Kieran C. Murphy

Congenital heart disease (CHD) affecting the conotruncal region of the heart, occurs in 40–50% of patients with 22q11.2 deletion syndrome (22q11.2DS). This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, encoding a T-box transcription factor, is one of the main genes responsible for the etiology of the syndrome. We suggest that genetic modifiers of conotruncal defects in patients with 22q11.2DS may be in the TBX1 gene network. To identify genetic modifiers, we analyzed rare, predicted damaging variants in whole genome sequence of 456 cases with conotruncal defects and 537 controls, with 22q11.2DS. We then performed gene set approaches and identified chromatin regulatory genes as modifiers. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2DS cases. Many of these genes were identified as risk factors for sporadic CHD in the general population. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. The genes KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models. Our findings indicate that disturbance of chromatin regulatory genes impact the TBX1 gene network serving as genetic modifiers of 22q11.2DS and sporadic CHD, suggesting that there are some shared mechanisms involving the TBX1 gene network in the etiology of CHD.

Irish medical schools attract an increasingly diverse student population and produce graduates who will practise in many parts of the world. There are particular implications in this for the planning and delivery of the undergraduate psychiatry curriculum. In all countries, mental health services struggle for equitable resourcing, and mental health care within general medical services remains relatively neglected. The traditional undergraduate psychiatry offering has been justifiably criticised for being excessively oriented towards secondary care when the vast majority of medical graduates will pursue careers in primary care or in specialties other than psychiatry. Recently published articles in the Irish Journal of Psychological Medicine address the current challenges and opportunities in providing an undergraduate experience that better prepares students for the mental health aspects of medical practice in a global context. We summarise and discuss these contributions and the recent Royal College of Psychiatrists publication Choose Psychiatry: Guidance for Medical Schools.

People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills. A cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery. The 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group. The findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS.

Introduction Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional underpinnings in 22q11DS remain unclear. We quantitatively investigate the cognitive processes and associated neuroanatomy of spatial working memory in people with 22q11DS compared to matched controls. We examine whether there are significant between‐group differences in spatial working memory using task related fMRI, Voxel based morphometry and white matter fiber tractography. Materials and Methods Multimodal magnetic resonance imaging employing functional, diffusion and volumetric techniques were used to quantitatively assess the cognitive and neuroanatomical features of spatial working memory processes in 22q11DS. Twenty‐six participants with genetically confirmed 22q11DS aged between 9 and 52 years and 26 controls aged between 8 and 46 years, matched for age, gender, and handedness were recruited. Results People with 22q11DS have significant differences in spatial working memory functioning accompanied by a gray matter volume reduction in the right precuneus. Gray matter volume was significantly correlated with task performance scores in these areas. Tractography revealed extensive differences along fibers between task‐related cortical activations with pronounced differences localized to interhemispheric commissural fibers within the parietal section of the corpus callosum. Conclusions Abnormal spatial working memory in 22q11DS is associated with aberrant functional activity in conjunction with gray and white matter structural abnormalities. These anomalies in discrete brain regions may increase susceptibility to the development of psychiatric disorders such as schizophrenia. Hum Brain Mapp 37:4689–4705, 2016.

The study aimed to determine the number of accumulated coercive events experienced by patients during inpatient admission, the patients' functioning and quality of life (QOL) one year after discharge, and associations between these variables and patient characteristics and between follow-up outcomes and number of accumulated coercive events. A prospective cohort study was undertaken at three community services and an independent hospital in Ireland (N=162). Accumulated coercive events scores were based on patients' legal status, perceived coercion, and exposure to physical restraint, seclusion, or forced medication. Most (68%) experienced at least one coercive event. Lower functioning predicted more coercive events. At follow-up, the mean subjective QOL score was 63% of the highest possible score, objective QOL improved for 15% of participants, and functioning improved for 70%. Accumulated coercive events did not predict these outcomes. Coercive events during psychiatric admission appeared unrelated to functioning and QOL at follow-up.

