Complete genome of Escherichia coli sequence type 73 with acquired blaTEM-1 and high genotypic virulence load identified in human saliva.

OBJECTIVES: Escherichia coli sequence type (ST) 73 is a pandemic lineage of the ExPEC (Extraintestinal Pathogenic E. coli) family associated with conserved virulence. We report the complete genome of a genomically hypervirulent E. coli ST73 strain isolated from the oral cavity of a patient with a diagnosis of treatment resistant schizophrenia and receiving clozapine treatment. METHODS: E. coli strain GABEEC132 underwent second and third generation sequencing with Illumina and Oxford-Nanopore-Technologies (ONT) platforms. Antibiotic Resistance Genes (ARGs) and Virulence Factors (VFs) were bioinformatically identified using the NCBI-AMR-Finder-Plus database and Virulence-Factors-database (VFDB), respectively. To contextualize the genome within a broader epidemiological framework, phylogenetic analysis was conducted using representative genomes of E. coli ST73 O6:H1 (n=55). RESULTS: E. coli strain GABEEC132 was identified as possessing the O6:H1 serotype and classified within the B2 phylogroup. The strain exhibited a high genomic virulence load, encoding for 194 VFs. Additionally, it encoded three ARGs, including an acquired blaTEM-1 located on a rep_cluster_2350 8 237 Kb mobilisable plasmid, presenting phenotypic resistance to ampicillin and piperacillin. CONCLUSION: This report provides novel insights into the oral prevalence of genotypically hypervirulent and drug-resistant E. coli ST73, a pandemic lineage.

Direct targets of MEF2C are enriched for genes associated with schizophrenia and cognitive function and are involved in neuron development and mitochondrial function.

Myocyte Enhancer Factor 2C (MEF2C) is a transcription factor that plays a crucial role in neurogenesis and synapse development. Genetic studies have identified MEF2C as a gene that influences cognition and risk for neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia (SCZ). Here, we investigated the involvement of MEF2C in these phenotypes using human-derived neural stem cells (NSCs) and glutamatergic induced neurons (iNs), which represented early and late neurodevelopmental stages. For these cellular models, MEF2C function had previously been disrupted, either by direct or indirect mutation, and gene expression assayed using RNA-seq. We integrated these RNA-seq data with MEF2C ChIP-seq data to identify dysregulated direct target genes of MEF2C in the NSCs and iNs models. Several MEF2C direct target gene-sets were enriched for SNP-based heritability for intelligence, educational attainment and SCZ, as well as being enriched for genes containing rare de novo mutations reported in ASD and/or developmental disorders. These gene-sets are enriched in both excitatory and inhibitory neurons in the prenatal and adult brain and are involved in a wide range of biological processes including neuron generation, differentiation and development, as well as mitochondrial function and energy production. We observed a trans expression quantitative trait locus (eQTL) effect of a single SNP at MEF2C (rs6893807, which is associated with IQ) on the expression of a target gene, BNIP3L. BNIP3L is a prioritized risk gene from the largest genome-wide association study of SCZ and has a function in mitophagy in mitochondria. Overall, our analysis reveals that either direct or indirect disruption of MEF2C dysregulates sets of genes that contain multiple alleles associated with SCZ risk and cognitive function and implicates neuron development and mitochondrial function in the etiology of these phenotypes.

Uncinate fasciculus microstructural organisation and emotion recognition in schizophrenia: controlling for hit rate bias.

Introduction: Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by functional and structural brain dysconnectivity and disturbances in perception, cognition, emotion, and social functioning. In the present study, we investigated whether the microstructural organisation of the uncinate fasciculus (UF) was associated with emotion recognition (ER) performance. Additionally, we investigated the usefulness of an unbiased hit rate (UHR) score to control for response biases (i.e., participant guessing) during an emotion recognition task (ERT). Methods: Fifty-eight individuals diagnosed with SCZ were included. The CANTAB ERT was used to measure social cognition. Specific ROI manual tract segmentation was completed using ExploreDTI and followed the protocol previously outlined by Coad et al. (2020). Results: We found that the microstructural organisation of the UF was significantly correlated with physical neglect and ER outcomes. Furthermore, we found that the UHR score was more sensitive to ERT subscale emotion items than the standard HR score. Finally, given the association between childhood trauma (in particular childhood neglect) and social cognition in SCZ, a mediation analysis found evidence that microstructural alterations of the UF mediated an association between childhood trauma and social cognitive performance. Discussion: The mediating role of microstructural alterations in the UF on the association between childhood trauma and social cognitive performance suggests that early life adversity impacts both brain development and social cognitive outcomes for people with SCZ. Limitations of the present study include the restricted ability of the tensor model to correctly assess multi-directionality at regions where fibre populations intersect.

