Genes Plus Environment May Predict PTSD

Deborah Brauser

September 23, 2011

September 23, 2011 — Genetics and environment may be important predictors of posttraumatic stress disorder (PTSD) after a traumatic event, new research suggests.

In a study that evaluated almost 300 female undergraduates before and after the mass shooting on the campus of Northern Illinois University in 2008, investigators found that those who experienced several exposure events, including being able to see the gunman and/or hear the gunfire, were more likely to develop symptoms of PTSD.

PTSD symptoms were also more likely to develop in those with certain genetic variants in the serotonin transporter.

"We found that when we examined women who had no prior or very low PTSD symptoms, there was a very clear interaction with the risk factor for the serotonin polymorphisms," principal investigator Kerry Ressler, MD, PhD, associate professor in the Department of Psychiatry and Behavioral Sciences at Emory University in Atlanta, Georgia, told Medscape Medical News.

Dr. Kerry Ressler

"For example, their proximity to the shooting, combined with genetic risks, increased the rate of PTSD symptoms in the weeks following the shooting. However, we were not able to see a difference in those who already had a high level of symptoms from past experiences," added Dr. Ressler.

He noted that "this is more evidence" that environmental risks from trauma plus genetic risks make up one mechanism for how PTSD develops, but more studies are needed.

"For today, we know that history of trauma is probably 1 of the biggest factors we can already test for. Because past trauma and interpersonal violence have become so prevalent in our society, asking and counseling about it can be a helpful adjunct to mental health treatment for all patients, as it's been shown to be a risk for depression and other psychiatric disorders," said Dr. Ressler.

The study was published online September 5 in the Archives of General Psychiatry.

Paucity of Genetic Studies

According to the investigators, there is a 6.8% lifetime prevalence of PTSD among adults in the United States.

"Research has shown risk factors for the development of PTSD to include severity of perceived life threat during trauma, prior trauma, family history of psychopathology, peritraumatic emotional responses, and peritraumatic dissociation," they write.

In addition, "while the heritability of PTSD has been accepted for some time, molecular genetic association studies of PTSD have been limited," they add.

Most of the studies that have been conducted in this area have focused on the polymorphism 5-HTTLPR, which is associated with a higher risk for psychopathology. In addition, the single-nucleotide polymorphism rs25531 "has been shown to have an effect on amygdala activity in response to angry, happy, or sad emotions," and may modulate 5-HTTLPR expression, report the researchers.

Although not as well studied, the variant STin2 has also been shown to modulate expression with 5-HTTLPR and has been linked to harm avoidance, suicidality, and psychosis.

The investigators sought to assess the link between these genetic variations within the serotonin transporter (SLC6A4) and symptoms of PTSD in a group of civilians.

"One of the limitations in the genetics field has been separating out who is at risk vs who is not, as a function of prior trauma. Most PTSD studies look retrospectively after a trauma has been experienced, and there's generally no way of knowing who had PTSD or were at risk for PTSD prior to an event," said Dr. Ressler.

He added that another complication is that researchers often look at people who have experienced all types of trauma, which can include war-related events, motor vehicle accidents, personal assault, and more.

Longitudinal Study

The mass shooting at Northern Illinois University by a lone gunman occurred on February 14, 2008, and resulted in 21 wounded and 5 dead. An ongoing longitudinal study on history of violence and trauma that included 1045 female undergraduate students was launched before the event occurred.

For this analysis, the investigators evaluated data on 204 of the study participants (mean age, 20.1 years; 77.5% white; 13.7% black) who underwent interviews before the shooting, had DNA extracted from salivary samples in the fall of 2009, and completed follow-up trauma-related measures, including an online survey sent out 17 days after the event.

The average time between the shooting and collection of the online surveys was 3.2 weeks. Another online survey was completed an average of 34 weeks after the shooting.

Prior trauma during the preshooting interview was assessed by using the Traumatic Life Events Questionnaire and the Distressing Event Questionnaire (DEQ). The DEQ was also used within the 2 online surveys to measure postshooting symptoms.

