Glial fibrillary acidic protein as blood biomarker for differential diagnosis and severity of major depressive disorder.

Neuroinflammation has been connected to the pathophysiology of major depressive disorder (MDD) and neurochemical biomarkers of glial pathology could aid the diagnosis and might support patient stratification and monitoring in clinical trials. Our study aimed to determine the utility of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, for the differential diagnosis and monitoring of MDD. Employing Simoa technology we measured levels of GFAP in prospectively collected serum samples from 81 age-matched patients with MDD, schizophrenia (SZ), bipolar disorder (BP), and healthy controls (HC). Highest GFAP levels were determined for MDD. At a cut-off of 130 pg/ml, MDD could be discriminated with 87% sensitivity from SZ and BP (specificity 70%) and from HC (specificity 56%). GFAP levels increased with age (r = 0.5236, p = 0.0002) and with MDD severity quantified based on the Montgomery-Åsberg Depression Rating Scale (r = 0.4308, p = 0.0221). Neurofilament light chain serum levels were not different in the diagnostic groups and not associated with GFAP levels (r = 0.0911, p = 0.576) pointing to an independence of astrocyte activation on neurodegeneration. Our study provides first evidence that serum GFAP levels could improve the differential diagnosis of MDD and that depression severity could be objectively quantified using serum GFAP levels. Furthermore, serum GFAP might represent a marker to monitor astroglial pathology in the course of MDD.