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Do circadian hormones fluctuations follow sleeping patterns or the time of day?

Do circadian hormones fluctuations follow sleeping patterns or the time of day?


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It is said that testosterone and cortisol are at their highest early in the morning, at 8 am, and lowest at night.

What happens, though, if someone regularly goes to sleep at 8 am and wakes up in the afternoon/evening over a long period? What happens if sleep times are inconsistent, sometimes sleeping overnight and sometimes in the morning? Do hormonal fluctuations follow the sleep pattern or do they follow the time of day?


Biological sleep clock researchers bag Nobel Prize in Physiology or Medicine

The Nobel Prize in Physiology or Medicine was awarded to three scientists from the United States. According to the Nobel committee, the scientists made great strides in the field of molecular mechanisms controlling the circadian rhythm, otherwise known as our biological clock. Their research showcases the way plants, humans and animals adapt their biological rhythm as per the day and night cycles of a planet and how it can actually change if we want it to.

BREAKING NEWS The 2017 #NobelPrize in Physiology or Medicine has been awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young. pic.twitter.com/lbwrastcDN

- The Nobel Prize (@NobelPrize) October 2, 2017

About the three Nobel Prize winners

The three winning scientists will be sharing a prize of 9 million Swedish kronor, which is around 1.1 million USD.

Jeffrey C Hall: He is an American geneticist and chronobiologist. He spent his career examining the neurological component of fly courtship and behavioral rhythms at the Brandeis University in Massachusetts.

Michael Rosbash: Michael Morris Rosbash is an American geneticist and chronobiologist. He is a professor at Brandeis University, same as Jefferey C Hall. His research group has been very active in different kinds of research on gene mutations.

Michael W Young: His lab at the Rockefeller University has been paramount in the field of chronobiology by identifying key genes associated with regulation of the internal clock responsible for circadian rhythms. He has dedicated over three decades to research studying genetically controlled patterns of sleep and wakefulness.

What does our biological clock do?

The circadian rhythm is an internal clock that all living organisms on Earth have. It is basically responsible for the phenomenon of us awake during the day and sleeping at night. Our biological clock also helps regulate eating habits, hormone release, blood pressure and body temperature.

More on the research with fruit flies

The scientists did their research on fruit flies and studied the sleep pattern.

A temporary mismatch between our external environment and this internal biological clock makes for the health disruptions in one's body. This can easily be described while travelling across multiple time zones as jet lag.

The research is built upon previous works by scientist Seymour Benzer and his student Ronald Konopka in the 1970s. They found mutations in an unknown gene disrupted the biological clock of flies and named the gene "period".

The current winners have have revealed how this "period" gene actually works by isolating it.

The protein this gene encodes called PER increases during the night and degrade during the day, highlighting that the protein fluctuates over a 24-hour cycle.

They discovered another gene which encodes a protein called TIM, that works in combination with the PER protein to regulate the activity of the period gene and named it "timeless".

Using fruit flies as a model organism, this years Nobel Laureates isolated a gene that controls the daily biological rhythm. pic.twitter.com/9nFzxiLsDB

- The Nobel Prize (@NobelPrize) October 2, 2017

How can the research help us?

The research could provide the platform to help those with degenerative diseases as well as blindness and schizophrenia. Therapeutic interventions could be made possible by mimicking light to regulate a person's body clock.

The 2017 #NobelPrize #Medicine for their discoveries of molecular mechanisms controlling the circadian rhythm?? pic.twitter.com/JWwo5kDfrA

- The Nobel Prize (@NobelPrize) October 2, 2017

Professor Russell Foster, head of the Nuffield Laboratory of Ophthalmology and director of the Sleep and Circadian Neuroscience Institute at the University of Oxford said, "This is a really important conceptual breakthrough. This part of biology is spreading to lots of different areas of biology and other areas of health."

Andrew Mackenzie, head of policy and communications at The Physiological Society in the UK said, "This is a very important piece of work and has huge implications. When the body clock is disrupted, you're more likely to suffer from diseases . this research means we can target particular aspects or components of the clock to help treat certain diseases. It shows that our brain and body require a good 24 hour rhythm to have optimum health," he said.

David Ray, a professor of medicine and endocrinology at the University of Manchester said, "These investigators were the first to discover a gene that controlled circadian behavior. It had been recognized for some time that animals and plants not only respond to changes in light as we move from day to night with the Earth's rotation, but that they anticipate such changes."


Introduction

Alzheimer's disease (AD) is a neurodegenerative disorder causing a variety of irreversible cognitive impairments leading to dementia. Apart from memory deficits [1], AD pathological symptoms involve impairments in regulation of various physiological processes, including circadian regulations of behavior, sleep patterns and hormonal secretion [2]. These physiological functions are temporally controlled by a circadian system which consists of the central clock in the suprachiasmatic nuclei (SCN) and peripheral clocks in neuronal and non-neuronal cells and tissues [3–5]. The central SCN clock drives systemic rhythms, mainly sleep/wake cycle and rhythm in pineal hormone melatonin levels [6], and synchronizes the peripheral clocks which drive rhythmically the tissue specific physiological programs [3]. The circadian signal is generated at the cellular level via autonomous molecular mechanism which drives rhythmically expression of clock genes, namely PER1,2, CRY1,2, REV-ERBα, and BMAL1. As a result of the molecular clock mechanism, circadian expression of PER1,2, CRY1,2, and REV-ERBα is in anti-phase to that of BMAL1 (reviewed in [7]).

