Definition and Overview
Stress is a biological defense response that the body activates to maintain homeostasis against threats from the external environment or internal pressure. Since Hans Selye first proposed the concept of general adaptation syndrome in 1936, stress response has been studied as a core topic in neuroendocrinology and autonomic medicine.
There are two key pathways for the stress response. One is the hypothalamic-pituitary-adrenal axis (HPA axis), which controls cortisol secretion, and the other is the sympathetic-adrenomedullary axis (SAM axis), which is responsible for the secretion of epinephrine and norepinephrine. These two axes are closely interconnected and have a direct impact on the balance of the autonomic nervous system.
In acute stress, activation of the autonomic nervous system is a normal response essential for survival. However, when stress becomes chronic, overactivity of the sympathetic nervous system persists and parasympathetic (vagus) nerve function is suppressed, resulting in autonomic imbalance. This imbalance is directly linked to cardiovascular disease, metabolic abnormalities, decreased immune function, and mental health problems.
Physiology of the Stress Response
HPA axis (hypothalamic-pituitary-adrenal axis)
When a stress stimulus is transmitted to the brain, corticotropin-releasing hormone (CRH) is secreted from the paraventricular nucleus of the hypothalamus. CRH stimulates the anterior pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream, and ACTH promotes cortisol synthesis in the adrenal cortex.
Cortisol functions to raise blood sugar levels, promote protein and fat breakdown, and regulate immune responses. Normally, when blood cortisol concentration rises, a feedback signal is sent to the hypothalamus and pituitary gland to suppress HPA axis activity. This negative feedback must operate properly for the stress response to be properly terminated.
In chronic stress, this feedback mechanism is slowed down, causing cortisol to remain at a persistently high level. Chrousos (2009), a flattening of the diurnal cortisol rhythm is observed in approximately 40-60% of patients with chronic stress.
SAM axis (sympathetic-adrenomedullary axis)
The SAM axis is a pathway that responds faster than the HPA axis. When a stress stimulus reaches the hypothalamus, the sympathetic nerves are activated within seconds, and epinephrine and norepinephrine are released into the bloodstream from the adrenal medulla.
Epinephrine causes the classic fight-or-flight response, including increased heart rate, increased blood pressure, bronchodilation, dilated pupils, and increased blood sugar through glycogen breakdown in the liver. Norepinephrine mainly plays a role in constricting peripheral blood vessels and maintaining blood pressure.
Activation of the SAM axis simultaneously suppresses the activity of the parasympathetic nerve (vagus nerve). This switch between sympathetic and parasympathetic is the direct cause of the decrease in heart rate variability (HRV) during stress response.
Interaction of Cortisol and Epinephrine
The HPA axis and SAM axis do not operate independently but work synergistically with each other. Cortisol amplifies the effects of epinephrine and norepinephrine by increasing the sensitivity of catecholamine receptors in sympathetic nerve terminals. Conversely, sympathetic nerve activation stimulates CRH secretion, forming a positive feedback loop that further activates the HPA axis.
This synergistic interaction enables efficient coping in acute stress situations, but becomes a vicious cycle mechanism that further intensifies autonomic imbalance in chronic conditions.
Acute stress and autonomic nervous system: normal response
The acute stress response is an adaptive mechanism essential for survival. When faced with sudden danger, the hypothalamus activates the sympathetic nervous system within seconds, followed by the HPA axis. The physical changes that occur at this time are as follows.
The heart rate increases from 60 to 80 beats per minute to over 100 to 120 beats per minute, and systolic blood pressure rises by 20 to 30 mmHg. Breathing becomes faster, the bronchi expand, oxygen supply increases, and blood flow is concentrated to the skeletal muscles. At the same time, digestive functions and immune responses are temporarily suppressed.
These changes return to normal within minutes to tens of minutes as the parasympathetic nerve (vagus nerve) becomes dominant again when the threat disappears. A healthy autonomic nervous system makes this transition fluidly, and this flexibility is reflected in HRV levels.
Thayer and Lane (2009) suggested that the flexibility of the autonomic nervous system is directly related to the top-down regulatory function of the prefrontal cortex in the neurovisceral integration model. People with high HRV have excellent prefrontal function and good emotional control abilities.
Chronic stress and autonomic nerve damage
Allostatic Load
McEwen (2007), the concept of allostatic load explains the process by which chronic stress causes cumulative damage to the body. Allostasis is an adaptive process in which the body adjusts physiological parameters in response to stress. However, if this adjustment continues for a long period of time, the adjustment system itself wears out and allostatic load accumulates.
Key indicators of allostatic load include flattening of the cortisol circadian rhythm, lower HRV, increased resting heart rate, increased blood pressure, abdominal obesity, and increased insulin resistance. According to McEwen's study, the risk of cardiovascular events was two to three times higher in the group with an allostatic load score in the top 25%.
