New research shows, that maternal Melatonin-levels have massive importance for fetal neurodevelopment, and can cause preterm birth and circadian disruption. In this article I explain how Melatonin can help you reduce these risks, for mothers with ADHD.
New research shows, that maternal Melatonin-levels have massive importance for fetal neurodevelopment, and can cause preterm birth and circadian disruption. In this article I explain how Melatonin can help you reduce these risks, for mothers with ADHD.
80% of people with ADHD/ASD also suffer from Circadian Disruption. Circadian Disruption causes Delayed Sleep Onset for in particular people with ADHD/ASD, and result in evening or Owl preference in sleep patterns. Since the human body was designed for a life on the open Savannah, our internal time management system, called Circadian Rhythm, have been tuned to follow the Sun’s movement across the sky, getting non-visual information in the sunlight, which travels from our eyes to a central part of our brain, which synchronises our internal time with the outside, universal spacetime. In this article, I explain how this system works, and how ADHD symptoms are worsened by the effect of misalignment of your circadian rhythm, causing chronodisruption, which in turn wreck havoc in your Melatonin-levels, and ultimately affect your unborn or newborn child’s lifelong health. Finally I suggest the use of Melatonin to reduce the harm from chronodisruption for both the mother and the child, based on brand-new scientific evidence from the cutting-edge research into melatonins role in preterm birth.
In a new study from 2022, Canu et al. have confirmed, what Dr. Russell A. Barkley, PhD showed to be at the root cause of ADHD symptoms like inattention, hyperactivity and impulsivity. Dr. Barkley had, in his pivotal book “ADHD and the Nature of Self-control” (1997) provided the evolutionary and neuroanatomical evidence for the neuropsychological manifestations of ADHD, which was later proven to due to a delayed maturation of the grey matter in children with ADHD (2008).
He provided an unifying theory of ADHD, which stated that the maturational delay was caused by the late arrival of the fundamental executive function, inhibition, which did not develop on time, so that the motor control function, which developed on time, was not under the management of the inhibitory control system.
Since inhibitory control is based on “actions to the self”, first through “self-speech” using the internal voice to guide behavior over time, and later using “self-play” to simulate future outcomes of imagined scenarios.
The physical brain areas and their neurological synaptic connections are delayed by between 30-40% compared to a neurotypically developed child, causing their behaviour to be less mature as compared to their peers of the same age.
By linking this new evidence for circadian & chronodisruption to the now confirmed by fMRi studies, establishing that it is related to delayed development of inhibition in neurodevelopmental disorders like ADHD and ASD, a picture begins to develop, which can be a potential “missing link” between ADHD, sleep disorders and a plethora of somatic diseases and disorders, for which individuals with ADHD have an increased risk ratio of developing during their lifespan.
We know from large genetic, epidemiological and longitudinal studies, that the shared genetics of 5 neurodevelopmental disorders; Intellectual Disability, Autism Spectrum Disorder, ADHD, Schizophrenia and Bipolar disorder, all share the same genetic pool, and that they may be one and the same disorder, with many different “presentations”, as evidenced by the high rate of “comorbidity” between these 5 disorders.
New scientific study into a novel “Neurodevelopmental Continuum” hypothesis suggests what the future may hold in store, a new definition, where one would be diagnosed with a Neurodevelopmental Disorder (NDD), with a subset of symptoms drawn from any of the 5 disorders, removing the need for “comorbidity”, and making it possible to more accurately describe and focus on the individuals capabilities when diagnosing, instead of the focusing on the dysfunctional aspect which becomes an impairment, or handicap, in the societal and cultural context.
Having all this new knowledge in mind, I propose the following hypothesis …
We know, that 60-80% with ADHD/ASF suffer from a sleep related disorder. Sleep disorders are most often caused by chronodisruption. Chronodisruption is linked to circadian misalignment due to low maternal melatonin-levels during pregnancy and in the breastfeeding period. Maternal Melatonin-level disruption is caused by the mother’s own circadian misalignment, and sleep disorder.
The combination of low (and de-syncronised) maternal melatonin with the neurodevelopmental delay due to ADHD genetics, coupled with an extended need for a prolonged breastfeeding period (extended beyond the neurotypical 8-16 weeks after birth), leads to the newborn baby to be predisposed to developing their own circadian disruption due to a never fully developed circadian rhythmicity.
Lack of circadian rhythmicity is evidenced to be linked to a plethora of somatic diseases, from asthma- and allergies (before the age of 3), increased risk of infections (middle ear infections before the age of 3), increased atopic dermatitis (before the age of 3), as well as Restless Legs Syndrome (RLS) (upwards of 30-35% of all children with ADHD/ASD suffers from RLS due to lack of dopamine to initiate the sleep/wake switch), and 60-80% suffering from either Delayed Sleep Onset, frequent sleep disruptions during the night, and Early-morning Wake-up.
This lack of high quality, consistent sleep has been evidenced to impair cognitive, as well as emotional functions, exacerbating the already present symptoms of inattention, hyperactivity and impulsivity (due to the delay in development of inhibition), while coelesing into frustration, lack of focus and concentration, and an increased sensitivity toward stimuli (sound, smell, touch etc.).
On top of this murky symptomatic “normality”, these children are expected to perform as well as their age-related peers, while battling their physically untethered motor control, overloading their immature and under-connected inhibitory control.
All this combines into a chronic state of hyper arousal, hyper vigilance, and hyper sensitivity, all very good if you are in a life-threatening situation, but very, very bad for your longterm health, since your hormonal levels are out-of-sync with your circadian rhythm, causing all of your bodily functions to put maximum pressure on your homeostatic system – all leading to one very sure thing … Allostatic Load …
Allostatic load leads to the activation of genes with have laid dormant/latent in the DNA of the person with ADHD, which in turn is causing the increased risk of developing diseases like Diabetes Type II, Crohn’s disease, and mental disorders like anxiety, depression, eating disorders, substance abuse disorders and an ten-fold increase in the suicide rate, compared to neurotypicals. All in all, these facts have been studied and the end result is, that unmedicated or undiagnosed ADHD, will reduce your Expected Life Expectancy with 12,7 years – on average!
