Medical Monday ..... Childhood Trauma, Epigenetics & Lupus

World Lupus Day

As I mentioned previously I began a graduate program in mental health counseling. I took a life-span development course last semester. The most interesting thing I have learned is that we have finally been able to end the argument of nature vs. nurture. The reality is both impact our development. You can be born with certain genetic traits and your environment can change them. As my professor said (and I am paraphrasing badly) - Your genetics you are born with, your epigenetics are up to you.

So, how do epigenetics work? In the most basic of terms, they are tags on your genetic code that turn on or off how your genes are expressed, your phenotype in a sense, and unlike your genetic code, these tags can be influenced by your environment. So what does that mean? My understanding (and please feel free to tell me if I am incorrect) is that if you smoke, or eat poorly, or are exposed to chemicals, your basic genetic make-up can be altered. It also means, that if you are raised in a traumatic or stressful household, your genetic make-up can be altered.

It is almost as if your DNA builds you as if you are going to live in a best case scenario. If your genetic make-up is never interfered with you will turn out a certain way, but if you live in less than ideal conditions, things may need to be altered to address that.

Gene therapy is based on this idea and some great strides have been made in the treatment of such diseases as Leukemia. So, I wrote my final paper on the connection between early childhood trauma, epigenetics and lupus. At the time I wrote the paper I could not find any conclusive research that showed a direct causal link between the three. I did however find lots of studies that indicated more study needed to be done. There are also indications that gene therapy could be the Holy Grail of Lupus treatment as well. 

Childhood Trauma, Epigenetics & Lupus

Leann Baldwin

COUNS 712 AE

Much research has connected childhood sexual abuse with psychological disorders such as depression, self-mutilation, suicidal ideation, personality disorders, substance abuse and post-traumatic stress disorder (PTSD) (Putnam & Trickett, 2006). Studies have also looked at how exposure to traumatic events (either in childhood or adulthood) impact overall health (Flett, Kazantzid, Long, MacDonald & Millar, 2002). Other studies have generally concluded that women with histories of childhood sexual or physical abuse are more likely to attempt suicide or have anxiety disorders than women with no such history (Heim & Memeroff, 2001). Several studies looked at the impact of childhood and cumulative stress on the epigenetics of autoimmune disease (Dube et al., 2009; Stojanovich & Marisavljevich, 2008; Stojanovich, 2010). For this paper I will review research in these different areas and see where there is overlap and where we can make hypothesizes for further study.

According to the 2011 Child Maltreatment report by the United States Department of Health and Human Services, 676,569 children were victims of maltreatment and of those 467,820 were reported for the first time. In Massachusetts alone, 14.4% of the child population (or 20,262 children) were victims of maltreatment. Nationally, 9.6% of maltreated children are sexually abused before the age of 17. With the relatively new discovery of epigenetics it has become more important than ever to determine what impact, if any, childhood trauma and neglect have on determining future health risks for these children.

The Role of Childhood Trauma in Adult Health

A 2002 New Zealand study explored the impact of trauma on physical health by interviewing 1,500 individuals from urban and rural populations in their homes (Flett, Kazantzid, Long, MacDonald & Millar, 2002). Trauma was defined as falling into 12 specific categories which included among other things childhood sexual assault and adult sexual assault; these were then grouped into three categories: crime, hazard and accident. Participants were asked specific questions about their history of trauma and their health; then participants completed the Pennebaker Inventory of Lumbic Languidness (PILL) to measure current health concerns (Flett et al., 2002).  This study concluded that individuals exposed to crime (particularly in childhood) had poorer health as defined by their current health problems. There was no indication that these individuals had a greater risk of chronic health concerns, such as SLE (Flett, et al., 2002). The limitations of this study were that they compressed many of the trauma categories, such as sexual assault, domestic violence and robbery into one category of crime. Because the results were generalized to crime we can’t use it to conclude that childhood sexual assault has an impact on even short term health risks.

