A recent report describes neurodevelopmental disorder in a total of three unrelated patients with de novo truncating variants in the HIRA gene. 200 632 subjects who have undergone exome sequencing by the UK Biobank were investigated to identify any variants predicted to cause HIRA haploinsufficiency. Four were found, three with frameshift variants and one with a stop variant. One of these subjects had depression but the others did not have any major neuropsychiatric phenotypes. Variants causing haploinsufficiency of HIRA are very rare but when they do occur it seems that they are not always associated with neurodevelopmental disorder.

Alexithymia is a personality trait characterized by difficulties in identifying and describing emotions, which is associated with various psychiatric disorders, including depression and posttraumatic stress disorder (PTSD). Its pathogenesis is incompletely understood but previous studies suggested that genetic as well as metabolic factors, are involved. However, no results on the role of vitamin D and the polymorphisms rs4588 and rs7041 of the vitamin D binding protein (VDBP) have been published so far. Serum levels of total 25(OH)D were measured in two general-population samples (total n = 5733) of the Study of Health in Pomerania (SHIP). The Toronto Alexithymia Scale-20 (TAS-20) was applied to measure alexithymia. Study participants were genotyped for rs4588 and rs7041. Linear and logistic regression analyses adjusted for sex, age, waist circumference, physical activity, season and study and, when applicable, for the batch of genotyping and the first three genetic principal components, were performed. In sensitivity analyses, the models were additionally adjusted for depressive symptoms. 25(OH)D levels were negatively associated with TAS-20 scores (β = -0.002; P < 0.001) and alexithymia according to the common cutoff of TAS-20>60 (β = -0.103; P < 0.001). These results remained stable after adjusting for depressive symptoms. The tested genetic polymorphisms were not significantly associated with alexithymia. Our results suggest that low vitamin D levels may be involved in the pathophysiology of alexithymia. Given that no associations between alexithymia and rs4588 as well as rs7041 were observed, indicates that behavioral or nutritional features of alexithymic subjects could also explain this association.

Depression is moderately heritable but there is no common genetic variant which has a major effect on susceptibility. A previous analysis of 50 000 exome-sequenced subjects failed to implicate any genes or sets of genes in which rare variants were associated with risk of affective disorder requiring specialist treatment. A much larger exome-sequenced dataset is now available. Data from 200 632 exome-sequenced UK Biobank participants was analysed. Subjects were treated as cases if they had reported having seen a psychiatrist for 'nerves, anxiety, tension or depression'. Gene-wise weighted burden analysis was performed to see if there were any genes or sets of genes for which there was an excess of rare, functional variants in cases. There were 22 886 cases and 176 486 controls. There were 22 642 informative genes but no gene or gene set produced a statistically significant result after correction for multiple testing. None of the genes or gene sets with the lowest P values appeared to be an obvious biological candidate. The results conform exactly with the expectation under the null hypothesis. It seems unlikely that the use of common, poorly defined phenotypes will produce useful advances in understanding genetic contributions to affective disorder and it might be preferable to focus instead on obtaining large exome-sequenced samples of conditions such as bipolar 1 disorder and severe, recurrent depression. This research has been conducted using the UK Biobank Resource.

Although autism spectrum disorder (ASD) occurs worldwide, most genomic studies on ASD were performed on those of Western ancestry. We hypothesized ASD-related copy number variations (CNVs) of Japanese individuals might be different from those of Western individuals. Subjects were recruited from the Hirosaki 5-year-old children's developmental health check-up (HFC) between 2013 and 2016 (ASD group; n = 68, control group; n = 124). This study conducted CNV analysis using genomic DNA from peripheral blood of 5-year-old Japanese children. Fisher's exact test was applied for profiling subjects and CNV loci. Four ASD-related CNVs: deletion at 12p11.1, duplications at 4q13.2, 8p23.1 and 18q12.3 were detected (P = 0.015, 0.024, 0.009, 0.004, respectively). Specifically, the odds ratio of duplication at 18q12.3 was highest among the 4 CNVs (odds ratio, 8.13). Four CNVs: microdeletion at 12p11.1, microduplications at 4q13.2, 8p23.1 and 18q12.3 were detected as ASD-related CNVs in Japanese children in this study. Although these CNVs were consistent with several reports by Western countries at cytoband levels, these did not consistent at detailed genomic positions and sizes. Our data indicate the possibility that these CNVs are characteristic of Japanese children with ASD. We conclude that Japanese individuals with ASD may harbor CNVs different from those of Western individuals with ASD.

