Time to put a spotlight on out-patient chronotherapy for depression

Summary The challenge of identifying efficacious out-patient treatments for depression is amplified by the increasing desire to find interventions that reduce the time to sustained improvement. One potential but underexplored option is triple chronotherapy (TCT). To date, use of TCT has been largely restricted to specialist units or in-patients. Recent research demonstrates that it may be possible to undertake sleep deprivation in out-patient settings, raising the possibility of delivering TCT to broader populations of individuals with depression. Emerging evidence suggests that out-patient TCT is a high-benefit, low-risk intervention but questions remain about how to target TCT and its mechanisms of action. Like traditional antidepressants, TCT probably acts through several pathways, especially the synchronisation of the ‘master clock’. Availability of reliable and valid methods of out-patient measurement of intra-individual circadian rhythmicity and light exposure are rate-limiting steps in the wider dissemination of TCT.

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111 Artificial Light-Triggered Sleep Deprivation May Lead to Allodynia in Rodent Model

SLEEP ◽

10.1093/sleep/zsab072.110 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A45-A46

Author(s):

Skyler Kanegi ◽

Armen Akopian

Keyword(s):

Sleep Deprivation ◽

Light Exposure ◽

Light Stimulus ◽

Continuous Light ◽

Artificial Light ◽

Light Cycle ◽

Tissue Samples ◽

Mechanical Threshold ◽

Dim Light ◽

Von Frey Filaments

Abstract Introduction The combination of artificial light and lack of exposure to natural light can delay the circadian clock, dysregulate the circadian cycle, and decrease alertness upon waking. This effect has been especially significant during the COVID-19 pandemic, where overexposure to artificial light at improper hours has contributed to increased rates of clinical insomnia. Artificial light may also contribute to concomitant neurological conditions such as primary headache, but the mechanisms by which light triggers sleep deprivation-induced headache are not well-understood. Methods To measure pain sensitivity, we habituated 13 wild-type male mice to von Frey filaments applied to the periorbital area until there was no response to 0.6g stimulus. We then applied 5 lux of continuous dim light to mice during their usual 12-hour dark cycle. The 12-hour light cycle remained unchanged with 200 lux continuous light. Three groups of mice experienced the dim light stimulus for one, three, or five consecutive days. Ambulation and rest activity were measured using SOF-812 Activity Monitor machines. After the experiment concluded, we waited 24 hours and measured mechanical threshold using von Frey filaments at 1, 3, 5, 8, and every 3 days subsequently until mice no longer responded to 0.6g stimulus. Results Artificial light triggered changes in circadian behavior including increased number of rest periods during 12-hour dark (dim light) cycle and shortened sleep duration during 12-hour light cycle. Following the artificial light stimulus, there was a significant decrease in mechanical threshold (P<0.05), representing allodynia. The one-day group displayed one day of significant allodynia. The three-day group displayed three days of significant allodynia. The five-day group displayed five days of significant allodynia. Conclusion Artificial light may trigger circadian dysregulation, and the duration of artificial light exposure seemed to be directly correlated to the duration of allodynia up to one week after the stimulus was removed. We will repeat these experiments and analyze CNS and PNS tissue samples to understand the underlying physiological and biochemical bases of how artificial light triggers sleep deprivation-induced headache. This knowledge could increase our understanding of the pathophysiology and comorbidity of sleep deprivation and headache. Support (if any) Funding was received from the National Institute of Health (NS104200).

