Exome sequence analysis and follow up genotyping implicates rare ULK1 variants to be involved in susceptibility to schizophrenia.

Schizophrenia (SCZ) is a severe, highly heritable psychiatric disorder. Elucidation of the genetic architecture of the disorder will facilitate greater understanding of the altered underlying neurobiological mechanisms. The aim of this study was to identify likely aetiological variants in subjects affected with SCZ. Exome sequence data from a SCZ cas-control sample from Sweden was analysed for likely aetiological variants using a weighted burden test. Suggestive evidence implicated the UNC-51-like kinase (ULK1) gene, and it was observed that four rare variants that were more common in the Swedish SCZ cases were also more common in UK10K SCZ cases, as compared to obesity cases. These three missense variants and one intronic variant were genotyped in the University College London cohort of 1304 SCZ cases and 1348 ethnically matched controls. All four variants were more common in the SCZ cases than controls and combining them produced a result significant at P = 0.02. The results presented here demonstrate the importance of following up exome sequencing studies using additional datasets. The roles of ULK1 in autophagy and mTOR signalling strengthen the case that these pathways may be important in the pathophysiology of SCZ. The findings reported here await independent replication.

Neurodevelopmental risk copy number variants in adults with intellectual disabilities and comorbid psychiatric disorders.

BACKGROUND: Copy number variants (CNVs) are established risk factors for neurodevelopmental disorders. To date the study of CNVs in psychiatric illness has focused on single disorder populations. The role of CNVs in individuals with intellectual disabilities and psychiatric comorbidities are less well characterised.AimsTo determine the type and frequency of CNVs in adults with intellectual disabilities and comorbid psychiatric disorders. METHOD: A chromosomal microarray analysis of 599 adults recruited from intellectual disabilities psychiatry services at three European sites. RESULTS: The yield of pathogenic CNVs was high - 13%. Focusing on established neurodevelopmental disorder risk loci we find a significantly higher frequency in individuals with intellectual disabilities and comorbid psychiatric disorder (10%) compared with healthy controls (1.2%, P<0.0001), schizophrenia (3.1%, P<0.0001) and intellectual disability/autism spectrum disorder (6.5%, P < 0.00084) populations. CONCLUSIONS: In the largest sample of adults with intellectual disabilities and comorbid psychiatric disorders to date, we find a high rate of pathogenic CNVs. This has clinical implications for the use of genetic investigations in intellectual disability psychiatry.Declaration of interestNone.

Genetic testing in intellectual disability psychiatry: Opinions and practices of UK child and intellectual disability psychiatrists.

BACKGROUND: An increasing number of genetic causes of intellectual disabilities (ID) are identifiable by clinical genetic testing, offering the prospect of bespoke patient management. However, little is known about the practices of psychiatrists and their views on genetic testing. METHOD: We undertook an online survey of 215 psychiatrists, who were contacted via the Royal College of Psychiatrist's Child and Adolescent and Intellectual Disability Psychiatry mailing lists. RESULTS: In comparison with child and adolescent psychiatrists, intellectual disability psychiatrists ordered more genetic tests, referred more patients to genetic services, and were overall more confident in the genetic testing process. Respondents tended to agree that genetic diagnoses can help patient management; however, management changes were infrequently found in clinical practice. CONCLUSIONS: Differences are apparent in the existing views and practices of child and adolescent and intellectual disability psychiatrists. Developing training and collaboration with colleagues working in genetic services could help to reduce discrepancies and improve clinical practice.

Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications.

Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnoses-particularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD.

My preferred pronoun is she: Understanding transgender identity and oral health care needs.

