Continuous glucose monitoring with structured education in adults with type 2 diabetes managed by multiple daily insulin injections: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to compare the effectiveness of stand-alone intermittently scanned continuous glucose monitoring (isCGM) with or without a structured education programme and blood glucose monitoring (BGM) in adults with type 2 diabetes on multiple daily insulin injections (MDI). METHODS: In this 24 week randomised open-label multicentre trial, adults with type 2 diabetes on intensive insulin therapy with HbA1c levels of 58-108 mmol/mol (7.5-12.0%) were randomly assigned in a 1:1:1 ratio to isCGM with a structured education programme on adjusting insulin dose and timing according to graphical patterns in CGM (intervention group), isCGM with conventional education (control group 1) or BGM with conventional education (control group 2). Block randomisation was conducted by an independent statistician. Due to the nature of the intervention, blinding of participants and investigators was not possible. The primary outcome was change in HbA1c from baseline at 24 weeks, assessed using ANCOVA with the baseline value as a covariate. RESULTS: A total of 159 individuals were randomised (n=53 for each group); 148 were included in the full analysis set, with 52 in the intervention group, 49 in control group 1 and 47 in control group 2. The mean (± SD) HbA1c level at baseline was 68.19±10.94 mmol/mol (8.39±1.00%). The least squares mean change (± SEM) from baseline HbA1c at 24 weeks was -10.96±1.35 mmol/mol (-1.00±0.12%) in the intervention group, -6.87±1.39 mmol/mol (-0.63±0.13%) in control group 1 (p=0.0367 vs intervention group) and -6.32±1.42 mmol/mol (-0.58±0.13%) in control group 2 (p=0.0193 vs intervention group). Adverse events occurred in 28.85% (15/52) of individuals in the intervention group, 26.42% (14/53) in control group 1 and 48.08% (25/52) in control group 2. CONCLUSIONS/INTERPRETATION: Stand-alone isCGM offers a greater reduction in HbA1c in adults with type 2 diabetes on MDI when education on the interpretation of graphical patterns in CGM is provided. TRIAL REGISTRATION: ClinicalTrials.gov NCT04926623. FUNDING: This study was supported by Daewoong Pharmaceutical Co., Ltd.

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

Bane or boon regarding urbanicity and psychotic spectrum disorders: a scoping review of current evidence.

PURPOSE OF REVIEW: This review aims to provide an update on the association between urbanization and psychotic spectrum disorders, focusing on specific aspects of the urban environment that could be a bane or boon for the risk of psychosis. RECENT FINDINGS: Majority of the included studies support previous evidence suggesting that urbanization is linked to a higher risk of psychotic experiences and psychotic spectrum disorders. A small minority, however, have also found specific factors in the urban environment that could give rise to positive outcomes, such as better social functioning and lower mortality rates in psychotic spectrum disorders, or mitigate the risks associated with urbanization. The perception of the urban environment was also an important factor that increased or mitigated stress levels in patients with psychosis, which in turn affected their susceptibility to psychotic symptoms. SUMMARY: Specific aspects of the urban environment such as the availability and density of greenspaces are crucial for mitigating the effect of urbanization on risk of psychotic spectrum disorders, and should be incorporated into urban planning. At the same time, there is a need to further explore how modifiable risk factors of the urban environment such as air and noise pollution can be minimized to allow for more liveable cities in the context of psychotic spectrum conditions.

Inter-Professional Education Interventions, and Practice Outcomes Related to Healthcare Setting and Patients Within Mental Healthcare: A Scoping Review.

Introduction: This scoping review aimed to examine 1) types of inter-professional (IPE) interventions using Strosahl's typology framework, 2) practice outcomes related to healthcare setting and patients using Kirkpatrick's model of training evaluation, and 3) enablers and challenges related to the effectiveness of IPE interventions specific to the mental healthcare setting in order to guide the development of such future programs. Methods: This scoping review was conducted in accordance with the methodology of the Joanna Briggs Institute for scoping reviews. Several databases were searched for relevant studies from database inception until December 2023. Articles were included if it 1) involved IPE interventions within mental healthcare, 2) reported practice outcomes related to healthcare setting and patients, and 3) was published in English. Variables of interest included the mode of IPE intervention using Strosahl's typology, enablers, and challenges related to IPE interventions. Results: Overall, 16 studies were included. IPE intervention outcomes within healthcare setting related to shifts in practice culture, engagement with family members, and increased collaborations with other inter-professional groups. Reported patient outcomes included clinical improvements (e.g., reduced depression and anxiety, psychotropic drug use, better psychosocial functioning), patient empowerment, satisfaction, and confidence in treatment. The enablers and challenges included resource limitations, inter-professional group and individual participation, and pedagogy. Discussion: Future efforts in IPE mental healthcare practice can focus on garnering sustained institutional support, identifying and investing in committed faculty, encouraging greater learner participation, and making iterative changes to the IPE program structure to facilitate involvement of inter-professional disciplines for better patient care.

Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

Stress and burnout amongst mental health professionals in Singapore during Covid-19 endemicity.

The COVID-19 pandemic has exerted a huge emotional strain on mental health professionals (MHP) in Singapore. As Singapore transited into an endemic status, it is unclear whether the psychological strain has likewise lessened. The aims of this study were to investigate the levels of stress and burnout experienced by MHP working in a tertiary psychiatric hospital in Singapore during this phase of COVID-19 endemicity (2022) in comparison to the earlier pandemic years (2020 and 2021) and to identify factors which contribute to as well as ameliorate stress and burnout. A total of 282 MHP participated in an online survey in 2022, which included 2 validated measures, namely the Perceived Stress Scale and the Oldenburg Burnout Inventory (OLBI). Participants were also asked to rank factors that contributed the most to their stress and burnout. Between-group comparisons were conducted regarding stress and burnout levels among MHP across different demographic groupings and working contexts. In addition, OLBI data completed by MHP in 2020 and 2021 were extracted from 2 published studies, and trend analysis was conducted for the proportion of MHP meeting burnout threshold across 3 time points. We found that the proportion of MHP meeting burnout threshold in 2020, 2021 and 2022 were 76.9%, 87.6% and 77.9% respectively. Professional groups, age, years of experience and income groups were associated with stress and/or burnout. High clinical workload was ranked as the top factor that contributed to stress and burnout while flexible working arrangement was ranked as the top area for improvement so as to reduce stress and burnout. As such, policy makers and hospital management may want to focus on setting clear mental health targets and facilitate manageable clinical workload, build manpower resiliency, optimize resources and provide flexible work arrangements to alleviate stress and burnout among MHP.

International Trends in Lithium Use for Pharmacotherapy and Clinical Correlates in Bipolar Disorder: A Scoping Review.

Lithium remains an effective option in the treatment of bipolar disorder (BD). Thus, we aim to characterize the pharmaco-epidemiological patterns of lithium use internationally over time and elucidate clinical correlates associated with BD using a scoping review, which was conducted using the methodological framework by Arksey and O'Malley (2005). We searched several databases for studies that examined the prescriptions for lithium and clinical associations in BD from inception until December 2023. This review included 55 articles from 1967 to 2023, which collected data from North America (n = 24, 43.6%), Europe (n = 20, 36.4%), and Asia (n = 11, 20.0%). The overall prescription rates ranged from 3.3% to 84% (33.4% before and 30.6% after the median year cutoffs). Over time, there was a decline in lithium use in North America (27.7% before 2010 to 17.1% after 2010) and Europe (36.7% before 2003 to 35.7% after 2003), and a mild increase in Asia (25.0% before 2003 to 26.2% after 2003). Lithium use was associated with specific demographic (e.g., age, male gender) and clinical factors (e.g., lower suicide risk). Overall, we found a trend of declining lithium use internationally, particularly in the West. Specific clinical correlates can support clinical decision-making for continued lithium use.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

Estimating multimodal brain variability in schizophrenia spectrum disorders: A worldwide ENIGMA study.

Objective: Schizophrenia is a multifaceted disorder associated with structural brain heterogeneity. Despite its relevance for identifying illness subtypes and informative biomarkers, structural brain heterogeneity in schizophrenia remains incompletely understood. Therefore, the objective of this study was to provide a comprehensive insight into the structural brain heterogeneity associated with schizophrenia. Methods: This meta- and mega-analysis investigated the variability of multimodal structural brain measures of white and gray matter in individuals with schizophrenia versus healthy controls. Using the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6139 individuals for a given brain measure, we examined variability in cortical thickness, surface area, folding index, subcortical volume and fractional anisotropy. Results: We found that individuals with schizophrenia are distinguished by higher heterogeneity in the frontotemporal network with regard to multimodal structural measures. Moreover, individuals with schizophrenia showed higher homogeneity of the folding index, especially in the left parahippocampal region. Conclusions: Higher multimodal heterogeneity in frontotemporal regions potentially implies different subtypes of schizophrenia that converge on impaired frontotemporal interaction as a core feature of the disorder. Conversely, more homogeneous folding patterns in the left parahippocampal region might signify a consistent characteristic of schizophrenia shared across subtypes. These findings underscore the importance of structural brain variability in advancing our neurobiological understanding of schizophrenia, and aid in identifying illness subtypes as well as informative biomarkers.

