Multi-Component Physiological Response Mediates Therapeutic Benefits of Bright Light in Winter Seasonal Affective Disorder

The set of investigations was designed to determine whether bright light improves both psychic and physiological functions in patients with winter seasonal affective disorder. The signs of such physiological effects of light as advance of circadian phase, increase in energy expenditure and activation of sympatho-adrenal system were examined in 61 female patients with winter depression and 36 age-matched controls before and after 1-week treatment (2,500 lux of white light for 2 h daily). Moreover, the indicators of the fourth physiological effect, intensification of non-rapid eye movement sleep, were studied in a subsample of 21 patients and 10 controls. Although the results provide little evidence for a strong association between different physiological responses to light, any of four responses appears to be positively associated with a remission of the depressive syndrome. The findings indicate that neither of physiological responses could play a dominant role, but several additive effects (e.g. responses of sleep-regulating, circadian, energy-regulating and sympatho-adrenal systems) could be necessary for the favorable therapeutic response to bright light. This result raises the possibility that physiology really participates in regulating the mood of winter depressives. However, any simple pathophysiological model of SAD seems not to be adequate.     

Antidepressant effects of light therapy and "natural" treatments for winter depression

Although bright light treatment may alleviate the symptoms of winter depression, it still remains to be clarified whether chronobiological mechanisms are involved in this antidepressant response. We studied the therapeutic action of bright light in 61 women with and 36 women without winter depression at the medical academic hospital near Novosibirsk (55 degrees North). Bright light was administered with cool-white incandescent lamp for seven days, two hours daily. The treatment started from either 8:00 (n = 29 patients and 16 controls) or 16:00 (n = 24 and 14, respectively) or 18:00 (n = 8 and 6, respectively). The subsets of bright light-treated subjects were then restudied in wintertime before and after one-week vacation in Firuza resort (south of Turkmeniya, 38 degrees North) (n = 19 and 0, respectively), in summertime (n = 42 and 18, respectively) and in the next winter before and after a week 30-min exposure in the morning hours to dim red light emitting “Light Cap” (n = 9 and 0, respectively). The results suggest that, in controls, mood slightly but statistically significantly improved after light treatment and in summer. In patients, the improvement of mood after one week of bright light was comparable with the effects of such “natural” treatments as trips south and transition from winter to summer seasons. Although next winter response to 0.5-h dim light was clinically significant, it was significantly worse compared to the previous response to 2-h bright light. Our therapeutic results indicate that, despite the different potential phase-shifting effect of bright light administered in the morning and in the second half of the day, the responses to all treatments are equally beneficial. This finding provides evidence against the view that circadian phase shifts are the key to the pathogenesis of winter depression and efficacy of light therapy. Although several different physiological effects of light therapy might be involved in the antidepressant response, none of them seems to be of more importance compared to psychological components of this response. Ours and earlier published reports on the independence of beneficial action of bright light from treatment timing support the suggestion that, in the open investigational trials, the placebo effect accounts for a large portion of the antidepressant response. We also reviewed several facts pointing to the close dependence of antidepressant effects of non-drug therapy upon patients' expectations and researchers' enthusiasm. In sum, unlike patients' chronobiology, their psychology seems to be most powerful mediator of the clinical response to bright light.     

Phase Typing of Patients with Seasonal Affective Disorder: A Test for the Phase Shift Hypothesis

The study evaluates the phase-shift hypothesis for seasonal affective disorder (Lewy et al., 1987, 1988) in parallel-design comparison of effects of morning (800-1000) or afternoon (1600-1800) light treatment on mood and circadian phase. Subjective arousal, body temperature, melatonin and cortisol were measured at 800, 1200, 1600, 2000 and 2400 in 23 women with seasonal depression and 20 controls before and after a week of bright light (2 hours per day). The rates of clinical response to both treatments were similar. Comparison of circadian variations did not provide evidence for significant phase-delay in patients compared to controls. However, morning light produced significant phase advance in patients, but not in controls. Also we found that advance phase shifts in well-responded patients were more often than in patients with worse response and controls. Before light treatment phase concordance between different variables in patients was lower compared to either themselves after light treatment or controls before and after light treatment. Dependence of antidepressant response to light from pretreatment circadian phases was also observed. Those patients who responded worse to morning light tended to have advance circadian phases, while those who responded worse to afternoon light tended to have delay phases. Although some results are lending support for the phase-shift hypothesis, other explanations for mechanisms by which biological rhythms are implicated in winter depression and light treatment might be suggested.     

