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Abstract Background Psychosis, even in its early stages, is associated with significant disability, causing it to be ranked ahead of paraplegia and blindness in those aged 18–35 in terms of years lived with disability. Current pharmacological and psychological interventions intervention have focused primarily on the reduction of positive symptoms (hallucinations and delusions), with little benefit to domains of psychosis such as cognitive difficulties and social and occupational functioning. Methods/design The CReSt-R intervention trial is a single center, pilot randomised controlled study based at the National University of Ireland (NUI), Galway. The trial will recruit participants from four clinical sites with assessment and intervention completed by the primary NUI Galway team. The trial will explore the feasibility, acceptability, and effectiveness of a novel psychosocial intervention for early psychosis based on a combined cognitive remediation training and cognitive behavioural therapy approach focused on social recovery. Participants, aged 16–35 within the first 5 years of a diagnosed psychotic disorder, will be recruited from the Children and Adolescent Mental Health Service and the Adult Mental Health Services in the region. Discussion Cognitive remediation training (for improving cognition) and social recovery focused cognitive behavioural therapy, have both separately demonstrated effectiveness. This trial will evaluate the feasibility, acceptability, and explore the efficacy of a treatment approach that combines both approaches as part of an integrated, multicomponent intervention. Trial registration Cognitive Remediation & Social Recovery in Early Psychosis (CReSt-R): ClincialTrials.gov Identifier NCT04273685. Trial registered Feb 18th, 2020. Last updated April 14th, 2021.

Currently, there are limited data comparing demographic and clinical characteristics of individuals who died by probable suicide and who did and did not previously attend mental health services (MHSs). This study compared demographic and clinical factors for both groups, in a Western region of Ireland over a 13-year period. Postmortem reports between January 1, 2006 and March 31, 2019 were reviewed for 400 individuals who died by probable suicide. Relevant sociodemographic and clinical data were extracted from individuals’ lifetime case notes. One hundred and fifty nine individuals (40%) had attended MHSs at some stage (“attendee”). Hanging was the most common method of suicide (61%), followed by drowning (18%) for both attendees and nonattendees of MHSs, with more violent methods utilized overall by nonattendees (p = 0.028). Sixty-eight percent of individuals who previously attempted hanging subsequently died utilizing this method. A higher proportion of attendees were female compared to nonattendees of MHSs (28.9 vs. 14.5%, p = 0.001). Recurrent depressive disorder (55%) was the most common diagnosed mental health disorder. For individuals with a diagnosis of schizophrenia, 39% had antipsychotic medications detectable in their toxicology reports. In conclusion, the majority of people who died by probable suicide had never had contact with MHSs, and nonattendees overall were more likely to utilize violent methods of suicide. Nonconcordance with psychotropic medications in psychotic patients and previous hanging attempt were highlighted as potential risk factors for death by probable suicide.

U.S. dairy operations are sorted via a multinomial logit model into three production systems - pasture-based, semi-pasture-based, and conventional. Region, farm size, financial situation, and production intensity measures impact system choice. Analysis follows to determine the impact of production system on enterprise profitability. Region, farm size, and demographic variables impact profitability, as does system choice - semi-pasture-based operations were less profitable than conventional operations on an enterprise, per hundredweight of milk produced basis. Significant differences were not found in the profitability of pasture-based operations versus those using other systems.

