Cerebrospinal fluid concentration of complement component 4A is increased in first-episode schizophrenia Article Swipe

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C4A Cerebrospinal fluid Schizophrenia (object-oriented programming) Complement (music) Synapse Complement system Synaptic pruning Psychosis Neuroscience Medicine Psychology Immunology Gene Biology Inflammation Psychiatry Microglia Antibody Genetics Phenotype Complementation

Jessica Gracias , Funda Orhan , Elin Hörbeck , Jessica Holmén‐Larsson , Neda Khanlarkani , Susmita Malwade , Sravan K. Goparaju , Lilly Schwieler , Helena Fatouros‐Bergman , Aurimantas Pelanis , Carleton P. Goold , Anneli Goulding , Kristina Annerbrink , Anniella Isgren , Timea Sparding , Martin Schalling , Viviana A. Carcamo Yañez , Jens Göpfert , Johanna Nilsson , Ann Brinkmalm , Kaj Blennow , Henrik Zetterberg , Göran Engberg , Fredrik Piehl , Steven D. Sheridan , Roy H. Perlis , Simon Červenka , Sophie Erhardt , Mikael Landén , Carl M. Sellgren ·

YOU? · · 2021 · Open Access · · DOI: https://doi.org/10.1101/2021.08.17.21262131 · OA: W3193374178

Excessive synapse loss is a core feature of schizophrenia and is linked to the complement component 4A gene ( C4A ). In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in first-episode psychosis patients who develop schizophrenia and correlates with CSF measurements of synapse density. Using patient-derived cellular modeling, we find that disease-associated cytokines increase neuronal C4A expression and that IL-1β associates with C4A in patient-derived CSF.