A groundbreaking study reveals that your genes may make you more vulnerable to Post Traumatic Stress Disorder (PTSD) from certain types of trauma—particularly childhood neglect—than from others.
The peer-reviewed findings, published today in the European Journal of Psychotraumatology , suggest that both what happens to you and your genetic makeup together affect your risk of developing the disorder.
PTSD; and who might be more vulnerable?
In the wake of a life-threatening event (trauma), many people experience strong emotional or physical reactions. These reactions can be overwhelming, but for most people they gradually ease over time. When they endure and begin to interfere with everyday life, they may evolve into PTSD.
Common symptoms of PTSD can include re-experiencing a traumatic event (e.g. through flashbacks, nightmares or intrusive thoughts), doing things to avoid being reminded of that event, and ongoing feelings of stress or negative emotions.
Not everyone who experiences trauma develops PTSD, with risk for the condition being shaped by both environmental and genetic factors. The largest genetic study of PTSD — a separate paper, which looked at 150,000 people with the condition — identified 95 genetic loci (a specific region on a chromosome) associated with PTSD and 43 genes with strong evidence for a causal effect.
The broad effect of the genome on PTSD differs across different experiences
"Differences in people's DNA have previously been linked to PTSD, but research on this topic has rarely considered how different types of traumatic experiences might affect these genetic links," explains senior author Dr Jonathan Coleman, a Senior Lecturer in Statistical Genetics at King's College London and an expert in psychiatric genomics.
"We found that the broad effect of the genome on PTSD does indeed differ across different experiences, and that this is also sometimes true when we look at the effects of specific genes."
The study team - funded by the Medical Research Council (a part of UKRI) – included a diverse range of experts from King's, including Dr Coleman and lead author Jacob Knyspel, a PhD student in psychiatric genetics and developmental psychology, as well as Professor Chérie Armour from Queen's University Belfast.
The researchers analysed mental health and genetic data from a total of 144,702 individuals in the UK Biobank and three studies in the National Institute for Health and Care Research (NIHR) BioResource and NIHR Biomedical Research Centre: Maudsley: Genetic Links to Anxiety and Depression (GLAD), Eating Disorders Genetic Initiative (EDGI) UK and COVID-19 Psychiatry and Neurological Genetics (COPING).
Individuals were assessed for PTSD symptoms and asked whether they had experienced eleven different traumatic experiences. These included five childhood traumas: emotional abuse or neglect, physical abuse or neglect, and sexual abuse; and six adulthood traumas: serious accident, serious illness, sexual assault, violent crime, war exposure, or witnessing death.
The researchers looked at whether the influence of a trauma on PTSD differs among people based on their genetics. They did this at three different scales: polygenic risk scores (that is, at a genome-wide level); individual genes; and specific genetic variants.
Childhood trauma often linked to PTSD symptoms and gene-trauma interaction
Overall, the researchers found that childhood traumas tended to be more strongly associated with PTSD symptoms and have greater levels of gene–trauma interaction than those experienced during adulthood. This suggests that genetics might have been particularly important in shaping how people responded to childhood trauma.
Childhood abuse was more strongly associated with PTSD symptoms than childhood neglect; the association with childhood neglect, although more moderate, was more likely to be influenced by genetic factors.
"Childhood is a very important time — a lot of changes are happening both biologically, in terms of your brain maturing, and also socially, in the formation of relationships and personal identity. Disruption to that can have long lasting effects, and that might help us explain particularly strong relationships between genetic risk, childhood trauma and PTSD," adds Dr Coleman, who co-leads the MSc in Developmental Psychology and Psychopathology at King's.
At the same time, he cautions, the findings might be influenced by the ways in which the researchers studied different types of traumatic experience: "Childhood is briefer than adulthood and we examined a narrower set of experiences in childhood — these differences might make childhood look more important than it really is."
The researchers also found that some of the main genes that have been linked to PTSD interacted particularly strongly with certain trauma types.
For example, FAM120A — a gene involved in the brain's processing of fear and stress — was found to interact significantly more strongly with childhood emotional neglect than any of the other traumas studied. Other genes, including ones involved in clearing old cellular proteins, neuronal communication, and bringing proteins to DNA, interacted strongly with a broad range of other traumas.
"Broadly, this fits with the biology of PTSD being based in how the brain develops, how the cells of the brain communicate, and how the body responds to stress," lead author Jacob Knyspel, a PhD student at King's, says.
"There were also outliers — one gene with strong trauma interactions, SGCD, is involved in muscle function, making its role in PTSD less clear.
"When we looked across genes, we didn't identify any particular biological process that could explain why certain traumas seemed more strongly linked to genetics, so more research is needed."
The future of PTSD and genetics in research – how treatment might improve
According to the researchers, their findings highlight the importance of factoring trauma exposure information into future PTSD genetics research.
"We might get a better understanding of how genetic changes affect people's risk of PTSD if we include information on the full range of experiences a person has had," Dr Coleman says.
In the future, this understanding could help to improve PTSD treatment.
"Ultimately, we would like to be able to measure people's DNA and use this to help screen people exposed to — or at risk of — particular traumatic events. That would help to ensure that the people most at risk of developing PTSD get support as early as possible, reducing the distress and disablement that PTSD can bring," Dr Coleman concludes.
