Does psychiatric illness start with an infection? New research published in npj Schizophrenia suggests people who are exposed to infectious viruses or parasites may develop behavioral anomalies and disorders during adulthood.

It’s not a new idea, but it is one that’s gaining traction: An increasing number of studies have found links between the risk for schizophrenia and an overactive immune system. Most recently, a study published in Nature linked the presence of a protein that tells the brain which neural connections to remove as a child ages to a higher risk of developing schizophrenia. And in a study published in the American Journal of Psychiatry, people who were both at high risk of developing the disorder and those who had already been diagnosed had higher activity among microglia, a type of cell located in the brain and spinal cord that acts as the central nervous system’s first line of defense. The researchers concluded that overactive microglia might harm rather than help the brain, destroying connections it needs to function properly.

Inspired, researchers from Johns Hopkins Medicine, the Sheppard Pratt Health System, and Heidelberg University in Germany conducted a similar investigation, only they focused on the most dominant bacteria species in the human body: Candida albicans. It lines the human respiratory, gastrointestinal, and genitourinary tracts, and if not properly balanced, it can grow out of control and result in a yeast infection. Most often we hear about vaginal infections, but bacterial overgrowth can occur in the mouth and throat too. They wanted to see if it had any influence on schizophrenia and bipolar disorder.

First, they took blood samples from 808 people aged 18 to 65, of which 261 had been diagnosed with schizophrenia; 270 with bipolar disorder; and 277 without a history of psychiatric disorders to act as a control. Antibody levels in the blood indicated whether a participant had ever had a yeast infection. There was no connection between C. albicans antibodies and the disorders overall — but when the scientists looked at only men, 26 percent of those with schizophrenia had the antibodies compared to 14 percent of those in the control group. While men with bipolar disorder also had high levels of antibodies, the researchers attributed it to their history of homelessness. In addition to yeast infections, a 2003 study published in Skinmed found homeless people also face high risks of trauma, foot problems, and skin diseases.

There wasn’t much of a difference between disordered and control women, which makes sense since females are more prone to yeast infections. However, the high-antibody women diagnosed with schizophrenia and bipolar disorder scored lower than anyone else on cognitive tests that measure immediate and delayed memory, attention skills, use of language, and visual-spatial skills. The scores for diagnosed men, as well as control men and women, could not be attributed to the bacteria.

Researchers acknowledged that their findings echo existing sex-specific differences when it comes to yeast infections, but the “most direct and strongest linkage” they observed was in schizophrenic men with increase antibody activity. This association, they added, was independent of confounding variables, like age, race, antipsychotic medication, and socioeconomic status.

It could be that yeast enables a breakdown in the body that enables it to cross blood-gut and blood-brain barriers, where it would be in a position to alter behavior. For now, the researchers can only speculate on the reasons why.

"It's far too early to single out Candida infection as a cause of mental illness or vice versa," Dr. Emily Severance, member of the Stanley Division of Developmental Neurovirology at the Johns Hopkins University School of Medicine, said in a press release. "However, most Candida infections can be treated in their early stages, and clinicians should make it a point to look out for these infections in their patients with mental illness."

Source: Severance EG, et al. Candida albicans Exposures, Sex Specificity and Cognitive Deficits in Schizophrenia and Bipolar Disorder. npj Schizophrenia. 2016.