CNS damage biomarkers in cerebrospinal fluid and other findings from a patient cohort enriched for suspected autoimmune psychiatric disease

Objective: To describe the prevalence of central nervous system (CNS) pathology in a psychiatric patient cohort enriched for clinical red flags of suspected autoimmune psychiatric disease, we explored associations between CNS damage biomarkers in cerebrospinal fluid (CSF), clinical red flags, and psychiatric symptoms. Methods: CSF routine findings and CNS damage biomarkers (neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAp) and total Tau (t-Tau)) in CSF from 127 patients with moderate to severe psychiatric symptoms were related to proposed clinical red flags, psychiatric features, MRI and EEG findings. Results: Twenty-seven percent had elevated levels of CNS damage biomarkers in CSF and Twenty-one percent of patients had other abnormal routine CSF findings. Six percent had anti-neuronal antibodies in serum and 2% in CSF. Sixty-six percent of patients examined with MRI (n=88) had pathological findings, mostly atrophy or non-specific white matter lesions. Twenty-five percent of patients with EEG recordings (n=70) had pathological findings. Elevated NfL was associated with comorbid autoimmunity and affective dysregulation symptoms. Elevated t-Tau was associated with catatonia and higher ratings of agitation/hyperactivity. Elevated GFAp was associated with acute onset, atypical presentation, prodromal infection, tics, depressive/anxiety symptom ratings and overall higher psychiatric symptom burden. Conclusions: Pre-selection based on clinical red flags for autoimmune psychiatric disease identifies a population with CSF alterations suggesting CNS pathology. Pathological levels of NfL, GFAp or t-Tau in CSF appear to be related to different red flags and psychiatric manifestations.