Abnormal Expression of Cell Recognition Molecules in Schizophrenia

Vawter, Marquis P.; Cannon-Spoor, H. E.; Hemperly, John J.; Hyde, Thomas M.; VanderPutten, Dale M.; Kleinman, Joel E.; Freed, William J.

doi:10.1006/exnr.1997.6721

Cited by 69 publications

(68 citation statements)

References 44 publications

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“…17,20 Several researches have reported that abnormalities of neural cell adhesion, neuronal function, and Wnt/Wingless exist in schizophrenia. [10][11][12][13][14][15]18,19,[23][24][25][26] Third, APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia. 27,28 Three SNPs of APC are associated with schizophrenia.…”

Section: Discussionmentioning

confidence: 98%

“…16,17 Several researches have reported that abnormalities of neural cell adhesion exist in schizophrenia. 18,19 APC colocalized with DLG (DLG, the human homolog of the Drosophila discs large tumor suppressor protein) at the lateral cytoplasm in rat colon epithelial cells and at the synapse in cultured hippocampal neurons. The APC-DLG complex participates in the regulation of both cell cycle progression and neuronal function.…”

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confidence: 99%

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The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

Cui

Jiang

et al. 2005

Mol Psychiatry

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The etiology of schizophrenia is unclear, although family, twin, and linkage studies implicate genetic factors. Here, we identified adenomatous polyposis coli (APC), a tumor suppressor gene, as a risk factor for schizophrenia. We compared leukocytic gene expression patterns of six pairs of patients with schizophrenia and healthy controls by microarray. APC expression levels were significantly increased in all patients compared to healthy controls. To confirm the findings of microarray analysis, we measured expression levels of APC in the leukocytes from 30 relapse patients taking antipsychotic medication, 29 first-episode drug-naïve patients, and 30 healthy controls using real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). APC expression levels were significantly increased in leukocytes of schizophrenics both taking and not taking antipsychotic medication and hence the increase of APC expression was not due to antipsychotic medication. APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia. Further, we performed the transmission disequilibrium test (TDT) and TDT based on haplotypes to search for the association between schizophrenia and APC by examining 163 parent-offspring trios of Chinese descent. We analyzed three single-nucleotide polymorphisms (SNPs) (rs2229992, rs42427, rs465899) at the exon region of APC. TDT showed that the three SNPs are significantly associated with schizophrenia (TDT v 2 ¼ 4.23, Po0.05; 4.15, Po0.05; 8.49 Po0.01, respectively; HHRRv 2 ¼ 5.54, Po0.05; 4.40, Po0.05; 9.79, Po0.01, respectively). We found a significant association between the APC haplotypes from rs2229992-rs42427-rs465899 and schizophrenia (Global v 2 ¼ 44.376,df ¼ 7, Po0.001). The C-A-T haplotype has a frequency of more than 57% and has a strong association with schizophrenia (v 2 ¼ 15.04, Po0.001). These results indicate that the APC may be a candidate gene conferring susceptibility to schizophrenia and also may be associated with reduced vulnerability to cancer in schizophrenia.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

Cui

Jiang

et al. 2005

Mol Psychiatry

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“…22,23 Increases in CSF N-CAM 100-120 kDa in patients with schizophrenia and bipolar disorder, type I were reported. 24,25 Further, increased levels of brain N-CAM have been found in patients with schizophrenia in the cingulate cortex, hippocampus, and prefrontal cortex, 26,27 but not in bipolar disorder patients. The N-CAM containing VASE isoform was found to be increased in the hippocampus and prefrontal cortex of bipolar patients, but not in patients with schizophrenia.…”

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confidence: 94%

“…28 The SEC N-CAM isoform is produced by the incorporation of an alternative exon resulting in premature termination of transcription. 29 The possibility that the prior findings of increased N-CAM in bipolar disorder and schizophrenia 24,25,27,28 were related to abnormal production of the secreted (SEC) form of N-CAM was investigated.…”

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Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia

et al. 1999

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“…4,5 A selective increase in levels of 105-to 115-kDa NCAM in the hippocampi and prefrontal cortices of patients with schizophrenia was found, though levels of other NCAMs and L1CAM were not altered. 6,7 Since NCAMs function can be impaired by viral neuroaminidase associated with maternal influenza infection during embryonic development, 8 and since increased CSF NCAM and decreased CSF L1CAM levels were found in affected but not non-affected twins in a study of monozygotic discordant twins, the changes in NCAMs observed in schizophrenia may not contribute to the genetic predisposition to schizophrenia. 4 However, schizophrenia is known to have a genetic component, and a cohort study suggested an interaction between genetic risk for schizophrenia and obstetric complications.…”

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An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia

et al. 2002

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Morphological alterations in the brains of schizophrenia patients suggest that neurodevelopmental dysfunction is involved in the etiology of the disease. 1 Such dysfunction may be due to functional alterations of cell adhesion molecules, which play important roles in cell migration, axonal growth, fasciculation, synaptogenesis, and synaptic remodeling. We screened for mutations in the coding region of the close homologue to L1 gene (CHL1), which is located on human chromosome 3p26, in 24 Japanese patients with schizophrenia. A missense polymorphism (Leu17Phe) in the signal peptide region was identified. A case-control comparison revealed significantly higher frequencies of the Leu/Leu genotype (P = 0.004) and the Leu allele (P = 0.006) in 282 Japanese schizophrenic patients than in 229 Japanese control subjects. The estimated odds ratio for schizophrenia was 1.83 (95% CI, 1.28-2.26) for the Leu/Leu genotype compared with the other genotypes. An association between this CHL1 gene polymorphism and schizophrenia supports the notion that cell adhesion molecules are involved in the etiology of schizophrenia. Molecular Psychiatry (2002) 7, 412-415. DOI: 10.1038/ sj/mp/4000973Cell adhesion molecules (CAMs) play important roles in specifying cell-cell interactions during development, regeneration, and modification of synaptic activity. In humans, mutations in the L1 cell adhesion molecule (L1CAM) are associated with a neurological syndrome termed CRASH, which includes corpus callosum agenesis, mental retardation, adducted thumbs, spasticity, hydrocephalus, and a wide spectrum of other clinical features. A mouse model with null mutation in the L1CAM gene suggests roles for L1CAM in the mechanism of cortical dendrite differentiation as well as in guidance of callosal axons and regulation of hippocampal development. 2 An abnormality in expression of one of the CAMs could result in the histologic abnormalities observed in the brains of individuals with schizophrenia. 3 Increased neural CAM (NCAM) and decreased L1CAM immunoreactivities have been observed in the cerebrospinal fluid (CSF) of schizophrenic patients in comparison to immunoreactivities in normal control subjects. 4,5 A selective increase in levels of 105-to 115-kDa NCAM in the hippocampi and prefrontal cortices of patients with schizophrenia was found, though levels of other NCAMs and L1CAM were not altered. 6,7 Since NCAMs function can be impaired by viral neuroaminidase associated with maternal influenza infection during embryonic development, 8 and since increased CSF NCAM and decreased CSF L1CAM levels were found in affected but not non-affected twins in a study of monozygotic discordant twins, the changes in NCAMs observed in schizophrenia may not contribute to the genetic predisposition to schizophrenia. 4 However, schizophrenia is known to have a genetic component, and a cohort study suggested an interaction between genetic risk for schizophrenia and obstetric complications. 9,10 It is possible that mutations in the genes encoding CAMs are part of the gene...

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Abnormal Expression of Cell Recognition Molecules in Schizophrenia

Cited by 69 publications

References 44 publications

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia

An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia

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