Phase Typing of Patients with Seasonal Affective Disorder: A Test for the Phase Shift Hypothesis

The study evaluates the phase-shift hypothesis for seasonal affective disorder (Lewy et al., 1987, 1988) in parallel-design comparison of effects of morning (800-1000) or afternoon (1600-1800) light treatment on mood and circadian phase. Subjective arousal, body temperature, melatonin and cortisol were measured at 800, 1200, 1600, 2000 and 2400 in 23 women with seasonal depression and 20 controls before and after a week of bright light (2 hours per day). The rates of clinical response to both treatments were similar. Comparison of circadian variations did not provide evidence for significant phase-delay in patients compared to controls. However, morning light produced significant phase advance in patients, but not in controls. Also we found that advance phase shifts in well-responded patients were more often than in patients with worse response and controls. Before light treatment phase concordance between different variables in patients was lower compared to either themselves after light treatment or controls before and after light treatment. Dependence of antidepressant response to light from pretreatment circadian phases was also observed. Those patients who responded worse to morning light tended to have advance circadian phases, while those who responded worse to afternoon light tended to have delay phases. Although some results are lending support for the phase-shift hypothesis, other explanations for mechanisms by which biological rhythms are implicated in winter depression and light treatment might be suggested.     

Antidepressant effects of combination of sleep deprivation and early evening treatment with melatonin or placebo for winter depression

Patients with winter depression (seasonal affective disorder) respond beneficially to sleep deprivation and bright light, but the mechanisms of these responses remain unknown. The study was designed to test whether afternoon/evening melatonin can prevent further relapse after sleep deprivation (presumably due to a pharmacologically induced advance shift of circadian phase). Compared to phase advancing by alteration of sleep - wake schedule or by bright light exposure, the melatonin intake is a more tolerated treatment procedure, and it provides a possibility of blind comparison between chronotherapeutic and placebo treatments. The depression was scored in 16 female patients with winter depression and 17 age-matched female controls before and after total night sleep deprivation and after subsequent six-day administration of melatonin (0.5 mg) or placebo under double blind conditions. The melatonin intake was scheduled at 17:00 in order to produce a phase advance of circadian rhythms. Sleep deprivation resulted in 38% reduction of depression score in patients, but it did not reduce depression score in controls. After subsequent treatment with placebo or melatonin, slight but significant improvement of mood was found in controls. These treatments also stabilized the antidepressant response to sleep deprivation in patients. However, neither differential effect of melatonin and placebo on depression score nor alteration of habitual sleep timing was found in patients and controls. Thus, the study results do not provide evidence for the antidepressant potential of melatonin in patients with winter depression under realistic clinical conditions. The finding of stabilization of mood in patients with placebo points to the contribution of psychological factors to the therapeutic action of this and other types of innovative treatments for winter depression. To include psychosocial aspects in the theoretical framework of seasonal depression, we conceptualized depression as an evolved feature of emotional response to psychosocial rather than physical environment. The seasonality of depression might be explained by cumulative effects of aperiodical psychosocial factors and periodical physical factors on one of the mechanisms of brain neurotransmission.     