Elucidating salient site-specific functional connectivity features and site-invariant biomarkers in schizophrenia via deep neural networks.

Schizophrenia is a highly heterogeneous disorder and salient functional connectivity (FC) features have been observed to vary across study sites, warranting the need for methods that can differentiate between site-invariant FC biomarkers and site-specific salient FC features. We propose a technique named Semi-supervised learning with data HaRmonisation via Encoder-Decoder-classifier (SHRED) to examine these features from resting state functional magnetic resonance imaging scans gathered from four sites. Our approach involves an encoder-decoder-classifier architecture that simultaneously performs data harmonisation and semi-supervised learning (SSL) to deal with site differences and labelling inconsistencies across sites respectively. The minimisation of reconstruction loss from SSL was shown to improve model performance even within small datasets whilst data harmonisation often led to lower model generalisability, which was unaffected using the SHRED technique. We show that our proposed model produces site-invariant biomarkers, most notably the connection between transverse temporal gyrus and paracentral lobule. Site-specific salient FC features were also elucidated, especially implicating the paracentral lobule for our local dataset. Our examination of these salient FC features demonstrates how site-specific features and site-invariant biomarkers can be differentiated, which can deepen our understanding of the neurobiology of schizophrenia.

Medical Humanities in Undergraduate Psychiatry Teaching: Learner Assessment and Mediators of Better Learning Outcomes.

OBJECTIVES: Previous studies have found that the inclusion of medical humanities in medical education was associated with improvements in learner reflectivity and empathy. There is less data, however, on the impact of medical humanities on perceived patient care and mediators of learner outcomes. Our study aimed to determine the impact of medical humanities on perceived learner well-being and patient care, and the mediators of these outcomes in medical undergraduates undergoing psychiatric training. METHODS: This cross-sectional study was conducted from August 2021 to December 2022 within undergraduate medical students undergoing psychiatry rotations and who attended sessions entitled "Humanities in Psychiatry." Both quantitative and qualitative data were obtained through anonymized online feedback forms. Path analysis was performed to examine the relationship between learners' perception of the medical humanities writing activity and its potential to improve their well-being, patient care, as well as mediators of these outcomes. RESULTS: Overall, 97 medical undergraduates (response rate 67.4%) participated in the study and more than four-fifths reported improvements in listening, reflection, empathy, personal well-being, and perceived patient care. Males showed more interest in additional medical humanities sessions (mean rank 57.9 vs 42.5, P = .005) and greater improvements in personal well-being (mean rank 55.1 vs 44.5, P = .044). Path analysis showed that reflective capacity of learners mediated the relationship between reflective writing and perceived improvements in learner well-being (ß = 0.596, 95% CI = 0.409-0.737) and patient care (ß = 0.557, 95% CI = 0.379-0.702). CONCLUSIONS: Our study found that the majority of learners responded positively to the medical humanities sessions, which suggests that its use could be beneficial in fostering empathy, reflection, learner well-being, and improved patient care. Using the PRISM model, we present practical implications for educators to consider when using medical humanities in relation to psychiatry training.

Cerebellar Dysfunction and Relationship With Psychopathology, Cognitive Functioning, Resilience, and Coping in Schizophrenia.

ABSTRACT: In this study, we examined the cerebellar dysfunction in schizophrenia by evaluating the clinical, cognitive, resilience, and coping correlates of cerebellar signs (CSs) in 162 subjects (63 patients with schizophrenia and 99 healthy controls). The presence of CS was evaluated based on six clinical tests. Measures to assess the severity of psychopathology, cognitive functioning, resilience, and frequency of coping strategies used were included. Patients had more CS than controls. Patients with more CS were older, had more severe psychopathology, had poorer performance on Brief Assessment of Cognition for Schizophrenia token motor task, and used less self-distraction as a coping strategy than those with fewer CS. Patients without CS used less self-blame coping at higher level of resilience. The association of less self-distraction with more CS may be related to cognitive inflexibility as a result of cerebellar dysfunction. Greater attentiveness to the presence of CS in schizophrenia patients may aid in better management of their psychotic condition.

Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study.

Formal thought disorder (FTD) is a key clinical factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, relationship between FTD symptom dimensions and patterns of regional brain volume deficiencies in schizophrenia remain to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles based on a large multi-site cohort through the ENIGMA Schizophrenia Working Group (752 individuals with schizophrenia and 1256 controls), to unravel the neuroanatomy of positive, negative and total FTD in schizophrenia and their cellular bases. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks for positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD was also linked to microglial cell types. These findings relate different dimensions of FTD to distinct brain structural changes and their cellular underpinnings, improve our mechanistic understanding of these key psychotic symptoms.

Moral injury and associated context, contributors and consequences within mental healthcare professionals: a scoping review.

OBJECTIVES: We sought to examine the contributory factors as well as consequences of moral injury amongst healthcare workers within mental healthcare settings. METHODS: Several databases were searched for relevant studies from database inception until May 2023. Keywords and concepts included moral injury and distress in mental healthcare and psychiatry. We identified 961 studies, of which 48 were assessed for eligibility. Eventually, 35 studies were included in the review. Papers were selected for inclusion if 1) they included mental healthcare professionals (MHP) regardless of practice setting, 2) moral injury as experienced by MHP was one of their main variables of interest, 3) were written in English. Year of publication, location of study, participant characteristics, study design, settings in which injury occur (context), factors contributing to moral injury (contributors), and its effects on MHP (consequences) were extracted from the studies. RESULTS: The majority of studies were conducted in the West (n = 26, 74.3%). Contributors to moral injury were found at the individual (e.g. poor competence), practice setting (e.g. lack of resources), and organizational levels (e.g. inconsistent policies). Moral injury had negative repercussions for the individual (e.g. psychological and physical symptoms), healthcare teams (e.g. lack of trust and empathy), and healthcare system (e.g. staff attrition). CONCLUSIONS: Seen through the moral habitability framework, interventions must include an acknowledgment of the influence of various factors on the ability of MHP to enact their moral agency, and seek to establish safe moral communities within a supportive moral climate.

The development of clinical reasoning throughout the training and career of psychiatrists in Singapore.

Objectives: The current study sought to explain how different professional experiences led Singaporean psychiatrists to alter their clinical reasoning processes as their careers evolved from psychiatry residents to senior consultant psychiatrists. Methods: The current qualitative study interviewed 26 clinicians at various stages of their psychiatric career, spanning residents to senior psychiatrists.  The authors used a constructivist grounded theory approach to structure the collection and analysis of data. Analyses produced a dense theoretical explanation rooted in the experiences of participants. Results: Several differences emerged between the way psychiatry residents and senior psychiatrists explained their reasoning process and the experiences on which they based their preference. Residents preferred using deductive logic-driven frameworks that were diagnosis-centric, because of the pressures they experienced during their training and assessments. Senior psychiatrists emphasized a more holistic and problem-centric approach. Participants attributed the changes that occurred over time to practical experiences, such as their greater clinical responsibility and independence, and individual experiences, such as growing sensitivity to the clinical reasoning process or their growing propensity for professional reflectiveness. These changes manifest as an increase in repertoire and flexibility in deployment of different clinical reasoning strategies. Conclusions: It is important for trainees to be aware of the deductive and inductive modes of clinical reasoning during supervision and to be comfortable with shifting clinical focus from diagnoses to specific individual problems. Training programs should provide and plan adequate longitudinal clinical exposure to develop clinical reasoning abilities in a way that allows consequences of decisions to be explored. Continued faculty development to ease the diversification of clinical reasoning skills should be encouraged, as should reflectivity in the learners during clinical supervision.

Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses.

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study.

Formal thought disorder (FTD) is a key clinical factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, relationship between FTD symptom dimensions and patterns of regional brain volume deficiencies in schizophrenia remain to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles based on a large multi-site cohort through the ENIGMA Schizophrenia Working Group (752 individuals with schizophrenia and 1256 controls), to unravel the neuroanatomy of positive, negative and total FTD in schizophrenia and their cellular bases. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks for positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD was also linked to microglial cell types. These findings relate different dimensions of FTD to distinct brain structural changes and their cellular underpinnings, improve our mechanistic understanding of these key psychotic symptoms.