It’s always been with us and has gone by varied names, including shell shock and Vietnam Veterans Disorder, both associated with traumatizing experiences on the battlefield. Today the condition now known as post-traumatic stress disorder, or PTSD, is also diagnosed in people who have never seen active combat, but it remains more common among those who bear the psychic scars of war. For U.S. veterans of recent wars, including Iraq, the Persian Gulf and Vietnam, the lifetime prevalence of PTSD is from 10.1 to 30.9 percent, compared with an estimated lifetime prevalence of about 7 percent in the general population. Despite the higher rates, some service members are reluctant to disclose the symptoms they’re experiencing. Hesitation may stem from the complicated stigma historically associated with PTSD and concerns about risks to reputation and livelihood if the “PTSD” label tracks them through their careers. Concealment, though, means that their condition may go untreated. To bridge this gap for service people, the U.S. government is on the hunt for effective ways to screen large populations for PTSD. Although psychological conditions have a reputation for being “all in the mind,” they can involve physical changes throughout the body, affecting metabolism, heart rate and hormones. In research funded in part by the U.S. Army Research Office and U.S. Department of Defense, a large team of investigators sorted through a haystack of possible blood markers of such changes and identified 27 that combine with heart rate measurement to make up an apparently effective screen. They published their results September 10 in Molecular Psychiatry. The blood test, says senior study author Charles Marmar, chair of the department of psychiatry at NYU School of Medicine, could provide an efficient means to look for PTSD signals in active-duty military personnel returning from combat or anticipating redeployment. This kind of population-level screening is needed to get people appropriate care, he says, when military personnel “are often quite reluctant to tell [about] symptoms that they do have.” To develop the 28-factor screen, Marmar and his colleagues began with almost a million genomic, protein, metabolic, and other molecular candidates that they assessed in blood samples of 77 veterans with diagnosed PTSD and 74 veterans without the condition. All participants were male, had been in a war zone in either Iraq or Afghanistan and had experienced at least one traumatic war zone event. In a process of elimination based on how consistently certain blood-based markers could be linked to PTSD, the researchers sieved out almost all of the candidate factors. They finally ended with a group of 27 chemical signatures that together with heart rate offered the best accuracy for identifying PTSD. Some but not all of the markers had previously been linked to the condition and include measures related to insulin levels and blood clotting. The research team then tested how well the markers they found worked in a separate pool of 52 veterans—26 with diagnosed PTSD and 26 without it. The markers achieved an accuracy of 81 percent in distinguishing the two groups. The test panel detected a person as having a positive PTSD result 85 percent of the time and properly identified that a person did not have the condition 77 percent of the time. The results aren’t diagnostic but instead serve to screen someone for how likely they are to have PTSD. Those numbers compare quite well with other screening tests used in medicine, Marmar says. The screening test in real-world use would return a probability value, he says, showing how likely a person is to have PTSD. In cases of high probability, the military could refer the person for appropriate interventions that it has in place. Looking that far down the road might be jumping the gun a bit. “While I applaud the study’s goal of defining a pool of biomarkers for diagnosis of PTSD, we have to be realistic that the cohorts used in the study are limited in size,” says Daniel Domingo-Fernandez, a bioinformatician at Fraunhofer Institute for Algorithms and Scientific Computing in Germany, who was not involved in the study. It’s not guaranteed that the panel will work in a larger independent cohort with that level of accuracy, he says. The plan, Marmar says, is to perform the test in bigger populations of male veterans, then to include female veterans, and then turn to mixed general populations before seeking FDA approval. “There will be attempts to validate these same markers in civilian contexts, such as for disaster victims, sexual assault survivors, or industrial accident survivors,” he says. But development should not move too quickly. “Introducing biomarker findings in PTSD diagnosis should proceed rather carefully,” says Dorothee Horstkötter, a neuroethicist at Maastricht University in the Netherlands. “In the end, PTSD as a mental health disorder is always also characterized by human suffering, a person’s personal perspective on her suffering, and behavioral and social problems.” She says research on the ethical and social implications of biomarker-based tools should parallel their development. “Biomarkers are likely to constitute a valuable addition to a complex diagnostic toolkit in the foreseeable future,” Horstkötter says. Yet they can be a “double-edged sword, reducing or enhancing stigmatization” among people who screen positive for the condition. A positive result on a test can furnish objective confirmation of being “really different” from one’s peers. Such concerns would be especially relevant, she says, if a biomarker test were used to screen the general population, which Marmar says is the ultimate goal. Marmar adds that it’s understandable that the idea of using biomarkers to identify a psychiatric condition might give pause. “People aren’t used to psychiatry being practiced as a laboratory medicine discipline,” he says. “It’s a little scary to the general public because people don’t like to think of psychiatric illnesses as having an objective biological basis.”