The solution seems to be right in front of our eyes … Melatonin …
ONE FINAL WARNING: I AM – NOT – STATING THAT CIRCADIAN & CHRONODISRUPTION – CAUSES – ADHD …
WHAT I – AM -SAYING IN THAT THESE CONDITIONS – WORSENS – THE SYMPTOMATOLOGY (cognitive, behavioral and somatic) OF ADHD … !!!
If you, like I have, read all of the suggested information that I reference below, you will find supporting scientific evidence for my hypothesis, that maternal circadian disruption leads to foetal circadian disruption, which is followed by a low melatonin-level in the breastfeeding period, that is at least 30% to short for the newborn to develop their own circadian rhythm, which all coalesce into a lifelong circadian disruption, chronic stress and long-term repercussions for somatic disease and mental disorders.
By introducing a melatonin-based, maternal circadian chronobiological approach to sleep disturbances and sleep disorders, already long before planned pregnancy, you can reduce your own risk for longterm consequences, as well as giving your child the best fighting chance we know of right now, for developing a slightly less dysfunctional or even a functional circadian rhythmicity, giving the child the chance to – NOT – end up like myself …
… forced into early retirement at age 48 due to Allostatic Load at age 40, developing Diabetes Type II at age 45, and having all my teeth pulled at age 47 to make way for my brand new shiny, but yet – fake smile …
/Peter ‘ADDspeaker‘ Vang
The following paragraphs describe the vast knowledge needed for your to understand how chronodisruption leads to significant increased, somatic and neurologic, risks for both your own health, as well as your unborn or new-born child.
Time can be thought of in many ways. One of the simplest is to think of time in terms of the past, the present, and the future. These three ever-changing bodies of experiences differ and change based upon the passage of time. For example, you’re reading this paragraph right now in the present. That last paragraph? You read that in the past. The next paragraph? You’re going to read that in the future. What separates these events? Probably no more than a few seconds. The past, present, and future can be separated by hours, days, weeks, months, and years. These are all units of measure that were created to help us keep track of the passage of time There are no inherent measures of time. Time just rolls on and on, never stopping. To help us better understand and navigate our lives, however, people long ago assigned standards of measurement that would help to get a grasp of the passage of time. The natural rotation of the Earth on its axis and the revolution of the Earth around the Sun give us our two most basic measurements of time. The time it takes the Earth to rotate once on its axis (about 24 hours) is called a day. The amount of time it takes the Earth to revolve once around the Sun (about 365 days) is called a year. These units have been further divided into even smaller units of measurement. Years are broken down into months and weeks; days are measured in hours, minutes, and seconds. And our environment impacts even these categories. The month, for example, developed from the cycles of the moon. These various units help us communicate about and keep track of time — past, present, and future.
The idea of a space-time continuum comes from the groundbreaking work of Albert Einstein. Through the process of developing his special and general theories of relativity, Einstein examined the laws of physics as they related to the speed of light. Einstein concluded that space and time, rather than separate and unrelated phenomena, are actually interwoven into a single continuum (called space-time) that spans multiple dimensions. So how many dimensions are there in the space-time continuum? The space-time continuum consists of four dimensions: the three dimensions of space (length, width, and height…or up/down, left/right, and forward/backward, depending upon how you wish to think of them) plus the fourth dimension of time. Einstein’s theories of relativity spurred other scientists to investigate the relationships between space and time. Does all this still seem a bit confusing? Don’t worry if it does! The space-time continuum and Einstein’s theories of relativity are advanced scientific ideas that even scientists sometimes have trouble grasping the meaning and significance of. Without going into confusing detail, let’s take a look at a couple of interesting ideas that stem from the space-time continuum. One way of envisioning the space-time continuum is to think of a large piece of fabric, such as a sheet. Einstein realized that objects with mass, such as a person or Planet Earth, create a distortion in space-time. Imagine placing a bowling ball in the middle of the sheet. The area around the bowling ball would be pressed down, creating a dimple in the sheet. These dimples represent curvatures in the fabric of the space-time continuum. Einstein identified these curves in the space-time continuum as gravity.
Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. These natural processes respond primarily to light and dark and affect most living things, including animals, plants, and microbes. Chronobiology is the study of circadian rhythms. One example of a light-related circadian rhythm is sleeping at night and being awake during the day. The Average Teen Circadian Cycle image shows the circadian rhythm cycle of a typical teen.
Biological clocks are organisms’ natural timing devices, regulating the cycle of circadian rhythms. They’re composed of specific molecules (proteins) that interact with cells throughout the body. Nearly every tissue and organ contains biological clocks. Researchers have identified similar genes in people, fruit flies, mice, plants, fungi, and several other organisms that make the clocks’ molecular components.
On a basic level, the circadian clock can be divided into 2 parts: the Circadian Master Clock (CMC), residing in the suprachiasmatic nucleus (SCN) of the brain, and the Circadian Peripheral Clocks (CPC) that are present in nearly every tissue and organ system tested. A circadian master clock in the brain coordinates all the biological clocks in a living thing, keeping the clocks in sync. In vertebrate animals, including humans, the master clock is a group of about 20,000 nerve cells (neurons) that form a structure called the suprachiasmatic nucleus, or SCN. The SCN is in a part of the brain called the hypothalamus and receives direct input from the eyes.
Light from the Sun, sunlight, contains non-visual information, such a time-of-day (amount of sunlight), time-of-year (the suns position on the horizon), and outside temperature. When sunlight enters through the retina of the eye, it is causing electrical signals to pass through the retinal hypothalamic tract, which are converted to chemical signals in the SCN, which then synchronizes the Circadian Master Clock, so that our internal time is synchronized with universal spacetime. These light signals and other physiological factors, such as feeding cues, entrain the circadian master clock.
In mammals and humans, the circadian clock consists of a circadian master clock and circadian peripheral (tissue) clocks. The circadian master clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus, which functions as the master pacemaker by synchronizing physiological rhythms in accordance with Earth’s cycling environment. The central clock operates to synchronize the circadian clocks in peripheral tissues.
There has been much debate among chronobiologists about the relationship between the circadian master clock and the circadian peripheral clocks with 2 major theories emerging.
Model 1: The first is the “master-slave” model, which gives complete synchronization power to the circadian master clock. In this model, the circadian peripheral clocks are synchronized solely by the central clock and are not otherwise affected by external or internal stimuli.
