柳橋 達彦

The LRP5 gene encodes a Wnt signaling receptor to which Wnt binds directly. In humans, pathogenic monoallelic variants in LRP5 have been associated with increased bone density and exudative vitreoretinopathy. In mice, LRP5 plays a role in tooth development, including periodontal tissue stability and cementum formation. Here, we report a 14-year-old patient with a de novo non-synonymous variant, p.(Val1245Met), in LRP5 who exhibited mildly reduced bone density and mild exudative vitreoretinopathy together with a previously unreported phenotype consisting of dental abnormalities that included fork-like small incisors with short roots and an anterior open bite, molars with a single root, and severe taurodontism. In that exudative vitreoretinopathy has been reported to be associated with heterozygous loss-of-function variants of LRP5 and that our patient reported here with the p.(Val1245Met) variant had mild exudative vitreoretinopathy, the variant can be considered as an incomplete loss-of-function variant. Alternatively, the p.(Val1245Met) variant can be considered as exerting a dominant-negative effect, as no patients with truncating LRP5 variants and exudative vitreoretinopathy have been reported to exhibit dental anomalies. The documentation of dental anomalies in the presently reported patient strongly supports the notion that LRP5 plays a critical role in odontogenesis in humans, similar to its role in mice.

<h4>Background/aim</h4>To our knowledge, no case-control study has investigated the relationships between stealing, clinical implications, and psychiatric diagnosis among child and adolescent psychiatric patients with or without a history of stealing. Thus, the associations between child and adolescent psychiatric disorders and a history of stealing remain unclear. Therefore, the aim of the present study was to evaluate the relationships between stealing, clinical implications, and psychiatric diagnosis among child and adolescent psychiatric patients with or without a history of stealing.<h4>Methods</h4>In this retrospective case-control study, the proportions of clinical implications among child and adolescent psychiatric patients with and without a history of stealing were compared. Data regarding age, sex, primary diagnosis, junior high school student or not, both father and mother are the caregivers or not, family history, abuse history, school refusal, depressive state, and obsessive-compulsive symptoms were retrieved from medical records. Participants consisted of Japanese junior high school students and younger patients (maximum age, 15 years) at the first consultation. All patients were examined and diagnosed by psychiatrists according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, or the Fifth Edition. Stealing was reported by the patients or caregivers to the psychiatrist, or the psychiatrist had inquired about a history of stealing at the first consultation.<h4>Results</h4>Among 1972 patients who consulted the clinic, at the first consultation, 56 (2.84%) had a history of stealing (cases), and 1916 (97.16%) did not (controls). Multivariate logistic regression analyses revealed that the proportions of males, junior high school students, abuse history, autism spectrum disorder (ASD), and conduct disorder were significantly higher, and the proportions of adjustment disorders and school refusal were significantly lower in cases than in controls. The multivariate adjusted odds ratio increased further when the two factors were considered together, such as ASD with abuse history and attention deficit-hyperactivity disorder (ADHD) with abuse history.<h4>Conclusions</h4>Children with a history of stealing were more likely to be diagnosed with ASD or ADHD with abuse history. Child and adolescent psychiatric outpatients with a history of stealing were more likely to be older and male. Our study should be understood without prejudice because this study is reporting associations, not causality. Therefore, a prospective study to investigate causality among ADHD, ASD, abuse history, and stealing is needed. If ADHD and ASD with abuse history can be correlated to a history of stealing, interventions can be more effective by understanding the mechanisms underlying these connections.

Background: Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood. Considering the recent explanation of establishing SoA from the standpoint of associative learning, the "agency network" may include not only the insula and inferior parietal lobule but also the striatum. We hypothesized that aberrant SoA in schizophrenia is based on a deficit in the "agency network." Methods: Functional magnetic resonance imaging data were acquired while patients with schizophrenia (n = 15) and matched controls (n = 15) performed our adaptation method of agency attribution task on a trial-by-trial basis to assess participants' explicit experience of the temporal causal relationship between an action and an external event with temporal biases. Analysis of functional connectivity was done using the right supramarginal gyrus and the right middle frontal gyrus as seed regions. Results: In healthy controls, analyses revealed increased activation of the right inferior parietal lobule (mainly the supramarginal gyrus), right insula, and right middle frontal gyrus as an activation of the agency condition. We defined activated Brodmann areas shown in the agency condition of healthy controls as the seed region for connectivity analysis. The connectivity analysis revealed lower connectivity between the head of the left caudate nucleus and right supramarginal gyrus in the patients compared to healthy controls. Conclusions: This dysconnectivity of the agency network in schizophrenia may lead to self-disturbance through deficits in associative learning of SoA. These findings may explain why pathological function of the striatum in schizophrenia leads to self-disturbance.