Despite the higher rates, some service members are reluctant to disclose the symptoms they’re experiencing. Hesitation may stem from the complicated stigma historically associated with PTSD and concerns about risks to reputation and livelihood if the “PTSD” label tracks them through their careers. Concealment, though, means that their condition may go untreated.
To bridge this gap for service people, the U.S. government is on the hunt for effective ways to screen large populations for PTSD. Although psychological conditions have a reputation for being “all in the mind,” they can involve physical changes throughout the body, affecting metabolism, heart rate and hormones. In research funded in part by the U.S. Army Research Office and U.S. Department of Defense, a large team of investigators sorted through a haystack of possible blood markers of such changes and identified 27 that combine with heart rate measurement to make up an apparently effective screen. They published their results September 10 in Molecular Psychiatry.
The blood test, says senior study author Charles Marmar, chair of the department of psychiatry at NYU School of Medicine, could provide an efficient means to look for PTSD signals in active-duty military personnel returning from combat or anticipating redeployment. This kind of population-level screening is needed to get people appropriate care, he says, when military personnel “are often quite reluctant to tell [about] symptoms that they do have.”
To develop the 28-factor screen, Marmar and his colleagues began with almost a million genomic, protein, metabolic, and other molecular candidates that they assessed in blood samples of 77 veterans with diagnosed PTSD and 74 veterans without the condition. All participants were male, had been in a war zone in either Iraq or Afghanistan and had experienced at least one traumatic war zone event.
In a process of elimination based on how consistently certain blood-based markers could be linked to PTSD, the researchers sieved out almost all of the candidate factors. They finally ended with a group of 27 chemical signatures that together with heart rate offered the best accuracy for identifying PTSD. Some but not all of the markers had previously been linked to the condition and include measures related to insulin levels and blood clotting.
The research team then tested how well the markers they found worked in a separate pool of 52 veterans—26 with diagnosed PTSD and 26 without it. The markers achieved an accuracy of 81 percent in distinguishing the two groups. The test panel detected a person as having a positive PTSD result 85 percent of the time and properly identified that a person did not have the condition 77 percent of the time. The results aren’t diagnostic but instead serve to screen someone for how likely they are to have PTSD.
Those numbers compare quite well with other screening tests used in medicine, Marmar says. The screening test in real-world use would return a probability value, he says, showing how likely a person is to have PTSD. In cases of high probability, the military could refer the person for appropriate interventions that it has in place.
Looking that far down the road might be jumping the gun a bit. “While I applaud the study’s goal of defining a pool of biomarkers for diagnosis of PTSD, we have to be realistic that the cohorts used in the study are limited in size,” says Daniel Domingo-Fernandez, a bioinformatician at Fraunhofer Institute for Algorithms and Scientific Computing in Germany, who was not involved in the study. It’s not guaranteed that the panel will work in a larger independent cohort with that level of accuracy, he says.
The plan, Marmar says, is to perform the test in bigger populations of male veterans, then to include female veterans, and then turn to mixed general populations before seeking FDA approval. “There will be attempts to validate these same markers in civilian contexts, such as for disaster victims, sexual assault survivors, or industrial accident survivors,” he says.
But development should not move too quickly. “Introducing biomarker findings in PTSD diagnosis should proceed rather carefully,” says Dorothee Horstkötter, a neuroethicist at Maastricht University in the Netherlands. “In the end, PTSD as a mental health disorder is always also characterized by human suffering, a person’s personal perspective on her suffering, and behavioral and social problems.” She says research on the ethical and social implications of biomarker-based tools should parallel their development.
“Biomarkers are likely to constitute a valuable addition to a complex diagnostic toolkit in the foreseeable future,” Horstkötter says. Yet they can be a “double-edged sword, reducing or enhancing stigmatization” among people who screen positive for the condition. A positive result on a test can furnish objective confirmation of being “really different” from one’s peers. Such concerns would be especially relevant, she says, if a biomarker test were used to screen the general population, which Marmar says is the ultimate goal.
Marmar adds that it’s understandable that the idea of using biomarkers to identify a psychiatric condition might give pause. “People aren’t used to psychiatry being practiced as a laboratory medicine discipline,” he says. “It’s a little scary to the general public because people don’t like to think of psychiatric illnesses as having an objective biological basis.”