Among people over 65 years old, more than 80% suffer from abnormalities in sleep/wake rhythmicity [8–10]. The function of the circadian system changes with age with an individually variable progression speed in elderly people even without AD pathology [11]. Therefore, it might be difficult to distinguish between the age- and AD-related modifications in circadian regulation These age-related changes of the circadian system involve alterations in amplitudes and phases of circadian rhythms [12], as well as changes in timing of the sleep/wake cycle with respect to the circadian cycle, i.e., shortening the phase angle of entrainment [13, 14]. In AD patients, incidence of sleep/wake cycle disturbances was found to be higher compared to age-matched controls. They mostly exhibit exacerbated disruption of sleep, such as fragmented nighttime sleep and a higher frequency and duration of nighttime awakenings and daytime sleep episodes (naps) [9, 15, 16]. Importantly, disruption of the sleep/wake cycle was diagnosed in AD patients already in mild and moderate stages of the disease [17].

Due to the SCN control, production of hormone melatonin exhibits pronounced circadian rhythms so that its levels are high during the subjective night and very low during the subjective day [18]. In healthy elderly people, the circadian rhythm in melatonin levels was dampened because their nocturnal melatonin secretion was decreased [19]. However, this issue is rather controversial because other studies did not confirm that reduction of plasma melatonin concentration is a general characteristic of healthy aging [20, 21]. In AD patients, more pronounced decrease in melatonin secretion was detected at early stages of the disease when their cognitive functions were still intact [22] and the rhythm dampening correlated with the AD neuropathology progression [22, 23]. These results suggest that in AD patients, the circadian function of the central SCN clock which drives rhythms in the aforementioned functions, might deteriorate further beyond that of what happens in elderly without the AD pathology [24].

It is still not known whether the worsening of the circadian regulation in AD is due to changes of the SCN morphology and function or due to changes of functions downstream the central clock. The age-dependent changes in the SCN were detected in healthy elderly but they occurred earlier and were more pronounced in AD patients [25–32]. However, whether the morphologic pathology causally accounts for the circadian SCN dysfunction is not clear. It is possible that the SCN clock mechanism itself is not affected in AD patients but the nuclei are disconnected from the rest of the brain. Such disconnection would result in aberrant circadian regulation of the downstream brain areas which contain subordinate circadian clocks. For example, in healthy subjects, clock gene expression was found to be rhythmic in the bed nucleus of stria terminalis (BNST), the cingulate cortex and the pineal gland [33, 34]. In the brains of AD patients, most of these clocks also exhibited well pronounced 24-hour rhythmicity, however, their mutual synchronization was altered compared to controls [35]. In contrast, the rhythms in clock gene expression in pineal glands were completely lost in both clinical and preclinical AD patients [33].

As mentioned above, the aberrant circadian regulation was shown to precede clinical onset of memory deficits in AD (reviewed in [36]) and might be associated with AD development [37], Therefore, the present study was aimed to find out whether disruption of the circadian system, more pronounced than that caused by physiological aging, is present in patients with the mild form of AD. Specifically, the study was designed to reveal whether the circadian disruption is present during the everyday life of patients who do not require hospitalization and live in their home environment. To achieve this, the couples of age-matched patients and their healthy spouses (who lived together and took care of them) were examined. The functional state of the circadian system was assessed based on the analysis of daily profiles of behavioral patterns, melatonin levels in saliva and clock gene expression in the peripheral cells of buccal mucosa.


Being comfortable in bed is crucial to ensuring a good night’s rest. Therefore, choose a mattress that oozes comfort. Temperature uniquely influences sleep in menopause. Thus, when it comes to the room temperature, you want to channel your inner Goldilocks and keep the temperature just right between 65°F to 75°F. However, when hot flashes are relentless, err on the cooler side. Consequently, experiment with opening up your windows, turning on a fan, or my personal favorite is using a device called a Chilipad. This device helps me to regulate my bed temperature. Also, don’t underestimate the power of reaching out and touching someone! Even if your desire for sex isn’t revved up. Holding a hand, a hug, or gentle caress can reduce stress and releases the feel-good hormone oxytocin. Trust me, don’t overlook the benefit of touch before sleep time.

Your sense of smell is one of your most powerful. Just like sound, certain scents can work for you or against you as you try to drift off.

Perhaps open your window. Or get an air filter. An air filter will improve the quality of air and also filter out any unwanted odors. Aromatherapy also creates a soothing environment. Lavender aromatherapy is notorious for promoting rest, relaxation, and sleep. It can be used with a diffuser or applied topically. Sleep in menopause is certainly more relaxing with a dab of lavender essential oil to the bottoms of your feet. My go-to essential oils right now are the organic blends Calm and Circadian Rhythm from Vibrant Blue Oils to ease me into slumber. I am digging these because they are effective and organically sourced. Bonus, they are also made by a local Seattle mom. Always got to give some PNW love!


