Saliva May Help Diagnose PTSD in Veterans
As a bioinformatician and young veteran, Guy Shapira welcomed the opportunity to help with conducting a study to determine if saliva can reveal if war veterans have post-traumatic stress disorder, or PTSD.
The research team, which drew mostly from Tel Aviv University’s Sackler Faculty of Medicine and Sagol School of Neuroscience, collected saliva samples from approximately 200 veterans who suffered psychological trauma stemming from the years they spent fighting in the First Lebanon War in 1982. The researchers also characterized the participants’ psychological, social and medical conditions, including a detailed analysis of their microbiomes.
They found that the former soldiers with PTSD have a certain set of bacteria in their saliva, a distinct microbiotic signature that is believed to be the first biological marker for PTSD. The finding suggests that, in the future, saliva tests could be used to help identify this disorder. As of now, PTSD is often challenging to diagnose.
Shapira, a Ph.D. student at Tel Aviv University, was responsible for examining genetic and health-related data of the veterans who participated – information that had been compiled steadily over four decades. The veterans provided this data voluntarily, Shapira says, at least partly because the study carries important implications for their own psychological health.
The research was led by Illana Gozes, professor emerita of clinical biochemistry. “We looked at the bacteria in their blood and their saliva,” Gozes explains. To discover the microbial signatures, they analyzed the biometric data for each soldier individually and as a group. Comparing the results of the participants’ microbial distribution to the results of their psychological examinations and their responses to personal welfare questionnaires, the researchers learned that veterans with PTSD – and, more generally, those with significant mental health issues – have the same bacterial content in their saliva.
“Having empirical metrics to assess whether or not someone has PTSD can help veterans who make their case to the Army to get reparations,” Shapira says.
More research is required to support this finding, published in July in Nature’s prestigious Molecular Psychiatry, but it could have important implications for identifying people with PTSD. Currently, it can be diagnosed only through psychological and behavioral symptoms such as flashbacks, nightmares, sleep disorders, increased irritability and physical aggressiveness. Veterans sometimes don’t report these symptoms to health providers or realize they’re related to the trauma they experienced during combat.
The researchers also identified a correlation that indicates people with a higher level of education show a lower occurrence of the microbiotic signature linked to PTSD, while people who experienced greater exposure to air pollution show a higher occurrence of this signature. That confirms their finding that the veterans’ health is dependent on their individual biology combined with the conditions of their environment.
“Thanks to this study, it may be possible in the future to use objective molecular and biological characteristics to distinguish PTSD sufferers, taking into account environmental influences,” Gozes said in an article in Israel21c. “We hope that this new discovery and the microbial signatures described in this study might promote easier diagnosis of post-traumatic stress in soldiers so they can receive appropriate treatment.”
Gozes added that roughly a third of the subjects in their study hadn’t been diagnosed with PTSD previously. That meant they had never received any support from Israel’s Ministry of Defense or other officials for treatment and reparations, the payments to compensate for injuries sustained during war.
Shapira’s motivation to participate in this study is personal as well as professional: in addition to being veteran himself, his father served in the First Lebanon War. “Fortunately, he did not develop any PTSD, despite being shot in the foot...some of his friends died, so it wasn’t easy on him,” says Shapira.
“Having empirical metrics to assess whether or not someone has PTSD can help veterans who make their case to the Army to get reparations,” Shapira says. “It is a very difficult and demanding process, so the more empirical metrics we have to assess PTSD, the less people will have to suffer in these committees and unending examinations that are mostly pitched against the veterans because the state is trying to avoid spending too much money.”
Podcast: Should Scientific Controversies Be Silenced?
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
The recent Joe Rogan/Spotify backlash over the misinformation presented in his recent episode on the Covid-19 vaccines raises some difficult and important bioethical questions for society: How can people know which experts to trust? What should big tech gatekeepers do about false claims promoted on their platforms? How should the scientific establishment respond to heterodox viewpoints from experts who disagree with the consensus? When is silencing of dissent merited, and when is it problematic? Journalist Kira Peikoff asks infectious disease physician and pandemic scholar Dr. Amesh Adalja to weigh in.
Dr. Amesh Adalja, Senior Scholar, Johns Hopkins Center for Health Security and an infectious disease physician
Listen to the Episode
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Scientists Are Studying How to Help Dogs Have Longer Lives, in a Bid to Further Our Own
The sad eyes. The wagging tail. The frustrated whine. The excited bark. Dogs know how to get their owners to fork over the food more often.
The extra calories dogs get from feeding patterns now used by many Americans may not be good for them from a health and longevity viewpoint. In research from a large study called the Dog Aging Project, canines fed once a day had better scores on cognition tests and lower odds of developing diseases of organs throughout the body: intestinal tract, mouth and teeth, bones and joints, kidneys and bladder, and liver and pancreas.
Fewer than 1 in 10 dog owners fed their furry friends once daily, while nearly three fourths provided two daily meals.
