Translational genetic modelling of 3D craniofacial dysmorphology: elaborating the facial phenotype of neurodevelopmental disorders through the prism of schizophrenia

Purpose of Review: In the context of human developmental conditions, we review the conceptualisation of schizophrenia as a neurodevelopmental disorder, the status of craniofacial dysmorphology as a clinically accessible index of brain dysmorphogenesis, the ability of genetically modified mouse models of craniofacial dysmorphology to inform on the underlying dysmorphogenic process and how geometric morphometric techniques in mutant mice can extend quantitative analysis. Recent Findings: Mutant mice with disruption of neuregulin-1, a gene associated meta-analytically with risk for schizophrenia, constitute proof-of-concept studies of murine facial dysmorphology in a manner analogous to clinical studies in schizophrenia. Geometric morphometric techniques informed on the topography of facial dysmorphology and identified asymmetry therein. Summary: Targeted disruption in mice of genes involved in individual components of developmental processes and analysis of resultant facial dysmorphology using geometric morphometrics can inform on mechanisms of dysmorphogenesis at levels of incisiveness not possible in human subjects

Learning strategies, study habits and social networking activity of undergraduate medical students

Objectives: To determine learning strategies, study habits, and online social networking use of undergraduates at an Irish medical school, and their relationship with academic performance. Methods: A cross-sectional study was conducted in Year 2 and final year undergraduate-entry and graduate-entry students at an Irish medical school. Data about participants’ demographics and educational background, study habits (including time management), and use of online media was collected using a self-report questionnaire. Participants’ learning strategies were measured using the 18-item Approaches to Learning and Studying Inventory (ALSI). Year score percentage was the measure of academic achievement. The association between demographic/educational factors, learning strategies, study habits, and academic achievement was statistically analysed using regression analysis. Results: Forty-two percent of students were included in this analysis (n=376). A last-minute “cramming” time management study strategy was associated with increased use of online social networks. Learning strategies differed between undergraduate- and graduate-entrants, with the latter less likely to adopt a ‘surface approach’ and more likely adopt a ‘study monitoring’ approach. Year score percentage was positively correlated with the ‘effort management/organised studying’ learning style. Poorer academic performance was associated with a poor time management approach to studying (“cramming”) and increased use of the ‘surface learning’ strategy. Conclusions: Our study demonstrates that effort management and organised studying should be promoted, and surface learning discouraged, as part of any effort to optimise academic performance in medical school. Excessive use of social networking contributes to poor study habits, which are associated with reduced academic achievemen

Semaphorin 6A knockout mice display abnormalities across ethologically-based topographies of exploration and in motor learning

Semaphorins are secreted or membrane-bound proteins implicated in neurodevelopmental processes of axon guidance and cell migration. Exploratory behaviour and motor learning was examined ethologically in Semaphorin 6A (Sema6A) mutant mice. The ethogram of initial exploration in Sema6A knockout mice was characterised by increased rearing to wall with decreased sifting; over subsequent habituation, locomotion, sniffing and rearing to wall were increased, with reduced habituation of rearing seated. Rotarod analysis indicated delayed motor learning in Sema6A heterozygous mutants. Disruption to the axonal guidance and cell migration processes regulated by Sema6A is associated with topographically specific disruption to fundamental aspects of behaviour, namely the ethogram of initial exploration and subsequent habituation to the environment, and motor learning

Relevance of anatomy to medical education and clinical practice: perspectives of medical students, clinicians, and educators

