Psychiatry - Research Publications

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    Economic evaluation of a dietary intervention for adults with major depression (the "SMILES" trial)
    Chatterton, ML ; Mihalopoulos, C ; O'Neil, A ; Itsiopoulos, C ; Opie, R ; Castle, D ; Dash, S ; Brazionis, L ; Berk, M ; Jacka, F (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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    The SMILES trial: an important first step
    Jacka, FN ; O'Neil, A ; Itsiopoulos, C ; Opie, R ; Cotton, S ; Mohebbi, M ; Castle, D ; Dash, S ; Mihalopoulos, C ; Chatterton, ML ; Brazionis, L ; Dean, OM ; Hodge, A ; Berk, M (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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    Diet and Common Mental Disorders: The imperative to Translate Evidence into Action
    Dash, SR ; O'Neil, A ; Jacka, FN (FRONTIERS MEDIA SA, 2016-04-29)
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    The impact of statins on psychological wellbeing: a systematic review and meta-analysis
    O'Neil, A ; Sanna, L ; Redlich, C ; Sanderson, K ; Jacka, F ; Williams, LJ ; Pasco, JA ; Berk, M (BMC, 2012-12-03)
    BACKGROUND: Cholesterol-lowering medications such as statins have anti-inflammatory and antioxidant properties, which may be beneficial for treating depression and improving mood. However, evidence regarding their effects remains inconsistent, with some studies reporting links to mood disturbances. We aimed to conduct a meta-analysis to determine the impact of statins on psychological wellbeing of individuals with or without hypercholesterolemia. METHODS: Articles were identified using medical, health, psychiatric and social science databases, evaluated for quality, and data were synthesized and analyzed in RevMan-5 software using a random effects model. RESULTS: The 7 randomized controlled trials included in the analysis represented 2,105 participants. A test for overall effect demonstrated no statistically significant differences in psychological wellbeing between participants receiving statins or a placebo (standardized mean difference (SMD) = -0.08, 95% CI -0.29 to 0.12; P = 0.42). Sensitivity analyses were conducted to separately analyze depression (n = 5) and mood (n = 2) outcomes; statins were associated with statistically significant improvements in mood scores (SMD = -0.43, 95% CI -0.61 to -0.24). CONCLUSIONS: Our findings refute evidence of negative effects of statins on psychological outcomes, providing some support for mood-related benefits. Future studies could examine the effects of statins in depressed populations.
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    So depression is an inflammatory disease, but where does the inflammation come from?
    Berk, M ; Williams, LJ ; Jacka, FN ; O'Neil, A ; Pasco, JA ; Moylan, S ; Allen, NB ; Stuart, AL ; Hayley, AC ; Byrne, ML ; Maes, M (BMC, 2013-09-12)
    BACKGROUND: We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is 'what is the source of this chronic low-grade inflammation?' DISCUSSION: This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency. SUMMARY: The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.
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    A randomised, controlled trial of a dietary intervention for adults with major depression (the "SMILES" trial): study protocol
    O'Neil, A ; Berk, M ; Itsiopoulos, C ; Castle, D ; Opie, R ; Pizzinga, J ; Brazionis, L ; Hodge, A ; Mihalopoulos, C ; Chatterton, ML ; Dean, OM ; Jacka, FN (BMC, 2013-04-15)
    BACKGROUND: Despite increased investment in its recognition and treatment, depression remains a substantial health and economic burden worldwide. Current treatment strategies generally focus on biological and psychological pathways, largely neglecting the role of lifestyle. There is emerging evidence to suggest that diet and nutrition play an important role in the risk, and the genesis, of depression. However, there are limited data regarding the therapeutic impact of dietary changes on existing mental illness. Using a randomised controlled trial design, we aim to investigate the efficacy and cost-efficacy of a dietary program for the treatment of Major Depressive Episodes (MDE). METHODS/DESIGN: One hundred and seventy six eligible participants suffering from current MDE are being randomised into a dietary intervention group or a social support group. Depression status is assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (Non Patient Edition) (SCID-I/NP). The intervention consists of 7 individual nutrition consulting sessions (of approximately 60 minutes), delivered by an Accredited Practising Dietitian (APD). Sessions commence within one week of baseline assessment. The intervention focuses on advocating a healthy diet based on the Australian Dietary Guidelines and the Dietary Guidelines for Adults in Greece. The control condition comprises a befriending protocol using the same visit schedule and length as the diet intervention. The study is being conducted at two locations in Victoria, Australia (a metropolitan and regional centre). Data collection occurs at baseline (pre-intervention), 3-months (post-intervention) and 6- months. The primary endpoint is MADRS scores at 3 months. A cost consequences analysis will determine the economic value of the intervention. DISCUSSION: If efficacious, this program could provide an alternative or adjunct treatment strategy for the management of this highly prevalent mental disorder; the benefits of which could extend to the management of common co-morbidities including cardiovascular disease (CVD), obesity, and type 2 diabetes. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820.
