Psychiatry - Research Publications

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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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    N-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms
    Neill, E ; Rossell, SL ; Yolland, C ; Meyer, D ; Galletly, C ; Harris, A ; Siskind, D ; Berk, M ; Bozaoglu, K ; Dark, F ; Dean, OM ; Francis, PS ; Liu, D ; Phillipou, A ; Sarris, J ; Castle, DJ (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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    Protocol for a systematic review of interventions targeting mental health, cognition or psychological well-being among individuals with long COVID
    Hawke, LD ; Brown, EE ; Rodak, T ; Rossell, S ; Ski, CF ; Strudwick, G ; Thompson, DR ; Wang, W ; Xu, D ; Castle, D (BMJ PUBLISHING GROUP, 2022-09)
    INTRODUCTION: For some people, COVID-19 infection leads to negative health impacts that can last into the medium or long term. The long-term sequelae of COVID-19 infection, or 'long COVID', negatively affects not only physical health, but also mental health, cognition or psychological well-being. Complex, integrated interventions are recommended for long COVID, including psychological components; however, the effectiveness of such interventions has yet to be critically evaluated. This protocol describes a systematic review to be conducted of scientific literature reporting on clinical trials of interventions to promote mental health, cognition or psychological well-being among individuals with long COVID. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A health sciences librarian will identify the relevant literature through comprehensive systematic searches of Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, medRxiv, PsyArXiv, China National Knowledge Internet and WANFANG Data databases, as well as The Cochrane Central Register of Controlled Trials, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Studies will be selected through a title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data extracted will include intervention descriptions and efficacy metrics. Data will be narratively synthesised; if the data allow, a meta-analysis will be conducted. Risk of bias assessment will be conducted using the Cochrane Risk of Bias 2.0 tool. ETHICS AND DISSEMINATION: Ethical approval for systematic reviews is not required. As researchers and clinicians respond to the new clinical entity that long COVID represents, this review will synthesise a rapidly emerging evidence base describing and testing interventions to promote mental health, cognition or psychological well-being. Results will therefore be disseminated through an open-access peer-reviewed publication and conference presentations to inform research and clinical practice. PROSPERO REGISTRATION NUMBER: CRD42022318678.
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    Acevedo et al. Therapeutic Neurostimulation in Obsessive-Compulsive and Related Disorders: A Systematic Review (vol 11, 948, 2021)
    Acevedo, N ; Bosanac, P ; Pikoos, T ; Rossell, S ; Castle, D (MDPI, 2022-04)
    The authors wish to correct the following error in this paper [...].
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    A psychosocial intervention for individuals with advanced chronic kidney disease: A feasibility randomized controlled trial
    Jenkins, ZM ; Tan, EJ ; O'Flaherty, E ; Knowles, S ; Thompson, DR ; Ski, CF ; Rossell, SL ; Coco, C ; Ierino, FL ; Gock, H ; Castle, DJ (WILEY, 2021-05)
    AIM: The current study evaluated the feasibility and preliminary efficacy of a psychosocial intervention, the Kidney Optimal Health Program, in reducing symptoms of depression and anxiety in individuals with advanced chronic kidney disease. METHODS: Patients with stage 4 or 5 chronic kidney disease were randomized to either a nine-session psychosocial intervention programme or usual care. Feasibility was assessed through recruitment and retention rates and programme acceptability. Participants completed assessments of depression, anxiety and psychosocial health at baseline and at 3-, 6- and 12-month follow-up. A repeated-measures analysis of variance was used to compare groups on outcomes over time. RESULTS: One hundred and twenty-eight patients were screened for eligibility; 84 consented to participant and were randomized to receive the intervention (N = 42) or usual care (N = 42). 27 (32.1%) participants withdrew prior to baseline assessment. Of those who completed the baseline assessment (N = 57), trial retention was high (75.4% at 3-month, 80.7% at 6-month and 70.2% at 12-month follow-up). Participants reported high levels of programme acceptability. The patients who completed the intervention (N = 17) demonstrated significantly decreased depression at 12-month follow-up compared to the usual care group (N = 13). CONCLUSION: The results support the feasibility of the Kidney Optimal Health Program intervention in recruitment, retention and programme acceptability with an improved screening protocol. Preliminary support is provided for improvement in depressive symptoms in patients with advanced chronic kidney disease. Further investigation through a fully powered randomized controlled trial is warranted.
