Using machine learning to mine mental health diagnostic groups from emergency department presentations before and during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic had a profound negative effect on mental health worldwide. The hospital emergency department plays a pivotal role in responding to mental health crises. Understanding data trends relating to hospital emergency department usage is beneficial for service planning, particularly around preparing for future pandemics. Machine learning has been used to mine large volumes of unstructured data to extract meaningful data in relation to mental health presentations. This study aims to analyse trends in five mental health-related presentations to an emergency department before and during, the COVID-19 pandemic. METHODS: Data from 690,514 presentations to two Australian, public hospital emergency departments between April 2019 to February 2022 were assessed. A machine learning-based framework, Mining Emergency Department Records, Evolutionary Algorithm Data Search (MEDREADS), was used to identify suicidality, psychosis, mania, eating disorder, and substance use. RESULTS: While the mental health-related presentations to the emergency department increased during the COVID-19 pandemic compared to pre-pandemic levels, the proportion of mental health presentations relative to the total emergency department presentations decreased. Several troughs in presentation frequency were identified across the pandemic period, which occurred consistently during the public health lockdown and restriction periods. CONCLUSION: This study implemented novel machine learning techniques to analyse mental health presentations to an emergency department during the COVID-19 pandemic. Results inform understanding of the use of emergency mental health services during the pandemic, and highlight opportunities to further investigate patterns in presentation.

The sex-dependent response to psychosocial stress and ischaemic heart disease.

Stress is an important risk factor for modern chronic diseases, with distinct influences in males and females. The sex specificity of the mammalian stress response contributes to the sex-dependent development and impacts of coronary artery disease (CAD). Compared to men, women appear to have greater susceptibility to chronic forms of psychosocial stress, extending beyond an increased incidence of mood disorders to include a 2- to 4-fold higher risk of stress-dependent myocardial infarction in women, and up to 10-fold higher risk of Takotsubo syndrome-a stress-dependent coronary-myocardial disorder most prevalent in post-menopausal women. Sex differences arise at all levels of the stress response: from initial perception of stress to behavioural, cognitive, and affective responses and longer-term disease outcomes. These fundamental differences involve interactions between chromosomal and gonadal determinants, (mal)adaptive epigenetic modulation across the lifespan (particularly in early life), and the extrinsic influences of socio-cultural, economic, and environmental factors. Pre-clinical investigations of biological mechanisms support distinct early life programming and a heightened corticolimbic-noradrenaline-neuroinflammatory reactivity in females vs. males, among implicated determinants of the chronic stress response. Unravelling the intrinsic molecular, cellular and systems biological basis of these differences, and their interactions with external lifestyle/socio-cultural determinants, can guide preventative and therapeutic strategies to better target coronary heart disease in a tailored sex-specific manner.

Reply to Obegi, J.H. Distinguishing Prevention from Treatment in Suicide Prevention. Comment on "Turner et al. The Paradox of Suicide Prevention. Int. J. Environ. Res. Public Health 2022, 19, 14983".

One of the aims of our paper "The Paradox of Suicide Prevention" is to promote greater discourse on suicide prevention, with a particular focus on the mental health models used for the identification of, and interventions with, individuals who come into contact with tertiary mental health services [...].

The Paradox of Suicide Prevention.

The recognition that we cannot use risk stratification (high, medium, low) to predict suicide or to allocate resources has led to a paradigm shift in suicide prevention efforts. There are challenges in adapting to these new paradigms, including reluctance of clinicians and services to move away from traditional risk categorisations; and conversely, the risk of a pendulum swing in which the focus of care swings from one approach to determining service priority and focus (e.g., diagnosis, formulation, risk and clinical care) to a new focus (e.g., suicide specific and non-clinical care), potentially supplanting the previous approach. This paper argues that the Prevention Paradox provides a useful mental model to support a shift in paradigm, whilst maintaining a balanced approach that incorporates new paradigms within the effective aspects of existing ones. The Prevention Paradox highlights the seemingly paradoxical situation where the greatest burden of disease or death is caused by those at low to moderate risk due their larger numbers. Current planning frameworks and resources do not support successful or sustainable adoption of these new approaches, leading to missed opportunities to prevent suicidal behaviours in healthcare. Adopting systems approaches to suicide prevention, such as the Zero Suicide Framework, implemented in a large mental health service in Australia and presented in this paper as a case study, can support a balanced approach of population- and individual-based suicide prevention efforts. Results demonstrate significant reductions in re-presentations with suicide attempts for consumers receiving this model of care; however, the increasing numbers of placements compromise the capacity of clinical teams to complete all components of standardised pathway of care. This highlights the need for review of resource planning frameworks and ongoing evaluations of the critical aspects of the interventions.