While it is true that our DeoxyriboNucleic Acid (DNA) is determined at birth, early traumatic experiences can turn on or off certain genetic traits and create stable phenotypes that are susceptible to certain diseases. Studies indicate that these phenotypes can be altered and shaped by external stress factors, which in turn induce physiological responses which create “further stress exposure” (Heim & Memeroff, 2001).  Heim and Memeroff (2001) explored studies dealing with the impact of stress on both rodents and children in an attempt to determine if there is a “stable phenotype of altered stress vulnerability.” They determined that there are many factors in humans that determine how and if early childhood stress will manifest itself in biological traits or psychopathology. They found that in both humans and rats early childhood stress created permanent changes in the corticotrop-in-releasing factor (CRF) neurotransmission, which in turn impacts the central nervous system making people more susceptible to psychiatric disorders, immune disorders and ongoing stress exposure. More studies need to be done to determine how different stressors at critical stages of development alter CRF so that more effective treatments can be determined. The authors recommend longitudinal twin studies for the future of this research as a way to better isolate the phenotype alterations (Heim & Memeroff, 2001).

Longitudinal studies have been done that show early childhood abuse impacts the health of children as they develop, where one traumatic exposure doubles the risk of poor childhood health and three exposures triple the risk of poor childhood health (Sachs-Ericsson, Medley, Kendall-Tackett & Taylor, 2011). Further studies indicate that trauma and risky behaviors used as coping mechanisms, such as drug use, smoking and alcohol use, increase the risk of poor health in early adulthood (Sachs-Ericsson, et al., 2011). Does this risk to overall health extend into middle and late adulthood; and can we separate the risky behavior to isolate the abuse as the cause of increased health risks? Positive self-efficacy has been shown to have a positive impact on adult health and the ability to deal with illness; “there is evidence of an association between indices of self-efficacy and childhood abuse such that abuse has been shown to negatively influence one’s cognitions about the self” (Sachs-Ericsson, et al., 2011). It is therefore a reasonable hypothesis that by looking self-efficacy in older adults who were victims of childhood abuse, we may begin to answer this question. A study that interviewed 1396 individuals over the age of 50 concluded that individuals who reported abuse (either physical, sexual or emotional) in childhood had lower self-efficacy. They also showed that individuals, who reported child abuse and lower self-efficacy were more likely to be disabled, suffer from diabetes, have chronic headaches or have bladder issues. What this study was not able to do was determine if the health issues were due to changes to neurobiology caused by the abuse or the continued risky behavior used as a coping mechanism to deal with the abuse (Sachs-Ericsson, et al., 2011).

These previous studies suggest that early childhood abuse and stress can influence one’s health in both the short and long term. Through alterations in our phenotype, our perception of ourselves and risky coping mechanisms we can reduce the quality of health we live with. This has serious implications for how we treat childhood trauma, not only do we need to heal the child’s psyche, we must also take more care to look for increasing health concerns and intervene to lessen the risk of serious health complications in adulthood. If we don’t, the victims of childhood abuse will become revictimized by their own body.

Epigenetics and Autoimmune Disease

“Epigenetics refers to changes in the DNA or surrounding chromatin that influences gene expression, but that do not change genetic composition” (Zouali, 2011). Studies of monozygotic twins have shown that factors beyond heredity, such as diet and lifestyle, impact a person’s gene expression (Ballestar, Esteller & Rishardson, 2006; Zouali, 2011). How do these changes in our phenotype influence a diagnosis of Lupus? Studies looking at the impact of epigenetic changes over time and their impact on SLE focus on DNA Methylation, B-cell modifications and T-cell modifications. The combination of these help to regulate a person’s immune system: DNA Methylation helps to suppress foreign particles from our environment, including viruses that accumulate in our bodies over time; while the T cells regulate our immune systems response and direct B cells to produce antigens to fight infection (NIH, 2008).

