UNDERSTANDING THE SCIENTIFIC BASIS OF POST-TRAUMATIC STRESS DISORDER (PTSD) AND DE-STIGMATIZATION: GENETICS OVERRIDES “BEING STRONG.”

Kenneth Blum, Ph.D., Co-discoverer of: The Reward Gene

Posttraumatic stress disorder (PTSD) is a mental health disorder with a genetic basis. The disorder develops from a stress reaction after a person is exposed to physiological or psychological trauma such as sexual assault, warfare, traffic collisions, or other life-threatening traumatic events. Symptoms may include re-experiencing the trauma (flashbacks), or nightmares (lucid and non-lucid) related to the events and mental or physical distress induced by trauma-related cues, as well as, attempts to avoid trauma-related cues. Symptoms include alterations in how a person thinks and feels, like amnesia about the event, fear of relationships, problems with sleeping, concentrating, and being hypervigilant; startled by loud noises. These symptoms can last for more than a month after the event and even years, and result in a higher suicide risk. Interestingly, most people who have experienced a traumatic event will not develop PTSD. People who experience interpersonal trauma like rape or child abuse are more likely to develop PTSD as compared to the experience of non-assault based trauma such as accidents and natural disasters. PTSD after experiencing traumatic environmental insults (like abuse) may be long lasting. About half of rape victims develop PTSD. Young children may be unable to process distress and might express their memories through play.

The term “posttraumatic stress disorder” was used in the 1970s due to the diagnoses of US military veterans of the Vietnam War. It was officially described in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM -111) and first recognized by the American Psychiatric Association in 1980.

According to the American Psychiatric Association (2013), about 3.5% of adults in the US each year have PTSD, and 9% develop it at some point in their life. In the rest of the world, yearly rates are between 0.5% and 1%, although they are much higher in regions of armed conflict. PTSD is also more common in women than men. Regarding political rhetoric about being able to “handle it” and “being strong,” it is well known that some soldiers have not, because of this stigma, been able to seek help. The truth is that many genetic studies from the 90’s until the present day have clearly revealed that certain gene variants (called alleles) set people up with an inability to handle trauma and stress.

Understanding Genetics of PTSD
David Comings from the City of Hope performed the first-ever study to show an association of a reward gene called the dopamine D2 receptor gene A1 form with people (military veterans) diagnosed with PTSD. In conjunction with Ernest Noble, this same gene form had been shown by my laboratory, to associate with severe alcoholism and cause carriers to have 30-40 less Dopamine D2 receptors in the brain. During combat stress, dopamine is released from neurons 100 times above the resting state. Therefore, less dopamine D2 receptors induced by genetics (compromised DNA) leads to lowered dopamine function. Low dopamine function is associated with increased risk for PTSD.

There is evidence that susceptibility to PTSD is hereditary. Genetics alone causes about 30% or more of the variance in PTSD. Identical (monozygotic) twins with PTSD exposed to combat in Vietnam were associated with an increased risk of the co-twin’s having PTSD compared to non-identical (dizygotic) twins. There is also evidence that those with a genetically smaller hippocampus (a region of the brain involving memory) are more likely to develop PTSD following traumatic stress. PTSD shares many genetic influences common to other psychiatric disorders. PTSD shares 60% of the same genetic variance as panic and generalized anxiety disorders. Alcohol, nicotine, and drugs of abuse share greater than 40% genetic similarities. One study reported that soldiers whose leukocytes had greater numbers of glucocorticoid receptors (involved in stress response) were more prone to developing PTSD after experiencing traumatic stress.

However, genetic antecedents may not tell the whole story, environmental insults or abuse (sexual and verbal) during childhood involve “epigenetic” changes. Specifically, instead of being caused by differences in the DNA sequence, epigenetic changes are cellular, physiological and behavioral characteristic (phenotypic trait) changes that are caused by external or environmental factors that switch genes on and off and affect how cells read genes. Unfortunately, it is now known that epigenetic effects can occur for at least two subsequent generations. The resultant effects of environmentally induced epigenetic changes in the chromatin structure of the DNA have been found, for example, to reduce the function and expression of the dopamine D2 receptor gene, thereby, increasing the chance for PTSD. The take home message here is that parental abuse in children may indeed help cause PTSD in adulthood when faced with horrific trauma like rape and war. So as scientists we now say “Love your pups.”

