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The Great Resignation: Brain Chemicals and Employee Burnout


Making sure your brain chemicals (neurotransmitters) are in a balanced state is critical to mental health and happiness. These chemicals can get thrown off balance by mental stress and leave you less able to cope with challenges at work. Imbalanced neurotransmitters can also leave you feeling sad, irritable, or unmotivated.

According to science, an imbalance in these brain chemicals is linked to employee burnout, a subject that’s gotten a lot of attention lately due to The Great Resignation. We’ll talk more about the science of burnout and brain chemicals later in this article. First, let’s talk about The Great Resignation, what it is, and why it’s been happening.


What Is The Great Resignation?

 Beginning in 2021, a phenomenon began where millions of employees left their jobs. The rate that employees were leaving their jobs was far higher than in the past.1 This mass exodus became known as The Great Resignation, or, as some people call it, the Big Quit.

The “quits rate” started soaring in spring 2021 with 19 million workers quitting their jobs between March and July, which is 7 million more employees than the same time the previous year.1 The quits rate first hit an all-time high in August when 4.3 million people left their jobs.2 That record broke in November 2021 when 4.5 million workers quit that month alone.3


Why Employees Leave Their Jobs

 Employees cite a number of reasons why they switched jobs, but burnout is on top of the list. A survey by Limeade, an employee well-being company, asked 1,000 full-time workers in the U.S. at companies that have 500 or more employees why they switched jobs.1 Burnout was the biggest reason for leaving their jobs. Here’s how the numbers played out:

  • Burnout (40%)
  • Company experiencing organizational changes (34%)
  • Lack of flexibility (20%)
  • Discrimination (20%)
  • Contributions and ideas undervalued (20%)
  • Not enough benefits (19%)
  • Company not supportive of well-being (16%)

Some people argue that burnout isn’t actually the cause of The Great Resignation; it’s simply what happens when a corporate culture isn’t supportive of an employee’s mental health. And many of the factors listed above, such as lack of flexibility and not feeling as if your contributions and ideas are valued, can play a major role in developing burnout. However, even if burnout is the end result of a flawed corporate culture, it’s still the primary reason why employees say they quit.

The COVID-19 pandemic has caused employees even more stress than usual. It has compounded the job-related feelings of burnout, which may have contributed even more to the large number of people quitting their jobs. With more employees working from home during the pandemic, they began to appreciate work-life balance more, and when their employers called them back into the office to work, they sought jobs where they had more flexibility to work at home.


What Is Burnout and What Are The Symptoms?

According to the World Health Organization (WHO), burnout is considered an “occupational phenomenon” and isn’t classified as a medical condition.4 It results from workplace stress that hasn’t been successfully addressed.

The symptoms of burnout include:

  • Fatigue or exhaustion
  • Feeling mentally detached from your job
  • Negativity or cynicism about your job
  • Reduced job efficiency

The WHO definition specifies that burnout only refers to workplace burnout and shouldn’t be used in other areas of life.


The Brain on Burnout

Job burnout is associated with an imbalance in brain neurotransmitters, hormones, and other molecules linked to excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis.5 The HPA axis governs your body’s stress response and the production of the stress hormone cortisol. This is the fight-or-flight hormone that sends you into action when you feel you are in danger.

If the HPA axis isn’t working properly, your adrenal glands will produce either too much or too little cortisol. For example, people who are burned out often have elevated cortisol levels in the morning, compared with healthy controls.6

  • Mental stress also causes a long-term imbalance in the neurotransmitters norepinephrine, dopamine, and serotonin.7 Each of these plays a role in helping the body cope with stress:7
  • Increased levels of norepinephrine cause a stressed person to shift focus from processing information to a more general overview of the environment.7 This helps the individual come up with more effective solutions for relieving stress.
  • Dopamine, which is released in the prefrontal cortex of the brain, helps a stressed person assess risks and make decisions.7
  • Serotonin plays a critical role in reducing post-stress anxiety.7

These brain chemicals help you come up with effective behavioral strategies to cope with the initial phase of a stressful event. However, if these brain chemicals are imbalanced, your ability to cope with stress diminishes and burnout ensues. One study of burned out medical workers found that exhaustion was linked to imbalanced levels of serotonin, dopamine, norepinephrine, and acetylcholine.8

Research in rats under stress found a significant decline in dopamine and γ-aminobutyric acid (GABA) and increased serotonin and glutamate.8 In addition, there’s a relationship between reduced serotonin and psychological stress and mood complaints.8  Stress can lead to an imbalance between excitatory (norepinephrine dopamine, glutamate) and inhibitory neurotransmitters (GABA and serotonin).8


How To Stop Being Burnt Out

Of course, if your job is stressing you out, changing your line of work may be a good solution. However, if you have a reason to stay or if you want to prevent the same burnout from happening in your next place of employment, consider working with your doctor to get your neurotransmitter levels assessed. Ordering neuroendocrine lab testing from Sanesco is a great first step to finding out where potential imbalances may be.

Once you’ve determined which neurotransmitters are off kilter, you can work with your healthcare provider to get things back in balance. Patients who work with their healthcare provider to balance neurotransmitters may experience improved energy, increased focus, and better memory. They also may cope better with the stressors of daily life.

Using this approach, the next time you face a lot of stress on the job you’ll be more resilient and ready to face challenges.



  1. Limeade. Published 2022.
  2. World Economic Forum. Published 2021.
  3. World Economic Forum. Published 2022.
  4. World Health Organization. Published 2019.
  5. Tao N, Zhang J, et al. Int J Environ Res Public Health. 2015;12(12):15154-15161.
  6. De Vente W, Olff M, et al. Occup Environ Med. 2003;60 Suppl 1(Suppl 1):i54-61.
  7. Joëls M, Baram TZ. Nat Rev Neurosci. 2009;10(6):459-466.
  8. Yao Y, Zhao S, et al. J Int Med Res. 2018;46(8):3226-3235.






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Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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Inhibitory Neurotransmitter


One of our feel-good neurotransmitters; Low levels of serotonin may relate to occasional symptoms like moodiness, sleep issues, and carb cravings.