To rescue cognition in schizophrenia with valaciclovir: a focus on hippocampal inflammation

Schizophrenia is a chronic and disabling brain disease, with unknown aetiology.
Recently, we have shown the presence of an inflammatory process in the
hippocampus of schizophrenic patients during psychosis. In addition, we found
evidence for the presence of herpes viruses in the temporal lobe of
schizophrenic patients during psychosis. Taken together, we hypothesize that
the hippocampal inflammation is caused by the presence of herpes viruses and
that this inflammation interferes with the normal involvement of the
hippocampus in cognition. Anti-viral treatment, with valaciclovir, that reduces
the presence of active herpes virus in the hippocampus could reduce the
neuroinflammation and thus improve cognition and symptoms in schizophrenia.

The main objective is to find a pre- and post-valaciclovir treatment difference
in hippocampal inflammation, as measured with positron emission tomography, in
schizophrenic patients exposed to a psychotic episode. The secondary objective
is to improve cognition by the supposed anti-inflammatory effect on the
hippocampus of valaciclovir.

The study is double-blind randomized placebo-controlled trial

Of the 24 included patients, 12 patients will receive 8 g (4x2 g per day) of
valaciclovir daily for a period of 7 consecutive 24-h periods and 12 patients
will receive 8 g (4x2 g per day) of placebo daily for 7 consecutive days.

Patients will be admitted to a psychiatric hospital, if not already admitted as
a part of their regular treatment, and treated with valaciclovir for a period
of 7 days. Patients have to fill in a questionnaire and have to undergo a part
of the SCAN2 interview and a MRI scan once, and have to undergo a PANSS
interview, attention, memory and IQ tests, and PET scan twice. A total of 345
ml of blood will be taken for the determination of kidney and liver function,
herpes virus antibodies, acyclovir levels in blood and for the PET scan
data-analysis. Treatment with valaciclovir may cause nausea and headache but
the risk of serious side effects is low (<1 out of 10.000). For the PET scan,
the arterial catheterization can cause discomfort and the patients are exposed
to radioactivity with minor to moderate risk. The patients treated with
valaciclovir can have direct benefit form the treatment, because it may reduce
symptoms. In general, when this study finds evidence for the involvement of
herpes viruses in schizophrenia, this can lead to improved treatment of these
patients in the near future.