The impact of badmouthing of medical specialties to medical students.

OBJECTIVES: This study aimed to evaluate the proportion of Irish medical students exposed to 'badmouthing' of different specialities and to ascertain: the degree of criticism of specialities based on the seniority of clinical or academic members of staff; if 'badmouthing' influenced student career choice in psychiatry; and attitudes of medical students towards psychiatry as a speciality and career choice. METHODS: Medical students in three Irish universities were invited to complete an online survey to determine the frequency and effect of non-constructive criticism on choice of medical specialty. The online questionnaire was distributed to Royal College of Surgeons in Ireland (RCSI), University of Galway (UoG) and University College Dublin (UCD) in the academic year 2020-2021. RESULTS: General practice (69%), surgery (65%) and psychiatry (50%) were the most criticised specialties. Criticism was most likely to be heard from medical students. 46% of students reported reconsidering a career in psychiatry due to criticism from junior doctors. There was a positive perception of psychiatry with 27% of respondents considering psychiatry as a first-choice specialty. CONCLUSIONS: Criticism of psychiatry by doctors, academics and student peers negatively influences students' career choice, which could be contributing to recruitment difficulties in psychiatry.

Corpus callosum microstructural organization mediates the effects of physical neglect on social cognition in schizophrenia.

Exposure to early life adversity is associated with both increased risk of developing schizophrenia and poorer performance on measures of social cognitive functioning. In this study, we examined whether interleukin-6 (IL-6) and Corpus Callosum (CC) microstructure mediated the association between childhood physical neglect and social cognition. Fifty-eight patients with a diagnosis of schizophrenia were included. The CANTAB emotion recognition task (unbiased hit rate) was used to assess social cognition. We found that the microstructural organization of the CC significantly mediated the association between physical neglect and emotion recognition. Furthermore, in a sequential mediation analysis that also considered the role of inflammatory response, the association between physical neglect, and lower emotion recognition performance was sequentially mediated by higher IL-6 and lower fractional anisotropy of the CC. This mediating effect of IL-6 was only present when simultaneously considering the effects of CC microstructural organization and remained significant while controlling for the effects of sex, BMI and medication dosage (but not age). Overall, the findings suggest that the association between physical neglect and poorer emotion recognition in schizophrenia occurs, at least in part, via its association with white matter microstructure.

Genetic and inflammatory effects on childhood trauma and cognitive functioning in patients with schizophrenia and healthy participants.

Recent studies have reported a negative association between exposure to childhood trauma, including physical neglect, and cognitive functioning in patients with schizophrenia. Childhood trauma has been found to influence immune functioning, which may contribute to the risk of schizophrenia and cognitive symptoms of the disorder. In this study, we aimed to test the hypothesis that physical neglect is associated with cognitive ability, and that this association is mediated by a combined latent measure of inflammatory response, and moderated by higher genetic risk for schizophrenia. The study included 279 Irish participants, comprising 102 patients and 177 healthy participants. Structural equation modelling was used to perform mediation and moderation analyses. Inflammatory response was measured via basal plasma levels of IL-6, TNF-α, and CRP, and cognitive performance was assessed across three domains: full-scale IQ, logical memory, and the emotion recognition task. Genetic variation for schizophrenia was estimated using a genome-wide polygenic score based on genome-wide association study summary statistics. The results showed that inflammatory response mediated the association between physical neglect and all measures of cognitive functioning, and explained considerably more variance than any of the inflammatory markers alone. Furthermore, genetic risk for schizophrenia was observed to moderate the direct pathway between physical neglect and measures of non-social cognitive functioning in both patient and healthy participants. However, genetic risk did not moderate the mediated pathway associated with inflammatory response. Therefore, we conclude that the mediating role of inflammatory response and the moderating role of higher genetic risk may independently influence the association between adverse early life experiences and cognitive function in patients and healthy participants.

