Cerebrospinal Fluid Pathologies in Schizophrenia-Spectrum Disorder—A Retrospective Chart Review

Abstract

Background The role of inflammatory processes in the etiology of schizophrenia is increasingly being investigated. A link between psychosis and inflammation measured with different biomarkers has been reported in the literature and needs to be further explored. To investigate the presence of inflammatory biomarkers in first-episode psychosis (FEP) we analyzed the largest available FEP cohort to date regarding routine CSF and blood diagnostics. Methods We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with a ICD-10 diagnosis of F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture. Results A total of n = 314 FEP patients were included in our sample. 42.7% patients (134/314) showed cerebrospinal fluid (CSF) alterations. Oligoclonal bands in the CSF were present in 21.8% of patients (67/307) with 12.4% (27/217) of patients presenting OCBs type 2 or 3. 15.8% (49/310) of our cohort revealed signs of blood-brain-barrier (BBB) dysfunction with increased albumin ratios. Mean serum CRP levels were 2.4 mg/l (SD = 9.5). CRP elevation was present in 116/280 cases (41.4%). Conclusions This large retrospective analysis on FEP cohort greatly enriches the clinical data available on this population and contributes to the discussion around inflammation in psychosis. Of note, even though several inflammatory alterations were found both in CSF and in blood tests, we found no evidence for a significant relationship between peripheral inflammation and inflammatory CSF. Furthermore, no significant relationship between CSF alterations and peripheral inflammation measured with CRP could be established.

Brain vasculature disturbance in schizophrenia

“…A meta-analysis indicated BBB leak in SZ, reflected by higher levels of CSF albumin [33 ▪▪ ]. Three subsequent studies corroborated this result and indicated BBB leakage across a relatively similar percentage of the patients (15.8% [52 ▪▪ ], 19% [53 ▪▪ ], 15% [34 ▪▪ ]). Reductions in the tight junction protein CLDN5 were reported in the hippocampus [43 ▪▪ ] and serum of the patients [42].…”

“…A group of first-episode SZ patients presented slightly increased systemic inflammation (41.4%, 116/280 SZ subjects), reflected by increased C-reac-tive protein levels in the blood, whereas signs of BBB leak were reported solely in 15.8% of the first-episode SZ patients (49/310 SZ), as reflected in higher CSF albumin [52 ▪▪ ]. In a cohort of 456 SZ patients, only 7% showed signs of neuroinflammation, although 19% of the SZ patients reported BBB leakage.…”

Blood-brain-barrier dysfunction and folate and vitamin B12 levels in first-episode psychosis

“…Reference values were adjusted by age with the following formula: Qalb = (4 + age/15) × 10 -3 , age indicated as years (27). In accordance with other publications (12,28), OCBs were classi ed in ve pattern types as recommended by previous reports (29,30). The ve patterns are de ned as follows: pattern 1: normal CSF, pattern 2: multiple CSF restricted OCBs, pattern 3: identical OCBs in CSF and serum plus CSF restricted OCBs, pattern 4: identical OCBs in both CSF and serum, pattern 5: monoclonal bands in CSF and serum.…”

Immunopsychiatry – Innovative Technology to Characterize Disease Activity in Autoantibody-Associated Psychiatric Diseases

“…We therefore need innovative new methods to detect mild inflammation, as the current standard diagnostic procedures are inadequate. Peripheral inflammation might be informative as additional information for deciphering CNS inflammation, but often fail to correlate with CSF inflammation, as a recent study showed in patients with a schizophrenia-spectrum disorder ( 34 ). However, whether peripheral inflammation is useful is controversial, as another study showed upregulated complement mRNA expression in blood samples linked to cortical thinning in schizophrenia ( 35 ).…”