Background: While omega-3 polyunsaturated fatty acids (PUFAs) have shown promise as an adjunctive treatment for schizophrenia and other psychotic disorders, the overall consensus about their efficacy across studies is still lacking and findings to date are inconclusive. No clinical trials or systematic reviews have yet examined if omega-3 PUFAs are associated with differential levels of efficacy at various stages of psychosis., Method: A systematic bibliographic search of randomized double-blind placebo-controlled trials (RCTs) examining the effect of omega-3 PUFAs as a monotherapy or adjunctive therapy versus a control group in adults and children at ultra-high risk (UHR) for psychosis, experiencing a first-episode psychosis (FEP), or diagnosed with an established psychotic disorder was conducted. Participants' clinical symptoms were evaluated using total and subscale scores on validated psychometric scales., Results: No beneficial effect of omega-3 PUFAs treatment was found in comparison with that of placebo ( G = -0.26, 95% CI -0.55 to 0.03, p = 0.08). Treatment of omega-3 PUFAs did not prove any significant improvement in psychopathology in UHR ( G = -0.09, 95% CI -0.45 to 0.27, p = 0.63), FEP ( G = -1.20, 95% CI -5.63 to 3.22, p = 0.59), or schizophrenia patients ( G = -0.17, 95% CI -0.38 to -0.03, p = 0.10)., Conclusion: These findings confirm previous evidence that disputes the original reported findings of the beneficial effect of omega-3 PUFAs in schizophrenia. Furthermore, accumulative evidence of the use of omega-3 as a preventive treatment option in UHR is not supported, suggesting that the need for future studies in this line of research should not be promoted.

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., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stevens, Ní Mhurchú, Corley, Egan, Hallahan, McDonald, Donohoe and Burke.)

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., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, O'Brien et al.)

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., (© 2023. The Author(s).)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abdullah, Khalily, Ruocco and Hallahan.)

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.

Objectives: Kalamiella piersonii is a newly identified bacterial species, first isolated from surfaces of the International Space Station (ISS). It also appears as a novel human pathogen reported to be implicated in bacteremia and kidney stone disease. Here, we report the first complete genome of a multidrug-resistant strain of K. piersonii (GABEKP28), isolated from the saliva of a patient with treatment-resistant schizophrenia (TRS), to determine the mobile genetic elements (MGEs), antibiotic resistance genes (ARGs), and virulence factors (VFs) harboured by such a strain of this novel species., Methods: Whole-genome sequencing was performed using DNABSEQ (PE150) and Nanopore MinION platforms. Hybrid assembly was conducted using Unicycler v0.5.0. Genome assembly quality was verified using QUAST v5.0.2. The assembly was annotated using PROKKA v1.14.5. ARGs and VFs were identified using Abricate v1.0.0., Results: K. piersonii strain GABEKP28 was classified as multidrug-resistant while also carrying plasmidic genetic determinants associated with a hypervirulent phenotype. The complete genome size is 3 881 479 bp and has a guanine-cytosine content of 57.76% while it encodes for 3 525 chromosome coding sequences. The strain was also identified to carry three plasmids of 513 647 bp, 261 771 bp, and 106 029 bp, respectively., Conclusions: K.piersonii GABEKP28 is the first complete genome of this species to be submitted to GenBank and only the second to be sequenced from a human host. The whole-genome sequencing data with multiple plasmids, ARGs, and VFs will aid in understanding the pathogenicity, evolution, and phylogeny of this novel opportunistic pathogen., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Alcohol use in bipolar disorder (BD) is associated with mood lability and negative illness trajectory, while also impacting functional networks related to emotion, cognition, and introspection. The adverse impact of alcohol use in BD may be explained by its additive effects on these networks, thereby contributing to a poorer clinical outcome., Methods: Forty BD-I (DSM-IV-TR) and 46 psychiatrically healthy controls underwent T1 and resting state functional MRI scanning and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) to assess alcohol use. Functional images were decomposed using spatial independent component analysis into 14 resting state networks (RSN), which were examined for effect of alcohol use and diagnosis-by-alcohol use accounting for age, sex, and diagnosis., Results: Despite the groups consuming similar amounts of alcohol (BD: mean score ± SD 3.63 ± 3; HC 4.72 ± 3, U = 713, p = .07), for BD participants, greater alcohol use was associated with increased connectivity of the paracingulate gyrus within a default mode network (DMN) and reduced connectivity within an executive control network (ECN) relative to controls. Independently, greater alcohol use was associated with increased connectivity within an ECN and reduced connectivity within a DMN. A diagnosis of BD was associated with increased connectivity of a DMN and reduced connectivity of an ECN., Conclusion: Affective symptomatology in BD is suggested to arise from the aberrant functionality of networks subserving emotive, cognitive, and introspective processes. Taken together, our results suggest that during euthymic periods, alcohol can contribute to the weakening of emotional regulation and response, potentially explaining the increased lability of mood and vulnerability to relapse within the disorder., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Both low-grade systemic inflammation and functional connectivity of the default mode network (DMN) during rest have recently been observed to mediate the association between childhood trauma (CT) and behavioural performance on an emotion recognition task. Whether inflammation also mediates the association between CT and functional connectivity of the DMN during social cognitive task performance is unknown., Methods: 51 patients with schizophrenia (SZ) or schizoaffective disorder (SZA) and 176 healthy participants completed a theory of mind (ToM) task during fMRI. IL-6 was measured in plasma using ELISA. DMN connectivity was measured during performance of the fMRI ToM task. To examine DMN connectivity, we selected 4 a priori seeds of the DMN, i.e., the medial prefrontal cortex (PFC), right lateral parietal (LP), left LP, and posterior cingulate cortex (PCC) according to the Harvard-Oxford Cortical and Subcortical Atlas (http://www.cma.mgh.harvard.edu/fsl&#95;atlas.html) as implemented in CONN., Results: Patients showed significantly increased DMN connectivity compared to healthy participants between each of the four seeds of the DMN and with other clusters in the brain. Across the entire sample, higher levels of IL-6 predicted increased connectivity between the mPFC and regions encompassing the cerebellum (<0.001 FWE). IL-6 mediated the association between physical neglect and weaker suppression of the posterior cingulate cortex (PCC) DMN seed -left precentral and postcentral gyrus (β INDIRECT  = .0170, CI: 0.0008 to.0506) connectivity during ToM performance., Discussion: This is the first study to our knowledge that provides evidence that higher plasma IL-6 mediates the association between higher childhood neglect and increased DMN connectivity during ToM task performance. Consistent with our previous study that IL-6 mediated the association between early life stress exposure and reduced connectivity of the DMN during rest, here IL-6 mediated the association between early life stress and increased connectivity of the DMN during ToM based cognitive processing. These findings suggest a biological mechanism for how chronic stress impacts social cognitive processing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2022 The Authors.)

