As the field of glycobiology grows, important roles for
glycolipids and
glycoproteins in
neurological disorders are being increasingly appreciated. However, few studies have explored the involvement of these molecules in the pathology of
psychiatric illnesses. We investigated molecular differences related to glycobiology in subjects with
schizophrenia by analyzing gene expression profiles using a focused glycogene chip, a custom-designed
oligonucleotide array containing genes encoding
proteins related to glycobiology, including
glycosyltransferases,
carbohydrate-
binding proteins,
proteoglycans, and adhesion molecules. We measured expression profiles in prefrontal cortical (BA46) samples from schizophrenic subjects and matched controls. We find differential expression of genes particularly related to
glycosphingolipid/
sphingolipid metabolism and N- and O-linked
glycan biosynthesis in subjects with
schizophrenia. Expression decreases of seven genes associated with these pathways, UGT8, SGPP1, GALC, B4GALT6, SPTLC2, ASAH1, and GAL3ST1, were validated by quantitative PCR in schizophrenic subjects with short-term illness. Only one of these genes, SPTLC2, showed differential expression in chronic schizophrenic subjects, although an increase in expression was observed. Covariate analysis showed that the expression of five of these genes was significantly positively correlated with age in schizophrenic, but not control, subjects. These changing patterns of expression could represent an adaptive response to pathology with
disease progression or a compensatory effect of
antipsychotic medication, although no significant correlations between gene expression levels and
drug doses were observed. Disruption of
sphingolipid metabolism early in illness could result in widespread downstream effects encompassing diverse pathological deficits already described in
schizophrenia, especially those involving myelination and oligodendrocyte function; hence, this system may represent an important link in
schizophrenia pathology.