The Silent Effects of Stress: How Trauma May Affect Our Biology

What if your worst childhood memories, hidden stress, and fears weren't just stored in your mind, but could also influence how your genes function? When you get sick, your doctor usually looks for a physical cause, such as a viral infection, a genetic issue, or a faulty cell. However, modern medicine is increasingly exploring how psychological stress can affect physical health through a field known as psychoneuroimmunology (PNI).

PNI explores how the mind, nervous system, and immune system interact, including through the hypothalamic-pituitary-adrenal (HPA) axis. This field provides biological evidence for a connection that health experts have been investigating for decades: emotional stress and physical health are closely linked.

Although many people believe that mental health is strictly “all in your head,” serious psychological stress, particularly childhood trauma and work-related stress, can have negative effects at the cellular level, influencing how our genes are expressed and how our immune cells behave. Ultimately, research into stress suggests that our environments and mental and emotional states can influence our bodies and affect our long-term health.

First, let's look at the epigenetics behind this process. Epigenetics is the study of how factors such as environmental conditions can influence gene activity without changing the underlying DNA sequence. Research suggests that childhood trauma may leave lasting epigenetic marks that influence how certain genes function.

On November 8, 2019, a study by Shui Jiang, Lynne Postovit, Annamaria Cattaneo, Elisabeth B. Binder, and Katherine J. Aitchison examined epigenetic modifications associated with childhood trauma, exploring how early-life experiences may be linked to changes in gene regulation.

Before exploring how chronic stress may influence gene activity, however, we need to understand what happens in the HPA axis during the stress response:

• When we experience stress, the brain's amygdala, which plays a role in processing threats and emotional responses, communicates with the hypothalamus, a region that helps maintain the body's internal balance, activating the HPA axis.

• The hypothalamus releases a hormone called corticotropin-releasing hormone (CRH), which signals the pituitary gland to release another hormone that stimulates the adrenal glands to produce cortisol.

• The cortisol released by the adrenal glands binds to glucocorticoid receptors in various tissues throughout the body.

• These receptors help regulate the stress response through a feedback mechanism that signals the brain to reduce further stress-hormone production.

When stress is chronic, severe, or occurs during critical periods of brain development, such as early childhood, this regulatory system may become disrupted. This is where epigenetics comes in. Chronic stress may influence enzymes in the nuclei of our cells called DNA methyltransferases (DNMTs). These enzymes add chemical tags called methyl groups to DNA, potentially affecting the activity of specific genes, including NR3C1.

Think of NR3C1 as an instruction manual for building glucocorticoid receptors, which help regulate the body's stress response. When methyl groups attach to particular regions of the NR3C1 gene, they can influence how actively that gene is expressed. Imagine it as partially covering the pages of an instruction manual: the information is still there, but the cell may have more difficulty accessing it. If NR3C1 expression decreases, the body may produce fewer glucocorticoid receptors, potentially making it harder to regulate the stress response.

When the stress-regulation system becomes disrupted, the body may also experience changes in immune function. A study by Helena Palma-Gudiel, Aric A. Prather, Jue Lin, Jake D. Oxendine, Jerry Guintivano, Kai Xia, David R. Rubinow, Owen Wolkowitz, Elissa S. Epel, and Anthony S. Zannas examined the relationship between HPA-axis regulation, chronic stress, and biological markers associated with physical health. The researchers used low-dose dexamethasone suppression tests (DSTs) to assess HPA-axis function in 57 chronically stressed women and a control group of 67 women who were not chronically stressed.

When examining the relationship between stress regulation and immune-related genes, the researchers investigated NR3C1 alongside two genes involved in inflammation: TNF (tumor necrosis factor) and IL6 (interleukin-6). TNF and IL-6 play important roles in the body's inflammatory response. They help coordinate immune activity, including the recruitment and activation of immune cells when the body needs to respond to injury or infection.

The problem arises when inflammatory responses become excessive or poorly regulated. TNF and IL-6 are involved in signaling pathways that help the body respond to threats, partly through proteins called pro-inflammatory cytokines. Under normal circumstances, these signals help coordinate the immune response. However, chronic stress may be associated with changes in inflammatory signaling, potentially contributing to prolonged inflammation even when there is no active infection.

This can create a situation in which the body's inflammatory response becomes poorly regulated. Over time, chronic inflammation may contribute to certain health problems, although the relationship between stress, immune function, and disease is complex. It is important to distinguish these changes from an autoimmune attack: inflammation does not automatically mean that the immune system is attacking the body's own organs.

Depending on the underlying biological and environmental factors, chronic stress may be associated with health conditions involving inflammation, including rheumatoid arthritis, lupus (systemic lupus erythematosus, or SLE), and psoriasis. However, these conditions have multiple contributing causes, and stress alone does not explain why they develop.

Ultimately, when we trace the connections between psychological distress and physical health, we can see that the mind and immune system are not two separate worlds, but parts of an interconnected system. When chronic, severe stress affects the body's regulatory processes, it may influence gene activity, hormonal signaling, and immune function. A response that once helped the body cope with a threat can become harmful when it remains activated for too long.

Although psychological stress can affect physical health, we must acknowledge that disease is multifactorial. Health is shaped by many influences, including genetics, environment, lifestyle, and access to medical care. Whether we are exploring how our social experiences influence our biology or investigating complex diseases, we need to look beyond symptoms alone. By understanding the whole person and the many factors that shape health, we can work toward a future in which care addresses both physical and psychological well-being.