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    The association between diet quality, dietary patterns and depression in adults: a systematic review
    Quirk, SE ; Williams, LJ ; O'Neil, A ; Pasco, JA ; Jacka, FN ; Housden, S ; Berk, M ; Brennan, SL (BMC, 2013-06-27)
    BACKGROUND: Recent evidence suggests that diet modifies key biological factors associated with the development of depression; however, associations between diet quality and depression are not fully understood. We performed a systematic review to evaluate existing evidence regarding the association between diet quality and depression. METHOD: A computer-aided literature search was conducted using Medline, CINAHL, and PsycINFO, January 1965 to October 2011, and a best-evidence analysis performed. RESULTS: Twenty-five studies from nine countries met eligibility criteria. Our best-evidence analyses found limited evidence to support an association between traditional diets (Mediterranean or Norwegian diets) and depression. We also observed a conflicting level of evidence for associations between (i) a traditional Japanese diet and depression, (ii) a "healthy" diet and depression, (iii) a Western diet and depression, and (iv) individuals with depression and the likelihood of eating a less healthy diet. CONCLUSION: To our knowledge, this is the first review to synthesize and critically analyze evidence regarding diet quality, dietary patterns and depression. Further studies are urgently required to elucidate whether a true causal association exists.
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    Preventing mental health problems in offspring by targeting dietary intake of pregnant women
    O'Neil, A ; Itsiopoulos, C ; Skouteris, H ; Opie, RS ; McPhie, S ; Hill, B ; Jacka, FN (BMC, 2014-11-14)
    BACKGROUND: The concept of 'early life programming' considers the importance of very early environmental exposures throughout the gestational period on the subsequent health outcomes of offspring. The role of maternal dietary intake, specifically, has been highlighted after recent studies have shown maternal diet quality to predict mental health problems in offspring. Even in the pre-conception period, maternal nutrition can have permanent and sustained phenotypic consequences for offspring. DISCUSSION: Here, we consider these findings in the context of the primary prevention of mental disorders and argue that interventions that target maternal diet could be of significant value. SUMMARY: It is clear that, in order to reduce the burden of mental health issues across the lifespan, urgent action is required, particularly in the field of prevention. We thus call for the application and evaluation of targeted, primary prevention strategies that focus on dietary intake with the view to improve mental health outcomes of mothers and offspring during the postnatal period and beyond.
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    Depression is a risk factor for incident coronary heart disease in women: An 18-year longitudinal study
    O'Neil, A ; Fisher, AJ ; Kibbey, KJ ; Jacka, FN ; Kotowicz, MA ; Williams, LJ ; Stuart, AL ; Berk, M ; Lewandowski, PA ; Taylor, CB ; Pasco, JA (ELSEVIER SCIENCE BV, 2016-05-15)
    BACKGROUND: According to a recent position paper by the American Heart Association, it remains unclear whether depression is a risk factor for incident Coronary Heart Disease (CHD). We assessed whether a depressive disorder independently predicts 18-year incident CHD in women. METHOD: A prospective longitudinal study of 860 women enrolled in the Geelong Osteoporosis Study (1993-2011) was conducted. Participants were derived from an age-stratified, representative sample of women (20-94 years) randomly selected from electoral rolls in South-Eastern Australia. The exposure was a diagnosis of a depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Outcomes data were collected from hospital medical records: (1) PRIMARY OUTCOME: a composite measure of cardiac death, non-fatal Myocardial Infarction or coronary intervention. (2) Secondary outcome: any cardiac event (un/stable angina, cardiac event not otherwise defined) occurring over the study period. RESULTS: Seven participants were excluded based on CHD history. Eighty-three participants (9.6%) recorded ≥1 cardiac event over the study period; 47 had a diagnosis that met criteria for inclusion in the primary analysis. Baseline depression predicted 18-year incidence, adjusting for (1) anxiety (adj. OR:2.39; 95% CIs:1.19-4.82), plus (2) typical risk factors (adj. OR:3.22; 95% CIs:1.45-6.93), plus (3) atypical risk factors (adj. OR:3.28; 95% CIs:1.36-7.90). This relationship held when including all cardiac events. No relationship was observed between depression and recurrent cardiac events. CONCLUSION: The results of this study support the contention that depression is an independent risk factor for CHD incidence in women. Moreover, the strength of association between depression and CHD incidence was of a greater magnitude than any typical and atypical risk factor.
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    Statin and Aspirin Use and the Risk of Mood Disorders among Men
    Williams, LJ ; Pasco, JA ; Mohebbi, M ; Jacka, FN ; Stuart, AL ; Venugopal, K ; O'Neil, A ; Berk, M (OXFORD UNIV PRESS, 2016-06)
    BACKGROUND: There is a growing understanding that depression is associated with systemic inflammation. Statins and aspirin have anti-inflammatory properties. Given these agents have been shown to reduce the risk of a number of diseases characterized by inflammation, we aimed to determine whether a similar relationship exists for mood disorders (MD). METHODS: This study examined data collected from 961 men (24-98 years) participating in the Geelong Osteoporosis Study. MD were identified using a semistructured clinical interview (SCID-I/NP). Anthropometry was measured and information on medication use and lifestyle factors was obtained via questionnaire. Two study designs were utilized: a nested case-control and a retrospective cohort study. RESULTS: In the nested case-control study, exposure to statin and aspirin was documented for 9 of 142 (6.3%) cases and 234 of 795 (29.4%) controls (P < .001); after adjustment for age, exposure to these anti-inflammatory agents was associated with reduced likelihood of MD (OR 0.2, 95%CI 0.1-0.5). No effect modifiers or other confounders were identified. In the retrospective cohort study of 836 men, among the 210 exposed to statins or aspirin, 6 (2.9%) developed de novo MD during 1000 person-years of observation, whereas among 626 nonexposed, 34 (5.4%) developed de novo MD during 3071 person-years of observation. The hazard ratio for de novo MD associated with exposure to anti-inflammatory agents was 0.55 (95%CI 0.23-1.32). CONCLUSIONS: This study provides both cross-sectional and longitudinal evidence consistent with the hypothesis that statin and aspirin use is associated with a reduced risk of MD.