Psychiatry - Research Publications
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ItemOptimizing Engagement in an Online Dietary Intervention for Depression (My Food & Mood Version 3.0): Cohort Study(JMIR PUBLICATIONS, INC, 2021-03-31)BACKGROUND: Online interventions can be a cost-effective and efficient way to deliver programs to large numbers of people regardless of geographic location. However, attrition in web-based interventions is often an issue. Developing ways to keep participants engaged is important for ensuring validity and limiting potential biases. We developed a web-based dietary intervention as part of The My Food & Mood study which aimed to optimize ways to engage participants with low mood or depressive symptoms to promote dietary behavior change. Different versions of the My Food & Mood program were tested during optimization. Iterations were developed based on user feedback and usage analysis. OBJECTIVE: The purpose of this study was to compare engagement and nonusage attrition across 4 program iterations-which differed by platform format, delivery mode, and activity type-to create an optimized version. METHODS: Each program version contained modular videos with key activities with respect to implementing behavior change techniques of equivalent levels of required participation and length: version 1.0, desktop program and smartphone app; version 2.1, desktop or smartphone program; version 2.2, desktop program; and version 3.0, smartphone app. Adults with PHQ-8 scores of 5 or greater were recruited online and assigned to 1 of the 4 versions. Participants were asked to use the program for 8 weeks and complete measures at weeks 4 and 8. Engagement data were collected from the web-based platform system logs and customized reports. Cox regression survival analysis examined nonusage attrition and Kruskal-Wallis tests compared engagement across each cohort. RESULTS: A total of 614 adults participated. Kruskal-Wallis tests showed significant differences across the 4 cohorts in all engagement measures. The smartphone app (version 3.0) had the greatest engagement as measured by weeks engaged, total usage time, total time key activities, number of active sessions, percentage of activities completed against protocol, goals completed, and percentage of videos watched. Cox regression multivariate survival analysis showed referral from a health practitioner (hazard ratio [HR] 0.344, P=.001) and greater proficiency with computers (HR 0.796, P=.049) reduced the risk of nonusage attrition. Computer confidence was associated with an increased risk of nonusage attrition. CONCLUSIONS: My Food & Mood version 3.0, a dietary intervention delivered via smartphone app with self-monitoring tools for diet quality and mood monitoring, was the version with greatest engagement in a population with low mood or depression. The iterative design techniques employed and analysis of feedback from participants resulted in a program that achieved lower rates of nonusage attrition and higher rates of intensity of use.
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ItemNo Preview AvailableThe cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2021-08)An analysis of published data appertaining to the cytokine storms of COVID-19, H1N1 influenza, cytokine release syndrome (CRS), and macrophage activation syndrome (MAS) reveals many common immunological and biochemical abnormalities. These include evidence of a hyperactive coagulation system with elevated D-dimer and ferritin levels, disseminated intravascular coagulopathy (DIC) and microthrombi coupled with an activated and highly permeable vascular endothelium. Common immune abnormalities include progressive hypercytokinemia with elevated levels of TNF-α, interleukin (IL)-6, and IL-1β, proinflammatory chemokines, activated macrophages and increased levels of nuclear factor kappa beta (NFκB). Inflammasome activation and release of damage associated molecular patterns (DAMPs) is common to COVID-19, H1N1, and MAS but does not appear to be a feature of CRS. Elevated levels of IL-18 are detected in patients with COVID-19 and MAS but have not been reported in patients with H1N1 influenza and CRS. Elevated interferon-γ is common to H1N1, MAS, and CRS but levels of this molecule appear to be depressed in patients with COVID-19. CD4+ T, CD8+ and NK lymphocytes are involved in the pathophysiology of CRS, MAS, and possibly H1N1 but are reduced in number and dysfunctional in COVID-19. Additional elements underpinning the pathophysiology of cytokine storms include Inflammasome activity and DAMPs. Treatment with anakinra may theoretically offer an avenue to positively manipulate the range of biochemical and immune abnormalities reported in COVID-19 and thought to underpin the pathophysiology of cytokine storms beyond those manipulated via the use of, canakinumab, Jak inhibitors or tocilizumab. Thus, despite the relative success of tocilizumab in reducing mortality in COVID-19 patients already on dexamethasone and promising results with Baricitinib, the combination of anakinra in combination with dexamethasone offers the theoretical prospect of further improvements in patient survival. However, there is currently an absence of trial of evidence in favour or contravening this proposition. Accordingly, a large well powered blinded prospective randomised controlled trial (RCT) to test this hypothesis is recommended.
