Antiviral treatment in schizophrenia: a randomized pilot PET study on the effects of valaciclovir on neuroinflammation

• Published in: Psychological medicine 2023-11, Vol.53 (15), p.7087-7095
• Main Authors: Jonker, Iris, Doorduin, Janine, Knegtering, Henderikus, van't Hag, Erna, Dierckx, Rudi A., de Vries, Erik F. J., Schoevers, Robert A., Klein, Hans C.
• Format: Article
• Language: English
• Subjects: Amygdala; Antiviral agents; Antiviral drugs; Brain stem; Clinical trials; Cognitive ability; Cognitive functioning; Cognitive impairment; Drug dosages; Encephalitis; Frontal lobe; Herpes viruses; Hippocampus; Infections; Inflammation; Intervention; Intravenous therapy; Kinases; Medical research; Mental disorders; Nucleus accumbens; Occipital lobe; Original; Original Article; Parahippocampal gyrus; Parietal lobe; Patients; Pharmacy; Positron emission tomography; Psychosis; Psychotic symptoms; Schizophrenia; Statistical significance; Temporal lobe; Temporal lobes; Tomography
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291723000430

Patients with schizophrenia experience cognitive impairment, which could be related to neuroinflammation in the hippocampus. The cause for such hippocampal inflammation is still unknown, but it has been suggested that herpes virus infection is involved. This study therefore aimed to determine whether add-on treatment of schizophrenic patients with the anti- viral drug valaciclovir would reduce hippocampal neuroinflammation and consequently improve cognitive symptoms. We performed a double-blind monocenter study in 24 male and female patients with schizophrenia, experiencing active psychotic symptoms. Patients were orally treated with the anti-viral drug valaciclovir for seven consecutive days (8 g/day). Neuroinflammation was measured with Positron Emission Tomography using the translocator protein ligand [ C]-PK11195, pre-treatment and at seven days post-treatment, as were psychotic symptoms and cognition. Valaciclovir treatment resulted in reduced TSPO binding (39%) in the hippocampus, as well as in the brainstem, frontal lobe, temporal lobe, parahippocampal gyrus, amygdala, parietal lobe, occipital lobe, insula and cingulate gyri, nucleus accumbens and thalamus (31-40%) when using binding potential (BPND) as an outcome. With total distribution volume (VT) as outcome we found essentially the same results, but associations only approached statistical significance ( = 0.050 for hippocampus). Placebo treatment did not affect neuroinflammation. No effects of valaciclovir on psychotic symptoms or cognitive functioning were found. We found a decreased TSPO binding following antiviral treatment, which could suggest a viral underpinning of neuroinflammation in psychotic patients. Whether this reduced neuroinflammation by treatment with valaciclovir has clinical implications and is specific for schizophrenia warrants further research.