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0171 The Impact of Short-Term Bright Green Light Exposure in Partially Sleep-Deprived Persons

SLEEP ◽

10.1093/sleep/zsaa056.169 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A67-A68

Author(s):

J J Pilcher ◽

J B Bisson ◽

E J Scircle

Keyword(s):

Reaction Time ◽

Sleep Deprivation ◽

Simple Reaction Time ◽

Light Exposure ◽

Green Light ◽

Light Condition ◽

Cognitive Inhibition ◽

Short Term ◽

Simple Reaction ◽

Bright Green

Abstract Introduction Many workers and students experience regular sleep deprivation and daytime sleepiness when they are expected to be performing at their best. The purpose of the current research was to investigate the potential effect of short-term bright green light exposure on daytime performance and sleepiness in partially sleep-deprived persons. Methods Participants were 30 students (19.4±0.89 years; 20 females). On Day 1, participants were loaned a Fitbit to provide an objective measure of activity/sleep and were instructed to sleep no more than 5 hours that night. On Day 2, participants provided information on their sleep time for the previous night and were randomly assigned to a bright light condition (bright green light, 381 Lux) or a standard light condition (control condition, indoor florescent light, 139 Lux). They completed a simple reaction time task, the Arrow Flankers task to measure cognitive inhibition, and the Stanford Sleepiness Scale during three testing periods (baseline, after 20 minutes of light exposure, and after 60 minutes of light exposure). Between the testing periods, participants read a non-fiction book while exposed to their respective light condition. At the end of the study, participants returned their FitBit. Results The Fitbit and self-report sleep data indicated that participants slept 4.9 hours the night between Day 1 and Day 2. Mixed 2 (light condition) x 3 (testing period) ANOVAs indicated that the bright green light condition resulted in a significant decrease in reaction time on the Flankers task but had no significant effect on simple reaction time or subjective sleepiness. Conclusion The current findings suggest that 60 minutes of bright green light exposure could improve performance on a cognitive inhibition task. This suggests that bright green light exposure could be a useful countermeasure for cognitive performance decrements in settings where sleep deprivation is common. Support None to report.

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Local Anesthesia - Solution to Pain : An Overview

Journal of Current Medical Research and Opinion ◽

10.15520/jcmro.v3i07.317 ◽

2020 ◽

Vol 3 (07) ◽

pp. 537-548

Author(s):

Asima Jaan ◽

Rudhra Munshi ◽

Kriti Sareen ◽

Ekta Parmar ◽

Purnima Thakur ◽

...

Keyword(s):

Local Anesthetic ◽

Local Anesthetics ◽

Motor Block ◽

Mechanisms Of Action ◽

Anesthetic Agents ◽

Rate Limiting Step ◽

Limiting Step ◽

Neuronal Membranes ◽

Site Of Action ◽

Rate Limiting

Local anesthetics have been used clinically for more than a century, but new insights into their mechanisms of action and their interaction with biological systems continue to surprise researchers and clinicians alike. Local anesthetics must traverse several tissue barriers to reach their site of action on neuronal membranes. In particular, the perineurium is a major rate-limiting step. Previously it was assumed that patients are rarely allergic to local anesthetic agents, but variation in individual patient’s response to local anesthetics is larger than previously assumed .adjuncts available to block sensory nerver are there, but these typically also prolong motor block.

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Minireview: Entrainment of the Suprachiasmatic Clockwork in Diurnal and Nocturnal Mammals

Endocrinology ◽

10.1210/en.2007-0804 ◽

2007 ◽

Vol 148 (12) ◽

pp. 5648-5655 ◽

Cited By ~ 188

Author(s):

Etienne Challet

Keyword(s):

