Standard medical tests can effectively diagnose such conditions as diabetes and heart disease, but mental health conditions remain elusive because biological markers are lacking. A recent pilot study suggests that this might soon change. Researchers investigated epigenetic shifts among children involved in family talk therapy for survivors of the 1998–1999 Kosovo war. Many women from this war experience post-traumatic stress disorder, affecting their families. Over 10 therapy sessions in 2021 and 2022, trained staff facilitated sensitive discussions, helping children to understand their mothers’ anxiety and depression without directly addressing the trauma. This approach may pave the way for biomarkers in psychology and elucidate how therapy can disrupt generational trauma.
Doctors can use blood glucose to diagnose and monitor diabetes, blood pressure for heart conditions and proteins in urine for liver disease. But what about biomarkers for mental health conditions?
“There are really no good biological markers for mental disorders,” says co-author Line Hjort, a human biologist and epigeneticist at the University of Copenhagen.
A pilot study published in Brain and Behavior suggests that biomarkers for mental health conditions could be on the horizon. Researchers identified shifts in the epigenome – the system that governs which genes are turned on and off – among children before and after family talk therapy.
“Although larger-scale studies will be essential to determine whether the biomarkers prove reliable, epigenetics holds ‘surprising’ promise for psychology, a field that has long lacked objective biological metrics,” says Line Hjort.
The groups’ findings also have implications for how generational trauma is passed on, the researchers say – and how talk therapy may be able to disrupt this.
Trauma and talk therapy
Talk therapy is often downplayed compared with other mental health interventions such as medication, researchers say – especially because of the lack of biomarkers providers can point to as evidence of the treatment’s impact.
Several years ago, a non-profit organisation in Kosovo reached out to researchers in Denmark and Australia to determine whether epigenetics could provide talk therapists the biomarker they have been looking for. Hjort recalls: “They were saying, ‘Isn’t there any molecular or biochemical way we can measure people with anxiety or post-traumatic stress disorder and determine whether they are sick?’”
The Kosova Rehabilitation Center for Torture Victims (KRCT) provides mental health services to survivors of the Kosovo war of 1998 and 1999, in which Yugoslav troops committed war crimes against ethnic Albanians. Today, 25 years later, many women who experienced sexual violence during the war cope with post-traumatic stress disorder – which can also affect their families.
As part of the epigenetics study, trained staff at KRCT offered family talk therapy to women who survived sexual violence in the war and their children and partners.
Over 10 sessions in 2021 and 2022, the KRCT staff guided conversations about each family’s dynamic, daily lives and any problems they were facing, the researchers write. Since the children in the study ranged in age from about 5 to 18 years old, conversations about the mothers’ mental health needed to be addressed delicately.
Rather than discuss the trauma itself, KRCT staff helped to explain to the children that “maybe mom has some anxiety or depression – whatever her symptoms of post-traumatic stress disorder are – and that it is not her fault. She experienced something traumatic,” Hjort says.
Blood and genetic bookmarks
To search for physical evidence of the impact of therapy, the researchers collected blood samples from 30 children who participated in the family therapy: one month before treatment began, to establish a baseline, and a second round after the therapy was complete. An additional 32 children served as a control group – they and their families received the same treatment, just delayed by several months. Both groups of children were similar in age, sex distribution and the area in which they lived.
Hjort set out to analyse changes to the children’s epigenome – an ever-changing system of molecular bookmarks called methyl groups that indicate which genes are switched on and off. Our DNA is “like a cookbook,” Hjort explains. “You can have a recipe for something, but all the little notes you put in the margins to remember to do this and that are what make it really work. That is epigenetics.”
Hjort and team sequenced the children’s epigenomes using a “platform that investigates almost a million sites across the whole genome,” she says.
Hjort says that she typically studies the epigenetics of such conditions as diabetes, with interventions including medication or lifestyle changes that are often considered to have stronger physiological effects than mental disorders and talk therapy. “To be honest, I did not think that we were going to observe many epigenetic differences between the children of mothers with post-traumatic stress disorder during pregnancy versus mothers without it,” Hjort says. “I was very wrong.”
The difference 1% makes
To her surprise, Hjort says that they found striking differences between the cortisol levels of children who had received the family therapy and those that had not, and at the same time there were modest changes in epigenetic signatures – from 1% to 10% methylation difference, which is considerable for epigenetic studies.
However, the finding should be taken with a grain of salt, Hjort says. Since epigenetic studies examine so many sites across the genome, researchers need tremendous sample sizes to be certain that the patterns they identify do not result from chance. “You would need maybe 1,000 participants” before drawing firm statistical conclusions, she says.
Studies of that size have a considerable cost, she adds – each epigenome analysis costs about €400.
Nevertheless, where were these differences in methylation between the children who received therapy and those who did not, and what could they be doing?
Gene linked to trauma resilience
The researchers identified a gene called HM13. HM13 is believed to play an important role in fetal development and has been associated with restricted growth of the fetus andplacental stress during pregnancy. But of greater interest to the researchers, a previous study involving adults with severe mental illness found that differences in the methylation of HM13 were associated with childhood trauma, specifically sexual abuse. Since epigenetic markers can be passed down from parent to child, this could suggest that therapy might be able to mitigate some inherited generational trauma.
Hjort says that several of the other spots with different methylation patterns unfortunately are not well described – in most instances, we do not know what these sections of DNA code for, if anything, or how methylation might affect their activity.
“Methylation changes can affect gene expression, but we do not know how much methylation change corresponds to gene expression change. This is not one to one.”
Hjort says that future studies also need to examine how long any methylation changes caused by therapy last – whether the biological signature persists for days, weeks, months or years after therapy is over is unclear. “A 1% methylation change – does it matter? Over a lifetime, it may,” Hjort says.