Quick Summary

  • Don't expose yourself to bright lights (specifically blue light) within 1-2 hours of going to bed.
  • Go to bed and wake up at the same time every night (including the weekends).
  • Expose yourself to sunlight early in the morning and throughout the day, and exercise early in the morning outside if possible.
  • Respect your chronotype or tendency to go to bed earlier or later when figuring out the best time for you to go to bed every night.
  • Limit your naps to 20 minutes at the most, and don't nap late in the day. The best time is around 1-1:30 pm if you're an early riser, or 2:30-3 if you're a late riser.

Your circadian rhythm s are physical, mental, and behavioral changes that follow a daily cycle, mainly influenced by light and darkness. Circadian rhythms are found in most living things, including animals, plants, and many tiny microbes.

Sleep Consistency - The main thing you can do to get in sync with your circadian rhythm is to fall asleep and wake up at the same times each morning and night. The hardest part of following this guideline is to not sleep in on the weekends.

Naps - If you&rsquore sleep deprived and you want to catch up, the best way is with naps. You have to be careful with napping though, as they should be limited to 20 minutes in the afternoon. Taking naps longer than 20 minutes and or taking a nap too late in the day can negatively affect your sleep at night. Sleep experts tell us that if you're an early riser, your afternoon siesta will probably be around 1 pm, and if you wake up a little later, it may be around 1:30 or 2 pm. If you thought that you got tired in the afternoon because of lunch, the data shows us that people often naturally get tired in the afternoon, even if they haven't eaten (hence the Spanish or Latin American "siesta."

Electronics before bed - Your brain sets its circadian rhythm by it&rsquos exposure to light. This is where a lot of people are making mistakes. Looking at TVs, tablets, and phones late at night expose your brain to blue light that tells your brain that it&rsquos light out and it needs to be awake.

Lights when you wake - You should be exposed to sunlight in the morning and throughout the afternoon, and a great habit is to expose yourself to sunlight after you wake up, and exercise outside if possible. The other factor that influences your circadian rhythm is temperature, so regularly exercising in the morning will raise your temperature, signaling your brain to wake up, and reducing the temperature of your room at night will signal your brain to sleep (the optimum temperature is 60-68 degrees, you'll have to experiment to find your optimal sleep temperature).

Blue light before bed - You should have no exposure to blue light within 1-2 hours of going to sleep. As TVs don&rsquot have blue light blockers, you can wear blue light blocking glasses, or watch programs on your computer, tablet or phone. Many phones have a blue light blocker that you can turn on at night, or you can install an app on your computer, tablet or phone that blocks blue light, such as f.lux.

Lights while you sleep - Put a nightlight in your bathroom and don&rsquot use your normal bathroom lights when getting ready to go to bed. When you get up during the night to go to the bathroom, you should only be exposed to the minimum amount of light. Make sure your bedroom is dark. You can use light-blocking or room-darkening shades, or you can use a sleep mask.

Make sure that you don&rsquot have a bright clock next to your bed. If you do, use the dimmest setting. And if there are any other lights in your room (such as on the tv), cover them.

Calculating Your Optimum Bedtime

We go through a full cycle of sleep in approximately 90 minutes:

  • Stage 1 (N1): light, non-rapid eye movement (NREM) sleep where the eyes move slowly and muscle activity slows, and you can be awakened easily.
  • Stage 2 (N2): the first stage of NREM sleep as eye movement stops, the brain slows down, the heart rate slows, and the body temperature begins to drop this is where the brain prepares for deep sleep. It is more difficult to be awakened in this stage than in stage 1.
  • Stage 3 (N3): this is where deep NREM sleep occurs this is the most restorative stage of sleep. Being awakened in this stage is rare.
  • Stage 4: This is the rapid eye movement stage (REM) where the eyes move rapidly from side to side and when dreaming occurs. You can be awakened more easily in this stage.

The National Sleep Foundation recommends a range of 7-9 hours for adults ages 26-64, 7-8 hours for those 65 and older. If you find that 7.5 hours isn't enough for you, add 15 more minutes of sleep to your routine until you find the number that works for you.

The next step is to adjust your sleep and wake time to slightly earlier or later until you're waking up 5-10 minutes ahead of your alarm. This is because everyone can have slight variations in their sleep cycles. If you're waking up much earlier than your alarm, then go to bed a few minutes later. If you're sleeping through your alarm, then you'll want to go to bed earlier.

Your Chronotype

In addition to figuring out how much sleep you need, it's also helpful to know your chronotype, or when you prefer to sleep. Everyone pretty much knows what their preference for when to sleep is, with the two categories being a morning person, or phase advanced, or a night person, or phase delayed. Dr. Winter explains that our chronotype is genetic, influenced by your clock genes, and can be manipulated to some degree by light exposure, light timing, exercise schedules, social interaction, and sleep schedules. Age is also a factor, with younger people tending towards going to bed late, and older people tending to go to bed earlier. Working with your chronotype will help you get quality sleep.

