Psychiatry - Research Publications
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ItemA biomarker and endophenotype for anorexia nervosa?(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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ItemN-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms(OXFORD UNIV PRESS, 2022-11-18)BACKGROUND AND HYPOTHESIS: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N-acetylcysteine (NAC). STUDY DESIGN: A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks. STUDY RESULTS: NAC did not significantly improve negative symptoms (P = .62), overall cognition (P = .71) or quality of life (Manchester quality of life: P = .11; Assessment of quality of life: P = .57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P = .26). CONCLUSIONS: NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with "Australian and New Zealand Clinical Trials" on the 30 May, 2016 (Registration Number: ACTRN12615001273572).
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ItemAnorexia nervosa or starvation?(WILEY, 2018-12)
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ItemDifferences in regional grey matter volumes in currently ill patients with anorexia nervosa(WILEY, 2018-01)Neurobiological findings in anorexia nervosa (AN) are inconsistent, including differences in regional grey matter volumes. Methodological limitations often contribute to the inconsistencies reported. The aim of this study was to improve on these methodologies by utilising voxel-based morphometry (VBM) analysis with the use of diffeomorphic anatomic registration through an exponentiated lie algebra algorithm (DARTEL), in a relatively large group of individuals with AN. Twenty-six individuals with AN and 27 healthy controls underwent a T1-weighted magnetic resonance imaging (MRI) scan. AN participants were found to have reduced grey matter volumes in a number of areas including regions of the basal ganglia (including the ventral striatum), and parietal and temporal cortices. Body mass index (BMI) and global scores on the Eating Disorder Examination Questionnaire (EDE-Q) were also found to correlate with grey matter volumes in a region of the brainstem (including the substantia nigra and ventral tegmental area) in AN, and predicted 56% of the variance in grey matter volumes in this area. The brain regions associated with grey matter reductions in AN are consistent with regions responsible for cognitive deficits associated with the illness including anhedonia, deficits in affect perception and saccadic eye movement abnormalities. Overall, the findings suggest reduced grey matter volumes in AN that are associated with eating disorder symptomatology.
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ItemAn Overlooked Brain Region in the Aetiology of Anorexia Nervosa: The Importance of Behaviourally Driven Neuroimaging Analysis(SAGE PUBLICATIONS LTD, 2018-12-20)The neurobiological contributions to anorexia nervosa (AN) remain poorly understood, hindering the development of effective neurobiological treatments such as medications and brain stimulation. A large number of studies have been undertaken utilising neuroimaging techniques, such as magnetic resonance imaging (MRI), to gain a better understanding of the brain mechanisms involved in the illness. However, the analyses undertaken by many studies have utilised a whole-brain analytical approach as much of this research has been exploratory in nature. This is, however, problematic as small brain regions that differ between groups may not have the statistical power to produce statistically significant results. This is highlighted in a recent study undertaken by our group utilising diffusion-weighted imaging. In this research, we identified widespread white matter microstructural differences in individuals with AN, but only showed differences in a small brain region (the superior colliculus) when a region-of-interest approach that was driven by behavioural findings was utilised. The importance of hypothesis-driven neuroimaging analyses is discussed in this article.
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ItemAre personality disturbances in anorexia nervosa related to emotion processing or eating disorder symptomatology?(BMC, 2015)BACKGROUND: Anorexia Nervosa (AN) is a psychiatric illness associated with a number of personality disturbances. However, whether these personality characteristics are related to eating disorder symptomatology or emotion regulation is unclear. The aim of this study was to investigate these relationships. RESULTS: Twenty-four individuals with AN and 25 age- and premorbid intelligence-matched controls completed the Personality Diagnostic Questionnaire, and scores were correlated with measures of emotionality and negative mood states, and eating disorder symptomatology. AN was associated with increased scores on schizoid, borderline, avoidant, dependent, obsessive compulsive, negativistic and depressive personality dimensions, relative to controls. In AN, eating disorder symptomatology did not significantly correlate with scores on any personality dimension. However, a number of personality characteristics were found to correlate with negative mood states. CONCLUSIONS: The findings suggest that personality disturbances in AN are not related to disorder-specific symptoms, but are related to negative mood states.