Other tools used included a modified Virginia Tech shooting exposure measure and the Multidimensional Scale of Perceived Social Support.

Assessments of the serotonin transporter polymorphisms STin2, 5-HTTLPR, and rs25531 were the primary outcome measures.

"This allowed us to evaluate the role of genetics and psychology in terms of the risk for developing PTSD after a shared trauma," explained Dr. Ressler.

Mounting Evidence

Results showed that the rs25531 variant alone and with 5-HTTLPR (forming a 5-HTTLPR multimarker genotype) was linked to a significant increase in acute stress disorder symptoms 2 to 4 weeks after the shooting (P < .05 for both).

The association remained significant when controlling for race and for level of shooting exposure, defined as the sum of exposure events experienced (P < .007).

The greatest effect was found for those with the 5-HTTLPR multimarker genotype and the PTSD subscale symptoms of avoidance (P = .003).

There was no association with increased PTSD symptoms found for either 5-HTTLPR alone or the STin2 variant. The number of preshooting traumatic events experienced by the participants was also not significantly associated with PTSD symptoms after the shooting.

However, the following 5 factors on the day of the shooting were significantly associated with PTSD symptom severity, as measured by the DEQ, 2 to 4 weeks later:

  • was in the building where the shootings took place (P < .05),

  • heard gunfire (P < .005),

  • saw someone fired on (P < .05),

  • saw the gunman during the shootings (P < .001); and

  • was injured during the event (P < .005).

The number of high-exposure events during the episode also had an effect on change in DEQ score from preshooting to online survey 1 and online survey 2 (both, P < .005).

Dr. Ressler said that although these data suggest that the serotonin transporter may affect severe trauma responses, more studies into the vast area of genetics are needed.

"I think eventually, maybe a decade from now, we might be at a point where we can know much more about what the genetic factors are for PTSD. The serotonin genetic factors are only 1 small part of the story, and it's probably going to be a combination of 10, 20, maybe even 100 different genes that add up together," he said.

"I certainly don't think we're at the point where we have a strong predictability at the level of genes, but we have more and more data that biology and genetics are certainly playing a role."

Screening Important

"Overall, I think this is a good contribution to the literature," Alexander Neumeister, MD, associate professor of psychiatry at Mount Sinai School of Medicine in New York City, told Medscape Medical News.

Dr. Alexander Neumeister

"However, it's not really a study about PTSD, but more about the emergence of trauma and stress symptoms after a shooting happened," said Dr. Neumeister.

He noted that the fact it was a genetics study was interesting and "shows very nicely the interaction between genes and the environment, and that even in the context of severe trauma, which all these people experienced, the majority did not develop any symptoms."

Dr. Neumeister added that the short version of the 5-HTTLPR variant has been shown previously to be predictive of the development of depression and anxiety symptoms in the context of adverse life events. Its involvement in PTSD symptoms has also been seen "experimentally" for several years.

"Still, I would be very hesitant to say, 'let's screen the entire population' for the presence or absence of this genetic variant to determine the risk a person will have to develop psychiatric symptoms. But I know those models are quite attractive, especially to the military or police officers, or firefighters."

He said that if these models prove reliable in predicting how a person with this variant will react during and after a traumatic situation, that could possibly determine how much pressure they can withstand while going about their job.

"It would be very helpful to have such tests. Nevertheless, I think genetics at this point is probably too simple to be able to tell whether a person is, for example, a good candidate for going into war or for being a fireman or not. There are many variables, such as personality traits, life difficulties, and genetics, all of which together contribute to the emergence or absence of psychiatric symptoms after a trauma," said Dr. Neumeister.

"What we learn from these types of studies is that we all face trauma, yet we are all not equally vulnerable to life traumatizations. So I think it's very important for clinicians to screen for traumatic events and to develop coping skills that help those who are affected."

The study was supported by grants from the Joyce Foundation, the Burroughs Wellcome Fund, the National Institute of Child Health and Human Development, and the National Institute of Mental Health. The study authors and Dr. Neumeister have disclosed no relevant financial relationships.

Arch Gen Psychiatry. Published online September 5, 2011. Abstract


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