Altered neuroaxonal integrity in schizophrenia and major depressive disorder assessed with neurofilament light chain in serum

Bavato, Francesco; Cathomas, Flurin; Klaus, Federica; Gütter, Karoline; Barro, Christian; Maceski, Aleksandra; Seifritz, Erich; Kuhle, Jens; Kaiser, Stefan; Quednow, Boris B.

doi:10.1016/j.jpsychires.2021.05.072

Cited by 57 publications

(54 citation statements)

References 66 publications

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“…The mechanisms underlying the associations between NfL and post-stroke mental health disorders could be multifactual and have not been thoroughly illustrated. NfL is also found to be increased in other psychiatric disorders, such as bipolar disorders (30), chronic insomnia disorder (29), and depression not due to stroke (31). These findings suggest that mental health disorders might contribute to neuronal damage, thus promoting the increase of NfL.…”

Section: Discussionmentioning

confidence: 77%

Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke

Wang

Guo

et al. 2022

Front. Psychiatry

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BackgroundMental health problems after acute ischemic stroke (AIS) have caused wide public concerns, and the study on early identification of these disorders is still an open issue. This study aims to investigate the predictive effect of circulating neurofilament light (NfL) on long-term mental health status of AIS patients.MethodsThis study collected demographic information and mental health measurements from 304 AIS patients from May 1, 2016 to Dec 31, 2019. Baseline serum neurofilament light (NfL) was determined within 2 h since patient admission. Six months after AIS onset, the degree of symptoms of depression, anxiety, and insomnia was assessed by the Chinese versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 7-item Insomnia Severity Index (ISI), respectively. Subjects were divided into the high NfL group and the low NfL group. Multivariate logistic regression analysis was performed to identify factors associated with these mental health problems.ResultsThe high NfL group had significantly higher PHQ-9, GAD-7, and ISI scores than the low NfL group. The prediction of serum NfL for major depression generated a sensitivity of 70.27%, a specificity of 67.79% and an AUC of 0.694. The prediction of serum NfL for anxiety generated a sensitivity of 69.23%, a specificity of 64.02%, and an AUC of 0.683. The prediction of serum NfL for insomnia generated a sensitivity of 75.00%, a specificity of 66.43% and an AUC of 0.723. Higher serum NfL was a risk factor of post-AIS depression [ORs (95% CI): 4.427 (1.918, 10.217)], anxiety [ORs (95% CI): 3.063 (1.939, 6.692)], and insomnia [ORs (95% CI): 4.200 (1.526, 11.562)].ConclusionsThese findings imply that circulating NfL might be a potential biomarker of long-term mental health problems after AIS.

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Section: Discussionmentioning

confidence: 77%

Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke

Wang

Guo

et al. 2022

Front. Psychiatry

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“…18 In particular, NfL levels have been shown to reflect active brain disease, dynamically respond to therapeutic interventions, and offer prognostic information in a number of neuropsychiatric disorders, such as multiple sclerosis, neurodegenerative disorders, traumatic brain injuries, and depression. 14,19,20 Our recent work also reported elevated NfL levels in patients with chronic ketamine addiction, demonstrating its sensitivity to substance-related brain pathology. 13…”

Section: Introductionmentioning

confidence: 67%

“…Higher NfL levels have previously been described in patients with MDD and in a sample of treatment-seeking ketamine users with a history of MDD. 13,14 However, in this study, we specifically excluded subjects with current major depressive episodes. Thus, the lack of associations between NfL levels and depressive symptoms in the present study is consistent with the view that neuroaxonal pathology in MDD is strongly stage-dependent.…”

Section: Discussionmentioning

confidence: 99%

A longitudinal investigation of blood neurofilament light chain levels in chronic cocaine users

Bavato

Kexel

Kluwe-Schiavon

et al. 2022

Preprint

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Objectives: To explore the hypothesis that plasma levels of neurofilament light chain (NfL), a marker of neuroaxonal pathology, are elevated in chronic cocaine users (CU) and longitudinally associated with changes in cocaine use. Methods: As part of the Social Stress Cocaine Study (SSCP), we assessed 35 CU and 35 stimulant-naive healthy controls (HC) at baseline and at a 4-month follow-up. Plasma NfL levels were determined from blood samples using single molecule array (SIMOA) technology. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. Results: In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in CU compared to HC (p<0.05). A moderate positive correlation between cocaine hair concentration and NfL levels was also found in CU (r(s)=0.36, p=0.03). Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up (p=0.002), indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the cocaine adulterant levamisole) and NfL levels were found (r(s)<0.28, p>0.05). Conclusions: Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related brain pathology, supporting the utility of blood NfL analysis in addiction research. The results also suggest that cocaine use should be considered a potential confounder in diagnostic applications and clinical studies using NfL.

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“…(Al Shweiki et al, 2019;Bavato et al, 2021;Katisko et al, 2020;Rodrigues-Amorim et al, 2020;Zerr et al, 2018) However, these studies had smaller numbers, less comprehensively characterised patients, mixed psychiatric cohorts rather than specifically exploring schizophrenia, and did not include many people with severe and treatment-resistant schizophrenia, and people on clozapine.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, following Bavato and colleagues (Bavato et al, 2021), we computed z scores from age-adjusted percentiles in the control group using generalised additive models for location, scale, and shape (GAMLSS), implemented in R. (Bavato et al, 2021) We then used single sample t-tests to test the hypothesis that the mean z score was 0 (i.e., equal to the mean of the control group). These results were not statistically significant for the TRS (M = -0.31, SD = 2.00, p = 0.17), NON-CLOZ (M = -0.49, SD = 1.08, p = 0.13), and sibling (M = -0.04, SD = 1.65, p = 0.91) group.…”

Section: Additional Sensitivity Analysesmentioning

confidence: 99%

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

Eratne

Bateman

Malpas

et al. 2021

Aust N Z J Psychiatry

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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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Altered neuroaxonal integrity in schizophrenia and major depressive disorder assessed with neurofilament light chain in serum

Cited by 57 publications

References 66 publications

Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke

Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke

A longitudinal investigation of blood neurofilament light chain levels in chronic cocaine users

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

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