High Sensitivity of Human Melatonin, Alertness, Thermoregulation, and Heart Rate to Short Wavelength Light

Abstract

Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.

Full text

High Sensitivity of Human Melatonin, Alertness,
Thermoregulation, and Heart Rate to Short
Wavelength Light
Christian Cajochen, Mirjam Mu¨ nch, Szymon Kobialka, Kurt Kra¨uchi, Roland Steiner, Peter Oelhafen,
Selim Orgu¨ l, and Anna Wirz-Justice
Centre for Chronobiology (C.C., M.M., S.K., K.K., A.W.-J.), Psychiatric University Clinic, CH-4025 Basel, Switzerland;
Institute of Physics (R.S., P.O.), University of Basel, CH-4056 Basel, Switzerland; and Eye Clinic, University Hospital
(S.O.), CH-4012 Basel, Switzerland
Light can elicit acute physiological and alerting responses in
humans, the magnitude of which depends on the timing, in-
tensity, and duration of light exposure. Here, we report that
the alerting response of light as well as its effects on thermo-
regulation and heart rate are also wavelength dependent. Ex-
posure to2hofmonochromatic light at 460 nm in the late
evening induced a significantly greater melatonin suppres-
sion than occurred with 550-nm monochromatic light, con-
comitant with a significantly greater alerting response and
increased core body temperature and heart rate (⬃2.8 ⴛ 10
13
photons/cm
2
/sec for each light treatment). Light diminished
the distal-proximal skin temperature gradient, a measure of
the degree of vasoconstriction, independent of wavelength.
Nonclassical ocular photoreceptors with peak sensitivity
around 460 nm have been found to regulate circadian rhythm
function as measured by melatonin suppression and phase
shifting. Our findings—that the sensitivity of the human alert-
ing response to light and its thermoregulatory sequelae
are blue-shifted relative to the three-cone visual photopic
system—indicate an additional role for these novel photore-
ceptors in modifying human alertness, thermophysiology, and
heart rate. (J Clin Endocrinol Metab 90: 1311–1316, 2005)
T
HE HUMAN CIRCADIAN timing system is sensitive to
ocular light exposure. The effects of light depend on the
circadian phase at which light is administered: light given
after the core body temperature (CBT) nadir advances the
phase of circadian rhythms, whereas light given before the
CBT nadir induces delays. This can be quantified by a
so-called “human phase-response curve to light” (1, 2).
Besides the timing of exposure, the intensity of light (i.e.
irradiance) also plays a crucial role in human circadian-
phase resetting (3, 4). The irradiance dose-response func-
tion to a single episode of light in the phase-delay region
can be characterized by a logistic function with high sen-
sitivity, such that half of the maximal resetting response
achieved in response to bright light (9100 lux) is obtained
with just 1% of this light (dim room light of ⬃100 lux; see
Ref. 4). Recent results indicate that very low intensity
monochromatic light in the short-wave range (460 nm)
also affects the human circadian timing system and is
capable of inducing a significantly greater phase shift than
monochromatic light at 555 nm (the peak of the three-cone
photopic visual system) (5). Furthermore, short wave-
length light between 436 and 456 nm induced a phase
advance similar to that for polychromatic light (i.e. white
light) containing 185-fold more photons (6). These studies
clearly demonstrate that the human circadian timing sys-
tem is highly sensitive to ocular light exposure, particu-
larly in the short wavelength range.
Besides circadian phase shifts, light also elicits acute phys-
iological effects in humans such as a rapid suppression of
melatonin at night (for review, see Ref. 7), an increase in CBT
(8–11) and heart rate (12), and an immediate dose-dependent
alerting response, measured subjectively and objectively via
the electroencephalogram (10). Brainard et al. (13, 14) have
consistently shown that short wavelength light at around 460
nm is most effective in acutely suppressing human melatonin
levels. Furthermore, Hankins and Lucas (15) have recently
shown that acute light responses in the human electroreti-
nogram (ERG) are highly dependent on wavelength, such
that light at 483 nm elicited the strongest reduction in cone
ERG b wave–implicit time.
The acute effects of light, as well as the circadian effects,
seem to be mediated by the eyes. Thus, acute elevation of
body temperature and suppression of melatonin are not
observed when the eyes are covered (11, 16) or when light
is administered to the skin in the popliteal region (17–19).