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ItemNo Preview AvailableCan endolysosomal deacidification and inhibition of autophagy prevent severe COVID-19?(PERGAMON-ELSEVIER SCIENCE LTD, 2020-12-01)The possibility is examined that immunomodulatory pharmacotherapy may be clinically useful in managing the pandemic coronavirus disease 2019 (COVID-19), known to result from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense single-stranded RNA virus. The dominant route of cell entry of the coronavirus is via phagocytosis, with ensconcement in endosomes thereafter proceeding via the endosomal pathway, involving transfer from early (EEs) to late endosomes (LEs) and ultimately into lysosomes via endolysosomal fusion. EE to LE transportation is a rate-limiting step for coronaviruses. Hence inhibition or dysregulation of endosomal trafficking could potentially inhibit SARS-CoV-2 replication. Furthermore, the acidic luminal pH of the endolysosomal system is critical for the activity of numerous pH-sensitive hydrolytic enzymes. Golgi sub-compartments and Golgi-derived secretory vesicles also depend on being mildly acidic for optimal function and structure. Activation of endosomal toll-like receptors by viral RNA can upregulate inflammatory mediators and contribute to a systemic inflammatory cytokine storm, associated with a worsened clinical outcome in COVID-19. Such endosomal toll-like receptors could be inhibited by the use of pharmacological agents which increase endosomal pH, thereby reducing the activity of acid-dependent endosomal proteases required for their activity and/or assembly, leading to suppression of antigen-presenting cell activity, decreased autoantibody secretion, decreased nuclear factor-kappa B activity and decreased pro-inflammatory cytokine production. It is also noteworthy that SARS-CoV-2 inhibits autophagy, predisposing infected cells to apoptosis. It is therefore also suggested that further pharmacological inhibition of autophagy might encourage the apoptotic clearance of SARS-CoV-2-infected cells.
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ItemNo Preview AvailableThe pathophysiology of SARS-CoV-2: A suggested model and therapeutic approach(PERGAMON-ELSEVIER SCIENCE LTD, 2020-10-01)In this paper, a model is proposed of the pathophysiological processes of COVID-19 starting from the infection of human type II alveolar epithelial cells (pneumocytes) by SARS-CoV-2 and culminating in the development of ARDS. The innate immune response to infection of type II alveolar epithelial cells leads both to their death by apoptosis and pyroptosis and to alveolar macrophage activation. Activated macrophages secrete proinflammatory cytokines and chemokines and tend to polarise into the inflammatory M1 phenotype. These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space. Activated vascular endothelial cells become a source of proinflammatory cytokines and reactive oxygen species (ROS) and contribute to the development of coagulopathy, systemic sepsis, a cytokine storm and ARDS. Pulmonary activated platelets are also an important source of proinflammatory cytokines and ROS, as well as exacerbating pulmonary neutrophil-mediated inflammatory responses and contributing to systemic sepsis by binding to neutrophils to form platelet-neutrophil complexes (PNCs). PNC formation increases neutrophil recruitment, activation priming and extraversion of these immune cells into inflamed pulmonary tissue, thereby contributing to ARDS. Sequestered PNCs cause the development of a procoagulant and proinflammatory environment. The contribution to ARDS of increased extracellular histone levels, circulating mitochondrial DNA, the chromatin protein HMGB1, decreased neutrophil apoptosis, impaired macrophage efferocytosis, the cytokine storm, the toll-like receptor radical cycle, pyroptosis, necroinflammation, lymphopenia and a high Th17 to regulatory T lymphocyte ratio are detailed.
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ItemThe Associations between Dairy Product Consumption and Biomarkers of Inflammation, Adipocytokines, and Oxidative Stress in Children: A Cross-Sectional Study(MDPI, 2020-10)The association between dairy product consumption and biomarkers of inflammation, adipocytokines, and oxidative stress is poorly studied in children. Therefore, these associations were examined in a representative subsample of 1338 schoolchildren with a mean age of 11.5 (±0.7) years in the Healthy Growth Study. Information on dairy product consumption was collected by dietary recalls. Total dairy consumption was calculated by summing the intake of milk, yogurt, and cheese. Inflammatory markers, i.e., high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and adipocytokines, i.e., leptin, adiponectin, and the antioxidant enzyme glutathione peroxidase (GPx) were analysed. Due to the skewed distribution hs-CRP, IL-6, and leptin were log transformed. Multivariable regression analyses adjusted for age, sex, energy intake, physical activity, parental education, Tanner stage, and fat mass were used to assess the associations between consumption of total dairy, milk, yogurt, cheese, and markers of inflammation, adipocytokines, oxidative stress, and adiponectin-leptin ratio. Our results showed that milk consumption was inversely associated with leptin (β: -0.101; 95% CI: -0.177, -0.025, p = 0.009) and positively associated with the adiponectin-leptin ratio (β: 0.116; 95% CI: 0.020, 0.211; p = 0.018), while total dairy, cheese, and yogurt consumption were not associated with inflammatory, adipocytokine, or antioxidant markers. Further prospective studies are needed to confirm these results.
