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Associations between structural brain changes and blood neurofilament light chain protein in treatment-resistant schizophrenia

Cilia, Brandon Joe ; Eratne, Dhamidhu ; Wannan, Cassandra ; Malpas, Charles ; Janelidze, Shorena LU ; Hansson, Oskar LU orcid ; Everall, Ian ; Bousman, Chad ; Thomas, Naveen and Santillo, Alexander F. LU orcid , et al. (2025) In Australian and New Zealand Journal of Psychiatry
Abstract

Objective: Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia). Abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often described in schizophrenia. Novel biomarkers of active brain pathology such as neurofilament light chain protein are now expected to improve current understanding of psychiatric disorders, including schizophrenia. This study explored whether treatment-resistant schizophrenia individuals exhibit different associations between plasma neurofilament light chain protein levels and regional cortical thickness reductions compared with controls. Methods: Plasma neurofilament light chain protein levels were measured,... (More)

Objective: Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia). Abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often described in schizophrenia. Novel biomarkers of active brain pathology such as neurofilament light chain protein are now expected to improve current understanding of psychiatric disorders, including schizophrenia. This study explored whether treatment-resistant schizophrenia individuals exhibit different associations between plasma neurofilament light chain protein levels and regional cortical thickness reductions compared with controls. Methods: Plasma neurofilament light chain protein levels were measured, and T1-weighted magnetic resonance imaging sequences were obtained and processed via FreeSurfer for each participant. General linear models adjusting for age and body mass index were estimated to determine whether the interaction between diagnostic group and plasma neurofilament light chain protein level predicted lower cortical thickness across frontotemporal structures and the insula. Results: A total of 79 participants were included: 37 treatment-resistant schizophrenia and 42 healthy controls. Significant (false discovery rate-corrected) cortical thinning of the left (p = 0.005, η2p = 0.100) and right (p = 0.002, η2p = 0.149) insula, and left inferior temporal gyrus (p < 0.001, η2p = 0.143) was associated with higher levels of plasma neurofilament light chain protein in treatment-resistant schizophrenia, but not in healthy controls. Conclusions: The association between regional thickness reduction of the bilateral insula and left inferior temporal gyrus with plasma neurofilament light chain protein may reflect a neuroprogressive component to schizophrenia, which is not observed in the normal population.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
biomarker, neurofilament, neuroimaging, Schizophrenia, treatment-resistant
in
Australian and New Zealand Journal of Psychiatry
publisher
SAGE Publications
external identifiers
  • pmid:39754499
  • scopus:85214350006
ISSN
0004-8674
DOI
10.1177/00048674241307906
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Royal Australian and New Zealand College of Psychiatrists 2025.
id
f5fc00fe-5d6a-4131-ad25-968ad0c76c71
date added to LUP
2025-01-21 08:02:28
date last changed
2025-07-08 21:44:31
@article{f5fc00fe-5d6a-4131-ad25-968ad0c76c71,
  abstract     = {{<p>Objective: Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia). Abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often described in schizophrenia. Novel biomarkers of active brain pathology such as neurofilament light chain protein are now expected to improve current understanding of psychiatric disorders, including schizophrenia. This study explored whether treatment-resistant schizophrenia individuals exhibit different associations between plasma neurofilament light chain protein levels and regional cortical thickness reductions compared with controls. Methods: Plasma neurofilament light chain protein levels were measured, and T1-weighted magnetic resonance imaging sequences were obtained and processed via FreeSurfer for each participant. General linear models adjusting for age and body mass index were estimated to determine whether the interaction between diagnostic group and plasma neurofilament light chain protein level predicted lower cortical thickness across frontotemporal structures and the insula. Results: A total of 79 participants were included: 37 treatment-resistant schizophrenia and 42 healthy controls. Significant (false discovery rate-corrected) cortical thinning of the left (p = 0.005, η<sup>2</sup><sub><sub>p</sub></sub> = 0.100) and right (p = 0.002, η<sup>2</sup><sub><sub>p</sub></sub> = 0.149) insula, and left inferior temporal gyrus (p &lt; 0.001, η<sup>2</sup><sub><sub>p</sub></sub> = 0.143) was associated with higher levels of plasma neurofilament light chain protein in treatment-resistant schizophrenia, but not in healthy controls. Conclusions: The association between regional thickness reduction of the bilateral insula and left inferior temporal gyrus with plasma neurofilament light chain protein may reflect a neuroprogressive component to schizophrenia, which is not observed in the normal population.</p>}},
  author       = {{Cilia, Brandon Joe and Eratne, Dhamidhu and Wannan, Cassandra and Malpas, Charles and Janelidze, Shorena and Hansson, Oskar and Everall, Ian and Bousman, Chad and Thomas, Naveen and Santillo, Alexander F. and Velakoulis, Dennis and Pantelis, Christos}},
  issn         = {{0004-8674}},
  keywords     = {{biomarker; neurofilament; neuroimaging; Schizophrenia; treatment-resistant}},
  language     = {{eng}},
  publisher    = {{SAGE Publications}},
  series       = {{Australian and New Zealand Journal of Psychiatry}},
  title        = {{Associations between structural brain changes and blood neurofilament light chain protein in treatment-resistant schizophrenia}},
  url          = {{http://dx.doi.org/10.1177/00048674241307906}},
  doi          = {{10.1177/00048674241307906}},
  year         = {{2025}},
}