Grief-enhanced Trauma-informed Care process(GTC)Grief-enhanced Trauma-informed Care process(GTC)

 

Other Markers For Traumatic Stress And Grief- PNI

Psychoneuroimmunology (PNI) investigates the bidirectional interactions between the

nervous, immune, and endocrine systems, especially under conditions of traumatic stress. In

individuals with traumatic stress disorder (e.g., PTSD), dysregulation in these systems leads

to measurable biological markers.

Main Key Points

Traumatic Stress and Immune Response:

Chronic or acute traumatic stress activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, leading to increased production of stress hormones. Persistent activation suppresses immune function, increasing vulnerability to infections and inflammatory conditions.

Impact of Grief on Immunity:

Grief, especially prolonged or complicated grief, is associated with elevated stress hormone levels, which can impair immune responses. Bereaved individuals may exhibit decreased natural killer (NK) cell activity and altered cytokine profiles, affecting overall health.

Inflammation and Psychological Distress:

Both traumatic stress and grief can contribute to chronic inflammation, mediated by overproduction of pro-inflammatory cytokines. Chronic inflammation is linked to conditions such as cardiovascular disease, autoimmune disorders, and depression.

In individuals with PTSD, the nervous system is in a prolonged state of hyperactivation. The hypothalamic-pituitary-adrenal (HPA) axis, a key component of the endocrine response to stress, becomes dysregulated, often resulting in abnormal cortisol levels. Cortisol, a hormone that helps regulate the immune response, is often blunted or erratic in PTSD, impairing its ability to modulate inflammation. This dysregulation contributes to heightened inflammatory responses, which have been linked to chronic diseases such as cardiovascular disorders, autoimmune conditions, and metabolic dysfunction.

The immune system also exhibits notable changes in PTSD. Elevated levels of inflammatory markers, such as C-reactive protein (CRP), interleukins (e.g., IL-6), and tumor necrosis factor-alpha (TNF-α), are commonly observed in individuals with PTSD. These markers reflect a pro-inflammatory state that not only affects physical health but also feeds back into the nervous system, exacerbating symptoms such as hypervigilance, fatigue, and cognitive impairments. This bidirectional relationship between the immune system and the nervous system exemplifies the principles of PNI.

PNI provides a framework for understanding how the biological markers of PTSD can inform treatment and intervention strategies. For example, persistent inflammatory states in PTSD may contribute to the brain’s inability to properly regulate mood and memory, particularly in regions such as the hippocampus and amygdala. These changes reinforce the cycle of trauma-related memories and emotional reactivity. Additionally, the autonomic nervous system, which governs the “fight or flight” response, becomes hypersensitive in PTSD, further fueling immune dysregulation and endocrine imbalances.

1. Neuroendocrine Markers

  • Cortisol
    • Cortisol is a glucocorticoid released from the adrenal cortex via activation of the hypothalamic-pituitary-adrenal (HPA) axis. In traumatic stress, cortisol levels can be abnormally low or show a flattened diurnal rhythm due to feedback dysregulation in the HPA axis. A PTSD patient may exhibit suppressed cortisol levels, indicating a maladaptive stress response.
  • DHEA (Dehydroepiandrosterone)
    • DHEA acts as a counter-regulatory hormone to cortisol, providing resilience to stress. An imbalanced cortisol/DHEA ratio is observed in individuals with traumatic stress(Grossman et al., 2004). Veterans with PTSD often exhibit lower DHEA levels compared to controls.

2. Immunological Markers

  • Pro-inflammatory Cytokines:
    • Cytokines such as IL-6, IL-1β, and TNF-α are immune signaling molecules. Chronic traumatic stress can upregulate these cytokines, indicating systemic inflammation. Elevated IL-6 levels in trauma survivors are linked to hyperarousal symptoms in PTSD.
  • C-reactive Protein (CRP)
    • CRP is a marker of systemic inflammation produced by the liver in response to cytokines like IL-6. Increased CRP levels are associated with higher symptom severity in PTSD, and increased cardiovascular risk.