Activity Pattern ◽

Molecular Mechanisms ◽

Clock Genes ◽

Light Exposure ◽

Hormone Secretion ◽

Receptor Activation ◽

Active Species ◽

Voluntary Exercise ◽

Nocturnal Species ◽

Master Clock

Daily rhythmicity, including timing of wakefulness and hormone secretion, is mainly controlled by a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN clockwork involves various clock genes, with specific temporal patterns of expression that are similar in nocturnal and diurnal species (e.g. the clock gene Per1 in the SCN peaks at midday in both categories). Timing of sensitivity to light is roughly similar, during nighttime, in diurnal and nocturnal species. Molecular mechanisms of photic resetting are also comparable in both species categories. By contrast, in animals housed in constant light, exposure to darkness can reset the SCN clock, mostly during the resting period, i.e. at opposite circadian times between diurnal and nocturnal species. Nonphotic stimuli, such as scheduled voluntary exercise, food shortage, exogenous melatonin, or serotonergic receptor activation, are also capable of shifting the master clock and/or modulating photic synchronization. Comparison between day- and night-active species allows classifications of nonphotic cues in two, arousal-independent and arousal-dependent, families of factors. Arousal-independent factors, such as melatonin (always secreted during nighttime, independently of daily activity pattern) or γ-aminobutyric acid (GABA), have shifting effects at the same circadian times in both nocturnal and diurnal rodents. By contrast, arousal-dependent factors, such as serotonin (its cerebral levels follow activity pattern), induce phase shifts only during resting and have opposite modulating effects on photic resetting between diurnal and nocturnal species. Contrary to light and arousal-independent nonphotic cues, arousal-dependent nonphotic stimuli provide synchronizing feedback signals to the SCN clock in circadian antiphase between nocturnal and diurnal animals.

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Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1504239112 ◽

2015 ◽

Vol 112 (21) ◽

pp. 6748-6753 ◽

Cited By ~ 68

Author(s):

Sander Kooijman ◽

Rosa van den Berg ◽

Ashna Ramkisoensing ◽

Mariëtte R. Boon ◽

Eline N. Kuipers ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Intracellular Signaling ◽

Light Exposure ◽

Underlying Mechanism ◽

Circadian Rhythmicity ◽

Day Length ◽

Bat Activity ◽

Brown Adipose ◽

Brown Adipose Tissue Activity

Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity.

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Motor activity in depressed patients during therapeutic sleep deprivation

European Psychiatry ◽

10.1016/j.eurpsy.2009.11.004 ◽

2010 ◽

Vol 25 (8) ◽

pp. 465-467 ◽

Cited By ~ 3

Author(s):

T.U. Brückner ◽

M.H. Wiegand

Keyword(s):

Motor Activity ◽

Sleep Deprivation ◽

Depression Scale ◽

Mechanisms Of Action ◽

Activity Levels ◽

Hamilton Depression Scale ◽

Depressed Patients ◽

Bidirectional Relationship ◽

Dsm Iv ◽

Insight Into

AbstractProblemBoth sleep and motor activity have a bidirectional relationship with depression. The existing literature on motor activity during therapeutic sleep deprivation in depressed patients is inconsistent and fragmentary. In the present study we measured motor activity continuously during 40 hours of sleep deprivation in depressed patients.MethodThirty-four inpatients suffering from a major depression (DSM-IV) underwent sleep deprivation with a continuous waking period of 40 hours. Motor activity of the patients was continuously recorded using an actigraph on the non-dominant wrist. The effect of sleep deprivation was assessed by the Hamilton Depression Scale (six-item version), thus separating the group into responders and non-responders to sleep deprivation.ResultsWe found no significant differences in motor activity between responders and non-responders on the day before sleep deprivation. During the night, responders to sleep deprivation exhibited a higher motor activity and less periods of rest. On the day after sleep deprivation, responders exhibited a higher activity, too.ConclusionsMotor activity levels differ between the two groups, thus giving more insight into possible mechanisms of action of the therapeutic sleep deprivation. We suggest that higher motor activity during the night prevents naps and leads to better response to sleep deprivation.

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Serotonergic mediation of constant light-potentiated nonphotic phase shifting of the circadian locomotor activity rhythm in Syrian hamsters

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00047.2006 ◽

2006 ◽

Vol 291 (1) ◽

pp. R180-R188 ◽

Cited By ~ 12

Author(s):

Megan E. Knoch ◽

Dustin Siegel ◽

Marilyn J. Duncan ◽

J. David Glass

Keyword(s):

