Cerebrospinal Fluid Neuromarker Levels in Patients With Schizophrenia and Healthy Control Participants: A Proximity Extension Assay Study

To further evaluate the association between cerebrospinal fluid (CSF) neuromarkers and schizophrenia, we measured CSF neuromarker levels using proximity extension assay (PEA) in patients with schizophrenia and healthy control (HC) participants. Participants included 97 patients with schizophrenia (mean age [SD] = 38.8 [10.3] years; 60 men and 37 women) and 71 HC participants (mean age [SD] = 46.9 [15.4] years; 42 men and 29 women). Symptoms in patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS). CSF protein levels were measured using the Olink PEA Neurology Panel. CSF levels of cadherin 3, FcRL2, granzyme A, NAAA, plexin-B1, and sFRP-3 were lower in patients with schizophrenia than in HC participants (p < .05). Levels of BCAN, beta-NGF, carboxypeptidases A2 and M, CD200, DDR1, GDF-8, MANF, MDGA1, NAAA, neprilysin, neuropilin-2, neutral ceramidase, Nr-CAM, NTRK2, NTRK3, PDGF-R-alpha, plexin-B3, RGMA, ROBO2, testican-1, THY1, and WFIKKN1 positively correlated with PANSS positive scores, whereas protogenin levels negatively correlated with PANSS negative and general psychopathology scores in patients with schizophrenia (p < .05). This PEA study identified candidate CSF trait and state markers in schizophrenia; however, these findings require confirmation in further studies, as this was a primarily exploratory and hypothesis-generating study.