Early-stage identification of schizophrenia subtypes using a multimodal biomarker fingerprints (NU22-04-00143)
Basic informations
Investigator: MUDr. Filip Španiel, Ph.D.
Main recipient: National Institute of Mental Health (NIMH)
Co-recipient: Institute of Physiology of the Czech Academy of Science
Research period: 1/5/2022 – 31/12/2025
Total budget: 13,372,000 CZK
NIHM budget: 6,189,000 CZK
Supported by: Czech Health Research Council (AZV ČR)
Annotation
Schizophrenia (SZ) represents a heterogeneous disorder. Diversity in etiology extends to heterogeneity in treatment responses and functional outcome. Identification of disease subtypes with different underlying mechanisms will ultimately aid in developing stratified treatments for biologically based patient profiles. Previously, we have applied a data-driven hierarchical clustering to the longitudinal MRI morphometry in a large-scale first-episode schizophrenia (FES) sample. We have identified three distinct schizophrenia neurotypes suggesting divergent pathological pathways behind diverse patterns of progressive cortical reorganization and divergent clinical course. The finding has been validated in independent patient sample. In this project, we will build upon this unique proof-of-concept subtypization algorithm. The brain-enriched protein biomarkers (BBs) S100B, NSE, NF-L, GFAP, UCH-L1 and inflammatory cytokine markers IL-6, IL-8, TNF-a, IFN-g, IL-1B will be serially sampled in blood (at baseline and one year later) in 370 FES patients. The BBs have been a priori selected to reflect a wide range of brain cellular damage (neurons, astrocytes, axonal degradation, microglial activation and inflammation). The aim of this study is to determine specific temporal patterning in those circulating probes of CNS tissue fate, pertaining to respective neurotypes identified in a previous research. Secondly, endophenotype in form of smooth pursuit eye movement (SPEM) dysfunction will allow us to infer different genetic load risk in those SZ subtypes.