Model 2: The second model is referred to as the “orchestra” model. In this model, the circadian master clock behaves as a conductor, with each circadian peripheral clock as an orchestra member. Each member has the ability to play its own “instrument,” but the conductor’s direction allows for efficient and guided direction of the melody, which would include physiological output rhythms. Thus, each circadian peripheral clock can adapt to its own external and internal stimuli, such as feeding cues for the liver, kidney, and pancreas, but is “conducted” by the light-dark cues sensed by the circadian master clock. This model implies a more balanced relationship between the circadian master clock and circadian peripheral clocks.
Recent studies provide increasing evidence for the independence of the circadian peripheral clocks. The importance of understanding the role of the circadian peripheral clocks in each tissue, and their relationship to one another is paramount in order to better comprehend the role of the peripheral clocks in circadian physiology.
The circadian clocks and sleep/wake cycles, two dynamically associated physiological systems, are fundamental for physiology and contribute to optimal behavior and performance.
The circadian clocks controls nearly all patterns of human biology, including brain-wave activity, sleep-wake cycles, body temperature, hormone secretion, blood pressure, cell regeneration, metabolism and behavior, which display ~24-hour periodicity. In addition, cognition and performance are also under circadian control.
Your body has a biological need for sleep that increases when you have been awake for a long time. This is controlled by homeostasis, the process by which your body keeps your systems, such as your internal body temperature, steady. A compound called adenosine is linked to this need for sleep. While you are awake, the level of adenosine in your brain continues to rise. The rising levels signal a shift toward sleep. Once a certain level is reached, the Sleep/Wake Switch flicks into to the Sleep position, and this triggers a plethora of hormonal a chemical signals that all work to readjust homeostasis to night-time functioning.
You might think of sleep pressure as a battery on your iPhone, at some time you need to recharge the battery, and in humans – “sleep” is where we recharge “wake”. When this crucial interplay between circadian rhythmicity and sleep/wake goes awry, it is termed Chronodisruption.
Think of chronodisruption (CD) as being a breakdown of phasing internal biological systems appropriately relative to the external, i.e. environmental changes, which leads to chronobiological disorders. Indeed, biological rhythms constitute a key means to establish physiological order], and to avoid pathological disorder.
Importantly, the very entrainment of internal rhythmic subsystems relative to the external, i.e. environmental changes, ultimately allows ‘rhythms of rest and excess’ or regular oscillations of sleep and waking which are critical conditions for human health.
Put simply, if there are no ordered sequences of biological rhythms during sleep and wake cycles, this would certainly neither be efficient nor healthy.
New scientific evidence have left no doubt about the fact that proper circadian regulation is essential for the well-being of organisms.
Consider as an analogy the inefficiency and, indeed, the damaging effects if drivers of automobiles were to use the accelerator and brakes simultaneously rather than in appropriate sequences, i.e. in successions of activity and rest cycles.
A necessary condition for the orderly sequences of cyclic events and their coordination is that in organisms there should be one master time rather than billions of independent peripheral times in billions of independent clocks.
More generally, this master time is provided by circadian master clocks (CMC) which are connected ‘chemically’ via melatonin as one key messenger and ‘physico-anatomically’ via melanopsin projections with many parts of the brain and can thus ‘set’ the clocks for innumerous downstream events to be coordinated and in physiological order.
More specifically, in the brain of mammals, including man, the central pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus receives light information directly from the eyes via melanopsin-containing retinal ganglion cells which have widespread overall projections to many regions of our brain.
In addition, the hypothalamus is the center for autonomic regulation via the sympathetic and parasympathetic nervous systems; certainly these assist the CMC in the coordination of peripheral clocks also and thus have critical influence on peripheral organs and cells and their interplay.
To illustrate with a further analogy, similar to Greenwich Mean Time providing the reference time independent of location for billions of other clocks world- wide, central timing and appropriate coordination of circadian rhythms are achieved by circadian master clocks in the brain which collectively set or govern or ‘tame’ an impressive abundance and variety of peripheral clocks. In doing so via the regulation of a temporal programme in response to ambient light, the CMC coordinates tissue- and organ-specific 24-hr rhythms, which would otherwise act independently of one another.
Chronodisruptors are exogenous and endogenous ‘exposures’ or ‘effectors’ which are chronobiolocially active and can thus disrupt the timing and order, i.e. temporal organization of physiologic functions and hierarchies.
In principle, whatever allows the establishment of temporal organizational order in organisms should also be capable of disrupting such order or temporal programme when present or applied in excess or deficit and, most importantly, at unusual and inappropriate times, especially if combined with further agonistic or antagonistic chronobiologial effectors.
With these premises, one key exogenous or external chronodisruptor is light at night. Under natural conditions, biological circadian and seasonal rhythms are synchronized to the regular 24-hr and seasonal light–dark cycles and the suprachiasmatic nuclei and melatonin have critical roles in these processes.
In fact, light is a key Zeitgeber (time-giver) affecting melatonin rhythms and the circadian rhythms of melatonin can provide clock (24 hr) and calendar (seasonal and yearly) information for many species, including humans.
But light, and its antithesis melatonin, when applied at unusual times, can also powerfully disrupt the circadian and seasonal rhythmicity of our biology, thus leading to CD.
Importantly, the interactions between light and melatonin may contribute to CD via two phenomena: a light-associated phase-shift of the melatonin rhythm on the one hand and acute suppression of melatonin by light of sufficient intensity on the other.
The former phenomenon may yield both secondary influences on the circadian master clocks and on peripheral oscillators, dual effects which may lead to unfavorable, and indeed detrimental, phase positions or oscillator uncoupling.
Moreover, the phenomenon of melatonin deficiency after light-induced acute melatonin suppression may in itself, i.e. irrespective of the former inappropriate phase position, cause or contribute to CD because the physiologically rhythmic endogenous regulator melatonin cannot exert its critical role in melatonin-dependent biochemistry at many organizational levels of individual cells, tissues and organs.
Further key chronodisruptors include not only food – a long-suspected food-dependent circadian master clock (CMC) has recently been located in the dorsomedial nucleus of the hypothalamus – but also physical activities and biological stress.
