Study Links Sexual Trauma and Polygenic Scores to Severe Mental Illness

Allison Lake, MD/PhD student

Credit: Vanderbilt University School of Medicine

A new study showed sexual trauma and mental health polygenic scores independently and jointly contribute to the risk of severe mental illness.¹

Investigators sought to examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder (MDD) in a clinical biobank setting. Particularly, they wanted to know whether the association between sexual trauma and the polygenic liability to the risk of mental illness was independent, joint, or interacting. The team hoped investigating the associations between genetic and environmental risk factors for mental illness could help clinical screening efforts.

“Evaluating how genetic risk interacts with environmental risk factors such as sexual trauma is important for understanding how mental illness develops and identifying high-risk groups for early intervention,” said Allison Lake, an MD/PhD student at Vanderbilt University School of Medicine and first author of the study, in a statement.²

The genetic association study leveraged clinical and genotyping data (1976 to 2023) from 96,002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center in Nashville (56.7% female; median age: 56.8 years) and Mass General Brigham in Boston (54.9% female; median age: 58 years).¹ The sample included participants from European (88.6%) and African (11.5%) ancestries. Participants were ≥ 18 years old and had ≥ 3 visits, starting when they were ≥ 10 years old.

Investigators collected data on diagnoses of schizophrenia, bipolar disorder, and MDD via diagnostic billing codes. Other data included sexual trauma disclosure status and polygenic scores. Lake and colleagues used a natural processing approach to detect sexual trauma disclosures, which included sexual abuse, assault, and rape.

“All natural language processing algorithms are limited by what data are available in the medical record, which is a consequence of what physicians screen for and document,” Lake said.² “As a future psychiatrist, I hope to advocate for routine screening and documentation of social determinants of health in the medical record to both enhance clinical care and improve the quality of clinical data that can be extracted from the EHR for research use.”

After analyzing the data from 2022 to 2024, the team found individuals with a history of sexual trauma have greater odds of being diagnosed with mental health disorders, such as schizophrenia, across the cohorts.¹ For instance, participants in the Vanderbilt University Medical Center cohort were approximately 8.8 times more likely to receive a schizophrenia diagnosis than those without trauma history (odds ratio [OR], 8.83; 95% confidence interval [CI], 5.50 to 14.18). Furthermore, the Mass General Brigham cohort had even greater odds, with a 17.7 times greater chance of a schizophrenia diagnosis for those with trauma history compared to those without (OR, 17.65; 95% CI, 12.77 to 24.40).

Moreover, sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of the mental health outcome variation. Investigators noted schizophrenia (OR, 0.70; 95% CI, 0.56 to 0.88) and bipolar disorder (OR, 0.83; 95% CI, 0.74 to 0.94) polygenic scores had greater associations with mental health outcomes in individuals without reported sexual trauma. Conversely, they found polygenic scores for schizophrenia and bipolar disorder had weaker links to mental health outcomes in participants with a history of sexual trauma.

“Our study suggests that schizophrenia and bipolar disorder polygenic scores generated using existing methods may be less predictive in the context of sexual trauma,” Lake said.² “As polygenic scores are being considered for use in clinical settings, our findings demonstrate the importance of expanding clinical screening efforts for trauma and other environmental risk factors that may impact the clinical interpretation of polygenic scores.”

References

1. ^{Lake AM, Zhou Y, Wang B, et al. Sexual Trauma, Polygenic Scores, and Mental Health Diagnoses and Outcomes. JAMA Psychiatry. Published online October 30, 2024. doi:10.1001/jamapsychiatry.2024.3426}
2. ^{Genetic Risk, Sexual Trauma Associated with Mental Illness: Study. EurekAlert! October 30, 2024. https://www.eurekalert.org/news-releases/1063203. Accessed October 30, 2024.}