The muscarinic-cholinergic system is involved in the pathophysiology of bipolar disorder (BD), and contributes to attention and the top-down and bottom-up cognitive and affective mechanisms of emotional processing, functionally altered in BD. Emotion processing can be assessed by the ability to inhibit a response when the content of the image is emotional. Impaired regulatory capacity of cholinergic neurotransmission conferred by reduced M 2 -autoreceptor availability is hypothesized to play a role in elevated salience of negative emotional distractors in euthymic BD relative to individuals with no history of mood instability. Thirty-three euthymic BD type-I (DSM-V-TR) and 50 psychiatrically-healthy controls underwent functional magnetic resonance imaging (fMRI) and an emotion-inhibition paradigm before and after intravenous cholinergic challenge using the acetylcholinesterase inhibitor, physostigmine (1 mg), or placebo. Mood, accuracy, and reaction time on either recognizing or inhibiting a response associated with an image involving emotion and regional functional activation were examined for effects of cholinergic challenge physostigmine relative to placebo, prioritizing any interaction with the diagnostic group. Analyses revealed that (1) at baseline, impaired behavioral performance was associated with lower activation in the anterior cingulate cortex in BD relative to controls during emotion processing; (2) physostigmine (vs. placebo) affected behavioral performance during the inhibition of negative emotions, without altering mood, and increased activation in the posterior cingulate cortex in BD (vs. controls); (3) In BD, lower accuracy observed during emotion inhibition of negative emotions was remediated by physostigmine and was associated with cingulate cortex overactivation. Our findings implicate abnormal regulation of cholinergic neurotransmission in the cingulate cortices in BD, which may mediate exaggerated emotional salience processing, a core feature of BD., (© 2022. The Author(s).)

