| 1 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007 Dec 144B: 1083-6 |
|---|---|
| PMID | 17541950 |
| Title | Polymorphisms in the homeobox gene OTX2 may be a risk factor for bipolar disorder. |
| Abstract | We investigated the possible involvement ofOTX2, a homeobox gene crucial for forebrain development, in the pathogenesis of精神分裂症and bipolar disorder. The disruption of this gene results in cortical malformations and causes serotonergic and dopaminergic cells in the midbrain to be expressed in aberrant locations. Resequencing of DNA fromOTX2exons and surrounding introns from 60 individuals (15精神分裂症, 15 bipolar disorder, 15 depression, and 15 control) revealed two intronic polymorphisms, rs2277499 (C/T) and rs28757218 (G/T), but no other variations. The minor allele of rs2277499 (T) did not associate with clinical diagnosis. However, using a Taqman genotyping assay, we found the rs28757218 minor allele (T) in 30 out of 720 (4.2%) individuals with bipolar disorder but only in 6 out of 526 (1.1%) control individuals (odds ratio 3.5, 95% confidence interval 1.4-10.4, P = 0.003). On the other hand, the rs28757218 minor allele was only found in 6 out of 458 (1.3%) individuals with精神分裂症. All individuals with the rs28757218 polymorphism were heterozygous for the allele. Based on this positive case-control association finding, we conclude that variations inOTX2might confer risk for the development of bipolar disorder. |
| SCZ Keywords | 精神分裂症 |
| 2 | Psychiatr. Genet. 2008 Dec 18: 295-301 |
| PMID | 19018235 |
| Title | Polymorphisms of coding trinucleotide repeats of homeogenes in neurodevelopmental psychiatric disorders. |
| Abstract | Autism (MIM#209850) and精神分裂症都是神经发育psychiatr (MIM # 181500)ic disorders characterized by a highly genetic component. Homeogenes and forkhead genes encode transcription factors, which have been involved in brain development and cell differentiation. Thus, they are relevant candidate genes for psychiatric disorders. Genetic studies have reported an association between autism and DLX2, HOXA1, EN2, ARX, and FOXP2 genes whereas only three studies of EN2,OTX2, and FOXP2 were performed on精神分裂症. Interestingly, most of these candidate genes contain trinucleotide repeats coding for polyamino acid stretch in which instability can be the cause of neurodevelopmental disorders. Our goal was to identify variations of coding trinucleotide repeats in精神分裂症, autism, and idiopathic mental retardation. We screened the coding trinucleotide repeats of OTX1, EN1, DLX2, HOXA1, and FOXP2 genes in populations suffering from精神分裂症(247 patients), autism (98 patients), and idiopathic mental retardation (56 patients), and compared them with control populations (112 super controls and 202 healthy controls). Novel deletions and insertions of coding trinucleotide repeats were found in the DLX2, HOXA1, and FOXP2 genes. Most of these variations were detected in controls and no difference in their distribution was observed between patient and control groups. Two different polymorphisms in FOXP2 were, however, found only in autistic patients and the functional consequences of these variations of repeats have to be characterized and correlated to particular clinical features. This study did not identify specific disease risk variants of trinucleotide repeats in OTX1, EN1, DLX2, HOXA1, and FOXP2 candidate genes in neurodevelopmental psychiatric disorders. |
| SCZ Keywords | 精神分裂症 |
| 3 | Eur. J. Neurosci. 2011 Dec 34: 1906-22 |
| PMID | 22132705 |
| Title | The genetic signature of perineuronal oligodendrocytes reveals their unique phenotype. |
| Abstract | Oligodendrocytes--best known for assembling central nervous system myelin--can be categorized as precursors, myelin-forming cells and non-myelinating perineuronal cells. Perineuronal oligodendrocytes have been well characterized morphologically and ultrastructurally, but knowledge about their function remains scanty. It has been proposed that perineuronal oligodendrocytes support neurons and, following injury, transform into myelin-synthesizing cells. Recent findings implicating perineuronal oligodendrocytes in cytoarchitectural abnormalities in the prefrontal cortex of精神分裂症and other psychiatric disorders shed new light on these cells. We have obtained the genetic signature of perineuronal oligodendrocytes by identifying gene expression differences between oligodendrocyte subpopulations using cell-specific tags, microarray technology, quantitative time-resolved polymerase chain reaction and bioinformatics tools. We show that perineuronal cells are the progeny of oligodendrocyte progenitors and, hence, are members of the oligodendrocyte lineage. Physiologically they exhibit a novel phenotype. Their expression of PDGFR-?? and its growth factor ligand PDGF-CC sets them apart from members of their lineage as this receptor precludes their response to the same growth factors that act on myelinating cells. Their coordinate expression and context-specific usage of transcription factors Olig2, Ascl1 and Pax6, together with the prominent presence of transcription factors Pea3, Lhx2 andOTX2--not hitherto linked to the oligodendrocyte lineage--suggested a cell with features that blur the boundary between a neuron and a glial cell. But they also maintain a reservoir of untranslated transcripts encoding major myelin proteins presumably for a demyelinating episode. This first molecular characterization of perineuronal oligodendrocytes revealed the striking difference between the myelinating and non-myelinating phenotypes. |
| SCZ Keywords | 精神分裂症 |
| 4 | Neuropsychopharmacology 2015 Mar 40: 839-48 |
| PMID | 25241801 |
| Title | Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder. |
| Abstract | Subtle mood fluctuations are normal emotional experiences, whereas drastic mood swings can be a manifestation of bipolar disorder (BPD). Despite their importance for normal and pathological behavior, the mechanisms underlying endogenous mood instability are largely unknown. During embryogenesis, the transcription factorOTX2orchestrates the genetic networks directing the specification of dopaminergic (DA) and serotonergic (5-HT) neurons. Here we behaviorally phenotyped mouse mutants overexpressingOTX2in the hindbrain, resulting in an increased number of DA neurons and a decreased number of 5-HT neurons in both developing and mature animals. Over the course of 1 month, control animals exhibited stable locomotor activity in their home cages, whereas mutants showed extended periods of elevated or decreased activity relative to their individual average. Additional behavioral paradigms, testing for manic- and depressive-like behavior, demonstrated that mutants showed an increase in intra-individual fluctuations in locomotor activity, habituation, risk-taking behavioral parameters, social interaction, and hedonic-like behavior. Olanzapine, lithium, and carbamazepine ameliorated the behavioral alterations of the mutants, as did the mixed serotonin receptor agonist quipazine and the specific 5-HT2C receptor agonist CP-809101. Testing the relevance of the genetic networks specifying monoaminergic neurons for BPD in humans, we applied an interval-based enrichment analysis tool for genome-wide association studies. We observed that the genes specifying DA and 5-HT neurons exhibit a significant level of aggregated association with BPD but not with精神分裂症or major depressive disorder. The results of our translational study suggest that aberrant development of monoaminergic neurons leads to mood fluctuations and may be associated with BPD. |
| SCZ Keywords | 精神分裂症 |