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The Psychiatry of Light

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Abstract

Bright light therapy and the broader realm of chronotherapy remain underappreciated and underutilized, despite their empirical support. Efficacy extends beyond seasonal affective disorder and includes nonseasonal depression and sleep disorders, with emerging evidence for a role in treating attention-deficit/hyperactivity disorder, delirium, and dementia. A practical overview is offered, including key aspects of underlying biology, indications for treatment, parameters of treatment, adverse effects, and transformation of our relationship to light and darkness in contemporary life.
The Psychiatry of Light
“You don’t hear a psychiatrist asking how much light you get,” Satchin Panda told
a reporter for The Economist (1). “It affects so much of our physiology, psychology, and
mood. But we take it for granted.” Panda is a scientist at the Salk Institute who first
identified melanopsin (a photopigment found in non-visual retinal ganglion cells) as the
primary light receptor for the regulation of circadian rhythm. He is an expert in the
biology of light. He also recognizes how little the rapidly expanding body of knowledge
about light and health has affected psychiatric practice, to the detriment of our patients.
In contrast to both medications and psychotherapy, there is remarkably little data
on the use of bright light therapy by psychiatrists or other mental health clinicians in the
United States (2), an absence that itself reflects a lack of attention to the clinical use of
light. The first survey we know of has just been published, an email survey of
Massachusetts psychiatrists (3). 72% of the psychiatrists who responded sometimes
recommend the use of bright light – most often for seasonal affective disorder, much less
frequently for non-seasonal depression, and rarely for inpatients. As the authors’ point
out, a very low response rate to the survey (14%) likely led to an overestimation of the
actual use of bright light therapy in clinical practice.
This impression is certainly confirmed by conversations we have had with a wide
range of colleagues. “Is there really evidence for its effectiveness in depression?” is a
response we hear surprisingly often from otherwise up-to-date psychiatrists. Before
reviewing the evidence of effectiveness in depression and other syndromes, it is worth
considering why an “evidence-based” treatment with an unusually benign side effect
profile remains in the shadows.
With obvious parallels to psychotherapy, the lack of industry-based funding to
supplement federal research grants has slowed the emergence of a compelling body of
research on light-based treatments, and the lack of industry-based funding for advertising
and speakers slows the dissemination of research findings to clinicians. Yet in contrast to
psychotherapy, bright light therapy lacks a large and established group of practitioners
ready to enthusiastically “rebroadcast” news of positive research results.
Other possible reasons have more to do with the nature of bright light therapy
itself. Unlike swallowing a pill, it requires time. The use of artificial light tethers a patient
to a light box. The use of natural light stirs concerns about UV exposure. Absent an
understanding of the importance of circadian rhythm to most bodily functions and
behaviors, along with an understanding of the importance of light to circadian rhythm,
light therapy can seem on the “alternative” margins of scientific medicine. And light just
sounds less potent and less precise than a medication. We will return to these questions,
which are extremely important in clinical practice, after a non-exhaustive review of the
evidence that supports more widespread use of light therapy in psychiatric care.
Bright Light Therapy for Affective Disorders
The therapeutic use of bright light in psychiatry began in 1984 with a
groundbreaking study published by a group at the NIMH that first described “seasonal
depression” and the use of bright light as an effective antidepressant in 11 patients (4). In
2005, the American Psychiatric Association Council on Research convened a work group
2
to review the subsequent 20 years of research on light therapy for the treatment of
depression. The number of studies that met their rigorous inclusion criteria was small (8
for seasonal and 3 for nonseasonal depression), but they concluded that light therapy was
an effective treatment not only for seasonal depression (SAD) but for nonseasonal
depression (5). Notably, the effects sizes for light therapy were “equivalent to those in
most antidepressant pharmacotherapy trials” (0.84 for SAD, 0.53 for nonseasonal
depression).
Subsequent research has supported, refined and extended these conclusions (6). A
“gold standard” treatment approach has emerged, using a fluorescent light box that
produces 10,000 lux of white light at a specified distance from the user’s eyes, beginning
with 30 minutes exposure in the early morning, as close to awakening as feasible (7). A
dose-response curve has been defined, with a threshold of 2500 lux for an antidepressant
effect. Two hours of exposure are required at 2500 lux and 45-60 minutes at 5000 lux.
There seems to be no further reduction in time required for efficacy at light intensities
greater than 10,000 lux (a bright sunny day can reach intensities of 50,000-100,000 lux).
At the other end of the brightness curve, it is important to note that, other than sitting in a
window with sunshine streaming in, indoor lighting, however bright it may seem (our
eyes adjust very effectively to immense variations in brightness), never approaches 2500
lux. Treatment parameters are adjusted based on individual response. Terman reports
that remission rates in SAD can be improved by timing the treatments to an individual’s
evening melatonin onset, using a self-rating scale called the Morningness-Eveningness
Questionnaire (MEQ) as a rough proxy for salivary melatonin assays (8). There is
preliminary evidence that SAD patients have a less sensitive light input pathway related
to variations in the melanopsin gene (9), which opens up the possibility of more
fundamental and individualized approaches to dosing in the future.
The key pathway for light’s role as primary time-keeper for circadian rhythm
begins with melanopsin-containing intrinsically photosensitive retinal ganglion cells
(ipRGCs), which project to the suprachiasmatic nuclei of the anterior hypothalamus, the
body’s master biological clock. The peak spectral sensitivity of the system is 460 nm, in
the blue range. Two studies by the same group found low-intensity blue-enriched light
(750 lux) as effective but not superior to standard bright light (10,000 lux) in treating
SAD (10,11). Most experts still recommend white light, however, since the evidence base
is much better established and the interplay of effects of differing wavelengths is complex
and not yet fully understood (6; pp 54-55).
