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Under Pressure — The Effects of Stress on the Brain

Written by Dr. Michael Ruscio, DC on November 25, 2024

Written by Dr. Michael Ruscio, DC on November 25, 2024 — Reviewed by Kellie Blake

• Stress and the Brain: The Basics|
• The Effects of Stress on the Brain|
• Amygdala Activation|
• Stress and Memory|
• The Toll of Stress on the Prefrontal Cortex|
• A “Leaky” Blood-Brain Barrier|
• Heal Your Stress|

Most of us are intimately familiar with the common effects of stress on the brain: racing thoughts, mental fatigue, anxiety, low mood, overwhelm, and procrastination. Sound familiar? It certainly is to me, and you can hear about my own journey with beating chronic brain fog on my YouTube channel.

But it turns out that stress’s harmful effects go much deeper than these symptoms—changing some structures of our brains, especially those involved in recall, decision-making, and emotional regulation. Meaning there’s a reason why our memory seems to go out the window when we are dealing with a period of stress.

As stress is an unavoidable part of our lives — up to 90% of primary care visits are due to a stress-related concern — this may seem fairly disheartening 1. But the good news is that these effects are far more characteristic of chronic stress — which we have significantly more control over than acute stress. In our stress-inducing, modern society, knowledge is power. And understanding the effects of stress on the brain is the jump-start many of us need to start taking our stress levels more seriously. 

Stress and the Brain: The Basics

I’ll get into the effects of stress on the brain in a moment, but if you are unfamiliar with what the stress response actually is, this is an important place to start. Understanding this cascade of chemical reactions will really help tie together the other topics covered in this article. 

Stress is a physiological response to an internal or external stimulus that causes a release of chemical reactions throughout the body 2. The brain is the major source (and target) for these chemicals, though the entire body plays a role when it comes to forming a complete stress response. 

When the body encounters some sort of perceived stressful stimulus, the hypothalamus — a structure located in the brain — begins the stress response by releasing corticotropin-releasing hormone (CRH) 2. 

This ultimately causes the adrenal glands to release cortisol, and this hormonal cascade works in tandem with the sympathetic nervous system to secrete epinephrine and norepinephrine. It is these three stress hormones that trigger most of the downstream effects of stress on the body,  rapidly forming the complete “fight-or-flight” response 2. 

Cortisol and epinephrine increase heart rate, respiration, and blood pressure while shunting blood to the extremities to prepare the body for action. The immune system is acutely suppressed by cortisol, and blood sugar levels go up to provide an immediate energy source 2. 

In the brain, the amygdala, responsible for emotional processing, is activated to help with future threat detection. The prefrontal cortex (responsible for decision-making) and the hippocampus (the memory center) shut down to direct energy to more immediate needs 3.

All of these effects of short-term stress can be highly beneficial when facing a serious threat (think running from a source of danger), but they aren’t really well-adapted to our modern society. We now live in a world where threats are often psychological and don’t require such a large physical response, and occur on a more day-to-day basis rather than being just an occasional event.

When we have a continuous and unregulated release of these chemicals — otherwise known as chronic stress — we can begin to develop chronic health problems like hypertension, chronic or frequent infections, high blood sugar, and poor brain function.

The Effects of Stress on the Brain

The full effects of stress on the brain are too extensive to cover in one article, but there are some broad trends that continuously appear in the scientific literature. 

On a general level, unregulated stress can shrink the brain, decrease its overall weight, and even cause it to lose its “plasticity” 3 4. Brain plasticity refers to the brain’s ability to adapt to new experiences, so when we are stressed, it means we are more likely to become “stuck”, and fixate on negative and stressful experiences as opposed to positive ones. 

Stress increases inflammation levels in the brain, leads to oxidative stress (an imbalance between free radicals and antioxidants), and damages our brain cells 3. Glucocorticoids, like cortisol, can decrease levels of our calming neurotransmitter GABA, which is strongly linked to developing anxiety symptoms. 

Stress also lowers our levels of brain-derived neurotrophic factor (BDNF), which plays a role in the growth of new neurons, causing impairments in our mood, energy levels, and cognition 2. 