This part is based on edited excerpts from the study by Reschke et al. (2018), as well as my own explanation for why circadian rhythmicity is linked to ancient hunter/gatherer societies on the African savannah.
Reschke L, McCarthy R, Herzog ED, Fay JC, Jungheim E, England SK, Chronodisruption: An Untimely Cause of Preterm Birth?, Best Practice & Research Clinical Obstetrics & Gynaecology (2018), doi: http://10.1016/j.bpobgyn.2018.08.001
Circadian rhythms influence reproduction, and chronodisruption may affect pregnancy outcomes such as preterm birth as depicted.
This idea is compelling, as interventions could reduce such disruptions and provide new means of preventing preterm birth.
KEY POINTS
Circadian rhythms, endogenous and entrainable adaptations to 24-hour cycles of light and dark, influence nearly all physiologic functions.
Emerging evidence suggests that disruption of normal circadian rhythms, termed chronodisruption, could affect a wide range of disease-related processes.
In this review, we describe the molecular generation of circadian rhythms, the effects of chronodisruption on human health, the circadian timing of birth in multiple species, the possible effects of chronodisruption on preterm birth, and some of the open questions in this field.
The sleep-wake cycle is regulated by complex interactions between the homeostatic and circadian processes.
Homeostatic drive for sleep arises from neuronal circuits that gradually promote sleep with increasing time spent awake, whereas circadian regulation arises from the near 24-hour oscillatory rhythm governed by the SCN that modulates arousal and sleep propensity.
Alignment of these homeostatic and circadian processes is essential for optimal sleep quality and cognitive performance.
Circadian rhythms define an individual’s chronotype, or biologically preferred sleep-wake schedule.
Chronotypes are the personal preferences for early morning or late evening wakefulness, defined as Larks or Owls.
LARKS: Those who rise early and have an early midpoint of sleep (“larks“) have an early chronotype.
| Begin | End | Activities |
| 10 pm | 5.30 am | Sleep |
| 5.30 am | 6 am | Wake-up, High Metabolic & Gastrointestinal functions |
| 6 am | 12.30 pm | High Alertness |
| 12.30 pm | 2.30 pm | High Attention & Learning |
| 2.30 pm | 4.30 pm | Best Reaction Time, Coordination, Cardiovascular functions |
| 4.30 | 8 pm | High Blood Pressure, High Body Temperature |
| 8 pm | 10 pm | High Melatonin, Low Metabolic & Gastrointestinal functions |
OWLS:, Those who wake up late and have a late midpoint of sleep (“owls“) have a late chronotype. The circadian rhythm follows this circadian phase model:
| Begin | End | Activities |
| 120 pm | 8 am | Sleep |
| 8 am | 10 am | Wake-up, High Metabolic & Gastrointestinal functions |
| 10 am | 12 pm | High Alertness |
| 12.pm | 3 pm | High Attention & Learning |
| 3 pm | 6 pm | Best Reaction Time, Coordination, Cardiovascular functions |
| 6 pm | 9 pm | High Blood Pressure, High Body Temperature |
| 9 pm | 12 pm | High Melatonin, Low Metabolic & Gastrointestinal functions |
Circadian Rhythmicity also influences the hormonal and neurotransmitter production, based on the time of day/night. These in turn activate or deactivate, cognitive, behavioral and somatic functions, as needed for tasks in the upcoming circadian phase.
… so lets do it, like they do it on Discovery Channel …”.
The human species, Homo sapiens sapiens, have been evolving to suit the needs of the African savannah for hundreds of thousands of years. With a sole purpose of surviving long enough to ensure that our species’ genes gets past along to the next generation.
Our circadian rhythmicity have evolved to make sure that; we have most energy and alertness in the morning, most attention and learning skills at noon, best coordination, planning and execution in the afternoon, and best rest and digest in the evening, leading up to the night’s sleep phase.
It makes sense if we look at this from a hunter/gatherer perspective; In the morning your reestablish social bonds with your tribe, spend time on finding food for breakfast, while “chatting” or “playing” with your peers until noon. At noon it gets to hot to move around much, so you sit and plan how, where and who’s going on this afternoons hunt for larger game animals, which you then actively hunt for in the afternoon, returning to the camp with your catch around dusk. After having eating your catch, you settle in to rest and digest, while the sunlight dissipates and the light turns into darkness around 8-9 pm. Then you spend some time “reproducing” until 10-12 pm where sleep sets in.
Importantly, chronotypes vary with factors such as age, sex, and genetics. Misalignment between endogenous circadian rhythms and the external environment (chronodisruption) can negatively affect physiologic, behavioral, and reproductive functions.
Notable examples of genetically encoded chronodisruption are advanced and delayed sleep phase disorders, in which polymorphisms in core clock genes cause sleep to be misaligned with the typical day/night cycle. Far more common than such variants in core clock genes is chronodisruption due to social pressures.
To align their sleep and wake times with social obligations, 80% of the U.S. population uses alarm clocks on workdays, and a growing number of people use sleep medication at night and stimulants to increase wakefulness during the day.
Another common form of chronodisruption occurs when people shift their daily schedules by several hours during the week (e.g., going to bed and rising earlier on work days than on free days).
Over 75% of people in the developed world, especially those between ages 15 and 35 years, experience this “social jetlag”, which is similar to traveling across multiple time zones.
Circadian rhythms influence multiple pathological conditions across different organ systems, including skin, gastrointestinal tract, nervous system, the kidney, and the eyes. For example, acute febrile onset of bacterial infections is most likely to occur in the morning; viral infections are more likely to occur in the afternoon and evening; cardiac events including angina pectoris, ST-segment depression, and sudden cardiac death are more likely to occur in the morning; and asthma sufferers are at greatest risk for exacerbated symptoms at night.
Additionally, chronic misalignment of circadian rhythms with environmental cues, as seen in night-shift workers, may increase the risk of a variety of adverse health consequences including cognitive impairment, obesity, metabolic dysfunction, cardiovascular disease, and cancer.
Recognizing these effects, researchers are beginning to find that scheduling a patient’s treatment.
The timing of birth is influenced by two interacting clocks:
1) a developmental clock that measures the overall length of gestation, and
2) a circadian clock that defines when, within a 24-hour period, birth occurs.
