Cerebrospinal fluid abnormalities in first- and multi-episode schizophrenia-spectrum disorders: impact of clinical and demographical variables

Abstract

Multiple lines of evidence indicate that immunological and inflammatory alterations contribute at least in a subgroup to the pathophysiology of schizophrenia. In this retrospective chart review, we investigated whether clinical factors contribute to altered cerebrospinal fluid (CSF) findings in schizophrenia-spectrum disorders. Clinical data from electronic medical records of patients with psychotic disorders (ICD-10: F20-F29) who received routine CSF diagnostics at the Department of Psychiatry and Psychotherapy, LMU Munich, Germany, were included. Chi² tests for dichotomous outcomes and independent t tests for continuous outcomes were used to compare differences between groups. A total of 331 patients were included in the analyses (43.2% female and 56.8% male). The mean age was 37.67 years (±15.58). The mean duration of illness was 71.96 months (±102.59). In all, 40% (128/320) were first-episode psychosis (FEP) patients and 60% (192/320) were multi-episode psychosis (MEP) patients. Elevated CSF protein levels were found in 19.8% and elevated CSF/serum albumin ratios (QAlb) in 29.4% of the cases. Pleocytosis was found in 6.1% of patients. MEP patients showed significantly higher mean QAlb compared with FEP patients (t(304.57) = −2.75, p = 0.006), which did not remain significant after correcting for age. QAlb elevation occurred more frequently in men (X2(1) = 14.76, p = <0.001). For treatment resistance, family history, and cMRI alterations, no significant differences in CSF-related outcomes were detected. Our work extends other retrospective cohorts confirming a relevant degree of CSF alterations in schizophrenia-spectrum disorders and shows the difficulty to relate these alterations to clinical and disease course trajectories. More research is needed to develop treatment response predictors from CSF analyses.

The Importance of Cerebrospinal Fluid Investigation in First-episode Psychosis

“…To answer the second question, multiple studies [26][27][28] indicate that the biomarker profile changes during the different stages of psychosis. It is unclear whether neuronal alterations in chronic stages develop with illness progression or appear as a long-term medication effect [30].…”

“…Thus, studies focusing on drug-naïve pFEP-stage patients could provide unaltered, early insights into the neurobiology of psychosis. Moreover, evaluating the development of biomarkers from early to later stages could aid in predicting outcomes [27].…”

“…Two studies comparing pFEP patients with healthy controls found no significant differences in the white blood count (WBC) or IgG index [15,33]. In addition, one study comparing non-affective pFEP with recurrent/chronic psychoses found no significant group differences in WBC count, protein level, or OCBs [27]. Moreover, Giné-Servén et al [34] found that protein levels were more frequently elevated in affective vs. non-affective pFEP, confirming earlier observations of Endres et al [31].…”

“…While Severance et al [33] found significantly higher QAlb in patients, a subsequent study performed by Theorell et al [15] found no significant differences between groups. Moreover, one study comparing non-affective pFEP with recurrent/ chronic psychoses found similar QAlb values between groups [27]. Yet, when considering threshold QAlb Lipidomic [58] lower nerve growth factor [43] and brain-derived neurotrophic factor (BDNF) [44] levels in patients.…”

The relationship between blood–brain barrier dysfunction and neurocognitive impairments in first-episode psychosis: findings from a retrospective chart analysis

“…A previous investigation led by our group regarding people with FEP found an increased albumin quotient in about a sixth of patients. 15 Another sample of 95 patients with FEP focused solely on total CSF protein levels and found said measures to be elevated in male patients. 16 Additional markers can be used to study BBB dysfunction.…”