Objectives: Little is known about the involvement of security personnel in Irish psychiatric care. Content analysis of inspection reports is a feasible way to investigate this under-researched topic. We aimed to (i) Describe the number of approved centres per year in which we observed comments about the presence of security personnel in published reports of inspections conducted from 2008 to 2012 (ii) Report the main themes of all text relating to security personnel published in these inspection reports.Method: We conducted a content analysis of all 349 inspection reports published between 2008 and 2012.Results: The number of approved centres in which security personnel were noted increased from 3% to 8% between the years 2008 and 2012. This increase was not statistically significant when the same unique centres were compared between years (p=0.684). Employment details such as contracted employment relationship, location relative to the approved centre and hours of work appeared inconsistent across centres. Role functions of security personnel differed across centres and ranged from monitoring the entrance of a unit to observing, restraining and secluding patients. Contrasting perceptions of suitability were evident in the inspection reports. The extent to which the training needs of security personnel were met was unclear from the reports.Conclusions: Activity of security personnel in psychiatric hospitals may not be role appropriate, compliant with legislation or conducive to treatment. Best practice guidelines should be developed in consultation with multiple stakeholders.

Persons with 22q11.2 deletion syndrome (22q11.2DS) are characterized inter alia by facial dysmorphology and greatly increased risk for psychotic illness. Recent studies indicate facial dysmorphology in adults with schizophrenia. This study evaluates the extent to which the facial dysmorphology of 22q11.2DS is similar to or different from that evident in schizophrenia. Twenty‐one 22q11.2DS‐sibling control pairs were assessed using 3D laser surface imaging. Geometric morphometrics was applied to 30 anatomical landmarks, 480 geometrically homologous semi‐landmarks on curves and 1720 semi‐landmarks interpolated on each 3D facial surface. Principal component (PC) analysis of overall shape space indicated PC2 to strongly distinguish 22q11.2DS from controls. Visualization of PC2 indicated 22q11.2DS and schizophrenia to be similar in terms of overall widening of the upper face, lateral displacement of the eyes/orbits, prominence of the cheeks, narrowing of the lower face, narrowing of nasal prominences and posterior displacement of the chin; they differed in terms of facial length (increased in 22q11.2DS, decreased in schizophrenia), mid‐face and nasal prominences (displaced upwards and outwards in 22q11.2DS, less prominent in schizophrenia); lips (more prominent in 22q11.2DS; less prominent in schizophrenia) and mouth (open mouth posture in 22q11.2DS; closed mouth posture in schizophrenia). These findings directly implicate dysmorphogenesis in a cerebral‐craniofacial domain that is common to 22q11.2DS and schizophrenia and which may repay further clinical and genetic interrogation in relation to the developmental origins of psychotic illness. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome [VCFS]) is a genetic disorder associated with interstitial deletions of chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders, children with 22q11DS have impairments of face processing, as well as IQ-independent deficits in visuoperceptual function and social and abstract reasoning. These face-processing deficits may contribute to the social impairments of 22q11DS. However, their neurobiological basis is poorly understood. We used event-related functional magnetic resonance imaging (fMRI) to examine neural responses when children with 22q11DS (aged 9–17 years) and healthy controls (aged 8–17 years) incidentally processed neutral expressions and mild (50%) and intense (100%) expressions of fear and disgust. We included 28 right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including nine siblings) controls. Within groups, contrasts showed that individuals significantly activated ‘face responsive’ areas when viewing neutral faces, including fusiform-extrastriate cortices. Further, within both groups, there was a significant positive linear trend in activation of fusiform-extrastriate cortices and cerebellum to increasing intensities of fear. There were, however, also between-group differences. Children with 22q11DS generally showed reduced activity as compared to controls in brain regions involved in social cognition and emotion processing across emotion types and intensities, including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an exploratory correlation analysis showed that within 22q11DS children reduced activation was associated with behavioural impairment—social difficulties (measured using the Total Difficulties Score from the Strengths and Difficulties Questionnaire [SDQ]) were significantly negatively correlated with brain activity during fear and disgust processing (respectively) in the left precentral gyrus (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18), and bilateral cerebellum. Regions involved in face processing, including fusiform-extrastriate cortices, anterior cingulate gyri, and superomedial prefrontal cortices (BA 6), are activated by facial expressions of fearful, disgusted, and neutral expressions in children with 22q11DS but generally to a lesser degree than in controls. Hypoactivation in these regions may partly explain the social impairments of children with 22q11DS.