Objective: This literature review summarizes current research and evidence regarding transgender persons and oral health. Methods: A search of the literature was conducted in the following databases: PubMed, Google Scholar, EBSCO Host, Science Direct, and Wiley Online Library using the keywords "transgender identity, gender non-conforming, discrimination, transition, binary systems, transgender oral cavity, transgender, transgender oral health, transgender dental health." Articles published from 2000 to 2017 in both peer-reviewed and non-peer reviewed journals, which reported information regarding the oral health status of transgender populations, were selected for review. Results: The search revealed 18 articles, only 7 of which pertained to the oral health status of transgender client populations. Five other articles were eliminated due to either poor quality or irrelevance. Discussion: The 13 articles included in the review revealed a need for oral health care professionals to be aware that gender is not binary, nor is it a mental health disorder. Transgender people face heightened risk of discrimination, violence, anxiety, depression, suicidality, substance abuse, and sexually transmitted diseases, as well as significant barriers to health care of which oral health professionals should be made aware. Conclusions: Transgender people have the same rights as everyone else to oral health care. Oral health care providers are responsible for ensuring that transgender clients receive care that aligns with their needs and for providing that care in a culturally competent manner. This requires an understanding of the basics of gender nonconformance and its impact on oral-systemic health. Additional research is needed to increase the scientific knowledge base to facilitate improved health outcomes for this client population.

Objectif: Cette analyse documentaire résume la recherche actuelle et les données probantes à l'égard des personnes transgenres et la santé buccodentaire. Méthodologie: Une recherche documentaire a été menée dans les bases de données suivantes : PubMed, Google Scholar, EBSCO Host, Science Direct et Wiley Online Library au moyen des mots clés anglais « transgender identity (identité transgenre), gender non-conforming (genre non conforme), discrimination (discrimination), transition (transition), binary systems (systèmes binaires), transgender oral cavity (cavité buccale du transgenre), transgender (transgenre), transgender oral health (santé buccodentaire du transgenre), transgender dental health (santé dentaire du transgenre) ¼. Des articles de journaux, publiés de 2000 à 2017 dans des journaux évalués par les pairs et non évalués par les pairs, qui ont fourni de l'information sur l'état de santé buccodentaire des populations transgenres, ont été sélectionnés pour être évalués. Résultats: La recherche a montré que sur les 18 articles retenus, seulement 7 se rapportaient à l'état de santé buccodentaire des populations de clients transgenres. Cinq autres articles ont été éliminés en raison de leur mauvaise qualité ou de leur manque de pertinence. Discussion: Les 13 articles qui ont fait partie de l'évaluation ont révélé le besoin de sensibiliser les professionnels de la santé buccodentaire au fait que le genre n'est ni binaire ni un trouble de la santé mentale. Les transgenres font face à un risque plus élevé de discrimination, de violence, d'anxiété, de dépression, de tendances suicidaires, d'abus de substances et de maladies transmises sexuellement, ainsi qu'à d'importantes barrières aux soins de santé, pour lesquels les professionnels de la santé buccodentaire devraient être sensibilisés. Conclusions: Les personnes transgenres ont les mêmes droits aux soins de santé buccodentaire que les autres. Les prestataires de soins de santé buccodentaire sont responsables de veiller à ce que les clients transgenres reçoivent des soins qui s'alignent avec leurs besoins et de fournir ces soins d'une façon culturellement compétente. Cela exige une compréhension des notions fondamentales sur la non-conformité du genre et de ses effets sur la santé buccodentaire et physique. De la recherche supplémentaire est nécessaire afin d'augmenter la base de connaissances scientifiques et de favoriser l'amélioration des résultats de santé de cette population de clients.

Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders.

Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. CNV pathogenicity was assessed using standard clinical diagnostic methods and participants underwent comprehensive medical and psychiatric phenotyping. We found an 11% yield of likely pathogenic CNVs (22/202). CNVs at recurrent loci, including the 15q11-q13 and 16p11.2-p13.11 regions were most frequently observed. We observed an increased frequency of 16p11.2 duplications compared with those reported in single-disorder cohorts. CNVs were also identified in genes known to effect neurodevelopment, namely NRXN1 and GRIN2B. Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services.

Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014.

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported.