This week in Immunology, we are discussing Adverse Childhood Events and the influence it has on the immune system. This module struck me deeply, as is inspired me to look more deeply at my own health history through the eyes of the functional medicine timeline. Having an autoimmune disease, I often wondered what the connection with my childhood was with the inflammation that has contributed to my disease. This information in this module was indeed eye opening.
Numerous studies have demonstrated that childhood adversities have the potential to increase the risk of many diseases that can increase the likelihood of premature mortality, due to increased levels of inflammation (Chen & Lacey, 2018). As we know, chronic inflammation is associated with increased risk of diseases such as autoimmune disease, cancer, and diabetes (Chen & Lacey, 2018). Having an autoimmune disease myself, I am always looking to dig deeper at my own root causes. I am not surprised that my childhood experiences could be playing a significant role. Being born in a first generation Middle Eastern family, there was much pressure put on me as a child in regards to cultural differences that affected me in many ways. Being repeatedly exposed to adverse childhood experiences (ACE) can affect the human stress regulatory system, which is accompanied by an increase in chronic inflammation. I recall as early as in my teens having trouble with managing stress. After I gave birth to my children, I felt as though my adrenals had “crashed” and was diagnosed with adrenal dysfunction at age 31. Chronic exposures to stress is associated with a dysregulation of the HPA axis and sympathetic adrenocortical axis, which are accompanied by increased inflammation. The chronic inflammation that results is associated with some of the underlying mechanisms of various illnesses, through activation of the immune system. In other worse, dysregulation of the HPA axis, induced by chronic inflammation, put me in a state of immune dysfunction. In FDN, this is called “Metabolic Chaos”. “The HPA axis is a powerful modulator of inflammatory activity and is in turn modulated by inflammatory processes, as well as being highly responsive to environmental adversities both in childhood and in adulthood” (Baumeister, Akhtar, Ciufolini, Pariante, & Mondelli, 2016).
Several previous studies have reported an association between childhood trauma and increased levels of pro-inflammatory markers, such as the acute phase protein C-reactive protein (CRP), and of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). This provides strong evidence that childhood traumatic events significantly impact on the inflammatory immune system, extending their influence into adult health (Baumeister et al., 2016). It was particularly interesting to note that childhood trauma can even lead to greater methylation of the glucocorticoid receptor (GR), which is correlated with reduced GR function as demonstrated by a negative feedback loop of the HPA axis (Baumeister et al., 2016). In addition, the increased inflammation can also impair GR function, leading to sustained GR resistance into adulthood. Moreover, the GR is crucial in regulating TNF-α signaling and TNF-induced cytokine production, as well as conveying protection against TNF-related tissue damage (Baumeister et al., 2016). It is apparent that dysregulation of the GR has far reaching impacts in regards to modulating inflammation.
Adverse childhood events can also contribute to metabolic syndrome. Depression is one of the drivers that can contribute to physiological changes associated with metabolic syndrome. In particular, depression can upregulate inflammatory processes that contribute to atherosclerosis, insulin resistance, and neurodegeneration (Danese et al., 2009). Depression has been linked to multiple biological abnormalities, including vascular pathologic changes, autonomic function changes, HPA axis dysfunction, and in particular, immune dysfunction. Depression is associated with increased numbers of circulating leukocytes and pro inflammatory cytokines such as interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-6 (IL-6). A hypothesis is that there is a positive feedback mechanism between depression and cardiovascular disease, as evidenced by increased levels of CRP in adulthood (which is often used to predict the development of cardiovascular disease). This is compounded by metabolic abnormalities such as obesity, dyslipidemia, glucose intolerance, and hypertension that exert bi-directional influences on hormone function that lead to hormone imbalances (Danese et al., 2009). “Many studies reported that the clinical depression can nearly double the risk of mortality and nonfatal cardiac events and that even subclinical elevations in depressive symptoms are related to a poorer prognosis in patients with established CVD” (Liu et al., 2017).
The progression is indeed bi-directional. Increased concentrations of pro inflammatory cytokines influence atherosclerotic plaque progression, poor lifestyle habits and sickness behavior. Poor lifestyle behaviors and sickness behavior can lead to an inactive depressed lifestyle that further heighten the risk of cardiovascular disease (Liu et al., 2017).
In regards to our role as clinical nutritionists, I think this is a great opportunity to education parents on the promotion of healthy psycho-social experiences for children as a potentially cost-effective strategy for the prevention of age-related disease.
Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V. (2016). Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-alpha. Mol Psychiatry, 21(5), 642-649. doi:10.1038/mp.2015.67
Chen, M., & Lacey, R. E. (2018). Adverse childhood experiences and adult inflammation: Findings from the 1958 British birth cohort. Brain Behav Immun, 69, 582-590. doi:10.1016/j.bbi.2018.02.007
Danese, A., Moffitt, T. E., Harrington, H., Milne, B. J., Polanczyk, G., Pariante, C. M., . . . Caspi, A. (2009). Adverse childhood experiences and adult risk factors for age-related disease: depression, inflammation, and clustering of metabolic risk markers. Arch Pediatr Adolesc Med, 163(12), 1135-1143. doi:10.1001/archpediatrics.2009.214
Liu, R. H., Pan, J. Q., Tang, X. E., Li, B., Liu, S. F., & Ma, W. L. (2017). The role of immune abnormality in depression and cardiovascular disease. J Geriatr Cardiol, 14(11), 703-710. doi:10.11909/j.issn.1671-5411.2017.11.006