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Aim: The aims of the present study were: (i) to examine the association between schizophrenia (SCZ) and 47, XXY or 47, XXX in a large case–control sample; and (ii) to characterize the clinical features of patients with SCZ with these X chromosome aneuploidies. Methods: To identify 47, XXY and 47, XXX, array comparative genomic hybridization (aCGH) was performed in 3188 patients with SCZ and 3586 controls. We examined the association between 47, XXY and 47, XXX and SCZ in males and females separately using exact conditional tests to control for platform effects. Clinical data were retrospectively examined for patients with SCZ with X chromosome aneuploidies. Results: Of the analyzed samples, 3117 patients (97.8%) and 3519 controls (98.1%) passed our quality control. X chromosome aneuploidies were exclusively identified in patients: 47, XXY in seven patients (0.56%), 47, XXX in six patients (0.42%). Statistical analysis revealed a significant association between SCZ and 47, XXY (P = 0.028) and 47, XXX (P = 0.011). Phenotypic data were available from 12 patients. Treatment‐resistance to antipsychotics and manic symptoms were observed in six patients each (four with 47, XXY and two with 47, XXX for both), respectively. Statistical analysis revealed that treatment‐resistance to antipsychotics, mood stabilizer use, and manic symptoms were significantly more common in patients with 47, XXY than in male patients without pathogenic copy number variations. Conclusion: These findings indicate that both 47, XXY and 47, XXX are significantly associated with risk for SCZ. Patients with SCZ with 47, XXY may be characterized by treatment‐resistance and manic symptoms. [ABSTRACT FROM AUTHOR]

Aim: Eating disorders (EDs) are complex, multifactorial psychiatric conditions. Previous studies identified pathogenic copy number variations associated with NDDs (NDD‐CNVs) in ED patients. However, no statistical evidence for an association between NDD‐CNVs and EDs has been demonstrated. Therefore, we examined whether NDD‐CNVs confer risk for EDs. Methods: Using array comparative genomic hybridization (aCGH), we conducted a high‐resolution CNV analysis of 71 severe female ED patients and 1045 female controls. According to the American College of Medical Genetics guidelines, we identified NDD‐CNVs or pathogenic/likely pathogenic CNVs in NDD‐linked loci. Gene set analysis was performed to examine the involvement of synaptic dysfunction in EDs. Clinical data were retrospectively examined for ED patients with NDD‐CNVs. Results: Of the samples analyzed with aCGH, 70 severe ED patients (98.6%) and 1036 controls (99.1%) passed our quality control filtering. We obtained 189 and 2539 rare CNVs from patients and controls, respectively. NDD‐CNVs were identified in 10.0% (7/70) of patients and 2.3% (24/1036) of controls. Statistical analysis revealed a significant association between NDD‐CNVs and EDs (odds ratio = 4.69, P = 0.0023). NDD‐CNVs in ED patients included 45,X and deletions at KATNAL2, DIP2A, PTPRT, RBFOX1, CNTN4, MACROD2, and FAM92B. Four of these genes were related to synaptic function. In gene set analysis, we observed a nominally significant enrichment of rare exonic CNVs in synaptic signaling in ED patients (odds ratio = 2.55, P = 0.0254). Conclusion: Our study provides the first preliminary evidence that NDD‐CNVs may confer risk for severe EDs. The pathophysiology may involve synaptic dysfunction. [ABSTRACT FROM AUTHOR]

Patients 3 and 4 had neurological traits associated with VGCC dysfunction, including tremor and hearing loss.[10] However, the deletions they carry also affect genes other than VGCC genes (Supplementary D3). Voltage-gated calcium channels (VGCCs) play an important role in synaptic functions and are implicated in the pathogenesis of schizophrenia (SCZ).[1] Rare or I de novo i genetic variants in VGCC genes have been shown to be associated with SCZ and other psychiatric disorders.[[2], [4]] However, clinical manifestations in psychiatric patients with such variants have not been well described. (a) Summary of the clinical data from four patients with SCZ with variants in VGCC genes. Here, we provide the first report of clinical manifestations of SCZ in patients with variants in VGCC genes. [Extracted from the article]

