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Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives
Eratne D, Janelidze S, Malpas CB, Loi S, Walterfang M, Merritt A, Diouf I, Blennow K et al.. The Australian and New Zealand journal of psychiatry, 2021-11-17
Topic: Brain proteins, microglia and lab models
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.
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APA 7th
Eratne, D., Janelidze, S., Malpas, C. B., Loi, S., Walterfang, M., Merritt, A., et al. (2022). Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives. The Australian and New Zealand journal of psychiatry. https://doi.org/10.1177/00048674211058684
Vancouver
Eratne D, Janelidze S, Malpas CB, Loi S, Walterfang M, Merritt A, et al. Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives. The Australian and New Zealand journal of psychiatry. 2022. doi:10.1177/00048674211058684. PMID: 35179048.
BibTeX
@article{eratne2022-35179048,
author = {Eratne, D. and Janelidze, S. and Malpas, C. B. and Loi, S. and Walterfang, M. and Merritt, A. and Diouf, I. and Blennow, K. and others},
title = {{Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives}},
journal = {The Australian and New Zealand journal of psychiatry},
year = {2022},
doi = {10.1177/00048674211058684},
pmid = {35179048},
url = {https://doi.org/10.1177/00048674211058684}
}
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Key findings
- Objective Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities.
- 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]).
- Conclusion Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration.
Why it matters
Plasma neurofilament light chain levels did not differ between people with treatment-resistant schizophrenia, their first-degree relatives, people with schizophrenia not on clozapine, and controls. The study found no increase in this marker of neuronal injury in these groups.
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Study details
- Participants82
- Evidence strengthModerate
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Australian and New Zealand journal of psychiatry) |
| Journal's citation record | 2 / 4 | Australian & New Zealand Journal of Psychiatry: journal h-index 180 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 82 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 35 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.8 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 3.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Tomáš Kalinčík: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35179048) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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Read the original
- DOI: 10.1177/00048674211058684
- PubMed: 35179048
- Original source →
- Free full text: discovery.ucl.ac.uk →
Full text: free to read — Unpaywall lists this copy as free to read: the link above (checked 10 Oct 2026).
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