Psychiatry - Research Publications

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    N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial.
    Sarris, J ; Byrne, G ; Castle, D ; Bousman, C ; Oliver, G ; Cribb, L ; Blair-West, S ; Brakoulias, V ; Camfield, D ; Ee, C ; Chamoli, S ; Boschen, M ; Dean, OM ; Dowling, N ; Menon, R ; Murphy, J ; Metri, N-J ; Nguyen, TP ; Wong, A ; Jordan, R ; Karamacoska, D ; Rossell, SL ; Berk, M ; Ng, CH (Elsevier BV, 2022-07-13)
    OBJECTIVE: Preliminary evidence has suggested that adjunctive N-acetylcysteine (NAC), an antioxidant precursor to glutathione, may reduce symptoms of obsessive-compulsive disorder (OCD). We conducted a 20-week, multi-site, randomized controlled trial to investigate the safety and efficacy of the adjunctive use of NAC in OCD. METHODS: The study was a phase III, 20-week, double-blind, randomized controlled trial across multiple sites in Australia investigating 2 g to 4 g per day of NAC (titrated according to response) in 98 participants with DSM-5 diagnosed OCD. Data were analysed using linear mixed effects models for the 89 participants who attended at least one follow-up visit. RESULTS: A modified intention-to-treat analysis of the primary outcome found no evidence that NAC reduced symptoms of OCD measured on the Yale-Brown Obsessive-Compulsive Scale, relative to placebo (mean difference at week 20 = 0.53, 95% compatibility interval = -2.18, 3.23; p = 0.70; favouring placebo). There was also no evidence that NAC, compared to placebo, improved outcomes on the secondary measures including anxiety, depression, quality of life, functioning, or clinician/participant impression. NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment. CONCLUSION: We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.
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    AB026. Cross-regional collaboration to promote digital mental health equity in the Asia Pacific in the context of coronavirus disease (COVID-19)
    Murphy, J ; Michalak, EE ; Greenshaw, A ; Ng, CH ; Ravindran, A ; Withers, M ; Charkraborty, PA ; Lam, RW (AME Publishing Company, 2021-12-01)
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    Treatment of refractory obsessive-compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study
    Sarris, J ; Byrne, GJ ; Oliver, G ; Cribb, L ; Blair-West, S ; Castle, D ; Dean, OM ; Camfield, DA ; Brakoulias, V ; Bousman, C ; Dowling, N ; Ee, C ; Murphy, J ; Menon, R ; Berk, M ; Chamoli, S ; Boschen, M ; Ng, CH (CAMBRIDGE UNIV PRESS, 2021-06-21)
    BACKGROUND: Obsessive-compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach. OBJECTIVE: To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5' phosphate, and selenium. METHODS: A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale (YBOCS), administered every 4 weeks. RESULTS: An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of -7.13 (95% confidence interval = -9.24, -5.01), with a mean reduction of -1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered "responders" (YBOCS ≥35% reduction and "very much" or "much improved" on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD. CONCLUSIONS: While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
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    Psychometric properties of the Clinically Useful Depression Outcome Scale supplemented with DSM-5 Mixed subtype questionnaire in Chinese patients with mood disorders
    Du, Y-L ; Hu, J-B ; Huang, T-T ; Lai, J-B ; Ng, CH ; Zhang, W-H ; Li, C ; Xu, Z-Y ; Zhou, H-T ; Ruan, L-M ; Xu, Y ; Hu, S-H (ELSEVIER, 2021-01-15)
    BACKGROUND: With the modification of DSM-5 mixed features specifier, a brief scale to screen mixed features in patients with mood disorders is needed in clinical practice. This study aimed to explore the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with DSM-5 Mixed subtype (CUDOS-M-C) for the Chinese patients with mood disorders. METHODS: Overall, 300 patients with major depressive episode were recruited. All participants were assessed using CUDOS-M-C, Young Mania Rating Scale, Hamilton Anxiety Scale and Montgomery-Asberg Depression Rating Scale. The receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cut-off values of CUDOS-M-C score. The reliability and validity of CUDOS-M-C were examined using Cronbach's alpha, intraclass correlation coefficient (ICC) and principal component analysis (PCA). RESULTS: The results of PCA indicated two-factor structure as the best solution for CUDOS-M-C, which explained 54.82% of cumulative variance. The Cronbach's alpha was 0.892 and the ICC was 0.853. The area under the ROC curve of the CUDOS-M-C for participants with mixed depression was 0.927 (p<0.001) and the suitable cut-off value was 8, with a sensitivity of 91.6% and specificity of 79.9%. LIMITATIONS: Most of the patients were recruited from eastern China and further research with larger sample is warranted. And this study did not perform confirmatory factor analysis to identify the generalization of factor structure of CUDOS-M-C. Besides, the study performed the test-retest reliability of CUDOS-M-C and further analysis is needed to ascertain the patient's post-treatment changes. CONCLUSION: The CUDOS-M-C demonstrated to have satisfactory psychometric properties as a self-report scale, and could be applied to screen patients with mixed depression in clinical practice.
