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

Eratne, Dhamidhu ; Janelidze, Shorena LU ; Malpas, Charles B. ; Loi, Samantha ; Walterfang, Mark ; Merritt, Antonia ; Diouf, Ibrahima ; Blennow, Kaj ; Zetterberg, Henrik and Cilia, Brandon , et al. (2022) In Australian and New Zealand Journal of Psychiatry 56(10). p.1295-1305
Abstract
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... (More)
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. (Less)
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contributor
Kalincik, Thomas
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Australian and New Zealand Journal of Psychiatry
volume
56
issue
10
pages
1295 - 1305
publisher
Informa Healthcare
external identifiers
  • scopus:85119493569
  • pmid:35179048
ISSN
0004-8674
DOI
10.1177/00048674211058684
language
English
LU publication?
yes
id
d9641489-7343-4f16-a97c-128a04377ac5
date added to LUP
2021-11-17 18:18:14
date last changed
2024-02-01 14:55:13
@article{d9641489-7343-4f16-a97c-128a04377ac5,
  abstract     = {{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.<br/>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).<br/>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]).<br/>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.}},
  author       = {{Eratne, Dhamidhu and Janelidze, Shorena and Malpas, Charles B. and Loi, Samantha and Walterfang, Mark and Merritt, Antonia and Diouf, Ibrahima and Blennow, Kaj and Zetterberg, Henrik and Cilia, Brandon and Wannan, Cassandra and Bousman, Chad and Everall, Ian and Zalesky, Andrew and Jayaram, Mahesh and Thomas, Naveen and Berkovic, Samuel F. and Hansson, Oskar and Velakoulis, Dennis and Pantelis, Christos and Santillo, Alexander}},
  issn         = {{0004-8674}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1295--1305}},
  publisher    = {{Informa Healthcare}},
  series       = {{Australian and New Zealand Journal of Psychiatry}},
  title        = {{Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives}},
  url          = {{http://dx.doi.org/10.1177/00048674211058684}},
  doi          = {{10.1177/00048674211058684}},
  volume       = {{56}},
  year         = {{2022}},
}