Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives

Dhamidhu Eratne, Shorena Janelidze, Charles B. Malpas, Samantha Loi, Mark Walterfang, Antonia Merritt, Ibrahima Diouf, Kaj Blennow, Henrik Zetterberg, Brandon Cilia, Cassandra Wannan, Chad Bousman, Ian Everall, Andrew Zalesky, Mahesh Jayaram, Naveen Thomas, Samuel F. Berkovic, Oskar Hansson, Dennis Velakoulis, Christos PantelisAlexander Santillo, MiND Study Group

Research output: Contribution to journalArticlepeer-review


Objective: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroim- aging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as poten- tially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegen- erative disorders such as Alzheimer and frontotemporal dementias.
Methods: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine (n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine (n=13), and age- and sex-matched controls (n=59).
Results: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M=6.3pg/ mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M=6.7pg/mL, 95% confidence interval: [5.2,8.2]; parents, M after adjusting for age=6.7pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M=5.8pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M=4.9pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman’s r=0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia (r=0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight (r = −0.305, 95% confidence interval: [−0.504, −0.076]).
Conclusion: Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizo- phrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode.
Original languageEnglish
Pages (from-to)1295-1305
JournalAustralian and New Zealand Journal of Psychiatry
Issue number10
Early online date2021
Publication statusPublished - 2022

Subject classification (UKÄ)

  • Neurosciences


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