# Linking peripheral low-grade inflammation and blood-cerebrospinal fluid barrier leakage in schizophrenia spectrum disorders – A retrospective analysis

## TL;DR

The study finds a link between low-grade inflammation in the blood and a leaky brain barrier in schizophrenia, with platelets playing a key role.

## Contribution

This is the first study to show a direct link between peripheral low-grade inflammation and blood-cerebrospinal fluid barrier dysfunction in schizophrenia.

## Key findings

- The inflammation score correlates with blood-cerebrospinal fluid barrier permeability in schizophrenia.
- Platelets are the main driver of the peripheral low-grade inflammation score in schizophrenia.
- A multiple regression model shows pLGI, age, and sex significantly predict BCSFB permeability.

## Abstract

Social impairments and low-grade inflammation (LGI) are associated with psychotic disorders (e.g. schizophrenia spectrum disorders). Social impairments are important symptoms of the disease nonetheless a disturbed social interaction and inflammatory processes are further discussed as being part of the underlying pathophysiology, which is also characterized by blood-cerebrospinal fluid barrier (BCSFB) dysfunction. The relationship between social impairments, peripheral LGI (pLGI) and BCSFB permeability in psychotic disorders, however, is poorly understood. Therefore, we hypothesized that social impairment might be linked to pLGI, which, in turn, might affect BCSFB function in schizophrenia.

We conducted a retrospective chart review of all psychiatric inpatients who underwent lumbar puncture as part of their diagnostic work-up between January 1, 2021, and June 30, 2023 (n = 53). Thirty-one patients diagnosed with SSD (n = 27) or affective psychosis (n = 4) with a C-reactive protein (CRP) serum level <10 mg/L upon admission, indicating the absence of acute inflammation, were included in the analysis.

The cerebrospinal fluid (CSF)/serum albumin ratio – as a measure of BCSFB permeability – was shown to be positively correlated with our measure of pLGI (r = 0.418, p = 0.019) using the pLGI score (previously also named “INFLA-score”, “LGI score”), as well as with age (r = 0.415, p = 0.020) . Additionally, a trend toward a negative correlation with global functioning (GAF) was observed (r = −0.349, p = 0.054).

A multiple linear regression including pLGI, age, and sex yielded the best-fitting model (p = 0.003, corrected R2 = 0.337), with all predictors showing independent significant effects.

Interestingly, regarding single parameters of the pLGI score a significant correlation between platelets and the CSF/serum albumin ratio (r = 0.490, p = 0.005) was found. Positive and Negative Syndrome Scale (PANSS6) and social isolation score did not correlate with the model.

These data demonstrate – for the first time – a link between an established peripheral marker of LGI and BCSFB permeability in schizophrenia. Platelets were found to be the main driver of the pLGI score regarding BCSFB permeability. Future research will need to replicate these findings and could explore whether measures of peripheral inflammation could be useful in the diagnostic work-up of patients with psychotic disorders.

•An established score demonstrates peripheral inflammation in schizophrenia.•Inflammation score correlates with BCSFB leakage in schizophrenia.•Platelets are driving the peripheral low-grade inflammation score in schizophrenia.

An established score demonstrates peripheral inflammation in schizophrenia.

Inflammation score correlates with BCSFB leakage in schizophrenia.

Platelets are driving the peripheral low-grade inflammation score in schizophrenia.