“Most veterinarians have been led to believe that feeding dogs twice a day is optimal, but this is a relatively new idea that has developed over the past few decades with little supportive evidence from a health standpoint,” said Matt Kaeberlein, PhD, Co-Director of the Dog Aging Project, a professor of pathology and Director of the Healthy Aging and Longevity Research Institute at the University of Washington. Kaeberlein studies basic mechanisms of aging to find ways of extending the healthspan, the number of years of life lived free of disease. It’s not enough to extend the lifespan unless declines in biological function and risks of age-related diseases are also studied, he believes, hence the healthspan.
The Dog Aging Project is studying tens of thousands of dogs living with their owners in the real world, not a biology laboratory. The feeding study is the first of several reports now coming from the project based on owners’ annual reports of demographics, physical activity, environment, dog behavior, diet, medications and supplements, and health status. It has been posted on bioRxiv as it goes through peer review.
“All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans. It just happens much faster in dogs.”
“The Dog Aging Project is one of the most exciting in the longevity space,” said David A. Sinclair, professor in the Department of Genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. “Not only is it important to help our companions live longer and healthier, but because they are like people and share the same environment and many of the lifestyles as their owners, they are the perfect model for human longevity interventions.”
The epigenetic clock — and specifically changes in gene expression resulting from methylation of cytosine and guanine in the DNA — provides the critical connection between aging in dogs and people. “All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans,” Kaeberlein said. “It just happens much faster in dogs.” These methylation changes, called the “methylomes,” have been associated with rates of aging in dogs, humans, and also mice.
In a 2020 study young dogs matched with young adults and aged dogs matched with older adults showed the greatest similarities in methylomes. In the Cell Systems report, Tina Wang of the University of California, San Diego, and colleagues wrote that the methylome “can be used to quantitatively translate the age-related physiology experienced by one organism (i.e., a model species like dog) to the age at which physiology in a second organism is most similar (i.e., a second model or humans).” This allows rates of aging in one species to be mapped onto aging in another species, providing “a compelling tool in the quest to understand aging and identify interventions for maximizing healthy lifespan.”
In the Dog Aging Project study, 8% of 24,238 owners fed their dogs once daily, the same as the percentage of owners serving three daily meals. Twice-daily feedings were most common (73%), and just over 1 in 10 owners (11%) “free fed” their dogs by just filling up the bowl whenever it was empty — most likely Rover’s favorite option.
“The notion of breakfast, lunch, and dinner for people in the United States is not based on large studies that compared three meals a day to two meals a day, or to four, “ said Kate E. Creevy, chief veterinary officer with the Dog Aging Project and associate professor at Texas A&M University. “It’s more about what we are accustomed to. Similarly, there are not large population studies comparing outcomes of dogs fed once, twice, or three times a day.”
“We do not recommend that people change their dogs’ diets based on this report,” Creevy emphasized. “It’s important to understand the difference between research that finds associations versus research that finds cause and effect.”
To establish cause and effect, the Dog Aging Project will follow their cohort over many years. Then, Creevy said, “We will be able to determine whether the associations we have found with feeding frequency are causes, or effects, or neither.”
While not yet actionable, the feeding findings fit with biology across a variety of animals, Kaeberlein said, including indicators that better health translates into longer healthspans. He said that caloric restriction and perhaps time-restricted eating or intermittent fasting — all ways that some human diets are structured — can have a positive impact on the biology of aging by allowing the gastrointestinal tract to have time each day to rest and repair itself, just as sleep benefits the brain through rest.
Timing of meals is also related to the concept of ketogenesis, Kaeberlein explained. Without access to glucose, animals switch over to a ketogenic state in which back-up systems produce energy through metabolic pathways that generate ketones. Mice go into this state very quickly, after a few hours or an overnight fast, while people shift to ketogenesis more slowly, from a few hours to up to 36 hours for people on typical Western diets, Kaeberlein said.
Dogs are different. They take at least two days to shift to ketogenesis, suggesting they have evolved to need fewer meals that are spaced out rather than the multiple daily meals plus snacks that people prefer.
As this relates to longevity, Kaeberlein said that a couple of studies show that mice who are fed a ketogenic diet have longer lifespans (years of life regardless of health). “For us, the next step is to analyze the composition of the dogs’ diets or the relationship of multiple daily feedings with obesity,” he said. “Maybe not being obese is related to better health.”
To learn more, the Dog Aging Project needs dogs — lots of dogs! Kaeberlein wants at least 100,000 dogs, including small dogs, large dogs, dogs of all ages. Puppies are needed for the researchers to follow across their lifespan. The project has an excellent website where owners can volunteer to participate.
Nutritional strategies are often not built around sound scientific principles, Kaeberlein said. In human nutrition, people have tried all kinds of diets over the years, including some that were completely wrong. Kaeberlein and his colleagues in the Dog Aging Project want to change that, at least for people’s canine companions, and hopefully, as a result, give dogs added years of healthy life and provide clues for human nutrition.
After that, maybe they can do something about those sad eyes and the frustrated whine.