Exploring serum biomarkers in paediatric psychiatry: the impact of NfL and GFAP

<jats:title>Abstract</jats:title> <jats:p> 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) ( <jats:italic>n</jats:italic>  = 52), depression ( <jats:italic>n</jats:italic>  = 237), and other psychiatric disorders ( <jats:italic>n</jats:italic>  = 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. </jats:p>