N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms

BACKGROUND: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60&nbsp;% of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered \u27clozapine resistant\u27. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. METHODS: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2&nbsp;g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. DISCUSSION: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a \u27go to\u27 adjunct in patients that are only partly responsive to clozapine.<br /

Informing the development of Australia's national eating disorders research and translation strategy : a rapid review methodology

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

Advances in the Aetiology and Treatment of Anorexia Nervosa

Anorexia nervosa (AN) is a complex psychiatric disorder [...

Vice-Chancellor's Research Excellence Award (Early Career)

Winner: Mental health and anorexia nervosa Recipient: Andrea Phillipo

The importance of terminology, lived experience inclusion and scientific discussion regarding end-of-life care in anorexia nervosa: a response to Gaudiani et al.

Abstract Whether or not to define ‘terminal anorexia nervosa’ has been a hotly debated topic in the eating disorders field recently. Being able to have open scientific debate on important topics such as this is essential for the progress of our field—but needs to be undertaken respectfully, allowing all perspectives to be heard. My personal perspective on this topic comes from being a researcher who sees individuals with anorexia nervosa (AN) across all stages of illness and recovery, as well as having had a loved one die from AN. Although I disagree with the terminology of ‘terminal AN’ and believe that establishing criteria has the potential to cause harm, I strongly believe in showing compassion to individuals with AN across all illness stages, including those who may wish to seek end-of-life care. This is a complex issue that our field requires guidance on, and we need to work in genuine collaboration with individuals with lived experience of AN to figure out how to appropriately approach end-of-life care when it is warranted

Investigating the neurobiological and cognitive features of anorexia nervosa

© 2015 Dr. Andrea PhillipouObjective: Anorexia nervosa (AN) is a serious psychiatric condition characterised by significantly low body weight, a fear of weight gain and a disturbance in the experience of one’s own body weight or shape. The 12-month prevalence of AN is approximately 0.4% among females, and approximately one-tenth of that among males. AN is associated with exceptionally high morbidity rates, and a mortality rate among the highest of any psychiatric illness. AN is also associated with exceptionally high relapse rates. A major contributing factor for the high rates of morbidity and mortality experienced by these individuals is that the factors involved in the genesis and maintenance of the illness remain unclear, resulting in a hindrance in the improvement of current treatments or the development of new and more effective treatments. Though a number of treatment modalities have emerging evidence for efficacy, many patients remain under- or unresponsive. Thus, gaining a better understanding of the factors involved in the illness has the potential to lead to the development of more effective treatments in the future. Therefore, the aim of this thesis was to investigate the neurobiological and cognitive features of AN through a range of cognitive assessments, eyetracking tasks and functional neuroimaging measures. Method: Twenty-six right-handed female participants with AN and 27 healthy controls, matched for age, gender and premorbid intelligence participated in the study. Participants were required to attend three test sessions within a one week period that involved the completion of a variety of tasks. Included among these tasks were a cognitive battery, basic saccade tasks (prosaccade/antisaccade/no-go, memory-guided and self-paced saccade tasks), an emotional face processing task, a body size estimation task, a resting state functional magnetic resonance imaging (fMRI) scan, and a fixation task. Results: Participants with AN were found to demonstrate differences in performance on a variety of measures, relative to controls. AN participants showed a trend for poorer performance on a working memory task component of the cognitive battery which required the manipulation of visuospatial information. AN participants also displayed shorter prosaccade latencies and an increased rate of inhibitory errors on the memory-guided saccade task, but no significant difference in antisaccade, no-go or self-paced saccade performance. AN participants also demonstrated intact emotion identification of others, and relatedly, no significant difference in blood oxygen level dependent (BOLD) activity to face stimuli depicting different emotions. BOLD activity was however found to significantly differ to participants’ own faces, with AN participants displaying increased activity in the right inferior and middle temporal gyri, and right lingual gyrus. AN participants also avoided fixating on salient features of their own face and showed hyperscanning behaviours to images of their own face, emotional face stimuli and biological motion stimuli. The estimation of body size of biological motion stimuli was, however, not found to differ between groups. Findings of the resting state analysis indicated reduced functional connectivity within the sensorimotor and visual network in AN, but no significant group difference in default mode network connectivity. Finally, AN participants were found to make saccadic intrusions, specifically square wave jerks (SWJs), at a greater rate than healthy controls during fixation. The rate of SWJs also negatively correlated with state anxiety in AN, but not in controls. Discussion: The findings of the study indicate distinctive eye movement differences and visuospatial processing deficits in individuals with AN. The findings are discussed in terms of their overlap with reported findings in anxiety disorders, and the potential brain areas contributing to these results. Specifically, the potential role of the superior colliculus and gamma-aminobutyric acid (GABA) in AN are implicated through a number of findings. Furthermore, the negative correlation between SWJ rate and state anxiety classified groups with very high accuracy and was identified as a distinctive biomarker for AN. The clinical implications of these findings are discussed, as are the potential directions for treatment focus

Can Cognitive Flexibility and Clinical Perfectionism Be Used to Identify People with Anorexia Nervosa?

Poor cognitive flexibility and perfectionism are common features in anorexia nervosa (AN). The current study aimed to investigate cognitive flexibility and clinical perfectionism as potential predictors of AN. Twenty women with a current diagnosis of AN (M age = 28.25, SD = 7.62) and 170 community participants with no lifetime history of an eating disorder (M age = 29.23, SD = 9.88) took part in an online cross-sectional study that included self-report questionnaires of cognitive flexibility and clinical perfectionism. It was found that compared to the community sample, women with AN self-reported significantly poorer cognitive flexibility and significantly greater clinical perfectionism. In a regression model, clinical perfectionism (but not self-reported cognitive flexibility) significantly predicted group membership. The specificity and sensitivity of the model were high. These preliminary findings indicate that clinical perfectionism may represent a key feature of AN and may accurately discriminate between participants with and without AN, though more research is required

Can Cognitive Flexibility and Clinical Perfectionism Be Used to Identify People with Anorexia Nervosa?

Poor cognitive flexibility and perfectionism are common features in anorexia nervosa (AN). The current study aimed to investigate cognitive flexibility and clinical perfectionism as potential predictors of AN. Twenty women with a current diagnosis of AN (M age = 28.25, SD = 7.62) and 170 community participants with no lifetime history of an eating disorder (M age = 29.23, SD = 9.88) took part in an online cross-sectional study that included self-report questionnaires of cognitive flexibility and clinical perfectionism. It was found that compared to the community sample, women with AN self-reported significantly poorer cognitive flexibility and significantly greater clinical perfectionism. In a regression model, clinical perfectionism (but not self-reported cognitive flexibility) significantly predicted group membership. The specificity and sensitivity of the model were high. These preliminary findings indicate that clinical perfectionism may represent a key feature of AN and may accurately discriminate between participants with and without AN, though more research is required