Along-Tract Statistical Mapping of Microstructural Abnormalities in Bipolar Disorder: A Pilot Study.

Investigating brain circuitry involved in bipolar disorder (BD) is key to discovering brain biomarkers for genetic and interventional studies of the disorder. Even so, prior research has not provided a fine-scale spatial mapping of brain microstructural differences in BD. In this pilot diffusion MRI dataset, we used BUndle ANalytics (BUAN)-a recently developed analytic approach for tractography-to extract, map, and visualize the profile of microstructural abnormalities on a 3D model of fiber tracts in people with BD (N=38) and healthy controls (N=49), and investigate along-tract white matter (WM) microstructural differences between these groups. Using the BUAN pipeline, BD was associated with lower mean fractional anisotropy (FA) in fronto-limbic and interhemispheric pathways and higher mean FA in posterior bundles relative to controls.Clinical Relevance- BUAN combines tractography and anatomical information to capture distinct along-tract effects on WM microstructure that may aid in classifying diseases based on anatomical differences.

Delusions of Vampirism in an Adolescent and Treatment With Clozapine: A Case Report.

This case describes delusions of vampirism among several other psychotic symptoms in a 15-year-old who has a diagnosis of schizophrenia, with these delusions first presenting when he was 13 years of age. Delusions of vampirism can be associated with a strong desire to suck human blood but these delusional beliefs were not acted upon here. This is the first report of delusions of vampirism in childhood to date. The introduction of the antipsychotic medication clozapine after failed treatment trials with two other antipsychotic agents has been associated with a significant amelioration in symptomatology and an improvement in functioning.

Bilateral anterior corona radiata microstructure organisation relates to impaired social cognition in schizophrenia.

OBJECTIVE: The Corona Radiata (CR) is a large white matter tract in the brain comprising of the anterior CR (aCR), superior CR (sCR), and posterior CR (pCR), which have associations with cognition, self-regulation, and, in schizophrenia, positive symptom severity. This study tested the hypothesis that the microstructural organisation of the aCR, as measured by Fractional Anisotropy (FA) using Diffusion Tensor Imaging (DTI), would relate to poorer social cognitive outcomes and higher positive symptom severity for people with schizophrenia, when compared to healthy participants. We further hypothesised that increased positive symptoms would relate to poorer social cognitive outcomes. METHODS: Data were derived from n = 178 healthy participants (41 % females; 36.11 ± 12.36 years) and 58 people with schizophrenia (30 % females; 42.4 ± 11.1 years). The Positive and Negative Symptom Severity Scale measured clinical symptom severity. Social Cognition was measured using the Reading the Mind in the Eyes Test (RMET) Total Score, as well as the Positive, Neutral, and Negative stimuli valence. The ENIGMA-DTI protocol tract-based spatial statistics (TBSS) was used. RESULTS: There was a significant difference in FA for the CR, in individuals with schizophrenia compared to healthy participants. On stratification, both the aCR and pCR were significantly different between groups, with patients showing reduced white matter tract microstructural organisation. Significant negative correlations were observed between positive symptomatology and reduced microstructural organisation of the aCR. Performance for RMET negative valence items was significantly correlated bilaterally with the aCR, but not the sCR or pCR, and no relationship to positive symptoms was observed. CONCLUSIONS: These data highlight specific and significant microstructural white-matter differences for people with schizophrenia, which relates to positive clinical symptomology and poorer performance on social cognition stimuli. While reduced FA is associated with higher positive symptomatology in schizophrenia, this study shows the specific associated with anterior frontal white matter tracts and reduced social cognitive performance. The aCR may have a specific role to play in frontal-disconnection syndromes, psychosis, and social cognitive profile within schizophrenia, though further research requires more sensitive, specific, and detailed consideration of social cognition outcomes.