The identification of melanopsin and the associated neural pathways has had
profound theoretical and practical implications for the use of light therapy. It may not be
the whole story however. One of the more intriguing hypotheses is humoral
phototransduction, in which blood-borne hemoglobin and bilirubin in the central retinal
vein act as photoreceptors and the resulting release of carbon monoxide serves as a signal
and regulator of circadian and seasonal changes (12). These ongoing investigations, along
with lingering questions about a role for the visual rod and cone receptors in circadian
regulation, may further refine our understanding of optimal spectra for light therapy.
The APA work group found no evidence for improved response from the
combination of bright light and antidepressant medication, but well-designed trials not
available at the time show both superior response and remission rates over medication
3
treatment alone in non-seasonal major depressive disorder (13). The combination of wake
therapy (sleep deprivation at the start of treatment), bright light therapy, and medication
is emerging as a particularly effective strategy in both major depressive disorder (14,15)
and bipolar depression (16,17). A recent study combining lithium with sleep deprivation
and light therapy showed not only rapid improvement but an immediate and persistent
decrease in suicidality after the first sleep deprivation cycle (18). Bright light treatment
carries a low but significant risk of switching in bipolar depression. A small study
suggests that initiating treatment with midday rather than the usual early morning light
may minimize that risk (19). Conversely, a pilot study of “dark therapy” (light
deprivation) in acute mania suggests it may lead to more rapid improvement when added
to standard treatments(20).
In other specialized patient populations, studies have shown bright light treatment
to be an effective treatment for nonseasonal major depression in the elderly (21,22) and a
promising treatment in perinatal depression (23).
Bright Light Therapy for Other Psychiatric Disorders
Bright light therapy has a conceptually straightforward and well supported role in
the treatment of circadian rhythm sleep disorders, disturbances in sleep that result from a
misalignment of an individual’s sleep-wake pattern with his or her internal circadian
system or with the demands of the external world (24). The major categories are delayed
sleep-phase disorder, advanced sleep-phase disorder, jet lag disorder, shiftwork disorder,
and free-running disorder in blind patients (some individual’s with blindness are still
responsive to light as a circadian regulator through the melanopsin-SCN pathway). Early
morning light is used to phase advance an individual’s sleep-wake cycle and late
afternoon/evening light to phase delay the cycle. Lose dose melatonin can also be used
with the opposite timing – early morning for phase delay and late afternoon/evening for
phase advance (25).
Beyond improving the immediate consequences of insomnia (fatigue, decreased
performance in both cognitive and motor tasks, decreased alertness), the treatment of
circadian rhythm sleep disorders links back to the treatment and prevention of mood
disorders. There appears to be a fundamental connection between phase-delay of internal
circadian rhythm and mood disturbances (25), so the effectiveness of similar
interventions (bright light and melatonin) in both conditions is not surprising. There is
also evidence that poor sleep in the elderly is a “considerable” risk factor for suicide over
a subsequent 10 year period independent of the presence of other depressive symptoms
(26.) Attention deficit/hyperactivity disorder (ADHD) is another condition in which
there is emerging evidence for improvement from exposure to bright light. An intriguing
study looked at the relationship between the prevalence of ADHD and solar intensity
(kilowatt hour/square meters/day), both across nations and, in the United States, across
states. Higher solar intensity was strongly associated with a lower prevalence of ADHD
in both children and adults (27). An open trial of bright light therapy in adult ADHD had
positive results (28.) And returning to circadian issues, a recent small pilot study found
evidence for sleep disruption, phase delays, unstable circadian rhythms, and seasonal
effects on circadian rhythm stability and symptomatology in ADHD (29).
4
Given the importance of circadian rhythms to optimal function in “normal” states,
there is currently a paucity of research on the effect of bright light enhancement in non-
clinical populations. Since modern life carries with it a notable reduction in exposure to
bright light (see below), we expect more research to be emerging. There is evidence that
bright light treatment “improves vitality and alleviates distress” in healthy office
employees during winter months (30), that bright light has important alerting effects apart
from the treatment of disordered states (31), and that these alerting effects directly
improve cognitive function (32). The latter study also suggests a new complexity to the
system, with the response to a test dose of light affected by the wavelength of light to
which individuals were exposed prior to the test (“photic memory”). Finally, a large study
of healthy older women (median age 67) found that increased light exposure was
associated with improved quality of life and both social and emotional functioning (33).
Bright Light Therapy for Medical/Psychiatric Conditions
Parkinson’s Disease (PD) is an illness closely associated with depression. Patients
with PD are at high risk for depression (34) and depression increases the risk of PD (35).
PD is also associated with circadian desynchronization and several studies have found
that bright light therapy has positive effects not only on sleep and mood in PD patients
but on motor function as well (36).
Circadian desynchronization is also a major problem in Alzheimer’s Disease (AD)
and related dementias. The use of bright light in a small number of studies has shown
mixed results (37). A promising new pilot study that used bluish-white light in the rooms
of nursing home patients with AD found significant improvement in sleep quality,
efficiency, and total sleep time, along with reduced depression and agitation (38). Early
studies of bright light as an adjunctive treatment for hospitalized patients with delirium
have also been encouraging (39,40).
The association between “winter blues” and weight gain raises questions about
the use of bright light for weight loss. A single placebo-controlled, randomized trial found
that morning bright light treatment reduced body fat and appetite in overweight woman
(41). Complicating the picture, there is also evidence that morning bright light improves
efficiency of carbohydrate digestion and absorption from an evening meal and evening
bright light has the opposite effects, which suggests that (unromantic) bright light at
supper could be an aid to weight loss (42,43). A recent and careful correlational study
however finds that exposure to moderately bright light (above 500 lux) earlier in the day
is associated with lower BMIs, independent of effects on sleep (44).