Behavioural disruption in diabetic mice: Neurobiological correlates and influences of dietary α-linolenic acid.

AIM: Evolving type 2 diabetes (T2D) may influence locomotion and affective state, promoting metabolic dysfunction. We examined behaviour and neurobiology in a model of T2D, testing for benefits with dietary n-3 polyunsaturated fatty acid (PUFA). METHODS: Male C57Bl/6 mice received vehicle or 75 mg/kg streptozotocin (STZ) and 21 wks of control or Western diets (43 % fat, 40 % carbohydrate, 17 % protein). Sub-sets received dietary α-linolenic acid (ALA; 10 % of fat intake) for 6 wks. Behaviour was examined via open field and sucrose preference tests, and hippocampal and frontal cortex (FC) leptin and dopamine levels and inflammatory signalling assessed. KEY FINDINGS: T2D mice exhibited weight gain (+15 %), hyperglycemia (+35 %), hyperinsulinemia (+60 %) and insulin-resistance (+80 % higher HOMA-IR), together with anxiety-like behaviour (without anhedonia) that appeared independent of body weight and glycemic status. Cortical leptin declined whereas receptor mRNA increased. Supplementation with ALA did not influence metabolic state, while enhancing locomotion and reducing anxiety-like behaviours in healthy but not T2D mice. Hippocampal dopamine was selectively increased by ALA in T2D mice, with a trend to reduced circulating leptin in both groups. Across all groups, anxiety-like behaviour was associated with declining cortical and hippocampal leptin levels and increasing receptor mRNA, while declining dopamine levels were accompanied by decreased dopamine/serotonin receptor transcripts. SIGNIFICANCE: Chronic T2D induced anxiogenesis in mice appears to be independent of metabolic homeostasis but linked to central leptin-resistance, together with disturbed dopamine and serotonin signalling. Despite anxiolytic effects of ALA in healthy mice, no metabolic or behavioural benefits were evident in T2D.

Forgetful, sad and old: Do vascular cognitive impairment and depression share a common pre-disease network and how is it impacted by ageing?

Vascular cognitive impairment (VCI) and depression frequently coexist in geriatric populations and reciprocally increase disease risks. We assert that a shared pre-disease state of the psycho-immune-neuroendocrine (PINE) network model mechanistically explains bidirectional associations between VCI and depression. Five pathophysiological sub-networks are identified that are shared by VCI and depression: neuroinflammation, kynurenine pathway imbalance, hypothalamic-pituitary-adrenal (HPA) axis overactivity, impaired neurotrophic support and cerebrovascular dysfunction. These do not act independently, and their complex interactions necessitate a systems biology approach to better define disease pathogenesis. The PINE network is already established in the context of non-communicable diseases (NCDs) such as depression, hypertension, atherosclerosis, coronary heart disease and type 2 diabetes mellitus. We build on previous literature to specifically explore mechanistic links between MDD and VCI in the context of PINE pathways and discuss key mechanistic commonalities linking these comorbid conditions and identify a common pre-disease state which precedes transition to VCI and MDD. We expand the model to incorporate bidirectional interactions with biological ageing. Diathesis factors for both VCI and depression feed into this network and the culmination of shared mechanisms (on an ageing substrate) lead to a critical network transition to one or both disease states. A common pre-disease state underlying VCI and depression can provide clinicians a unique opportunity for early risk assessment and intervention in disease development. Establishing the mechanistic elements and systems biology of this network can reveal early warning or predictive biomarkers together with novel therapeutic targets. Integrative studies are recommended to elucidate the dynamic networked biology of VCI and depression over time.

Environmental Stressors and the PINE Network: Can Physical Environmental Stressors Drive Long-Term Physical and Mental Health Risks?