All animals studied to date (including hamsters, rats, mice, sheep, and humans) exhibit reliable, species-specific, circadian rhythms in the onset of labor.
For example, after the 24th week of pregnancy in humans, uterine contractile activity shows a diurnal pattern, with 67% of contractions occurring at night.
Likewise, clinical data demonstrate that spontaneous rupture of the fetal membranes and onset of labor most commonly occur between late night and early morning (between 11:00 pm and 4:00 am) in both term and preterm human births.
Similarly, rats typically give birth around dawn. Studies in animal models have revealed that circadian timing of birth depends on both the SCN and peripheral oscillators.
For example, rodents in which the SCN was lesioned delivered after normal gestational lengths but at random times of day.
Circadian clock genes are expressed in several reproductive tissues including the gravid uterus, fetal membranes, and the placenta, where they appear to participate in birth timing.
Whereas 92% of control mice delivered during the night, only 64% of mice lacking the core clock gene Bma1 in the myometrium delivered during the night.
Furthermore, pregnant mice lacking a functional clock gene either failed to enter labor or had a prolonged labor and non-productive contractions.
Given the important role of melatonin in regulating circadian rhythms, many researchers have focused on this hormone and reported several lines of evidence indicating that melatonin contributes to regulating birth timing.
The strongest evidence for a role of melatonin in birth timing comes from rat studies. Takayama et al. ablated the pineal gland of female rats, thus eliminating production of melatonin, which normally peaks during the night.
Instead of delivering during the light period (rest period in this nocturnal species), these rats delivered during the dark period. However, when the pinealectomized rats received daily injections of melatonin at the beginning of the dark period, they delivered during the day.
Studies have shown that maternal shift work (which causes chronodisruption) is associated with adverse pregnancy outcomes including small for gestational age, spontaneous abortion, miscarriage, and preterm birth.
The fetus develops an intrinsic circadian rhythm by the last 10 weeks of gestation, and fetal physiological outputs, including heart rate and hormone secretion, show daily oscillations at late gestation.
Similarly, the placenta has its own circadian rhythms, but how the maternal, fetal, and placental circadian systems interact to regulate gestational length is unclear. Misalignment between the maternal, placental, and fetal clocks could contribute to risk of preterm birth.
Finally, future work should address the long-term effects of maternal chronodisruption on developmental programming of the offspring.
Canu, D., Ioannou, C., Müller, K., Martin, B., Fleischhaker, C., Biscaldi, M., Beauducel, A., Smyrnis, N., van Elst, L. T., & Klein, C. (2022). Evidence towards a continuum of impairment across neurodevelopmental disorders from basic ocular-motor tasks. Scientific reports, 12(1), 16521. https://doi.org/10.1038/s41598-022-19661-z
[…] These findings have various implications. They suggest that inhibition is core to ADHD, as suggested by symptoms. Following fMRI evidence, similarities in behavioural inhibition among patients with Schizophrenia, ADHD or ASD could result from overlapping functional abnormalities. Such evidence may suggest overlapping pathophysiologies. Follow-up behavioural, fMRi and pharmacological evidence. Deficits in inhibition have also been identified early on in the course of ASD and schizophrenia; they remain stable over time (expressing developmental stability) and have been variously linked to distinct schizophrenia and ASD core symptoms, although the nature of such association is less clear than for ADHD. […]
This section is based on edited excerpts from Khan et al. (2020).
Khan, Z., Mondal, G., Sharma, C. et al. (2020), “Role of Melatonin in Preterm Birth”, Chronobiol Med 2020;2(4):148-154, DOI: https://doi.org/10.33069/cim.2020.0024
RESUMÈ
Melatonin (5-methoxy-N-acetyltryptamine) is a multifunctional hormone known for its role in numerous psychological and physiological responses including:
Key Points
In this review …
It is hypothesized that melatonin supplementation may improve the developmental and cognitive disorders in preterm infants.
It is hypothesized that deprivation of long-term endogenous melatonin levels may link with neurological and developmental disabilities in premature neonates. In fact, after full-term birth, the neonate unable to generate melatonin for the first 8 – 16 weeks — a phase is called transient melatonin deficiency.
Although previous studies showed that the suprachiasmatic nucleus and the pineal gland had appeared to mature in early fetal life, however, the neurological circuitry that controls these structures remain immature.
Therefore, in both preterm and full-term neonates (absence of maternal melatonin), the uprising of the circadian pattern is crucially dependent on the neurodevelopmental status rather than the home environment.
Prematurity itself is negatively associated with the maturation of the neurological network, which controls melatonin secretion.
Evidence suggests that the impairment for the development of the neurological network delayed the onset of pineal melatonin secretion.
Consequently, in the preterm neonates, the deficiency of endogenous melatonin levels is significantly longer than the full-term neonate.
Extensive research has shown that abnormal brain, lungs, and respiratory system development most frequently occur in the premature infant.
Data from the previous study suggest that this may be associated with a prolonged deficiency of pineal melatonin levels, which may be restored with melatonin supplementation.
For more on the recent progress regarding the beneficial effects of melatonin on preterm birth, with particular emphasis on respiratory diseases and brain injury, I advice you to visit the full text article, as referenced above.
Hartstein, L. E. et al. (2022). Evidence of circalunar rhythmicity in young children’s evening melatonin levels. Journal of sleep research, e13635. Advance online publication. https://doi.org/10.1111/jsr.13635
Abstract
In adults, recent evidence demonstrates that sleep and circadian physiology change across lunar phases, including findings that endogenous melatonin levels are lower near the full moon compared to the new moon.
Here, we extend these results to early childhood by examining circalunar fluctuations in children’s evening melatonin levels.
We analysed extant data on young children’s circadian rhythms (n = 46, aged 3.0-5.9 years, 59% female).
After following a strict sleep schedule for 5-7 days, children completed an in-home, dim-light circadian assessment (<10 lux).
Salivary melatonin was assessed at regular 20- to 30-min intervals until 1 h past each child’s scheduled bedtime.
Melatonin levels varied significantly across lunar phases, such that melatonin was lower in participants assessed near the full moon as compared to near the new moon.