Finally, one of the more intriguing new findings is that bright light (sunlight) in
childhood may be an essential element for healthy eye development. Concern about an
“epidemic” of myopia in urban east Asia (the prevalence of myopia in young adults is
80% (45)), led researchers to investigate a possible associate between myopia,
educational pressure, and time spent outdoors. Not only did a strong correlation emerge
between outdoor time and a lower prevalence of myopia in children (45). A simple
(randomized) program encouraging elementary school children to spend one hour of
daily recess outdoors led to a significant reduction in new-onset cases of myopia by the
end of the school year (46).
5
Contemporary Exposure to Light and Darkness
Over the past century, electric lighting has transformed the relationship between
human activity and the natural cycles of light and darkness in which our physiology
evolved. Most of our days are spent in light that is significantly dimmer than sunlight and
much of our nights are spent in light that is significantly brighter than starlight or
moonlight. As summarized in a 2008 review by Turner and Mainster:
Young adults in industrialized countries typically receive only 20–120 min
of daily light exposure exceeding 1000 lux. Elderly adults’ bright light
exposures average only 1/3 to 2/3 that duration. Institutionalized elderly
receive less than 10 min per day of light exposure exceeding 1000 lux,
with median illuminances as low as 54 lux (47).
The effect of decreasing exposure to bright light in the elderly in amplified by a
dramatic decline in transmittance of light through the eye as we age, the result of both
crystalline lens yellowing and pupillary miosis (47). Compared to a 10 year old, the eyes
of a 45 year old transmit only half the light active in circadian photoreception to the
retina and by 95 years old, it has dropped to one tenth the level of a 10 year old. The
relevance to sleep disorders, mood disorders and cognitive decline in the elderly is a
subject of active investigation.
Wright has begun to examine directly the changes in circadian function that occur
when individuals move from a modern electrically lit “constructed environment” to
natural lighting alone during camping trips with no artificial light sources available. His
findings emphasize that natural sunlight is a more powerful “zeitgeiber” (timing cue) for
circadian rhythm than electric lighting and without it, internal difference in circadian
periodicity express themselves more strongly and move an individual away from a state
of light-based entrainment to the 24 solar day (48).
At the other end of the day, the ubiquitous presence of electric light and
illumination from electronic screens (which emit significant amounts of blue light at the
peak sensitivity of ipRGCs) has captured public attention (49). The upper limits of
nighttime illumination that do not disrupt circadian function is unclear, but there are
suggestions that remarkably low levels can have significant effects (50). Light-based
nighttime disturbances of circadian rhythm and melatonin secretion may not only lead to
sleep and mood problems, but have also been associated with increased risk for breast
cancer and intrinsic resistance to tamoxifen therapy in breast cancer (51). Technology can
also help with this problem. For patients who cannot avoid exposure to light from
computer and smart phone screens as bedtime approaches, there are now programs and
apps that will gradually red-shift the screen illumination based on time of day (like the
free program f.lux).
Adverse Effects
Like all effective treatments of depression, bright light therapy can trigger a shift
to mania or hypomania in patients with bipolar depression. Otherwise, immediate side
6
effects are mild and can usually be managed by temporary reductions in light intensity or
duration. Most common are reports of eye discomfort, headache, and feeling “wired”
(7,pp33-35).
Long-term exposure to solar UVB radiation is associated with an increased risk of
cataract formation. Therapeutic light boxes effectively filter out all UV light. For patients
using natural light, the UV component of sunlight is low in the early morning hours,
when bright light treatment is optimal for most patients. Eye protection in the form of
sunglasses and brimmed hats is recommended only during the middle of the day (52). A
new retrospective study shows an association between lifetime solar exposure and
exfoliation syndrome (XFS), a form of ocular aging associated with increased risk for a
number of deleterious conditions, including cataract formation (53). The researchers
asked subjects about time outdoors only between the hours of 10 AM and 4 PM,
presumably positing the safety of early morning sunlight. (Supporting the importance of
eye protection during the middle of the day when UV radiation is high, sunglasses were
protective in the US but not Israel and brimmed hats were not protective at all, perhaps
because of significant reflected UV radiation.) Since bright light therapy works through
the eyes, protecting the skin from solar radiation does not reduce its efficacy.
Most manuals on light treatment offer cautions about its use in patients with
underlying retinal disease, suggesting guidance from an ophthalmologist, with baseline
and annual follow-up eye exams (6, p57; 7,p37). Patients with age-related macular
degeneration (AMD) are regularly cautioned against unprotected exposure to sunlight and
environmental light exposure has long been suspected to be a risk factor in AMD. A
current review however concludes that decades of research does not support the view that
environmental light is a significant factor in AMD (54).
Patients on photosensitizing medications, including phenothiazines, lithium, and
St. Johns wort, should similarly be assessed before treatment and followed with regular
eye exams. Melatonin also causes retinal photosensitization but can safely be combined
with bright light therapy when used correctly, since it should be administered at the
opposite end of the day from light therapy and has a short half life (6, p 57).
In our own practices, the “side effect” that most often leads patients to discontinue
light therapy is that it requires time. A typical comment from one patient: ”If you think
my kids and wife will let me sit at the table in front of a light box while everyone else is
getting ready for school or work, you just don’t understand my life.” By contrast, it only
takes a moment to take a pill. The possibility of better engineering of indoor light both in
the workplace and the home, as well as the use of wearable sensors to “dose” natural light
may eventually minimize these practical obstacles to the use of bright light therapy.
