Nueva investigación sobre cómo el estrés afecta la inflamación, la neurodegeneración, el microbioma intestinal, el tratamiento del cáncer y las relaciones

El estrés es una de mis pasiones en particular; me encanta aprender a reducir el estrés negativo y me fascina la forma en que el estrés afecta nuestra salud. Esta es la primera de una serie de publicaciones que escribiré sobre el estrés en los próximos meses.

No sabemos todo lo que hay que saber sobre el estrés. En el gran esquema de las cosas, los científicos apenas están comenzando a comprender las innumerables formas en que el estrés crónico nos afecta, y cada año se realizan nuevos descubrimientos importantes. En esta publicación, discutiré investigaciones recientes sobre estos temas:

• El estrés daña las mitocondrias y provoca enfermedades y envejecimiento.
• El estrés provoca resistencia a los receptores de glucocorticoides, lo que aumenta la inflamación
• El estrés cambia las conexiones neuronales, disminuye el volumen del cerebro y contribuye a la enfermedad de Alzheimer
• El estrés cambia la composición y el comportamiento de las bacterias intestinales y causa "intestino permeable"
• El estrés aumenta la metástasis y disminuye la eficacia del tratamiento del cáncer
• El estrés es contagioso a nivel celular

Las mitocondrias traducen el estrés psicológico en enfermedad y envejecimiento, proporcionando una prueba biológica de la conexión entre la mente y el cuerpo.

Las mitocondrias son orgánulos (subunidades de células) que se encuentran en la mayoría de las células de nuestro cuerpo. Las funciones más importantes de las mitocondrias son producir energía para las células, regular el metabolismo celular y enviar señales a otras células. Cuando las mitocondrias no funcionan como deberían, pueden resultar enfermedades graves que involucran muchos sistemas corporales diferentes.

A revealing 2018 review describes how acute and chronic stress affect mitochondrial structure and function, especially in the brain. These changes can then lead to inflammation throughout the body, increasing the risk of many inflammatory diseases. It’s believed that mitochondria play a role in regulating our physiological stress response, so stress-induced changes in mitochondria may result in even more stress. In addition, mitochondria have their own DNA, and damage to mitochondrial DNA caused by stress speeds up aging in mammals.

Evidence shows that mitochondria “sense, integrate, and signal information about their environment.” The growing body of evidence demonstrating how mitochondria translate stress into disease is exciting for the field of psychosomatic medicine, because it provides biological proof of how the mind and body interact.

El estrés crónico conduce a la resistencia del receptor de glucocorticoides y al aumento de la inflamación

When we perceive stress, a series of hormones released in the brain triggers the adrenal gland to secrete hormones called glucocorticoids. These bind to glucocorticoid receptors, which are present in almost every cell in our body. Glucocorticoids play a critical role in regulating our stress response, including how much inflammation occurs.

Glucocorticoids must be able to bind to their receptors in order to do their job. Research now shows that chronic stress leads to glucocorticoid receptor resistance, making it difficult or impossible for glucocorticoids to bind. This resistance causes our inflammatory response to be longer and/or more intense, and our risk for suffering from the common cold, asthma, autoimmune diseases, cardiovascular disease, type 2 diabetes, and other inflammatory conditions is increased.

El estrés cambia las conexiones neuronales, disminuye el volumen del cerebro y contribuye a la enfermedad de Alzheimer

Researchers from Zurich, Switzerland were surprised and excited by what they discovered about how stress changes the brain in a 2019 study published in Neuron.

When we perceive a threat, the neurotransmitter noradrenaline (aka norepinephrine) is released. Previous research has suggested that noradrenaline probably facilitates connections between parts of the brain. The research team from Zurich manipulated the brains of mice so that they could control when noradrenaline was released. They found that noradrenaline instantly “rewired” the mouse brains, making actual structural changes to neural connections. This finding suggests that the long-term effects of stress on the brain may be more profound than previously thought.

