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Aim: The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case–control sample. Method: Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP‐CNVs) in PRKN and examined their association with SCZ and ASD. Results: In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP‐CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP‐CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early‐onset Parkinson's disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson's symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit. Conclusion: The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous neurodevelopmental disorder with a strong genetic basis. Conducting the first comprehensive whole‐genome sequencing (WGS) analysis of Japanese ASD trios, this study aimed to elucidate the clinical significance of pathogenic variants and enhance the understanding of ASD pathogenesis.WGS was performed on 57 Japanese patients with ASD and their parents, investigating variants ranging from single‐nucleotide variants to structural variants (SVs), short tandem repeats (STRs), mitochondrial variants, and polygenic risk score (PRS).Potentially pathogenic variants that could explain observed phenotypes were identified in 18 patients (31.6%) overall and in 10 of 23 patients (43.5%) with comorbid intellectual developmental disorder (IDD). De novo variants in PTEN, CHD7, and HNRNPH2 were identified in patients referred for genetic counseling who exhibited previously reported phenotypes, including one patient with ASD who had profound IDD and macrocephaly with PTEN L320S. Analysis of the AlphaFold3 protein structure indicated potential inhibition of intramolecular interactions within PTEN. SV analysis identified deletions in ARHGAP11B and TMLHE. A pathogenic de novo mitochondrial variant was identified in a patient with ASD who had a history of encephalitis and cognitive decline. GO enrichment analysis of genes with nonsense variants and missense variants (Missense badness, PolyPhen‐2, and Constraint >1) showed associations with regulation of growth and ATP‐dependent chromatin remodeler activity. No reportable results were obtained in the analysis of STR and PRS.Characterizing the comprehensive genetic architecture and phenotypes of ASD is a fundamental step towards unraveling its complex biology. [ABSTRACT FROM AUTHOR]

The accumulation of clinical data of patients with I NBEA i deletion including the present case may contribute to establishment of appropriate clinical management of these patients in the future. Therefore, we report a 10-year clinical course of an ASD patient with I NBEA i deletion, who had comorbidities of OCD, ED, and intellectual disability (ID). We reported an ASD patient with OCD, ED, ID, and I NBEA i deletion. There is a high rate of comorbidity between autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD) and eating disorders (EDs). [Extracted from the article]

We report a case of a 61‐year‐old female with 22q11.2 deletion syndrome (22q11.2DS) and a novel heterozygous nonsense variant in MAP1A, identified through whole‐genome sequencing (WGS). The patient presented with intellectual developmental disorder, treatment‐resistant schizophrenia (SCZ), and multiple congenital anomalies. Despite aggressive pharmacotherapy, she experienced persistent auditory hallucinations and negative symptoms. WGS revealed a 3 Mb deletion at 22q11.2 and a nonsense variant in MAP1A (c.4652T>G, p.Leu1551*). MAP1A, encoding microtubule‐associated protein 1A, is crucial for axon and dendrite development and has been implicated in autism spectrum disorder and SCZ. The MAP1A variant may contribute to the severe psychiatric phenotype, as it is thought to influence synaptic plasticity, a process also affected by 22q11.2 deletion. This case highlights the importance of WGS in identifying additional pathogenic variants that may explain phenotypic variability in 22q11.2DS. Thus, WGS can lead to a better understanding of the genetic architecture of 22q11.2DS. However, further studies are needed to elucidate the role of secondary genetic contributors in the diverse clinical presentations of 22q11.2DS. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Bipolar disorder (BD) is a common psychiatric disorder characterized by alterations between manic/hypomanic and depressive states. Rare pathogenic copy number variations (CNVs) that overlap with exons of synaptic genes have been associated with BD. However, no study has comprehensively explored CNVs in synaptic genes associated with BD. Here, we evaluated the relationship between BD and rare CNVs that overlap with synaptic genes, not limited to exons, in the Japanese population.Using array comparative genome hybridization, we detected CNVs in 1839 patients with BD and 2760 controls. We used the Synaptic Gene Ontology database to identify rare CNVs that overlap with synaptic genes. Using gene‐based analysis, we compared their frequencies between the BD and control groups. We also searched for synaptic gene sets related to BD. The significance level was set to a false discovery rate of 10%.The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66–14.89], false discovery rate < 10%). The BD‐associated CNV that corresponded with RNF216 also partially overlapped with the minimal critical region of the 7p22.1 microduplication syndrome. The integral component of the postsynaptic membrane (Gene Ontology:0099055) was significantly associated with BD. The CNV overlapping with the intron region of GRM5 in this gene set showed a nominal significant association between cases and controls (P < 0.05).We provide evidence that CNVs in RNF216 and postsynaptic membrane–related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD. [ABSTRACT FROM AUTHOR]

Objective: Executive functions are important factors that affect the well-being of children with ADHD. Therefore, inclusion of a convenient assessment of executive dysfunction in diagnosis and treatment of ADHD patients is warranted. However, executive dysfunction assessment presently relies on lab-based neuropsychological tests and symptom rating scales. The present study examined the potential of a 3-D action puzzle video game to reflect ecologically valid executive functioning in pediatric ADHD patients., Methods: Participant gameplay metrics were compared to both their Cambridge Neuropsychological Test Automated Battery (CANTAB) and Conners 3 Parent Form's executive functioning subscale scores. Participants consisted of 33 ADHD and non-ADHD patients aged 8-21., Results: Metrics from gameplay were associated with distinct CANTAB test scores, and a composite score from gameplay was significantly correlated with executive dysfunction from Conners 3., Conclusion: For children with ADHD, cognitive domains related to executive function and overall real-life executive functioning appear to both be measurable via video games. It may be possible to develop individualized behavioral therapy based on the quantitative data obtained from the video game used in this study., Competing Interests: TO and SK are employed by Almaprism Inc. and may own stock options. TO, SK, KT, and NT are named in a relevant pending patent. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Takahashi, Ono, Omori, Iizumi, Kato, Kasuno, Persing and Tsuchiya.)