Conclusions
Our own experience with the use of light therapy began in the mid-1980s, soon
after the publication of the earliest studies on SAD. In the absence of commercially
manufactured light boxes, a colleague down the hall had drawn up a shopping list and
instructions that let patients build their own with parts from their local hardware store.
Our colleague soon withdrew his instructions from circulation because of liability issues
(so we will sadly not give credit for his work), but fortunately a commercial light box
soon became available from a company started by someone who was participant in the
7
original NIMH study and was appalled to find that there was no way for him to continue
an effective treatment once the study was over. We have been fascinated to follow the
emergence of research over the past three decades that has not only extended our
understanding of the use of light in psychiatry but helps us to appreciate the complex
effects of light on circadian and seasonal regulation, the importance of circadian
regulation in an expanding array of functions at both the cellular and organismic levels,
and the unanticipated health effects from the transformation of our daily relationship to
light in a modern “constructed environment.”
The story continues to emerge. Along the way, a better integration of the
psychiatry of light and the indications for bright light therapy into the “standard”
education of psychiatrists offers many benefits to our patients. It is not a panacea. The
history of psychiatry is strewn with the overselling of a favorite approach to treatment.
But bright light therapy can be both effective and uncommonly safe. It deserves more
attention and more frequent use.
8
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... Cortisol levels tended to get back to usual values after withdrawing of the strategy. Recent studies have shown that light might play an important role in the treatment of seasonal and non-seasonal depression (Perera et al., 2016;Schwartz and Olds, 2015), mainly by modulating circadian rhythms. Evidence suggests that humans (as most mammals) are vulnerable to the manipulation of light cues, entraining circadian rhythms accordingly (Wehr et al., 2001). ...
... Evidence suggests that humans (as most mammals) are vulnerable to the manipulation of light cues, entraining circadian rhythms accordingly (Wehr et al., 2001). Using this theoretical background, chronotherapeutic strategies are increasingly under scrutiny as possible treatments for mood and metabolic disorders (Coogan and Thome, 2011;Dyar and Eckel-Mahan, 2017;Schwartz and Olds, 2015). Light seems to play an important role in energy regulation and symptomatic improvement in SAD, but how this relates to HPA axis modulation is still unclear. ...
Article
Objective: Seasonal Affective Disorder (SAD) is a form of cyclic mood disorder that tends to manifest as winter depression. SAD has anecdotally been described as a hypocortisolemic condition. However, there are no systematic reviews on SAD and Hypothalamic-Pituitary-Adrenal (HPA) axis function. This review intends to summarize these findings. Methods: Using the PRISMA (2009) guideline recommendations we searched for relevant articles indexed in databases including MEDLINE, EMBASE, PsycINFO, and PsychArticles. The following keywords were used: "Seasonal affective disorder", OR "Winter Depression", OR "Seasonal depression" associated with: "HPA Axis" OR "cortisol" OR "CRH" OR "ACTH". Results: Thirteen papers were included for qualitative analysis. Studies used both heterogeneous methods and populations. The best evidence comes from a recent study showing that SAD patients tend to demonstrate an attenuated Cortisol Awakening Response (CAR) in winter, but not in summer, compared to controls. Dexamethasone Suppression Test (DST) studies suggest SAD patients have normal suppression of the HPA axis. Conclusion: There is still insufficient evidence to classify SAD as a hypocortisolemic condition when compared to controls. Heterogeneous methods and samples did not allow replication of results. We discuss the limitations of these studies and provide new methods and targets to probe HPA axis function in this population. SAD can provide a unique window of opportunity to study HPA axis in affective disorders, since it is highly predictable and can be followed before, during and after episodes subsides.
... From the literature study we observed that many researchers in medical field have found the cause of Mood change due to change in CT. The mood is affected by Light in several forms: One is by direct modulation of the neurotransmitters like serotonin, a mood regulator, and other by training and stabilizing circadian rhythms, which addresses sleep disorders and desynchronisation of circadian rhythms [4,5]. Study also reveals that the human pineal gland is also sensitive to shade of ambient light [6]. ...
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Normally, when a person moves from outdoor area having bright light to an indoor area with light of not similar brightness, it affects mood and also rhythmic activities within body. This paper presents the possibility of keeping the Mood consistent by implementing the Arduino based system to control the Colour Temperature of working space as that of ambient light. Here we have used high sensitivity, IR blocking RGB sensor to acquire ambient light. Colour Temperature thus obtained from RGB is sent through interfaced Arduino Nano controller. The range of 1000K to 10000K is considered for the study. These values are mapped for controlling pure white and warm white to glow LEDs similar to ambient light. General appearance of light is categorized in three forms viz. warm white, cool white and day light according to its varied Colour Temperature. The system was successfully implemented by varying Colour Temperature through different sources and mapped those values for glow of LEDs so as to maintain the light ambience. When the indoor light ambience becomes same as that of outdoor ambient light it helps to keep mood consistent.
... In the field of non-pharmacological treatment options to decrease depressive symptoms in the general population, bright light therapy (BLT) is an evidence-based treatment to decrease depressive symptoms in seasonal and non-seasonal depression (Even et al., 2008;Golden et al., 2005;Kripke, 1998;Lieverse et al., 2011;Martiny, 2004;Nussbaumer et al., 2015;Pail et al., 2011;Schwartz & Olds, 2015;Tuunainen et al., 2004;Wirz-Justice et al., 1993, 2011. Previous research has shown that BLT influences cortisol concentrations in depressed adults of the general population (Leproult et al., 2001;Lieverse et al., 2011;Thalen et al., 1997). ...