Multi-Site Statistical Mapping of Along-Tract Microstructural Abnormalities in Bipolar Disorder with Diffusion MRI Tractometry.

Investigating alterations in brain circuitry associated with bipolar disorder (BD) may offer a valuable approach to discover brain biomarkers for genetic and interventional studies of the disorder and related mental illnesses. Some diffusion MRI studies report evidence of microstructural abnormalities in white matter regions of interest, but we lack a fine-scale spatial mapping of brain microstructural differences along tracts in BD. We also lack large-scale studies that integrate tractometry data from multiple sites, as larger datasets can greatly enhance power to detect subtle effects and assess whether effects replicate across larger international datasets. In this multisite diffusion MRI study, we used BUndle ANalytics (BUAN, Chandio 2020), a recently developed analytic approach for tractography, to extract, map, and visualize profiles of microstructural abnormalities on 3D models of fiber tracts in 148 participants with BD and 259 healthy controls from 6 independent scan sites. Modeling site differences as random effects, we investigated along-tract white matter (WM) microstructural differences between diagnostic groups. QQ plots showed that group differences were gradually enhanced as more sites were added. Using the BUAN pipeline, BD was associated with lower mean fractional anisotropy (FA) in fronto-limbic, interhemispheric, and posterior pathways; higher FA was also noted in posterior bundles, relative to controls. By integrating tractography and anatomical information, BUAN effectively captures unique effects along white matter (WM) tracts, providing valuable insights into anatomical variations that may assist in the classification of diseases.

Impact factor and future directions for the Irish Journal of Psychological Medicine.

Impact factor (IF) is a concept dating back over half a century, created to evaluate the impact of a journal within a particular scientific field. In spite of limitations, IF remains a widely used metric for journals to establish the average number of citations for articles published in a journal. The Irish Journal of Psychological Medicine (IJPM) recently received an IF of 5.1, the first IF for the journal. We believe that this is a reflection of the hard work and dedication of our authors, reviewers, publishers and editorial board. The IJPM is the official research journal of the College of Psychiatrists of Ireland, and while psychiatry is the primary discipline of the journal, the current multidisciplinary approach will continue into the future. The journal has a strong Irish and international readership; while the journal will continue to publish research with an Irish focus, the editorial team are aware of the importance of ongoing global contributions to ensure the journal maintains high-quality publications of an international standard. This is an exciting time to be involved in mental health research, and the journal will continue to publish cutting edge themes with the goal of improving mental healthcare in Ireland and beyond.

Complete genome of an inhibitor-resistant blaTEM-30 encoding Escherichia coli sequence type 127 isolate identified in human saliva with a high genotypic virulence load.

OBJECTIVES: Escherichia coli sequence type (ST) 127 is a pandemic lineage that belongs to the extraintestial pathogenic (ExPEC) family, mainly associated with urinary tract infections and bloodstream infections. Here, we report the complete genome of an E. coli ST 127 isolate which was identified in the saliva of a patient with treatment-resistant schizophrenia (TRS) exhibiting no signs of infection. The objective of this work is to determine the mobile genetic elements (MGEs), antibiotic resistance genes (ARGs), and virulence factors (VFs) that contribute to the pathogenicity of such ST127 isolates. METHODS: Whole-genome sequencing (WGS) of isolate GABEEC10 was performed using DNABseq and Nanopore MinION platforms. Hybrid assembly of GABEEC10 was conducted with Unicycler v. 0.5.0. and annotated using PROKKA v1.14.5. Comparative genomics and phylogenomics were conducted using average nucleotide identity (ANI) and approximately-maximum-likelihood phylogenetic inference. ARGs, VFs, and serotyping were identified with Abricate v1.0.0 using CARD, vfdb, and EcOH databases, respectively. RESULTS: Escherichia coli salivary isolate GABEEC10 was identified to belong to phylogroup B2 and have a serotype of O6 H31 with a total genome length of 4,940,530 bp and a mean guanine-cytosine (GC) content of 50.40 %. GABEEC10 was identified to have a highly virulent genotype with the presence of 84 VFs in addition to 44 ARGs, including an acquired blaTEM-30. The strain was identified to additionally carry four mobilisable plasmids. CONCLUSION: We report the complete genome of E. coli GABAEEC10 that can be used for gaining insights into the pathogenicity, drug resistance mechanisms, and dissemination patterns of the emerging pandemic lineage ST 127.

