Neuropsychiatric manifestations in a patient with prolonged COVID-19 encephalopathy: case report and literature review.

While the respiratory complications of COVID-19 infection are now well known, psychiatric manifestations are an emerging issue. We report a case of prolonged encephalopathy secondary to COVID-19 which was associated with prominent neuropsychiatric features. The patient went on to develop sub-clinical seizures, a rare but recognised complication of SARS-CoV-2.

A psychoeducational intervention increases use of a delirium protocol by Neurologists and Neurosurgeons in patients with brain disorders.

OBJECTIVES: Over 50% of inpatients with neurological disorders may present with a co-morbid psychiatric illness. Delirium has a reported point prevalence of 20% in hospital inpatients and is frequently undetected. We aimed to (1) examine inpatient referrals to a Liaison Neuropsychiatry service and (2) review the diagnosis and management of delirium before and after an educational intervention. METHODS: An initial 6-month audit of referrals to the inpatient Liaison Neuropsychiatry service was conducted in 2018. We then undertook a psychoeducational intervention to raise awareness of the diagnosis and management of delirium. We conducted a re-audit of referrals to the service in 2019. RESULTS: On initial audit, of 84 referrals, the most common referral was for mood (38%; n = 32). Just 4% (n = 3) had a specific delirium query. Following assessment by Neuropsychiatry, organic disorders (43%; n = 32), including delirium (33%; n = 25), were the most common diagnoses. On re-audit, of 86 referrals, mood assessment remained the most common reason for referral (38%; n = 33) and 2% (n = 2) were referred for possible delirium. Organic disorders remained the most common diagnoses (53%; n = 45) including delirium (38%; n = 32). We found a significant increase in the use of the delirium protocol from 12% (n = 3) on initial audit to 47% (n = 15); p < 0.01 on re-audit despite no increase in the number of specific delirium queries. CONCLUSIONS: A psychoeducational intervention improves the management of delirium by Neurologists and Neurosurgeons in patients with brain disorders.

Psychiatric and psychosocial morbidity 1 year after epilepsy surgery.

OBJECTIVES: There is a high rate of psychiatric comorbidity in patients with epilepsy. However, the impact of surgical treatment of refractory epilepsy on psychopathology remains under investigation. We aimed to examine the impact of epilepsy surgery on psychopathology and quality of life at 1-year post-surgery in a population of patients with epilepsy refractory to medication. METHODS: This study initially assessed 48 patients with refractory epilepsy using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life in Epilepsy Inventory 89 (QOLIE-89) on admission to an Epilepsy Monitoring Unit (EMU) as part of their pre-surgical assessment. These patients were again assessed using the SCID-I, QOLIE-89 and HADS at 1-year follow-up post-surgery. RESULTS: There was a significant reduction in psychopathology, particularly psychosis, following surgery at 1-year follow-up (p < 0.021). There were no new cases of de novo psychosis and surgery was also associated with a significant improvement in the quality of life scores (p < 0.001). CONCLUSIONS: This study demonstrates the impact of epilepsy surgery on psychopathology and quality of life in a patient population with refractory surgery. The presence of a psychiatric illness should not be a barrier to access surgical treatment.

A comparison of undergraduate teaching of psychiatry across medical schools in the Republic of Ireland.

OBJECTIVES: To examine the delivery and assessment of psychiatry at undergraduate level in the six medical schools in the Republic of Ireland offering a medical degree programme. METHODS: A narrative description of the delivery and assessment of psychiatry at undergraduate level by collaborative senior faculty members from all six universities in Ireland. RESULTS: Psychiatry is integrated to varying degrees across all medical schools. Clinical experience in general adult psychiatry and sub-specialities is provided by each medical school; however, the duration of clinical attachment varies, and the provision of some sub-specialities (i.e. forensic psychiatry) is dependent on locally available resources. Five medical schools provide 'live' large group teaching sessions (lectures), and all medical schools provide an array of small group teaching sessions. Continuous assessment encompasses 10-35% of the total assessment marks, depending on the medical school. Only one medical school does not provide a clinical examination in the form of an Objective Structured Clinical Examination with viva examinations occurring at three medical schools. CONCLUSIONS: Many similarities exist in relation to the delivery of psychiatry at undergraduate level in Ireland. Significant variability exists in relation to assessment with differences in continuous assessment, written and clinical exams and the use of vivas noted. The use of e-learning platforms has increased significantly in recent years, with their role envisaged to include cross-disciplinary teaching sessions and analysis of examinations and individual components within examinations which will help refine future examinations and enable greater sharing of resources between medical schools.

Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia.

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin-5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.

Increased use of security personnel in Irish psychiatric hospitals: 2008-2012.

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.

The digital age: is this the future of medical education? A cross-sectional study to assess medical students' opinions about e-learning in psychiatry undergraduate medical education.

OBJECTIVES: The main objectives were to assess medical students' opinions about e-learning in psychiatry undergraduate medical education, and to investigate a possible relationship between learning styles and preferences for learning modalities. METHOD: During the academic year 2009/2010, all 231 senior Royal College of Surgeons in Ireland (RCSI) medical students in their penultimate year of study were invited to answer a questionnaire that was posted online on Moodle, the RCSI virtual learning environment. RESULTS: In all, 186 students responded to the questionnaire, a response rate of 80%. Significantly more students stated a preference for live psychiatry tutorials over e-learning lectures. Students considered flexible learning, having the option of viewing material again and the ability to learn at one's own pace with e-learning lectures, to be more valuable than having faster and easier information retrieval. CONCLUSION: Students prefer traditional in-class studying, even when they are offered a rich e-learning environment. Understanding students' learning styles has been identified as an important element for e-learning development, delivery and instruction, which can lead to improved student performance.

Mood congruent psychotic symptoms and specific cognitive deficits in carriers of the novel schizophrenia risk variant at MIR-137.

OBJECTIVE: The Schizophrenia Psychiatric Genome-wide Association (GWAS) Consortium recently reported on five novel schizophrenia susceptibility loci. The most significant finding mapped to a micro-RNA, MIR-137, which may be involved in regulating the function of other schizophrenia and bipolar disorder susceptibility genes. METHOD: We genotyped 821 patients with confirmed DSM-IV diagnoses of schizophrenia, bipolar affective disorder I and schizoaffective disorder for the risk SNP (rs1625579) and investigated the clinical profiles of risk allele carriers using a within-case design. We also assessed neurocognitive performance in a subset of cases (n=399) and controls (n=171). RESULTS: Carriers of the risk allele had lower scores for an OPCRIT-derived positive symptom factor (p=0.04) and lower scores on a lifetime measure of psychosis incongruity (p=0.017). Risk allele carriers also had more cognitive deficits involving episodic memory and attentional control. CONCLUSION: This is the first evidence that the MIR-137 risk variant may be associated with a specific subgroup of psychosis patients. Although the effect of this single SNP was not clinically relevant, investigation of the impact of carrying multiple risk SNPs in the MIR-137 regulatory network on diagnosis and illness profile may be warranted.

The influence of biomimetic topographical features and the extracellular matrix peptide RGD on human corneal epithelial contact guidance.

A major focus in the field of tissue engineering is the regulation of essential cell behaviors through biophysical and biochemical cues from the local extracellular environment. The impact of nanotopographical cues on human corneal epithelial cell (HCEC) contact guidance, proliferation, migration and adhesion have previously been demonstrated. In the current report we have expanded our study of HCEC responses to include both biophysical and controlled biochemical extracellular cues. By exploiting methods for the layer-by-layer coating of substrates with reactive poly(ethylene imine)/poly(2-vinyl-4,4-dimethylazlactone)-based multilayer thin films we have incorporated a single adhesion peptide motif, Arg-Gly-Asp (RGD), on topographically patterned substrates. This strategy eliminates protein adsorption onto the surface, thus decoupling the effects of the HCEC response to topographical cues from adsorbed proteins and soluble media proteins. The direction of cell alignment was dependent on the scale of the topographical cues and, to less of an extent, the culture medium. In EpiLife® medium cell alignment to unmodified-NOA81 topographical features, which allowed protein adsorption, differed significantly from cell alignment on RGD-modified features. These results demonstrate that the surface chemical composition significantly affects how HCECs respond to topographical cues. In summary, we have demonstrated modulation of the HCEC response to environmental cues through critical substrate and soluble parameters.

