New research provides increased evidence that pathogens — particularly vector-borne infectious agents — may play a role in mental illness.
Investigators found that patients diagnosed with schizophrenia or another psychotic disorder were about three times more likely to have evidence of Bartonella spp DNA in their blood than adults without such disorders.
"Bartonella may be one of several pathogens that can induce neuroinflammation and neuropsychiatric symptoms," study investigator Edward Breitschwerdt, DVM, professor of medicine and infectious diseases at North Carolina State University College of Veterinary Medicine in Raleigh, North Carolina, told Medscape Medical News.
Bartonella spp are a group of vector-borne bacteria most often transmitted by arthropod vectors or animal bites and scratches. There are at least 45 known Bartonella spp, 18 of which have been shown to infect humans.
The study was published online on June 7 in Frontiers in Psychiatry.
Causal Role of Infection in Mental Illness?
For example, the species Bartonella henselae is associated with cat scratch disease, which, until recently, was thought to be a self-limiting infection.
"In contrast to the historical literature, particularly as related to cat scratch fever, which has been considered an immunologically self-limiting illness, it is now clinically important to recognize that bartonelloses can induce a chronic, stealth bacteremia in healthy individuals and in patients with neurological and neuropsychiatric symptoms," Breitschwerdt added.
To determine whether Bartonella spp exposure or infection is associated with psychosis, the researchers analyzed blood samples from 116 individuals for the presence of Bartonella DNA and Bartonella-specific antibodies.
The cohort included 29 control participants unaffected by psychosis, 16 prodromal individuals (with symptoms but no formal diagnosis), seven children or adolescents with psychosis, 44 adults with psychosis, and 20 close relatives of participants with psychosis.
The researchers found there was no significant difference in Bartonella-specific antibodies between adults with psychosis and adult control participants unaffected by psychosis.
However, a significantly higher proportion of adults with psychosis had Bartonella spp DNA in their bloodstream than adult unaffected control participants (43% vs 14%; P = .021).
Using DNA sequencing, the researchers determined the presence of Bartonella spp in 18 of the 31 participants with bacteremia, including infection or co-infection with B henselae in 11 individuals, B vinsonii subsp berkhoffii in six individuals, B quintana in two, and B alsatica and B rochalimae in one each.
Driver of Psychosis?
This is the second study by the same researchers to identify Bartonella in the blood of patients with psychosis.
In a 2020 study, interrupted by the COVID pandemic, investigators found Bartonella spp DNA in 11 of 17 (65%) patients with schizophrenia vs one of 13 (8%) healthy control participants.
"We've now demonstrated the presence of Bartonella species in the blood of two separate cohorts of patients with neuropsychiatric symptoms, which indicates that these bacteria are worth studying further as a potential driver of these symptoms," Breitschwerdt said in a news release.
He noted that the finding that the frequency of positive antibody tests for Bartonella infection was not significantly different for the control participants vs the individuals with psychosis "suggests that exposure to Bartonella is common in the general population and that reliance on serologic test results alone can be misleading."
A limitation of the study is that culturing for Bartonella spp was not performed, meaning viable bacterial infection could not be confirmed.
The investigators wrote that it's also important to note that the study does not establish whether the presence of Bartonella bacteremia in adults with psychosis is a "cause, a cofactor, or contributor to disease progression."
If future studies support an association between Bartonella spp bacteremia and psychosis, Bartonella-targeted antimicrobial therapy trials could be initiated to determine if treatment improves or resolves psychotic behavior, they noted.
Commenting on the research for Medscape Medical News, Adrian Preda, MD, professor of clinical psychiatry and human behavior at the University of California, Irvine, School of Medicine, said this study supports the hypothesis that infection could be related to schizophrenia "but we are far from proving it, and this study doesn't really advance us much in that direction."
"It's a well-conducted study, but a significant limitation," as noted by the authors, is the lack of culturing for Bartonella, meaning the viable bacterial infection was not confirmed. "That would be the next step," said Preda.
Preda also cautioned that "before we start thinking about screening and treating, we need to make sure that this is not an incidental or opportunistic infection."
This research was supported through donations to the Bartonella/Vector Borne Diseases Research Fund at the North Carolina State University College of Veterinary Medicine, through a grant from the Steven & Alexandra Cohen Foundation, and by the state of North Carolina.
Breitschwerdt holds US Patent No. 7,115,385 Media and Methods for Cultivation of Microorganisms and is a co-founder, shareholder, and chief scientific officer for Galaxy Diagnostics, a company that provides advanced diagnostic testing for the detection of Bartonella spp infections. Preda had no relevant disclosures.