Sleep Deprivation ◽

Phase Response Curve ◽

Light Exposure ◽

Activity Rhythm ◽

Early Morning ◽

Phase Shifting ◽

Constant Light ◽

Phase Advance ◽

Way 100635 ◽

Receptor Phase

Short-term (1–3 days) constant light exposure (brief LL) potentiates nonphotic phase shifting induced by sleep deprivation and serotonin (5-HT) agonist stimulation. The present assessments reveal that exposure to brief LL markedly alters the magnitude and shape of the 5-HT1A,7 receptor agonist, 8-(+)2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahyronapthalene (8-OH-DPAT) phase-response curve, facilitating (∼12 h) phase-advance shifts during the early morning when serotonergics have no phase-shifting effect. Brief LL also reduces the threshold for 8-OH-DPAT shifting at midday, evidenced by 5- to 6-h phase-advance shifts elicited by dosages that have no effect without the LL treatment. The brief LL-potentiated phase advances to intraperitoneal 8-OH-DPAT at zeitgeber time 0 (ZT 0) were blocked by the 5-HT1A antagonists, pindolol and WAY 100635, indicating that this shifting is mediated by 5-HT1A receptors. Antagonists with action at 5-HT7 receptors, including ritanserin and metergoline, were without effect. Although autoradiographic analyses of [3H]8-OH-DPAT binding indicate that brief LL does not upregulate suprachiasmatic nucleus (SCN) 5-HT1A receptor binding, intra-SCN microinjection of 8-OH-DPAT at ZT 0 in brief LL-exposed hamsters induced shifts similar to those produced by intraperitoneal injection, suggesting that SCN 5-HT1A receptors mediate potentiated 8-OH-DPAT-induced shifts during the early morning. Lack of shifting by intra-SCN 8-OH-DPAT at ZT 6 or 18 (when intraperitoneal 8-OH-DPAT induces large shifts), further indicates that brief LL-potentiated shifts at these time points are mediated by 5-HT target(s) outside the SCN. Significantly, sleep deprivation-induced phase-advance shifts potentiated by brief LL (∼9 h) at ZT 0 were blocked by pindolol, suggesting that these behavioral shifts could be mediated by the same SCN 5-HT1A receptor phase-resetting pathway as that activated by 8-OH-DPAT treatment.

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Blood-Gene Expression Reveals Reduced Circadian Rhythmicity in Individuals Resistant to Sleep Deprivation

SLEEP ◽

10.5665/sleep.4064 ◽

2014 ◽

Vol 37 (10) ◽

pp. 1589-1600 ◽

Cited By ~ 44

Author(s):

Erna S. Arnardottir ◽

Elena V. Nikonova ◽

Keith R. Shockley ◽

Alexei A. Podtelezhnikov ◽

Ron C. Anafi ◽

...

Keyword(s):

Gene Expression ◽

Sleep Deprivation ◽

Circadian Rhythmicity ◽

Blood Gene Expression

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Psychological Factors Affecting Pain Response in Critically Ill Patients

Open Access Indonesian Journal of Medical Reviews ◽

10.37275/oaijmr.v1i2.35 ◽

2021 ◽

Vol 1 (2) ◽

pp. 32-34

Author(s):

Rani Iswara

Keyword(s):

Pain Management ◽

Sleep Deprivation ◽

Psychological Factors ◽

Recent Trend ◽

Multimodal Analgesia ◽

Mechanisms Of Action ◽

Traumatic Experience ◽

Factors Affecting ◽

Control Pain ◽

Harmful Effects

Pain is a traumatic experience and discomfort for all patients, especially criticallyill patients; if not treated properly, it can have harmful effects. Critical illnessesare usually painful, both because of the underlying source of the disease and thenecessary procedures performed to monitor and care for these patients. Paininduces anxiety, sleep deprivation, disorientation, agitation, delirium, and oftenbecome chronic depression. Psychological factors (sleep deprivation, anxiety, anddelirium) can also increase the perception of pain. Pain assessment is requiredfor proper pain management. Opioids are commonly used in pain management,but acetaminophen, dexmedetomidine, and gabapentin have more advantages.The recent trend is multimodal analgesia, which uses a combination of analgesicdrugs with different mechanisms of action. Another trend is the increasing useof pain relievers, which can control pain and relieve anxiety.

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