Psychiatry - Research Publications

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    Clinical outcomes of deep brain stimulation for obsessive-compulsive disorder: Insight as a predictor of symptom changes
    Acevedo, N ; Rossell, S ; Castle, D ; Groves, C ; Cook, M ; Mcneill, P ; Olver, J ; Meyer, D ; Perera, T ; Bosanac, P (WILEY, 2024-02)
    AIM: Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. METHODS: Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. RESULTS: Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6-9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. CONCLUSION: The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).
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    Investigating the cause and maintenance of Anorexia Nervosa - The I-CAN study: Protocol and open call for study sites and collaboration
    Phillipou, A ; Croce, S ; Abel, LA ; Castle, DJ ; Dean, B ; Eikelis, N ; Elwyn, R ; Gurvich, C ; Jenkins, Z ; Meyer, D ; Miles, S ; Neill, E ; Ralph-Nearman, C ; Rocks, T ; Rossell, SL ; Ruusunen, A ; Simpson, TN ; Urbini, G ; West, M ; Malcolm, A (ELSEVIER IRELAND LTD, 2023-10)
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    Arterial stiffness in underweight and weight-restored anorexia nervosa
    Jenkins, ZM ; Phillipou, A ; Castle, DJ ; Eikelis, N ; Lambert, EA (WILEY, 2021-11)
    Cardiovascular complications have been demonstrated in patients with anorexia nervosa (AN) in both the state of starvation and during weight restoration, however, the underlying mechanisms remain unclear. The current study aimed to assess arterial stiffness via carotid-femoral pulse wave velocity (cfPWV) in the acute and weight-restored states of AN. The study also aimed to determine the association between psychological distress and cfPWV. The sample included 37 participants; 10 participants with AN, 17 who were weight-restored (AN-WR; minimum body mass index >18.5 for at least 12 months) and 10 healthy controls (HCs). cfPWV via applanation tonometry was conducted to assess arterial stiffness. Psychological distress was assessed using the depression anxiety stress scale (DASS-21) and the state-trait anxiety inventory (STAI). Between-group comparisons were performed to determine differences between groups, a two-stage hierarchical regression model was performed to determine the contribution of physiological and psychological variables on cfPWV and correlation analyses were also performed. Vascular stiffness was significantly increased in the AN and AN-WR groups, relative to HCs. The total DASS score was the only significant predictor of cfPWV across the sample. There were positive associations between cfPWV and depression, anxiety and stress, as assessed by the DASS. Furthermore, cfPWV was positively associated with STAI trait anxiety. Arterial stiffness was increased in individuals in the acute and weight-restored states of AN, demonstrating early signs of the development of arteriosclerotic cardiovascular disease. Increased arterial stiffness was associated with increased psychological distress, which may be a contributing mechanism to the increased cardiovascular risk in AN.
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    Borderline personality disorder symptoms in individuals with eating disorder: Association with severity, psychological distress, and psychosocial function
    Vivarini, P ; Jenkins, ZM ; Castle, DJ ; Gwee, K (WILEY, 2023-05)
    We aimed to determine the prevalence of borderline personality disorder (BPD) symptoms in a sample of eating disorder (ED) outpatients and assess how BPD symptoms correlate with severity, distress, and function. A total of 119 individuals were assessed and divided into high BPD symptoms (H-BPD) and low BPD symptoms (L-BPD) using a cut-off score of seven on the McLean Screening for Borderline Personality Disorder (MSI-BPD). Groups were compared on ED diagnosis, age at ED onset, age at assessment, illness duration, body mass index (BMI), ED symptomatology, psychological distress, and psychosocial function. Correlation analyses were performed to assess the relationship between BPD symptoms and these variables. The 45.4% of the participants scored ≥7 on the MSI-BPD, indicating a diagnosis of BPD. There were no differences between the H-BPD (N = 54) and L-BPD (N = 65) groups on age at onset, age at assessment, duration of illness, BMI, or proportion of ED diagnosis. The H-BPD group reported significantly higher ED symptomatology, psychological distress, and poorer psychosocial functioning. MSI-BPD scores were positively associated with these variables. This study suggests a high prevalence of BPD symptoms within outpatients seeking ED treatment, and use of a brief screening instrument for BPD in this group may contribute to a greater understanding of the patient.