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Background Depressive symptoms and stress are common in adults with intellectual disabilities. Our aim was to explore long-term biological stress levels, assessed by hair cortisol (HairF) and cortisone (HairE) concentrations, in adults with intellectual disabilities and depressive symptoms and to investigate the effects of bright light therapy (BLT) on hair glucocorticoids. Method Scalp hair samples (n = 14) were retrospectively examined at baseline and post-BLT (10.000 and 300 lux). Liquid chromatography–tandem mass spectrometry was used to measure hair glucocorticoids. Results A significant correlation was found between baseline HairF and depression scores (r = .605, p = .028). Post-intervention HairE levels were significantly increased ([95% CI: 11.2–17.4 pg/mg], p = .003), in particular after dim light (300 lux) ([95% CI: 10.0–18.3 pg/mg], p = .020). Conclusions This study showed that retrospectively examining biological levels of stress in adults with intellectual disabilities seems a potentially promising and objective method to gain insight in the stress level of adults with intellectual disabilities.
... Phototherapy is also used in the treatment of eating disorders and obesity [4,5]. The mechanisms that mediated the influence of bright light on the CNS can be associated with the "biological clock" responsible for synchronization of circadian rhythms with photoperiod parameters [9]. The central regulatory elements of "biological clock" are the suprachiasmatic nuclei (SCN) of the hypothalamus and the pineal gland. ...
Article
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Phototherapy (therapy with bright light) is widely used to treat seasonal affective disorders, different types of depression, sleep disorders, and other diseases; it has no significant contraindications, but its effects on functional state and biological rhythms of the cardiovascular system in hypertension are poorly studied. In experiments on Wistar-Kyoto and SHR (spontaneously hypertensive rats) rats, the effect of bright light therapy on the daily profile of BP, HR, and production of epiphyseal melatonin was investigated. Phototherapy was simulated by exposure to 9000-lux cold light at the level animal eyes over 1 h (from 10.00 to 11.00 h) with LED lamps. In freely moving rats (free access to food), daily profiles of BP and HR were studied by 24-h continuous telemetry monitoring. The production of epiphyseal melatonin was assessed by measuring urinary concentration of its stable metabolite 6-sulfatoxymelatonin (aMT6s) during the day and night. During phototherapy, systolic BP significantly increased in in animals of both lines and diastolic BP increased in SHR rats. This effect persisted after the end of phototherapy session. Bright light had no effect on HR. In Wistar-Kyoto rats, phototherapy induced a significant decrease in daily concentration of aMT6s, but its nocturnal level did not change. In SHR rats, bright light therapy significantly decreased nighttime concentration of aMT6s in the urine and had no effect on daytime concentration of this metabolite. As a result, the difference between the night and day levels of aMT6s in the urine was leveled. Phototherapy produced more pronounced and less favorable effect on animals with primary arterial hypertension.
... Light can affect mood in several ways: by directly modulating the availability of neurotransmitters such as serotonin, which is involved in mood regulation, and by entraining and stabilising circadian rhythms, thereby addressing circadian desynchronisation and sleep disorders, which are rather common in people suffering from mental disorders. Therefore, in the last decades, light as an intervention-light therapy-has found an increasingly widespread use for treating mood and other psychiatric disorders [73,97]. ...
Article
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Humans live in a 24-hour environment, in which light and darkness follow a diurnal pattern. Our circadian pacemaker, the suprachiasmatic nuclei (SCN) in the hypothalamus, is entrained to the 24-hour solar day via a pathway from the retina and synchronises our internal biological rhythms. Rhythmic variations in ambient illumination impact behaviours such as rest during sleep and activity during wakefulness as well as their underlying biological processes. Rather recently, the availability of artificial light has substantially changed the light environment, especially during evening and night hours. This may increase the risk of developing circadian rhythm sleep–wake disorders (CRSWD), which are often caused by a misalignment of endogenous circadian rhythms and external light–dark cycles. While the exact relationship between the availability of artificial light and CRSWD remains to be established, nocturnal light has been shown to alter circadian rhythms and sleep in humans. On the other hand, light can also be used as an effective and noninvasive therapeutic option with little to no side effects, to improve sleep, mood and general well-being. This article reviews our current state of knowledge regarding the effects of light on circadian rhythms, sleep, and mood.
... Light can affect mood in several ways: by directly modulating the availability of neurotransmitters such as serotonin, which is involved in mood regulation, and by entraining and stabilising circadian rhythms, thereby addressing circadian desynchronisation and sleep disorders, which are rather common in people suffering from mental disorders. Therefore, in the last decades, light as an intervention-light therapy-has found an increasingly widespread use for treating mood and other psychiatric disorders [73,97]. ...
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Full-text available
Humans live in a 24-hour environment, in which light and darkness follow a diurnal pattern. Our circadian pacemaker, the suprachiasmatic nucleui (SCN) in the hypothalamus, is entrained to the 24-hour solar day via a pathway from the retina and synchronises our internal biological rhythms. Rhythmic variations in ambient illumination impact on behaviours such as sleep and wakefulness and their underlying biological processes. Rather recently, the availability of artificial light has substantially changed the light environment, especially during evening and night hours. At the same time, circadian rhythm sleep-wake disorders (CRSWD) are on the rise, which are often caused by a misalignment of endogenous circadian rhythms and external light-dark cycles. While the exact relationship between the availability of artificial light and CRSWD remains to be established, nocturnal light has been shown to alter circadian rhythms and sleep in humans. On the other hand, light can also be used as an effective and non-invasive therapeutic option with little to no side-effects, thereby also improving sleep, mood and general well-being. This article reviews our current state of knowledge regarding the effects of light on circadian rhythms, sleep, and mood.