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]

Large recurrent copy number variations (CNVs) at multiple loci have been identified as risk factors for psychiatric disorders.1-3 One such example is the 17q12 deletion (~1.4 Mb); its phenotype is characterized not only by psychiatric/neurodevelopmental disorders, but also by congenital abnormalities of the kidney and urinary tract (CAKUT), and maturity-onset diabetes of the young type (MODY).4,5 Patients with 17q12 deletion and reciprocal duplication share common phenotypes, but differ in the prevalence of each phenotype, with a higher prevalence of kidney involvement and facial dysmorphisms in patients with the deletion.5 The 17q12 deletion confers a high risk for schizophrenia (SCZ) and autism spectrum disorder (ASD), and approximately 70% occur I de novo i . We recently identified a I de novo i 17q12 deletion in one SCZ patient and one ASD patient.1 Their clinical data were retrospectively reviewed from medical records. [Extracted from the article]

Patients in cases 3 and 4 had ASD and ADHD, and the patient in case 4 also had psychotic and manic symptoms. While the patient in case 1 was diagnosed with schizophrenia, symptoms or episodes of ASD, ADHD, and BD were observed during her clinical course. Duplication of chromosome 16p11.2 is associated with intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), and schizophrenia.1-3 However, there are no case reports detailing the psychiatric phenotypes of patients with 16p11.2 duplication. [Extracted from the article]

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]

Aim: A Japanese individual with schizophrenia harboring a novel exonic deletion in RELN was recently identified by genome‐wide copy‐number variation analysis. Thus, the present study aimed to generate and analyze a model mouse to clarify whether Reln deficiency is associated with the pathogenesis of schizophrenia. Methods: A mouse line with a novel RELN exonic deletion (Reln‐del) was established using the CRISPR/Cas9 method to elucidate the underlying molecular mechanism. Subsequently, general behavioral tests and histopathological examinations of the model mice were conducted and phenotypic analysis of the cerebellar granule cell migration was performed. Results: The phenotype of homozygous Reln‐del mice was similar to that of reeler mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin. The expression of reelin in heterozygous Reln‐del mice was approximately half of that in wild‐type mice. Conversely, behavioral analyses in heterozygous Reln‐del mice without cerebellar atrophy or dysplasia showed abnormal social novelty in the three‐chamber social interaction test. In vitro reaggregation formation and neuronal migration were severely altered in the cerebellar cultures of homozygous Reln‐del mice. Conclusion: The present results in novel Reln‐del mice modeled after our patient with a novel exonic deletion in RELN are expected to contribute to the development of reelin‐based therapies for schizophrenia. [ABSTRACT FROM AUTHOR]

Aim: Although the effects of psychotropics on driving ability have received much attention, little research is available on driving performance of stable outpatients with depression undergoing real‐world treatment. This observational study investigated driving performance, cognitive functions, and depressive symptomatology of partly remitted outpatients with depression under daily‐practice psychopharmacologic treatment. Methods: Seventy stable outpatients with depression and 67 healthy volunteers were enrolled. Patients’ prescriptions were not controlled in order to capture the real‐world treatment environment. Participants underwent three driving tasks – road‐tracking, car‐following, and harsh‐braking – using a driving simulator, and three cognitive tasks – Continuous Performance Test, Wisconsin Card Sorting Test, and Trail‐Making Test. The Symptom Assessment Scale – Structured Interview Guide for the Hamilton Depression Rating Scale, Beck Depression Inventory‐II, Social Adaptation Self‐Evaluation Scale, and Stanford Sleepiness Scale were also completed. Results: Although many patients received various pharmacologic treatments, there were no significant differences in the three driving tasks between outpatients with depression and healthy controls. Difficulty of maintaining set in the Wisconsin Card Sorting Test was significantly increased in patients with depression. Results on the Social Adaptation Self‐Evaluation Scale were significantly associated with road‐tracking and car‐following performance, in contrast to results on the Hamilton Depression Rating Scale and the Beck Depression Inventory‐II. Conclusion: We conclude that partly remitted depressive patients under steady‐state pharmacologic treatment do not differ from healthy controls with respect to driving performance, which seems to be more affected by psychosocial functioning than by pharmacologic agents. This, however, should be investigated systematically in an off/on study. [ABSTRACT FROM AUTHOR]