A forced desynchrony study of circadian pacemaker characteristics in seasonal affective disorder

The circadian pacemaker is an endogenous clock that regulates oscillations in most physiological and psychological processes with a near 24-h period. In many species, this pacemaker triggers seasonal changes in behavior. The seasonality of symptoms and the efficacy of light therapy suggest involvement of the circadian pacemaker in seasonal affective disorder (SAD), winter type. In this study, circadian pacemaker characteristics of SAD patients were compared with those of controls. Seven SAD patients and matched controls were subjected to a 120-h forced desynchrony protocol, in which core body temperature and melatonin secretion profiles were measured for the characterization of circadian pacemaker parameters. During this protocol, which enables the study of unmasked circadian pacemaker characteristics, subjects were exposed to six 20-h days in time isolation. Patients participated twice in winter (while depressed and while remitted after light therapy) and once in summer. Controls participated once in winter and once in summer. Between the SAD patients and controls, no significant differences were observed in the melatonin-derived period or in the phase of the endogenous circadian temperature rhythm. The amplitude of this rhythm was significantly smaller in depressed and remitted SAD patients than in controls. No abnormalities of the circadian pacemaker were observed in SAD patients. A disturbance in thermoregulatory processes might explain the smaller circadian temperature amplitude in SAD patients during winter.     

The Dim Light Melatonin Onset as a Marker for Orcadian Phase Position

Masking is known to affect a variety of circadian rhythms, making it difficult to use them as reliable markers of circadian phase position. Melatonin may be unique in that it appears to be masked only by (bright) light. Sleep and activity do not appear to influence the melatonin rhythm. By measuring the onset of melatonin production, a clearly demarcated event, we can reliably assess circadian phase position, provided blood is sampled under dim light (the dim light melatonin onset, or DL.MO). The DLMO has been useful in assessing the phase-shifting properties of bright light and in phase typing patients with chronobiologic disorders, such as winter depression.     

Circadian uses of melatonin in humans

Melatonin in humans can be an independent or dependent variable. Measurement of endogenous melatonin levels under dim-light conditions, particularly the dim-light melatonin onset (DLMO), has received increasing attention among researchers, and for clinicians it may soon become a convenient test that can be done at home using saliva collections in the evening, without interfering with sleep. Melatonin, even at low physiological doses, can cause advances (shifts to an earlier time) or delays (shifts to a later time) depending on when it is administered on its phase-response curve (in most sighted people, these times are approximately in the p.m. and in the a.m., respectively). Although both bright light and melatonin can be used separately or together in the treatment of circadian phase disorders in sighted people-such as advanced and delayed sleep phase syndromes, jet lag, shift-work maladaptation, and winter depression (seasonal affective disorder, or SAD)-melatonin is the treatment of choice in totally blind people. These people provide a unique opportunity to study the human circadian system without the overwhelming effects of ocularly mediated light, thus permitting us to establish that all blind free-runners (BFRs) studied under high resolution appear to have phase-advancing and phase-delaying responses to as yet unidentified zeitgebers (time givers) that are usually too weak to result in entrainment.     

Circadian Uses of Melatonin in Humans

Melatonin in humans can be an independent or dependent variable. Measurement of endogenous melatonin levels under dim‐light conditions, particularly the dim‐light melatonin onset (DLMO), has received increasing attention among researchers, and for clinicians it may soon become a convenient test that can be done at home using saliva collections in the evening, without interfering with sleep. Melatonin, even at low physiological doses, can cause advances (shifts to an earlier time) or delays (shifts to a later time) depending on when it is administered on its phase‐response curve (in most sighted people, these times are approximately in the p.m. and in the a.m., respectively). Although both bright light and melatonin can be used separately or together in the treatment of circadian phase disorders in sighted people—such as advanced and delayed sleep phase syndromes, jet lag, shift‐work maladaptation, and winter depression (seasonal affective disorder, or SAD)—melatonin is the treatment of choice in totally blind people. These people provide a unique opportunity to study the human circadian system without the overwhelming effects of ocularly mediated light, thus permitting us to establish that all blind free‐runners (BFRs) studied under high resolution appear to have phase‐advancing and phase‐delaying responses to as yet unidentified zeitgebers (time givers) that are usually too weak to result in entrainment.     

Bright light therapy for winter depression--is phase advancing beneficial?