Background: Current treatment options for the management of depressive episodes in bipolar disorder are often sub-optimal, with some treatments either noted to be only partially effective or to require long durations of treatment prior to a therapeutic response. Therefore, pharmaco-therapeutic options that reduce depressive symptoms in a more rapid manner might provide a viable therapeutic option for some people. Intravenous (IV) scopolamine, a pan muscarinic antagonist, has been demonstrated in a number of studies to confer a rapid antidepressant effect, albeit no study to date has exclusively evaluated its potential therapeutic effect in a cohort consisting solely of individuals with bipolar disorder., Methods: Individuals with bipolar disorder who are currently experiencing a depressive episode of at least moderate severity will be included in this study. Eligible participants will undergo a screening and placebo-run in visit and will be randomised at visit 3 to the treatment or placebo group. Participants will receive the three blinded infusions over the course of 2 weeks, with two subsequent follow-up visits, 1 and 3 weeks after the last infusion visit. The total duration of the study will be approximately 6 weeks. Patients will continue their regular treatment regime in addition to study medication. Objective and subjective mood questionnaires, cognitive assessments and other psychometric instruments will be administered and recorded., Discussion: To our knowledge, this is the first study to investigate the antidepressant effects of IV scopolamine in an exclusively bipolar disorder cohort. Trial findings will contribute to the evidence base regarding the cholinergic hypothesis of mood disorders and specifically might result in an additional safe therapeutic option for the management of depressive episodes in bipolar disorder., Trial Registration: ClinicalTrials.gov NCT04211961 . December 26, 2019. EudraCT Number 2017-003112-39., (© 2022. The Author(s).)

A 35-year-old primigravida presented with significant anxiety symptoms at 26 weeks' gestation. Symptoms were preceded by a nightmare about her upcoming labour. She developed repetitive intrusive thoughts of being trapped emotionally and physically in her pregnancy. Her symptoms were suggestive of new-onset claustrophobia associated with pregnancy, which has not been previously reported on. Her symptoms ameliorated with a combination of cognitive-behavioural therapy and pharmacotherapy (sertraline and low dose quetiapine). The later stages of pregnancy were associated with minimal symptoms and the resolution of her subjective 'entrapment'. A subsequent pregnancy resulted in similar although less severe symptomatology. No postpartum anxiety symptoms were demonstrated on both occasions. Anxiety symptoms can adversely impact both the mother and fetus, and thus correct identification and management of pregnancy-related claustrophobia improved symptomatology and functioning and allowed for earlier detection and reduced symptomatology in a subsequent pregnancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: There is considerable evidence of dysconnectivity within the default-mode network (DMN) in schizophrenia, as measured during resting-state functional MRI (rs-fMRI). History of childhood trauma (CT) is observed at a higher frequency in schizophrenia than in the general population, but its relationship to DMN functional connectivity has yet to be investigated., Methods: CT history and rs-fMRI data were collected in 65 individuals with schizophrenia and 132 healthy controls. Seed-based functional connectivity between each of 4 a priori defined seeds of the DMN (medial prefrontal cortex, right and left lateral parietal lobes, and the posterior cingulate cortex) and all other voxels of the brain were compared across groups. Effects of CT on functional connectivity were examined using multiple regression analyses. Where significant associations were observed, regression analyses were further used to determine whether variance in behavioral measures of Theory of Mind (ToM), previously associated with DMN recruitment, were explained by these associations., Results: Seed-based analyses revealed evidence of widespread reductions in functional connectivity in patients vs controls, including between the left/right parietal lobe (LP) and multiple other regions, including the parietal operculum bilaterally. Across all subjects, increased CT scores were associated with reduced prefrontal-parietal connectivity and, in patients, with increased prefrontal-cerebellar connectivity also. These CT-associated differences in DMN connectivity also predicted variation in behavioral measures of ToM., Conclusions: These findings suggest that CT history is associated with variation in DMN connectivity during rs-fMRI in patients with schizophrenia and healthy participants, which may partly mediate associations observed between early life adversity and cognitive performance., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

