How excess cortisol perturbs melatonin, sleep and neuro-immune exchanges

[LucH]

How excess cortisol perturbs melatonin, sleep and neuro-immune exchanges
After reading Cathy ASSENHEIM's book, "The 4-Step Anti-Exhaustion Program", I thought it would be interesting to focus a little on the impact of cortisol on the serotonin <> melatonin cycle.

In short
High cortisol inhibits melatonin release, disrupts the SCN's clock, and triggers immune cells (microglia, astrocytes) to become reactive, causing neuro-inflammation via the HPA axis, impacting synaptic health, and worsening sleep quality, linking stress, immunity, and rest, creating a vicious circle.
Full pathway
Stress → ↑ Cortisol → ↓ serotonin → ↓ melatonin → ↓ Insufficient recovery → ↓ emotional regulation (HPA) → neuro-immune disturbances → Microbiota → ↑ stress → ↓ energy and sleep / ↓ mood /
↑ anxiety and irritability.

Why do these psychological symptoms appear?
Of course, most of you know how to kick off!
As long you can disconnect and recuperate, you shouldn’t feel – let’s say “emotional weak” or too often in a bad temper. Yes, you know; you know you’ve always been able to keep control. And you don’t see why you couldn’t yet do it again, even if …
Even if you smoke a little more, or need a glass of wine or a beer to unwind at lunchtime, or a drink after work before heading home… Maybe that doesn't apply to you. You look like an athlete, at least for your age…Wait! Hold on, lad! Don't think you're smarter than the others. By the way, intelligence and abilities have nothing to do with this concern…
It's just a fuse issue. Can you observe, analyze, and disconnect when the body requests it; or are you under pressure, given the context (performance, deadlines, and yield): They're counting on you, aren’t they? They've always been able to count on you. You're reliable...

What is the relationship to the gut microbiota?
The state of our gut system influences our state of mind and mood. This goes beyond the stability and proper functioning of our digestive system. In fact, 90 to 95% of serotonin is produced in the gut (enterochromaffin cells), with an indirect effect on brain serotonin… (via inflammation, tryptophan metabolism, the vagus nerve, and cytokines).
The microbiota:

• produces neuroactive metabolites
• influences immunity and inflammation
• communicates with the brain via the vagus nerve.
  Specialists often say that the microbiota represents our "second brain." Furthermore, the microbiota accounts for 75-80% of our immunity (through communication via the vagus nerve). The vagus nerve is the main bidirectional communication pathway between the brain and the organs, regulating the parasympathetic nervous system ("rest-and-digest"). Indeed, the microbiome plays a critical role in programming bodily systems and influencing host health (adaptive system).
  • HPA axis : hypothalamus → hypophysis (pituitary gland) → adrenal glands (cortisol)
  • Vagus nerve: A major pathway of the parasympathetic system, anti-stress.
  The vagus nerve slows down the HPA axis. This detail is important to understand why breathing, heart coherence, and sophrology work quite well.

What is the impact of serotonin on sleep?
Serotonin is the precursor to melatonin, the sleep hormone. When melatonin isn't produced in adequate amounts at the end of the day, falling asleep becomes more difficult, nighttime awakenings increase, and sleep becomes less restorative. A vicious cycle begins. Exhaustion looms…

Boosting Serotonin Production
Serotonin production depends on the intake of an amino acid, tryptophan. Tryptophan is present in proteins and, when combined with carbohydrates, serves as a precursor to serotonin synthesis.
Tryptophan is found in oily fish, dairy products, eggs, poultry, chocolate, and certain fruits (almonds, bananas).
Yes, but here's the thing: in cases of chronic stress, cortisol disrupts the availability of serotonin, the pathway for the assimilation of tryptophan is modified (kynurenine pathway), and the metabolism gradually goes into overheat mode.
A host of consequences
A series of secondary consequences and reinforcing loops can then occur:

