New Clues to Schizophrenia Pathogenesis

The composition of the oropharyngeal virome in patients with schizophrenia differs from that of healthy persons, and understanding the pathologic consequences of these differences may open up new avenues for therapeutic intervention, new research suggests.

Robert Yolken, MD, Johns Hopkins School of Medicine, Baltimore, Maryland, and colleagues found that a single bacteriophage - Lactobacillus phage phi-adh - was more likely to be present and to be present in higher concentrations in the oropharyngeal virome of patients with schizophrenia compared with control individuals.

Bacteriophages are viruses that infect bacteria and alter their metabolism and replication.

When present in patients with schizophrenia, levels of Lactobacillus phage phi-adh correlated with a higher prevalence of immunologic disorders as well.

Intriguingly, none of the patients with schizophrenia in the study who were taking valproate had evidence of this particular bacteriophage, in contrast with about half of those who were not taking valproate.

In animal models, valproate acid has been shown to alter the microbiome, although its mechanism of action in patients with schizophrenia has not been fully elucidated.

We don’t yet know if this particular bacteriophage is altering the microbiome in any way,” Dr Yolken told Medscape Medical News.

“But we can say that patients presenting to our study with a diagnosis of schizophrenia had certain changes in their microbiome, and one of the changes was the presence of this particular bacteriophage,” he added.

“And the biological consequences of this difference and the potential effect of altering bacteriophage levels through therapeutic interventions are worthy of further investigation.”

The study was presented here at the 12th World Congress of Biological Psychiatry.

Probiotics a Potential Treatment?

According to Dr Yolken, studies have clearly demonstrated that alterations in the microbiome can profoundly affect both cognition and behavior in rodents.

New Clues to Schizophrenia Pathogenesis” class=“border” alt=“New Clues to Schizophrenia Pathogenesis”  align=“right”  /> Changes in the bacterial and viral composition of the intestinal tract also alter the ability of molecules to cross the blood-brain barrier, which has clear implications in a range of neurologic and psychiatric disorders.

However, most studies to date have focused on the bacterial components of the microbiome, and focusing only on bacteria misses out on the possible contribution that viruses - including viruses that infect bacteria - fungi, and protozoa could make to different pathologic processes, said Dr Yolken.

Using metagenomic analysis, the investigators set out to characterize bacteriophage genomes in the oral pharynx of 41 patients with schizophrenia and 33 control participants who had no psychiatric diagnosis.

Of more than 100,000,000 sequence reads generated from each sample, investigators identified 79 distinct bacteriophage sequences in the oropharyngeal samples.

Of these, one bacteriophage genome, Lactobacillus phage phi-adh, was present in 17 of 41 (41.5%) patients with schizophrenia compared with just 1 of 33 (3.3%) control individuals (P < .001).

The differential levels of this single bacteriophage remained significant when controlling for age, sex, race, socioeconomic status, and cigarette smoking (P < .006).

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