Another SCZ patient with 3q29 deletion was also reported to be treatment resistant.5 As D2 receptor antagonists were not effective, a hyperdopaminergic state in the mesolimbic dopamine pathways may not play a crucial role in 3q29 deletion-associated psychosis. The 3q29 deletion is one of the strongest risk factors (odds ratio > 40) for schizophrenia (SCZ)1 and is associated with other psychiatric disorders including intellectual disability (ID), autism spectrum disorder, and bipolar disorder.2 However, details of psychiatric manifestations and treatment responses have not been described in these patients. CPZ, chlorpromazine; EEG, electroencephalography; ID, intellectual disability; IQ, intelligence quotient; MRI, magnetic resonance imaging; N/A, not available; SCZ, schizophrenia. gl Patient 1, a 55-year-old female, was born with low birth weight. Treatment-resistant schizophrenia in patients with 3q29 deletion: A case series of four patients. [Extracted from the article]

Bipolar disorder (BD) has a substantial genetic component, but progress in identification of BD risk genes has been slow. In conclusion, we report a new BD patient with I MBD5 i deletion. The phenotypic spectrum of MAND includes intellectual disability, autism spectrum disorder, and epilepsy.1-3 Detailed phenotypic evaluation revealed that 2 (9.1%) of 22 patients with I MBD5 i deletion had BD.4 I MBD5 i is considered to be a new candidate gene for BD.5 We recently identified a new BD patient with I MBD5 i deletion. [Extracted from the article]

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ( DSM-5) was published in 2013, and its official Japanese version was published in 2014. The Japanese Government uses classifications from the 10th revision of the I nternational C lassification of D iseases ( ICD-10) to categorize disorders and determine treatment fees. However, since the publication of the DSM-III, the use of the DSM system has become prevalent in research and educational settings in Japan. In addition to traditional psychiatry, both the ICD and the DSM are taught by many Japanese medical schools, and virtually all clinical research and trials refer to the DSM to define targeted disorders. Amid the current backdrop in which the reputation of the DSM-5 is being established, the editorial board of P sychiatry and C linical N eurosciences has asked Japanese experts across 12 specialties to examine the structure of the DSM-5, including the following categories: Neurodevelopmental Disorders, Schizophrenia Spectrum Disorders, Major Depression, Bipolar Disorders, Obsessive-Compulsive Disorders, Somatic Symptom Disorder, Eating Disorders, Substance-Related and Addictive Disorders, Gender Dysphoria, and Neurocognitive Disorders. Although opinions were only obtained from these selected experts, we believe that we have succeeded, to a certain extent, in presenting views that are representative of each specialty. [ABSTRACT FROM AUTHOR]

Schizophrenia, a debilitating disease with 1% prevalence in the general population, is characterized by major neuropsychiatric symptoms, including delusions, hallucinations, and deficits in emotional and social behavior. Previous studies have directed their investigations on the mechanism of schizophrenia towards neuronal dysfunction and have defined schizophrenia as a 'neuron-centric' disorder. However, along with the development of genetics and systematic biology approaches in recent years, the crucial role of glial cells in the brain has also been shown to contribute to the etiopathology of schizophrenia. Here, we summarize comprehensive data that support the involvement of glial cells (including oligodendrocytes, astrocytes, and microglial cells) in schizophrenia and list several acknowledged glia-related genes or molecules associated with schizophrenia. Instead of purely an abnormality of neurons in schizophrenia, an additional 'glial perspective' provides us a novel and promising insight into the causal mechanisms and treatment for this disease. [ABSTRACT FROM AUTHOR]

