The relationship between chronic stress and neurological health

By Alissa Sofia Maria Bocance

Introduction

Hans Selye, a Canadian endocrinologist of Hungarian origin, known as the "father of stress research”, defines stress as the nonspecific general reaction of the body to external stressors. His concept aligns with ideas proposed by ancient philosophers. For example, the Greek philosopher Epictetus asserts, "People are not disturbed by things, but by the views they take of them." Modern research expands on these ideas, emphasizing the role of chronic stress in neurological health, particularly its impact on the hypothalamic-pituitary-adrenal (HPA) axis and systemic inflammation.

The hypothalamus plays a crucial role in regulating the body's homeostasis. Its neural networks contain information about our internal environment, which they compare to actual values. Its goal is to maintain homeostasis — the balance of our bodily systems. When it detects differences in monitored values, it reacts. Changes in the body's internal functions are initiated with the help of the HPA axis system or through the autonomic nervous system (ANS). The ANS controls the function of internal organs and smooth muscles. To do this, it uses the enteric, parasympathetic, and sympathetic nervous systems. At the same time, the hypothalamus not only controls these organs and muscles but also receives feedback from them through the ANS regarding their current state.

At the core of the stress response is the hypothalamic-pituitary-adrenal axis (HPA), which plays a central role in regulating cortisol release, the main stress hormone. In chronic stress conditions, this axis remains constantly activated, leading to elevated cortisol levels in the blood. In the long term, excessive cortisol can damage neurons, particularly in the hippocampus, the region involved in memory and learning (Lupien et al., 2009). This explains why chronic stress is associated with cognitive disorders and difficulties in concentration, as prolonged exposure to cortisol can reduce hippocampal volume and affect cognitive functions (Sapolsky, 2000).

Inflammation and Neurological Health

Chronic stress activates the immune system, leading to low-grade systemic inflammation. Increased levels of pro-inflammatory cytokines such as IL-6 and TNF-α characterize this. In the brain, this inflammation can affect microglia function and the immune cells of the central nervous system, leading to the deterioration of neuronal connections and increasing the risk of neurodegenerative conditions such as Alzheimer's or Parkinson's disease (Perry et al., 2010).

The body's response to stress factors depends on the individual's objective evaluation of the situation and their capacity for adaptation. How a person responds to stressors varies depending on their personality traits, gender, age, life experiences, and even genetic factors. According to the Holmes and Rahe Stress Scale, the most stressful life events include the loss of a partner, divorce, separation, incarceration, job loss, or retirement. Among these, chronic stress stands out due to its long-term negative effects on health.

What is Chronic Stress?

Chronic stress refers to prolonged exposure to physiological, biological, or psycho-emotional stressors, often accompanied by a sense of being unable to escape a particular situation or context. The human body's response to stress factors occurs in three phases: the alarm stage, the resistance stage, and the exhaustion stage. In the presence of chronic stress, the body no longer has the resources to cope with demands which often leads to anxiety, insomnia, irritability, and decreased performance. Unlike acute stress, which can be beneficial in emergencies, chronic stress has significant negative consequences for overall health and the brain in particular (McEwen, 2004). Chronic stress generates both hormonal and psychological disturbances that can lead to burnout in advanced stages.

1. The HPA Axis and Overload on the Brain

First, what is HPA?

The abbreviation HPA stands for hypothalamic-pituitary-adrenal axis. It is one of the main neuroendocrine autoregulatory systems of the body. As its name suggests, the HPA axis involves connections between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus, mentioned first, is a small part of the mesenchyme. The hypothalamus plays a crucial role in regulating the body's homeostasis. Its neural networks contain information about our internal environment, which they compare to actual values. Its goal is to maintain homeostasis — the balance of our bodily systems.

When it detects differences in monitored values, it reacts. With the help of the HPA axis system or through the autonomic nervous system (ANS), changes in the body's internal functions are initiated. The ANS controls the function of internal organs and smooth muscles. To do this, it uses the enteric, parasympathetic, and sympathetic nervous systems. At the same time, the hypothalamus not only controls these organs and muscles, but also receives feedback from them through the ANS regarding their current state.

