- Centre for Youth Mental Health - Research Publications
Centre for Youth Mental Health - Research Publications
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ItemThe Beyond Ageing Project Phase 2-a double-blind, selective prevention, randomised, placebo-controlled trial of omega-3 fatty acids and sertraline in an older age cohort at risk for depression: study protocol for a randomized controlled trialCockayne, NL ; Duffy, SL ; Bonomally, R ; English, A ; Amminger, PG ; Mackinnon, A ; Christensen, HM ; Naismith, SL ; Hickie, IB (BMC, 2015-06-03)BACKGROUND: Late-life depression is associated with high rates of morbidity, premature mortality, disability, functional decline, caregiver burden and increased health care costs. While clinical and public health approaches are focused on prevention or early intervention strategies, the ideal method of intervention remains unclear. No study has set out to evaluate the role of neurobiological agents in preventing depressive symptoms in older populations at risk of depression. METHODS/DESIGN: Subjects with previously reported sub-threshold depressive symptoms, aged 60 to 74 years, will be screened to participate in a single-centre, double-blind, randomised controlled trial with three parallel groups involving omega-3 fatty acid supplementation or sertraline hydrochloride, compared with matching placebo. Subjects will be excluded if they have current depression or suicide ideation; are taking antidepressants or any supplement containing omega-3 fatty acid; or have a prior history of stroke or other serious cerebrovascular or cardiovascular disease, neurological disease, significant psychiatric disease (other than depression) or neurodegenerative disease. The trial will consist of a 12 month treatment phase with follow-up at three months and 12 months to assess outcome events. At three months, subjects will undergo structural neuroimaging to assess whether treatment effects on depressive symptoms correlate with brain changes. Additionally, proton spectroscopy techniques will be used to capture brain-imaging markers of the biological effects of the interventions. The trial will be conducted in urban New South Wales, Australia, and will recruit a community-based sample of 450 adults. Using intention-to-treat methods, the primary endpoint is an absence of clinically relevant depression scores at 12 months between the omega-3 fatty acid and sertraline interventions and the placebo condition. DISCUSSION: The current health, social and economic costs of late-life depression make prevention imperative from a public health perspective. This innovative trial aims to address the long-neglected area of prevention of depression in older adults. The interventions are targeted to the pathophysiology of disease, and regardless of the effect size of treatment, the outcomes will offer major scientific advances regarding the neurobiological action of these agents. The main results are expected to be available in 2017. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12610000032055 (12 January 2010).
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ItemPerformance of joint modelling of time-to-event data with time-dependent predictors: an assessment based on transition to psychosis dataYuen, HP ; Mackinnon, A (PEERJ INC, 2016-10-19)Joint modelling has emerged to be a potential tool to analyse data with a time-to-event outcome and longitudinal measurements collected over a series of time points. Joint modelling involves the simultaneous modelling of the two components, namely the time-to-event component and the longitudinal component. The main challenges of joint modelling are the mathematical and computational complexity. Recent advances in joint modelling have seen the emergence of several software packages which have implemented some of the computational requirements to run joint models. These packages have opened the door for more routine use of joint modelling. Through simulations and real data based on transition to psychosis research, we compared joint model analysis of time-to-event outcome with the conventional Cox regression analysis. We also compared a number of packages for fitting joint models. Our results suggest that joint modelling do have advantages over conventional analysis despite its potential complexity. Our results also suggest that the results of analyses may depend on how the methodology is implemented.