If you're an "early bird," set an earlier bed time and stick with it. If you do better waking up very early, do an early morning workout to free up your evenings and prevent exercising late, which for some people can delay the onset of sleep.

If you're a "night owl," try to arrange your schedule so your day starts later. Talk to your boss about starting a little later and ending later. Don't set early morning appointments for yourself. Just because the rest of the world seems to be on an early morning start time doesn't mean that you have to be.


CONCLUSION

Factors underlying clinical manifestations of sundowning are usually multifaceted, and requiring biopsychosocial approaches to assessment and treatment. Various behavioral disruptions, including sundowning syndrome in AD and other types of dementia, have become an increasingly important topic of clinical investigations. The emergence or worsening of behavioral disturbances in cognitively impaired individuals has been recognized by clinicians for the last several decades, which prompted researchers to utilize different methods to investigate the circadian rhythm, hormonal, physio-logical, pharmacological, iatrogenic, psychological, and other possible correlations with sundowning symptoms. Frequently observed behavioral abnormalities in demented patients with exacerbation in the late afternoon, evening, or at night, pose a significant burden and challenge to caregivers, families, and nursing staff. Finding complex etiological relationships between triggering factors and various manifestations of sun-downing syndrome may lead to effective management of this clinical phenomenon.


Unit 5: States of Consciousness

a sleep disorder characterized by uncontrollable sleep attacks. The suffered may lapse directly into REM sleep, often at inopportune times.

periodic, overwhelming sleepiness

attacks usually last less than 5 minutes, but can last 10-20

in severe cases, person may collapse directly into brief period of REM sleep, with its loss of muscle tension (paralyzed)

absence of hypothalamic neural center that produces orexin, neurotransmitter linked to alertness

People intermittently stop breathing during sleep. After a minute or so, decreased blood oxygen arouses them and they wake up enough to snort in air for a few seconds process repeated hundreds of times a night (up to 400), depriving them of slow-wave sleep

sufferers often unaware of disorder and don't recall episodes next morning just report feeling fatigued and depressed

mask like device with air pump to keep sleeper's airway open and breathing regular is treatment

target mostly children who, who may sit up or walk around, talk incoherently, experience a doubling of heart rate and breathing rates, and appear terrified

don't fully wake up during and remember little

during stage 4, screaming, panic, rapid heart rate, abrupt awakening (may not completely awaken)

conditions that run in families

children are most prone because deepest, longest stage 4

sleepwalking usually harmless and not recalled in the morning sleepwalkers return to bed on their own or guided by family member

after sleep deprived, people sleep deeper, increasing sleepwalking

sleepwalking is also called somnambulism

notable for their hallucinatory imagery, discontinuities, and incongruities, and for the dreamer's delusional acceptance of the content and later difficulties remembering it.

so vivid we may confuse them with reality

six years of our life spent in dreams

8 in 10 dreams marked by at least one negative event or emotion (repeated failure, attacked, pursued, rejected, misfortune)

dreams with sexual imagery don't occur often (1 in 10 for men 1 in 30 for women)

manifest content incorporates traces of previous day's nonsexual experiences and preoccupations

sensory stimuli in our sleeping environment may also intrude

withdrawing REM-supressing sleep medications also increases REM sleep but with nightmares

follows hypnotic introduction

power resides not in the hypnotist but in the subject's openness to suggestion they engage people's ability to focus on certain images or behaviors

has help alleviate headaches, asthma, and stress related skin disorders, also obesity

drug, alcohol, smoking addictions haven't responded well

hypnotic dissociation if vivid form of everyday mind splits like doodling during lecture

divided conscious theory: hypnosis has caused a split in awareness- hypnosis dissociates sensation of pain stimulus and emotional suffering

divided conscious theory is controversial but we for sure do much more thinking and acting than we are conscious of our info-processing starts with selective attention and is divided into conscious and unconscious realms much of behavior occurs on autopilot in hypnosis, like life

yoga and maharishi (transcendental meditation)

brain waves slow (alpha and theta), heart rate and respiration decline (can be produced with other methods of relaxation are results due to mediation or just relaxation

skeptical of sources of research/information

sample-bias, self-report, not always based on good research design

user's primary focus becomes obtaining and using the drug

particularly stress-relieving drugs

alcohol, heroin, rohypnol, barbiturates, and opiates

caffeine, nicotine, more powerful amphetamines cocaine and ecstasy

stimulant euphoria,alertness, energy

-irritability, insomnia, hypertension, seizures

a powerfully addictive drug that stimulates the central nervous system, with speeded up body functions and associated energy and mood changes over time appears to reduce baseline dopamine levels

a synthetic stimulant and mild hallucinogen emotional election, disinhibition

-dehydration, overheating, depressed mood, impaired cognitive and immune functioning

produces euphoria and social intimacy but with short term health risks and longer term harm to serotonin producing neurons and to mood and cognition

powerful hallucinogenic drug also known as acid

through cardiac arrest) often similar to drug induced hallucinations

visions of tunnels, bright light or bright figures, old memories, out of body sensations