Both psychosocial and physical environmental stressors have been linked to chronic mental health and chronic medical conditions. The psycho-immune-neuroendocrine (PINE) network details metabolomic pathways which are responsive to varied stressors and link chronic medical conditions with mental disorders, such as major depressive disorder via a network of pathophysiological pathways. The primary objective of this review is to explore evidence of relationships between airborne particulate matter (PM, as a concrete example of a physical environmental stressor), the PINE network and chronic non-communicable diseases (NCDs), including mental health sequelae, with a view to supporting the assertion that physical environmental stressors (not only psychosocial stressors) disrupt the PINE network, leading to NCDs. Biological links have been established between PM exposure, key sub-networks of the PINE model and mental health sequelae, suggesting that in theory, long-term mental health impacts of PM exposure may exist, driven by the disruption of these biological networks. This disruption could trans-generationally influence health; however, long-term studies and information on chronic outcomes following acute exposure event are still lacking, limiting what is currently known beyond the acute exposure and all-cause mortality. More empirical evidence is needed, especially to link long-term mental health sequelae to PM exposure, arising from PINE pathophysiology. Relationships between physical and psychosocial stressors, and especially the concept of such stressors acting together to impact on PINE network function, leading to linked NCDs, evokes the concept of syndemics, and these are discussed in the context of the PINE network.

Sex-specific behavioral, neurobiological, and cardiovascular responses to chronic social stress in mice.

Psychosocial stress promotes and links mood and cardiovascular disorders in a sex-specific manner. However, findings in animal models are equivocal, in some cases opposing human dimorphisms. We examined central nervous system (CNS), behavioral, endocrine, cardiac, and hepatic outcomes in male or female C57Bl/6 mice subjected to chronic social stress (56 days of social isolation, with intermittent social confrontation encounters twice daily throughout the final 20 days). Females exhibited distinct physiological and behavioral changes, including relative weight loss, and increases in coronary resistance, hepatic inflammation, and thigmotaxic behavior in the open field. Males evidence reductions in coronary resistance and cardiac ischemic tolerance, with increased circulating and hippocampal monoamine levels and emerging anhedonia. Shared CNS gene responses include reduced hippocampal Maoa and increased Htr1b expression, while unique responses include repression of hypothalamic Ntrk1 and upregulation of cortical Nrf2 and Htr1b in females; and repression of hippocampal Drd1 and hypothalamic Gabra1 and Oprm in males. Declining cardiac stress resistance in males was associated with repression of cardiac leptin levels and metabolic, mitochondrial biogenesis, and anti-inflammatory gene expression. These integrated data reveal distinct biological responses to social stress in males and females, and collectively evidence greater biological disruption or allostatic load in females (consistent with propensities to stress-related mood and cardiovascular disorders in humans). Distinct stress biology, and molecular to organ responses, emphasize the importance of sex-specific mechanisms and potential approaches to stress-dependent disease.

The pathophysiology of major depressive disorder through the lens of systems biology: Network analysis of the psycho-immune-neuroendocrine physiome.

BACKGROUND/AIMS: The psycho-immune-neuroendocrine (PINE) network is a predominantly physiological (metabolomic) model constructed from the literature, inter-linking multiple biological processes associated with major depressive disorder (MDD), thereby integrating putative mechanistic pathways for MDD into a single network. MATERIAL AND METHODS: Previously published metabolomic pathways for the PINE network based on literature searches conducted in 1991-2021 were used to construct an edge table summarizing all physiological pathways in pairs of origin nodes and target nodes. The Gephi software program was used to calculate network metrics from the edge table, including total degree and centrality measures, to ascertain key network nodes and construct a directed network graph. RESULTS: An edge table and directional network graph of physiological relationships in the PINE network is presented. The network has properties consistent with complex biological systems, with analysis yielding key network nodes comprising pro-inflammatory cytokines (TNF- α, IL6 and IL1), glucocorticoids and corticotropin releasing hormone (CRH). These may represent central structural and regulatory elements in the context of MDD. CONCLUSION: The identified hubs have a high degree of connection and are known to play roles in the progression from health to MDD. These nodes represent strategic targets for therapeutic intervention or prevention. Future work is required to build a weighted and dynamic simulation of the network PINE.

Central and cardiac stress resilience consistently linked to integrated immuno-neuroendocrine responses across stress models in male mice.

