Inflammatory Molecular Signature Associated With Infectious Agents in Psychosis.

Schizophrenia (SZ) is a devastating mental condition with onset in young
adulthood. The identification of molecular biomarkers that reflect
illness pathology is crucial. Recent evidence suggested immune and
inflammatory cascades in conjunction with infection may play a role in
the pathology. To address this question, we investigated molecular
changes in cerebrospinal fluid (CSF) from antipsychotic-naïve patients
with SZ and at risk mental status for psychosis (ARMS), in comparison
with healthy controls (HCs). We measured 90 analytes using a broad
multiplex platform focusing on immune and inflammatory cascades then
selected 35 with our quality reporting criteria for further analysis. We
also examined Toxoplasma gondii (TG) and herpes simplex virus 1
antibody levels in CSF. We report that expression of 15 molecules was
significantly altered in the patient groups (SZ and ARMS) compared with
HCs. The majority of these molecular changes (alpha-2-macroglobulin
[α2M], fibrinogen, interleukin-6 receptor [IL-6R], stem cell factor
[SCF], transforming growth factor alpha [TGFα], tumor necrosis factor
receptor 2 [TNFR2], IL-8, monocyte chemotactic protein 2 [MCP-2/CCL8],
testosterone [for males], angiotensin converting enzyme [ACE], and
epidermal growth factor receptor) were consistent between SZ and ARMS
patients, suggesting these may represent trait changes associated with
psychotic conditions in general. Interestingly, many of these analytes
(α2M, fibrinogen, IL-6R, SCF, TGFα, TNFR2, IL-8, MCP-2/CCL8, and
testosterone [for males]) were exacerbated in subjects with ARMS
compared with subjects with SZ. Although further studies are needed, we
optimistically propose that these molecules may be good candidates for
predictive markers for psychosis from an early stage. Lastly, reduction
of IL-6R, TGFα, and ACE was correlated with positivity of TG antibody in
the CSF, suggesting possible involvement of TG infection in the

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