Plasma neurofilament light chain is not elevated in people with first-episode psychosis or those at ultra-high risk for psychosis.

Introduction: Neurofilament light chain (NfL), a blood biomarker of neuronal injury, shows promise in distinguishing neurodegenerative disorders from psychiatric conditions. This is especially relevant in psychosis, given neurological conditions such as autoimmune encephalitis and Niemann Pick Type C disease (NPC) may initially present with psychotic symptoms. Whilst NfL levels have been studied in established schizophrenia cases, their levels in first-episode psychosis (FEP) and ultra-high risk (UHR) for psychosis individuals remain largely unexplored. This study aimed to compare plasma NfL in people with FEP or UHR with healthy controls, as well as explore its associations with clinical data.
Method: We retrospectively analysed plasma NfL in 63 participants, consisting of 29 individuals with FEP, 10 individuals with UHR, and 24 healthy controls. We used general linear models (GLM), which were bootstrapped, to compute bias-corrected and accelerated (BCa) 95 % confidence intervals (CIs).
Results: Mean NfL levels were 5.2 pg/mL in FEP, 4.9 pg/mL in UHR, and 5.9 pg/mL in healthy controls. Compared to healthy controls, there were no significant differences in NfL levels in the FEP group (β = -0.22, 95 % CI [-0.86, 0.39], p = 0.516) nor UHR group (β = -0.37, 95 % CI [-0.90, 0.19], p = 0.182). There were no significant associations between NfL levels and clinical variables in the FEP group.
Discussion: Our study is the first to demonstrate that plasma NfL levels are not significantly elevated in individuals at UHR for psychosis compared to healthy controls, a finding also observed in the FEP cohort. These findings bolster the potential diagnostic utility of NfL in differentiating between psychiatric and neurodegenerative disorders.
Competing Interests: Declaration of competing interest We are grateful for the funding that supported this work: the Trisno Family Research Grant in Old Age Psychiatry, three NorthWestern Mental Health Research Seed Grants, MACH MRFF, and NHMRC (1185180). MK is supported by the Research Training Program Scholarship from the Department of Psychiatry, University of Melbourne with contributions from the Australian Commonwealth Government, and the Ramsay Hospital Research Foundation. AFS is supported by the Swedish federal government under the ALF agreement. VLC is supported by a National Health and Medical Research Council Investigator Fellowship (1177370) and the University of Melbourne Dame Kate Campbell Fellowship. CP was supported by a National Health and Medical Research Council (NHMRC) L3 Investigator Grant (1196508) and NHMRC Program Grant (ID: 1150083).
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