| 1 | Ann. Med. 2007 -1 39: 145-53 |
|---|---|
| PMID | 17453677 |
| Title | Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia? |
| Abstract | Published data support genetic variants, as well as certain infectious agents, as potential risk factors forschizophrenia. Less is known about interactions between the risk factors. To evaluate exposure to infectious agents and host genetic variation as joint risk factors. We investigated four infectious agents: cytomegalovirus (CMV), herpes simplex viruses 1 and 2 (HSV1, HSV2), andTOXoplasma gondii (TOX). We initially compared exposure using specific serum antibodies, among simplex and multiplex nuclear families (one or more than one affected offspring, respectively). If interactions between infectious agents and host genetic variation are important risk factors forschizophrenia, we reasoned that they would be more prominent among multiplex versus simplex families. We also evaluated the role of variation at chromosome 6p21-p23 in conjunction with exposure. We used 22 short tandem repeat polymorphisms (STRPs) dispersed across this region. Though exposure to all four agents was increased among multiplex families versus simplex families, the difference was consistently significant only for CMV (odds of exposure to CMV in multiplex families: 2.47, 95% CI: 1.48-5.33). Transmission disequilibrium tests and case-control comparisons using STRPs revealed significant linkage/association with D6S2672 among CMV+schizophreniapatients. Polymorphisms near D6S2672 could confer risk forschizophreniain conjunction with CMV exposure. |
| SCZ Keywords | schizophrenia |
| 2 | Schizophr Bull 2012 Nov 38: 1149-54 |
| PMID | 22966150 |
| Title | Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure. |
| Abstract | Genome-wide association studies (GWAS) implicate single nucleotide polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA) region, as common risk factors forschizophrenia(SZ). Other studies implicate viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on SZ risk with and without exposure. GWAS-significant SNPs and ancestry-informative marker SNPs were analyzed among African American patients with SZ (n = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (HSV-1), cytomegalovirus (CMV), andTOXoplasma gondii (TOX) was assayed using specific antibody assays. Five SNPs were nominally associated with SZ, adjusted for population admixture (P < .05, uncorrected for multiple comparisons). These SNPs were next analyzed in relation to infectious exposure. Multivariate analysis indicated significant association between rs3130297 genotype and HSV-1 exposure; the associated allele was different from the SZ risk allele. We propose a model for the genesis of SZ incorporating genomic variation in the HLA region and neurotropic viral exposure for testing in additional, independent African American samples. |
| SCZ Keywords | schizophrenia |
| 3 | Neurobiol. Dis. 2015 Apr 76: 137-58 |
| PMID | 25684539 |
| Title | Motor and behavioral phenotype in conditional mutants with targeted ablation of cortical D1 dopamine receptor-expressing cells. |
| Abstract | D1-dopamine receptors (Drd1a) are highly expressed in the deep layers of the cerebral cortex and the striatum. A number of human diseases such as Huntington disease andschizophreniaare known to have cortical pathology involving dopamine receptor expressing neurons. To illuminate their functional role, we exploited a Cre/Lox molecular paradigm to generate Emx-1(TOX转基因线)狗老鼠,皮质博士d1a-expressing pyramidal neurons were selectively ablated. Emx-1(TOX) MUT mice displayed prominent forelimb dystonia, hyperkinesia, ataxia on rotarod testing, heightened anxiety-like behavior, and age-dependent abnormalities in a test of social interaction. The latter occurred in the context of normal working memory on testing in the Y-maze and for novel object recognition. Some motor and behavioral abnormalities in Emx-1(TOX) MUT mice overlapped with those in CamKII?(TOX) MUT transgenic mice, a line in which both striatal and cortical Drd1a-expressing cells were ablated. Although Emx-1(TOX) MUT mice had normal striatal anatomy, both Emx-1(TOX) MUT and CamKII?(TOX) MUT mice displayed selective neuronal loss in cortical layers V and VI. This study shows that loss of cortical Drd1a-expressing cells is sufficient to produce deficits in multiple motor and behavioral domains, independent of striatal mechanisms. Primary cortical changes in the D1 dopamine receptor compartment are therefore likely to model a number of core clinical features in disorders such as Huntington disease andschizophrenia. |
| SCZ Keywords | schizophrenia |