A New Paradigm for Mental Disorders

Circadian Entropy, Causality in Research, and Chronotherapies for Mental Illness

Mental disorders are the leading cause of disability worldwide¹.

The most pressing ones are different by age, but as we learn more about them, we learn they are related. It turns out, having one mental disorder is highly predictive of later having another.

So, someone diagnosed with a developmental disorder in childhood is likely to be diagnosed with an affective disorder in adulthood, and ultimately, a neurodegenerative disorder in their elder years.

Scientists looking for a common pathology have found one factor common to every single mental disorder: circadian rhythm disruption.

And even more urgently, this disruption initially starts with maternal disruption affecting fetal development in the womb.

The most common mental disorders in children are known as neurodevelopmental disorders and include:

• Attention deficit and hyperactivity disorder (ADHD)

• Autism spectrum disorder (ASD)

• and Tourette’s syndrome (TS)

The most common mental disorders in adolescents and adults are known as affective disorders and include:

• Schizophrenia (SCZ)

• Bipolar disorder (BD)

• Major depressive disorder (MDD)

• Various anxiety disorders (AXD)

• and various Eating disorders

The most common mental disorders in seniors are known as neurodegenerative disorders and include:

• Alzheimer’s (AD)

• and Age-related neurodegeneration

Today’s question is: do the different mental illnesses share a common pathology?

This question arises when you look at the comorbidities among disorders.

Many individuals with one will end up diagnosed with many across their lifespan.

Plus, the experts keep rearranging the borders between all these conditions.

Here's what the map currently looks like:

Comorbidities among mental disorder groups: if someone is diagnosed with one, they are likely to be diagnosed with others in the future.

When looking at these data, one uniting factor emerges.

At least, that's what researchers from the University of California think.

Circadian rhythmicity disruption begins in the womb and remains impactful across the lifespan.

According to this recently published review, the uniting factor among mental disorders may be circadian rhythmicity disruption (CRD) manifesting as sleep disruption.

What can we learn from this 2022 paper on Circadian Entropy and Mental Health Disorders?

Here are the most useful takeaways (IMHO):

1. To prevent the cascade of mental illness, we need to start with maternal rhythmicity. The progression through these overlapping mental illnesses may begin in the womb. It then seems to cascade through childhood, adolescence, adulthood, midlife, and seniority.

2. Aim interventions at people manifesting the "Evening" chronotype. Being an “Evening” chronotype correlates with being diagnosed with mental disorders in the future.

If you’d like to read this paper in it’s entirety, here’s the PDF:

The hidden link between circadian entropy and mental health disorders (2022)

1.66MB ∙ PDF file

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The high overlapping nature of various features across multiple mental health disorders suggests the existence of common psychopathology factor(s) (p-factors) that mediate similar phenotypic presentations across distinct but relatable disorders. In this perspective, we argue that circadian rhythm disruption (CRD) is a common underlying p-factor that bridges across mental health disorders within their age and sex contexts. We present and analyze evidence from the literature for the critical roles circadian rhythmicity plays in regulating mental, emotional, and behavioral functions throughout the lifespan. A review of the literature shows that coarse CRD, such as sleep disruption, is prevalent in all mental health disorders at the level of etiological and pathophysiological mechanisms and clinical phenotypical manifestations. Finally, we discuss the subtle interplay of CRD with sex in relation to these disorders across different stages of life. Translational Psychiatry (2022) 12:281 ; https://doi.org/10.1038/s41398-022-02028-3

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Use of the term “circadian entropy” here is interesting.

Circadian refers to biological processes recurring naturally on a 24-hour basis.

Entropy refers to lack of order or predictability; or a gradual decline to disorder.

Researchers around the world are using a variety of similar terms to describe this topic. Here are some:

• Circadian entropy

• Circadian disruption

• Circadian rhythm disruption

• Circadian rhythmicity disruption

• Desynchronization of circadian rhythms

• and Chronodisruption

When talking about these biological functions happening well, we see terms like:

• Stable circadian rhythms

• Strong circadian rhythms

• Strengthened circadian rhythms

• Entrained circadian rhythms

• Synchronized circadian rhythms

• and Circadian rhythmicity

Being aware of all these terms is helpful if you want to look up any conditions you might be curious about.