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    A biomarker and endophenotype for anorexia nervosa?
    Phillipou, A ; Rossell, SL ; Gurvich, C ; Castle, DJ ; Meyer, D ; Abel, LA (SAGE PUBLICATIONS LTD, 2022-08-01)
    OBJECTIVE: Recent research has suggested that a type of atypical eye movement, called square wave jerks, together with anxiety, may distinguish individuals with anorexia nervosa from those without anorexia nervosa and may represent a biomarker and endophenotype for the illness. The aim of this study was to identify the presence of this proposed marker in individuals currently with anorexia nervosa relative to healthy controls, and to identify the state independence and heritability of this putative marker by exploring whether it also exists in individuals who are weight-restored from anorexia nervosa and first-degree relatives (i.e. sisters of people with anorexia nervosa). METHODS: Data from 80 female participants (20/group: current anorexia nervosa, weight-restored from anorexia nervosa, sisters of people with anorexia nervosa and healthy controls) were analysed. Square wave jerk rate was acquired during a fixation task, and anxiety was measured with the State Trait Anxiety Inventory. RESULTS: Current anorexia nervosa, weight-restored from anorexia nervosa and sisters of people with anorexia nervosa groups made significantly more square wave jerks than healthy controls, but did not differ from one another. Square wave jerk rate and anxiety were found to discriminate groups with exceptionally high accuracy (current anorexia nervosa vs healthy control = 92.5%; weight-restored from anorexia nervosa vs healthy control = 77.5%; sisters of people with anorexia nervosa vs healthy control = 77.5%; p < .001). CONCLUSION: The combination of square wave jerk rate and anxiety was found to be a promising two-element marker for anorexia nervosa, and has the potential to be used as a biomarker or endophenotype to identify people at risk of anorexia nervosa and inform future treatments.
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    The value of compassionate support to address smoking: A qualitative study with people who experience severe mental illness
    McCarter, K ; McKinlay, MLL ; Cocks, N ; Brasier, C ; Hayes, L ; Baker, ALL ; Castle, D ; Borland, R ; Bonevski, B ; Segan, C ; Kelly, PJJ ; Turner, A ; Williams, J ; Attia, J ; Sweeney, R ; Filia, S ; Baird, D ; Brophy, L (FRONTIERS MEDIA SA, 2022-10-06)
    INTRODUCTION: People experiencing severe mental illness (SMI) smoke at much higher rates than the general population and require additional support. Engagement with existing evidence-based interventions such as quitlines and nicotine replacement therapy (NRT) may be improved by mental health peer worker involvement and tailored support. This paper reports on a qualitative study nested within a peer researcher-facilitated tobacco treatment trial that included brief advice plus, for those in the intervention group, tailored quitline callback counseling and combination NRT. It contextualizes participant life experience and reflection on trial participation and offers insights for future interventions. METHODS: Qualitative semi-structured interviews were conducted with 29 participants in a randomized controlled trial (intervention group n = 15, control group n = 14) following their 2-month (post-recruitment) follow-up assessments, which marked the end of the "Quitlink" intervention for those in the intervention group. Interviews explored the experience of getting help to address smoking (before and during the trial), perceptions of main trial components including assistance from peer researchers and tailored quitline counseling, the role of NRT, and other support received. A general inductive approach to analysis was applied. RESULTS: We identified four main themes: (1) the long and complex journey of quitting smoking in the context of disrupted lives; (2) factors affecting quitting (desire to quit, psychological and social barriers, and facilitators and reasons for quitting); (3) the perceived benefits of a tailored approach for people with mental ill-health including the invitation to quit and practical resources; and (4) the importance of compassionate delivery of support, beginning with the peer researchers and extended by quitline counselors for intervention participants. Subthemes were identified within each of these overarching main themes. DISCUSSION: The findings underscore the enormity of the challenges that our targeted population face and the considerations needed for providing tobacco treatment to people who experience SMI. The data suggest that a tailored tobacco treatment intervention has the potential to assist people on a journey to quitting, and that compassionate support encapsulating a recovery-oriented approach is highly valued. CLINICAL TRIAL REGISTRATION: The Quitlink trial was registered with ANZCTR (www.anzctr.org.au): ACTRN12619000244101 prior to the accrual of the first participant and updated regularly as per registry guidelines.