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ItemImproving Mood with Physical ACTivity (IMPACT) trial: a cluster randomised controlled trial to determine the effectiveness of a brief physical activity behaviour change intervention on depressive symptoms in young people, compared with psychoeducation, in addition to routine clinical care within youth mental health services - a protocol studyParker, AG ; Markulev, C ; Rickwood, DJ ; Mackinnon, A ; Purcell, R ; Alvarez-Jimenez, M ; Yung, AR ; McGorry, P ; Hetrick, SE ; Jorm, A (BMJ PUBLISHING GROUP, 2019-10-01)INTRODUCTION: Depression is highly prevalent and the leading contributor to the burden of disease in young people worldwide, making it an ongoing priority for early intervention. As the current evidence-based interventions of medication and psychological therapy are only modestly effective, there is an urgent need for additional treatment strategies. This paper describes the rationale of the Improving Mood with Physical ACTivity (IMPACT) trial. The primary aim of the IMPACT trial is to determine the effectiveness of a physical activity intervention compared with psychoeducation, in addition to routine clinical care, on depressive symptoms in young people. Additional aims are to evaluate the intervention effects on anxiety and functional outcomes and examine whether changes in physical activity mediate improvements in depressive symptoms. METHODS AND ANALYSIS: The study is being conducted in six youth mental health services across Australia and is using a parallel-group, two-arm, cluster randomised controlled trial design, with randomisation occurring at the clinician level. Participants aged between 12 years and 25 years with moderate to severe levels of depression are randomised to receive, in addition to routine clinical care, either: (1) a physical activity behaviour change intervention or (2) psychoeducation about physical activity. The primary outcome will be change in the Quick Inventory of Depressive Symptomatology, with assessments occurring at baseline, postintervention (end-point) and 6-month follow-up from end-point. Secondary outcome measures will address additional clinical outcomes, functioning and quality of life. IMPACT is to be conducted between May 2014 and December 2019. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Melbourne Human Research Ethics Committee on 8 June 2014 (HREC 1442228). Trial findings will be published in peer-reviewed journals and presented at conferences. Key messages will also be disseminated by the youth mental health services organisation (headspace National Youth Mental Health Foundation). TRIAL REGISTRATION NUMBER: ACTRN12614000772640.
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ItemYouth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirinBerk, M ; Mohebbi, M ; Dean, OM ; Cotton, SM ; Chanen, AM ; Dodd, S ; Ratheesh, A ; Amminger, GP ; Phelan, M ; Weller, A ; Mackinnon, A ; Giorlando, F ; Baird, S ; Incerti, L ; Brodie, RE ; Ferguson, NO ; Rice, S ; Schafer, MR ; Mullen, E ; Hetrick, S ; Kerr, M ; Harrigan, SM ; Quinn, AL ; Mazza, C ; McGorry, P ; Davey, CG (BMC, 2020-01-17)BACKGROUND: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years). METHODS: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15-25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (- 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (- 4.2, 95% CI (- 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. CONCLUSIONS: The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.
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ItemThe addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): study protocol for a randomised control trialDavey, CG ; Chanen, AM ; Cotton, SM ; Hetrick, SE ; Kerr, MJ ; Berk, M ; Dean, OM ; Yuen, K ; Phelan, M ; Ratheesh, A ; Schaefer, MR ; Amminger, GP ; Parker, AG ; Piskulic, D ; Harrigan, S ; Mackinnon, AJ ; Harrison, BJ ; McGorry, PD (BMC, 2014-11-04)BACKGROUND: The aim of the Youth Depression Alleviation-Combined Treatment (YoDA-C) study is to determine whether antidepressant medication should be started as a first-line treatment for youth depression delivered concurrently with psychotherapy. Doubts about the use of medication have been raised by meta-analyses in which the efficacy and safety of antidepressants in young people have been questioned, and subsequent treatment guidelines for youth depression have provided only qualified support. METHODS/DESIGN: YoDA-C is a double-blind, randomised controlled trial funded by the Australian government's National Health and Medical Research Council. Participants between the ages of 15 and 25 years with moderate to severe major depressive disorder will be randomised to receive either (1) cognitive behavioural therapy (CBT) and fluoxetine or (2) CBT and placebo. The treatment duration will be 12 weeks, and follow-up will be conducted at 26 weeks. The primary outcome measure is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) after 12 weeks of treatment. The MADRS will be administered at baseline and at weeks 4, 8, 12 and 26. Secondary outcome measures will address additional clinical outcomes, functioning, quality of life and safety. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ID: ACTRN12612001281886 (registered on 11 December 2012).