Significant differences were observed at 50 min (meanfull = 2.5 pg/ml; meannew = 5.4 pg/ml) and 10 min (meanfull = 7.3 pg/ml; meannew = 15.8 pg/ml) before children’s scheduled bedtime, as well as at 20 min (meanfull = 15.5 pg/ml; meannew = 26.1 pg/ml) and 50 min (meanfull = 19.9 pg/ml; meannew = 34.3 pg/ml) after bedtime.
To our knowledge, these are the first data demonstrating that melatonin secretion, a process regulated by the human circadian system, is sensitive to changes in lunar phase at an early age.
Future research is needed to understand the mechanisms underlying this association (e.g., an endogenous circalunar rhythm) and its potential influence on children’s sleep and circadian health.
Special thanks to my friend and “unofficial” mentor – Dr. Russell A. Barkley, PhD, who took my insisting, yet annoying, burning passion for understanding all I could about this complex, mysteries and mythical new “Mental Disorder”, that I had just realised that I had been living with – undiagnosed and unmedicated – for 40 years – back in 2012, and by honouring me since 2015, by having shared his precious time, his vast knowledge and maverick-like insights from his 40+ years in researching ADHD – thank you – Russ!
Barkley, R. A. (1997). Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD. Psychological Bulletin, 121(1), 65–94. https://doi.org/10.1037/0033-2909.121.1.65
Sterling P. (2014). Homeostasis vs allostasis: implications for brain function and mental disorders. JAMA psychiatry, 71(10), 1192–1193. doi:10.1001/jamapsychiatry.2014.1043
Sterling P. (2012). Allostasis: a model of predictive regulation. Physiology & behavior, 106(1), 5–15. doi:10.1016/j.physbeh.2011.06.004
Lee SW (2019) A Copernican Approach to Brain Advancement: The Paradigm of Allostatic Orchestration. Front. Hum. Neurosci. 13:129. doi: 10.3389/fnhum.2019.00129
Dibner, C., Schibler, U., & Albrecht, U. (2010). The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annual review of physiology, 72, 517–549. doi:10.1146/annurev-physiol-021909-135821
Ramsay, D. S., & Woods, S. C. (2014). Clarifying the roles of homeostasis and allostasis in physiological regulation. Psychological review, 121(2), 225–247. doi:10.1037/a0035942
Canu, D., Ioannou, C., Müller, K., Martin, B., Fleischhaker, C., Biscaldi, M., Beauducel, A., Smyrnis, N., van Elst, L. T., & Klein, C. (2022). Evidence towards a continuum of impairment across neurodevelopmental disorders from basic ocular-motor tasks. Scientific reports, 12(1), 16521. https://doi.org/10.1038/s41598-022-19661-z
Khan, Z., Mondal, G., Sharma, C. et al. (2020), “Role of Melatonin in Preterm Birth”, Chronobiol Med 2020;2(4):148-154, DOI: https://doi.org/10.33069/cim.2020.0024
Reschke L, McCarthy R, Herzog ED, Fay JC, Jungheim E, England SK, Chronodisruption: An Untimely Cause of Preterm Birth?, Best Practice & Research Clinical Obstetrics & Gynaecology (2018), doi: http://10.1016/j.bpobgyn.2018.08.001
Hartstein, L. E. et al. (2022). Evidence of circalunar rhythmicity in young children’s evening melatonin levels. Journal of sleep research, e13635. Advance online publication. https://doi.org/10.1111/jsr.13635
Zhang, E. E., & Kay, S. A. (2010, November). Clocks not winding down: Unravelling circadian networks. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/nrm2995
[…]An intrinsic clock enables an organism to anticipate environmental changes and use energy sources more efficiently, thereby conferring an adaptive advantage. Having an intrinsic clock to orchestrate rhythms is also important for human health. The use of systems biology approaches has advanced our understanding of mechanistic features of circadian oscillators over the past decade. The field is now in a position to develop a multiscale view of circadian systems, from the molecular level to the intact organism, and to apply this information for the development of new therapeutic strategies or for enhancing agricultural productivity in crops. […]
Dibner, C., Schibler, U., & Albrecht, U. (2010). The Mammalian Circadian Timing System: Organization and Coordination of Central and Peripheral Clocks. Annual Review of Physiology, 72(1), 517–549. https://doi.org/10.1146/annurev-physiol-021909-135821
[…] Most physiology and behavior of mammalian organisms follow daily oscillations. These rhythmic processes are governed by environmental cues (e.g., fluctuations in light intensity and temperature), an internal circadian timing system, and the interaction between this timekeeping system and environmental signals. In mammals, the circadian timekeeping system has a complex architecture, composed of a central pacemaker in the brain’s suprachiasmatic nuclei (SCN) and subsidiary clocks in nearly every body cell. The central clock is synchronized to geophysical time mainly via photic cues perceived by the retina and transmitted by electrical signals to SCN neurons. In turn, the SCN influences circadian physiology and behavior via neuronal and humoral cues and via the synchronization of local oscillators that are operative in the cells of most organs and tissues. Thus, some of the SCN output pathways serve as input pathways for peripheral tissues. Here we discuss knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system. […]
Honma, S., Ono, D., Suzuki, Y., Inagaki, N., Yoshikawa, T., Nakamura, W., & Honma, K. I. (2012). Suprachiasmatic nucleus: Cellular clocks and networks. In Progress in Brain Research (Vol. 199, pp. 129–141). Elsevier B.V. https://doi.org/10.1016/B978-0-444-59427-3.00029-0
[…] The suprachiasmatic nucleus (SCN), the master circadian clock of mammals, is composed of multiple circadian oscillator neurons. Most of them exhibit significant circadian rhythms in their clock gene expression and spontaneous firing when cultured in dispersed cells, as well as in an organotypic slice. The distribution of periods depends on the SCN tissue organization, suggesting that cell-to-cell interaction is important for synchronization of the constituent oscillator cells. This cell-to-cell interaction involves both synaptic interactions and humoral mediators. Cellular oscillators form at least three separate but mutually coupled regional pacemakers, and two of them are involved in the photoperiodic regulation of behavioral rhythms in mice. Coupling of cellular oscillators in the SCN tissue compensates for the dysfunction due to clock gene mutations, on the one hand, and desynchronization within and between the regional pacemakers that suppresses the coherent rhythm expression from the SCN, on the other hand. The multioscillator pacemaker structure of the SCN is advantageous for responding to a wide range of environmental challenges without losing coherent rhythm outputs. […]
Christ, E., Korf, H. W., & von Gall, C. (2012). When does it start ticking? Ontogenetic development of the mammalian circadian system. In Progress in Brain Research (Vol. 199, pp. 105–118). Elsevier B.V. https://doi.org/10.1016/B978-0-444-59427-3.00006-X
