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

Abstract

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.

Sialic acid biosynthesis pathway blockade disturbs neuronal network formation in human iPSC‐derived excitatory neurons

“…Furthermore, sialic acid is connected to multiple neurodevelopmental disorders. In patients with schizophrenia, elevated levels of serum polySia have been detected (Muller-Miny et al, 2023).…”

“…Furthermore, sialic acid is connected to multiple neurodevelopmental disorders. In patients with schizophrenia, elevated levels of serum polySia have been detected (Muller‐Miny et al, 2023). In a schizophrenia mouse model, polySia was less prevalent, and the present polySia was shorter in length within the hypothalamus (Takahashi et al, 2022).…”

Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases

“…Thereby, ST8SIA2 gene expression levels negatively correlated with the childhood autism rating scale (CARS) score, indicating more serious stereotype behaviors and sensory abnormalities with decreasing ST8SIA2 expression ( 107 ). Furthermore, a correlation between polysialic acid serum levels and structural brain changes related to the schizophrenia spectrum and bipolar disorder was observed, suggesting that soluble polysialic acid, released as part of the disease process in the brain, can be detected in the patients’ serum ( 109 ). While no direct link between schizophrenia and the CD33-related SIGLECs has been described so far, patient-specific polymorphisms in the SIGLEC4/MAG gene expressed in oligodendrocytes have been significantly associated with the disease ( 110 , 111 ).…”