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ItemThe effectiveness of simple psychological and physical activity interventions for high prevalence mental health problems in young people: A factorial randomised controlled trialParker, AG ; Hetrick, SE ; Jorm, AF ; Mackinnon, AJ ; McGorry, PD ; Yung, AR ; Scanlan, F ; Stephens, J ; Baird, S ; Moller, B ; Purcell, R (ELSEVIER SCIENCE BV, 2016-05-15)BACKGROUND: The prevalence and burden of disease of depression and anxiety disorders in young people necessitates effective early intervention strategies. The aim of this study was to evaluate the effectiveness of low-intensity interventions (problem solving therapy (PST) and physical activity promotion) in young people (15-25 years) with mild-moderate depression and/or anxiety. METHOD: A 2×2 factorial randomised controlled trial (RCT) with factors of PST versus supportive counselling (control) and behavioural activation physical activity versus lifestyle psychoeducation (control). Help-seeking participants (n=176) were randomised to receive up to 6 manualised intervention sessions. Primary outcomes were post-intervention depressive symptoms (Beck Depression Inventory-II (BDI-II), anxiety symptoms (Beck Anxiety Inventory), and Montgomery-Åsberg Depression Rating Scale (MADRS)). Trial registration ACTRN12608000550303. RESULTS: Depression symptoms were significantly reduced in the physical activity group compared to psychoeducation (BDI-II: d=0.41 (95% CI: 0.07-0.76); MADRS: d=0.48 (95% CI: 0.13-0.82), but not post-intervention anxiety symptoms. PST was not superior to supportive counselling, nor were any interactions between interventions significant. LIMITATIONS: As self reported levels of physical activity did not significantly differ between baseline and end-point in those randomised to the physical activity intervention, it is unclear as to whether some form of physical activity not measured in the trial may have led to the difference in depression symptoms. CONCLUSIONS: PST was not superior to supportive counselling in reducing depression and anxiety symptoms in young people. Participants who received the physical activity intervention reported the greatest reduction in depression symptoms, however further research is required to establish the mechanism of action and to determine its effectiveness as an adjunct intervention in routine clinical practice.
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ItemYouth depression alleviation: the Fish Oil Youth Depression Study (YoDA-F): A randomized, double-blind, placebo-controlled treatment trialRice, SM ; Hickie, IB ; Yung, AR ; Mackinnon, A ; Berk, M ; Davey, C ; Hermens, DF ; Hetrick, SE ; Parker, AG ; Schafer, MR ; McGorry, PD ; Amminger, GP (WILEY, 2016-08-01)AIM: US authorities have recommended 'black-box' warnings for antidepressants because of the increased risk of suicidality for individuals up to age 25. There is thus a clinical and ethical imperative to provide effective treatment for youth depression with an acceptable risk-benefit balance. Long-chain omega-3 polyunsaturated fatty acids (PUFAs) play an important role in a range of physiological processes in living organisms. Supplementation with omega-3 PUFAs has been shown to have a range of beneficial effects on both physical and mental health, and results of previous trials suggest that omega-3 PUFAs may be a safe and effective treatment for depression. However, conclusions from these trials have been limited by their relatively small sample sizes. METHODS: This trial will test the effectiveness of a 12-week parallel group, double-blind, randomized, placebo-controlled trial of 1.4 g day(-1) omega-3 PUFAs in help seeking 15- to 25-year-olds (N = 400) presenting with major depressive disorder. The primary hypothesis is that young people will show greater improvement of depressive symptoms after 12 weeks of treatment with omega-3 PUFAs plus cognitive behavioural case management compared with treatment with placebo plus cognitive behavioural case management. CONCLUSION: Because of using a large sample, results from this study will provide the strongest evidence to date to inform the use of omega-3 PUFAs as first-line therapy in young people presenting with major depressive disorder. The study also heralds an important step towards indicated prevention of persistent depression, which may reduce the burden, stigmatization, disability and economic consequences of this disorder.
