Combined pattern of childhood psycho-behavioral characteristics in patients with schizophrenia: a retrospective study in Japan.

BACKGROUND: Although epidemiological and genetic studies have provided scientific evidence that places schizophrenia into the framework of early neurodevelopmental disorders, the psycho-behavioral characteristics of children that later go on to develop schizophrenia have not been sufficiently clarified. This study aimed to retrospectively identify characteristics specific to patients with schizophrenia during childhood via their guardians' reporting of these characteristics. METHODS: Participants included 54 outpatients with schizophrenia in their twenties who fulfilled DSM-IV-TR criteria. Additionally, 192 normal healthy subjects participated as sex- and age-matched controls. The guardians of all participants were recruited to rate participants' childhood characteristics from 6 to 8 years of age on a modified version of the Child Behavior Checklist (CBCL), which was used as a retrospective assessment questionnaire. Using t-tests, logistic regression, and Receiver Operating Characteristic (ROC) curve analysis, we estimated the psycho-behavioral characteristics specific to schizophrenia during childhood. Using the obtained logistic regression model, we prototyped a risk-predicting algorithm based on the CBCL scores. RESULTS: Among the eight CBCL subscale t-scores, "withdrawn" (p = 0.002), "thought problems" (p = 0.001), and "lack of aggressive behavior" (p = 0.002) were each significantly associated with the later diagnosis of schizophrenia, although none of these mean scores were in the clinical range at the time of childhood. The algorithm of the logistic regression model, based on eight CBCL subscales, had an area under the ROC curve of 82.8% (95% CI: 76-89%), which indicated that this algorithm's prediction of late development of schizophrenia has moderate accuracy. CONCLUSIONS: The results suggest that according to guardian reports, participants showed psycho-behavioral characteristics during childhood, different to those of healthy controls, which could be predictive of the later development of schizophrenia. Our newly developed algorithm is available to use in future studies to further test its validity.

DNA methylation regulates long-range gene silencing of an X-linked homeobox gene cluster in a lineage-specific manner.

DNA methylation is a major epigenetic mechanism that has been suggested to control developmental gene regulation during embryogenesis, but its regulatory mechanisms remain unclear. In this report, we show that CpG islands associated with the X-linked homeobox gene cluster Rhox, which is highly expressed in the extraembryonic trophectoderm, are differentially methylated in a stage- and lineage-specific manner during the post-implantation development of mice. Inactivation of both Dnmt3a and Dnmt3b, DNA methyltransferases essential for the initiation of de novo DNA methylation, abolished the establishment of DNA methylation and the silencing of Rhox cluster genes in the embryo proper. The Dnmt3-dependent CpG-island methylation at the Rhox locus extended for a large genomic region ( approximately 1 Mb) containing the Rhox cluster and surrounding genes. Complementation experiments using embryonic stem (ES) cells deficient in the DNA methyltransferases suggested that the CpG-island methylation by Dnmt3a and Dnmt3b was restricted within this large genomic region, and did not affect the neighboring genes outside it, implicating the existence of region-specific boundaries. Our results suggest that DNA methylation plays important roles in both long-range gene silencing and lineage-specific silencing in embryogenesis.

First report on Schizophyllum commune from a dog.

This report describes the first isolation of Schizophyllum commune from a granulomatous lesion on the neck of a dog. The biopsy specimen from the lesion disclosed granulomatous inflammation with branching fungal hyphae without clamp connections. The clinical isolate was identified as S. commune by mycological examination and analysis of ribosomal DNA sequences.