Psychological intervention for a person living with amblyopia: a case study from home-based integrated care.

Amblyopia is a common developmental disability resulting in reduced visual acuity and gaze stability; it occurs in approximately 5% of the general population. Here, we present the case of an 18-year-old girl diagnosed with amblyopia. Subsequent to her diagnosis of amblyopia, she developed a depressive episode with co-morbid anxiety symptoms. She was treated with low intensity psychological intervention, Problem Management Plus, as home-based intervention. This intervention was associated both subjectively and objectively utilising psychometric measures (i.e. psychiatric interview, depression, anxiety and stress scale, general health questionnaire) with a significant amelioration of her mental state. This case provides preliminary evidence for the effectiveness of Problem Management Plus intervention and suggests that this intervention should be considered for other individuals with similar clinical presentations.

Early life stress, low-grade systemic inflammation and weaker suppression of the default mode network (DMN) during face processing in Schizophrenia.

Childhood trauma (CT) is associated with lower cognitive and social cognitive function in schizophrenia. Recent evidence suggests that the relationship between CT and cognition is mediated by both low-grade systemic inflammation and reduced connectivity of the default mode network (DMN) during resting state. This study sought to test whether the same pattern of associations was observed for DMN connectivity during task based activity. Fifty-three individuals with schizophrenia (SZ) or schizoaffective disorder (SZA) and one hundred and seventy six healthy participants were recruited from the Immune Response and Social Cognition (iRELATE) project. A panel of pro-inflammatory markers that included IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNFa), and C-reactive protein (CRP), were measured in plasma using ELISA. DMN connectivity was measured during an fMRI social cognitive face processing task. Patients showed evidence of low grade systemic inflammation and significantly increased connectivity between the left lateral parietal (LLP) cortex-cerebellum and LLP-left angular gyrus compared to healthy participants. Across the entire sample, IL-6 predicted increased connectivity between LLP-cerebellum, LLP-precuneus, and mPFC-bilateral-precentral-gyri and left postcentral gyrus. In turn, and again in the entire sample, IL-6 (but no other inflammatory marker) mediated the relationship between childhood physical neglect and LLP-cerebellum. Physical neglect scores also significantly predicted the positive association between IL-6 and LLP-precuneus connectivity. This is to our knowledge the first study that provides evidence that higher plasma IL-6 mediates the association between higher childhood neglect and increased DMN connectivity during task based activity. Consistent with our hypothesis, exposure to trauma is associated with weaker suppression of the DMN during a face processing task, and this association was mediated via increased inflammatory response. The findings may represent part of the biological mechanism by which CT and cognitive performance are related.

Dysfunctional schema modes as determinants of psychiatric comorbidities: a study in a cohort of people with epilepsy.

INTRODUCTION AND AIMS: Symptomatology of epilepsy and its' associated alteration in brain processes, stigma of experiencing seizures, and adverse sequelae of anti-epileptics have been demonstrated to impact behaviour and exacerbate psychopathology. This study examines the role of dysfunctional schema modes in People with Epilepsy (PWE) and their association with psychiatric symptoms. METHODS: Semi-structured interviews were conducted with 108 PWE treated with anti-epileptics for at least one year and with no history or mental disorder or psycho-active substance use. Clinical symptoms were measured utilising the Symptom Checklist-90 (SCL-90) with schema modes measured utilising the Schema Mode Inventory (SMI). RESULTS: Maladaptive coping and child schema modes were significantly higher in individuals from lower socio-economic status group (p < 0.01), with several maladaptive schema modes more prevalent in males. Hostility symptoms were increased in individuals from lower socio-economic classes and were more prevalent early in disease course. Several psychological symptoms including somatisation, interpersonal, obsession, depression, paranoia, hostility, phobia, anxiety, and psychoticism, were predicted by various maladaptive schema modes (p < 0.001). CONCLUSION: This study highlights the impact of maladaptive schemas, suggesting that PWE might benefit from the introduction of appropriate psychotherapeutic interventions such as schema-focused therapy, particularly if from lower socio-economic classes or in the early stages of theirdisease course.