Any of these make good search terms and give different kinds of information.

So, does circadian disruption cause mental health disorders?

Scientists are always cautious about throwing around the “cause.”

Every statistics student learns the phrase “correlation does not equal causation”.

With circadian rhythmicity research, we have a problem: it would be completely unethical to design a double-blind study that proved/disproved the thesis that maternal circadian disruption caused lifelong mental illness.

I wrote more about this here:

We will likely never see the headline “circadian disruption causes mental illness” because it’s not the kind of thing we can ethically test using the scientific method.

Instead, we can must draw our conclusions about circadian mental health from related factors we can prove, such as:

• Artificial light at night (incandescent, LED, fluorescent, halogen, etc) causes circadian disruption because it is brighter than moonlight, starlight, and flame-lights.

• Artificial light during the day causes circadian disruption because it is dimmer than sunlight.

• Eating at night causes circadian disruption because the body needs to fast in darkness.

• Circadian disruption is a common factor underlying every known mental disorder.

• Artificial light exposure and disordered eating habits may be behind the severity of many mental illnesses (read my report on the connections with Bipolar here)

When it comes to stabilizing and strengthening circadian rhythms, here are some tips:

• Natural light at night (starlight, moonlight, candlelight, firelight, etc) entrains circadian rhythms because it is perfectly dim.

• Natural light during the day entrains circadian rhythms because it is perfectly bright.

• Eating during the day entrains circadian rhythms because we need to eat in the light.

• Stabilizing circadian rhythms treats and prevents symptoms of mental disorders that are otherwise untreatable, including manic episodes in bipolar disorder² and sundowning episodes in dementia.

• Stabilizing maternal circadian rhythms could simultaneously stem the tide of every single mental disorder for the coming generation!

And so on!

Here is a simplified graphic showing the ins (afferents) and outs (efferents) of the suprachiasmatic nucleus (SCN)³.

This is the brain’s main command center for circadian processes all throughout the body.

This is the information we MUST get to expecting families because the timing of the light we are under, and the timing of our meals, are what determine the quality of our circadian rhythm (not sleep, even though that’s what most people think of first when they think of the circadian rhythm):

The two primary zeitgebers (time-givers) in the human circadian system are light and food.

The two primary time-givers for the human circadian system:

1. (Sun)light/darkness cycle (which is also a heat/coolness cycle) ←shown as the sun icon at the left of the above graphic

2. Eating/fasting schedule ← shown as the meal icon at the left of the above graphic

Besides our light and food consumption, everything else we do either supports or detracts from those primary signals (or, "zeitgebers")⁴.

Chronotherapies for Mental Health

We see this proactive circadian approach with "bright light therapy", "enforced darkness regimes", and "chronotherapeutics".

These interventions are emerging as a whole class of "chronotherapies."

They are proving to be the only way to treat subsets of symptoms such as bipolar mania and sundowning.

After all, as Hatori, et al., so aptly stated in their 2017 paper “Global rise of potential health hazards caused by blue light-induced circadian disruption in modern aging societies”⁵:

Light is known to affect human chronobiology more than any drug on the market.

-Hatori, et al

DISCLAIMER

All material contained in this publication is for informational purposes only. This information is not intended to diagnose, prevent, or cure any medical condition, nor to replace medical advice offered by qualified health care providers. Any application of the material provided is at your own discretion and is your own, sole responsibility.

1. Alachkar, A., Lee, J., Asthana, K., et al. (2022). The hidden link between circadian entropy and mental health disorders.

2. Walker, W., Walton, J., DeVries, C, Nelson, R. (2020). Circadian rhythm disruption and mental health.

3. Froy, O. (2010). Metabolism and Circadian Rhythms—Implications for Obesity.

4. Roenneberg, T. and Merrow, M. (2007). Entrainment of the Human Circadian Clock.

5. Hatori, M., Gronfier, C., Van Gelder, R., Bernstein, P., et al. (2017). Global rise of potential health hazards caused by blue light-induced circadian disruption in modern aging societies.