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    Comparison of Hypomanic Symptoms Between Bipolar I and Bipolar II Disorders: A Network Perspective.
    Bai, W ; Feng, Y ; Sha, S ; Zhang, Q ; Cheung, T ; Zhang, D ; Su, Z ; Ng, CH ; Xiang, Y-T (Frontiers Media SA, 2022)
    Background: Hypomanic symptoms between bipolar-I disorder (BD-I) and bipolar-II disorder (BD-II) are often indistinguishable in clinical practice. This study compared the network structure of hypomanic symptoms between patients with BD-I and BD-II. Methods: The 32-item Hypomania Checklist (HCL-32) was used to assess hypomanic symptoms. Network model was generated in BD-I and BD-II patients. Centrality index of strength was used to quantify the importance of each symptom in the network. The Network Comparison Test (NCT) was used to assess the differences in hypomanic symptoms between BD-I and BD-II patients. Results: Altogether, 423 patients with BD (BD-I: 191 and BD-II: 232) were included. The most central symptom was HCL17 "I am more flirtatious and/or am more sexually active" (strength BD-I = 5.21) and HCL12 "I have more ideas, I am more creative" (strength BD-II = 6.84) in BD-I and BD-II samples, respectively. The results of NCT showed that four nodes (HCL12 "I have more ideas, I am more creative," HCL17 "I am more flirtatious and/or am more sexually active," HCL23 "My thoughts jump from topic to topic," and HCL31 "I drink more alcohol") were significantly different between the BD-I and BD-II samples. Two edges (HCL3 "I am more self-confident"-HCL17 "I am more flirtatious and/or am more sexually active," and HCL10 "I am physically more active (sport, etc.)"-HCL24 "I do things more quickly and/or more easily") were significantly stronger in BD-I compared to BD-II patients. Conclusion: The network structure of hypomanic symptoms is different between BD-I and BD-II patients. Interventions targeting the respective central symptoms and edges should be developed for BD-I and BD-II separately.
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    Gut Microbiota - A Potential Contributor in the Pathogenesis of Bipolar Disorder.
    Zhang, P ; Kong, L ; Huang, H ; Pan, Y ; Zhang, D ; Jiang, J ; Shen, Y ; Xi, C ; Lai, J ; Ng, CH ; Hu, S (Frontiers Media SA, 2022)
    Bipolar disorder (BD) is one of the major psychiatric disorders that is characterized by recurrent episodes of depression and mania (or hypomania), leading to seriously adverse outcomes with unclear pathogenesis. There is an underlying relationship between bacterial communities residing in the gut and brain function, which together form the gut-brain axis (GBA). Recent studies have shown that changes in the gut microbiota have been observed in a large number of BD patients, so the axis may play a role in the pathogenesis of BD. This review summarizes briefly the relationship between the GBA and brain function, the composition and changes of gut microbiota in patients with BD, and further explores the potential role of GBA-related pathway in the pathogenesis of BD as well as the limitations in this field at present in order to provide new ideas for the future etiology research and drug development.
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    Mapping Network Connectivity Among Symptoms of Depression and Pain in Wuhan Residents During the Late-Stage of the COVID-19 Pandemic.
    Yang, Y ; Zhang, S-F ; Yang, BX ; Li, W ; Sha, S ; Jia, F-J ; Cheung, T ; Zhang, D-X ; Ng, CH ; Xiang, Y-T (Frontiers Media SA, 2022)
    Background: Symptoms of depression and pain often overlap, and they negatively influence the prognosis and treatment outcome of both conditions. However, the comorbidity of depression and pain has not been examined using network analysis, especially in the context of a pandemic. Thus, we mapped out the network connectivity among the symptoms of depression and pain in Wuhan residents in China during the late stage of the COVID-19 pandemic. Methods: This cross-sectional study was conducted from May 25, 2020 to June 18, 2020 in Wuhan, China. Participants' depressive and pain symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ9) and a pain numeric rating scale (NRS), respectively. Network analyses were performed. Results: In total, 2,598 participants completed all assessments. PHQ4 (fatigue) in the depression community showed the highest strength value, followed by PHQ6 (worthlessness) and PHQ2 (depressed or sad mood). PHQ4 (fatigue) was also the most key bridge symptom liking depression and pain, followed by PHQ3 (sleep difficulties). There were no significant differences in network global strength (females: 4.36 vs. males: 4.29; S = 0.075, P = 0.427), network structure-distribution of edge weights (M = 0.12, P = 0.541), and individual edge weights between male and female participants. Conclusion: Depressive and pain symptoms showed strong cross-association with each other. "Fatigue" was the strongest central and bridge symptom in the network model, while "sleep difficulties" was the second strongest bridge symptom. Targeting treatment of both fatigue and sleep problems may help improve depressive and pain symptoms in those affected.
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    Risk factors for non-suicidal self-injury (NSSI) in adolescents: A meta-analysis.