-sensory experiences as falling (hypnagogic jerks/ muscle contractions)

- brief transition (1-7 minutes)

-sleep talking most likely to occur here

-sleep walking, talking, bed wetting

dreams provide a "psychic safety valve" - expressing otherwise unacceptable feelings contain manifest (remembered) content and a deeper layer of latent content

but lacks scientific support, and dreams can be interpreted many different ways

dreams help us sort out the day's events and consolidate our memories

when you go to bed stressing over a problem and you wake up having a realized a solution to your problem

people tested the next day improve on a learned task after a night of memory consolidation

regular brain stimulation from REM sleep may help develop and preserve neural pathways

stimulating experiences develop and preserve brains neural pathway

-theory attempts to explain why in your dram you may start flying then suddenly you might be fighting a dragon and moments later your mom walks in and tells you to clean your room

REM sleep triggers neural activity the evokes random visual memories, which our sleeping brain weaves into stories

PET scans of sleeping people reveal increased activity of emotion related limbic system during REM sleep

dream content reflects dreamer's cognitive development- their knowledge and understanding

darkness is dangerous, better off asleep in a cave than looking for food

hormone responsible for regulating your circadian rhythms

everybody daydreams- not just fantasies

mental preparation, rehearsal, replay

obstructive sleep apnea is more common

periodical physical fluctuations

1. annual - duck migration, hibernation
2. 28 day - menstrual cycle
3. 24 hour cycle - varying levels of alertness, temperature, hormone levels
4. 90 min - sleep cycles

depressant initial high followed by relaxation and disinhibition

depressant rush of euphoria, relief from pain

-depressed physiology, agonizing withdrawal

stimulant rush of euphoria, confidence, energy

-cardiovascular stress, suspiciousness, depressive crash

-impaired learning and memory, increase risk of psychological disorders, lung damage from smoke

reduced sperm production, disrupted menstrual cycle, liver damage, high blood pressure, heart attacks

preconscious level- memories, stored knowledge

conscious processing is serial processing (requires attention, step by step)

treatment: bright light, spending time outdoors, avoid caffeine

easier to adjust to west than east

teens need about 9.25 but get 6

everyone needs 8 hours of sleep not true

9 hours if left unhindered (refreshed, better mood, more efficient and accurate work)

brain keeps sleep debt for about 2 weeks (sleep always wins tiredness battle)

people sleep about 1/3 of their life (25 years)

infants spend about 50% if REM during first couple months, declines to 30% in first year, then declines to 20%

slow wave sleep declines with age

sleep doesn't really vary across cultures

newborns spend nearly 2/3 of day asleep adults no more than 1/3

differences in sleep needed is partially due to age

sleep patterns may be genetically influenced, some also culturally influenced

pattern and duration of sleep similar among identical twins, not fraternal twins

with no sleep debt and 7.5-9 hours a night you're more energized and happier

teens who need 8-9 hours of sleep now getting 7

sleep strengthens memory, increases concentration, boosts mood, moderates hunger and obesity, fortifies the disease-fighting immune system, and lessens the risk of fatal accidents

sleep may play a role in the ______________- during deep sleep, pituitary gland releases growth hormone as we age, we release less of this hormone and spend less time in deep sleep

sleep is for making _____________________- for restoring and rebuilding our fading memories of the day's experiences

people trained to perform tasks recall better after sleep

neural activity during slow-wave sleep reenacts and promotes recall of prior novel experiences

omplete night's sleep boosts thinking and learning

people more insightfully solve problems after working on a task and sleeping on it

better discern connections between novel pieces of information

stress, anxiety, depression, medications

recurring problems in falling or staying asleep (falling asleep initially, difficulty remaining asleep, persistent early morning awakening)

1 in 10 adults complain of this 1 in 4 elderly

many overestimate (by double) how long it takes them to fall asleep and underestimate (by half) how long they have actually slept because it's the waking part we remember

common quick fixes (alcohol and sleeping pills) can aggravate the problem, reducing REM sleep and leaving person with next day blahs person may need increasing doses for affect when drug discontinued, insomnia worsens

natural alternatives: exercise regularly (not late), avoid caffeine and chocolate and high foods in evening (drink milk), relax before bed with dim light, follow sleep schedule (don't nap), hope clock face, manage stress levels

although does feel like an altered state, EEG does not indicate it

lack of special physiological change

research disputes this ability

statement that hypnosis enables people to recover accurate memories as far back as birth is inaccurate

(same effects can be duplicated with non hypnotized subjects, no help in recall of information, in age regression hypothesis inaccurate recall of information

some researchers believe that hypnotic phenomena reflect the working of normal consciousness and the power of social influence point out how powerfully our interpretations and attentional spotlight influence our ordinary perceptions

subjects begin to feel and behave in ways appropriate for "good hypnotic subjects" more trust, more allowed hypnotist can direct attentions and fantasies continue to do hypnotic stuff if they think the experiment in still going if experimenter eliminates their motivation for acting hypnotized, they become unresponsive

advocates of this theory contend that hypnotic phenomenon are an extension of everyday social behavior, not unique to hypnosis

most grant that normal social and cognitive processes play a part in hypnosis, but believe hypnosis is more than inducing someone to play the role of "good subject" (hypnotized subjects sometimes carry out even when believing no one is watching / distinctive brain activity accompanies hypnosis / mere imagination becomes compelling hallucination)

surgery argument- unlikely to risk severe pain just to please physician and fulfill role