Non-graduate and graduate entry medical students attitudes to psychiatry.

OBJECTIVE: Graduate entry medical students' views of psychiatry may differ from those of school leavers. This study hypothesised that (i) exposure to a psychiatry attachment is associated with a positive change in attitudes towards psychiatry in both graduate entry and non-graduate entry students, (ii) graduate entry students exhibit a more positive attitude to psychiatry compared to non-graduate entry students and (iii) graduate entry students are more interested in a career in psychiatry than non-graduate entry students. METHODS: In this study 247 medical students (118 females and 129 males) completing their psychiatry rotation were invited to complete questionnaires examining career choice, attitudes to psychiatry and career attractiveness for a range of specialties including surgery, medicine, general practice and psychiatry before and after their psychiatry attachment. Questionnaires were distributed prior to commencement of their attachment and redistributed on the final day of the attachment. RESULTS: Of the 165 participants in the study, 75 students entered medicine via the traditional route (without a primary degree), 49 entered via the graduate entry programme and 41 had a primary degree. Overall, medical students displayed positive attitudes towards psychiatry. However, while there was an improvement in attitudes towards psychiatry and the career attractiveness of psychiatry on completion of the rotation, no differences were found between graduate and non-graduate entry students. Psychiatry and general practice had lower ratings for career attractiveness than other specialities. No significant changes were found in the first and second choice of specialty. CONCLUSION: Our results show that improvements in attitude and career attractiveness do not necessarily correlate with increased choice of psychiatry as a specialty. Graduate entry has been considered a possible opportunity for increasing recruitment in psychiatry but our results suggest that this may not be the case. Follow-up studies are required to determine whether career attractiveness correlates with future career choice.

Anatomy and aging of the amygdala and hippocampus in autism spectrum disorder: an in vivo magnetic resonance imaging study of Asperger syndrome.

It has been proposed that people with autism spectrum disorder (ASD) have abnormal morphometry and development of the amygdala and hippocampus (AH). However, previous reports are inconsistent, perhaps because they included people of different ASD diagnoses, ages, and health. We compared, using magnetic resonance imaging, the in vivo anatomy of the AH in 32 healthy individuals with Asperger syndrome (12-47 years) and 32 healthy controls who did not differ significantly in age or IQ. We measured bulk (gray + white matter) volume of the AH using manual tracing (MEASURE). We first compared the volume of AH between individuals with Asperger syndrome and controls and then investigated age-related differences. We compared differences in anatomy before, and after, correcting for whole brain size. There was no significant between group differences in whole brain volume. However, individuals with Asperger syndrome had a significantly larger raw bulk volume of total (P<0.01), right (P<0.01), and left amygdala (P<0.05); and when corrected for overall brain size, total (P<0.05), and right amygdala (P<0.01). There was a significant group difference in aging of left amygdala; controls, but not individuals with Asperger syndrome, had a significant age-related increase in volume (r = 0.486, P<0.01, and r = 0.007, P = 0.97, z = 1.995). There were no significant group differences in volume or age-related effects in hippocampus. Individuals with Asperger syndrome have significant differences from controls in bulk volume and aging of the amygdala.

The Letter-Number Sequencing Test and its association with potential to work among people with psychotic illness.

Post hoc analysis of occupational attainment and performance on a standard neurocognitive battery suggests that performance on letter-number sequencing is strongly associated with work attainment. Letter-number sequencing may warrant further investigation as a clinically useful tool to inform decisions around vocational rehabilitation.

Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study.

BACKGROUND: Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype. METHOD: We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender. RESULTS: VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome. CONCLUSIONS: Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.

Brain morphometry volume in autistic spectrum disorder: a magnetic resonance imaging study of adults.