Introduction: Against a backdrop of ever-changing diagnostic and treatment modalities, stakeholder perceptions (medical students, clinicians, anatomy educators) are crucial for the design of an anatomy curriculum which fulfils the criteria required for safe medical practice. This study compared perceptions of students, practising clinicians, and anatomy educators with respect to the relevance of anatomy education to medicine. Methods: A quantitative survey was administered to undergraduate entry (n = 352) and graduate entry students (n = 219) at two Irish medical schools, recently graduated Irish clinicians (n = 146), and anatomy educators based in Irish and British medical schools (n = 30). Areas addressed included the association of anatomy with medical education and clinical practice, mode of instruction, and curriculum duration. Results: Graduate-entry students were less likely to associate anatomy with the development of professionalism, teamwork skills, or improved awareness of ethics in medicine. Clinicians highlighted the challenge of tailoring anatomy education to increase student readiness to function effectively in a clinical role. Anatomy educators indicated dissatisfaction with the time available for anatomy within medical curricula, and were equivocal about whether curriculum content should be responsive to societal feedback. Conclusions: The group differences identified in the current study highlight areas and requirements which medical education curriculum developers should be sensitive to when designing anatomy courses

Does cannabis use predict psychometric schizotypy via aberrant salience?

Cannabis can induce acute psychotic symptoms in healthy individuals and exacerbate pre-existing psychotic symptoms in patients with schizophrenia. Inappropriate salience allocation is hypothesised to be central to the association between dopamine dysregulation and psychotic symptoms. This study examined whether cannabis use is associated with self-reported salience dysfunction and schizotypal symptoms in a non-clinical population. 910 University students completed the following questionnaire battery: the cannabis experience questionnaire modified version (CEQmv); schizotypal personality questionnaire (SPQ); community assessment of psychic experience (CAPE); aberrant salience inventory (ASI). Mediation analysis was used to test whether aberrant salience mediated the relationship between cannabis use and schizotypal traits. Both frequent cannabis consumption during the previous year and ASI score predicted variation across selected positive and disorganised SPQ subscales. However, for the SPQ subscales ‘ideas of reference’ and ‘odd beliefs’, mediation analysis revealed that with the addition of ASI score as a mediating variable, current cannabis use no longer predicted scores on these subscales. Similarly, cannabis use frequency predicted higher total SPQ as well as specific Positive and Disorganised subscale scores, but ASI score as a mediating variable removed the significant predictive relationship between frequent cannabis use and ‘odd beliefs’, ‘ideas of reference’, ‘unusual perceptual experiences’, ‘odd speech’, and total SPQ scores. In summary, cannabis use was associated with increased psychometric schizotypy and aberrant salience. Using self-report measures in a non-clinical population, the cannabis-related increase in selected positive and disorganised SPQ subscale scores was shown to be, at least in part, mediated by disturbance in salience processing mechanisms

Disruption to social dyadic interactions but not emotional/anxiety-related behaviour in mice with heterozygous \u27knockout\u27 of the schizophrenia risk gene neuregulin-1.

Clinical genetic studies have implicated neuregulin-1 [NRG1] as a leading susceptibility gene for schizophrenia. NRG1 is known to play a significant role in the developing brain, which is consistent with the prevailing neurodevelopmental model of schizophrenia. Thus, the emotional and social phenotype of adult mice with heterozygous \u27knockout\u27 of transmembrane [TM]-domain NRG1 was examined further in both sexes. Emotional/anxiety-related behaviour was assessed using the elevated plus-maze and the light-dark test. Social behaviour was examined in terms of dyadic interactions between NRG1 mutants and an unfamiliar C57BL6 conspecific in a novel environment. There was no effect of NRG1 genotype on performance in either test of emotionality/anxiety. However, previous reports of hyperactivity in NRG1 mutants were confirmed in both paradigms. In the test of social interaction, aggressive following was increased in NRG1 mutants of both sexes, together with an increase in walkovers in female mutants. These findings elaborate the specificity of the NRG1 phenotype for the social rather than the emotional/anxiety-related domain. They indicate that NRG1 is involved in the regulation of reciprocal social interaction behaviour and thus suggest a putative role for NRG1 in a schizophrenia-related endophenotype

Mutation of Semaphorin-6A Disrupts Limbic and Cortical Connectivity and Models Neurodevelopmental Psychopathology

Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism

Convergence and translation: attitudes to inter-professional learning and teaching of creative problem-solving among medical and engineering students and staff

