Table 1 Summary of evidence for altered glycosylation in schizophrenia and/or in association with antipsychotic administration.
From: Post-translational protein modifications in schizophrenia
GWAS of patients over the progression of illness22 | Early stage: carbohydrate metabolism, lipid metabolism, protein localization, protein transport/modification | |
Intermediate stage: biopolymer glycosylation, protein amino acid glycosylation, glycoprotein biosynthesis, glycosylation/glycoprotein, lipid metabolism, protein localization, protein transport/modification | ||
Late stage: glycosylation/glycoprotein, lipid metabolism, protein localization, protein transport/modification | ||
GWAS of patients on antipsychotic medication23 | Schizophrenia patients on typical antipsychotics versus controls: ER, ER-Golgi transport, Golgi transport | |
Schizophrenia patients on atypical antipsychotics versus controls: stress response, protein binding | ||
Schizophrenia patients on typical versus atypical antipsychotics: cellular lipid metabolism, lipid biosynthesis, lipid metabolism | ||
Canonical pathway analyses70 | Schizophrenia patients on typical antipsychotics versus controls: N- and O-linked glycan biosynthesis, glycosphingolipid biosynthetic pathways | |
Glycoprotein expression levels in schizophrenia | ||
Urine (males) | Lower 24-h secretion of urinary glycoproteins24 | |
Serum | Increased concentration of protein-bound carbohydrates26 | |
Increased levels of α2- and β-globulin glycoproteins26 | ||
Monosaccharide composition of glycoprotein glycans in schizophrenia | ||
Urine (males) | Presence of rhamnose detected (trace amounts detected in only a few non-psychiatrically ill subjects)24 | |
Increased ratio of glucosamine:galactosamine24 | ||
Decreased ratios of Fuc: Neu5Ac, Fuc: hexose, hexose: hexosamine, and Fuc: hexosamine24 | ||
Urine | (acidic glycopeptide and oligosaccharide fraction) | Decreased hexose levels25 |
Increased ratio of Gal: Man25 | ||
(basic, neutral, or slightly acidic glycopeptide and oligosaccharide fraction) | Decreased rhamnose25 | |
Increased Fuc25 | ||
Serum | Increased Glc and arabanose26 | |
Altered monosaccharide composition of α2- and β-globulin glycans26 | ||
Serum (age 13–17) | Increased Fuc, Man, Glc, Gal, Neu5Ac, glucosamine, and galactosamine27 | |
Increased total hexose and hexosamine levels27 | ||
N-glycosylation of neurotransmission associated proteins in schizophrenia | ||
ACC | Smaller N-glycans on EAAT1 monomer28 | |
DLPFC | Smaller N-glycans on EAAT2 multimer28 | |
Decreased ratio of EndoH sensitive versus insensitive GluA229 | ||
Decreased binding of ConA to GluA229 | ||
Larger immature N-glycans on GluK230 | ||
STG | Smaller immature N-glycans on GABRA131 | |
More immature N-glycosylation of GABRB1 49 kDa isoform31 | ||
Altered N-glycosylation of GABRB2 concurrent with increased molecular mass of GABRB2 isoforms31 | ||
Gene and protein expression of glycosylation enzymes in schizophrenia (see Table 2) | ||
Altered glycosylation enzyme activity in schizophrenia | ||
Plasma | Increased α-2,6-sialyltransferase activity109 | |
Glycomic differences in first onset schizophrenia patients | ||
Serum | (high abundance protein fraction) | Peak (H6) containing 5 N-glycan structures is increased in male patients and decreased in female patients relative to non-psychiatrically ill subjects80 |
(low abundance protein fraction) | Peaks (U23 and U19) are increased in male schizophrenia patients80 | |
Altered N-glycans contain sialylated N-acetyllactosamine motifs80 | ||
CSF | Peaks (C17, C18, C20) are decreased in schizophrenia80 | |
Peak (C3) is increased in female patients and decreased in male patients relative to non-psychiatrically ill subjects80 | ||
Gene expression of glycosylation enzymes related to antipsychotic administration | ||
Liver | Increased expression of B4GALT1 in patients treated with atypical antipsychotics23 | |
Glycomic and glycoprotein differences related to antipsychotic administration (olanzapine) in schizophrenia | ||
Serum | Peak (16) containing a disialylated digalactosylated biantennary N-glycan is increased81 | |
Peak (20) containing 3 disialylated N-glycans is decreased81 | ||
α1 acid glycoprotein (AGP) has increased peak 16 and decreased peak 24 (containing multiple tetra-antenarry N-glycans)81 | ||
Decreased levels of non- and mono-galactosylated glycans concurrent with increased levels of digalactosylated glycans81 | ||
Decreased level of mono-sialylated glycans concurrent with an increased level of disialylated glycans81 | ||
Altered NCAM polysialylation in schizophrenia | ||
Hippocampus | Fewer PSA-NCAM-immunoreactive cells88 | |
Decreased polysialylation of NCAM88 | ||
DLPFC | Decreased PSA-NCAM in cortical layers IV and V89 | |
CSF | 105–115 kDa NCAM isoform represents a cleavage product of non-polysialylated NCAM (cNCAM), and cNCAM is increased95 | |
Cleaved NCAM level is positively correlated with ventricular volume changes in brain and patient score on the Scale for Assessment of Positive Symptoms (SANS)95 | ||
ST8SIA2 association with schizophrenia | ||
Genomic DNA | SNPs/SNP haplotypes of ST8SIA2 are associated with schizophrenia risk97,99,100,101,103 | |
