Association of polysialic acid serum levels with schizophrenia spectrum and bipolar disorder-related structural brain changes and hospitalization

• Published in: Scientific reports Vol. 13; no. 1; pp. 2085 - 10
• Main Authors: Müller-Miny, Louisa, Thiel, Katharina, Meinert, Susanne, Hahn, Tim, Kircher, Tilo, Nenadić, Igor, Krug, Axel, Hufschmidt, Felix, Liao, Huan, Neumann, Harald, Dannlowski, Udo, Lünemann, Jan D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.02.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/340; 692/308/409; 692/308/53; 692/420; 692/499; 692/53; Adult; Bipolar disorder; Bipolar Disorder - metabolism; Brain - metabolism; Depressive Disorder, Major - metabolism; Genome-wide association studies; Genome-Wide Association Study; Genomes; Glycosylation; Hippocampal plasticity; Hippocampus; Humanities and Social Sciences; Humans; Mental depression; Mental disorders; multidisciplinary; Neurogenesis; Polysialic acid; Schizophrenia; Schizophrenia - genetics; Science; Science (multidisciplinary); Serum levels; Sialic Acids - metabolism; Substantia grisea
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-29242-3

Expression of polysialic acid (polySia) in the adult brain is enriched in areas of continuous neurogenesis and plasticity such as the hippocampus. Genome-wide association studies identified variants of glycosylation enzyme-encoding genes, required for the generation of polySia, to be associated with the development of schizophrenia and bipolar disorder. Here, we report that serum levels of polySia are increased in patients with schizophrenia spectrum disorder compared to patients with major depressive disorders or demographically matched healthy controls. Furthermore, elevated polySia serum levels are associated with structural hippocampal gray matter decline in schizophrenia spectrum and bipolar disorder. In patients with schizophrenia spectrum disorder, polySia serum levels correlate with the number, duration of disease-related hospitalizations, early retirement and medical leave as estimators of detrimental long-term disease trajectories. Our data show that polySia serum levels are linked to structural hippocampal brain changes in schizophrenia spectrum and bipolar disorders, and suggest a contribution of polySia to the pathophysiology of these diseases.