Bright light is the recommended treatment for winter seasonal affective disorder (SAD). Previously we showed that the antidepressant effect of morning (but not evening) light was greater than placebo after 3 weeks of treatment. Here, we determined if the magnitude and direction of circadian rhythm phase shifts produced by the bright light in the previous study were related to the antidepressant effects. Twenty-six SAD patients from the original sample of 96 had their rectal temperature continuously monitored while they participated in a placebo-controlled parallel design conducted over six winters. After a baseline week, there were three treatments for 4 weeks-morning light, evening light, or morning placebo. Bright light was produced by light boxes (approximately 6000 lux). Placebos were sham negative ion generators. All treatments were 1.5 h in duration. Depression ratings were made weekly by blind raters. Circadian phase shifts were determined from changes in the timing of the core body temperature minimum (Tmin). Morning light advanced and evening light delayed the Tmin by about 1 h. The placebo treatment did not alter circadian phase. As the sleep schedule was held constant, morning light increased and evening light decreased the Tmin to wake interval, or phase angle between circadian rhythms and sleep. Phase advance shifts and increases in the phase angle were only weakly associated with antidepressant response. However, there was an inverted U-shaped function showing that regardless of treatment assignment the greatest antidepressant effects occurred when the phase angle was about 3h, and that patients who moved closer to this phase angle benefited more than those who moved farther from it. However 46% of our sample had a phase angle within 30 min of this 3 h interval at baseline. So it does not appear that an abnormal phase angle can entirely account for the etiology of SAD. A majority (75%) of the responders by strict joint criteria had a phase angle within this range after treatment, so it appears that obtaining the ideal phase relationship may account for some, but not all of the antidepressant response. In any case, regardless of the mechanism for the antidepressant effect of morning light, it can be enhanced when patients sleep at the ideal circadian phase and reduced when they sleep at a more abnormal circadian phase.     

Bright Light Therapy for Winter Depression—Is Phase Advancing Beneficial?

Bright light is the recommended treatment for winter seasonal affective disorder (SAD). Previously we showed that the antidepressant effect of morning (but not evening) light was greater than placebo after 3 weeks of treatment. Here, we determined if the magnitude and direction of circadian rhythm phase shifts produced by the bright light in the previous study were related to the antidepressant effects. Twenty-six SAD patients from the original sample of 96 had their rectal temperature continuously monitored while they participated in a placebo-controlled parallel design conducted over six winters. After a baseline week, there were three treatments for 4 weeks—morning light, evening light, or morning placebo. Bright light was produced by light boxes (~6000 lux). Placebos were sham negative ion generators. All treatments were 1.5 h in duration. Depression ratings were made weekly by blind raters. Circadian phase shifts were determined from changes in the timing of the core body temperature minimum (Tmin). Morning light advanced and evening light delayed the Tmin by about 1 h. The placebo treatment did not alter circadian phase. As the sleep schedule was held constant, morning light increased and evening light decreased the Tmin to wake interval, or phase angle between circadian rhythms and sleep. Phase advance shifts and increases in the phase angle were only weakly associated with antidepressant response. However, there was an inverted U-shaped function showing that regardless of treatment assignment the greatest antidepressant effects occurred when the phase angle was about 3 h, and that patients who moved closer to this phase angle benefited more than those who moved farther from it. However 46% of our sample had a phase angle within 30 min of this 3 h interval at baseline. So it does not appear that an abnormal phase angle can entirely account for the etiology of SAD. A majority (75%) of the responders by strict joint criteria had a phase angle within this range after treatment, so it appears that obtaining the ideal phase relationship may account for some, but not all of the antidepressant response. In any case, regardless of the mechanism for the antidepressant effect of morning light, it can be enhanced when patients sleep at the ideal circadian phase and reduced when they sleep at a more abnormal circadian phase.     

Bright Light Therapy for Winter Depression—Is Phase Advancing Beneficial?