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    Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness?
    Mc Namara, KP ; Alzubaidi, H ; Murray, M ; Samorinha, C ; Dunbar, JA ; Versace, VL ; Castle, D (WILEY, 2022-10-02)
    Substantially reduced life expectancy for people with serious mental illness compared with the general population is primarily driven by physical health issues, of which cardiovascular disease is the leading cause. In this narrative review, we examine the evidence base for use of metformin and other antidiabetic agents as a means for reducing this excess cardiometabolic disease burden. Evidence from randomised controlled trials (RCTs) suggests substantial potential for metformin to prevent or manage weight gain and glycaemic impairment induced by atypical antipsychotic medications, whereas the impact of metformin on other cardiometabolic risk factors is less consistent. Evidence from RCTs also suggests potential benefits from glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly for addressing cardiometabolic risk factors in people using atypical antipsychotic medications, but this is based on a small number of trials and remains an emerging area of research. Trials of both metformin and GLP-1RAs suggest that these medications are associated with a high prevalence of mild-moderate gastrointestinal side effects. The heterogeneous nature of participant eligibility criteria and of antipsychotic and antidiabetic drug regimens, alongside short trial durations, small numbers of participants and paucity of clinical endpoints as trial outcomes, warrants investment in definitive trials to determine clinical benefits for both metformin and GLP-1RAs. Such trials would also help to confirm the safety profile of antidiabetic agents with respect to less common but serious adverse effects. The weight of RCT evidence suggests that an indication for metformin to address antipsychotic-induced weight gain is worth considering in Australia. This would bring us into line with other countries.
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    Embedding lived experience into mental health academic research organizations: Critical reflections
    Hawke, LD ; Sheikhan, NY ; Jones, N ; Slade, M ; Soklaridis, S ; Wells, S ; Castle, D (WILEY, 2022-10)
    BACKGROUND: As part of a growing emphasis on engaging people with lived experience of mental health conditions in mental health research, there are increasing calls to consider and embed lived experience throughout academic research institutes. This extends beyond the engagement of lay patients and also considers the potential roles of academic researchers with lived experience. When the lived experience of academic researchers is applied to academic work, there is the potential to improve the relevance of the research, while destigmatizing mental illness within academia. However, there are different and often contrasting perspectives on the way a lived experience academic researcher initiative should be implemented. OBJECTIVES: This article describes some of the key issues to be considered when planning an initiative that leverages and values the lived experience of academic researchers, including the advantages and disadvantages of each potential approach. DISCUSSION & RECOMMENDATIONS: Institutions are encouraged to reflect on the ways that they might support and value lived experience among academic researchers. In developing any such initiative, institutions are encouraged to be transparent about their objectives and values, undertake a careful planning process, involve researchers with lived experience from the outset and consistently challenge the stigma experienced by academic researchers with lived experience. PATIENT OR PUBLIC CONTRIBUTION: Multiple authors are academic researchers with lived experience of mental health conditions.
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    Informing the development of Australia's National Eating Disorders Research and Translation Strategy: a rapid review methodology
    Aouad, P ; Bryant, E ; Maloney, D ; Marks, P ; Le, A ; Russell, H ; Hay, P ; Miskovic-Wheatley, J ; Touyz, S ; Maguire, S (BMC, 2022-03-04)
    BACKGROUND: Eating disorders (EDs) are highly complex mental illnesses associated with significant medical complications. There are currently knowledge gaps in research relating to the epidemiology, aetiology, treatment, burden, and outcomes of eating disorders. To clearly identify and begin addressing the major deficits in the scientific, medical, and clinical understanding of these mental illnesses, the Australian Government Department of Health in 2019 funded the InsideOut Institute (IOI) to develop the Australian Eating Disorder Research and Translation Strategy, the primary aim of which was to identify priorities and targets for building research capacity and outputs. A series of rapid reviews (RR) were conducted to map the current state of knowledge, identify evidence gaps, and inform development of the national research strategy. Published peer-reviewed literature on DSM-5 listed EDs, across eight knowledge domains was reviewed: (1) population, prevalence, disease burden, Quality of Life in Western developed countries; (2) risk factors; (3) co-occurring conditions and medical complications; (4) screening and diagnosis; (5) prevention and early intervention; (6) psychotherapies and relapse prevention; (7) models of care; (8) pharmacotherapies, alternative and adjunctive therapies; and (9) outcomes (including mortality). While RRs are systematic in nature, they are distinct from systematic reviews in their aim to gather evidence in a timely manner to support decision-making on urgent or high-priority health concerns at the national level. RESULTS: Three medical science databases were searched as the primary source of literature for the RRs: Science Direct, PubMed and OVID (Medline). The search was completed on 31st May 2021 (spanning January 2009-May 2021). At writing, a total of 1,320 articles met eligibility criteria and were included in the final review. CONCLUSIONS: For each RR, the evidence has been organised to review the knowledge area and identify gaps for further research and investment. The series of RRs (published separately within the current series) are designed to support the development of research and translation practice in the field of EDs. They highlight areas for investment and investigation, and provide researchers, service planners and providers, and research funders rapid access to quality current evidence, which has been synthesised and organised to assist decision-making.
