1J. Neurosci. Res. 2009 Jan 87: 278-88
PMID18683247
TitleEvidence for disruption of sphingolipid metabolism in schizophrenia.
AbstractAs 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.
SCZ Keywordsschizophrenia, schizophrenic
2J. Neurosci. Res. 2009 Jan 87: 278-88
PMID18683247
TitleEvidence for disruption of sphingolipid metabolism in schizophrenia.
AbstractAs 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.
SCZ Keywordsschizophrenia, schizophrenic
3World J. Biol. Psychiatry 2012 Feb 13: 106-13
PMID21375364
TitleIdentification of the N-acylsphingosine amidohydrolase 1 gene (ASAH1) for susceptibility to schizophrenia in a Han Chinese population.
AbstractTo study the involvement of the N-acylsphingosine amidohydrolase 1 gene (ASAH1) in the susceptibility to schizophrenia in the Han Chinese population.
We performed cDNA microarray analysis to exam the gene expression profile in six schizophrenic patients and six healthy controls. We evaluated the ASAH1 expression levels in 30 subjects with chronic schizophrenia and 30 healthy controls by using real-time polymerase chain reaction (PCR). A total of 254 unrelated probands with schizophrenia and their biological parents were also genotyped at three single nucleotide polymorphisms (SNPs: rs3753118, rs3753116, and rs7830490) of the ASAH1 gene for association analysis.
In the microarray analysis, the ASAH1 gene was down-regulated in all schizophrenic patients compared with healthy controls. In real-time PCR, the ASAH1 expression levels for schizophrenic patients with positive family history were significantly decreased (P = 0.020). In the association analyses, two SNPs (rs7830490 and rs3753118) and one haplotype (rs7830490 (A)-rs3753116 (G)) of ASAH1 showed significant evidence of nominal associations with schizophrenia (P = 0.026; P = 0.046; P = 0.007, respectively). The haplotype remained statistically significant (empirical P = 0.045) after correction for multiple testing.
This study supports that the ASAH1 gene may be a potential candidate gene for schizophrenia in Han Chinese subjects.
SCZ Keywordsschizophrenia, schizophrenic
4World J. Biol. Psychiatry 2012 Feb 13: 106-13
PMID21375364
TitleIdentification of the N-acylsphingosine amidohydrolase 1 gene (ASAH1) for susceptibility to schizophrenia in a Han Chinese population.
AbstractTo study the involvement of the N-acylsphingosine amidohydrolase 1 gene (ASAH1) in the susceptibility to schizophrenia in the Han Chinese population.
We performed cDNA microarray analysis to exam the gene expression profile in six schizophrenic patients and six healthy controls. We evaluated the ASAH1 expression levels in 30 subjects with chronic schizophrenia and 30 healthy controls by using real-time polymerase chain reaction (PCR). A total of 254 unrelated probands with schizophrenia and their biological parents were also genotyped at three single nucleotide polymorphisms (SNPs: rs3753118, rs3753116, and rs7830490) of the ASAH1 gene for association analysis.
In the microarray analysis, the ASAH1 gene was down-regulated in all schizophrenic patients compared with healthy controls. In real-time PCR, the ASAH1 expression levels for schizophrenic patients with positive family history were significantly decreased (P = 0.020). In the association analyses, two SNPs (rs7830490 and rs3753118) and one haplotype (rs7830490 (A)-rs3753116 (G)) of ASAH1 showed significant evidence of nominal associations with schizophrenia (P = 0.026; P = 0.046; P = 0.007, respectively). The haplotype remained statistically significant (empirical P = 0.045) after correction for multiple testing.
This study supports that the ASAH1 gene may be a potential candidate gene for schizophrenia in Han Chinese subjects.
SCZ Keywordsschizophrenia, schizophrenic