Bright light is the recommended treatment for winter seasonal affective disorder (SAD). Previously we showed that the antidepressant effect of morning (but not evening) light was greater than placebo after 3 weeks of treatment. Here, we determined if the magnitude and direction of circadian rhythm phase shifts produced by the bright light in the previous study were related to the antidepressant effects. Twenty-six SAD patients from the original sample of 96 had their rectal temperature continuously monitored while they participated in a placebo-controlled parallel design conducted over six winters. After a baseline week, there were three treatments for 4 weeks—morning light, evening light, or morning placebo. Bright light was produced by light boxes (?6000 lux). Placebos were sham negative ion generators. All treatments were 1.5 h in duration. Depression ratings were made weekly by blind raters. Circadian phase shifts were determined from changes in the timing of the core body temperature minimum (Tmin). Morning light advanced and evening light delayed the Tmin by about 1 h. The placebo treatment did not alter circadian phase. As the sleep schedule was held constant, morning light increased and evening light decreased the Tmin to wake interval, or phase angle between circadian rhythms and sleep. Phase advance shifts and increases in the phase angle were only weakly associated with antidepressant response. However, there was an inverted U-shaped function showing that regardless of treatment assignment the greatest antidepressant effects occurred when the phase angle was about 3 h, and that patients who moved closer to this phase angle benefited more than those who moved farther from it. However 46% of our sample had a phase angle within 30 min of this 3 h interval at baseline. So it does not appear that an abnormal phase angle can entirely account for the etiology of SAD. A majority (75%) of the responders by strict joint criteria had a phase angle within this range after treatment, so it appears that obtaining the ideal phase relationship may account for some, but not all of the antidepressant response. In any case, regardless of the mechanism for the antidepressant effect of morning light, it can be enhanced when patients sleep at the ideal circadian phase and reduced when they sleep at a more abnormal circadian phase.     

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.     

Circadian organization and photoreception in an Australian dasyurid marsupial (Sminthopsis macroura)

Much is known about the formal properties of circadian rhythm regulation and the physiological substrates underlying rhythmicity in nocturnal rodents, but relatively few studies have addressed circadian rhythm regulation in other mammalian taxonomic groups. In this study, some formal and functional aspects of circadian organization in a nocturnal dasyurid marsupial, the stripe-faced dunnart (Sminthopsis macroura), were analyzed. To determine phasic responses to discrete pulses of light, dunnarts were placed in constant darkness (DD) and were periodically administered pulses of bright light at different times of the animals' circadian day. Analysis of phase shifts in response to light indicated a phase response curve that was similar to responses observed in nocturnal rodents. To determine the possibility of extraretinal photoreception mediating photic entrainment, dunnarts were anesthetized and orbitally enucleated while maintained in a light-dark regimen (LD 14:10). All blinded dunnarts free-ran with periods (tau) that were similar to those observed in DD, indicating that entrainment is mediated through ocular photoreception. However, the data also indicated a decrease in activity in blind dunnarts during the last 3-5 hr of the dark phase, raising the possibility of some retention of photoreceptive capacities.     

Biological rhythms during residence in polar regions

At Arctic and Antarctic latitudes, personnel are deprived of natural sunlight in winter and have continuous daylight in summer: light of sufficient intensity and suitable spectral composition is the main factor that maintains the 24-h period of human circadian rhythms. Thus, the status of the circadian system is of interest. Moreover, the relatively controlled artificial light conditions in winter are conducive to experimentation with different types of light treatment. The hormone melatonin and/or its metabolite 6-sulfatoxymelatonin (aMT6s) provide probably the best index of circadian (and seasonal) timing. A frequent observation has been a delay of the circadian system in winter. A skeleton photoperiod (2 × 1-h, bright white light, morning and evening) can restore summer timing. A single 1-h pulse of light in the morning may be sufficient. A few people desynchronize from the 24-h day (free-run) and show their intrinsic circadian period, usually >24 h. With regard to general health in polar regions, intermittent reports describe abnormalities in various physiological processes from the point of view of daily and seasonal rhythms, but positive health outcomes are also published. True winter depression (SAD) appears to be rare, although subsyndromal SAD is reported. Probably of most concern are the numerous reports of sleep problems. These have prompted investigations of the underlying mechanisms and treatment interventions. A delay of the circadian system with "normal" working hours implies sleep is attempted at a suboptimal phase. Decrements in sleep efficiency, latency, duration, and quality are also seen in winter. Increasing the intensity of ambient light exposure throughout the day advanced circadian phase and was associated with benefits for sleep: blue-enriched light was slightly more effective than standard white light. Effects on performance remain to be fully investigated. At 75°S, base personnel adapt the circadian system to night work within a week, in contrast to temperate zones where complete adaptation rarely occurs. A similar situation occurs on high-latitude North Sea oil installations, especially when working 18:00-06:00 h. Lack of conflicting light exposure (and "social obligations") is the probable explanation. Many have problems returning to day work, showing circadian desynchrony. Timed light treatment again has helped to restore normal phase/sleep in a small number of people. Postprandial response to meals is compromised during periods of desynchrony with evidence of insulin resistance and elevated triglycerides, risk factors for heart disease. Only small numbers of subjects have been studied intensively in polar regions; however, these observations suggest that suboptimal light conditions are deleterious to health. They apply equally to people living in temperate zones with insufficient light exposure.     

