Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative...

Schizophrenia spectrum disorders (SSDs) produce severe symptoms, disability, and premature mortality, but only partially effective symptomatic treatments exist. Treatment development is impeded by lack of insight into disease mechanisms or objective biomarkers for clinical trials. Advances in genetics and neurobiology have converged on strong pathogenic hypotheses for SSDs centered on synapse dysfunction and excessive pruning, pathogenic processes that may produce measurable proteomic evidence in cerebrospinal fluid (CSF). Leveraging design precedents from successful fluid biomarkers discovery for Alzheimer's disease, we undertook a pilot study to test the feasibility of repeated CSF and blood samples collection from individuals with SSDs. Here we report on successful implementation of longitudinal bio-behavioral phenotyping in SSDs and establishment of a repository to permit broad sample and data sharing.

The Schizophrenia Spectrum Biomarkers Consortium (SSBC) study principles included longitudinal study design, paired CSF and plasma collection associated with robust phenotypic characterization, at 3 academic sites and the establishment of a biorepository. Participants underwent clinical and cognitive assessments, neuroimaging, blood draws, and CSF collection via lumbar puncture (LP) every 6 months.

SSBC successfully enrolled 48 SSD and 41 Healthy Controls with a 73% longitudinal retention. Clinical, cognitive, and neuroimaging results were consistent across sites and with existing studies. Study procedures were well tolerated, and almost all LPs (99%) resulted in either no or minor headache/backache that resolved without medical interventions.

The pilot SSBC study demonstrates that a multi-site, longitudinal study with repeat CSF collection is feasible, with excellent participant acceptability and retention.