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By Grant H. Brenner
Post-traumatic Stress Disorder (PTSD) is a condition affecting a subset of people exposed to traumatic experiences. Not all people who endure traumatic experiences will develop PTSD as most people are resilient due to biological, psychological, and social factors. Most responses to trauma are normal, including short-term stress responses, sleep disturbances, fears of trauma happening again, and related reactions, but they resolve after the trauma without becoming more severe or ongoing.
PTSD Is Endemic
Nevertheless, in any given year up to nearly 5.5 percent of people meet the criteria for PTSD, according to the National Institutes of Mental Health. Of those people, over two-thirds are estimated to have moderate to high severity symptoms. Adverse childhood experiences are more common than recognized, leading to life-altering changes which often extend far into adulthood, and to future generations.
PTSD can develop after people are exposed to a traumatic event involving death, threats to life, actual or threatened injury, or sexual violence. Exposure to trauma can be direct, via witnessing trauma, learning about a relative or friend who was traumatized, and through hearing about details of traumatic events, typically in the course of professional duties.
The causes of PTSD are not fully understood but are considered to be related to altered fear-based conditioning. Traumatic experiences, rather than being integrated into a person’s memory and sense of self so that they become part of who they are, affect the brain in such a way that they become amplified, not just leading to symptoms but becoming a defining feature of a person’s life and identity. Psychotherapy treatment involves desensitization to triggers via careful exposure to traumatic material, as well as restructuring ways of thinking about traumatic experiences to correct cognitive distortions. Understanding who is likely to develop PTSD following trauma, and why, is key for prevention and treatment.
PTSD has symptoms in four main areas, with specific required criteria for diagnosis including how long the symptoms last, when they begin, how many symptoms are present, and so on. Symptoms include:
- Intrusive symptoms, such as nightmares, recurring unwanted thoughts or memories, emotional distress to reminders, and flashbacks;
- Avoidance, of trauma-related thoughts, feelings or reminders;
- Negative changes in thinking and mood, such as being unable to remember parts of the trauma, negative thoughts or beliefs about oneself and the world, excessive blame, loss of interest, feelings of isolation, and difficulty having positive feelings;
- Changes in arousal and activity level, including irritability or anger, destructive or risky behaviors, hypervigilance, difficulty with sleep and concentration, and having a strong reaction to small triggers (“heightened startle reaction”).
Genes Are Not Written in Stone
In addition to traditional biological and genetic factors, in the last couple of decades, the importance of “epigenetic” factors has received great attention. Epigenetics is the study of how gene expression is changed by environmental factors. The underlying code may stay the same, but the way DNA is read and translated varies.
This may be passed on from one generation to the next, for example changing stress responses in the children and grandchildren of Holocaust survivors, and food-related reactions in the children and grandchildren of famine survivors. Research shows increasingly important roles for epigenetics in psychiatric and various general medical conditions.
There are a few ways epigenetic changes are transmitted, and one of the most important is “DNA methylation”—a small chemical group (methyl) binds to different genetic switches on DNA, increasing or decreasing levels of that gene product and ultimately leading to behavioral changes. DNA methylation has been likened to the dimmer switch on a light, raising or lowering intensity.
Epigenetic changes are thought to play an important role in PTSD, both whether or not it develops—as epigenetic stress-related responses affect resilience—and as a factor in treatment and recovery. Epigenetic processes could be therapeutic targets for new drug development, as well as markers for treatment response. Clinicians and researchers have long speculated that psychotherapy might change epigenetics.
Discovering the Epigenetic Impact of Therapy on PTSD
To look at the question of whether therapy changes epigenetics, and to identify specific epigenetic targets for future study, a multinational research group involving major academic and clinical centers in the US and the Netherlands (Vinkers et al., 2019) worked with a group of veterans to look for associations between DNA methylation regions (DMRs, key to epigenetics), PTSD, combat-related trauma, and response to psychotherapy.
Participants were 44 male combat veterans with PTSD and 23 without, who had been deployed at least once for a period of at least 4 months. They were tested using the Clinician-Administered PTSD Scale (CAPS), the Structured Clinical Interview for DSM-IV (SCID), and the Mood and Anxiety Symptom Questionnaire. Epigenetic testing was conducted based on prior research to test for common DMRs.
Veterans with PTSD were treated with eye movement desensitization processing (EMDR) or trauma-focused cognitive behavioral therapy (tf-CBT), the two most evidence-based therapeutic treatments for PTSD which involve exposure/desensitization, and cognitive restructuring and reprocessing. A subset was also being treated with various medications, including antidepressants and sedatives. Factors such as smoking, medication use, coffee drinking, and related confounding factors were statistically controlled to make sure the findings were from epigenetic effects only.
Findings
Treatment for PTSD was effective as 21 out of 44 veterans were in remission after treatment, based on CAPS scores and symptoms. Both EMDR and tf-CBT were equally effective clinically, but EMDR was associated with a small but significant difference in epigenetic effect.
Twelve DMRs were associated with changes in PTSD status over the course of treatment, but most of them did not change in a consistent way over the course of psychotherapy. However, one region did show a clear response: the ZFP57 DMR.
This region showed lower methylation with greater PTSD symptoms, and increased methylation with treatment. ZFP57 was significantly associated with both reduced symptoms and PTSD remission. By factoring out changes in symptom level, researchers showed that psychotherapy was independently correlated with ZFP57, suggesting that therapy itself may have a direct biological effect on DNA methylation.
The Dawn of a New Age?
This research is important because it is a step toward understanding how psychotherapy may reverse epigenetic changes caused by trauma. It further clarifies which genetic regions are involved in the development of trauma and resilience (and possibly posttraumatic growth), and it also establishes that psychotherapy can change gene expression, identifying ZFP57 as an area of focus for future investigation.
This DMR regulates “genomic imprinting,” in which genes are selectively silenced, so that even if one inherits genes for the same thing from both mother and father, only one copy of the gene actually goes to work. ZFP57 in rat models has been shown to alter stress vulnerability, and so epigenetic changes in this gene region appear to govern an important aspect of PTSD development and recovery.
Though this study needs to be repeated and expanded, it suggests that psychotherapy alone has a specific biological effect on a specific genetic region which can, to an extent, serve as an antidote for the effects of traumatic experience. It will be important to look at whether other types of therapy have different epigenetic effects across a range of conditions.
In general, gaining a deeper understanding of epigenetics in both disease and health will help us better understand not only clinical matters, but also who we are, how we remember what happened to our ancestors, and how we may be able to shape the future of our species.
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