Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders.

CX3CR1, a G protein-coupled receptor solely expressed by microglia in the brain, has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in transcriptomic and animal studies but not in genetic studies. To address the impacts of variants in CX3CR1 on neurodevelopmental disorders, we conducted coding exon-targeted resequencing of CX3CR1 in 370 Japanese SCZ and 192 ASD patients using next-generation sequencing technology, followed by a genetic association study in a sample comprising 7054 unrelated individuals (2653 SCZ, 574 ASD and 3827 controls). We then performed in silico three-dimensional (3D) structural modeling and in vivo disruption of Akt phosphorylation to determine the impact of the detected variant on CX3CR1-dependent signal transduction. We detected a statistically significant association between the variant Ala55Thr in CX3CR1 with SCZ and ASD phenotypes (odds ratio=8.3, P=0.020). A 3D structural model indicated that Ala55Thr could destabilize the conformation of the CX3CR1 helix 8 and affect its interaction with a heterotrimeric G protein. In vitro functional analysis showed that the CX3CR1-Ala55Thr mutation inhibited cell signaling induced by fractalkine, the ligand for CX3CR1. The combined data suggested that the variant Ala55Thr in CX3CR1 might result in the disruption of CX3CR1 signaling. Our results strengthen the association between microglia-specific genes and neurodevelopmental disorders.

Self-structuring of stable dissipative breathing vortex solitons in a colloidal nanosuspension.

The self-structuring of laser light in an artificial optical medium composed of a colloidal suspension of nanoparticles is demonstrated using variational and numerical methods extended to dissipative systems. In such engineered materials, competing nonlinear susceptibilities are enhanced by the light induced migration of nanoparticles. The compensation of diffraction by competing focusing and defocusing nonlinearities, together with a balance between loss and gain, allow for self-organization of light and the formation of stable dissipative breathing vortex solitons. Due to their robustness, the breathers may be used for selective dynamic photonic tweezing of nanoparticles in colloidal nanosuspensions.

Effect of Adjunctive Aripiprazole on Sexual Dysfunction in Schizophrenia: A Preliminary Open-Label Study.

Introduction: Although adjunctive aripiprazole improves hyperprolactinemia, sufficient evidence for its effects on sexual dysfunction has not been obtained. We assessed the usefulness of adjunctive aripiprazole for schizophrenia with sexual dysfunction. Methods: 22 Japanese schizophrenia patients with antipsychotic-induced hyperprolactinemia and sexual dysfunction were enrolled, and 19 of them completed the study. Aripiprazole was administrated in a flexible titration schedule to participants according to the judgment of each doctor, and patients were followed for 24 weeks. Serum prolactin, Clinical Global Impression Scales-Severity (CGI-S), and Nagoya Sexual Function Questionnaire (NSFQ) were measured at baseline and at 4, 8, 12, and 24 weeks. Results: Prolactin at week 4 and later was significantly lower than that at baseline. Compared to baseline, we observed a significant improvement in total sexual dysfunction as measured by NSFQ at week 8 and later. In males, erectile dysfunction was significantly reduced at week 24. In females, menstrual irregularity and galactorrhea were significantly reduced at week 24. CGI-S did not significantly change. Discussion: Although the small sample size is a limitation in this study, adjunctive aripiprazole may be useful treatment for sexual dysfunction including hyperprolactinemia in schizophrenia.

High-resolution copy number variation analysis of schizophrenia in Japan.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Detection of bacteria and analyses of Chlamydia trachomatis viability in patients with postvenereal reactive arthritis.

Postvenereal reactive arthritis is an inflammatory form of arthritis that commonly develops after urogenital infection, predominantly in human leucocyte antigen-B27-positive men in the third decade of life. In our hospital, patients underwent synovectomy before a 4-month course of antibiotics (ciprofloxacin, tetracycline and roxithromicin). The clinical remission was achieved in approximately 70% patients. At molecular level, the remission was associated with the negative polymerase chain reaction findings of bacteria.

Vortex bubble formation in pair plasmas.

It is shown that delocalized vortex solitons in relativistic pair plasmas with small temperature asymmetries can be unstable for intermediate intensities of the background electromagnetic field. Instability leads to the generation of ever-expanding cavitating bubbles in which the electromagnetic fields are zero. The existence of such electromagnetic bubbles is demonstrated by qualitative arguments based on a hydrodynamic analogy, and by numerical solutions of the appropriate nonlinear Schrödinger equation with a saturating nonlinearity.

Oxidative stress and anti-oxidative defense in schoolchildren residing in a petrochemical industry environment.

OBJECTIVE: To evaluate the possible relationship between industrial air pollution and oxidative stress in schoolchildren by comparing parameters from children residing in two nearby localities with contrasting environmental conditions. PARTICIPANTS: 42 schoolchildren (12-15 years) from Pancevo (site of Serbias largest petrochemical installation) formed the exposed group. 82 schoolchildren from Kovacica village, located 30 km north of Pancevo, formed the non-exposed group. METHODS: Oxidative stress status, anti-oxidative defense parameters, paraoxonase-1 status, lipid status, glucose concentration and leukocyte counts were compared in two groups. RESULTS: The children from Pancevo showed higher level of oxidative stress demonstrated by an elevated malondialdehyde concentration (P <0.001) and decreased superoxide dismutase activity (P<0.01) in comparison to the non-exposed group. CONCLUSIONS: The results suggested a relationship between the presence of air pollutants and increased oxidative stress in schoolchildren residing in an industrial environment.

Association study of the calcineurin A gamma subunit gene (PPP3CC) and methamphetamine-use disorder in a Japanese population.

Several lines of evidence from animal and genetic analyses showed that the calcineurin A gamma subunit gene (PPP3CC) plays an important role in the pathogenesis of schizophrenia. Moreover, a recent large Japanese case-control study confirmed the genetic association of PPP3CC with schizophrenia. The symptoms of methamphetamine (MAP)-induced psychosis are similar to those of schizophrenia, suggesting that PPP3CC is an attractive candidate gene not only for schizophrenia, but also for METH-related disorders. In this study, we carried out a genetic association study of PPP3CC with MAP-use disorder in a Japanese population. We selected five haplotype-tagging SNPs from the aforementioned replication study and genotyped 393 samples (MAP abuse, 128; control, 265). We could not detect a significant association of all tagging SNPs with each condition. In conclusion, our data suggest that PPP3CC does not elevate the risk of MAP-use disorder in the Japanese population.