Zouali (2011) has studied how environmental factors such as air pollution, polycyclic aromatic hydrocarbons (PAH), cigarette smoke and certain drug combinations impact the epigenetics of our immune response in a negative way, making people more susceptible to autoimmune illness. Environmental factors change gene expression in a way that the body is unable to identify and fight against infection and can cause the immune system to actually harm its host. He has concluded that we can go back as far as “ … in utero exposure to epigenetic modifiers” (Zouali, 2011) to determine susceptibility. While Zouali (2011) acknowledges that “deciphering the precise contribution of epigenetic factors to autoimmunity, and in particular to SLE, is in its infancy,” he concludes that the role of epigenetics in the delivery of human immune response is critical. Other studies have gone beyond Zouali concluding that epigenetics can not only help us to determine an individual’s predisposition to autoimmunity, but also may be the key to successful treatment of the diseases and perhaps one day a cure (Ballestar, Esteller & Rishardson, 2006).

While Heim and Memeroff looked at the impact of childhood stress on overall health, Stojanovich and Marisavljevich have looked at how general stress contributes specifically to autoimmune disease. “… The stress system orchestrated the responses of the body and of the brain to the environment” (Stojanovich & Marisavljevich, 2008), meaning that cells remain dormant until a stressor (which could be good or bad) activates the cell; the cell either adapts to the situation in a healthy way or a negative way (Stojanovich, 2010). Previous studies had concluded that patients who suffer from PTSD are more likely to have elevated T-cell lymphocytes and lower levels of cortisol, both of which are primary indicators of autoimmune disease (Stojanovich & Marisavljevich, 2008).  Patients with many autoimmune disorders are symptomatic in flairs, according to Stojanovich (2010) stress is the primary trigger for symptomatic flairs in patients with SLE and Rheumatoid Arthritis (RA); more so than other environmental factors or family history. These studies explored how chronic stress can be one of many factors, including duration and severity of stress, social support, and patient’s optimism, which contributes to ongoing autoimmune issues, but did not conclude that childhood trauma had any greater impact than stress reported in adulthood.

The medical field has clearly made the connection between epigenetics and the onset of autoimmunity. The field of psychology has shown that early childhood trauma and stress can contribute to health problems well into adult life. These studies have a tremendous impact on how we should treat patients with autoimmune disease, incorporating a more holistic approach to treating lupus, incorporating nutrition, meditation, and counseling alongside medication.

Childhood Trauma and Autoimmune Disease in Adults

It is estimated that 80% of patients diagnosed with autoimmune disease are women (Dube, Fairweather, Pearson, Felitti, Anda, & Croft, 2009), and in 2011, 51.1% of maltreated children were female (Children’s Bureau, 2012).  It is generally accepted that women are more often victims sexual abuse as both children and as adults and studies have shown that women are more likely to be diagnosed with autoimmune disease, especially lupus. Therefore it is vital that it be determined whether or not trauma increases the risk  of adult onset autoimmune disease.

Increased C-reactive protein (CRP) levels are an indicator of inflammation in the body, this inflammation is an indicated for many autoimmune disorders, including Rheumatoid Arthritis and SLE. Studies indicate that child abuse not only increases C-reactive protein (CRP) at the time of the abuse, but the increase continues being elevated up to 20 years after the abuse (Dube, et al., 2009). A review of the Adverse Childhood Experiences (ACE) study indicated that each increase in the amount of childhood trauma a person experienced, the more likely they would be hospitalized for autoimmune complications; “however, the relationship was statistically significant only for women” (Dube, et al., 2009) and each increased episode of trauma increased a woman’s likelihood of hospitalization by twenty percent.

