Disturbances of synaptic connectivity during perinatal and adolescent periods have been hypothesized to be related to the pathophysiology of schizophrenia. Rho guanine nucleotide exchange factor 11 (ARHGEF11) is a specific guanine nucleotide exchange factors (GEF) for RhoA, which is a critical regulator of actin cytoskeleton dynamics and organization of dendritic spines and inhibitor of spine maintenance. ARHGEF11 variants are reported to be associated with a higher risk for the onset of schizophrenia in a Japanese population; however, how ARHGEF11 contributes to the pathogenesis of schizophrenia in dendritic spines is unknown. Therefore, we first studied the distribution, binding, and function of ARHGEF11 in the dendritic spines of the rat cerebral cortex. After subcellular fractionation of the rat cerebral cortex, ARHGEF11 was detected with synaptophysin and post-synaptic density protein 95 (PSD-95) in the P2 fractions including synaptosomal fractions containing presynaptic and postsynaptic density proteins. Endogenous ARHGEF11 was coimmunoprecipitated with synaptophysin or PSD-95. In cortical primary neurons at 28 days in vitro, immunostaining revealed that ARHGEF11 located in the dendrites and dendritic spines and colocalized with PSD-95 and synaptophysin. Overexpression of exogenous ARHGEF11 significantly decreased the number of spines (p = 0.008). These results indicate that ARHGEF11 is likely to be associated with synaptic membranes and regulation of spine.

Sensory impairments are common features of autism spectrum disorder (ASD) and are associated with its social impairments. However, there is no established treatment for these impairments in adults with ASD. The Safe & Sound Protocol (SSP) is a listening program designed to improve social communication skills by reducing auditory hypersensitivity. We investigated the effectiveness of the SSP for adults with ASD. We administered the SSP to six participants with ASD aged 21–44 years old, and the effects were assessed using the Social Responsiveness Scale, Second Edition (SRS-2). Secondary outcomes were assessed using the Center for Epidemiological Studies Depression Scale (CES-D), State-Trait Anxiety Inventory (STAI), WHO Quality of Life 26 (WHOQOL-BREF), and Adolescent/Adult Sensory Profile (A/ASP). In this study, only the Social Awareness scale of the SRS-2 Family-Report showed a significant improvement after the intervention. In addition, it was significantly correlated with physical health of WHOQOL-BREF (r = −0.577, p = 0.012), state and trait anxiety of STAI (r = 0.576, p = 0.012; r = 0.708, p = 0.00009, respectively), and CES-D (r = 0.465, p = 0.05). In conclusion, the SSP has a partial effect on social impairments in adults with ASD, specifically on the Social Awareness subscale of the SRS-2.

This study explored whether metaverse-based support groups could address social isolation and suicide risks among LGBTQ+ youths by providing enhanced anonymity, avatar-based self-expression, and improved accessibility. Over one year, 53 individuals aged 14–23 participated in regular online sessions facilitated via the "cluster" metaverse platform by a non-profit LGBTQ+ organization. Each 90-minute session included voice and text-based interactions within a specially designed single-floor virtual space featuring conversation areas and a designated "safe area" for emotional regulation. Post-session questionnaires (5-point Likert scales) captured demographics, avatar preferences, self-confidence, and perceived safety, self-expression, and accessibility; responses were analyzed with Pearson's chi-squared test and Mann–Whitney U tests (α=0.05). Results indicated that 79.2% of participants selected avatars aligned with their gender identity, reporting high satisfaction (mean = 4.10/5) and minimal discomfort (mean = 1.79/5). Social confidence was significantly higher in the metaverse compared with real-world settings (p

Experimental studies have demonstrated that not only dopaminergic signaling but also glutamatergic/NMDA receptor signaling play indispensable roles in the development of methamphetamine psychosis. Our recent genetic studies provided evidence that genetic variants of glutamate-related genes such as DTNBP1, GLYT1, and G72, which are involved in glutamate release and regulation of co-agonists for NMDA receptors, conferred susceptibility to methamphetamine psychosis. Serine racemase converts l-serine to d-serine, which is an endogenous co-agonist for NMDA receptors. Three single nucleotide polymorphisms (SNPs) in the promoter region of the serine racemase gene (SRR), rs224770, rs3760229, and rs408067, were proven to affect the transcription activity of SRR. Therefore, we examined these SNPs in 225 patients with methamphetamine psychosis and 291 age- and sex-matched controls. There was no significant association between methamphetamine psychosis and any SNP examined or between the disorder and haplotypes comprising the three SNPs. However, rs408067 was significantly associated with the prognosis for methamphetamine psychosis and multi-substance abuse status. The patients with C-positive genotypes (CC or CG) of rs408067 showed better prognosis of psychosis after therapy and less abuse of multiple substances than the patients with GG genotypes. Because the C allele of rs408067 reduces the expression of SRR, a lower d-serine level or reduced NMDA receptor activation may affect the prognosis of methamphetamine psychosis and multiple substance abuse. Our sample size is, however, not large enough to eliminate the possibility of a type I error, our findings must be confirmed by replicate studies with larger samples.