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.

Figure 1

Serum levels of polySia are increased in SZ/SZA. Shown are mean serum levels of polySia in different patient subgroups (a) and comparison between the polySia serum level and the chlorpromazine equivalent (b). (a) Serum levels of polySia were increased in SZ/SZA compared to HC (*p < .05; **p < 0.01). (b) No correlation (p =  < .97) between the polySia serum levels and the chlorpromazine (CPZ) equivalent in the medication treated cohort of patients with SZ/SZA, BD and MDD. Error bars represent standard deviation from the mean.

Figure 2

Negative association between polySia serum levels and bilateral parahippocampal gray matter volume in patients with SZ/SZA (a–c) and BD (d–f) (a) Sagittal views (x =  − 20, x = 18) of the significant clusters depicting gray matter volumes correlating with polySia levels in SZ/SZA patients. (b) Scatter plot depicting the negative correlation (r =  − .199, p = .025) of polySia levels and the peak voxel value (x =  − 20, y = 0, z =  − 32) of the cluster shown in A on the left. (c) Scatter plot depicting the negative correlation (r =  − .372, p = .010) of polySia levels and the peak voxel value (x = 18, y = -42, z = −6) of the cluster shown in A on the right. (d) Sagittal views (x = -21, x = 26) of the significant clusters depicting gray matter volumes correlating with polySia levels in BD patients. (e) Scatter plot depicting the negative correlation (r =  − .231, p = .004) of polySia levels and the peak voxel value (x =  − 27, y =  − 30, z =  − 3) of the cluster shown n in (d) on ther left. (f) Scatter plot depicting the negative correlation (r =  − .220, p = .013) of polySia levels and the peak voxel value (x = 26, y =  − 32, z =  − 2) of the cluster r shown in (d) other right. Color bars: negative correlation coefficient − r.

Figure 3

PolySia serum levels correlate with longterm disease trajectories. Correlation of polySia serum levels in SZ/SZA patients with (a) the number of hospitalization (p =  < .001)) (b) and duration of hospitalizations in months (p < .001),  (c) medical leave (p = .012) and  (d) early retirement due to medical reasons (p = .014).