• Low-grade neuro-inflammation
• Alterations in the gut microbiota
• Latent anxiety and impaired emotional control (impaired brain plasticity)
• Compulsive behaviors and decreased emotional flexibility
• Blood sugar imbalances
  ️ Anxiety, irritability and compulsive behaviors are not psychological weaknesses, but neurobiological responses to prolonged stress.
  But this isn't the first direction we should look in if we want to correct the problem. We must first calm/moderate the hyperactivity of the HPA axis and redirect tryptophan metabolism. We need to redirect tryptophan metabolism away from the kynurenine pathway and toward serotonin synthesis.
  Therefore, we would need to reverse the following pathway: Stress → ↑ Cortisol → ↓ serotonin.
  As long as the stress is occasional, the system is adaptive.
  When it is continuous, it becomes neurotoxic. Cortisol disrupts the availability of serotonin, and a vicious cycle can begin if nothing corrects the loop:
  Stress → ↑ cortisol → ↓ tryptophan → ↓ serotonin → ↓ sleep → ↓ recovery.
  For example, with a sophrology exercise, but not only that (breathing – exhaling in 5 to 6 counts) 3 times a day.
  Slow breathing (5–6 cycles/min):
  • stimulates the vagus nerve
  • reduces cortisol
  • improves heart rate variability
  • addresses the root cause of the problem
  This is consistent with current data in psycho-neuro-endocrinology.

Useful link:
https://mirzoune-ciboulette.forumactif.org/t2155-gerer-le-stress-la-fatigue-l-anxiete-et-evitez-le-burn-out#30498

Ask for help to AI
Context: 3 stages of recovery to try to reverse the following path: Stress → ↑ Cortisol → ↓ serotonin.
Helping to overcome addictive behavior, with adrenal fatigue: Which molecules? (=> Phytotherapy, supplements, nutrients and behavior).
Warnings.
Specific request to AI
Propose a progressive, coordinated plan to recover from stage 3 (burnout). This plan should include follow-up with a therapist (report). Note that I suggest several clues, coming from Cathy Assenheim, neuro-biologist.
Stage 1: Anxiety, irritability, denial, and possibly compulsive behavior, poor sleep quality, etc.
Stage 2: Exhaustion due to lack of recovery and adaptation.
Stage 3: Burnout.
See details on my forum. In French. If you requires a translation, copy the link in a search engine. Do not directly click on.
https://mirzoune-ciboulette.forumactif.org/t2156-stress-cortisol-et-serotonine-quels-supplements-tactique#30508

Sources and References
*) Research progress on the role of microbiome-immune-neurotransmitter network in post-stroke sleep disorders. Front. Aging Neurosci. December 2025. Wanting Shi et al.
https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1694709/full
=> Dysregulation of the microbiome-immune-neurotransmitter network. Reduced short-chain fatty acids and lipopolysaccharide (LPS) translocation exacerbate systemic inflammatory responses and neurotransmitter imbalances (inhibited serotonin synthesis and excitotoxic glutamate production).
*) Stress-Induced Sleep Dysregulation: The Roles of Astrocytes and Microglia in Neurodegenerative and Psychiatric Disorders. doi: 10.3390/biomedicines13051121 2025 May
*) How does cortisol affect sleep?
https://sleepcycle.com/sleep-talk/cortisol-and-sleep
Perturbing Melatonin & Sleep:
Increases Arousal: Elevated cortisol levels keep you alert and aroused, counteracting the "sleep pressure" from adenosine, leading to insomnia, fragmented sleep, and less restorative deep sleep, creating a vicious cycle with stress.
Disrupts Circadian Rhythms: Chronic stress overactivates the HPA axis, dysregulating the suprachiasmatic nucleus (SCN) in the brain, the master clock, further throwing off the sleep-wake cycle.
Disrupts Circadian Rhythms: Chronic stress overactivates the HPA axis, dysregulating the suprachiasmatic nucleus (SCN) in the brain, the master clock, further throwing off the sleep-wake cycle.
So, in essence: when something disrupts the HPA axis, it disrupts your sleep cycle as well. Increased cortisol suppresses melatonin and dilutes adenosine – the molecule responsible for the sleep pressure that ‘tips you over the edge’ and into perfect slumber. The result is elevated arousal levels at bedtime, insomnia, fragmented sleep, and difficulty getting the much needed deep, restorative sleep. This stimulates cortisol secretion even more (to fight the stressors) which prevents a good night’s sleep. It’s a vicious cycle.
*) The gut microbiota-immune-brain axis: Therapeutic implications
Cell Rep Med. March 2025. doi: 10.1016/j.xcrm.2025.101982
In this review, we discuss the mechanisms as to how the gut microbiota interacts with the brain, focusing on innate and adaptive immunity that are often disrupted in gut-brain axis disorders.