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ItemEconomic evaluation of a dietary intervention for adults with major depression (the "SMILES" trial)(BMC, 2018-05-22)BACKGROUND: Recently, the efficacy of dietary improvement as a therapeutic intervention for moderate to severe depression was evaluated in a randomised controlled trial. The SMILES trial demonstrated a significant improvement in Montgomery-Åsberg Depression Rating Scale scores favouring the dietary support group compared with a control group over 12 weeks. We used data collected within the trial to evaluate the cost-effectiveness of this novel intervention. METHODS: In this prospective economic evaluation, sixty-seven adults meeting DSM-IV criteria for a major depressive episode and reporting poor dietary quality were randomised to either seven sessions with a dietitian for dietary support or to an intensity matched social support (befriending) control condition. The primary outcome was Quality Adjusted Life Years (QALYs) as measured by the AQoL-8D, completed at baseline and 12 week follow-up (endpoint) assessment. Costs were evaluated from health sector and societal perspectives. The time required for intervention delivery was costed using hourly wage rates applied to the time in counselling sessions. Food and travel costs were also included in the societal perspective. Data on medications, medical services, workplace absenteeism and presenteesim (paid and unpaid) were collected from study participants using a resource-use questionnaire. Standard Australian unit costs for 2013/2014 were applied. Incremental cost-effectiveness ratios (ICERs) were calculated as the difference in average costs between groups divided by the difference in average QALYs. Confidence intervals were calculated using a non-parametric bootstrap procedure. RESULTS: Compared with the social support condition, average total health sector costs were $856 lower (95% CI -1247 to - 160) and average societal costs were $2591 lower (95% CI -3591 to - 198) for those receiving dietary support. These differences were driven by lower costs arising from fewer allied and other health professional visits and lower costs of unpaid productivity. Significant differences in mean QALYs were not found between groups. However, 68 and 69% of bootstrap iterations showed the dietary support intervention was dominant (additional QALYs at less cost) from the health sector and societal perspectives. CONCLUSIONS: This novel dietary support intervention was found to be likely cost-effective as an adjunctive treatment for depression from both health sector and societal perspectives. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820 . Registered on 29 February 2012.
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ItemThe SMILES trial: an important first step(BMC, 2018-12-28)The SMILES trial was the first intervention study to test dietary improvement as a treatment strategy for depression. Molendijk et al. propose that expectation bias and difficulties with blinding might account for the large effect size. While we acknowledge the issue of expectation bias in lifestyle intervention trials and indeed discuss this as a key limitation in our paper, we observed a strong correlation between dietary change and change in depression scores, which we argue is consistent with a causal effect and we believe unlikely to be an artefact of inadequate blinding. Since its publication, our results have been largely replicated and our recent economic evaluation of SMILES suggests that the benefits of our approach extend beyond depression. We argue that the SMILES trial should be considered an important, albeit preliminary, first step in the field of nutritional psychiatry research.
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ItemDiet and Common Mental Disorders: The imperative to Translate Evidence into Action(FRONTIERS MEDIA SA, 2016-04-29)
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ItemLifestyle medicine for depression(BioMed Central Ltd., 2014)The prevalence of depression appears to have increased over the past three decades. While this may be an artefact of diagnostic practices, it is likely that there are factors about modernity that are contributing to this rise. There is now compelling evidence that a range of lifestyle factors are involved in the pathogenesis of depression. Many of these factors can potentially be modified, yet they receive little consideration in the contemporary treatment of depression, where medication and psychological intervention remain the first line treatments. “Lifestyle Medicine” provides a nexus between public health promotion and clinical treatments, involving the application of environmental, behavioural, and psychological principles to enhance physical and mental wellbeing. This may also provide opportunities for general health promotion and potential prevention of depression. In this paper we provide a narrative discussion of the major components of Lifestyle Medicine, consisting of the evidence-based adoption of physical activity or exercise, dietary modification, adequate relaxation/sleep and social interaction, use of mindfulness-based meditation techniques, and the reduction of recreational substances such as nicotine, drugs, and alcohol. We also discuss other potential lifestyle factors that have a more nascent evidence base, such as environmental issues (e.g. urbanisation, and exposure to air, water, noise, and chemical pollution), and the increasing human interface with technology. Clinical considerations are also outlined. While data supports that some of these individual elements are modifiers of overall mental health, and in many cases depression, rigorous research needs to address the long-term application of Lifestyle Medicine for depression prevention and management. Critically, studies exploring lifestyle modification involving multiple lifestyle elements are needed. While the judicious use of medication and psychological techniques are still advocated, due to the complexity of human illness/wellbeing, the emerging evidence encourages a more integrative approach for depression, and an acknowledgment that lifestyle modification should be a routine part of treatment and preventative efforts.
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ItemAltered cardiac autonomic nervous function in depression(BMC, 2013-07-10)BACKGROUND: Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia. METHODS: Individuals (n = 53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score ≥20 and a Zung Self-Rating Depression Scale score > 53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals > 50 ms different from preceding interval (pNN50). Pearson's correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)). RESULTS: The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P<.05). The mean value of the LF in the depression group was higher than the in control group (P<.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P<.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P<.05), particularly supraventricular arrhythmias. CONCLUSIONS: Our findings suggest that depression is accompanied by dysfunction of the cardiac autonomic nervous system, and further, that depression severity is linked to severity of this dysfunction. Individuals with depression appear to be susceptible to premature atrial and/or ventricular disease.