Stress resilience, and behavioural and cardiovascular impacts of chronic stress, are theorised to involve integrated neuro-endocrine/inflammatory/transmitter/trophin signalling. We tested for this integration, and whether behaviour/emotionality, together with myocardial ischaemic tolerance, are consistently linked to these pathways across diverse conditions in male C57Bl/6 mice. This included Restraint Stress (RS), 1 h restraint/day for 14 days; Chronic Unpredictable Mild Stress (CUMS), seven stressors randomised over 21 days; Social Stress (SS), 35 days social isolation with brief social encounters in final 13 days; and Control conditions (CTRL; un-stressed mice). Behaviour was assessed via open field (OFT) and sucrose preference (SPT) tests, and neurobiology from frontal cortex (FC) and hippocampal transcripts. Endocrine factors, and function and ischaemic tolerance in isolated hearts, were also measured. Model characteristics ranged from no behavioural or myocardial changes with homotypic RS, to increased emotionality and cardiac ischaemic injury (with apparently distinct endocrine/neurobiological profiles) in CUMS and SS models. Highly integrated expression of HPA axis, neuro-inflammatory, BDNF, monoamine, GABA, cannabinoid and opioid signalling genes was confirmed across conditions, and consistent/potentially causal correlations identified for (i) locomotor activity (noradrenaline, ghrelin; FC Crhr1, Tnfrsf1b, Il33, Nfkb1, Maoa, Gabra1; hippocampal Il33); (ii) thigmotaxis (adrenaline, leptin); (iii) anxiety-like behaviour (adrenaline, leptin; FC Tnfrsf1a; hippocampal Il33); (iv) depressive-like behaviour (ghrelin; FC/hippocampal s100a8); and (v) cardiac stress-resistance (noradrenaline, leptin; FC Il33, Tnfrsf1b, Htr1a, Gabra1, Gabrg2; hippocampal Il33, Tnfrsf1a, Maoa, Drd2). Data support highly integrated pathway responses to stress, and consistent adipokine, sympatho-adrenergic, inflammatory and monoamine involvement in mood and myocardial disturbances across diverse conditions.

Interventional Response of Hospital and Health Services to the Mental Health Effects of Viral Outbreaks on Health Professionals.

The aim of this integrative review was to examine the impact of past viral epidemics on staff mental health interventional responses, with a specific focus on healthcare provider response in the context of the COVID-19 pandemic. Following PRISMA methodology, databases were searched for relevant articles. A total of 55 articles with a range of methodologies (e.g., commentary papers, cohort studies, qualitative studies) were included to ensure broad coverage of this rapidly emerging research area. The literature showed that many healthcare providers implemented a variety of wellbeing initiatives to support their staff during a viral outbreak. Most of these interventions, however, were not formally evaluated. Interventions included leadership/team support; online psychoeducational resources and updated information on the pandemic; respite spaces; peer support outreach; staff resilience training; telephone hotline support; staff support groups; and individual counseling. Staff were generally supportive of the initiatives offered by hospital and health services, with certain interventions being more appreciated (e.g., staff respite areas). Rapid, locally, and culturally appropriate workplace-based responses may counter the negative mental health impact on staff; but a stepped response is required for a smaller number of staff at risk of mental illness, or those with pre-existing mental illness. Systematic Review Registration: Unique Identifier: CRD42020222761.

Consumer and Carer Perspectives of a Zero Suicide Prevention Program: A Qualitative Study.

This study explored the experiences of healthcare consumers who had recently attempted suicide, and their carers, following placement on a Suicide Prevention Pathway based on the Zero Suicide framework. Qualitative interviews were conducted with 10 consumers and 5 carers using a semi-structured interview schedule. Interviews were transcribed and thematic analysis was applied to identify prominent themes and sub-themes. Three interrelated themes were identified. The first theme was 'Feeling safe and valued' with the associated sub-theme pertaining to perceived stigmatizing treatment and self-stigma. The second was 'Intersection of consumer and staff/organizational needs' with a related sub-theme of time pressure and reduced self-disclosure. The final theme was 'Importance of the 'whole picture', highlighting the relevance of assessing and addressing psychosocial factors when planning for consumer recovery. Overall, consumers and their carers reported a favorable experience of the Suicide Prevention Pathway; however, there were several areas identified for improvement. These included reconciling the time-pressures of a busy health service system, ensuring consumers and carers feel their psychosocial concerns are addressed, and ensuring that adequate rapport is developed. Key to this is ensuring consumers feel cared for and reducing perceptions of stigma.

A lived experience co-designed study protocol for a randomised control trial: the Attempted Suicide Short Intervention Program (ASSIP) or Brief Cognitive Behavioural Therapy as additional interventions after a suicide attempt compared to a standard Suicide Prevention Pathway (SPP).