[…] Circadian rhythms in physiology and behavior ensure that vital functions are temporally synchronized with cyclic environmental changes. In mammals, the circadian system is conducted by a central circadian rhythm generator that resides in the hypothalamic suprachiasmatic nucleus (SCN) and controls multiple subsidiary circadian oscillators in the periphery. The molecular clockwork in SCN and peripheral oscillators consists of autoregulatory transcriptional/translational feedback loops of clock genes. The adult circadian system is synchronized to the astrophysical day by light whereas the fetal and neonatal circadian system entrains to nonphotic rhythmic maternal signals. This chapter reviews maturation and entrainment of the central circadian rhythm generator in the SCN and of peripheral oscillators during ontogenetic development. […]
Landgraf, D., McCarthy, M. J., & Welsh, D. K. (2014). Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders. Current Psychiatry Reports. Current Medicine Group LLC 1. https://doi.org/10.1007/s11920-014-0483-7
[…] Many psychiatric disorders are characterized by circadian rhythm abnormalities, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian “clock genes” commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual’s experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders. […]
Bollinger, T., & Schibler, U. (2014). Circadian rhythms – From genes to physiology and disease. Swiss Medical Weekly, 144. https://doi.org/10.4414/smw.2014.13984
[…] Most physiological processes in our body oscillate in a daily fashion. These include cerebral activity (sleep-wake cycles), metabolism and energy homeostasis, heart rate, blood pressure, body temperature, renal activity, and hormone as well as cytokine secretion. The daily rhythms in behaviour and physiology are not just acute responses to timing cues provided by the environment, but are driven by an endogenous circadian timing system. A central pacemaker in the suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, coordinates all overt rhythms in our body through neuronal and humoral outputs. The SCN consists of two tiny clusters of ~100,000 neurones in humans, each harbouring a self-sustained, cell-autonomous molecular oscillator. Research conducted during the past years has shown, however, that virtually all of our thirty-five trillion body cells possess their own clocks and that these are indistinguishable from those operative in SCN neurones. Here we give an overview on the molecular and cellular architecture of the mammalian circadian timing system and provide some thoughts on its medical and social impact. […]
Houdek, P., & Sumová, A. (2014). In vivo initiation of clock gene expression rhythmicity in fetal rat suprachiasmatic nuclei. PLoS ONE, 9(9). https://doi.org/10.1371/journal.pone.0107360
[…] The mammalian suprachiasmatic nuclei (SCN) and their intrinsic rhythmicity develop gradually during ontogenesis. In the rat, the SCN forms between embryonic day (E) 14 and E17, with gestation terminating at E21-22. Overt SCN rhythmicity is already present in the late embryonic stage. The aim of the present study was to determine when the fetal SCN clock develops in vivo and whether overt rhythmicity results from a functional fetal clock. To achieve this goal, the prenatal development of rhythmic expression of clock genes was measured with a more sensitive method for detection of the clock gene expression than previously. Fetal SCN were collected at 3 h intervals during the 24 h period on E19 and E21 by laser dissection and expression of clock genes (Per2, Nr1d1 and Bmal1) and genes related to cellular activity (c-fos, Avp and Vip) was measured by qRT PCR. At E19, the expression of canonical clock genes Per2 and Bmal1 was not rhythmic; however, the expression of all other studied genes followed clear circadian rhythms. At E21, Per2 and Bmal1 expression exhibited low amplitude but significant rhythmicity. From E19 to E21, the levels of the non-rhythmic transcripts (Per2 and Bmal1) decreased; however, the levels of the rhythmic transcripts (Nr1d1, c-fos, Avp and Vip) increased. In summary, these data demonstrate that at E19, rhythms in Per2 and Bmal1 expression were absent in the fetal SCN; however, the expression of Nr1d1 and other genes related to cellular activity was driven rhythmically. Therefore, at the early stage in vivo, the developing fetal SCN clock could theoretically be entrained by oscillation of Nr1d1 which may be driven by the maternal rather than fetal circadian system. […]
Coogan, A. N., & McGowan, N. M. (2017, September 1). A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder. ADHD Attention Deficit and Hyperactivity Disorders. Springer-Verlag Wien. https://doi.org/10.1007/s12402-016-0214-5
[…] Reports of sleep disturbances in attention deficit hyperactivity disorder (ADHD) are common in both children and adults; however, the aetiology of such disturbances is poorly understood. One potentially important mechanism which may be implicated in disrupted sleep in ADHD is the circadian CLOCK, a known key regulator of the sleep/wake cycle. In this systematic review, we analyse the evidence for circadian rhythm changes associated with ADHD, as well as assessing evidence for therapeutic approaches involving the circadian CLOCK in ADHD. We identify 62 relevant studies involving a total of 4462 ADHD patients. We find consistent evidence indicating that ADHD is associated with more eveningness/later chronotype and with phase delay of circadian phase markers such as dim light melatonin onset and delayed sleep onset. We find that there is evidence that melatonin treatment may be efficacious in addressing ADHD-related sleep problems, although there are few studies to date addressing other chronotherapeutic approaches in ADHD. There are only a small number of genetic association studies which report linkages between polymorphisms in circadian CLOCK genes and ADHD symptoms. In conclusion, we find that there is consistent evidence for circadian rhythm disruption in ADHD and that such disruption may present a therapeutic target that future ADHD research might concentrate explicitly on. […]
Varcoe, T. J., Gatford, K. L., & Kennaway, D. J. (2017). Maternal circadian rhythms and the programming of adult health and disease. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 314(2), R231–R241. https://doi.org/10.1152/ajpregu.00248.2017
[…] The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability and other environmental factors change predictably and repeatedly every 24 hours. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias and circadian rhythm disorders (e.g., advanced/delayed sleep phase disorder), with a growing consensus that this chronodisruption can have deleterious consequences for an individual’s health and wellbeing. However, the impact of chronodisruption during pregnancy on the health of both the mother and fetus is not well understood. In this review we outline circadian timing system ontogeny in mammals, and examine emerging research from animal models demonstrating long term negative implications for progeny health following maternal chronodisruption during pregnancy. […]
