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

Authors

• Mohini Ranganathan, Yale University
• Susanne Jakob, Broad Institute of MIT and Harvard
• Felecia Cerrato, Broad Institute of MIT and Harvard
• Lia Urban Spillane, Yale University
• Tarlan S. Daryoush, University of Pennsylvania
• Sophie Shuster, Clark University
• Katherine Dokholyan, Icahn School of Medicine at Mount Sinai
• Shaynna Herrera, Icahn School of Medicine at Mount Sinai,
• Brian Koo, Yale University
• Clyde Markowitz, University of Pennsylvania
• Pojen Deng, Icahn School of Medicine at Mount Sinai
• Sage Rush, University of Pennsylvania
• Monica E. Calkins, University of Pennsylvania
• Scott Troyan, University of Pennsylvania
• Kosha Ruparel, University of Pennsylvania
• Ruben C. Gur, University of Pennsylvania
• Holly Reynolds, Indiana University
• Claire Wegel, Indiana University
• Matthew B. Johnson, Broad Institute of MIT and Harvard
• Lauren Hom, Broad Institute of MIT and Harvard
• Sam Bryant, Broad Institute of MIT and Harvard
• Ross W. Mair, Harvard University
• Randy L. Buckner, Harvard University
• Rebecca Birnbaum, Harvard University
• Christian G. Kohler, University of Pennsylvania
• Cheryl M. Corcoran, Icahn School of Medicine at Mount Sinai,
• Raquel E. Gur, University of Pennsylvania
• Steven E. Hyman, Harvard University

Document Type

Article

Abstract

Background and Hypothesis: 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. Study Design: 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. Study Results: 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. Conclusions: The pilot SSBC study demonstrates that a multi-site, longitudinal study with repeat CSF collection is feasible, with excellent participant acceptability and retention.

Publication Title

Schizophrenia Bulletin

Publication Date

9-2026

Volume

52

Issue

5

ISSN

0586-7614

DOI

10.1093/schbul/sbag113

Keywords

biorepository, cognition, fluid biomarkers, longitudinal study, lumbar puncture, schizophrenia

Repository Citation

Ranganathan, Mohini; Jakob, Susanne; Cerrato, Felecia; Urban Spillane, Lia; Daryoush, Tarlan S.; Shuster, Sophie; Dokholyan, Katherine; Herrera, Shaynna; Koo, Brian; Markowitz, Clyde; Deng, Pojen; Rush, Sage; Calkins, Monica E.; Troyan, Scott; Ruparel, Kosha; Gur, Ruben C.; Reynolds, Holly; Wegel, Claire; Johnson, Matthew B.; Hom, Lauren; Bryant, Sam; Mair, Ross W.; Buckner, Randy L.; Birnbaum, Rebecca; Kohler, Christian G.; Corcoran, Cheryl M.; Gur, Raquel E.; and Hyman, Steven E., "Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers" (2026). Student Publications [Scholarly]. 116.
https://commons.clarku.edu/student_publications/116

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Copyright Conditions

Ranganathan, M., Jakob, S., Cerrato, F., Urban Spillane, L., Daryoush, T. S., Shuster, S., ... & Hyman, S. E. (2026). Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers. Schizophrenia Bulletin, 52(5), sbag113. https://doi.org/10.1093/schbul/sbag113