... A meta-analytic review has reported increased variability of reaction time in children, adolescents and adults with ADHD compared to typically developing controls [60] and increased reaction time variability is considered one neuropsychological endopenotype for ADHD [60,62]. Additionally, circadian disturbances have been described in ADHD [63]. Thus, it would be interesting to apply our study design to individuals with ADHD and examine in how far blue-enriched light in the morning may lead to improved performance, in this case reduced variability of reaction time, in a group with known impairments in this performance parameter. ...
Article
Differential effects of blue- and red-enriched light on attention and sleep have been primarily described in adults. In our cross-over study in typically developing adolescents (11–17 years old), we found attention enhancing effects of blue- compared to red-enriched light in the morning (high intensity of ca. 1000 lx, short duration: <1 h) in two of three attention tasks: e.g. better performance in math tests and reduced reaction time variability in a computerized attention test. In our pilot study, actigraphy measures of sleep indicated slight benefits for red- compared to blue-enriched light in the evening: tendencies toward a lower number of phases with movement activity after sleep onset in the complete sample and shorter sleep onset latency in a subgroup with later evening exposure times. These findings point to the relevance of light concepts regarding attention and sleep in typically developing adolescents. Such concepts should be developed and tested further in attention demanding contexts (at school) and for therapeutic purposes in adolescents with impaired attention or impaired circadian rhythms.
... The pivotal role of light in the regulation of circadian rhythm has been well-established, with mealonopsincontaining retinal ganglion cells and suprachiasmatic nucleus involved in the process. 129) One epidemiological study in the United States reported a lower prevalence of ADHD in geographic regions with high solar intensity, suggesting that improvement in circadian rhythm disturbances are attributed to exposure to sunlight. 130) Few studies have been conducted to test the efficacy of the bright light treatment in ADHD patients with sleep problems. ...
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Attention-deficit hyperactivity disorder (ADHD) is notorious for its debilitating consequences and early age of onset. The need for early diagnosis and intervention has frequently been underscored. Previous studies have attempted to clarify the bidirectional relationship between ADHD and sleep problems, proposing a potential role for sleep problems as early predictors of ADHD. Sleep deprivation, sleep-disordered breathing, and circadian rhythm disturbances have been extensively studied, yielding evidence with regard to their induction of ADHD-like symptoms. Genetic-phenotypic differences across individuals regarding the aforementioned sleep problems have been elucidated along with the possible use of these characteristics for early prediction of ADHD. The long-term consequences of sleep problems in individuals with ADHD include obesity, poor academic performance, and disrupted parent-child interactions. Early intervention has been proposed as an approach to preventing these debilitating outcomes of ADHD, with novel treatment approaches ranging from melatonin and light therapy to myofunctional therapy and adjustments of the time point at which school starts.
Article
Context Light therapy is a non-pharmacological therapy that is currently being studied in cancer-related symptoms and is certificated as a low-risk intervention by FDA. Cancer-related fatigue (CRF) is the most common symptom reported by cancer patients. Objective To examine the effectiveness of light therapy for CRF in cancer patients through a systematic review and meta-analysis. Methods We conducted a systematic review of 4 electronic databases targeted randomized clinical trials evaluating light therapy for CRF (CRD42020215446), from inception to May 2021. The primary outcome was changes of CRF scores; secondary outcomes included depression, sleep, and quality of life (QoL). We quantitatively pooled outcomes using meta-analysis with random-effects models and assessed methodological bias. Results We identified thirteen RCTs representing 551 cancer patients, encompassing breast (n=5), ovarian or endometrial (n=1), multiple myeloma (n=1), lung (n=1), or combined (n=5) cancers. The comparison groups included dim light (n=12) and waiting list (n=1). Duration of intervention ranged from 1 to 12 weeks. Light intensities ranged from 417.9 to 12,000 lux. Light therapy was associated with a significant improvement in CRF (SMD = 0.45, p = 0.007), depression (SMD = -0.26, p = 0.03) and sleep difficulty (SMD = -2.46, p = 0.0006); a statistically non-significant trend was observed for QoL (SMD = 0.33, p = 0.09). Funnel plots for CRF suggest not significant publication bias. Conclusions Light therapy could be a feasible and effective option for improving CRF in cancer patients. Larger sample, rigor trials design and a standard protocol of intervention are needed to draw more conclusive conclusions.
Article
Mood disorders are wide spread with estimates that one in seven of the population are affected at some time in their life (Kessler et al., 2012). Many of those affected with severe depressive disorders have cognitive deficits which may progress to frank neurodegeneration. There are several peripheral markers shown by patients who have cognitive deficits that could represent causative factors and could potentially serve as guides to the prevention or even treatment of neurodegeneration. Circadian rhythm misalignment, immune dysfunction and oxidative stress and circadian rhythm misalignment are key pathologic processes implicated in neurodegeneration and cognitive dysfunction in depressive disorders. Novel treatments targeting these pathways may therefore potentially improve patient outcomes whereby the primary mechanism of action is outside of the monoaminergic system. Moreover, targeting immune dysfunction, oxidative stress and circadian rhythm misalignment (rather than primarily the monoaminergic system) may hold promise for truly disease modifying treatments that may prevent neurodegeneration rather than simply alleviating symptoms with no curative intent. Further research is required to more comprehensively understand the contributions of these pathways to the pathophysiology of depressive disorders to allow for disease modifying treatments to be discovered.
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Background: Pill-taking, expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder (MDD). Aims To examine the effects of medication, placebo and supportive care on treatment outcome, and the relationships of expectations and therapeutic alliance to improvement. Method: A total of 88 participants were randomised to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication. Expectations of medication effectiveness, general treatment effectiveness and therapeutic alliance were measured (trial registration at ClinicalTrials.gov: NCT00200902). Results: Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone. Therapeutic alliance predicted response to medication and placebo; expectations of medication effectiveness at enrolment predicted only placebo response. Conclusions: Pill treatment yielded better outcome than supportive care alone. Medication expectations uniquely predicted placebo treatment outcome and were formed by time of enrolment, suggesting that they were shaped by prior experiences outside the clinical trial.