There is evidence of genetic polymorphism influences on brain structure and function, genetic risk in bipolar disorder (BD), and neuroimaging correlates of BD. How genetic influences related to BD could be reflected on brain changes in BD has been efficiently reviewed in a 2017 systematic review. We aimed to confirm and extend these findings through a Preferred Reporting Items for Systematic reviews and Meta-Analyses-based systematic review. Our study allowed us to conclude that there is no replicated finding in the timeframe considered. We were also unable to further confirm prior results of the BDNF gene polymorphisms to affect brain structure and function in BD. The most consistent finding is an influence of the CACNA1C rs1006737 polymorphism in brain connectivity and grey matter structure and function. There was a tendency of undersized studies to obtain positive results and large, genome-wide polygenic risk studies to find negative results in BD. The neuroimaging genetics in BD field is rapidly expanding.

Yuan, Fan; Hou, Binyin; Ji, Lei; Ren, Decheng; Liu, Liangjie; Bi, Yan; Guo, Zhenming; Ma, Gaini; Yang, Fengping; Dong, Zaiquan; Sun, Xueli; He, Lin; Yu, Tao; Wu, Xi; Li, Xingwang; Shi, Yi; He, Guang Author Information

Bipolar disorder is a high prevalent psychiatric condition entailing recurrent episodes of elevated mood and depression, but also diverse cognitive problems. One deficit observed in patients concerns to auditory-verbal processing. Being a hereditary condition with a complex genetic architecture, it is not clear which genes contribute to this deficit. We show that candidates for bipolar disorder significantly overlap with candidates for clinical conditions resulting from a deficit in the phonological loop of working memory, particularly, developmental dyslexia and specific language impairment. The overlapping genes are involved in aspects of brain development and function (particularly, brain oscillations) potentially underlying phonological processing and accordingly, emerge as promising candidates for auditory-verbal deficits in bipolar disorder.

The aim of the investigation was to test whether genetic variants predicted to impair the functionality of SLC6A9, which codes for the GlyT-1 glycine transporter, are protective against schizophrenia. In an exome sequenced sample of 4225 schizophrenia cases and 5834 controls, variants occurring in SLC6A9 were annotated and weights were assigned using GENEVARASSOC. Genotype counts were compared using SCOREASSOC. Variants predicted to be deleterious by SIFT and damaging by PolyPhen were examined. Genotypes at 1:44466494-G/A seemed likely to be erroneous. If these were ignored then there were 15 damaging variants in controls and five in cases. The results are consistent with the hypothesis that variants which damage SLC6A9 are protective against schizophrenia but a larger sample would be required to confirm this.

The Fragile X syndrome is the leading hereditary cause of intellectual disability and Autism Spectrum Disorders. There is paucity of information about psychoses in such patients with little follow up. We report a case of schizophrenia in a male patient diagnosed with Fragile X syndrome. The patient has been followed up for a period of 3 years. The diagnostic and management challenges are discussed. This is a unique case of schizophrenia in Fragile X syndrome. We discuss the common molecular pathways to the expression of both schizophrenia and Fragile X syndrome. This is the first case report of schizophrenia in a patient with diagnosis of Fragile X syndrome in Australia.

ARID1B mutations in Coffin-Siris syndrome are a cause of intellectual disability (0.5-1%), with various degrees of autism and agenesis of the corpus callosum (10%). Little is known regarding the cognitive and motor consequences of ARID1B mutations in humans and no link has been made between corpus callosum anomalies and visuospatial and neuromotor dysfunctions. We have investigated the visuospatial and neuromotor phenotype in eight patients with ARID1B mutations. A paramedian sagittal section of the brain MRI was selected, and corpus callosum was measured in anteroposterior length, genu and trunk width. Spearman's rank order coefficients were used to explore correlations between visuospatial and social cognitive variables and dimensions of the corpus callosum. A significant correlation between genu width size and visual cognition was observed. Retrocerebellar cysts were associated with corpus callosum anomalies. Here, we show that corpus callosum anomalies caused in ARID1B mutations may be predictive of the visuospatial and motor phenotype in Coffin-Siris syndrome.