En el estudio, los cambios estructurales más significativos ocurrieron en áreas del cerebro que procesan información sensorial (como lo que vemos y oímos) y en la amígdala. La amígdala es un grupo de núcleos en el sistema límbico que juega un papel importante en las respuestas emocionales de miedo, ansiedad y agresión, así como en la memoria y la toma de decisiones. La amígdala suele ser hiperactiva en personas con afecciones relacionadas con el estrés, como ansiedad y depresión.

Chronic stress affects the amygdala by another means as well. Prolonged high levels of glucocorticoids stimulate neuron growth in the amygdala and make synapses more active and sensitive.

Stress and the release of glucocorticoids have also been shown to hardwire neural connections between the hippocampus and the amygdala, potentially creating a cycle in which the brain becomes stuck in a constant state of stress.

Of equal concern is the fact that effect that chronic stress has on decreasing brain volume and connectivity. Data from 2,231 participants in the Framingham Heart Study shows that people with increased levels of cortisol (one of the glucocorticoids) experience brain shrinkage and memory loss.

And a study of 103 healthy subjects showed decreased brain volume in the medial prefrontal cortex and the insula in people who had experienced repeated exposure to stress as well as those who had only experienced a recent stressful event. The affected areas of the brain regulate emotions, stress, reward regulation, memory, decision-making, and impulse control. The study authors suggest that this decrease in brain matter may help to explain the connection between stressful life events and an increased risk of depression, addiction, and other stress-related disorders.

Glucocorticoids have also been shown to decrease volume of the hippocampus, a part of the brain involved in memory, learning, attention, and ironically, regulating glucocorticoid secretion. So the more stress you experience and the more damage is done to your hippocampus, the less effective it is at regulating glucocorticoid levels, and the more glucocorticoids build up in your system. This is a vicious cycle that can make it difficult to reduce your level of stress.

There is a growing body of research on how stress contributes to Alzheimer’s disease. Based on current research, stress increases the expression of Amyloid Precursor Protein (APP) and the production of Aβ peptide, which then gets deposited into amyloid plaques. Amyloid plaques trigger an inflammatory response in the brain, and it’s believed that neurotoxic inflammatory substances contribute to the neurodegeneration that occurs in Alzheimer’s. Stress also elevates levels of the Tau protein, which leads to neurofibrillary tangle formation and neurodegeneration.

El estrés cambia la composición y el comportamiento de las bacterias intestinales y causa "intestino permeable"

The human microbiome describes the trillions of microorganisms (aka microbiota or microbes) that reside within our body. Our gut microbiome has been getting a lot of attention lately because of the discoveries researchers have made about how our gut microbiome affects our overall health. These discoveries have led to a booming market for pre- and probiotics that claim to improve our gut health.

There is “bidirectional cross-talk” between our gut and our brain. Our enteric nervous system (aka ENS; the network of 200-600 million neurons in our digestive system) communicates with our central nervous system (CNS) in a number of ways, including via the vagus and pelvic nerves and systemically via immune system cells. The cross-communication between our digestive system and our brain means that there is a high rate of comorbidity of gastrointestinal and psychiatric disorders; for example, up to 94% of people with irritable bowel syndrome also suffer from a psychiatric disorder.

A 2019 study shows that social stress changes both the composition and the behavior of gut bacteria. After subjecting mice to repeated stress, the mice had significant differences in their gut bacteria, most notably in two types of bacteria linked to multiple sclerosis in humans. And in the stressed mice, some gut bacteria turned into destructive pathogens which are likely to infect tissue, trigger the immune response, and lead to autoimmune conditions.

A number of studies show how psychological stress increases gut permeability (aka “leaky gut”), a condition in which bacteria and toxins are able to leak through the intestinal wall, causing a wide variety of health problems.

We’re only beginning to understand the vast ways in which stress affects our gut microbiome, and vice versa. To learn more about this topic, check out The Mind-Gut Connection by Dr. Emeran Mayer.

