Study suggests shared genetic roots between psychiatric disorders and COVID-19 risk

A new study published in Molecular Psychiatry reveals that some psychiatric disorders share genetic risk factors with COVID-19 infection and severity. Using large-scale genetic data, the researchers found overlapping biological pathways—especially those related to immune system function—between disorders such as depression, attention-deficit/hyperactivity disorder, and post-traumatic stress disorder, and both COVID-19 infection and hospitalization risk. These findings suggest that the link between mental illness and vulnerability to COVID-19 may stem not only from environmental or behavioral factors, but also from shared genetic foundations.

The COVID-19 pandemic has had a profound impact on mental health around the world. But long before the virus disrupted daily life, researchers knew that people with psychiatric conditions tend to experience worse physical health outcomes in general. Over the course of the pandemic, several studies confirmed that individuals with pre-existing psychiatric disorders were more likely to contract the virus, experience more severe symptoms, and face higher mortality rates.

This raised the question: is the link between psychiatric disorders and COVID-19 outcomes solely due to environmental or lifestyle factors, such as living conditions, medications, or health behaviors—or are there shared biological underpinnings?

To explore this possibility, a team of researchers from institutions in Spain and Australia conducted an in-depth analysis using data from the largest available genome-wide association studies. These studies identify common genetic variants that are more frequently found in individuals with specific traits or conditions. The team focused on seven psychiatric disorders: depression, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, anxiety, autism spectrum disorder, and post-traumatic stress disorder. They also included a general “P-factor,” which represents a shared genetic liability across mental health conditions.

They compared these datasets with two COVID-19 outcomes: confirmed infection and hospitalization. Importantly, the researchers did not just look at whether the disorders and COVID-19 were linked—they tested whether there were shared genetic variants and whether those variants might play a causal role in increasing susceptibility.

Their analyses revealed significant genetic correlations between depression, ADHD, PTSD, and the P-factor with both COVID-19 infection and hospitalization. Anxiety also showed a positive correlation with hospitalization, but not with infection. In contrast, bipolar disorder, schizophrenia, and autism spectrum disorder did not show significant genome-wide associations with COVID-19 outcomes, though local overlaps were still detected in specific regions of the genome.

To understand where these overlaps occurred, the researchers divided the genome into over 1,700 independent regions and used a method called pairwise GWAS to identify which regions were shared between psychiatric disorders and COVID-19 traits. They identified several specific genomic regions that appeared to be causally shared—mostly located on chromosome 17, a region already linked to immune and neurological functions. These regions contained genes involved in immune response, stress regulation, and thyroid function.

One notable gene identified was THRA, which is involved in thyroid hormone signaling. It was found to be shared between depression, bipolar disorder, and COVID-19 infection. Dysfunctions in thyroid hormone receptors have been linked to mood disorders and immune deficiency, which could explain how this gene contributes to both psychiatric conditions and vulnerability to infection.

Another gene, CRHR1, was shared between schizophrenia, autism spectrum disorder, and COVID-19 hospitalization. CRHR1 plays a central role in the body’s stress response and also affects immune regulation. This dual role suggests that individuals with altered CRHR1 function may be more vulnerable to stress-related psychiatric disorders and at the same time experience an impaired immune response to viral infections.

The gene BPTF, linked to immune cell function and neurodevelopment, was shared between the general P-factor, depression, PTSD, and COVID-19 hospitalization. This convergence hints at the possibility that common disruptions in immune regulation may increase both the risk for psychiatric conditions and the likelihood of serious complications from COVID-19.

To go a step further, the researchers also used causal inference methods to explore whether genetic predisposition to psychiatric disorders could directly increase the risk of COVID-19 infection and hospitalization. These methods mimic randomized controlled trials by using genetic variants as natural experiments. They found evidence suggesting that depression, ADHD, and PTSD might causally increase the likelihood of COVID-19 infection. PTSD and the general P-factor also showed evidence of a causal effect on hospitalization risk. Interestingly, bipolar disorder appeared to be linked to a slightly reduced risk of hospitalization, though this finding was not consistent across all statistical tests.

The researchers also explored potential drug interactions with the identified genes. For example, CRHR1 interacts with medications like fluoxetine—an antidepressant that has shown anti-inflammatory effects in some studies—and corticosteroids like budesonide, which are used to treat respiratory conditions. This opens up the possibility of repurposing existing medications to improve COVID-19 outcomes among people with psychiatric conditions, especially those who may be genetically predisposed to worse illness.

Despite these compelling findings, the study has several limitations. All of the genetic data came from people of European ancestry, so the results may not apply to other populations. Some of the psychiatric disorders, such as anxiety and ADHD, may have lacked sufficient statistical power to detect certain effects. And while genetic methods can suggest potential causal relationships, they rely on assumptions that can be difficult to fully verify, especially when datasets share overlapping participants.

Sex differences were not examined due to data constraints, and other important variables like body weight or vaccination status could not be included. The study also did not examine complex interactions between genes, which may play a role in shaping both mental health and infection risk.

Nevertheless, this research offers a new perspective on the biological relationship between mental illness and infectious disease. Rather than viewing the increased vulnerability of people with psychiatric disorders to COVID-19 as a purely social or behavioral issue, the findings suggest that underlying genetic factors—especially those linked to immune system function—may play an important role.

The study, “Genetic analyses point to alterations in immune-related pathways underpinning the association between psychiatric disorders and COVID-19,” was authored by Anna Monistrol-Mula, Santiago Diaz-Torres, Mireia Felez-Nobrega, Josep Maria Haro, Sarah E. Medland, and Brittany L. Mitchell.