Can We Prevent or Treat PTSD?
Early access to cognitive behavioral and trauma therapy have been of modest benefit. Also, Critical Incident Stress Management (CISM) has been suggested as a means of preventing PTSD. CISM is most accurately defined as an integrated multi-component continuum of psychological interventions to be provided in the context of acute adversity, trauma, and disaster on an as needed basis to appropriate recipient populations. CISM is not a singular technique, nor a treatment for acute stress disorder, posttraumatic stress disorder, posttraumatic depression, or bereavement and grief, and may
even cause negative outcomes. Interestingly, the World Health Organization recommends against the use of benzodiazepines and anti-depressants in those having experienced trauma. Some evidence supports the use of the anti-stress molecule hydrocortisone for prevention in adults. However, there is limited or no evidence supporting other drugs such as propranolol, escitalopram, temazepam or gabapentin. Indeed, Gabapentin is a drug that stimulates the neurotransmitter GABA that reduces dopamine effects and should not be used to treat PTSD, especially in the long-term.

In response to these unfounded recommendations and therapeutic evidence, my laboratory has proposed the use of “Pro-Dopamine Regulation” (KB220z). Dr. Thomas McLaughlin, from the Center for Psychiatric Medicine, in Massachusetts, and our laboratory and others, carried out three independent published studies showing that chronic administration of a nutraceutical KB220z eliminated terrifying lucid nightmares in at least 82 percent of PTSD-ADHD patients treated. The reduction or elimination of terrifying Lucid Dreams seemed to be dependent on KB220Z, whereby voluntary stopping of the agent results in reinstatement of the terrifying non-pleasant nature of the dreams (see figure 1). In most cases, patients reported a gradual but, then, complete amelioration of their long-term, terrifying, lucid dreams, while taking KB220Z. However, we also show that in at least four cases the persistent amelioration of these dreams continued for up to 12 months, after a self-initiated cessation of use of KB220Z. These particular cases support the scientific possibility that KB200Z increases dopamine stability as well as functional connectivity between networks (cross talk between different brain regions) of brain reward circuitry shown in fMRI studies of both rodents and humans. The increase in connectivity volume (recruitment of more dopamine neurons firing in the reward site of the brain) in rodents suggest the induction of epigenetic changes (neuroplastic adaptation), which may be like those involved in human lucid dreaming.

Conclusion
In summary, there is a need for understanding and treating PTSD in soldiers returning to the United States after combat and finding a way to reduce the suffering and violence committed by soldiers, here and abroad, who have untreated PTSD. Reducing the stigma of PTSD by embracing both genetic and epigenetic effects of traumatic stress might influence all people with PTSD to seek out treatment without fear.

We hypothesize that even before combat, soldiers with a childhood background of violence (or with a familial susceptibility risk) would benefit from being genotyped for high-risk alleles (DNA variants). Such a process could help to identify candidates who would be less suited for combat than those without high-risk alleles. Of secondary importance is finding safe methods to treat individuals already exposed to combat and known to have PTSD. Since hypodopaminergic function in the brain’s reward circuitry due to gene polymorphisms (variations) is known to increase substance use disorder in individuals with PTSD, it might be a good idea to administer pro-dopamine regulators like KB220z to affect the epigenetic expression (mRNA) to overcome this deficiency. In this way, people would be less vulnerable to traumatic stress and more likely to be able to “handle trauma” which is not based on “being strong.”

Kenneth Blum, B.Sc. (Pharmacy), M.Sc., Ph.D. & DHL; received his Ph.D. in Neuropharmacology from New York Medical College and graduated from Columbia University and New Jersey College of Medicine. He also received a doctor of humane letters from Saint Martin’s University Lacey, WA. He has published more than 550 abstracts; peer-reviewed articles and 14-books.