Persistent stress appears to direct many of its harmful effects on a few key structures in the brain that I’ll be focusing on today. 

When Amygdala Activation Goes Haywire

The amygdala is well-known for its role in post-traumatic stress disorder (PTSD) where extreme, acute, or repeated stress exposure can make it hyperactive 5. It is responsible for processing our emotions and detecting threats in our environment. 

This almond-shaped structure is remarkably good at its job, and it keeps these threats on file so it can more easily detect them in the future. This helps it tell the hypothalamus (a “master” endocrine gland in our brain) when it’s time to initiate the stress response, in a matter of milliseconds.

Unfortunately, the amygdala is unable to tell the difference between a “real” and a perceived threat. It registers a stimulus as a threat when it’s accompanied by a large, emotional stress response and/or when a stress response occurs to the same stimulus repeatedly over time. This is how a “trigger” is born, and it can cause the amygdala to become hyper-responsive and increase in size 3 6.

Anytime you encounter something that reminds your amygdala of the initial threat, it jumps in to kick-start your stress response. 

The amygdala-hypothalamus communication bypasses your prefrontal cortex, so there is no conscious control over this process — in other words, you can’t “will yourself” to stop being triggered.

A dysregulated amygdala-hypothalamic connection is believed to be behind many health conditions, including 7:

• Anxiety
• Depression
• PTSD
• Panic disorder and agoraphobia
• Fear
• Anhedonia (inability to experience pleasure)

However, the amygdala isn’t all bad, as it tells the hypothalamus when to secrete hormones, like oxytocin for social bonding, and is responsible for “fear extinction”. This occurs when it inhibits the hypothalamus’s ability to initiate the stress response after sensing a trigger 8. This is typically done while in a controlled environment and in a calm manner (think exposure therapy). 

While chronic stress leads to an overactive and dysregulated amygdala, it is also the ticket to recovering from an overactive stress response. The Gupta Program is one excellent option for retraining the amygdala and other parts of the limbic system, and many of my clients have experienced success with limbic retraining.

Is Stress Why Our Memories Are Declining?

Turns out there is a plausible reason why everyone seems to have a bad memory these days, and it may have something to do with our stress levels. The hippocampus is our “memory center”, located deep within the brain, and is particularly vulnerable to the products of chronic stress.

When cortisol is released during the stress response it can travel into the brain where it releases an overabundance of glutamate, an excitatory neurotransmitter 6. In healthy levels, glutamate is essential for normal nervous system communications. But in elevated concentrations, especially when it’s chronic, it is highly toxic to the hippocampus and other areas of the brain. 

Chronic stress may also inhibit your ability to clear excess glutamate from the brain, which further perpetuates the issue 6. Exposure to high glutamate can kill neurons, leading to poor memory formation and difficulty with learning new information (this is why it can be difficult to remember a highly stressful event). 

This is especially true when it becomes chronic and it leads to decreased neurogenesis — the formation of new neurons  — in the hippocampus. It can lead to shrinkage of this memory center over time, and is linked to the development of Alzheimer’s disease 3 4 6. 

The hippocampus is also responsible for mood regulation, and impaired nerve function in this important region of the brain can lead to emotional dysregulation and even social anxiety 3.

The good news is that your brain is highly resilient and adaptable, and it is completely possible to regain your memory and heal your hippocampus. Studies show that exercise can help reverse age-related shrinking of the hippocampus and improve memory, and these benefits likely apply to younger age groups, too 9 10. 

Engaging in regular physical activity and other activities that promote neuroplasticity can repair your neurons and get you back to feeling sharp as a tack.

The Toll of A Stressed Prefrontal Cortex

When stress targets the prefrontal cortex — located in the frontal lobe of the brain, beneath the forehead — it can lead to poor decision-making, decreased productivity, scattered attention, and emotional lability. 

You can think of the prefrontal cortex as the “aware” part of the brain that is responsible for making many of our conscious decisions and gets us through our day-to-day tasks, interactions, and work. If you have ever been upset but chose to “pick your battles” and brush it off, that was your prefrontal cortex hard at work. 

