Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives. (October 2022)

• Record Type: Journal Article
• Authors: Eratne, Dhamidhu; Janelidze, Shorena; Malpas, Charles B; Loi, Samantha; Walterfang, Mark; Merritt, Antonia; Diouf, Ibrahima; Blennow, Kaj; Zetterberg, Henrik; Cilia, Brandon; Wannan, Cassandra; Bousman, Chad; Everall, Ian; Zalesky, Andrew; Jayaram, Mahesh; Thomas, Naveen; Berkovic, Samuel F; Hansson, Oskar; Velakoulis, Dennis; Pantelis, Christos; Santillo, Alexander
• Other Names: Li Qiao-Xin non-byline-author.; Stehmann Christiane non-byline-author.; Cadwallader Claire non-byline-author.; Fowler Christopher non-byline-author.; Ravanfar Parsa non-byline-author.; Farrand Sarah non-byline-author.; Keem Michael non-byline-author.; Kang Matthew non-byline-author.; Watson Rosie non-byline-author.; Yassi Nawaf non-byline-author.; Kaylor-Hughes Cath non-byline-author.; Kanaan Richard non-byline-author.; Perucca Piero non-byline-author.; Vivash Lucy non-byline-author.; Ali Rashida non-byline-author.; O'Brien Terence J. non-byline-author.; Masters Colin L non-byline-author.; Collins Steven non-byline-author.; Kelso Wendy non-byline-author.; Evans Andrew non-byline-author.; King Anna non-byline-author.; Kwan Patrick non-byline-author.; Gunn Jane non-byline-author.; Goranitis Ilias non-byline-author.; Pan Tianxin non-byline-author.; Lewis Courtney non-byline-author.; Kalincik Tomas non-byline-author.
• Is Part Of: Australian and New Zealand journal of psychiatry. Volume 56:Number 10(2022)
• Page Start: 1295
• Page End: 1305
• Publication Date: 2022-10
• Subjects: Schizophrenia -- treatment-resistant -- biomarker -- neurofilament -- diagnosis; Psychiatry -- Periodicals; Psychiatry -- Australia -- Periodicals; Psychiatry -- New Zealand -- Periodicals; 616.89005
• DOI: 10.1177/00048674211058684
• Languages: English
• ISSNs: 0004-8674

Abstract

Objective: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging 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 potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative 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 = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/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 schizophrenia 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.