Get the results you deserve

Chronobiology: Utilizing the Circadian Rhythm to prevent Obesity

Introduction: (skip if you want)

The human body is such a beautiful and stunning machine that is designed to adapt very efficiently to its constantly changing environment. Humans have muscles that will grow and strengthen when exercised, metabolism that will slow down and speed up according to food availability, and most importantly a circadian rhythm that is designed to anticipate and prepare for changes in the external environment.

The circadian rhythm is also known more commonly as the “biological clock”. Our biological clock is a combination of complex systems inside the human body that work together in synchronization to make internal changes (metabolically, psychologically, behaviorally, etc.) at specific times of the day to predict and prepare for external changes that will occur in the environment so our body can respond and function appropriately. This article will go deep into the understandings and complexities of the circadian rhythm and its role in our body and the adverse effects circadian disruption can cause. A lot of scientific research has found that chronodisruption is associated with obesity and metabolic syndrome symptoms as well as premature aging, cancer, cardiovascular disease and psychological problems. After reading this article, one will easily understand why.

Click to enlarge image
Supporting Research (skip if you want)
In a study [3] investigating the circadian rhythm of lipoproteinlipase [a protein enzyme that cleaves triglycerides into Free Fatty Acids and helps the uptake of Free Fatty Acids into adipose (fat) tissue] and obesity in nocturnal mice, it was found that when the mice were fed a high-fat diet during the day they gained significantly more weight than when fed during the night. This occurred because lipoproteinlipase oscillations did not peak during the day to properly metabolize fat. From this we can conclude that it is important to eat at the right times while our metabolism (lipoproteinlipase for example) is at its peak to correctly metabolize food (such as fat).

How does the circadian rhythm work?
The main circadian rhythm is maintained by the Suprachiasmatic Nucleus found in the hypothalamus. It can receive photic (light) inputs from the environment via melanopsin ganglionar cells. These cells signal the brain via the non-visual pathway through the retinohypothalamic tract to perceive whether it is day or night . Under natural conditions of sleeping when the sun sets and waking when the sun rises, our suprachiasmatic nucleus is reset correctly each day to tell our body whether it is day or night. Other organs and various tissues in our body also have a self-sustained circadian rhythm but receive input regularly from the suprachiasmatic nucleus so the whole body can be correctly synchronized together and with the external environment (see diagram below).

Click to enlarge image above

Causes of Chronodisruption: (skip if you want to)
Now it is easy to see how modern society can promote disruption of the circadian rhythm. With the invention of televisions, computers and an increase in nightly leisure activities it is easy for individuals to stay up late at night staring into bright screens with enough photic signalling to cause our suprachiasmatic nucleus to perceive it is daytime . Consequently, when our suprachiasmatic nucleus sends the incorrect signal to our organs and peripheral tissues it forces their rhythm to change as well . The various rhythms in our body do not all change at the same rate and can take up to 7 days to re-synchronize. This means for an entire week our body is sub-optimal and unprepared to perform correct functions when required , such as the ability to metabolize food eaten at lunchtime because our body still thinks it is morning.

Other societal habits which can disrupt our circadian rhythm are by having high energy intake (from single meals), alternating meal times and frequent snacking throughout the day. The reason behind this is stomach-derived hormones , such as leptin and ghrelin ( that control food intake ) are normally expressed in circadian rhythmicity but experience great fluctuations when exposed to irregular eating patterns . If these fluctuations in expression of stomach-derived hormones continue it will eventually lead to its de-synchronization from the main circadian rhythm. The possible implications from such an occurrence would be an imbalance between energy intake and expenditure which can lead to obesity.

  1. Increase in nightly leisure activities that result in people sleeping later
  2. Followed by reduced sleep hours
  3. Frequent snacking throughout the day (and well into the night)
  4. Alternating meal times
  1. Sleep at the same time every night (can be at any time as long as you are consistent)
  2. Sleep for 8 hours (give or take an hour) consistently
  3. Wake up at the same time each day
  4. Eat regular meals at the same times each day
  5. Exercise regularly
  6. Expose yourself (eyes in particular) to sunlight* during the day as much as you can

"But I like to sleep late on weekends". THEN HAVE REGULAR MEAL TIMES!
You can maintain your metabolic circadian rhythm as long as you have regular meal times . Researchers found that animal models that had their suprachiasmatic nucleus removed (yes literally removed from the brain surgically) were still able to maintain their metabolic circadian rhythm by eating their meals at regular times. This indicates that the circadian rhythm for metabolism is independent from the suprachiasmatic nucleus’s rhythm (the main biological clock) and can be entrained by restricted feeding times. So even though you can't maintain a regular sleeping/waking cycles, it is important to eat meals at the same time each day (give or take 30 minutes) to ensure food is metabolized correctly and not deposited as visceral fat. However I must stress it is still important to sleep at the right time, to learn more about why read my article: "Preventing obesity with sleep"

Exercise at the same time each day
The final advice is to exercise regularly for the same amount of time, at the same time each day to further entrain your body’s circadian rhythm . The best time to exercise is right before you eat because over time this scheduling will entrain your body’s circadian rhythm (and perhaps through classical conditioning) to prepare for food after every workout. In addition there has been research [2] that indicates the body is most effective at protein uptake right after a workout.