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. (Author correspondence: bparry@ucsd.edu)     

Authors' response

At Arctic and Antarctic latitudes, personnel are deprived of natural sunlight in winter and have continuous daylight in summer: light of sufficient intensity and suitable spectral composition is the main factor that maintains the 24-h period of human circadian rhythms. Thus, the status of the circadian system is of interest. Moreover, the relatively controlled artificial light conditions in winter are conducive to experimentation with different types of light treatment. The hormone melatonin and/or its metabolite 6-sulfatoxymelatonin (aMT6s) provide probably the best index of circadian (and seasonal) timing. A frequent observation has been a delay of the circadian system in winter. A skeleton photoperiod (2?×?1-h, bright white light, morning and evening) can restore summer timing. A single 1-h pulse of light in the morning may be sufficient. A few people desynchronize from the 24-h day (free-run) and show their intrinsic circadian period, usually >24?h. With regard to general health in polar regions, intermittent reports describe abnormalities in various physiological processes from the point of view of daily and seasonal rhythms, but positive health outcomes are also published. True winter depression (SAD) appears to be rare, although subsyndromal SAD is reported. Probably of most concern are the numerous reports of sleep problems. These have prompted investigations of the underlying mechanisms and treatment interventions. A delay of the circadian system with “normal” working hours implies sleep is attempted at a suboptimal phase. Decrements in sleep efficiency, latency, duration, and quality are also seen in winter. Increasing the intensity of ambient light exposure throughout the day advanced circadian phase and was associated with benefits for sleep: blue-enriched light was slightly more effective than standard white light. Effects on performance remain to be fully investigated. At 75°S, base personnel adapt the circadian system to night work within a week, in contrast to temperate zones where complete adaptation rarely occurs. A similar situation occurs on high-latitude North Sea oil installations, especially when working 18:00–06:00?h. Lack of conflicting light exposure (and “social obligations”) is the probable explanation. Many have problems returning to day work, showing circadian desynchrony. Timed light treatment again has helped to restore normal phase/sleep in a small number of people. Postprandial response to meals is compromised during periods of desynchrony with evidence of insulin resistance and elevated triglycerides, risk factors for heart disease. Only small numbers of subjects have been studied intensively in polar regions; however, these observations suggest that suboptimal light conditions are deleterious to health. They apply equally to people living in temperate zones with insufficient light exposure. (Author correspondence: arendtjo@gmail.com)     

Acute and phase-shifting effects of ocular and extraocular light in human circadian physiology