There is mounting evidence that nonrod and noncone
photoreceptors might form the basis of this nonimage-
forming photoreceptive pathway mediating both the
circadian and direct effects of light in rodents (20, 21)
(for review, see Ref. 22). Therefore, we hypothesized that
the acute effect of light on melatonin, alertness, thermo-
regulation, and heart rate is blue-shifted, such that short
wavelength light at 460 nm induces a greater melatonin-
suppressing, alerting, hyperthermic, and tachycardic effect
than light at 550 nm.
First Published Online December 7, 2004
Abbreviations: CBT, Core body temperature; CP, constant posture;
DPG, distal-proximal skin temperature gradient; ERG, electroretino-
gram; SCN, suprachiasmatic nuclei.
JCEM is published monthly by The Endocrine Society (http://www.
endo-society.org), the foremost professional society serving the en-
docrine community.
0021-972X/05/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 90(3):1311–1316
Printed in U.S.A. Copyright © 2005 by The Endocrine Society
doi: 10.1210/jc.2004-0957
1311
on April 11, 2005 jcem.endojournals.orgDownloaded from

Subjects and Methods
Study participants
Ten male volunteers (age range, 21–29 yr; mean, 25.9 ⫾ 3.8 sd) were
studied. All study participants were nonsmokers, free from medical,
psychiatric, and sleep disorders as assessed by history, a physical ex-
amination, and questionnaires. An ophthalmological examination was
carried out before the study began and after completion of the study by
one of our coauthors (S.O.) to exclude volunteers with visual impair-
ments as well as to be certain that our light application was not harmful.
The volunteers were instructed to abstain from caffeine and alcohol for
1 wk before the study; their compliance was verified with urinary
toxicological analysis on the day of admission to the laboratory. They
were asked to keep a regular sleep-wake schedule (bedtimes and wa-
ketimes within ⫾30 min of self-selected target time) during the week
before their admission to the laboratory. Adherence to this regular
schedule was verified with a wrist actigraph (Cambridge Neurotech-
nologies, Cambridge, UK) and daily sleep diaries. All volunteers gave
written informed consent. The protocol, screening questionnaires, and
consent form were approved by the Ethical Committee of Basel (Basel,
Switzerland) and were in agreement with the Declaration of Helsinki.
Study protocol
The study consisted of three arms, performed in a balanced order,
separated by a 1-wk intervening period (Fig. 1). There were no changes
in sleep quality or sleep-wake cycles during the intervening week. On
the basis of the habitual bedtimes of the volunteers, a constant posture
(CP) protocol started 10 h after usual waketime in the early evening (e.g.
1800 h) and ended the next day, 2 h after usual waketime (e.g. 1000 h).
Under CP conditions, the volunteers experienced a controlled, lying-
down episode of 1.5 h under 2 lux, followed by a 2-h dark adaptation
episode under complete darkness (zero lux). After that, light exposure
was initiated for the next 2 h. During this 2-h episode, the volunteers
received either monochromatic light at 460 nm, monochromatic light at
550 nm, or no light (zero lux). After this, the volunteers remained awake
for another 1.5-h episode under 2 lux (polychromatic white light), before
they were allowed to sleep for 7.75 h. One study participant developed
a mild cold during one of the study legs and was therefore excluded from
additional analysis.
Light exposure
Monochromatic light exposure (2 h) was scheduled at a circadian
phase at which polychromatic, white light exposure induces robust
phase delays (1, 2, 23) and alerting effects (24). The monochromatic light
was generated by a 300-W arc-ozone-free Xenon lamp (Thermo Oriel,
Spectra Physics, Stratford, CT), filtered by either 460 or 550 nm (Inter-
ference filter, ⫾10 nm half-peak bandwidth, Spectra Physics, Stratford,
CT). Monochromatic light was transmitted via two glass-fiber bundles
(L.O.T. Oriel-Suisse, Romanel-sur Morges, Switzerland) through the
wall, into the soundproofed and temperature-controlled chronobiology
suite, onto the goggles that covered the volunteers’ eyes. The custom-
built goggles (K. Haug AG, Basel, Switzerland) consisted of two spheres
(27.5-mm inner radius) coated with white reflectance paint (two com-
ponents polyurethane-acryl antifading paint; Lachenmeier & Co. AG,
Basel, Switzerland). Each sphere was illuminated via three branches of
the main fiber-optic cable to provide constant uniform illumination.