Chronoenhancement (Optional)
“Chronoenhancement” can maximize the body's efficiency to metabolize food and help to prevent fat accumulation. For those of you interested, chronoenhancement is the entrainment of our body’s circadian rhythm to become perfectly synchronized with the rhythm of the external environment (i.e. the sleep-wake cycle in-sync with the sunrise and sunset). Since we are biologically diurnal creatures (that are active in the day time), we can enhance our circadian rhythm by living as evolution has intended for us to live. How I try to enhance my rhythm in addition to the points I previously mentioned above is by:

1. Eating and completing all my work and errands during the daytime
2. Restrict eating to only three meals (and 3 small snacks if you desire) each day I do
not eat at any other times
3. I do not look directly at any light sources (i.e. I stop using electronic devices with
bright screens) within an hour after the sunsets
4. I sleep within an hour after the sunsets
5. I sleep for 8 hours (give or take 1 hour)
6. I wake up early in the morning and try to expose myself to as much sunlight as I
can throughout the day

8 hours
- Eat at regular meal times
- Exercise regularly (preferably before your largest meal of the day)

  1. Garaulet M, Ordovás JM, Madrid JA: The chronobiology, etiology and pathophysiology of obesity. Int J Obes (Lond). 2010 Jun 22. [Epub ahead of print]
  2. Weinert DJ: Nutrition and muscle protein synthesis: a descriptive review. J Can Chiropr Assoc. 2009 Aug. 53(3):186-93.
  3. Elmquist JK, Ahima RS, Elias CF, Flier JS, Saper CB: Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei. Proc Natl Acad Sci USA. 1998. 95:741�.


For your Scientific Interest: Chronodisruption on health related issues other than obesity

Having an in-sync circadian rhythm is very important because not only will it help with obesity and metabolic function, but it will help to prevent many other associated diseases such as impaired glucose tolerance that can lead to diabetes, hypertension, dyslipidemia, endothelial dysfunction. Having an in-sync circadian rhythm will also help prevent against premature aging, and cancer and mental illnesses. The reasons why Chronodisruption can cause accelerated aging is because it causes cells to work when they don’t have to and work harder than normal. Chronodisruption can also lead to the development of certain types of cancer because when our body's rhythm goes out of sync the various systems in our body cannot effectively communicate and work well together resulting in one system having uncontrolled malignant growth. Chronodisruption can also cause psychological illnesses because hormones and neurotransmitters are secreted in the brain at the wrong times resulting in mood disorders and emotional impairments. In a study with mice that had their sleep-wake cycle shifted 6 hours every week, it was found they experienced a significant reduction in life span. As well, they found that when (new) fetal suprachiasmatic nucleus (the main biological clock) were implanted into older animals, it helped restore the circadian rhythm and in effect they experienced increased longevity.


Acknowledgements

We thank H. Rodriguez and the Penn Molecular Profiling Facility for the RNA and Microarray work.

Declarations

About this supplement

This article has been published as part of BMC Genomics Volume 17 Supplement 8: Selected articles from the Sixth International Conference of the Iberoamerican Society for Bioinformatics on Bioinformatics and Computational Biology for Innovative Genomics. The full contents of the supplement are available online at https://bmcgenomics.biomedcentral.com/articles/supplements/volume-17-supplement-8.

Funding

Research reported in this article was supported by the National Institute of Mental Health of the National Institutes of Health under award number R01MH099544 to M.G.F. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The publication charges for this article were funded by start-up funds provided by Washington State University to L.P.

Availability of data and materials

Data generated in this study is publicly available through GEO (GSE78215).

Authors’ contributions

Study design by AW and MGF. Data collection by AW and NZ. Data analysis by JK, DR and LP, manuscript preparation by JRG with editing by JK, DR, TPS, MGF and LP. All authors approve of the final version of this manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Ethics approval and consent to participate

The Institutional Animal Care and Use Committee (IACUC) of the University of Pennsylvania and Washington State University approved all animal work conducted during the research presented in this article.


How Poor Sleep Impacts Our Microbiome

Spring ahead. Sure, it means the daylight will stretch farther into the evening, but the loss of an hour’s sleep as the clock skips forward into daylight savings time, leaves many of us feeling foggy and out of synch for the days that follow.