BACKGROUND: Several prior reports have found that some young children with autism spectrum disorder [ASD; including autism and Asperger's syndrome and pervasive developmental disorder - not otherwise specified (PDD-NOS)] have a significant increase in head size and brain weight. However, the findings from older children and adults with ASD are inconsistent. This may reflect the relatively small sample sizes that were studied, clinical heterogeneity, or age-related brain differences. METHOD: Hence, we measured head size (intracranial volume), and the bulk volume of ventricular and peripheral cerebrospinal fluid (CSF), lobar brain, and cerebellum in 114 people with ASD and 60 controls aged between 18 and 58 years. The ASD sample included 80 people with Asperger's syndrome, 28 with autism and six with PDD-NOS. RESULTS: There was no significant between-group difference in head and/or lobar brain matter volume. However, compared with controls, each ASD subgroup had a significantly smaller cerebellar volume, and a significantly larger volume of peripheral CSF. CONCLUSIONS: Within ASD adults, the bulk volume of cerebellum is reduced irrespective of diagnostic subcategory. Also the significant increase in peripheral CSF may reflect differences in cortical maturation and/or ageing.

Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome.

BACKGROUND: Velo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (Val158Met) affecting enzyme activity. Here, we investigated the effect of COMT Val158Met polymorphism on brain anatomy and cognition in adults with VCFS. METHOD: The COMT Val158Met polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery. RESULTS: After corrections for multiple comparisons Val-hemizygous subjects, compared with Met-hemizygotes, had a significantly larger volume of frontal lobes. Also, Val-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found. CONCLUSIONS: COMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.

Genome wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes.

BACKGROUND: Schizophrenia shows substantial clinical heterogeneity. One common important clinical variable in presentation is the occurrence of episodes of major depression. METHODS: We undertook analyses in an attempt to detect loci that influence susceptibility to, or modify the clinical expression of, schizophrenia according to the occurrence of episodes of major depression. We used a logistic regression framework in which lifetime presence/absence of major depression was entered as a covariate in the linkage analysis of our UK schizophrenia affected sibling pair series (168 affected sibling pairs typed for a 10 cM map of microsatellite markers). RESULTS: Inclusion of presence/absence of depression as a covariate detected a genome wide significant linkage signal on chromosome 4q28.3 at 130.7 cM (LOD = 4.59; p = 0.038; increase in maximum LOD over univariate analysis (ILOD) = 3.62). Inclusion of the depression covariate also showed suggestive evidence of linkage on 20q11.21 (LOD = 4.10; expected to occur by chance 0.093 times per genome scan, ILOD = 2.83). CONCLUSIONS: Our findings identify loci that may harbour genes that play a role in susceptibility to, or modify the risk of, episodes of major depression in people with schizophrenia.

Annotation: velo-cardio-facial syndrome.

BACKGROUND: Velo-cardio-facial syndrome (VCFS), the most frequent known interstitial deletion identified in man, is associated with chromosomal microdeletions in the q11 band of chromosome 22. Individuals with VCFS are reported to have a characteristic behavioural phenotype with high rates of behavioural, psychiatric, neuropsychological and linguistic disorders. METHODS: A selective literature review was undertaken. RESULTS: Children and adults with VCFS have high rates of behavioural, psychiatric and communication disorders. While VCFS children have high rates of ADHD, anxiety and affective disorders, adults have high rates of psychotic disorders, particularly schizophrenia. In addition, the presence of a chromosome 22q11 deletion is associated with specific neuropsychological and neuroanatomical abnormalities. CONCLUSIONS: People with VCFS have a characteristic behavioural phenotype with high rates of behavioural, psychiatric, neuropsychological and communication disorders. Early diagnosis and treatment within a multidisciplinary framework is of paramount importance for VCFS individuals as this will have a major effect in determining the long-term outcome in affected individuals. Longitudinal studies of VCFS children are currently under way to identify precursor symptoms and areas of dysfunction which precede the later development of major psychiatric disorder. Identification of such prodromal features in VCFS may have enormous implications for the clinical management of major psychiatric disorder in VCFS and in the wider population.