Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuroaxonal and astrocytic damage but remain understudied in adolescent psychiatric populations. This study investigated sNfL and GFAP levels in 412 adolescents diagnosed with anorexia nervosa (AN) (n = 52), depression (n = 237), and other psychiatric disorders (n = 123). We assessed their diagnostic utility, correlation with disease severity, and longitudinal changes during AN treatment. Biomarkers were measured using Single Molecule Array technology, with Z-scores derived from reference datasets. Compared to population norms, both biomarkers were elevated in AN (sNfL: 1.15 ± 1.17; GFAP: 1.50 ± 0.84) and in depression (sNfL: 0.34 ± 1.10; GFAP: 0.58 ± 1.00). Patients with AN showed significantly higher biomarker levels than those with depression or other psychiatric disorders; importantly, this distinction remained evident in sensitivity analyses restricted to underweight individuals with depression. In AN, sNfL levels correlated with baseline weight loss (β = −0.45, R² = 0.20) and declined significantly during treatment, while GFAP changes were less pronounced. Neither marker correlated with depressive symptom severity. Bootstrapped ROC analyses showed moderate-to-good discriminatory power (AUCs 0.70–0.84) for distinguishing AN from depression. These findings suggest that neuroaxonal and astrocytic stress is a component of adolescent psychopathology, particularly in AN. sNfL appears sensitive to starvation-related neurobiological changes, with levels normalizing alongside weight restoration. GFAP showed similar but less robust trends. Accordingly, the observed biomarker changes reflect more than underweight alone, supporting a potential role in differential diagnosis and treatment monitoring.
Marc Pawlitzki, L. Masanneck, L. Schlarbaum et al.· Translational Psychiatry· 0 citations
Therapy with anti-CD20 monoclonal antibodies is highly efficacious in various autoimmune diseases including multiple sclerosis (MS), a prototypic autoimmune inflammatory disease of the central nervous system (CNS). However, which B cell subsets and altered B cell-regulating factors mediate the clinical efficacy of anti-CD20 treatment is unclear. To address this gap in knowledge, we performed longitudinal high-dimensional single-cell transcriptomic and proteomic profiling of blood, cerebrospinal fluid (CSF), and intestinal samples from people with MS (pwMS), combined with immune profiling in a preclinical autoimmune encephalomyelitis model during anti-CD20 therapy. CSF analyses were performed using previously published datasets. Multisite intestinal profiling was conducted in one anti-CD20-treated patient with MS and one control participant. By applying algorithm-guided analyses of flow cytometry, single-cell transcriptomic, and immune receptor repertoire data, we found that anti-CD20 B cell depletion was associated with increased frequencies of regulatory mucosal-derived IgA-producing B cells in the periphery and CSF, together with increased B cell receptor clonal overlap between mucosal and systemic compartments, indicating enhanced trafficking of IgA B cells from gut mucosal tissues to the systemic circulation and the CNS. Moreover, we demonstrated that higher levels of B cell-activating factor and a proliferation-inducing ligand were related to favorable outcomes in pwMS during anti-CD20 treatment. Together, our findings suggest that mucosal immune regulatory mechanisms may be harnessed by anti-CD20 B cell depletion, opening previously unknown therapeutic avenues for MS.
T. Neziraj, Elisabeth Pössnecker, Angela A. Wang et al.· Science Translational Medici...· 0 citations
Importance
Capturing individual multiple sclerosis (MS) progression is difficult; few studies have evaluated glial fibrillary acidic protein (GFAP) in large longitudinal cohorts with independent validation.
Objective
To investigate whether serum GFAP levels and treatment-related changes are associated with future progression independent of relapse activity (PIRA).
Design, Setting, and Participants
This was a prospective observational study using 2 large MS cohorts: the Swiss MS Cohort (SMSC; initiated in June 2012; data extraction September 22, 2025) and the Expression, Proteomics, Imaging, Clinical study (EPIC; initiated in July 2004; data extraction February 21, 2024). The study took place at tertiary MS centers (8 for SMSC and 1 for EPIC). A total of 2329 persons with MS from both cohorts with at least 1 available time point with neurofilament light chain (NfL) and GFAP measurements were included (overall 18 629 measurements).
Exposures
Clinical data and NfL and GFAP z scores, collected and calculated every 6 or 12 months.
Main Outcomes and Measures
Risk of future PIRA, defined as Expanded Disability Status Scale score worsening confirmed after 6 or more months without relapses (in SMSC), or a composite additionally including greater than 20% worsening in the 9-hole peg test or timed 25-ft walk test (in EPIC).
Results
The SMSC and EPIC cohorts consisted of 1709 (13 375 samples; median [IQR] follow-up, 6.9 [2.5-10.7] years and age, 40.6 [32.1-50.1] years; 1128 [66.0%] female) and 620 (5254 samples; median [IQR] follow-up, 13.1 [9.4-14.0] years and age, 42.0 [35.0-50.0] years; 432 [69.7%] female) persons with MS, respectively. Consistent with prior work, high NfL was associated with relapse risk within the next year, whereas high GFAP was associated with long-term PIRA risk. In addition, elevated GFAP (z score >1.0 [84th percentile]) was associated with an average 40% higher hazard of short-term PIRA in the subsequent visit interval (SMSC: median [IQR] 346 [190-375] days; hazard ratio [HR], 1.45, 95% CI, 1.21-1.75; P < .001; EPIC: 385 [355-518] days; HR, 1.36; 95% CI, 1.07-1.71; P = .01). GFAP-based cohort enrichment in clinical trials targeting PIRA as an end point could reduce sample size by approximately 20%. Further, in SMSC, every yearly GFAP z score unit reduction during the first 2 years receiving fingolimod or B-cell-depleting therapy was associated with a lower risk of subsequent PIRA (54% risk reduction; HR, 0.46; 95% CI, 0.26-0.84; P = .01 and 67% risk reduction; HR, 0.33; 95% CI, 0.18-0.61; P < .001), respectively.
Conclusions and Relevance
In this cohort study, elevated GFAP was associated with a higher risk of PIRA, while treatment-associated reductions were associated with a lower PIRA risk. Together, these results suggest that serum GFAP may serve as a biomarker for personalized risk stratification and treatment monitoring and as a screening tool to reduce cohort size in clinical trials targeting MS progression.
M. Einsiedler, S. Sandgren, S. Schaedelin et al.· JAMA Neurology· 0 citations
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