BACKGROUND: Despite being preventable, suicide is a leading cause of death and a major global public health problem. For every death by suicide, many more suicide attempts are undertaken, and this presents as a critical risk factor for suicide. Currently, there are limited treatment options with limited underpinning research for those who present to emergency departments with suicidal behaviour. The aim of this study is to assess if adding one of two structured suicide-specific psychological interventions (Attempted Suicide Short Intervention Program [ASSIP] or Brief Cognitive Behavioural Therapy [CBT] for Suicide Prevention) to a standardised clinical care approach (Suicide Prevention Pathway [SPP]) improves the outcomes for consumers presenting to a Mental Health Service with a suicide attempt. METHODS: This is a randomised controlled trial with blinding of those assessing the outcomes. People who attempt suicide or experience suicidality after a suicide attempt, present to the Gold Coast Mental Health and Specialist Services, are placed on the Suicide Prevention Pathway (SPP), and meet the eligibility criteria, are offered the opportunity to participate. A total of 411 participants will be recruited for the study, with 137 allocated to each cohort (participants are randomised to SPP, ASSIP + SPP, or CBT + SPP). The primary outcomes of this study are re-presentation to hospitals with suicide attempts. Presentations with suicidal ideation will also be examined (in a descriptive analysis) to ascertain whether a rise in suicidal ideation is commensurate with a fall in suicide attempts (which might indicate an increase in help-seeking behaviours). Death by suicide rates will also be examined to ensure that representations with a suicide attempt are not due to participants dying, but due to a potential improvement in mental health. For participants without a subsequent suicide attempt, the total number of days from enrolment to the last assessment (24 months) will be calculated. Self-reported levels of suicidality, depression, anxiety, stress, resilience, problem-solving skills, and self- and therapist-reported level of therapeutic engagement are also being examined. Psychometric data are collected at baseline, end of interventions, and 6,12, and 24 months. DISCUSSION: This project will move both ASSIP and Brief CBT from efficacy to effectiveness research, with clear aims of assessing the addition of two structured psychological interventions to treatment as usual, providing a cost-benefit analysis of the interventions, thus delivering outcomes providing a clear pathway for rapid translation of successful interventions. TRIALS REGISTRATION: ClinicalTrials.gov NCT04072666 . Registered on 28 August 2019.

A Discrete-Event, Simulated Social Agent-Based Network Transmission (DESSABNeT) model for communicable diseases: Method and validation using SARS-CoV-2 data in three large Australian cities.

IMPORTANCE: During pandemics Agent Based Models (ABMs) can model complex, fine-grained behavioural interactions occurring in social networks, that contribute to disease transmission by novel viruses such as SARS-CoV-2. OBJECTIVE: We present a new agent-based model (ABM) called the Discrete-Event, Simulated Social Agent based Network Transmission model (DESSABNeT) and demonstrate its ability to model the spread of COVID-19 in large cities like Sydney, Melbourne and Gold Coast. Our aim was to validate the model with its disease dynamics and underlying social network. DESIGN: DESSABNeT relies on disease transmission within simulated social networks. It employs an epidemiological SEIRD+M (Susceptible, exposed, infected, recovered, died and managed) structure. One hundred simulations were run for each city, with simulated social restrictions closely modelling real restrictions imposed in each location. MAIN OUTCOME(S) AND MEASURE(S): The mean predicted daily incidence of COVID-19 cases were compared to real case incidence data for each city. Reff and health service utilisation outputs were compared to the literature, or for the Gold Coast with daily incidence of hospitalisation. RESULTS: DESSABNeT modelled multiple physical distancing restrictions and predicted epidemiological outcomes of Sydney, Melbourne and the Gold Coast, validating this model for future simulation work. CONCLUSIONS AND RELEVANCE: DESSABNeT is a valid platform to model the spread of COVID-19 in large cities in Australia and potentially internationally. The platform is suitable to model different combinations of social restrictions, or to model contact tracing, predict, and plan for, the impact on hospital and ICU admissions, and deaths; and also the rollout of COVID-19 vaccines and optimal social restrictions during vaccination.

The impact of viral epidemics and pandemics on acute mental health service use: an integrative review.