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Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of estrogen receptor (ERα(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen. Cancer Res; 74(15); 1-12. ©2014 AACR.
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Light exposure can influence sleep and circadian timing, both of which have been shown to influence weight regulation. The goal of this study was to evaluate the relationship between ambient light, sleep and body mass index. Participants included 54 individuals (26 males, mean age 30.6, SD = 11.7 years). Light levels, sleep midpoint and duration were measured with wrist actigraphy (Actiwatch-L) for 7 days. BMI was derived from self-reported height and weight. Caloric intake was determined from 7 days of food logs. For each participant, light and activity data were output in 2 minute epochs, smoothed using a 5 point (10 minute) moving average and then aggregated over 24 hours. The mean light timing above 500 lux (MLiT500) was defined as the average clock time of all aggregated data points above 500 lux. MLiT500 was positively correlated with BMI (r = 0.51, p<0.001), and midpoint of sleep (r = 0.47, p<0.01). In a multivariable linear regression model including MLiT500 and midpoint of sleep, MLiT500 was a significant predictor of BMI (B = 1.26 SE = 0.34, β = 0.53 p = 0.001, r2Δ = 0.22). Adjusting for covariates, MLiT500 remained an independent predictor of BMI (B = 1.28 SE = 0.36, β = 0.54, p = 0.002, r2Δ = 0.20). The full model accounted for 34.7% of the variance in BMI (p = 0.01). Exposure to moderate levels of light at biologically appropriate times can influence weight, independent of sleep timing and duration.
Book
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"'Light therapy' is the only treatment in psychiatry that directly evolved out of basic neurobiology research. It is recognized as the treatment of choice for seasonal affective disorder and has been successfully used in nonseasonal depression and other psychiatric or neurologic illnesses, including bulimia nervosa and Alzheimer's disease. At the same time, 'wake therapy' is the fastest antidepressant known. Chronotherapeutic combinations of light and wake therapy achieve fast results and, by reducing residual symptoms, also minimize relapse. This manual introduces chronotherapeutics for depression, a new synthesis of non-pharmacologic interventions designed to accelerate remission in bipolar and unipolar patients alike. It examines the underlying clinical research, explains the involvement of the circadian timing system, and provides hands-on instructions for treating inpatients and outpatients. Written by three of the most prominent experts in the research and clinical applications of chronotherapy, this book enables clinicians to implement its principles and let their patients benefit from its practicality and effectiveness. In this manual psychiatrists, psychologists, primary care physicians and health care administrators find comprehensive overviews of theory, research background, practical guidelines, and future prospects. It is also essential reading for practitioners of sleep medicine." (Second edition, revised, was published in 2013.)
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Light is a powerful stimulant for human alertness and cognition, presumably acting through a photoreception system that heavily relies on the photopigment melanopsin. In humans, evidence for melanopsin involvement in light-driven cognitive stimulation remains indirect, due to the difficulty to selectively isolate its contribution. Therefore, a role for melanopsin in human cognitive regulation remains to be established. Here, sixteen participants underwent consecutive and identical functional MRI recordings, during which they performed a simple auditory detection task and a more difficult auditory working memory task, while continuously exposed to the same test light (515 nm). We show that the impact of test light on executive brain responses depends on the wavelength of the light to which individuals were exposed prior to each recording. Test-light impact on executive responses in widespread prefrontal areas and in the pulvinar increased when the participants had been exposed to longer (589 nm), but not shorter (461 nm), wavelength light, more than 1 h before. This wavelength-dependent impact of prior light exposure is consistent with recent theories of the light-driven melanopsin dual states. Our results emphasize the critical role of light for cognitive brain responses and are, to date, the strongest evidence in favor of a cognitive role for melanopsin, which may confer a form of "photic memory" to human cognitive brain function.
Article
In order to determine the usage pattern of light therapy (LT), we performed a survey of all psychiatric hospitals in Germany in 1992. Our data reveal that 13% of all psychiatric hospitals perform LT and another 7% indicate their interest in this treatment. Stratification into different treatment facilities demonstrates that 57% of the psychiatric university hospitals use LT. The usage of LT started in Germany in 1982 and there was a sharp rise from 1987 onwards. The majority of hospitals (89% of those hospitals which use LT) use LT successfully for the treatment of seasonal affective disorder (SAD) and its subsyndromal form followed by non-SAD depression (68%). LT is used as monotherapy in 71% of SAD patients compared with 34% in non-SAD depression.
Article
Importance It has been observed that suicidal behavior is influenced by sunshine and follows a seasonal pattern. However, seasons bring about changes in several other meteorological factors and a seasonal rhythm in social behavior may also contribute to fluctuations in suicide rates.Objective To investigate the effects of sunshine on suicide incidence that are independent of seasonal variation.Design, Setting, and Participants Retrospective analysis of data on all officially confirmed suicides in Austria between January 1, 1970, and May 6, 2010 (n = 69 462). Data on the average duration of sunshine per day (in hours) were calculated from 86 representative meteorological stations. Daily number of suicides and daily duration of sunshine were differentiated to remove variation in sunshine and variation in suicide incidence introduced by season. Thereafter, several models based on Pearson correlation coefficients were calculated.Main Outcomes and Measures Correlation of daily number of suicides and daily duration of sunshine after mathematically removing the effects of season.Results Sunshine hours and number of suicides on every day from January 1, 1970, to May 6, 2010, were highly correlated (r = 0.4870; P < 10−9). After differencing for the effects of season, a mathematical procedure that removes most of the variance from the data, a positive correlation between number of suicides and hours of daily sunshine remained for the day of suicide and up to 10 days prior to suicide (rmaximum = 0.0370; P < 10−5). There was a negative correlation between the number of suicides and daily hours of sunshine for the 14 to 60 days prior to the suicide event (rminimum = −0.0383; P < 10−5). These effects were found in the entire sample and in violent suicides.Conclusions and Relevance Duration of daily sunshine was significantly correlated with suicide frequency independent of season, but effect sizes were low. Our data support the hypothesis that sunshine on the day of suicide and up to 10 days prior to suicide may facilitate suicide. More daily sunshine 14 to 60 days previously is associated with low rates of suicide. Our study also suggests that sunshine during this period may protect against suicide.