3. Neuroimmune Markers

  • Microglial Activation
    • Microglia, the brain’s immune cells, play a critical role in synaptic pruning and neuroinflammation. Persistent microglial activation contributes to neural inflammation and cognitive dysfunction in PTSD.

4. Neurobiological Markers

  • Brain-Derived Neurotrophic Factor (BDNF)
    • BDNF supports neuronal survival, plasticity, and repair. PTSD patients often exhibit reduced BDNF levels, which may impair hippocampal neurogenesis and memory consolidation.
  • Amygdala-PFC Connectivity
    • The amygdala processes fear, while the prefrontal cortex (PFC) regulates emotional responses. Traumatic stress leads to hyperactive amygdala responses and weakened PFC-amygdala connectivity.

5. Epigenetic Markers

  • DNA Methylation of FKBP5
    • FKBP5 is a co-chaperone protein involved in HPA axis regulation. Trauma-associated epigenetic changes in the FKBP5 gene lead to altered stress hormone signaling. PTSD patients show hypermethylation of FKBP5 promoter regions, modulating glucocorticoid receptor sensitivity.

6. Gene Expression Markers- Social Transcriptional Gene Expression (STGE)

  • Pro-inflammatory Gene Expression
    • upregulation of genes encoding pro-inflammatory cytokines such as IL1B, IL6, and TNF. Chronic activation of the sympathetic nervous system increases norepinephrine release, binding to β-adrenergic receptors on immune cells, and enhancing transcription of inflammatory genes. Trauma-exposed individuals show higher transcription of pro-inflammatory genes, correlating with PTSD severity.
  • Antiviral Gene Suppression
    • downregulation of interferon-related genes (e.g., IFNB1) leads to weakened antiviral defenses. Cortisol from prolonged HPA-axis activation binds glucocorticoid receptors, suppressing type I interferon gene transcription. Trauma survivors exhibit suppressed interferon-stimulated genes, increasing susceptibility to infections.
  • Glucocorticoid Resistance
    • Altered expression of glucocorticoid receptor-related genes like NR3C1, impairing cortisol-mediated immune regulation. Chronic trauma decreases sensitivity of immune cells to glucocorticoids, perpetuating inflammation. PTSD patients display reduced glucocorticoid receptor activity in peripheral blood mononuclear cells (PBMCs), maintaining a pro-inflammatory state.

References

1. Yehuda, R., et al. (1995). Low urinary cortisol excretion in PTSD. Biological Psychiatry.

2. Grossman, R., et al. (2004). The cortisol/DHEA ratio as a marker of resilience. Endocrinology Journal.

3. Pace, T. W., & Heim, C. M. (2011). PTSD, inflammation, and cytokines. Psychoneuroendocrinology.

4. Gola, H., et al. (2013). Inflammation and PTSD: Elevated IL-6. Journal of Affective Disorders.

5. Logan, D., et al. (2021). Microglial activation in PTSD. Neuro Image: Clinical.

6. Krystal, J. H., et al. (2019). BDNF in PTSD. Neuroscience Research.

7. Etkin, A., & Wager, T. D. (2007). Amygdala and PFC in PTSD. Archives of General Psychiatry.

8. Zannas, A. S., et al. (2015). Epigenetic regulation of FKBP5 in PTSD. Nature Communications.

9. Cole, S. W. (2013). Social regulation of human gene expression. Current Directions in Psychological Science.

10. Miller, G. E., et al. (2008). Glucocorticoid resistance in PTSD. Biological Psychiatry.

11. Hagenaars, M. A., et al. (2014). Freezing behavior in PTSD. Journal of Anxiety Disorders.

12. Germain, A., et al. (2008). Sleep disturbance and motor activity in PTSD. Journal of Traumatic Stress.

13. Powell, N. D., et al. (2019). Social stress and antiviral gene suppression. Psychoneuroimmunology Review.

14. Zannas, A. S., et al. (2015). Epigenetic regulation in trauma. Nature Communications.