    Wang, Y-J ; Li, X ; Ng, CH ; Xu, D-W ; Hu, S ; Yuan, T-F (Elsevier BV, 2022-04)
    Background: Non-suicidal self-injury (NSSI) in adolescents is a significant mental health problem around the world. Here, we performed a meta-analysis to systematically delineate the risk factors for NSSI. Method: We searched Medline, Embase, Web of Science and Cochrane for relevant articles and abstracts published prior to 12 November 2021. Pooled odds ratios (ORs) and 95% confident intervals (CIs) were used to assess various risk factors, and publication bias was assessed by Egger's test, the trim and fill method and meta-regression. This study is registered with PROSPERO, CRD42021265885. Results: A total of 25 articles were eventually included in the analysis. Eighty risk factors were identified and classified into 7 categories: mental disorders (ORs, 1·89; 95% CI, 1·60-2·24), bullying (ORs, 1·98; 95% CI, 1·32-2·95), low health literacy (ORs, 2·20; 95% CI, 1·63-2·96), problem behaviours (ORs, 2·36; 95% CI, 2·00-2·77), adverse childhood experiences (ORs, 2·49; 95% CI, 1·85-3.34), physical symptoms (ORs, 2·85; 95% CI, 1·36-5·97) and the female gender (ORs, 2·89; 95% CI, 2·43-3·43). The range of heterogeneity (I2) was from 20·3% to 99·2%. Conclusion: This meta-analysis found that mental disorders, low health literacy, adverse childhood experiences, bullying, problem behaviours, the female gender and physical symptoms appear to be risk factors for NSSI.
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    Implementation of Therapeutic Virtual Reality Into Psychiatric Care: Clinicians' and Service Managers' Perspectives
    Chung, OS ; Robinson, T ; Johnson, AM ; Dowling, NL ; Ng, CH ; Yucel, M ; Segrave, RA (FRONTIERS MEDIA SA, 2022-01-04)
    Objectives: Virtual reality (VR) has emerged as a highly promising tool for assessing and treating a range of mental illnesses. However, little is known about the perspectives of key stakeholders in mental healthcare, whose support will be critical for its successful implementation into routine clinical practise. This study aimed to explore the perspectives of staff working in the private mental health sector around the use of therapeutic VR, including potential implementation barriers and facilitators. Methods: Semi-structured qualitative interviews were conducted with cross-disciplinary clinicians (n = 14) and service managers (n = 5), aged 28-70 years working in a major private mental health hospital in Victoria, Australia. Transcripts were analysed using general inductive coding to allow themes to naturally emerge. Results: Three major themes were identified: clinical factors (four subthemes), organisational factors (five subthemes), and professional factors (three subthemes). The themes encompassed enabling factors and potential barriers that need to be addressed for successful implementation of VR. Clinical factors highlighted the influence of knowledge or perceptions about appropriate clinical applications, therapeutic efficacy, safety and ethical concerns, and patient engagement. Organisational factors emphasised the importance of service contexts, including having a strong business case, stakeholder planning, recruitment of local opinion leaders to champion change, and an understanding of resourcing challenges. Professional factors highlighted the need for education and training for staff, and the influence of staff attitudes towards technology and perceived usability of VR. Conclusions: In addition to enabling factors, potential implementation barriers of therapeutic VR were identified, including resourcing constraints, safety and ethical concerns, negative staff attitudes towards technology and VR system limitations. Future dissemination should focus on addressing knowledge and skills gaps and attitudinal barriers through development of clinical guidelines, training programs, and implementation resources (e.g., adoption decision tools, consultation opportunities).
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    Are Australian Mental Health Services Ready for Therapeutic Virtual Reality? An Investigation of Knowledge, Attitudes, Implementation Barriers and Enablers
    Chung, OS ; Johnson, AM ; Dowling, NL ; Robinson, T ; Ng, CH ; Yuecel, M ; Segrave, RA (FRONTIERS MEDIA SA, 2022-02-04)
    Therapeutic virtual reality (VR) has the potential to address the challenges of equitable delivery of evidence-based psychological treatment. However, little is known about therapeutic VR regarding the perspectives and needs of real-world service providers. This exploratory study aimed to assess the acceptability, appropriateness, and feasibility of therapeutic VR among clinicians, managers, and service staff working in mental healthcare and explore potential implementation barriers and enablers. Eighty-one staff from a network of private psychiatric hospitals in Victoria, Australia (aged M + SD: 41.88 + 12.01 years, 71.6% female; 64% clinical staff) completed an online survey, which included the Acceptability of Intervention Measure (AIM), Appropriateness of Intervention Measure (IAM), and Feasibility of Intervention Measure (FIM). While 91% of participants had heard about VR technology, only 40% of participants had heard of therapeutic VR being used in mental healthcare, and none had used therapeutic VR in a clinical setting. Most participants perceived VR to be acceptable (84%), appropriate (69%), and feasible (59%) to implement within their role or service and envisioned a range of possible applications. However, participants expressed concerns regarding safety, efficacy, and logistical challenges across clinical settings. Findings suggest a strong interest for therapeutic VR among Australian mental health providers working in the private system. However, dissemination efforts should focus on addressing identified barriers to ensure mental health providers are adequately informed and empowered to make implementation decisions.