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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    Lifestyle medicine for depression
    Sarris, J ; O'Neil, A ; Coulson, CE ; Schweitzer, I ; Berk, M (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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    Altered cardiac autonomic nervous function in depression
    Wang, Y ; Zhao, X ; O'Neil, A ; Turner, A ; Liu, X ; Berk, M (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.
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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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    Assessing Regional Cerebral Blood Flow in Depression Using 320-Slice Computed Tomography
    Wang, Y ; Zhang, H ; Tang, S ; Liu, X ; O'Neil, A ; Turner, A ; Chai, F ; Chen, F ; Berk, M ; Chen, H (PUBLIC LIBRARY SCIENCE, 2014-09-24)
    While there is evidence that the development and course of major depressive disorder (MDD) symptomatology is associated with vascular disease, and that there are changes in energy utilization in the disorder, the extent to which cerebral blood flow is changed in this condition is not clear. This study utilized a novel imaging technique previously used in coronary and stroke patients, 320-slice Computed-Tomography (CT), to assess regional cerebral blood flow (rCBF) in those with MDD and examine the pattern of regional cerebral perfusion. Thirty nine participants with depressive symptoms (Hamilton Depression Rating Scale 24 (HAMD24) score > 20, and Self-Rating Depression Scale (SDS) score > 53) and 41 healthy volunteers were studied. For all subjects, 3 ml of venous blood was collected to assess hematological parameters. Transcranial Doppler (TCD) ultrasound was utilized to measure parameters of cerebral artery rCBFV and analyse the Pulsatility Index (PI). 16 subjects (8 =  MDD; 8 =  healthy) also had rCBF measured in different cerebral artery regions using 320-slice CT. Differences among groups were analyzed using ANOVA and Pearson's tests were employed in our statistical analyses. Compared with the control group, whole blood viscosity (including high\middle\low shear rate)and hematocrit (HCT) were significantly increased in the MDD group. PI values in different cerebral artery regions and parameters of rCBFV in the cerebral arteries were decreased in depressive participants, and there was a positive relationship between rCBFV and the corresponding vascular rCBF in both gray and white matter. rCBF of the left gray matter was lower than that of the right in MDD. Major depression is characterized by a wide range of CBF impairments and prominent changes in gray matter blood flow. 320-slice CT appears to be a valid and promising tool for measuring rCBF, and could thus be employed in psychiatric settings for biomarker and treatment response purposes.
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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.