Microbial Infections and Mental Illness: Bridging Psychiatry and Infectious Disease

A growing body of evidence is highlighting the role of microbial infections in the development and progression of various mental illnesses, according to a comprehensive review published in Healthcare by Bransfield and colleagues. The review identifies a range of pathogens, including Borrelia burgdorferi, Toxoplasma gondii, Bartonella species, Group A Streptococcus, Epstein–Barr virus, and SARS-CoV-2, as being associated with psychiatric conditions such as autism spectrum disorder, schizophrenia, bipolar disorder, depression, and anxiety. These infections have also been linked to suicidality, aggressive behavior, and other behavioral disturbances.

“We did the journal article with microbes and mental illness. That was with two co-authors: Dr. Greenberg and Dr. Mao. Dr. Greenberg is a child psychiatrist. Dr. Mao is a pediatric infectious disease doctor,” said Robert Bransfield, MD, lead author and clinical psychiatrist. “So, we went over the entire literature, and we looked at, first of all, six conditions—well, we looked at three—the conditions that were most associated with disability, and that was autism, schizophrenia, bipolar disorder, depression, anxiety. But then we also looked at suicide and violence.”

The review explores several mechanisms by which infections may influence brain function. These include direct microbial invasion of the central nervous system, immune activation that leads to neuroinflammation, autoimmune responses, and long-term immune dysregulation even after the infection has resolved. “So, you can get developmental impairments. You could get mental illnesses. You could also get behavior problems, such as suicidality or aggressive behavior, substance abuse—you can see increased,” Bransfield explained. “It’s quite a spectrum of psychiatric impairments and cognitive impairments.”

The authors highlight the concept of cumulative pathogen exposure, or total pathogen load, as a possible contributor to persistent neuropsychiatric symptoms in vulnerable individuals. In these cases, the interplay between the immune response and brain function may result in lasting changes in behavior, cognition, and mood. “Think of what the infections can do. They can cause impairments. So, it can be from active infection, or what might be a hit-and-run—a prior infection that causes a permanent impairment, even though the infection is gone—or it could be chronic relapsing infection that can come and go,” Bransfield said.

A key focus of the article is what the authors term “serious mental illness,” which encompasses autism, schizophrenia, and bipolar disorder. “Now, there’s a condition that we call serious mental illness. And serious mental illness is autism, schizophrenia, and bipolar. This is the group that are very disabled,” Bransfield said. “Now, serious mental illness isn’t just a mental illness. If you look at those three illnesses, it’s a multi-system illness that has a cardiometabolic component also, and it affects other systems.”

In one documented case, Bransfield described a 32-year-old patient with Lyme disease who died by homicide-suicide. “We did an autopsy exam. And autopsies are really the gold standard for this. We found Borrelia in his pancreas and in his heart, even though he was 32. And we also found a biochemical effect of the infection in his brain, which is quinolinic acid,” he said. “So, there is the triad that we often see where there’s a psychiatric, cardiac, and metabolic component in serious mental illness.”

The review also incorporates insights from emerging disciplines such as psychoimmunology and psychoneuroimmunology, which study how immune signaling within the brain affects mood and cognition. “Part of our brain transmission is neurotransmitters, but part of it is immune transmitters,” said Bransfield. “So, we need to connect the dots and see that connection.”

This evolving biological model represents a shift from traditional views of psychiatric illness. “Historically, perspectives on the etiology of mental illness have evolved from demonic possession toward multisystem biologically based models that include gene expression, environmental triggers, immune mediators, and infectious diseases,” the authors wrote. Bransfield added, “Genes don’t change that fast, so we can’t blame it on genes. There may be susceptibility genes, but there’s some environmental trigger. There is about 20 different infections there.”

The implications extend beyond psychiatric diagnosis. The authors cite mounting evidence linking microbial agents to neurodegenerative conditions, including dementia. “Now, with something like dementia—and now there’s recent looking at dementia—for instance, the shingles vaccine reduces the risk of dementia. What is the link there?” Bransfield asked. “They find dental spirochetes, they find Lyme, they find other Borrelia, they find microbes that they haven’t even been categorized yet.”

Despite growing recognition of these associations, a significant knowledge gap persists. “A problem is that many psychiatrists don’t know much about infectious disease, and many infectious disease doctors don’t know much about psychiatry,” Bransfield said. “The link between the two is the immune system, and it’s often how the immune system functions within the brain.”

To navigate contentious terminology around persistent infections, Bransfield offers a practical framework: “One way to think of it is infection-associated chronic illness. That’s a way of wording it. People would fight with the word ‘chronic,’ where they argue, ‘Well, is it chronic infection? Is it chronic symptoms?’” He continued, “Infection-associated chronic illness gets around that argument, knowing that there’s probably multiple mechanisms that occur, and some of these are inflammatory-mediated, and some are autoimmune-mediated.”

In conclusion, Bransfield and his colleagues emphasize the importance of interdisciplinary research and clinical strategies to advance prevention, diagnosis, and treatment. “So, when we look at that, we’re really seeing things to treat people in ways we never could before. And that’s a great thing that we can move forward,” he said. Reflecting on the evolving science, Bransfield added, “I’d say the quote of Yogi Berra: ‘I never would have seen it if I didn’t believe it.’ And I think once you start looking for it and paying attention to it, you’ll see this connection, and that can help prevent a lot of these chronic illnesses that are very burdensome to our patients and to our society.”

For our introduction to this topic, listen to Part 1 here. Stay tuned for the next two parts coming over the next few days.

Reference

Bransfield RC, Mao C, Greenberg R. Microbes and Mental Illness: Past, Present, and Future. Healthcare. 2024; 12(1):83. https://doi.org/10.3390/healthcare12010083