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    Screening, assessment and diagnosis in the eating disorders: findings from a rapid review
    Bryant, E ; Spielman, K ; Le, A ; Marks, P ; Touyz, S ; Maguire, S (BMC, 2022-06-07)
    BACKGROUND: Limited screening practices, minimal eating disorder training in the healthcare professions, and barriers related to help-seeking contribute to persistent low rates of eating disorder detection, significant unmet treatment need, and appreciable associated disease burden. The current review sought to broadly summarise the literature and identify gaps relating to the screening, assessment, and diagnosis of eating disorders within Western healthcare systems. METHODS: This paper forms part of a Rapid Review series scoping the evidence base for the field of eating disorders, conducted to inform the Australian National Eating Disorders Research and Translation Strategy 2021-2031, funded and released by the Australian Government. ScienceDirect, PubMed and Ovid/Medline were searched for studies published between 2009 and mid 2021 in English. High-level evidence such as meta-analyses, large population studies and Randomised Control Trials were prioritised through purposive sampling. Data from selected studies relating to Screening, Assessment and Diagnosis of eating disorders were synthesised and are disseminated in the current review. RESULTS: Eighty seven studies were identified, 38% relating to screening and 62% to assessment and diagnosis. The majority of screening studies were conducted in university student samples, showing high prevalence but only modest improvements in help-seeking in those studies that followed up post-screen. In healthcare settings, clinicians continue to have difficulty identifying eating disorder presentations, particularly Binge Eating Disorder, Other Specified Feeding or Eating Disorders, and sub-threshold eating disorders. This is preceded by inadequate and frequently homogenous screening mechanisms and exacerbated by considerable personal and health-system barriers, including self-stigma and lack of resourcing. While all groups are at risk of delayed or no diagnosis, those at particular risk include LGBTQ+ and gender diverse individuals, individuals living in larger bodies, and males. CONCLUSIONS: A majority of individuals with eating disorders remain undiagnosed and untreated despite a high prevalence of these conditions and increased advocacy in recent years. Research into improving detection and clinician diagnostic skill is extremely limited. Innovative empirical research is strongly recommended to address significant individual and health-system barriers currently preventing appropriate and timely intervention for many. Limited screening in healthcare settings and low rates of eating disorder training in the healthcare professions are just some of the barriers to help-seeking which may contribute to delayed intervention and diagnosis in the eating disorders. This has significant impacts, prolonging treatment when it is finally received, and increasing healthcare costs for both the individual and the healthcare system. The current review is part of a larger Rapid Review series conducted to inform the development of Australia's National Eating Disorders Research and Translation Strategy 2021-2031. A Rapid Review is designed to comprehensively summarise a body of literature in a short timeframe, often to guide policy-making and address urgent health concerns. The Rapid Review synthesises the current evidence-base and identifies gaps in eating disorder research and care, in order to guide decision making and address urgent health concerns. This paper gives a critical overview of the scientific literature relating to the current state of screening, assessment, and diagnosis of eating disorders within Western healthcare systems that may inform health policy and research in an Australian context. It covers screening initiatives in both general and high-risk populations; personal, clinician and healthcare system challenges relating to help-seeking; and obstacles to accurate and timely clinical diagnosis across the eating disorders.