Equal photon densities (2.8 ⫻ 10
13
photons/cm
2
/sec) for the 460- and
550-nm wavelength light were administered. This irradiance level (12.1
␮
W/cm
2
for 460 nm and 10.05
␮
W/cm
2
for 550 nm) was chosen ac
-
cording to recently reported results on monochromatic light on the
human circadian timing system (5). Irradiances were measured with a
laser power meter (Laser Check, Coherent, Auburn, CA) before the
beginning and at the end of each light exposure. During light exposure
as well as during the no-light condition, volunteers were asked to keep
their eyes open and to fix their gaze on the middle of the spheres. A
technician checked the latter by online monitoring the polysomno-
graphic recordings and also verifying that the subjects remained awake.
The volunteers’ pupils were not dilated to avoid possible repercussions
of the dilation agent per se on thermoregulation, heart rate, and alertness.
However, we tested the effects of the light stimulus on pupil constriction
by applying monocular light exposure (light via the goggle of the right
eye) and concomitantly measuring the pupil size on the left eye via an
infrared camera. The entire control protocol was conducted at the same
time of day (evening), with the same light intensity on six subjects.
Results from the control experiment revealed a significantly smaller
pupil size after the short wavelength light at 460 nm than after light at
550 nm in comparison to the dark condition [P ⬍ 0.01; Duncan’s multiple
range test performed after a one-way ANOVA for repeated measures
with the factor light condition (P ⬍ 0.02; dark, 460 and 550 nm)].
Assessment of subjective sleepiness
Subjective sleepiness was assessed every 30 min on the Karolinska
Sleepiness Scale (25), with a visual analog scale throughout scheduled
wakefulness. Because the participants wore goggles during the light
exposure and during the no-light condition, the Karolinska Sleepiness
Scale and the visual analog scale were read out loud by a technician and
transmitted via the interphone to the volunteers’ room.
Thermometry
CBT and eight surface skin temperatures from different body regions
were recorded continuously throughout the study, using a rectal probe
and skin thermocouples, with data stored in 20-sec epochs. Distal and
proximal skin temperatures as well as the distal-proximal skin temper-
ature gradient (DPG) were calculated according to the procedures de-
scribed in Ref. 26.
Heart rate
Standard electrocardiogram leads were placed on the lateral thorax
and on the sternum. The signal was recorded on the Vitaport-3 digital
system at 256 Hz. An off-line algorithm (System Hofstetter, SHS,
Allschwil, Switzerland) detected heart rate by the length of R-R intervals.
Salivary melatonin
Saliva was collected at 30-min intervals during scheduled wakeful-
ness. A direct double-antibody RIA was used for the melatonin assay,
validated by gas-chromatography-mass spectroscopy (Bu¨ hlmann Lab-
FIG. 1. Overview of the protocol design.
After 1.5 h under 2 lux, subjects were
dark adapted for 2 h, followed by an-
other2hindarkness or light exposure
at 460 nm or 550 nm (for details about
the light exposures, see Subjects and
Methods). Subsequently, subjects spent
1.5 h under 2 lux before they were al-
lowed to sleep for 8 h. The entire pro-
tocol was carried out under constant re-
cumbent posture conditions in bed.
Saliva samples were collected, and
sleepiness ratings were taken, both in
half-hourly intervals.
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oratories, Scho¨nenbuch, Switzerland) (27). The minimum detectable
dose of melatonin (analytical sensitivity) was determined to be 0.2 pg/
ml. The functional least-detectable dose using the less than 20% coef-
ficient of interassay variation criterion was less than 0.65 pg/ml, and
individual serum and saliva melatonin profiles showed excellent par-
allelism (r ⫽ 0.977– 0.999; slopes ⫽ 0.21–0.63) (27).