For a person with mental illness, travelling abroad can be challenging but it can be easier when the traveller and healthcare practitioner have a clear understanding of the likely impact of travel on the illness and of the illness on the travel experience. Travel may also precipitate first presentations of mental illness or unmask previously undiagnosed mental disorders. We propose that mental health problems should receive greater recognition in travel medicine and that psychiatrists should collaborate more closely with travel medicine clinicians to ensure that their patients benefit from the opportunities afforded by international travel.

Background: Deficits in facial emotion recognition are a core feature of schizophrenia and predictive of functional outcome. Higher plasma levels of the cytokine interleukin 6 (IL-6) have recently been associated with poorer facial emotion recognition in individuals with schizophrenia and healthy participants, but the neural mechanisms affected remain poorly understood., Methods: Forty-nine individuals with schizophrenia or schizoaffective disorder and 158 healthy participants were imaged using functional magnetic resonance imaging during a dynamic facial emotion recognition task. Plasma IL-6 was measured from blood samples taken outside the scanner. Multiple regression was used in statistical parametric mapping software to test whether higher plasma IL-6 predicted increased neural response during task performance., Results: Higher plasma IL-6 predicted increased bilateral medial prefrontal response during neutral face processing compared to angry face processing in the total sample (N = 207, t max  = 5.67) and increased left insula response during angry face processing compared to neutral face processing (N = 207, t max  = 4.40) (p < 0.05, family-wise error corrected across the whole brain at the cluster level)., Conclusions: These findings suggest that higher peripheral IL-6 levels predict altered neural response within brain regions involved in social cognition and emotion during facial emotion recognition. This is consistent with recent neuroimaging research on IL-6 and suggesting a possible neural mechanism by which this cytokine might affect facial emotion recognition accuracy., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Childhood trauma, and in particular physical neglect, has been repeatedly associated with lower performance on measures of social cognition (e.g. emotion recognition tasks) in both psychiatric and non-clinical populations. The neural mechanisms underpinning this association have remained unclear. Here, we investigated whether volumetric changes in three stress-sensitive regions-the amygdala, hippocampus and anterior cingulate cortex (ACC)-mediate the association between childhood trauma and emotion recognition in a healthy participant sample (N = 112) and a clinical sample of patients with schizophrenia (N = 46). Direct effects of childhood trauma, specifically physical neglect, on Emotion Recognition Task were observed in the whole sample. In healthy participants, reduced total and left ACC volumes were observed to fully mediate the association between both physical neglect and total childhood trauma score, and emotion recognition. No mediating effects of the hippocampus and amygdala volumes were observed for either group. These results suggest that reduced ACC volume may represent part of the mechanism by which early life adversity results in poorer social cognitive function. Confirmation of the causal basis of this association would highlight the importance of resilience-building interventions to mitigate the detrimental effects of childhood trauma on brain structure and function., (© The Author(s) 2020. Published by Oxford University Press.)