Background: Healthcare worldwide needs translation of basic ideas from engineering into the clinic. Consequently, there is increasing demand for graduates equipped with the knowledge and skills to apply interdisciplinary medicine/engineering approaches to the development of novel solutions for healthcare. The literature provides little guidance regarding barriers to, and facilitators of, effective interdisciplinary learning for engineering and medical students in a team-based project context. Methods: A quantitative survey was distributed to engineering and medical students and staff in two universities, one in Ireland and one in Belgium, to chart knowledge and practice in interdisciplinary learning and teaching, and of the teaching of innovation. Results: We report important differences for staff and students between the disciplines regarding attitudes towards, and perceptions of, the relevance of interdisciplinary learning opportunities, and the role of creativity and innovation. There was agreement across groups concerning preferred learning, instructional styles, and module content. Medical students showed greater resistance to the use of structured creativity tools and interdisciplinary teams. Conclusions: The results of this international survey will help to define the optimal learning conditions under which undergraduate engineering and medicine students can learn to consider the diverse factors which determine the success or failure of a healthcare engineering solution

Bridging the divide between medical school and clinical practice: identification of six key learning outcomes for an undergraduate preparatory course in radiology.

Background: There exists a significant divide between what is learnt in medical school and subsequently what is required to practice medicine effectively. Despite multiple strategies to remedy this discordance, the problem persists. Here, we describe the identification of a comprehensive set of learning outcomes for a preparation for practice course in radiology. Methods: Assessment of interns' readiness to interact with the radiology department was conducted using a national survey of both interns and radiologists. In parallel, group concept mapping (GCM) which involves a combination of qualitative and quantitative techniques was used to identify the shared understanding of participants from a diverse range of medical specialties regarding what topics should be included in an intern preparatory course for interacting with the radiology department. Results: The survey demonstrated that most interns and radiologists felt that undergraduate medical training did not prepare interns to interact with the radiology department. GCM identified six learning outcomes that should be targeted when designing a preparatory module: requesting investigations; clinical decision support; radiology department IT and communication; adverse reactions and risks; interpretation of radiology results and urgent imaging. The thematic clusters from the group concept mapping corroborated the deficiencies identified in the national survey. Conclusion: We have identified six key learning outcomes that should be included in a preparation for practice module in radiology. Future courses targeting these thematic clusters may facilitate a smoother transition from theory to practice for newly graduated doctors

Medical student knowledge regarding radiology before and after a radiological anatomy module: implications for vertical integration and self-directed learning.

Objectives: To examine the impact that anatomy-focused radiology teaching has on non-examined knowledge regarding radiation safety and radiology as a specialty. Methods: First-year undergraduate medical students completed surveys prior to and after undertaking the first-year anatomy programme that incorporates radiological anatomy. Students were asked opinions on preferred learning methodology and tested on understanding of radiology as a specialty and radiation safety. Results: Pre-module and post-module response rates were 93 % (157/168) and 85 % (136/160), respectively. Pre-module and post-module, self-directed learning (SDL) ranked eighth (of 11) for preferred gross-anatomy teaching formats. Correct responses regarding radiologist/radiographer roles varied from 28-94 % on 16 questions with 4/16 significantly improving post-module. Identification of modalities that utilise radiation significantly improved for five of eight modalities post-module but knowledge regarding relative amount of modality-specific radiation use was variable pre-module and post-module. Conclusions: SDL is not favoured as an anatomy teaching method. Exposure of students to a radiological anatomy module delivered by senior clinical radiologists improved basic knowledge regarding ionising radiation use, but there was no improvement in knowledge regarding radiation exposure relative per modality. A possible explanation is that students recall knowledge imparted in didactic lectures but do little reading around the subject when the content is not examined. Teaching Points: Self-directed learning is not favoured as a gross anatomy teaching format amongst medical students; An imaging anatomy-focused module improved basic knowledge regarding ionising radiation use; Detailed knowledge of modality-specific radiation exposure remained suboptimal post-module; Knowledge of roles within a clinical radiology department showed little change post-module