Goodwin and Stein (2004) isolated specific illness and the impact that childhood physical abuse has on physical disorders in adults. They concluded that physical abuse significantly increased the likilhood of many health issues including autoimmune disease independent of issues with anxiety, depression and substance abuse. Further, looking specifically at gender, childhood abuse was more likely to indicate a predisposition for autoimmune disease in women, but not in men (Goodwin & Stein, 2004). Interestingly, once adjusted for instances of sexual abuse it was concluded that women had an increased likelihood of hospitalization only for cardiac related issues (Goodwin & Stein, 2004).

Both of these studies conclude that while they were able to show a potential relationship between childhood abuse and autoimmune disease, both indicate that other factors such as risky coping behavior or other environmental factors may also be culprits (Dube, et al., 2009; Goodwin & Stein, 2004).

Conclusion

Causality is impossible to prove when looking at things as complicated as early sexual trauma and autoimmune disease. With that said, current research strongly supports that a cross-discipline approach to treatment is absolutely necessary and should begin early in the treatment process. Treatment that includes medical care, psychological care and a strong support system may be the best way to insure that victims of childhood assault lead long healthy adult lives. 

Ballestar, E., Estellar, M., & Richardson, B. C. (2006). The Epigenetic Face of Systemic Lupus Erythematosus. The Journal of Immunology, 176, 7143–7147. Retrieved from http://www.jimmunol.org/content/176/12/7143

Children’s Bureau, U.S. Department of Health and Human Services, Administration for Children and Families. (2012). Child Maltreatment 2011. Retrieved from http://www.acf.hhs.gov/programs/cb/research-data-technology/statistics-research/child-maltreatment

Dube, S. R., Fairweather, D., Pearson, W. S., Felitti, V. J., Anda, R. F., & Croft, J. B. (2009). Cumulative Childhood Stress and Autoimmune Diseases in Adults. Psychosomatic Medicine, 71, 243–250.

Flett, R. A., Kazantzis, N., Long, N. L., MacDonald, C., & Millar, M. (2002). Traumatic Events and Physical Health in a New Zealand Community Sample. Journal of Traumatic Stress, 15(4), 303–312.

Goodwin, R. D., & Stein, M. B. (2004). Association between childhood trauma and physical disorders among adults in the United States. Psychological Medicine, (3), 509–520. doi:10.1017/s003329170300134x

Heim, C., & Nemeroff, C. B. (2001). The Role of Childhood Trauma in the Neurobiology of Mood and Anxiety Disorders: Preclinical and Clinical Studies. Biological Psychiatry, 49, 1023–1039.

National Institute of Health (NIH). (2008). Immune System: T Cells. Retrieved from http://www.niaid.nih.gov/topics/immunesystem/immunecells/pages/tcells.aspx

Putnam, F. W., & Trickett, P. K. (2006). Psychobiological Effects of Sexual Abuse:  a longitudinal study. Annals of the New York Academy of Sciences, 821(1). Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1997.tb48276.x/full

Sachs-Ericsson, N., Medley, A. N., Kendall-Tackett, K., & Taylor, J. (2011). Childhood Abuse and Current Health Problems Among Older Adults: The Mediating Role of Self-Efficacy. Psychology of Violence, 1(2), 106–120. doi:10.1037/a0023139

Stojanovich, L. (2010). Stress and autoimmunity. Autoimmunity Reviews, 9, A271–A276. doi:10.1016/j.autrev.2009.11.014

Stojanovich, L., & Marisavljevich, D. (2008). Stress as a trigger of autoimmune disease. Autoimmunity Reviews, 7, 209–213. doi:10.1016/j.autrev.2007.11.007

Sachs-Ericsson, N., Medley, A. N., Kendall-Tackett, K., & Taylor, J. (2011). Childhood Abuse and Current Health Problems Among Older Adults: The Mediating Role of Self-Efficacy. Psychology of Violence, 1(2), 106–120. doi:10.1037/a0023139

Zouali, M. (2011). Epigenetics in Lupus. Annals of the New York Academy of Sciences, 1217(1), 154–165. doi:10.111/j.1749-6632.2010.05831.x