Background: Hospital-based specialized palliative care teams (HSPC) are important for symptom management and ethics support, especially during complex decision-making, but the needs of patients with noncancer diseases and their families from the HSPC are unclear. This study aimed to (I) compare the prevalence of symptom between patients with and without cancer and explore changes in symptom intensity after HSPC consultation in patients with noncancer; (II) determine factors related to ethics support; and (III) compare the percentage of request contents from patients and their families when a certified nurse specialist in gerontological nursing (geriatric care nurse below) is present in the HSPC to that when a certified nurse specialist in palliative care (palliative care nurse below) is present in the HSPC., Methods: We utilized a retrospective cohort study to analyze 761 patients (360 with noncancer and 401 with cancer) referred to our HSPC at the National Center for Geriatrics and Gerontology using 10-year data (since 2011) available in an electronic medical record database. (I) Symptom scores of the Support Team Assessment Schedule were compared between noncancer and cancer groups and between initial and 1-week assessments for noncancer patients. (II) Ethics support was compared between noncancer (including dementia) and cancer. The presence or absence of ethics support requests, which was set as the objective variable, was examined using logistic regression analysis. (III) The percentage of request contents selected from nine items defaulted on the electronic medical record when a geriatric care nurse was present in our HSPC were compared to those when a palliative care nurse was present in our HSPC., Results: Compared to those with cancer, patients with noncancer suffered more from dyspnea and sputum accumulation. More than 10% of patients with noncancer had suffered from pain, dyspnea, sputum accumulation, and anorexia that required treatment, with symptom scores showing improvement after 1 week of HSPC involvement, except for the sputum accumulation. Moreover, for anorexia, symptom scores improved, but >10% of these patients continued to suffer. Patients with noncancer diseases, including dementia, received ethics support than those with cancer without dementia. More requests for ethics support were received when a geriatric care nurse was in the HSPC than when a palliative care nurse was in the HSPC. Logistic regression analysis revealed that requests for ethics support were more frequent from patients or families with impaired decision-making capacity or when the patient lacked an advocate., Conclusions: The needs of patients with noncancer diseases and families from the HSPC in Japan included (I) symptom management for intractable conditions, such as sputum accumulation; (II) ethics support for patients with noncancer diseases, including dementia, with impaired decision-making capacity, and without advocates; and (III) advice on ethics issues from a geriatric care nurse.

Psychiatric disorders are highly inheritable, and most psychiatric disorders exhibit genetic overlap. Recent studies associated the 3q29 recurrent deletion with schizophrenia (SCZ) and autism spectrum disorder (ASD). In this study, we investigated the association of genes in the 3q29 region with SCZ and ASD. TM4SF19 and PAK2 were chosen as candidate genes for this study based on evidence from previous research. We sequenced TM4SF19 and PAK2 in 437 SCZ cases, 187 ASD cases and 524 controls in the Japanese population. Through targeted sequencing, we identified 6 missense variants among the cases (ASD & SCZ), 3 missense variants among controls, and 1 variant common to both cases and controls; however, no loss-of-function variants were identified. Fisher's exact test showed a significant association of variants in TM4SF19 among cases (p=0.0160). These results suggest TM4SF19 variants affect the etiology of SCZ and ASD in the Japanese population. Further research examining 3q29 region genes and their association with SCZ and ASD is thus needed.

A number of genomic mutations that are thought to be strongly involved in the development of schizophrenia (SCZ) and autism spectrum disorder (ASD) have been identified. Abnormalities involving oligodendrocytes have been reported in SCZ, and as a related gene, oligodendrocyte lineage transcription factor 2 ( OLIG2 ) has been reported to be strongly associated with SCZ. In this study, based on the common disease-rare variant hypothesis, target sequencing of candidate genes was performed to identify rare mutations with a high effect size and the possibility that the identified mutations may increase the risks of SCZ and ASD in the Japanese population. In this study, the exon region of OLIG2 was targeted; 370 patients with SCZ and 192 with ASD were subjected to next-generation sequencing. As a result, one rare missense mutation (A33T) was detected. We used the Sanger method to validate this missense mutation with a low frequency (<1%), and then carried out a genetic association analysis involving 3299 unrelated individuals (1447 with SCZ, 380 with ASD, and 1472 healthy controls) to clarify whether A33T was associated with SCZ or ASD. A33T was not found in either case group, and in only one control. We did not find evidence that p.A33T is involved in the onset of ASD or SCZ; however, associations with this variant need to be evaluated in larger samples to confirm our results., Competing Interests: All authors have no conflicts of interest to declare.