For half a century, psychiatrist Robert C Bransfield, MD, has practiced psychiatry in New Jersey, dedicating his career to one of the field’s most challenging areas: treatment-resistant psychiatric illness. Over time, his curiosity and clinical observation led him to a striking and often underrecognized contributor to mental illness, infectious disease.
“In doing that,” says Bransfield, “many cases, particularly here in New Jersey, they had an infectious disease component, and when we looked at that infectious disease component, it helped us to get more effective treatment for people who would otherwise be treatment resistant.”
Bransfield has long been fascinated by the complex etiology of mental illness. “I’ve always been interested in what exactly causes mental illness. That’s always been a mystery,” he reflects. “And if you look at it historically, there were old beliefs of demon possession. It was your mother’s fault, low serotonin, you had bad genes. And in reality, it’s a very complicated formula of what causes it.”
He challenges the notion that mental illness arises spontaneously. “Some people feel that it just comes from nowheres, which doesn’t make sense. Everything’s caused by something. Nothing’s caused by nothing,” he asserts.
From Genetics to Infection
While genetics have played a central role in modern psychiatry’s understanding of mental illness, Bransfield urges caution. “Developmental genes alone don’t make sense. There’s only about half a dozen clear mental illness genes. But in reality, there’s susceptibility genes.”
These susceptibility genes, he explains, can be activated by environmental triggers—one of the most compelling being infection. “The environmental trigger can be many things, but infection does come up a lot, and we found 60 different infectious diseases that are associated with different mental illnesses when we did a literature search.”
From an evolutionary standpoint, the prevalence of mental illness remains paradoxical. “If the brain is perfected so well with evolution, why is there so much mental illness?” he asks. His working theory: “You have susceptibility genes that are triggered by certain environmental conditions and that can cause mental illness, either congenitally or early development or fairly recently, and there’s often an immune mediator.”
Understanding Disease Progression
Bransfield emphasizes the importance of mapping disease progression in psychiatric disorders. “If you understand the susceptibility, the early stages, the later stages—think of it like a row of dominoes. And if you intervene at any one of those dominoes, that could prevent disease progression.”
He continues, “Once the disease occurs, then you can look at what perpetuates it, which may be different than what caused it. So it’s like a vicious cycle. You’re trying to break that, knowing there’s many contributors, many deterrents, and sometimes acute triggers.”
A Historical Perspective
The link between infection and mental illness isn’t new. “Syphilis drew attention to it. Noguchi, he wrote about that. So that was clear infection in the brain. But then once we had penicillin, there was kind of a shifting away from that.”
He recalls the work of Dr. Henry Cotton in New Jersey’s Trenton State Hospital, who hypothesized infection’s role in psychiatric illness and employed a now-infamous method of removing infected organs. “That went over the top, even though there may be some basis to that. It was a radical treatment approach.”
Later, the slow virus theory of the 1960s, along with work from the Stanley Lab at Johns Hopkins, brought renewed attention to infectious contributors—particularly Toxoplasma gondii. “We would meet in Germany every two years, in Gunzburg, and we would look at the psychoimmunology—the neuropsychoimmunology—which is the intermediate link. You have the infection, then it affects the immune system, and then the immune system contributes to a lot of symptoms.”
The Role of Tick-Borne Diseases
In recent decades, tick-borne diseases have emerged as a significant contributor to neuropsychiatric symptoms—especially in New Jersey. “A lot of people have tick-borne disease, and you see a lot of mental illness associated with tick-borne diseases. That happens a lot, often many years after initial infection.”
He identifies Borrelia as a key pathogen. “The most frequent infection can be Borrelia. Different kinds of Borrelia—it could be relapsing fever Borrelia, it could be Lyme Borrelia. There’s a lot of different types of Borrelia.”
He also highlights Bartonella, often in tandem with other infections. “Bartonella—think of it almost like with HIV or COVID or Lyme. You see it, one organism. It’s a complex, interactive infection, and there may be one organism that may be immunosuppressant, and then that activates other infections that might otherwise be latent.”
Such coinfections complicate diagnosis and treatment. “It’s a very complicated formula, it seems, how these infections interact with each other, and we’re still trying to understand how that works. It’s not a simple postulate, where you get one organism and one clear manifestation.”
Indeed, two patients with the same infection may present very differently. “Many different people can have the same infection, have many different manifestations of it, depending on their vulnerabilities or genetic vulnerabilities.”
Depression as a Common Link
Among the various psychiatric outcomes, depression stands out. “The most common manifestation is really depression—depression particularly with tick-borne disease. With Lyme disease, there have been about 10 different studies on depression.”
But depression is only the tip of the iceberg. “Then there are other, less common manifestations that you see. You can see a broad range of psychiatric illnesses, cognitive impairments, neurological, and general medical impairments.”
Stay tuned for Part 2-4, where we’ll dive deeper into the specific infectious agents linked to mental illness and explore how they interact with the immune system to influence psychiatric symptoms. This series will shed light on new perspectives in understanding and treating complex psychiatric conditions.