Light can influence physiology and performance of humans in two distinct ways. It can acutely change the level of physiological and behavioral parameters, and it can induce a phase shift in the circadian oscillators underlying variations in these levels. Until recently, both effects were thought to require retinal light perception. This view was challenged by Campbell and Murphy, who showed significant phase shifts in core body temperature and melatonin using an extraocular stimulus. Their study employed popliteal skin illumination and exclusively considered phase-shifting effects. In this paper, the authors explore both acute effects and phase-shifting effects of ocular as well as extraocular light. Twelve healthy males participated in a within-subject design and received all of three light conditions--(1) dim ocular light/no light to the knee, (2) dim ocular light/bright extraocular light to the knee, and (3) bright ocular light/no light to the knee--on separate nights in random order. The protocol consisted of an adaptation night followed by a 26-h period of sustained wakefulness, during which a 4-h light pulse was presented at a time when maximal phase delays were expected. The authors found neither immediate nor phase-shifting effects of extraocular light exposure on melatonin, core body temperature (CBT), or sleepiness. Ocular bright-light exposure reduced the nocturnal circadian drop in CBT, suppressed melatonin, and reduced sleepiness significantly. In addition, the 4-h ocular light pulse delayed the CBT rhythm by -55 min compared to the drift of the CBT rhythm in dim light. The melatonin rhythm shifted by -113 min, which differed significantly from the drift in the melatonin rhythm in the dim-light condition (-26 min). The failure to find immediate or phase-shifting effects in response to extraocular light in a within-subjects design in which effects of ocular bright light are confirmed strengthens the doubts raised by other labs of the impact of extraocular light on the human circadian system.     

Effects of the Seasons and of Bright Light Administered at Different Times of Day on Sleep EEG and Mood in Patients with Seasonal Affective Disorder

The study examines objective characteristics of sleep in women (n=31) with and without seasonal affective disorder, winter type, before and after a week of light treatment (at either 0800-1000 h, 1600-1800 h or 1800-2000 h). Subsamples of 13 patients and 7 controls were studied additionally in summer, and, among these patients, 9 were also recorded in spring and fall. Ranking the results from the lowest to the largest degree of deviation of sleep structure in patients from the norm yields the sequence: spring -> summer -> winter after light treatment -> fall -> winter before light treatment. In winter before light treatment the total amounts and percentage of slow wave sleep were significantly lower in responders to light (n=13) compared to both nonresponders (n=8) and controls (n=10), while following light treatment the difference disappeared. The reduced amounts of slow wave sleep in the depressive state predicted higher reduction and low posttreatment scores on psychiatric scales. Light treatment and summer season showed similar effects on patients' sleep: they caused an increase of slow wave sleep and a decline of sleep stage 2. Our data do not suggest that time of light treatment is important to achieve an antidepressant effect. Moreover, phase shifting effects of light treatment and of changing season on sleep EEG were not considerable. At the same time, subjective ratings of arousal demonstrated an advance shift of the arousal rhythm after morning and a delay shift after afternoon LT. We did not find significant changes in total amounts and percentage of REM sleep over time. The data suggest that abnormally increased need for REM sleep results in the hypersomnia and may be considered as a trait marker of winter depression. An abnormal architecture of nonREM sleep appears to be a state marker of those patients who benefit from bright light administered during waking hours.     

Phase Resetting of the Human Circadian Pacemaker with Use of a Single Pulse of Bright Light

Since the initial studies reporting that light can alter the phase position of the human circadian system, there has been increasing interest in the use of bright light as a tool for manipulating the phase position of the circadian pacemaker. Exposure protocols typically require subjects to receive 2–5 h of exposure over several circadian cycles. As a consequence, bright light treatment can involve a considerable time investment. However, recent studies indicate that a single pulse of bright light can produce significant phase shifts in the circadian pacemaker. If a single pulse of bright light can produce significant phase-shifting effects, multiple-pulse designs may be unnecessary. This study examined the phase-shifting effects of a single 4-h pulse of bright light (12,000 lux) in 14 male and one female subject aged between 19–45 years. With use of a “constant routine” to estimate circadian phase, a single 4-h pulse of light produced significant shifts in the phase of the core temperature rhythm. The timing of the exposure, relative to the core temperature rhythm, determined the degree and direction of the phase shift. Exposure immediately prior to habitual bedtime produced a mean phase delay in the core temperature of 2.39 h (SD = 1.37 h). In contrast, exposure immediately following habitual wake-up produced a mean phase advance of 1.49 h (SD = 2.06 h). In addition, the magnitude of the shift increased the closer the light pulse was to the individual's estimated endogenous core temperature minimum. There was, however, considerable interindividual variability in this relationship. Overall, these results confirm that a single pulse of bright light can produce significant phase shifts in the phase of the circadian pacemaker controlling core temperature.