Mogavero, F., Jager, A., & Glennon, J. C. (2018, August 1). Clock genes, ADHD and aggression. Neuroscience and Biobehavioral Reviews. Elsevier Ltd. https://doi.org/10.1016/j.neubiorev.2016.11.002
[…] Attention deficit/hyperactivity disorder (ADHD) is frequently associated with comorbid aggression and sleep disturbances. The sleep/wake cycle is under the control of the circadian system which is moderated by clock genes. Clock genes can regulate the transcription of monoamine oxidase A, which is involved in the degradation of monoamines. Disturbances in monoamine interaction with clock genes in those with monoamine gene polymorphisms may regulate susceptibility of ADHD and comorbid aggression/sleep disturbances. While monoamines influence circadian rhythm and clock gene expression, circadian rhythm components modulate aggressive behavior, and altered clock genes expression have been associated with ADHD. We propose a mechanism by which circadian rhythm and clock gene expression may influence ADHD and comorbid aggression through the modulation of neurotransmitters. The role of clock genes in ADHD patients with comorbid aggression awaits further research; therefore we also indicate directions for future studies to help increase understanding of the underlying mechanisms in ADHD with comorbid aggression and sleep disturbances. […]
Bijlenga, D., Vollebregt, M. A., Kooij, J. J. S., & Arns, M. (2019, March 4). The role of the circadian system in the etiology and pathophysiology of ADHD: time to redefine ADHD? ADHD Attention Deficit and Hyperactivity Disorders. Springer-Verlag Wien. https://doi.org/10.1007/s12402-018-0271-z
[…] Attention-deficit/hyperactivity disorder (ADHD) is highly associated with the delayed sleep phase disorder, a circadian rhythm sleep-wake disorder, which is prevalent in 73-78% of children and adults with ADHD. Besides the delayed sleep phase disorder, various other sleep disorders accompany ADHD, both in children and in adults. ADHD is either the cause or the consequence of sleep disturbances, or they may have a shared etiological and genetic background. In this review, we present an overview of the current knowledge on the relationship between the circadian rhythm, sleep disorders, and ADHD. We also discuss the various pathways explaining the connection between ADHD symptoms and delayed sleep, ranging from genetics, behavioral aspects, daylight exposure, to the functioning of the eye. The treatment options discussed are focused on improvement of sleep quality, quantity, and phase-resetting, by means of improving sleep hygiene, chronotherapy, treatment of specific sleep disorders, and by strengthening certain neuronal networks involved in sleep, e.g., by sensorimotor rhythm neurofeedback. Ultimately, the main question is addressed: whether ADHD needs to be redefined. We propose a novel view on ADHD, where a part of the ADHD symptoms are the result of chronic sleep disorders, with most evidence for the delayed circadian rhythm as the underlying mechanism. This substantial subgroup should receive treatment of the sleep disorder in addition to ADHD symptom treatment. […]
Lee, S. W. (2019). A Copernican Approach to Brain Advancement: The Paradigm of Allostatic Orchestration. Frontiers in Human Neuroscience, 13. https://doi.org/10.3389/fnhum.2019.00129
[…] There are two main paradigms for brain-related science, with different implications for brain-focused intervention or advancement. The paradigm of homeostasis (“stability through constancy,” Walter Cannon), originating from laboratory-based experimental physiology pioneered by Claude Bernard, shows that living systems tend to maintain system functionality in the direction of constancy (or similitude). The aim of physiology is to elucidate the factors that maintain homeostasis, and therapeutics aim to correct abnormal factor functions. The homeostasis paradigm does not formally recognize influences outside its controlled experimental frames and it is variable in its modeling of neural contributions. The paradigm of allostatic orchestration (PAO) extends the principle of allostasis (“stability through change”) as originally put forth by Peter Sterling. The PAO originates from an evolutionary perspective and recognizes that biological set points change in anticipation of changing environments. The brain is the organ of central command, orchestrating cross-system operations to support optimal behavior at the level of the whole organism. Alternative views of blood pressure regulation and posttraumatic stress disorder (PTSD) illustrate differences between the paradigms. For the PAO, complexities of top-down neural effects and environmental context are foundational (not to be “factored out”), and anticipatory regulation is the principle of their interface. The allostatic state represents the integrated totality of brain-body interactions. Health itself is an allostatic state of optimal anticipatory oscillation, hypothesized to relate to the state of criticality, a mathematical point of poise between phases, on the border between order and disorder (or the “edge of chaos”). Diseases are allostatic states of impaired anticipatory oscillations, demonstrated as rigidifications of set points across the brain and body (disease comorbidity). Conciliation of the paradigms is possible, with “reactive homeostasis” resolved as an illusion stemming from the anticipation of environmental monotony. Considerations are presented with respect to implications of the two paradigms for brain-focused intervention or advancement; the hypothesis that the state of criticality is a vehicle for evolutionary processes; concordance with a philosophy of freedom based on ethical individualism as well as self- creativity, non-obsolescence, empowerment, and citizenship; and concluding reflections on the science and ethics of the placebo, and the potential for virtuous cycles of brain-Anthropocene interactions. […]
Dibner, C. (2019). The importance of being rhythmic: living in harmony with your body clocks. Acta Physiologica, e13281. doi: https://doi.org/10.1111/apha.13281
[…] Circadian rhythms have developed in all light sensitive organisms, including humans, as a fundamental anticipatory mechanism that enables proactive adaptation to environmental changes. The circadian system is organized in a highly hierarchical manner, with clocks operative in most cells of the body ensuring the temporal coordination of physiological processes. Circadian misalignment, stemming from modern life style, draws increasing attention due to its tight association with the development of metabolic, cardiovascular, inflammatory and mental diseases as well as cancer. This review highlights recent findings emphasizing the role of the circadian system in the temporal orchestration of physiology, with a particular focus on implications of circadian misalignment in human pathologies. […]
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