At the core of the stress response is the hypothalamic-pituitary-adrenal axis (HPA), which plays a central role in regulating cortisol release, the main stress hormone. In chronic stress conditions, this axis remains constantly activated, leading to elevated cortisol levels in the blood. In the long term, excessive cortisol can damage neurons, particularly in the hippocampus, the region involved in memory and learning (Lupien et al., 2009). This explains why chronic stress is associated with cognitive disorders and difficulties in concentration, as prolonged exposure to cortisol can reduce hippocampal volume and affect cognitive functions (Sapolsky, 2000).

2. Inflammation and Neurological Health

Chronic stress activates the immune system, leading to low-grade systemic inflammation. Increased levels of pro-inflammatory cytokines such as IL-6 and TNF-α characterize this. In the brain, this inflammation can affect the function of microglia and the immune cells of the central nervous system, leading to degeneration of neuronal connections and increasing the risk of neurodegenerative conditions such as Alzheimer's or Parkinson's disease (Perry et al., 2010).

3. Stress and Mental Health Disorders

Prolonged exposure to stress is closely linked to the development of psychiatric disorders such as anxiety, depression, and post-traumatic stress disorder (PTSD). The brain becomes hypersensitive to stress stimuli, and increased activity in the amygdala, the fear center, amplifies negative emotional reactions. At the same time, connections between the amygdala and the dorsolateral prefrontal cortex, which help regulate emotions, are weakened (Arnsten, 2009). This deregulation contributes to difficulties in decision-making and increased vulnerability to further stress.

4. Reduced Plasticity and Long-Term Effects

Chronic stress affects neuroplasticity, which is the brain's ability to form and reorganize neural connections. This negatively impacts learning and adapting to new situations. Additionally, it can contribute to reduced hippocampal volume and alter neuronal circuits involved in memory, decision-making, and emotion regulation.

5. Strategies for Protecting Neurological Health

Although the effects of chronic stress can be severe, numerous strategies can help minimize these impacts. To prevent the negative effects of chronic stress on neurological health, it is essential to adopt effective stress management strategies. These include:

Practicing meditation and mindfulness exercises: These reduce amygdala activity and enhance connections with the prefrontal cortex (Hölzel et al., 2011).

• Regular physical activity, which reduces inflammation and improves neuroplasticity: increases BDNF levels and stimulates neurogenesis (Cotman et al., 2007).

• Maintaining restorative sleep is essential for neuron repair and regeneration, as it plays a crucial role in diminishing the effects of stress on the brain. Conversely, sleep disturbances worsen these negative effects.(Walker, 2009).

• Creating a supportive social network and participating in recreational activities.

References

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2. Lupien, S. J., et al. (2009). Stress and the brain: From vulnerability to resilience. Nature Reviews Neuroscience, 10(6), 434–445.

3. Sapolsky, R. M. (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Archives of General Psychiatry, 57(10), 925–35.

4. Perry, V. H., et al. (2010). The impact of systemic inflammation on the brain. Nature Reviews Neuroscience, 11(2), 312–22.

5. Arnsten, A. F. T. (2009). Stress signaling pathways that impair prefrontal cortex structure and function. Nature Reviews Neuroscience, 10(6), 410–22.

6. Duman, R. S., et al. (1997). Neurobiology of depression: Stress, BDNF, and synaptic plasticity. Nature Medicine, 3(12), 1181–89.

7. Hölzel, B. K., et al. (2011). Mindfulness practice leads to increases in regional brain gray matter density. Psychiatry Research: Neuroimaging, 191(1), 36–43.

8. Cotman, C. W., et al. (2007). Exercise builds brain health: Key roles of growth factor cascades and inflammation. Trends in Neurosciences, 30(9), 464–72.

9. Walker, M. P. (2009). The role of sleep in cognition and emotion. Annals of the New York Academy of Sciences, 1156(1), 168–79.