857. NfL and GFAP in psychiatry: large-scale evidence across the lifespan

Abstract

Abstract Background Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are blood-based markers of neuroaxonal injury and astroglial activation, respectively. While established in neurology, their relevance in psychiatry remains unclear. Aims & Objectives To investigate the associations between circulating markers of neuroaxonal and astroglial structural integrity and psychiatric disorders in older adults, and between these markers and substance use in younger adults. Method We analyzed blood NfL and GFAP in UK Biobank (ages 40–65) and the Zurich z-proso cohort (ages 20–21), applying normative modeling across age and sex, clinical variables (UK Biobank), and propensity scores from multimodal substance use assessments combined with structural MRI (z-proso). Results In UK Biobank, NfL was modestly elevated in affective disorders but not in psychotic or anxiety disorders, with larger increases in neurological conditions. In z-proso, both markers were partially associated with polysubstance use and with structural brain alterations. Discussion & Conclusions Across the lifespan, NfL and, to a lesser extent, GFAP capture neuroaxonal and astroglial processes relevant to psychiatric vulnerability and substance use, supporting their use as scalable biomarkers for population-level studies of brain plasticity and mental health.