Statistics
Statistical analysis of the time course was carried out for each variable
using two-way ANOVAs for repeated measures on factor light condition
and time interval with Huynh-Feldt’s statistics. P values were based on
corrected degrees of freedom, but the original degrees of freedom are
reported. The statistical package SAS (version 6.12, SAS Institute Inc.,
Cary, NC) was used. For post hoc comparisons, one-sided Duncan’s
multiple range tests were used. To correct for multiple comparisons, the
resulting P values were alpha-corrected according to the procedures
described in Ref. 28.
Results
Melatonin suppression and subjective sleepiness
Monochromatic light exposure caused a wavelength-
dependent suppression of salivary melatonin (Fig. 1, top
panel), as indicated by a significant two-way interaction of the
factors light condition and time interval (F
14,122
⫽ 3.6; P ⬍
0.001). Post hoc comparisons yielded a significant melatonin
suppression after light at 460 nm compared with no light and
to light at 550 nm 30 min after the start of light exposure,
which continued for the remainder of the light-exposure
episode (for post hoc comparisons, see Fig. 2). Salivary mel-
atonin levels during monochromatic light at 550 nm were
only slightly but significantly suppressed during the first
hour of light exposure (Fig. 2). Subjective sleepiness ratings
changed in parallel [interaction light condition ⫻ time in-
terval (F
14,112
⫽ 1.7; P ⬍ 0.05)]. Post hoc comparisons yielded
a significant decrease in subjective sleepiness during the
460-nm light exposure compared with 550-nm light exposure
and no light, starting 30 min after lights on (Fig. 2, second
panel). There was no significant difference in sleepiness be-
tween the 550-nm light exposure and the no-light condition.
Thermoregulation and heart rate
Light exposure changed the time course of CBT [interac-
tion light condition ⫻ time interval (F
20,160
⫽ 2.9; P ⬍ 0.02)
(Fig. 2, third panel)]. The evening decline of CBT was signif-
icantly attenuated by light at 460 nm starting about 1 h after
lights on (Fig. 2), remaining significantly higher throughout
the remainder of the 1.5-h interval before sleep. No differ-
ences were found between the condition with light at 550 nm
and the no-light condition. A similar pattern was found for
heart rate, as indexed by beats per min [interaction light
condition ⫻ time interval (F
20,160
⫽ 3.1; P ⬍ 0.01) (Fig. 2,
bottom panel)]. Although the effect was short lasting, post hoc
comparisons revealed a significantly higher heart rate during
the 460- nm light condition starting 1.5 h after lights on
compared with 550 nm and the no-light condition and lasting
for the first 20 min of the after-light exposure episode.
Although repercussions of light at 460 and 550 nm were
clearly visible in the time course of both proximal and distal
skin temperatures, no significant interaction terms were
found (Fig. 3, top two panels). However, the derived measure
of the DPG that is used as an estimate of the degree of
vasodilation (29) yielded a significant interaction term (F
20,160
⫽ 1.8; P ⬍ 0.03) (Fig. 3, bottom panel). Post hoc comparisons
revealed a significant decrease in the DPG during both 460-
and 550-nm light exposures compared with the no-light
condition.
Discussion
These results demonstrate that the alerting response to
light is wavelength dependent, such that short wavelength
light (460 nm) is more effective than longer wavelength light
(550 nm) in reducing sleepiness in the evening. Furthermore,
our controlled study provides evidence that the effects of
light on thermoregulation and heart rate are similarly wave-
length dependent.
Our data are in good agreement with recent findings that
the human circadian pacemaker is highly sensitive to short
wavelength light (13, 30), as indexed by action spectra for
human melatonin suppression and assessment of human
circadian phase resetting (5, 6). On the basis of these previous
studies, we expected a significantly more pronounced atten-
uation of the nocturnal melatonin increase after light at the
shorter wavelength (460 nm), a hypothesis that was clearly
verified. We have obtained very similar results as Brainard
et al. (13) who reported approximately 60% suppression of
melatonin after2hoflight at 460 nm and at 12.1
␮
W/cm
2
.