Aim Postnatal depression has demonstrated long-term consequences on child cognitive and emotional development; however, the link between maternal and child pathology has not been clearly identified. We conducted a prospective study using self-rating questionnaires to clarify the association between bonding disorder and maternal mood during pregnancy and after childbirth. Methods A total of 389 women participated in this study and completed questionnaires. Participants were asked to complete the Edinburgh Postnatal Depression Scale ( EPDS) and the Mother-to-Infant Bonding Scale four times during pregnancy and the postpartum period. Results We found statistically significant weak to moderate correlations (r = 0.14-0.39) between the EPDS and Mother-to-Infant Bonding Scale scores at each testing period. Women who experienced low mood tended to have stronger bonding disorder. Furthermore, the effectiveness of attachment between the mother and child was closely related to the mood of the mother as measured by the EPDS. Conclusion We observed different patterns of bonding and maternal mood. Distinct subtypes regarding maternal mood and formation of mother-to-infant attachment suggests that analysis of bonding disorder should be performed considering the course of maternal depressive symptoms. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder is a neurodevelopmental disorder present in 1% of the population, characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Approximately 10% of the autism spectrum disorder population is thought to have large chromosomal rearrangements. Copy-number variations (CNV) alter the genome structure either by duplication or deletion of a chromosomal region. The association between CNV and autism susceptibility has become more apparent through the use of methods based on comparative genomic hybridization in screening CNV. The nature of the high CNV rate in the human genome is partly explained by non-allelic homologous recombination between flanking repeated sequences derived from multiple copies of transposons or mobile genetic elements. There are hotspots for CNV in the human genome, such as 16p11.2 and 22q11.2. Genes involved in CNV are supposed to have copy-number dose-dependent effects on the behavior of affected individuals. Animal models give insight into the possible interactions between core genetic loci and additional factors contributing to the phenotypes of each individual. If affected genes code for cellular signaling molecules, reducing the dosage in the intracellular signaling pathway may result in the malfunction of the nervous system. The genetic background of autism spectrum disorder is highly heterogenic and most common or rare CNV do not lead to autism spectrum disorders in the majority of cases, but may occasionally increase the risk of developing an autism spectrum disorder. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which the authors discuss the importance of conducting psychiatric studies in the aftermath of a natural disaster like the 2011 earthquake in Japan as it provides data that can be used to facilitate emergency management and prevent future disaster events.

Aim Although the association between maternal depression and bonding failure during pregnancy and after delivery has been investigated, the causal relationships remain unclear. Methods A total of 751 women (mean [SD] age, 32.1 [4.4] years) completed the Mother-Infant Bonding Questionnaire and the Edinburgh Postnatal Depression Scale during early pregnancy before week 25 (T1), during late pregnancy around week 36 (T2), and at 5 days after delivery (T3). We created a structural regression model to clarify the relationships between depressive mood and bonding failure during pregnancy and at 5 days after delivery. The model was tested with structural equation modeling. Results Our non-recursive model fit the data well, and we found that: (i) during T2, bonding failure predicted depressive mood ( P < 0.01, r = 0.23); (ii) at T3, bonding failure predicted depressive mood ( P < 0.05, r = 0.31); (iii) during T1, depressive mood was correlated with bonding failure ( P < 0.01, r = 0.45); (iv) depressive mood during T1 predicted depressive mood during T2 ( P < 0.01, r = 0.58); (v) depressive mood during T2 predicted depressive mood at T3 ( P < 0.01, r = 0.45); (vi) bonding failure during T1 predicted bonding failure during T2 ( P < 0.01, r = 0.84); and (vii) bonding failure during T2 predicted bonding failure at T3 ( P < 0.01, r = 0.44). The determinant coefficients of depressive mood and bonding failure at T3 were 0.41 and 0.28, respectively. Conclusion Our large-scale cohort study indicates that bonding failure predicts depressive mood during pregnancy and 5 days after delivery. These findings suggest that protection and support for pregnant women with depressive mood and bonding failure may prevent both issues during pregnancy and the early stage after delivery. [ABSTRACT FROM AUTHOR]

The article presents a case study of 62-year-old female patient with Parkinson's disease (PD) and mental depression. The patient was treated with milnacipran 75 milligrams (mg) per day without improvement of the depressive symptoms. Her treatment was then changed to mirtazapine 30 mg/day, which resulted to an improvement in her depressive symptoms. The authors suggest the potential of mirtrazapine as treatment of choice for PD patients with depression.