HRV decline
The autonomic indicator that changes most sensitively in chronic stress is heart rate variability (HRV). HRV measures small fluctuations in the time interval between heart beats and reflects the flexibility and adaptive capacity of the autonomic nervous system.
Lucini et al. (2002) analyzed healthy adults exposed to chronic workplace stress, and found that the low-frequency/high-frequency ratio (LF/HF ratio) of the stress group was significantly higher than that of the control group, indicating dominance of the sympathetic nerve and inhibition of the parasympathetic nerve. In the study, the HRV high frequency component (HF power) of the chronic stress group decreased by about 30% compared to the control group.
Thayer and Sternberg (2006) reported that low HRV is not only a result of chronic stress but also an independent predictor of future cardiovascular disease, depression, and increased mortality.
Fixation of sympathetic overactivity
If chronic stress persists, the sympathetic nervous system becomes stuck in an overactive state. During this process, norepinephrine secretion from sympathetic nerve terminals increases, and epinephrine secretion from the adrenal medulla remains higher than the basal level.
When sympathetic nerve hyperactivity persists, heart rate rises, blood pressure rises, and peripheral vascular resistance increases even at rest. Brosschot et al. (2010) reported that this phenomenon is maintained not only by conscious worry but also by unconscious rumination (unconscious perseverative cognition). In other words, even after the stressful situation ends, sympathetic nerve activity continues as the brain unconsciously processes threat-related information.
According to this study, heart rate and blood pressure remained significantly higher than baseline even during times when subjects did not subjectively perceive stress, and this was observed for a significant portion of the day (including sleep time in some subjects).
stress-related symptoms
Autonomic imbalance caused by chronic stress causes symptoms throughout various organs throughout the body. This is because the autonomic nervous system regulates almost all body functions, including cardiovascular, breathing, digestion, and immunity.
cardiovascular symptoms
Palpitations are common due to sympathetic nerve overactivity. Resting heart rate continues above 90 beats per minute, or sudden heart rate fluctuations occur repeatedly. Blood pressure also becomes unstable, and some patients complain of dizziness due to poor blood pressure control when standing.
digestive symptoms
When the sympathetic nerve becomes dominant in a state of stress, movement and secretion of the digestive tract are suppressed. Gastrointestinal blood flow decreases and gastric acid secretion control becomes unstable, causing heartburn, abdominal distension, decreased appetite, and symptoms similar to irritable bowel syndrome (IBS). It is reported that approximately 40-60% of patients with chronic stress are accompanied by functional digestive symptoms.
sleep disorder
Sympathetic overactivity reduces sleep quality. When the circadian rhythm of cortisol is disturbed, cortisol remains high at night, making it difficult to fall asleep and frequent awakenings during sleep. In polysomnography of patients with chronic stress, the rate of deep sleep (slow wave sleep) is reduced, and the index of sympathetic nerve activity during sleep is higher than that of normal controls.
Headache and musculoskeletal symptoms
If chronic tension persists, the tension in the neck and shoulder muscles increases, and tension-type headaches recur. Constriction of scalp and neck blood vessels due to sympathetic nerve overactivity also contributes to the occurrence of headaches.
changes in immune function
Cortisol has an immunosuppressive effect. Cortisol, which is continuously elevated from chronic stress, reduces the activity of natural killer cells and disrupts the regulation of inflammatory cytokines. As a result, a paradoxical situation arises in which the person becomes vulnerable to infection while maintaining a chronic inflammatory state.
Diagnosis and Evaluation
Autonomic imbalance caused by stress is evaluated by combining several indicators rather than being diagnosed with a single test.
Heart rate variability (HRV) analysis
HRV analysis is a key tool for assessing autonomic balance. The variation of R-R interval in ECG is interpreted by time domain analysis (SDNN, RMSSD) and frequency domain analysis (LF, HF, LF/HF ratio). The RMSSD and HF components reflect parasympathetic (vagal) activity, and the LF/HF ratio reflects sympathetic-parasympathetic balance.
Typically observed in patients with chronic stress are decreased SDNN, decreased RMSSD, decreased HF power, and increased LF/HF ratio. Thayer (2009), the overall mortality rate in the group with low HRV was about 32-45% higher than in the group with high HRV.
Cortisol test
A salivary cortisol test is performed four times a day (immediately after waking up, in the morning, afternoon, and before bedtime) to check the circadian rhythm of cortisol. Normally, cortisol peaks 30 to 45 minutes after waking and reaches its lowest level at night, but under chronic stress, this fluctuation decreases and levels out overall.
