Groundbreaking study shows women more genetically prone to PTSD

A new study published in the American Journal of Psychiatry has revealed that women may be at a higher genetic risk for developing post-traumatic stress disorder (PTSD) compared to men. This study, led by researchers from Virginia Commonwealth University and Lund University, is the largest twin-sibling study on PTSD conducted to date. The findings suggest that while both men and women are genetically susceptible to PTSD, the underlying genetic risk may be stronger in women.

Post-traumatic stress disorder is a psychiatric condition that occurs after experiencing or witnessing traumatic events. Individuals with PTSD often suffer from distressing symptoms such as flashbacks, nightmares, anxiety, and emotional numbness. While PTSD can affect anyone, studies have shown that women are twice as likely as men to develop the condition. Despite this disparity, the reasons behind the higher prevalence of PTSD in women remain unclear.

Many hypotheses have been proposed, including differences in trauma exposure, coping mechanisms, and biological factors. However, there has been limited research investigating the genetic underpinnings of these sex differences.

Previous studies hinted that PTSD might have a genetic component, but they left a gap in understanding whether these genetic risks differ between men and women. Additionally, earlier studies were often limited by small sample sizes or reliance on self-reported data, which can introduce biases. To address these shortcomings, the research team aimed to test whether genetic risk factors for PTSD vary between men and women using a large, nationally representative sample from Sweden.

“PTSD is an important disorder that has received less attention compared to other psychiatric disorders in genetic epidemiologic studies. Thus, estimates of heritability, that is, the degree to which genes influence risk for the disorder, and sex differences in the heritability of PTSD were important to study,” said Ananda B. Amstadter, a professor in the Virginia Commonwealth University School of Medicine’s departments of Psychiatry and Human and Molecular Genetics and lead author of the study.

For their study, the researchers analyzed data from over 16,000 twin pairs and more than 376,000 sibling pairs from Swedish national health and population registries. This large sample allowed them to explore both the genetic and environmental components of PTSD in a way that previous studies, with smaller sample sizes, could not.

The researchers gathered their data from several Swedish national registers, including the Swedish Twin Registry, which provided information on twins, and the Multi-Generation Register, which tracked full siblings. They also accessed health data from hospital records, outpatient care, and primary care clinics, which included PTSD diagnoses based on the International Classification of Diseases (ICD) codes.

By using these registry-based medical diagnoses, the researchers avoided potential biases related to self-reported data, such as memory errors or reporting inconsistencies. This gave their study a solid foundation for more accurate analysis.

To isolate the genetic factors contributing to PTSD, the researchers employed statistical models that compared different sets of twins and siblings. Monozygotic twins, who share 100% of their genes, were compared to dizygotic twins and full siblings, who share about 50% of their genes. This allowed the researchers to estimate the heritability of PTSD, which refers to the proportion of variation in PTSD risk that can be attributed to genetic differences.

“If you think of risk for PTSD like a pie chart, we’re trying to better understand what factors make up the pieces of this pie,” Amstadter said. “Some of the risk is influenced by a person’s environment, such as the experiences they have while growing up. On the other hand, some of the risk will be influenced by the genes they inherit from their parents.”

The study’s findings revealed that PTSD is moderately heritable, with genetic factors accounting for approximately 35% of the risk in women and 29% in men. This means that while both sexes inherit some genetic susceptibility to PTSD, the genetic contribution is stronger in women. This quantitative difference in heritability suggests that women have a higher genetic risk for developing PTSD compared to men, even after accounting for environmental factors.

Moreover, the study found evidence for qualitative differences in the genetic risk for PTSD between men and women. Although many of the same genes contribute to PTSD in both sexes, some genes appear to have sex-specific effects. This qualitative difference indicates that the genetic architecture of PTSD is not entirely the same in men and women, which could explain part of the observed disparity in PTSD prevalence.

“PTSD was found to be moderately heritable in both males and females,” Amstadter told PsyPost. “However, the heritability was significantly higher in females, meaning that genetic risk for PTSD is higher in females compared to males. Further, although the heritability was correlated substantially between the sexes, the findings suggest that some of the genes that contribute to the heritability for the sexes differ. This means that future research should focus on sex-specific pathways of risk for the disorder, which may have important implications for treatments.”

In addition to genetic factors, the researchers found that unique environmental experiences—such as individual life events or specific traumatic exposures—played a significant role in the development of PTSD. These environmental factors accounted for the majority of the variance in PTSD risk for both men and women.

Interestingly, the researchers found no evidence that shared family environments, such as growing up in the same household, had a significant influence on PTSD risk. This suggests that while genetics and personal experiences are important, the general family environment does not seem to contribute much to the likelihood of developing PTSD.

One intriguing direction for future research is investigating the role of sex hormones, such as estrogen and testosterone, in PTSD. Previous studies have suggested that hormonal fluctuations, particularly in women, may influence the development of PTSD by affecting the body’s stress response systems.

For example, estrogen has been shown to regulate genes involved in the stress response, and changes in estrogen levels during the menstrual cycle may make women more vulnerable to stress-related disorders like PTSD. Future studies could examine how these hormonal effects interact with genetic risk factors to increase or decrease the likelihood of developing PTSD.

Another area for future research is examining how genetic factors influence responses to PTSD treatments. While trauma-focused therapies, such as cognitive processing therapy, are effective for both men and women, some studies have suggested that women may respond better to these treatments than men. Understanding the genetic basis of treatment response could help personalize PTSD interventions, ensuring that individuals receive the most effective treatments based on their unique genetic and environmental risk factors.

The study, “Testing Quantitative and Qualitative Sex Effects in a National Swedish Twin-Sibling Study of Posttraumatic Stress Disorder,” was authored by Ananda B. Amstadter, Sara L. Lönn, Shannon Cusack, Jan Sundquist, Kenneth S. Kendler, and Kristina Sundquist.