El estrés aumenta la metástasis y disminuye la eficacia del tratamiento del cáncer

A healthy immune system is our #1 line of defense against cancer. Unfortunately, a 2017 study showed that chronic stress suppresses the immune system’s response to cancer and reduces the efficacy of immunotherapy treatments. The researchers suggest that improving immune system function may improve the rate of success of conventional therapies like chemotherapy as well, because many of these therapies rely on the immune system for their efficacy. The researchers stated that “there is now pre-clinical evidence to suggest that treatments and lifestyle interventions to manage or reduce stress levels will improve the chances of these patients responding to therapies.”

A 2019 study made two important discoveries about how stress hormones affect breast cancer metastasis and treatment. First, the study showed that increased levels of stress hormones led to increased colonization (growth in secondary locations) and heterogeneity (diversity) of cancer cells—both of which make cancer more difficult to treat and decrease the survival rate of the patient.

Second, the study showed that synthetic derivatives of stress hormones (corticosteroids), which are often used as anti-inflammatories in cancer treatment, actually decrease the efficacy of chemotherapy. This finding suggests that corticosteroids should be used with caution in cancer therapy. One of the researchers, Mohamed Bentires-Alj, states that “These findings highlight the importance of stress management in patients…Moderate exercise and relaxation techniques have been shown to correlate with enhanced quality of life and greater survival in patients.”

El estrés es contagioso a nivel celular

Si tienes un familiar, amigo o pareja romántica que siempre está estresado, es posible que hayas notado el efecto que tiene ese estrés en ti. Es posible que sienta que "absorbe" su estrés o que no puede relajarse con ellos. Bueno, los científicos ahora han descubierto cómo el estrés es contagioso a nivel celular.

A 2018 study found that stress transmitted from someone else can change your brain in the same way that “real stress” (stress that you are exposed to) does. Corticotrophin-releasing hormone (CRH) neurons in the hypothalamus are activated when we perceive stress, and the researchers discovered that the activation of these CRH neurons in mice triggers the release of an “alarm pheromone” that chemically signals a non-stressed mouse nearby. Remarkably, this chemical signal activated CRH neurons in the non-stressed mice in the same way as in the mice that were exposed to stress.

Esta forma automática de comunicarse y responder al estrés probablemente ayude a varias especies a sobrevivir en grupos; el miembro que detecta la amenaza puede alertar silenciosamente a otros miembros del grupo. Pero en las relaciones humanas de hoy, la mayoría de las veces sirve para aumentar el estrés innecesario que experimentamos.

And it turns out that you don’t even need to be physically close to someone in order to be affected by their stress. Researchers found that merely observing stressed people on video makes us release the stress hormone cortisol. This finding suggests that watching stressful television shows on a regular basis is likely not good for our stress level. On a larger scale, it speaks to the rising level of stress-related health conditions in the world, and suggests that we might experience stress in response to observing any stressed person in any manner, like on the street or via the internet. Stress is literally contagious, and we are all more connected than ever before.

Even our pets are affected by our stress level. A 2019 study found that owners with high levels of cortisol have dogs with high levels of cortisol, and owners with low levels of cortisol have dogs with low levels. Based on the study’s assessment of the owners’ and dogs’ personalities, the researchers determined that dogs mirror their owner’s stress, and not the other way around.

En conclusión

Si bien no sabemos todo lo que hay que saber sobre los efectos negativos del estrés psicológico crónico, lo que sí sabemos es suficiente para poner la reducción del estrés a la altura del ejercicio y una dieta saludable en lo que respecta a la salud y la longevidad. Tomarse un tiempo para relajarse puede resultar egoísta, indulgente e innecesario, pero cuanta más investigación lea sobre este tema, más se sentirá obligado a incorporar la relajación y el cuidado personal en su rutina diaria. Reducir su nivel de estrés y cambiar sus reacciones automáticas al estrés también mejorará inmediatamente sus relaciones. ¡Pruébelo y verá!

Lectura recomendada:

The Pain Relief Secret: How to Retrain Your Nervous System, Heal Your Body, and Overcome Chronic Pain by Sarah Warren, CSE

Somatics: Reawakening the Mind’s Control of Movement, Flexibility and Health by Thomas Hanna