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    A systematic review of visual processing and associated treatments in body dysmorphic disorder
    Beilharz, F ; Castle, DJ ; Grace, S ; Rossell, SL (WILEY, 2017-07)
    OBJECTIVE: Recent advances in body dysmorphic disorder (BDD) have explored abnormal visual processing, yet it is unclear how this relates to treatment. The aim of this study was to summarize our current understanding of visual processing in BDD and review associated treatments. METHOD: The literature was collected through PsycInfo and PubMed. Visual processing articles were included if written in English after 1970, had a specific BDD group compared to healthy controls and were not case studies. Due to the lack of research regarding treatments associated with visual processing, case studies were included. RESULTS: A number of visual processing abnormalities are present in BDD, including face recognition, emotion identification, aesthetics, object recognition and gestalt processing. Differences to healthy controls include a dominance of detailed local processing over global processing and associated changes in brain activation in visual regions. Perceptual mirror retraining and some forms of self-exposure have demonstrated improved treatment outcomes, but have not been examined in isolation from broader treatments. CONCLUSION: Despite these abnormalities in perception, particularly concerning face and emotion recognition, few BDD treatments attempt to specifically remediate this. The development of a novel visual training programme which addresses these widespread abnormalities may provide an effective treatment modality.
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    Childhood maltreatment and trauma is common and severe in body dysmorphic disorder
    Malcolm, A ; Pikoos, TD ; Grace, SA ; Castle, DJ ; Rossell, SL (W B SAUNDERS CO-ELSEVIER INC, 2021-08)
    BACKGROUND: Childhood maltreatment and trauma may be risk factors for the development of body dysmorphic disorder (BDD). However, the limited research to date on these topics has been constrained by either the absence of a matched healthy control group or non-comprehensive assessments. METHODS: This study assessed the prevalence and severity of childhood maltreatment and other traumatic events in 52 BDD participants (56% female) and 57 matched controls (51% female) with no history of mental illness, using the Childhood Trauma Questionnaire and a checklist assessing broader traumatic events. RESULTS: In comparison with controls, participants with BDD showed a higher prevalence of emotional abuse (61.5% vs. 33.3%) and physical neglect (59.6% vs. 28.1%), as well as more severe overall maltreatment, emotional abuse, and emotional and physical neglect. BDD participants were also more likely to meet cut-offs for multiple types of maltreatment and reported an elevated number and variety of broader traumatic childhood events (e.g., life-threatening illness). In BDD, increasingly severe maltreatment was correlated with greater severity of BDD symptoms, anxiety and suicidal ideation. CONCLUSIONS: These data suggest that childhood maltreatment and exposure to other traumatic events are common and severe in BDD and are cross-sectionally associated with the severity of clinical symptoms. Adversity linked to maladaptive family functioning during childhood may therefore be especially relevant to people with BDD and could relate to social and emotional processing problems in the disorder.
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    Therapeutic Neurostimulation in Obsessive-Compulsive and Related Disorders: A Systematic Review
    Acevedo, N ; Bosanac, P ; Pikoos, T ; Rossell, S ; Castle, D (MDPI, 2021-07)
    Invasive and noninvasive neurostimulation therapies for obsessive-compulsive and related disorders (OCRD) were systematically reviewed with the aim of assessing clinical characteristics, methodologies, neuroanatomical substrates, and varied stimulation parameters. Previous reviews have focused on a narrow scope, statistical rather than clinical significance, grouped together heterogenous protocols, and proposed inconclusive outcomes and directions. Herein, a comprehensive and transdiagnostic evaluation of all clinically relevant determinants is presented with translational clinical recommendations and novel response rates. Electroconvulsive therapy (ECT) studies were limited in number and quality but demonstrated greater efficacy than previously identified. Targeting the pre-SMA/SMA is recommended for transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). TMS yielded superior outcomes, although polarity findings were conflicting, and refinement of frontal/cognitive control protocols may optimize outcomes. For both techniques, standardization of polarity, more treatment sessions (>20), and targeting multiple structures are encouraged. A deep brain stimulation (DBS) 'sweet spot' of the striatum for OCD was proposed, and CBT is strongly encouraged. Tourette's patients showed less variance and reliance on treatment optimization. Several DBS targets achieved consistent, rapid, and sustained clinical response. Analysis of fiber connectivity, as opposed to precise neural regions, should be implemented for target selection. Standardization of protocols is necessary to achieve translational outcomes.
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    Anorexia nervosa or starvation?
    Phillipou, A ; Rossell, SL ; Castle, DJ (WILEY, 2018-12)
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