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ItemSelf perception and facial emotion perception of others in anorexia nervosa(FRONTIERS MEDIA SA, 2015-08-10)BACKGROUND: Whether individuals with anorexia nervosa (AN) are able to accurately perceive emotions from faces of others is unclear. Furthermore, whether individuals with AN process images of their own face differently to healthy individuals has thus far not been investigated. Therefore, the aim of this study was to investigate facial affect processing and the processing of one's own face through measures of emotion identification, functional magnetic resonance imaging (fMRI) and eyetracking. METHODS: Twenty-four females with AN and 25 matched healthy control participants were presented with an implicit emotion processing task during fMRI and eyetracking, followed by an explicit emotion identification task. RESULTS: The AN group were found to 'hyperscan' stimuli and avoided visually attending to salient features of their own face images. RESULTS of the fMRI revealed increased activity to own face stimuli in AN in the right inferior and middle temporal gyri, and right lingual gyrus. AN participants were not found to display emotion identification deficits to the standard emotional face stimuli. DISCUSSION: The findings are discussed in terms of increased anxiety to disorder-relevant stimuli in AN. Potential clinical implications are discussed in relation to the use of eyetracking techniques to improve the perception of self in AN.
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ItemSaccadic Eye Movements in Anorexia Nervosa(PUBLIC LIBRARY SCIENCE, 2016-03-24)BACKGROUND: Anorexia Nervosa (AN) has a mortality rate among the highest of any mental illness, though the factors involved in the condition remain unclear. Recently, the potential neurobiological underpinnings of the condition have become of increasing interest. Saccadic eye movement tasks have proven useful in our understanding of the neurobiology of some other psychiatric illnesses as they utilise known brain regions, but to date have not been examined in AN. The aim of this study was to investigate whether individuals with AN differ from healthy individuals in performance on a range of saccadic eye movements tasks. METHODS: 24 females with AN and 25 healthy individuals matched for age, gender and premorbid intelligence participated in the study. Participants were required to undergo memory-guided and self-paced saccade tasks, and an interleaved prosaccade/antisaccade/no-go saccade task while undergoing functional magnetic resonance imaging (fMRI). RESULTS: AN participants were found to make prosaccades of significantly shorter latency than healthy controls. AN participants also made an increased number of inhibitory errors on the memory-guided saccade task. Groups did not significantly differ in antisaccade, no-go saccade or self-paced saccade performance, or fMRI findings. DISCUSSION: The results suggest a potential role of GABA in the superior colliculus in the psychopathology of AN.
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ItemVisual training program for body dysmorphic disorder: protocol for a novel intervention pilot and feasibility trial.(Springer Science and Business Media LLC, 2018)BACKGROUND: Body dysmorphic disorder (BDD) is a characterised by perceived defects or flaws in appearance which are associated with distressing thoughts, repetitive or obsessive behaviours, and significant impairment in social and occupational functioning. A core feature of BDD involves abnormalities of visual processing, although this is not typically a focus of psychological and psychiatric treatments. While current treatments generally show moderate effectiveness in the short-term, those with BDD can have high relapse rates, as they still 'see' their flaws or defects. The current research trials a visual training program designed to remediate visual abnormalities and reduce symptom severity of BDD. METHODS: This is a single-group open-label pilot study assessing the feasibility and potential efficacy of a 10-week visual training program. This pilot trial will be conducted at Swinburne University of Technology, Melbourne, Australia, and will recruit up to 20 participants diagnosed with BDD. These participants will complete pre- and post-assessments and a 10-week visual training program encompassing three phases of basic visual processing, face and emotion recognition, and self-perception. The primary outcomes focus on feasibility and acceptability of the intervention, with secondary outcomes exploring clinical outcomes related to symptom severity, quality of life and eye movements. DISCUSSION: This pilot trial will translate the empirical findings of abnormalities in visual processing among those diagnosed with BDD, to an innovative treatment method across a range of visual processing levels. This trial will assess the feasibility and potential efficacy of such a visual training program, paving the way for further research including a future definitive randomised control trial. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN 12618000274279, Registered 22nd February 2018.