When high levels of cortisol overload the prefrontal cortex, we can experience 1 11 12:

• “Burnout”
• Performance anxiety
• Emotional overreaction
• Decreased attention and focus
• Lowered motivation
• Confusion
• Decreased performance
• Perfectionism

Between these effects and amygdala activation, this is why it can be incredibly difficult to make logical decisions in a stressful situation, no matter how “rational” you normally are. 

If you are familiar with attention deficit hyperactivity disorder (ADHD), some of the above symptoms likely sound familiar, and it turns out that chronic stress does strongly mimic this condition. To be clear, there are a lot of factors that contribute to ADHD, but chronic stress, including childhood stress, is strongly implicated in its development 13. 

A 2016 meta-analysis with 1,829 participants showed that laboratory-induced stress led to decision-making that was not self-serving, with a greater emphasis on reward and pleasure-seeking 14.

So how does this show up in real life? When you are chronically stressed, sitting down to finish a project at work feels way more challenging than it used to, and you are far more susceptible to closing your computer and scrolling through social media instead. 

It also makes it harder to say “no” to things like sugar and alcohol, and is why chronic stress is tightly linked to these and other addictive behaviors. Dopamine is implicated in these “pleasure-seeking” behaviors, as chronic stress is known to cause fluctuations in this reward-related neurotransmitter 15.

The study also showed that the effects of stress were more likely to be debilitating when facing a “processive” stressor, otherwise known as an emotional stressor, like fear 14. Along with dysregulating the amygdala and hippocampus, this means that stress can really take a toll on your ability to self-regulate after experiencing strong and/or painful emotions. 

The Vicious Cycle of Stress

Our prefrontal cortex is also partly responsible for our expectations of how we will react to stress. A 2020 clinical trial showed that those who expected to deal with stressful challenges well had a lower physiological response to stress, marked by lower cortisol secretion and better parasympathetic nervous system tone 16. 

Those who expected to handle stress poorly had a greater stress response, which (as we know) can have further negative effects on the brain, and continue the cycle of feeling like you can’t cope with challenging experiences. The authors hypothesized that this anticipation of stress is implicated in developing stress-related disorders, which include 11:

• General anxiety disorder (GAD)
• ADHD
• Obsessive-compulsive disorder (OCD)
• Major depressive disorder
• PTSD
• Bipolar disorder
• Panic disorder 
• Alzheimer’s disease
• Headaches

As mentioned above, limbic retraining is a great way to regulate your response to these emotional stressors, and the emotional freedom technique (EFT) can help your prefrontal cortex regain control. It can positively shift your focus and help you stop this cycle.  

To combat the cognitive effects of chronic stress, brain training exercises and other forms of mental stimulation have been shown to boost mental function and improve memory. Many, like learning a new skill, can be done at home and at no or low cost. 

A “Leaky” Blood-Brain Barrier

The blood-brain barrier (BBB) is the cellular wall that separates the brain from the rest of the body, and it closely regulates which substances can cross into the brain. And for good reason, as many normal metabolites and other molecules that float around the bloodstream are highly toxic to the brain, and can even cause neuronal death 17. 

When we are stressed, this lining becomes inflamed and weakened, creating gaps in the tight junction between cells (if you are thinking of leaky gut, you are on the right track). These “leaks” allow for particles that would otherwise be blocked from entering the brain to pass through uninhibited, leading to inflammation in the brain, known as neuroinflammation. 

Psychological stress can cause a leaky blood-brain barrier, but it’s physical stress that can significantly weaken the BBB and increase inflammation levels in the body. Common stressors that are linked to a leaky barrier include 17:

• Chronic pain
• Autoimmunity
• Alcohol abuse
• Traumatic brain injuries (TBI)
• Chronic infections
• Chronic inflammation 
• Leaky gut syndrome
• Gut dysbiosis
• High blood glucose and diabetes

Top Neuroinflammation Triggers

When the blood-brain barrier is weakened, all bets are off as really anything can freely pass into the brain. However, there are some specific top contenders that are linked to the detrimental effects of neuroinflammation that include brain fog, poor cognition, mental health disorders, and neurodegenerative diseases.

