Prognostic Value of FasL, BDNF, and IL-1β as Predictors of Therapeutic Response in Schizophrenia

Background/Objectives: Pro-inflammatory, neurotrophic, and proapoptotic factors affect the course of schizophrenia; however, their impact on the clinical response during relapse is not well recognized. A member of TNF family, Fas ligand (FasL), participates in apoptosis, but its connection with treatment-resistant schizophrenia is unknown. Methods: For this preliminary exploratory study, 53 patients with schizophrenia relapse and 45 healthy subjects were enrolled. Pro-inflammatory interleukin IL-1β, brain-derived neurotrophic factor (BDNF), FasL levels, and clinical evaluations (PANSS, SANS, SAPS) were studied at admission, after a 4-week therapy, and at remission. Results: In the clozapine-treated therapy-resistant group, IL-1β correlated negatively with clinical improvement (admission, 4-week treatment). In patients not treated with clozapine, IL-1β correlated negatively with disease duration (admission). A negative correlation occurred between FasL and clinical improvement in general symptoms (admission, 4-week treatment), FasL and leukocyte count (admission), and IL-1β and BDNF levels (4-week treatment). In the clozapine-treated group, the negative correlation between FasL levels and the leukocyte count was absent. Conclusions: The severity of psychopathology in patients with schizophrenia seems to correlate with higher IL-1β and lower BDNF. The novelty of our findings is the observation that higher FasL is negatively associated with the degree of clinical improvement. Thus, a decline of FasL during treatment may be proposed as a predictor of clinical recovery. With caution, we suggest that clozapine use may be linked to a protective effect against FasL signaling and the alleviation of apoptotic processes.