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ItemYouth Depression Alleviation-Augmentation with an anti-inflammatory agent (YoDA-A): protocol and rationale for a placebo-controlled randomized trial of rosuvastatin and aspirinQuinn, AL ; Dean, OM ; Davey, CG ; Kerr, M ; Harrigan, SM ; Cotton, SM ; Chanen, AM ; Dodd, S ; Ratheesh, A ; Amminger, GP ; Phelan, M ; Williams, A ; Mackinnon, A ; Giorlando, F ; Baird, S ; Rice, S ; O'Shea, M ; Schaefer, MR ; Mullen, E ; Hetrick, S ; McGorry, P ; Berk, M (WILEY, 2018-02-01)AIM: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well-documented, anti-inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti-inflammatory agent (YoDA-A) study is to determine whether individuals receiving adjunctive anti-inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. METHODS: YoDA-A is a 12-week triple-blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15-25, with moderate-to-severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. CONCLUSION: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and 'real-world', but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD.
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ItemStigmatising attitudes of undergraduates towards their peers with depression: a cross-sectional study in Sri LankaAmarasuriya, SD ; Jorm, AF ; Reavley, NJ ; Mackinnon, AJ (BMC, 2015-06-19)BACKGROUND: There is limited research examining mental health-related stigma of undergraduates in non-western developing countries. This study examined stigma of undergraduates in Sri Lanka towards another depressed undergraduate. METHODS: A hypothetical vignette of an undergraduate suffering from depression was presented. A total of 4650 undergraduates responded to scales assessing their personal stigma towards and desire for social distance from this individual. Exploratory structural equation modelling (ESEM) was performed to determine the dimensionality and loading pattern of the items on these two stigma scales. Multiple linear regressions were used to explore correlates of the identified dimensions of stigma. RESULTS: Previous findings that the Social Distance Scale forms a single dimension and that the Personal Stigma Scale consists of two dimensions were supported. However, the measurement structure of the dimensions of stigma on the latter scales, labelled 'Weak-not-Sick' and 'Dangerous-Undesirable' , differed from previous work. A high level of stigma in relation to the 'Weak-not-Sick' Scale was observed. However, some correlates associated with lower levels of stigma on this scale, such as being in the Medical Faculty, were associated with higher levels of stigma on the 'Dangerous-Undesirable' and 'Social Distance' scales. In contrast, labelling the problem as a mental health-related problem, with absence of specific psychiatric terminology, was associated with lower levels of stigma on these latter two scales. Exposure to a mental health problem in family or friends or from personal experience was also associated with lower stigma on the Social Distance Scale. However, the effect sizes of these relationships were small. CONCLUSIONS: The findings highlight differences in the measurement structure and score distribution of the 'Weak-not-Sick' and 'Dangerous-Undesirable' scales when used in different cultural and demographic contexts. The dimensionality of stigma relevant to these scales must always be established prior to their use in different contexts. Furthermore, campaigns targeted at improving knowledge about depression as a real illness and as a psychiatric condition need to ensure that such attempts are not associated with increases in other aspects of stigma.
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ItemPrevalence and impact of childhood abuse in people with a psychotic illness. Data from the second Australian national survey of psychosisShah, S ; Mackinnon, A ; Galletly, C ; Carr, V ; McGrath, JJ ; Stain, HJ ; Castle, D ; Harvey, C ; Sweeney, S ; Morgan, VA (ELSEVIER, 2014-10-01)Child abuse has been associated with risk of mental illness, including schizophrenia and other psychotic disorders and, among those with mental illness, with a more severe clinical profile. Using an extensively characterised and epidemiologically representative sample of 1825 Australians with a psychotic illness aged 18-64 years and in contact with mental health services, we estimated the proportion of individuals with psychotic disorders who self-reported child abuse and examined its relationship with clinical and other characteristics. The prevalence of child abuse in this nationally representative sample of people with psychotic illness was 30.6%. Women were almost three times more likely to report child abuse compared to males (OR, 2.8, 95% CI 2.3-3.4). When adjusted for age at interview and socio-economic status, there was no significant relationship between self-reported child abuse and type of psychosis or course of illness. Participants with child abuse were significantly more likely to have subjective thought disorder, lifetime suicide attempt and premorbid personality disorder (females only) and anxiety (males only). Our findings demonstrate that child abuse is relatively common across the range of psychotic disorders, with an elevated risk for women in particular, compounding the already high burden associated with psychotic illness. Clinicians need to inquire routinely about child abuse in order to develop appropriate treatment plans tailored to individual needs.