Stress Questionnaire Assessment
Quantify subjective stress levels using the Perceived Stress Scale (PSS), stress response scale, and burnout assessment tool. These survey results are interpreted together with objective indicators such as HRV and used to determine the degree of autonomic imbalance and treatment direction.
standing tilt test
If dysregulation of the autonomic nervous system due to stress is suspected, a tilt table test can be performed. This test evaluates the ability of the autonomic nervous system to respond to changes in position and helps differentiate between orthostatic hypotension and postural orthostatic tachycardia syndrome (POTS).
Treatment and Management
Treatment of autonomic imbalance caused by stress aims to suppress sympathetic nerve overactivity and restore parasympathetic (vagus) function. Non-pharmacological treatment is primarily recommended, and drug treatment and neuromodulation treatment are combined as needed.
breathing training
Slow breathing is the most accessible way to increase parasympathetic nerve activity by directly stimulating the vagus nerve. If you breathe 6 times per minute (inhalation 4-5 seconds, exhalation 5-6 seconds) for 10-15 minutes a day, the HF component of HRV significantly increases. This breathing frequency corresponds to the resonance frequency of the cardiovascular system, maximizing the efficiency of autonomic nervous system control.
regular exercise
Moderate aerobic exercise is a treatment with a strong basis for restoring autonomic balance. If you continue 30-60 minutes of aerobic exercise (brisk walking, jogging, swimming, cycling) 3-5 times a week for more than 12 weeks, a decrease in resting heart rate, an increase in HRV, and normalization of cortisol circadian rhythm are observed.
However, excessive high-intensity exercise can actually worsen sympathetic nerve overactivity, so it is recommended to start at 60-70% of maximum heart rate and gradually increase intensity.
Cognitive Behavioral Therapy (CBT)
Cognitive behavioral therapy (CBT) is a structured psychotherapy that recognizes and corrects thinking patterns and behavior patterns that cause stress. Brosschot et al. (2010) reported that it is effective in blocking continuous sympathetic nerve activation caused by unconscious rumination, and improvement in HRV and reduction in cortisol levels were reported after treatment.
biofeedback
HRV biofeedback is a method of training your autonomic nervous system control ability while monitoring your heart rate variability in real time. Patients control breathing and relaxation while watching HRV data displayed on the screen, thereby strengthening their autonomic nervous system's self-regulation ability.
HRV biofeedback training combined with resonance frequency breathing shows significant improvement in HRV after 10 to 20 sessions and is also reported to be effective in reducing stress-related symptoms.
Neuromodulation treatment
Vagus nerve stimulation (VNS) is a neuromodulation treatment that directly strengthens parasympathetic nerve function. Transcutaneous VNS increases parasympathetic nerve activity by non-invasively stimulating branches of the vagus nerve in the ear or neck.
In addition, brain stimulation techniques such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are being studied as ways to strengthen the prefrontal cortex-autonomic nerve connection.
life guide
The following lifestyle guidelines are recommended to prevent and manage autonomic imbalance caused by stress.
Sleep management is basic. Go to bed and wake up at the same time every day to maintain a consistent sleep-wake rhythm. Seven to eight hours of sleep is recommended, and it is helpful to reduce exposure to smartphones and computer screens two hours before bedtime.
Dietary management also affects autonomic balance. Limit caffeine intake to 200 mg or less (less than 2 cups of coffee) per day, and reduce or stop alcohol as it disrupts autonomic nervous system regulation. A diet rich in omega-3 fatty acids and magnesium helps maintain vagus nerve function.
Social connections also contribute to autonomic health. Conversations and emotional interactions with trusted people promote the secretion of oxytocin and increase vagus nerve activity. Conversely, social isolation is known to be a risk factor for sympathetic overactivity.
Activities in natural environments are also effective. It has been reported that spending more than 20 minutes in a forest or park significantly reduces cortisol levels and increases parasympathetic nerve activity.
Lastly, you need to get into the habit of regularly checking your stress level. If symptoms such as palpitations, indigestion, and insomnia persist for more than two weeks, it is advisable to undergo an autonomic nerve function test to objectively check the condition.
Information on Osang Neurosurgery
At Osang Neurosurgery, neurologists and neurosurgeons examine autonomic nervous system dysfunction and develop individual treatment plans based on the results and symptoms of heart rate variability (HRV) analysis, standing tilt test, and comprehensive evaluation of autonomic function.
We provide evidence-based treatments such as breathing training guidance, HRV biofeedback, and neuromodulation therapy, and operate an integrated stress management program including cognitive behavioral therapy and exercise prescription when necessary.
Inquiries: Osang Neurosurgery 1599-5453 | osns.co.kr
---
This information is provided for medical educational purposes and is not a substitute for individual medical care or treatment. If you have any symptoms, be sure to seek professional advice.