Article
To investigate the long-term antidepressant effect of a chronotherapeutic intervention. We randomized 75 patients with major depression to fixed duloxetine and either a chronotherapeutic intervention (wake group) with three initial wake therapies, daily bright light therapy, and sleep time stabilization or to a group using daily exercise. Patients were followed 29 weeks. We report the last 20 weeks, a follow-up phase, where medication could be altered. Patients were assessed every 4 weeks. Remission rates were primary outcome. Patients in the wake group had a statistically significant higher remission rate of 61.9% vs. 37.9% in the exercise group at week 29 (OR = 2.6, CL = 1.3-5.6, P = 0.01). This indicated continued improvement compared with the 9 weeks of treatment response (44.8% vs. 23.4%) with maintenance of the large difference between groups. HAM-D17 endpoint scores were statistically lower in the wake group with endpoint scores of 7.5 (SE = 0.9) vs. 10.1 (SE = 0.9) in the exercise group (difference 2.7, CL = 0.5-4.8, P = 0.02). Patients continued to improve in the follow-up phase and obtained very high remission rates. This is the first study to show adjunct short-term wake therapy and long-term bright light therapy as an effective and feasible method to attain and maintain remission. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Article
Importance Residential (geographic) history and extent of solar exposure may be important risk factors for exfoliation syndrome (XFS) but, to our knowledge, detailed lifetime solar exposure has not been previously evaluated in XFS.Objective To assess the relation between residential history, solar exposure, and XFS.Design, Setting, and Participants This clinic-based case-control study was conducted in the United States and Israel. It involved XFS cases and control individuals (all ≥60-year-old white individuals) enrolled from 2010 to 2012 (United States: 118 cases and 106 control participants; Israel: 67 cases and 72 control participants).Main Outcomes and Measures Weighted lifetime average latitude of residence and average number of hours per week spent outdoors as determined by validated questionnaires.Results In multivariable analyses, each degree of weighted lifetime average residential latitude away from the equator was associated with 11% increased odds of XFS (pooled odds ratio [OR], 1.11; 95% CI, 1.05-1.17; P < .001). Furthermore, every hour per week spent outdoors during the summer, averaged over a lifetime, was associated with 4% increased odds of XFS (pooled OR, 1.04; 95% CI, 1.00-1.07; P = .03). For every 1% of average lifetime summer time between 10 am and 4 pm that sunglasses were worn, the odds of XFS decreased by 2% (OR, 0.98; 95% CI, 0.97-0.99; P < .001) in the United States but not in Israel (OR, 1.00; 95% CI, 0.99-1.01; P = .92; P for heterogeneity = .005). In the United States, after controlling for important environmental covariates, history of work over water or snow was associated with increased odds of XFS (OR, 3.86; 95% CI, 1.36-10.9); in Israel, there were too few people with such history for analysis. We did not identify an association between brimmed hat wear and XFS (P > .57).Conclusions and Relevance Lifetime outdoor activities may contribute to XFS. The association with work over snow or water and the lack of association with brimmed hat wear suggests that ocular exposure to light from reflective surfaces may be an important type of exposure in XFS etiology.
Article
Importance Older adults have high rates of sleep disturbance, die by suicide at disproportionately higher rates compared with other age groups, and tend to visit their physician in the weeks preceding suicide death. To our knowledge, to date, no study has examined disturbed sleep as an independent risk factor for late-life suicide.Objective To examine the relative independent risk for suicide associated with poor subjective sleep quality in a population-based study of older adults during a 10-year observation period.Design, Setting, and Participants A longitudinal case-control cohort study of late-life suicide among a multisite, population-based community sample of older adults participating in the Established Populations for Epidemiologic Studies of the Elderly. Of 14 456 community older adults sampled, 400 control subjects were matched (on age, sex, and study site) to 20 suicide decedents.Main Outcomes and Measures Primary measures included the Sleep Quality Index, the Center for Epidemiologic Studies–Depression Scale, and vital statistics.Results Hierarchical logistic regressions revealed that poor sleep quality at baseline was significantly associated with increased risk for suicide (odds ratio [OR], 1.39; 95% CI, 1.14-1.69; P < .001) by 10 follow-up years. In addition, 2 sleep items were individually associated with elevated risk for suicide at 10-year follow-up: difficulty falling asleep (OR, 2.24; 95% CI, 1.27-3.93; P < .01) and nonrestorative sleep (OR, 2.17; 95% CI, 1.28-3.67; P < .01). Controlling for depressive symptoms, baseline self-reported sleep quality was associated with increased risk for death by suicide (OR, 1.30; 95% CI, 1.04-1.63; P < .05)Conclusions and Relevance Our results indicate that poor subjective sleep quality is associated with increased risk for death by suicide 10 years later, even after adjustment for depressive symptoms. Disturbed sleep appears to confer considerable risk, independent of depressed mood, for the most severe suicidal behaviors and may warrant inclusion in suicide risk assessment frameworks to enhance detection of risk and intervention opportunity in late life.