The association of antipsychotic medication with abnormal brain morphometry in schizophrenia remains uncertain. This study investigated subcortical morphometric changes 6 months after switching treatment to clozapine in patients with treatment-resistant schizophrenia compared with healthy volunteers, and the relationships between longitudinal volume changes and clinical variables. In total, 1.5T MRI images were acquired at baseline before commencing clozapine and again after 6 months of treatment for 33 patients with treatment-resistant schizophrenia and 31 controls, and processed using the longitudinal pipeline of Freesurfer v.5.3.0. Two-way repeated MANCOVA was used to assess group differences in subcortical volumes over time and partial correlations to determine association with clinical variables. Whereas no significant subcortical volume differences were found between patients and controls at baseline (F(8,52) = 1.79; p = 0.101), there was a significant interaction between time, group and structure (F(7,143) = 52.54; p < 0.001). Corrected post-hoc analyses demonstrated that patients had significant enlargement of lateral ventricles (F(1,59) = 48.89; p < 0.001) and reduction of thalamus (F(1,59) = 34.85; p < 0.001), caudate (F(1,59) = 59.35; p < 0.001), putamen (F(1,59) = 87.20; p < 0.001) and hippocampus (F(1,59) = 14.49; p < 0.001) volumes. Thalamus and putamen volume reduction was associated with improvement in PANSS (r = 0.42; p = 0.021, r = 0.39; p = 0.033), SANS (r = 0.36; p = 0.049, r = 0.40; p = 0.027) and GAF (r = -0.39; p = 0.038, r = -0.42; p = 0.024) scores. Reduced thalamic volume over time was associated with increased serum clozapine level at follow-up (r = -0.44; p = 0.010). Patients with treatment-resistant schizophrenia display progressive subcortical volume deficits after switching to clozapine despite experiencing symptomatic improvement. Thalamo-striatal progressive volumetric deficit associated with symptomatic improvement after clozapine exposure may reflect an adaptive response related to improved outcome rather than a harmful process.

Aims and methodWe aimed to evaluate clinical note documentation of valproate prescribing and establish the level of knowledge among women of child-bearing potential regarding valproate-associated adverse effects, including teratogenesis, in a regional Irish mental health service. RESULTS: Of the 42 women prescribed sodium valproate, 21.4% (n = 9) had some documentation in relation to associated risks and 33.3% (n = 14) described an awareness of these risks from consultation with their treating mental health team. On clinical interview, 9.5% (n = 4) of individuals with clear documentation of the risks of teratogenesis described no such awareness. Augmentation with lithium was associated with greater awareness of the teratogenic risks of valproate (P = 0.011).Clinical implicationsA clear description of the teratogenic risks of valproate and potential management strategies, including advice regarding contraception and supplementation with folic acid, should be clearly documented and provided repeatedly and in context to all women of child-bearing age who are prescribed valproate.Declaration of interestNone.

Background: A theoretical model of individuals' experiences before, during and after involuntary admission has not yet been established., Aims: To develop an understanding of individuals' experiences over the course of the involuntary admission process., Method: Fifty individuals were recruited through purposive and theoretical sampling and interviewed 3 months after their involuntary admission. Analyses were conducted using a Straussian grounded theory approach., Results: The 'theory of preserving control' (ToPC) emerged from individuals' accounts of how they adapted to the experience of involuntary admission. The ToPC explains how individuals manage to reclaim control over their emotional, personal and social lives and consists of three categories: 'losing control', 'regaining control' and 'maintaining control', and a number of related subcategories., Conclusions: Involuntary admission triggers a multifaceted process of control preservation. Clinicians need to develop therapeutic approaches that enable individuals to regain and maintain control over the course of their involuntary admission., Declaration of Interest: None.

Background: Involuntary admission can be traumatic and is associated with negative attitudes that persist after the episode of illness has abated., Aims: We aimed to prospectively assess satisfaction with care at the points of involuntary admission and symptomatic recovery, and identify their sociodemographic, clinical and service experience predictors., Method: Levels of satisfaction with care, and clinical and sociodemographic variables were obtained from a representative cohort of 263 patients at the point of involuntary admission and from 155 of these patients 3 months after termination of the involuntary admission. Data were analysed with multiple linear regression modelling., Results: Higher baseline awareness of illness ( B = 0.19, P < 0.001) and older age ( B = 0.05, P = 0.001) were associated with more satisfaction with care at baseline and follow-up. Transition to greater satisfaction with care was associated with improvements in awareness of illness ( B = 0.13, P < 0.001) and in symptoms ( B = 0.05, P = 0.02), as well as older age ( B = 0.04, P = 0.01). Objective coercive experiences were not associated with variation in satisfaction with care., Conclusions: There is wide variation in satisfaction with coercive care. Greater satisfaction with care is positively associated with clinical variables such as increased awareness of illness., Declaration of Interest: None.