Cerebrospinal fluid findings in patients with psychotic symptoms—a retrospective analysis

Abstract

In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.

City Environment and Occurrence of Neural Autoantibodies in Psychiatric Patients

“…More large-scale studies are therefore necessary to investigate any systematic age effect that might affect our findings. Surprisingly, we have also detected a higher proportion of patients with a paranoid hallucinatory syndrome in the group of psychiatric patients without neural autoantibodies as a tendency, a finding that contradicts previous reports on autoantibody-mediated psychosis in patients (18)(19)(20)(21) and animal models (10) and that might depend on cohort size; this result should be replicated in larger cohorts. Another limitation is that we did not systematically screen for any head injuries, none of the patients' clinical data suggested any trauma.…”

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

“…Of these 39 bands, 9 were type II and 29 were type III bands, while one single band could not be classified to either of the categories. These rates are higher than those presented in the most recent meta-analysis [ 11 ] and other large-scale cohorts [ 12 , 26 ], but in line with one report from 2010 based on 61 cases [ 27 ]. Of note, the prevalence of OCBs type 2 and 3 among healthy subjects has been reported to be ~4% [ 28 ].…”

Cerebrospinal fluid flow cytometry distinguishes psychosis spectrum disorders from differential diagnoses

“…Previous studies have reported CSF abnormalities in psychosis spectrum patients (e.g., elevated total protein concentration, and albumin ratio) [ 40 – 42 ] and we first aimed to replicate these findings. We therefore analyzed whether basic CSF parameters differed between F2x and IIH patients and added RRMS and NMDARE patients as unique inflammatory controls.…”