The aim of this integrative review was to examine the impact of past viral epidemics on mental health, with a specific focus on changes in numbers of acute mental health presentations and mental health service recommendations in response to this, in the context of the COVID-19 pandemic. Following PRISMA methodology, databases were searched for relevant publications. A total of 83 articles with a range of methodologies were included to ensure broad coverage of this rapidly emerging research area. The literature supports an initial increase in mental health concerns which generally do not reach the threshold for diagnosis with a mental illness, but present to frontline telephone services. There is a potential delay before community and hospital-based mental health services see an increase in new or relapsing mental illness presentations. However vulnerable populations, such as people with pre-existing mental illness, are at increased risk of mental health issues during such public health crises. Many of the general recommendations distilled from the literature are closely aligned with existing strategic frameworks for mental health service provision. However, in review of these frameworks, gaps in the literature become more apparent, such as a failure to include people with lived experience, peer workers, and First Nations People in the COVID-19 mental health response.

Efficacy of the Zero Suicide framework in reducing recurrent suicide attempts: cross-sectional and time-to-recurrent-event analyses.

BACKGROUND: The Zero Suicide framework is a system-wide approach to prevent suicides in health services. It has been implemented worldwide but has a poor evidence-base of effectiveness. AIMS: To evaluate the effectiveness of the Zero Suicide framework, implemented in a clinical suicide prevention pathway (SPP) by a large public mental health service in Australia, in reducing repeated suicide attempts after an index attempt. METHOD: A total of 604 persons with 737 suicide attempt presentations were identified between 1 July and 31 December 2017. Relative risk for a subsequent suicide attempt within various time periods was calculated using cross-sectional analysis. Subsequently, a 10-year suicide attempt history (2009-2018) for the cohort was used in time-to-recurrent-event analyses. RESULTS: Placement on the SPP reduced risk for a repeated suicide attempt within 7 days (RR = 0.29; 95% CI 0.11-0.75), 14 days (RR = 0.38; 95% CI 0.18-0.78), 30 days (RR = 0.55; 95% CI 0.33-0.94) and 90 days (RR = 0.62; 95% CI 0.41-0.95). Time-to-recurrent event analysis showed that SPP placement extended time to re-presentation (HR = 0.65; 95% CI 0.57-0.67). A diagnosis of personality disorder (HR = 2.70; 95% CI 2.03-3.58), previous suicide attempt (HR = 1.78; 95% CI 1.46-2.17) and Indigenous status (HR = 1.46; 95% CI 0.98-2.25) increased the hazard for re-presentation, whereas older age decreased it (HR = 0.92; 95% CI 0.86-0.98). The effect of the SPP was similar across all groups, reducing the risk of re-presentation to about 65% of that seen in those not placed on the SPP. CONCLUSIONS: This paper demonstrates a reduction in repeated suicide attempts after an index attempt and a longer time to a subsequent attempt for those receiving multilevel care based on the Zero Suicide framework.

Synergistic effects of low-level stress and a Western diet on metabolic homeostasis, mood, and myocardial ischemic tolerance.

How low-level psychological stress and overnutrition interact in influencing cardiometabolic disease is unclear. Mechanistic overlaps suggest potential synergies; however, findings are contradictory. We test whether low-level stress and Western diet (WD) feeding synergistically influence homeostasis, mood, and myocardial ischemic tolerance. Male C57BL6/J mice were fed a control diet or WD (32%/57%/11% calories from fat/carbohydrates/protein) for 12 wk, with subgroups restrained for 30 min/day over the final 3 wk. Metabolism, behavior, tolerance of perfused hearts to ischemia-reperfusion (I/R), and cardiac "death proteins" were assessed. The WD resulted in insignificant trends toward increased body weight (+5%), glucose (+40%), insulin (+40%), triglycerides (+15%), and cholesterol (+20%) and reduced leptin (-20%) while significantly reducing insulin sensitivity [100% rise in homeostasis model assessment of insulin resistance (HOMA-IR), P < 0.05]. Restraint did not independently influence metabolism while increasing HOMA-IR a further 50% (and resulting in significant elevations in insulin and glucose to 60-90% above control) in WD mice (P < 0.05), despite blunting weight gain in control and WD mice. Anxiogenesis with restraint or WD was nonadditive, whereas anhedonia (reduced sucrose consumption) only arose with their combination. Neuroinflammation markers (hippocampal TNF-α, Il-1b) were unchanged. Myocardial I/R tolerance was unaltered with stress or WD alone, whereas the combination worsened dysfunction and oncosis [lactate dehydrogenase (LDH) efflux]. Apoptosis (nucleosome accumulation) and death protein expression (BAK, BAX, BCL-2, RIP-1, TNF-α, cleaved caspase-3, and PARP) were unchanged. We conclude that mild, anxiogenic yet cardio-metabolically "benign" stress interacts synergistically with a WD to disrupt homeostasis, promote anhedonia (independently of neuroinflammation), and impair myocardial ischemic tolerance (independently of apoptosis and death protein levels).