Therefore, melatonin levels in 460 nm did not increase during
the light exposure, whereas in the 550-nm condition, they
additionally increased very similarly as shown by Lockley et
al. (5). To our knowledge, this is the first report showing that
human alertness levels as well as thermophysiology are
highly sensitive to this short wavelength light. With the
exception of the proximal and distal skin temperatures, all
other variables (i.e. salivary melatonin, subjective sleepiness,
CBT, and heart rate) responded more strongly to 460- than
550-nm light. However, light at 550 nm was not inactive
because it induced a subtle, short-lasting but significant mel-
atonin suppression. What is interesting is that both wave-
lengths decreased the DPG to a similar extent. Why the
effects of light on the skin temperatures were not wavelength
dependent remains to be elucidated. Although our study was
conducted under very controlled laboratory conditions (i.e.
CP, room temperature, and food intake), skin temperatures
exhibit large inter- and intraindividual variance (31). There-
fore, it may be that this measure did not provide enough
power to differentiate between the two wavelengths. How-
ever, there are two possibilities: 1) the DPG may indeed be
a very sensitive measure for subtle illuminance changes;
and/or 2) that it immediately reflects a minute-to-minute
level of cognitive arousal independent of the sensory mo-
dality of the signal. The DPG increase during the dark-ad-
aptation episode, which was unusual at this circadian phase
as previously measured under 8 lux of ambient-light levels
in a constant routine protocol (26, 31), can be interpreted in
both ways—a diminution to zero lux and a diminution of
sensory input, leading to relaxation. Interestingly, this in-
creased DPG was also paralleled by an unusually early in-
crease in subjective sleepiness and an unusually early
evening melatonin onset. Furthermore, evidence for the re-
sponsiveness of DPG comes from the decrease in this mea-
Cajochen et al. • Effects of Monochromatic Light on Humans J Clin Endocrinol Metab, March 2005, 90(3):1311–1316 1313
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sure seen after the 4-h dark episode in the no-light condition,
when the volunteers were under 2 lux (Fig. 2, bottom panel).
The DPG reflected very sensitively whether the lights were
on or off. Besides the DPG, the increase in heart rate during
the 460-nm light exposure may well be another indication
that the autonomous nervous system acutely responds to
light with an increase in sympathetic tone—a response that
seems particularly susceptible to short wavelength light.
Many studies have shown that exposure to white poly-
chromatic light during the evening or nighttime increases
alertness (8, 10, 24, 32–35) and CBT (8 –10, 19, 34, 35). There
is also evidence that light may acutely affect heart rate (12).
Previously, we have found a dose-response relationship be-
tween the magnitude of the alerting response to light and its
irradiance, such that half of the maximum alerting response
to bright light at 9100 lux was obtained with room light of
approximately 100 lux (10). However, the duration of light
exposure in this study was rather long (6.5 h), and the dose
relationship was only present in the latter part of the light
exposure (10). In contrast, the present study revealed that
light at 460 nm of very low intensity (5 photopic lux or 116.6
scotopic lux) was already effective after about 40 min of
exposure, which corroborates high specificity for light in the
short wavelength range, and shows that the nonimage-form-
ing visual system does not simply count or average photons,
but rather depends on exposure to particular wavelengths of
energy. In fact, during the 460-nm light condition, volunteers
in our experiment probably received fewer photons, because
their pupil size was smaller than in the 550-nm light condi-
tion (based on our data from the control experiment; see
Subjects and Methods). Therefore, the melatonin suppression
and the alerting response was underestimated from what
they would have been had the subjects’ pupils been artifi-
cially dilated. Despite fewer photons, 460-nm light was more
efficient on the above-described variables than 550 nm,
which corroborates its effectiveness also in the absence of
pupil dilators.
Our results demonstrate that besides regulating human
circadian rhythms, the nonclassical photoreceptors are also
involved in the regulation of the acute effects of light, which
has until now only been shown for ERG responses (15).