Remember glutamate from earlier? The blood-brain barrier prevents excess levels of glutamate, often a result of eating certain foods, from entering the brain. When the barrier is compromised, it passes through to the nervous tissue where it exerts its toxic effects on the structures of the brain 17. 

Xenobiotics are foreign chemicals, like pesticides, that can travel to the brain and wreak havoc on your nervous system after being consumed with food (namely produce) 18. Plastics, found in the water supply, and synthetic fragrances also fall into this category, and while they may not be an issue for everyone, they can cause brain inflammation in those with a weakened BBB.

Lipopolysaccharide (LPS) is a toxic metabolite produced by the gut microbiome. In the presence of dysbiosis (a gut flora imbalance), it can contribute to developing leaky gut syndrome. From there, it then passes into the bloodstream, where the rest of the body recognizes it as foreign, triggering an immune response. When it encounters the blood-brain barrier, it can cause a leaky blood-brain barrier and neuroinflammation, once it slips into the brain 18.

A leaky blood-brain barrier and neuroinflammation are implicated in many different health conditions, such as 17 18:

• Poor cognition
• Alzheimer’s disease
• Anxiety
• Autism
• Seizures
• Multiple sclerosis
• Stroke
• Parkinson’s disease 
• Huntington’s disease
• Amyotrophic lateral sclerosis (ALS)
• Depression

Lowering inflammation levels in your body is one of the best ways to heal the BBB and lower inflammation in the brain. Below you’ll find a few therapies that can help get you started on your journey to better brain health.

Get Back to the Low-Stress Life You Deserve

A stressed brain is overwhelming, but there are a plethora of ways that are available to you to help stop this cycle. As mentioned above, limbic retraining, EFT, mental stimulation (there’s never been a better time to finally start a hobby), and exercise are great ways to break free from your stress. 

Walking in nature (if you have access) can be a huge help, and if you live in a more urban setting consider adopting a plant so you can dig your hands into some dirt. If keeping a plant alive feels more stressful than helpful, research shows that “digital nature” is the next best thing. Looking at pictures of flowers, green landscapes, and wooden materials can lower your stress response and decrease fatigue 19.

Treating any co-existing conditions like PTSD and anxiety through therapies like EMDR (eye movement desensitization and reprocessing), EFT, and/or cognitive behavioral therapy is important, as is reaching out to a healthcare professional for medication-based support, if you need it.

Targeting inflammation can heal a leaky gut, a leaky blood-brain barrier, and restore the stress response. An anti-inflammatory diet is the crux of getting widespread inflammation and a distressed microbiome under control, as it cuts out common food sensitivities (think dairy, gluten, sugar, alcohol, etc.). I find that my clients routinely respond well to a Paleo-style elimination diet, and the good news is that it doesn’t mean cutting out your favorite foods for life. It typically takes just 3–4 weeks to see results, making diet a fundamental addition to any stress management plan.

Lastly, probiotics are an excellent way to lower inflammation and heal the gut flora and lining, preventing the toxic cascade that leads to a leaky BBB and dysregulated stress response. Research shows that these therapeutic organisms can lower anxiety, stress, and depressive symptoms 20 21, which makes them an effective and safe way to reduce the effects of stress on the brain.

The Effects of Stress on the Brain: Stop the Cycle

The effects of stress on the brain can be debilitating, but don’t have to be permanent. You can regain your cognitive function, including your memory, and your emotional health by addressing your stress levels and healing the changes to key areas of your brain. 

Reach out to the Ruscio Institute for Functional Health for help with your brain health, or check out my book, Healthy Gut, Healthy You, for a DIY approach to healing your gut that can lower inflammation and help heal your nervous system.

The Ruscio Institute has developed a range of high-quality formulations to help our clients and audience. If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you. The information on DrRuscio.com is for educational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.