h after the light exposure. Median % melatonin suppression was significantly greater in PMDD (30.8%) versus NC (-0.2%) women (p = .040), and was significantly greater in PMDD in the MF (30.8%) than in the LL (-0.15%) phase (p = .047). Additionally, in the LL (but not the MF) phase, % suppression after 200 lux light was significantly positively correlated with serum estradiol level (p = .007) in PMDD patients, but not in NC subjects (p > .05).

Increased melatonin and delayed offset in menopausal depression: role of years past menopause, follicle-stimulating hormone, sleep end time, and body mass index.

CONTEXT: The constellation of endocrine patterns accompanying menopausal depression remains incompletely characterized. OBJECTIVE: Our objective was to test the hypothesis that the amplitude or phase (timing) of melatonin circadian rhythms differs in menopausal depressed patients (DP) vs. normal controls women (NC). DESIGN: We measured plasma melatonin every 30 min from 1800-1000 h in dim light (<30 lux) or dark, serum gonadotropins and steroids (1800 and 0600 h), and mood (Hamilton and Beck depression ratings). SETTING: The study was conducted at a university hospital. PARTICIPANTS AND SETTING: Twenty-nine (18 NC, 11 DP) peri- or postmenopausal women participated. MAIN OUTCOME MEASURES: We measured plasma melatonin (onset, offset, synthesis offset, duration, peak concentration, and area under the curve) and mood. RESULTS: Multi- and univariate analyses of covariance showed that melatonin offset time was delayed (P = 0.045) and plasma melatonin was elevated in DP compared with NC (P = 0.044) across time intervals. Multiple regression analyses showed that years past menopause predicted melatonin duration and that melatonin duration, body mass index, years past menopause, FSH level, and sleep end time were significant predictors of baseline Hamilton (P = 0.0003) and Beck (P = 0.00004) depression scores. CONCLUSIONS: Increased melatonin secretion that is phase delayed into the morning characterized menopausal DP vs. NC. Years past menopause, FSH, sleep end time, and body mass index may modulate effects of altered melatonin secretion in menopausal depression.

Illumination of upper and middle visual fields produces equivalent suppression of melatonin in older volunteers.

Bright light treatment has become an important method of treating depression and circadian rhythm sleep disorders. The efficacy of bright light treatment may be dependent upon the position of the light-source, as it determines the relative illumination in each portion of the visual field. This study compared illumination of upper and middle visual fields to determine whether melatonin suppression is different or equivalent. Thirteen older volunteers received three illumination conditions in counterbalanced orders: 1000 lux in the upper visual field, 1000 lux in the middle visual field, or dim diffuse illumination < 5 lux. A four-choice reaction time task was performed during tests to ensure eye direction and illumination of the intended portion of the visual field. Illumination in the upper and middle visual fields significantly suppressed melatonin compared to < 5 lux (p < 0.001). Melatonin suppression was not significantly different with upper or middle field illumination. These results indicate that bright light treatments placed above the eye level might be as effective as those requiring patients to look directly at the light source. Clinical comparative testing would be valuable. In addition, this study demonstrates that significant suppression of melatonin may be achieved through the use of bright light in healthy older volunteers.