Suicidal Presentations to Emergency Departments in a Large Australian Public Health Service over 10 Years.

This paper presents trends and characteristics for 32,094 suicidal presentations to two Emergency Departments (EDs) in a large health service in Australia across a 10-year period (2009-2018). Prevalence of annual suicidal presentations and for selected groups of consumers (by sex, age groups, and ethnicity) was determined from a machine learning diagnostic algorithm developed for this purpose and a Bayesian estimation approach. A linear increase in the number of suicidal presentations over 10 years was observed, which was 2.8-times higher than the increase noted in all ED presentations and 6.1-times higher than the increase in the population size. Females had higher presentation rates than males, particularly among younger age groups. The highest rates of presentations were by persons aged 15-24. Overseas-born persons had around half the rates of suicidal presentations than Australian-born persons, and Indigenous persons had 2.9-times higher rates than non-Indigenous persons. Of all presenters, 70.6% presented once, but 5.7% had five or more presentations. Seasonal distribution of presentations showed a peak at the end of spring and a decline in winter months. These findings can inform the allocation of health resources and guide the development of suicide prevention strategies for people presenting to hospitals in suicidal crisis.

Short stay unit for patients in acute mental health crisis: A case-control study of readmission rates.

INTRODUCTION: Past evaluations of psychiatric short stay units have shown positive outcomes for patients, yet very little is known about the factors related to readmissions. METHODS: A Short Stay Pathway (SSP) has been introduced on the Gold Coast, Australia, for patients in acute mental health crisis with admissions of up to 3 days. Rates of readmissions within 28 days were compared for SSP patients (N = 678), and a diagnosis-matched control group of patients from acute mental health beds (N = 1356). Demographic and clinical factors were considered as predictors of subsequent readmissions. RESULTS: Average length of stay for SSP patients was 3.4 days, compared to 7.6 days in the control group. 10.6% of SSP patients and 18.4% of the control group were readmitted within 28 days (P < .001). For both groups, a 7-day follow up significantly reduced readmissions (P < .05). Indigenous patients on SSP had higher odds of readmissions than non-Indigenous patients (P < .05), and a diagnosis of a personality disorder increased readmission in the control group but not the SSP group (P < .001). DISCUSSION: SSP reduced repeated hospitalizations for patients in acute crisis by 42%. An identification of factors related to future admissions can inform future tailoring of this model of care to subgroups of patients.

The brain-adipocyte-gut network: Linking obesity and depression subtypes.

Major depressive disorder (MDD) and obesity are dominant and inter-related health burdens. Obesity is a risk factor for MDD, and there is evidence MDD increases risk of obesity. However, description of a bidirectional relationship between obesity and MDD is misleading, as closer examination reveals distinct unidirectional relationships in MDD subtypes. MDD is frequently associated with weight loss, although obesity promotes MDD. In contrast, MDD with atypical features (MDD-AF) is characterised by subsequent weight gain and obesity. The bases of these distinct associations remain to be detailed, with conflicting findings clouding interpretation. These associations can be viewed within a systems biology framework-the psycho-immune neuroendocrine (PINE) network shared between MDD and metabolic disorders. Shared PINE subsystem perturbations may underlie increased MDD in overweight and obese people (obesity-associated depression), while obesity in MDD-AF (depression-associated obesity) involves more complex interactions between behavioural and biomolecular changes. In the former, the chronic PINE dysfunction triggering MDD is augmented by obesity-dependent dysregulation in shared networks, including inflammatory, leptin-ghrelin, neuroendocrine, and gut microbiome systems, influenced by chronic image-associated psychological stress (particularly in younger or female patients). In MDD-AF, behavioural dysregulation, including hypersensitivity to interpersonal rejection, fundamentally underpins energy imbalance (involving hyperphagia, lethargy, hypersomnia), with evolving obesity exaggerating these drivers via positive feedback (and potentially augmenting PINE disruption). In both settings, sex and age are important determinants of outcome, associated with differences in emotional versus cognitive dysregulation. A systems biology approach is recommended for further research into the pathophysiological networks underlying MDD and linking depression and obesity.