Post-Traumatic Stress Disorder Linked To Genetics
Written by Rupert Shepherd
Research from UCLA is showing that the reason some people exhibitpost-traumatic stress disorder (PTSD), while others are seemingly able to cope with life threatening situations more easily, is at least in part, down to their genes.
Researchers found that two genes associated with serotonin production lead to a higher risk of the problem. Their article, published in the Journal of Affective Disorders, suggests not only a way of identifying people that may be susceptible to the problem, but also points the way to new and more comprehensive treatments.
Lead author Dr. ArmenGoenjian, a research professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA continues :
"People can develop post-traumatic stress disorder after surviving a life-threatening ordeal like war, rape or a natural disaster ... If confirmed, our findings could eventually lead to new ways to screen people at risk for PTSD and target specific medicines for preventing and treating the disorder."
Examples of PTSD include: psychological fallout from a variety of harrowing situation from: child abuse, terrorist attacks, sexual or physical assault, major accidents, natural disasters, or exposure to war or combat. The Vietnam War veterans being the classic example that has been popularized in various movies and TV shows. Afterwards, those affected experience symptoms such as flashbacks, feeling emotionally numb or hyper-alert to danger, as well as trying to avoid scenarios that remind them of the trauma.
Goenjian analyzed DNA from 200 adults from Armenia who survived the devastating 1988 earthquake. The people spanned several generations and were from 12 extended families who suffered PTSD symptoms after the disaster. The families' genes showed that those who had specific variants of two genes were more prone to PTSD symptoms. The genes, called TPH1 and TPH2, control the production of serotonin. Serotonin is a brain chemical that regulates mood, sleep and alertness, all of these are disrupted in PTSD. Serotonin problems have been shown to be responsible in some mental health problems, and are also associated with the effects that opiate based drugs, such as morphine, have on a person.
Goenjian continues that :
"We suspect that the gene variants produce less serotonin, predisposing these family members to PTSD after exposure to violence or disaster ... Our next step will be to try and replicate the findings in a larger, more heterogeneous population ... A diagnostic tool based upon TPH1 and TPH2 could enable military leaders to identify soldiers who are at higher risk of developing PTSD and reassign their combat duties accordingly ... Our findings may also help scientists uncover alternative treatments for the disorder, such as gene therapy or new drugs that regulate the chemicals responsible for PTSD symptoms."
PTSD has become more of an issue with the Iraq and Afgan wars which are still ongoing, and troops being exposed to similar dire attacks, roadside bombings and other unexpected traumas. The UCLA's work could be used not only to help treat people, but also to avoid putting those that are more prone to the problem into situations that are likely to cause them long-term problems.
Until now, psychiatrists have relied more or less on trial and error and past experience to treat patients. In the future, they should be able to pinpoint a patient's problems more accurately.
Serotonin is the target of the popular antidepressants known as SSRIs, or selective serotonin re-uptake inhibitors, which prolong the effect of serotonin in the brain by slowing its absorption by brain cells. More physicians are prescribing SSRIs to treat psychiatric disease beyond depression, including PTSD and obsessive-compulsive disorder.
The role of genes and family in trauma exposure and posttraumatic stress disorder
S Seedat, D J Niehaus and D J Stein
Most human behavioral traits are likely to result from an interplay of genes and environment. The field of psychiatric genetics, in this regard, is rapidly growing… Although the precise weighting of genes for anxiety disorders is undetermined, twin studies have demonstrated that genetic factors are at least as important as familial aggregation for some anxiety disorders (eg panic disorder and generalized anxiety disorder).
PTSD is a peculiar anxiety disorder in that it requires the presence of exposure to an extremely traumatic environmental event. Previous research has focused on identifying factors that put exposed persons at 'risk': female gender, previous trauma exposure, neuroticism, and pre-existing anxiety and depression.2,3 However, more recent data indicate that both the risk of trauma exposure and PTSD may be influenced by genetic make-up and family environment; for example, studies show an increased prevalence of PTSD in the adult children of Holocaust survivors even though these children as a group did not have greater exposure to life-threatening events.4
Furthermore, population prevalence studies have demonstrated a markedly disproportionate risk between trauma exposure and PTSD, suggesting that other environmental and genetic factors also contribute to one's liability to develop the disorder. While trauma exposure rates vary between 40-80%, the prevalence rate of PTSD in exposedindividuals is only 8%.3 The contribution of genes in PTSD is further supported in animal models of the stress response: genetic differences in sensitivity to environmental stress have been noted in rhesus monkeys5 and variations in the fear response to inescapable shocks have been documented in different mice strains reared in identical environments.6 The results of fear-conditioning studies in animals are consistent with a model of PTSD in humans that posits pathological dysfunction within a network of brain regions.
