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Pilot study finds evidence of bartonella infection in schizophrenia patients

Raleigh, NC, USA (March 23, 2021) — A pilot study from North Carolina State University and the University of North Carolina at Chapel Hill has found evidence of Bartonella infection in the blood of people with schizophrenia and schizoaffective disorder.

„Researchers have been looking at the connection between bacterial infection and neuropsychiatric disease for some time,“ says Dr. Erin Lashnits, a former veterinary internist at NC State, current faculty member at the University of Wisconsin and first author of the study.

„Specifically, there has been research suggesting that cat ownership is associated with schizophrenia due to the zoonotic parasite Toxoplasma gondii, but to date there has been no conclusive evidence in support of a causative role for this parasite. So we decided to look at another cat-associated infectious agent, Bartonella, to see if there could be a connection.“

Bartonella are bacteria historically associated with cat-scratch disease, which until recently was thought to be solely a short-lived (or self-limiting) infection. Cats can become infected with Bartonella via exposure to fleas and potentially ticks, which are natural vectors of the bacteria. The cat is a host for at least three of the 40 known Bartonella species: Bartonella henselae, Bartonella clarridgeiae and Bartonella koehlerae.

„While there is emerging understanding of neuropsychiatric illnesses such as schizophrenia as disorders of brain networks, the question about the actual causes remains unanswered,“ says corresponding author Flavio Frohlich, associate professor of psychiatry at the UNC School of Medicine. „It was an exciting opportunity for us in the UNC Department of Psychiatry to team up with the leading experts on Bartonella to pursue this innovative idea of a potential link to schizophrenia. To our knowledge, this is the very first work that examines a potential role of Bartonella in schizophrenia.“

The research team enrolled a group of 17 people with stable, medically managed schizophrenia or schizoaffective disorder, and a control group of 13 healthy adults, to test for evidence of Bartonella infection.

All participants filled out questionnaires on severity of symptoms and potential Bartonella exposure. Blood samples were taken from participants twice in a one-week period. The samples were cultured in a growth medium, and both cultured and whole blood samples underwent qPCR and droplet digital, or ddPCR testing, at seven-, 14- and 21-day intervals, to look for evidence of Bartonella organism-specific DNA. Blood samples were also tested for Bartonella species-specific antibodies.

Of the 17 patients with schizophrenia, 12 had Bartonella DNA in their blood, as compared to only one of 13 in the control group. According to the questionnaires, both patients and controls reported similar pet ownership and flea exposures.

„Bartonella ddPCR, a very new diagnostic technology, provides a more sensitive molecular test than we’ve previously had access to,“ says Dr. Ed Breitschwerdt, Melanie S. Steele Distinguished Professor of Internal Medicine at NC State and study coauthor. „If we had not used ddPCR to test this cohort of individuals, we would not have found Bartonella DNA in any of the participants, either case or control.“

„It is important to remember that our study was by design not able to demonstrate a causal link between Bartonella infection and schizophrenia,“ Frohlich says. „However, we believe this initial observational study strongly supports the need for follow-up research.“

The researchers plan to proceed with a larger study to see whether their preliminary results are borne out.

„Many of these patients have been undergoing care for years,“ Breitschwerdt says. „What we’re starting to see is a pattern – Bartonella can persist for a long time. And for the subset of people who can’t eliminate the infection, the bacteria can cause chronic or progressive illness.“

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The research appears in Vector Borne and Zoonotic Diseases and was supported in part by the National Institutes of Health (grants UL1TR002489 and T32OD011130). Ricardo Maggi and Julie Bradley of NC State, as well as L. Fredrik Jarskog of UNC-Chapel Hill, contributed to the work.

Note to editors: The abstract of the paper follows.

„Schizophrenia and Bartonella spp. infection: a pilot case-control study“

DOI: 10.1089/vbz.2020.2729

Authors: Erin Lashnits, Ed Breitschwerdt, Ricardo Maggi, Julie Bradley, North Carolina State Univerity; L. Fredrik Jarskog, Flavio Frolich, University of North Carolina at Chapel Hill

Published: March 15, 2021 in Vector-Borne and Zoonotic Diseases

Abstract: Recently, infections with emerging zoonotic bacteria of the genus Bartonella have been reported in association with a range of central nervous system (CNS) symptoms. Currently, it remains unknown if Bartonella spp. infection is associated with symptoms of schizophrenia/schizoaffective disorder (SCZ/SAD). The objective of this study was to determine if there is an association between Bartonella species infection and SCZ/SAD. A secondary objective was to determine if SCZ/SAD symptoms were more severe among participants with documented Bartonella spp. infection. Using a case-control study design, 17 cases and 13 controls were evaluated with a series of clinical and cognitive assessments. Blood samples were collected and tested for Bartonella spp. infection using serological, microbiological, and molecular techniques. People with SCZ/SAD were more likely than healthy volunteers to have Bartonella spp. DNA in their bloodstream, with 11 of 17 cases (65%) positive by Bartonella spp. droplet digital PCR (ddPCR). In comparison, only one healthy volunteer was Bartonella spp. ddPCR positive (8%, p = 0.0024). Based on serology, Bartonella spp. exposure was common among people with SCZ/SAD (12 of 17) as well as among healthy volunteers (12 of 13), with no significant difference between the groups ( p = 0.196). Within the case group of people with SCZ/SAD, there was no significant difference in SCZ/SAD severity scores between people with and without ddPCR evidence of Bartonella spp. infection. This pilot study provides preliminary evidence in support of future investigations that should examine a potential contribution of Bartonella spp. infection to SCZ/SAD.

North Carolina State University, 23.03.2021 (tB).