Impulsivity, suicidal thoughts, psychological distress, and religiosity in adolescents and young adults.

Background: Impulsivity is associated with suicidal acts and ideation, whereas higher religious commitment has been identified as a potential protective factor linked to lower suicidal ideation. Objectives: We examined the extent to which higher religious commitment is associated with lower suicidal ideation and whether religious commitment modifies the relationship between impulsivity and suicidal ideation. Methods: Adolescent and young adult males, with a prior history of suicidal act and ideations, completed standardized questionnaires [i.e., Beck Scale for Suicidal Ideation (BSS), Barratt Impulsivity Scale-II (BIS-II), Depression Anxiety Stress Scale (DASS), and Religious Commitment Inventory-10 (RCI-10)], to assess impulsivity, suicidal ideation, distress, and religious commitment. Regression and mediation analyses were performed to investigate the relationships among impulsivity, religious commitment, and suicidal ideation. Results: Of the 747 study participants (mean age 18.8 years, SD = 4.1), 151 (20.2%) had a history of suicidal acts and 177 (23.7%) had a history of suicidal ideation. Non-planning impulsivity (predictor) was inversely associated with religious commitment (r = -0.33, p < 0.01), and religious commitment (mediator) was inversely related to suicidal ideation (outcome) (r = -0.32, p < 0.01). These findings remained statistically significant when controlling for either religious commitment or non-planning impulsivity, as appropriate. Higher religious commitment reduced the association between non-planning impulsivity and suicidal ideation (p < 0.01). Conclusion: The findings highlight the potential for cultivating spirituality to buffer against higher suicidal ideation, and thus could be considered as an additional therapeutic strategy for individuals with higher levels of impulsivity and co-morbid suicidal ideation.

Along-Tract Statistical Mapping of Microstructural Abnormalities in Bipolar Disorder: A Pilot Study.

Investigating brain circuitry involved in bipolar disorder (BD) is key to discovering brain biomarkers for genetic and interventional studies of the disorder. Even so, prior research has not provided a fine-scale spatial mapping of brain microstructural differences in BD. In this pilot diffusion MRI dataset, we used BUndle ANalytics (BUAN), a recently developed analytic approach for tractography, to extract, map, and visualize the profile of microstructural abnormalities on a 3D model of fiber tracts in people with BD (N=38) and healthy controls (N=49), and investigate along-tract white matter (WM) microstructural differences between these groups. Using the BUAN pipeline, BD was associated with lower mean Fractional Anisotropy (FA) in fronto-limbic and interhemispheric pathways and higher mean FA in posterior bundles relative to controls. BUAN combines tractography and anatomical information to capture distinct along-tract effects on WM microstructure that may aid in classifying diseases based on anatomical differences.

Childhood trauma is associated with altered white matter microstructural organization in schizophrenia.

It has been reported that childhood trauma (CT) is associated with reductions in fractional anisotropy (FA) in individuals with schizophrenia (SZ). Here, we hypothesized that SZ with high levels of CT will show the greatest reductions in FA in frontolimbic and frontoparietal regions compared to healthy controls (HC) with high trauma levels and participants with no/low levels of CT. Thirty-seven SZ and 129 HC with CT experience were dichotomized into groups of 'none/low' or 'high' levels. Participants underwent diffusion-weighted MRI, and Tract-based spatial statistics were employed to assess the main effect of diagnosis, main effect of CT severity irrespective of diagnosis, and interaction between diagnosis and CT severity. SZ showed FA reductions in the corpus callosum and corona radiata compared to HC. Irrespective of a diagnosis, high CT levels (n = 48) were related to FA reductions in frontolimbic and frontoparietal regions compared to those with none/low levels of CT (n = 118). However, no significant interaction between diagnosis and high levels of CT was found (n = 13). Across all participants, we observed effects of CT on late developing frontolimbic and frontoparietal regions, suggesting that the effects of CT severity on white matter organization may be independent of schizophrenia.