Both twin and family studies have been used to explore genetic influence in PTSD ... Additionally, there is the issue of trying to separate hereditary predisposition to trauma exposure from hereditary predisposition to PTSD. Two elegant twin studies, however, provide fairly robust support for the heritability of PTSD. The Vietnam Era Twin Registry project of 4029 malemale Vietnamese twin pairs (2224 monozygotic pairs, 1818 dizygotic pairs) was an informative design for studying genetic and non-genetic factors that influenced wartime exposure to trauma.7 The project examined specific variables such as volunteering for service in Vietnam, time served in Southeast Asia, combat experiences, and combat decoration awards. Genetic factors accounted for 36% of the variance in service in Southeast Asia, 47% of the variance in combat exposure, and 54% of the variance in the likelihood of receiving a combat medal. In addition, genes accounted for approximately 30% of the variance in liability for most PTSD symptoms in all three symptom clusters: re-experiencing, avoidance, and hyperarousal, even after differences in concordance for combat exposure between monozygotic (MZ) and dizygotic (DZ) twin pairs were accounted for.8 Significantly, family environment (such as family upbringing, schooling, and parental socio-economic status) shared by twin siblings did not contribute to the development of PTSD.
In summary, several factors need to be considered when examining the heritability issue in PTSD. Family studies are difficult to interpret since it is difficult to know to what extent the increased vulnerability to PTSD in family members results from genetic factors, other biological factors, or shared experience. Also, the relative contribution of genes and shared environment may well vary across the phenotype: nature of trauma, severity of trauma, gender, age of onset, and cultural background; for example, the genetics and family risk of PTSD arising in a child exposed to incest may differ from PTSD arising in an adult who is physically assaulted…
Future twin, family, and genetic marker studies must endeavor to tease out heritability factors for trauma exposure from heritability factors for PTSD. Exciting possibilities exist for exploring genetic mechanisms involved in conditioned fear responses in PTSD… as well as deficits in hippocampal structure and function. In addition, molecular genetics might be useful in highlighting the contribution of heritability to the various pathogenic aspects of PTSD; for example, the relationship, if any, between aggression-proneness in PTSD and genetically-determined abnormalities in serotonin synthesis,19 and startle-proneness and chromosomal abnormalities.20
Neurotransmitter Linked to Post-Traumatic Stress
byMichael Smith North American Correspondent, MedPage Today
Post-traumatic stress disorder (PTSD) is associated with lowered levels of a neurotransmitter in a brain region that plays a role in panic and stress, researchers reported.
In a cohort study, positron emission tomography (PET Scants) also linked the availability of the molecule, norepinephrine transporter (NET), to one of the five facets of the syndrome, according to Alexander Neumeister, MD, of NYU School of Medicine in New York City, and colleagues.
One possible implication of the finding is that medications aimed at norepinephrine or the norepinephrine transporter might be useful as PTSD therapies, Neumeister and colleagues reported online in JAMA Psychiatry.
NET is part of the family of sodium chloride neurotransmitter transporters, the researchers noted, and weakens neuronal signaling by promoting rapid clearance of norepinephrine, which plays a central role in the fight-or-flight response.
Data from animal experiments have suggested that chronic stress is associated with a reduction in the availability of NET in the locus coeruleus, a small region in the pons (in the brain) where concentrations of the molecule are highest, Neumeister and colleagues noted.
But it hasn't been clear if those findings have any bearing in PTSD, they added. To help fill the gap, they recruited 56 participants for a positron emission tomography study, including 18 healthy controls, 22 people with PTSD, and 16 people who had suffered trauma, but had not developed PTSD.
One objective of the study, which used a radioactively labeled compound to reveal norepinephrine transporter levels, was to see if there was an association with PTSD, compared with healthy and non-PTSD trauma controls.
The other objective was to see if norepinephrine transporter levels in the PTSD participants were associated with anxiety arousal, one of the five symptom clusters (including re-experiencing, avoidance, numbing, and dysphoric arousal) in PTSD.
Analysis showed that NET levels in the PTSD participants was 41% lower than in the healthy controls, they reported, which was statistically significant (P=0.003). The differences between the health controls and the non-PTSD trauma group and between the two trauma groups -- 31% and 15%, respectively -- did not reach significance.
The presence or absence of major depressive disorder or alcohol abuse or dependence did not affect NET levels, nor did the type of trauma, numbers of traumas, or age at onset, Neumeister and colleagues reported.
Among the PTSD participants, the investigators reported, NET availability in the locus coeruleus was independently and positively associated with the severity of anxious arousal symptoms, such as hypervigilance, but not with re-experiencing, avoidance, numbing, or dysphoric arousal symptoms.
Treatments for PTSD have included exposure and cognitive therapy, but the study "addresses a concern that there has been limited progress in the development of truly innovative novel neurobiology-based treatment models," the researchers concluded.