Sleep is a very precious commodity. While there is still no answer as to ‘why we sleep,’ we do know that sleep (or lack thereof) dramatically impacts our capacity for learning, memory, safety, health and longevity. 1

As many of us will feel the effects of an extra early wake-up this upcoming Monday morning, we thought we would look at how poor sleep affects our health and the health of our microbiome.

How Lack of Sleep Impacts Our Health

Yes, daylight savings time does leave many of us feeling the acute effects of a lack of sleep, but in fact, our modern-day lifestyle has shifted our schedules dramatically. The blue light emitted from our devices tricks our minds into believing it is still daylight out, suppressing our sleep hormone melatonin. 2 Many of us also use our smartphones as alarm clocks meaning the pull of the internet (and email, social media, text, and DMs) are at an arm’s length away making it hard for our brain to shut down and unwind for the deep, restful sleep our body needs.

Feeling groggy, unable to focus and irritable the next day are the short-term effects of lack of sleep, but if the pattern continues it sets us up for some fairly serious long-term health issues as well.

The Common Cold: people who averaged less than seven hours of sleep per night were about 3x likely to develop the common cold when exposed to the virus as people who were well rested. 1

Type 2 Diabetes: people who sleep fewer than 5 hours per night have greater risk of developing type 2 diabetes. 1

Cardiovascular Disease: reduced sleep (six to seven hours per night) increases the risk of artery calcification a predictor for future heart attack. 1

Weight Gain & Obesity: poor quality sleep increases obesity by interfering with hormones that regulate hunger and satiety, increasing food intake without compensating for energy expenditure. 3

How Poor Sleep Impacts Our Microbiome

Our microbiome is composed of about 2-6 pounds of bacteria, and like the human’s they live in, they work on a 24-hour cycle, known as a circadian rhythm. 4

Due to various complexities, researching the rhythmic fluctuations of the microbiome in humans remains somewhat tricky, yet animal models are giving us a good insight into how our bacteria respond over a 24-hour period. 4

It is currently believed that cycling bacteria communities within the gastrointestinal tract produce the ideal amount of active hormones, precursors, or metabolites for the regulation of our metabolism and circadian rhythm. 4

Mice with a disturbed circadian rhythm (aka jet lag-like conditions) have been shown to display an increased progression of weight gain, blood glucose levels, body fat, and increased metabolic disease. Many of the issues we see in humans who do not make sleep a priority in their day-to-day lives. 4

We already know that our immune system and gut microbiome is intrinsically related, but studies are now showing host-microbe circadian rhythm-mediated disturbances to the immune system could influence diseases such as Crohn’s disease, inflammatory bowel disease, systemic autoimmune diseases, and cancer risk. 4, 5

How to Protect Your Microbiome When Sleep Is Lacking

As we learn more about health and wellness, paying attention to the valuable role sleep plays is hard to ignore. But sometimes that is easier said than done. Whether you are travelling, under a hectic deadline, dealing with a stressful situation in your life, or just up against daylight savings time, sometimes we just don’t get the sleep that we should.

If you can’t get the hours of shut-eye that your body needs to function optimally, here are tips to support your body and keep it healthy until you can get back to regularly scheduled programming (aka, sleeping).

Protect Your Gut

Whether it’s to give your immune system a boost or keep things moving, a high-quality probiotic will provide you with the added help you need.

Bio-K+ includes three unique, patented strains of bacteria that have been clinically proven to work synergistically together to keep bad bacteria in check, create a healthy environment for good bacteria to grow and maintain gut integrity to support your immune system. With 50 billion CFU per bottle, dairy and non-dairy options, and a variety of flavours, it’s an easy addition to your routine, no matter how tired you are.

Skip the Junk

When we are feeling tired, it is tempting to want to reach for sugary snacks or an extra cup of coffee that will give us the hit of energy we are looking for, but those quick fixes only set us up for more trouble in the long run.

High-sugar diets favour the growth of bad bacteria. Too much coffee (or more accurately the caffeine in the coffee) can lead to exacerbated cortisol levels, increasing gut permeability and thus inflammation throughout the body.

Skip the junk and fuel your body on fibre rich foods like roasted sweet potatoes, squash or whole grains like brown rice, and quinoa that will still satisfy cravings for carbs but feed your healthy bacteria thanks to their high fibre content. If you’re craving a coffee, try to keep it before noon, when cortisol levels are naturally high.

If You Can’t Go for Quantity, Go for Quality

If you know you aren’t going to be able to get the required amount of sleep, you need to set yourself up to maximize the time you have. Aim to turn off electronic devices an hour before bedtime and dim the lights to signal the production of melatonin. Practice good sleep hygiene by ensuring your bedroom is as dark and cold as possible to promote optimal conditions for deep sleep. If you’re having a hard time winding down, try following a guided meditation or practice some deep breathing to help both body, mind and microbiome relax.

Sleep plays a vital role in both our health and the health of our microbiome. When you can’t get enough shut-eye, be sure to take extra care to support both body and mind so that you can get back on track quickly.

Do you have any other questions concerning the health of your gut microbiome? Let us know in comments below! Join our community for more healthy tips. Click here to find a store near you. Contact us or follow us on Facebook or Instagram.