Although it is possible that the central circadian pacemaker
located in the suprachiasmatic nuclei (SCN) is involved in
both phase shifting and acute responses to light, it is not clear
that these share a common mechanism. It has been proposed
that acute changes in CBT may be primary events mediating
circadian phase-shift responses (36). There is, however, con-
trary evidence; previous administration of melatonin can
completely reverse the acute CBT elevation induced by
nighttime bright light without greatly altering light-induced
phase shifts (23, 37, 38). Whether the delayed decline in CBT
represents only an acute effect of light or whether it is the
initiation of a circadian phase delay would have required a
longer study. We may interpret the sustained evening max-
imum in CBT only after 460-nm light exposure as evidence
FIG. 2. Effects of a 2-h light exposure at 460 nm (F), 550 nm (Œ), and
no light (f) in the evening under CP conditions (i.e. supine in bed) on
salivary melatonin levels, subjective sleepiness as rated on the Karo-
linska Sleepiness Scale, CBT, and heart rate [mean values (n ⫽ 9) and
⫾SEM]. For clarity, the SEM values for the 550-nm light condition were
not plotted. Significant post hoc comparisons (P ⬍ 0.05; Duncan’s
multiple range test corrected for multiple comparisons) are indicated
by the following symbols: *, 460-nm light vs. no light; E, 550-nm light
vs. no light; and ƒ, 460-nm light vs. 550-nm light. The prelight ex-
posure episode represents a 2-h dark adaptation episode under zero
lux, whereas the light level in the 1.5-h post-light exposure was 2 lux.
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for the latter explanation of a selective circadian phase delay
shift.
The mechanisms by which light induces acute physiolog-
ical responses and shifts circadian phase seem to diverge at
some level. Besides the SCN, candidate retinal projections for
the acute effects of light are the pretectal area (39), the in-
tergeniculate leaflet (40), and the ventromedial preoptic area
(41). It is clear that for light to rapidly suppress melatonin
secretion, retinal projections to the SCN are necessary. There-
fore, it has been suggested that the mechanism by which light
exposure may reduce sleepiness is by its suppression of
melatonin synthesis (8, 10, 24). However, there is recent
evidence that these effects appear to be mediated by mech-
anisms that are separate from melatonin suppression (42). It
is more likely to be the ventromedial preoptic area that in-
nervates all of the major nuclei of the ascending monoam-
inergic and, in particular, the histaminergic system and plays
a key role in wakefulness and electroencephalogram arousal
(43, 44).
All of the above-mentioned brain regions receive projec-
tions from intrinsically photosensitive retinal ganglion cells
for which the photopigment melanopsin has recently been
identified (45). Melanopsin is present in the human retina
(46), and melanopsin-containing retinal ganglion cells are
directly photosensitive at a
␭
max
of 484 nm in the rat (47).
Melanopsin expression defines a subset of retinal ganglion
cells that play a broad role in the regulation of nonvisual
photoreception, providing projections that contribute to cir-
cadian entrainment, negative masking, the regulation of
sleep-wake states, and the pupillary reflex (for citations, see
Ref. 45). Our results add to these functions, suggesting that
changes in human alertness and aspects of autonomic control
(thermoregulation and heart rate) are influenced, if not reg-
ulated, by the nonvisual system via the photopigment mela-
nopsin. A definite answer to this would be to investigate
people lacking the classical receptors, or having a melanop-
sin deficiency, to the see repercussions this may have on
light-induced changes in alertness, thermoregulation, and
heart rate. At least in blind mice, melanopsin is required for
nonimage-forming photic responses. However, there is still a
debate (see Ref. 48) as to whether the photopigment melanopsin
is the only candidate for nonvisual ocular photoreception.
It will be interesting to test whether short wavelength light
is more efficient in the workplace environment, where high
alertness levels are required, and in the treatment of seasonal
affective disorder; although in all putative applications, the
blue-light damage potential needs to be evaluated (49). An
important physiological question is whether the decline in
alertness and thermoregulation with age is a consequence of
age-related changes in lens transmittance at the short-wave
range (50).
Acknowledgments
We thank Dr. Corinna Schnitzler for medical screenings; Claudia
Renz, Giovanni Balestrieri, and Marie-France Dattler for their help in
data acquisition; and the volunteers for participating.
Received May 27, 2004. Accepted November 23, 2004.
Address all correspondence and requests for reprints to: Christian
Cajochen, Ph.D., Centre for Chronobiology, Psychiatric University
Clinic, Wilhelm Kleinstr. 27, CH-4025 Basel, Switzerland. E-mail:
christian.cajochen@pukbasel.ch.
This research was supported by the Velux Foundation (Glarus, Swit-
zerland) and in part by The Swiss National Foundation Grants START
3130-054991.98 and 3100-055385.98 (to C.C.).
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