A new study has uncovered evidence suggesting that common viral infections may have a direct causal role in altering the risk for several major psychiatric disorders. The research found that while some viruses appear to increase the risk for conditions like major depression, others were surprisingly associated with a decreased risk for disorders such as anxiety, obsessive-compulsive disorder, and schizophrenia. These findings were published in the scientific journal Brain, Behavior, & Immunity – Health.
Scientists have long observed that people with serious mental illnesses often have higher rates of viral infections. This has led to questions about whether the infections contribute to the mental health conditions, or if other factors, like lifestyle or healthcare access, might explain the connection. Traditional observational studies struggle to separate correlation from causation because many unmeasured variables can influence both virus exposure and mental health.
A research team led by Jian-Wei Huang at Sun Yat-Sen University sought to overcome this challenge by using a genetic approach to investigate if a predisposition to certain viral infections could directly cause specific psychiatric disorders.
To untangle this complex relationship, the scientists employed a sophisticated statistical method known as Mendelian randomization. This technique uses genetic variations as a proxy for an exposure, in this case, a viral infection. The logic is that since genes are randomly assigned at birth, they are not influenced by lifestyle or environmental confounders that typically complicate health research. If a genetic variant that increases a person’s susceptibility to a particular virus is also consistently linked to a higher or lower risk of a psychiatric disorder, it provides stronger evidence for a causal connection between the virus and the disorder.
The researchers analyzed large-scale genetic data from pooled databases of individuals with European ancestry, primarily drawing from the FinnGen project, which includes genomic information for over 410,000 participants. They examined genetic markers associated with susceptibility to twelve different viruses, including hepatitis B virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, human papillomavirus, and Epstein-Barr virus. They then tested for causal links between these viruses and five psychiatric conditions: generalized anxiety disorder, obsessive-compulsive disorder, schizophrenia, major depressive disorder, and manic episodes.
The analysis revealed several significant and, in some cases, unexpected connections. The results indicated that a genetic predisposition to hepatitis B virus infection was causally linked to a reduced risk of generalized anxiety disorder. The odds of developing the disorder were about 6 percent lower for individuals with a genetic liability for this infection. This suggests a potentially protective effect of the virus or the immune response it triggers.
Similarly, some viruses appeared to lower the risk of obsessive-compulsive disorder. A genetic predisposition to human immunodeficiency virus was associated with a 16 percent reduced risk of the disorder. A genetic liability for severe acute respiratory syndrome coronavirus 2, the virus responsible for the COVID-19 pandemic, was linked to an even greater risk reduction of 22 percent for obsessive-compulsive disorder.
The study authors note this genetic finding contrasts with some observational reports of increased psychiatric symptoms after a COVID-19 infection, suggesting that any acquired psychological effects may not stem from an underlying genetic vulnerability shared between the virus and the disorder.
Another protective association emerged for schizophrenia. The analysis showed that a genetic liability for human papillomavirus infection was connected to a 16 percent decreased risk of developing schizophrenia. These findings showing protective effects from four different viruses challenge the simple idea that infections are universally detrimental to mental health and point toward a more intricate interaction between the immune system and the brain.
Not all findings were protective. The study also provided genetic evidence supporting a causal link between certain viral infections and an increased risk of major depressive disorder. A genetic predisposition to Epstein-Barr virus, a common herpesvirus known for causing mononucleosis, was associated with a slightly elevated risk of developing major depressive disorder.
A genetic liability for poliovirus infection was also linked to a 3 percent increased risk of the disorder. These results align with previous research suggesting that neuroinflammation triggered by viruses like Epstein-Barr may play a role in the biology of depression. For manic episodes, however, the researchers found no significant causal links with any of the twelve viruses they investigated.
The researchers conducted numerous sensitivity analyses to confirm the robustness of their results. These tests helped rule out the possibility that the genetic variants were influencing the psychiatric disorders through pathways unrelated to the viral infections, a potential issue known as horizontal pleiotropy. The consistency of the findings across different statistical models strengthened the authors’ conclusions about the causal relationships.
The study has some important limitations. The genetic data used in the analysis came exclusively from individuals of European ancestry. As a result, the findings may not be applicable to people from other ethnic backgrounds, where genetic predispositions and environmental factors can differ. The data also did not allow for analyses based on age or sex, which could be significant variables in the relationship between infections and mental health.
Future research will be needed to explore these connections in more diverse populations and to investigate the specific biological mechanisms behind both the risk-increasing and the protective effects. Understanding how an immune response to a virus might shield the brain from certain psychiatric conditions could open new avenues for prevention and treatment.
The study, “Viral infections and risk of mental illness: A Mendelian randomization study,” Jian-Wei Huang, Yi-Fei Wang, Miao Tang, Qian-Qian Cui, Ying Guo, and Shuang-Qi Gao.
