Peak visual gamma frequency is modified across the healthy menstrual cycle

Fluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABAA receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females’ mid‐luteal phase when progesterone and estradiol are highest, and early follicular phase when progesterone and estradiol are lowest. Significantly higher (∼5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modeling, these changes were linked to stronger self‐inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition, the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma‐band oscillations

OPCAT:How an international treaty regarding torture is relevant to the Australian mental health system

The United Nations Subcommittee on the Prevention of Torture visits signatory nations to the Optional Protocol to the Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment (OPCAT). Its role is to monitor and support signatory nations in implementing and complying with the Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment (CAT). In October 2022, the United Nations Subcommittee on the Prevention of Torture visited Australia but was barred from visiting mental health wards in Queensland and all detention facilities in New South Wales leading to the termination of its visit. This breach of Australia’s obligations under the OPCAT presents a significant setback for the rights of people with mental illness and other involuntarily detained populations. This piece sets out to demonstrate the relevance of OPCAT to the mental health system in Australia. Individuals who are detained for compulsory treatment in locked facilities such as acute psychiatric inpatient wards and forensic mental health facilities are deprived of their liberty, often out of public view. Thus, it highlights the ethical and professional obligations of all mental health professionals, especially psychiatrists, to safeguard the human rights of individuals being detained in mental health facilities as enshrined in Australia’s international legal obligations under the OPCAT. Adhering to these obligations diminishes the risk of future human rights violations of people with mental illness.</p

Moral injury related to immigration detention on Nauru: a qualitative study

Background: Immigration detention is associated with detrimental mental health outcomes but little is known about the underlying psychological processes. Moral injury, the experience of transgression of moral beliefs, may play an important role. Objective: Our aim was to explore moral injury appraisals and associated mental health outcomes related to immigration detention on Nauru. Methods: In this retrospective study, we conducted in-depth interviews with 13 individuals who had sought refuge in Australia and, due to arriving by boat, had been transferred to immigration detention on Nauru. At the time of the study, they lived in Australia following medical transfer. We used reflexive thematic analysis to develop themes from the data. Results: Major themes included 1) how participants' home country experience and the expectation to get protection led them to seek safety in Australia; 2) how they experienced deprivation, lack of agency, violence, and dehumanization after arrival, with the Australian government seen as the driving force behind these experiences; and 3) how these experiences led to feeling irreparably damaged. The participant statement 'In my country they torture your body but in Australia they kill your mind.' conveyed these three key themes in our analysis. Conclusion: Our findings suggest that moral injury may be one of the processes by which mandatory immigration detention can cause harm. Although refugees returned to Australia from offshore detention may benefit from interventions that specifically target moral injury, collective steps are needed to diminish deterioration of refugee mental health. Our results highlight the potentially deleterious mental health impact of experiencing multiple subtle and substantial transgressions of one's moral frameworks. Policy makers should incorporate moral injury considerations to prevent eroding refugee mental health. Keywords: Moral injury; Nauru; asylum seeker; immigration detention; post-migration living difficulties; refugee mental health

The EMPOWER blended digital intervention for relapse prevention in schizophrenia : a feasibility cluster randomised controlled trial in Scotland and Australia

Funding Information: AIG reports personal fees from University of Manchester, personal fees from University of Exeter, personal fees from British Association for Behavioural and Cognitive Psychotherapies and other interests with UK National Health Service (NHS) Education for Scotland outside the submitted work. JA, SL, and SB report other interests with CareLoop Health, outside the submitted work. SB reports grants from the Medical Research Council and UK National Institute for Health Research (NIHR) during the conduct of the study. SL reports grants from the UK Medical Research Council (MRC) during the conduct of the study. JA reports grants from MRC, Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR, and the US National Institute for Health, and was a Fellow of the Alan Turing Institute during the conduct of the study. AB reports personal fees from Bayer, Merck, Janssen, Novartis, Sword Health, Amgen, and Daiichi Sankyo outside the submitted work. JF reports grants from National Health and Medical Research Council (Australia) during the conduct of the study and other interests with Melbourne Health (NorthWestern Mental Health) outside the submitted work. HMcL reports grants from NIHR Health Technology Assessment (HTA) during the conduct of the study, and grants with Academy of Medical Sciences, Glasgow Children's Hospital Charity, and Scotland's Chief Scientist's Office. CM reports grants from National Health and Medical Research Council (Australia) during the conduct of the study. JN reports grants from the University of Aberdeen and the University of Edinburgh during the conduct of the study and declares membership of the following NIHR boards: Cardio Pulmonary Resusitation decision making committee; HTA commissioning board; HTA commissioning sub-board (expression of interest); HTA funding boards policy group; HTA general board; HTA post-board funding teleconference; NIHR clinical trials unit standing advisory committee; NIHR HTA and Efficacy Mechanism Evaluation editorial board; pre-exposure prophylaxis impact review panel. PF is a member of the HTA mental health prioritisation panel. CW reports grants from NIHR during the conduct of the study and from the Royal College of Psychiatrists, and other interests with Five Areas outside the submitted work. AY reports an NIHR Senior Investigator Grant. JG reports grants from the National Health Medical Research Council. All other authors declare no competing interests. Funding Information: This project was funded in the UK by the NIHR-HTA programme (project number 13/154/04) and in Australia by the National Heath and Medical Research Council (APP1095879). The research will be published in full in the HTA. This study is supported by NHS Research Scotland, through the Chief Scientist Office and the NHS Scotland Mental Health Network. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. MA-J is supported by an Investigator Grant (APP1177235) from the National Health and Medical Research Council and a Dame Kate Campbell Fellowship from The University of Melbourne. MB and SS are supported by NIHR Applied Research Centre (ARC) West Midlands. SA is supported by a Cremore Research Fellowship, donated to the University of Glasgow. This independent research study was funded by the UK NIHR-HTA. The views expressed in this publication are those of the authors and not necessarily of the NHS, the National Institute for Health Research, or the UK Department of Health and Social Care. The study sponsors and funders were not involved in the study design; collection, management, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication. We would like to thank health and care providers in Scotland and Australia who contributed to the study and of course to all the service users and their supporters who participated in this research. We sincerely hope we have met your expectations in taking part. We would like to acknowledge and recognise the contribution of members of the research team not listed as authors. These include Imogen Bell, Emily Castagnini, Andrea Clark, Amy Hood, Maria Lambrou, Casey Lynch, Casey McCrae, Ishani Majmudar, Claire Matrunola, Giada Micolucci, Sophie Norman, Lesley Smith, Suzy Syrett, David Thomson, Helen Whitehill, and Alison Wilson Kay. We also express our gratitude to our Study Steering Committee members: Prof David Kingdon (Chair), Prof Daniel Freeman (independent member), Prof Fiona Lobban (independent member), David Kavanagh (independent member), and Graham Morgan (Independent Public and Patient Involvement Representative). We also express our gratitude to our Data Monitoring and Ethics Committee members: Prof Emmanuelle Peters (Chair), Dr Alison Brabban (Independent Clinician), Prof Rod Taylor (Independent Statistician), and Prof Greg Murray (Independent Statistician). Funding Information: This project was funded in the UK by the NIHR-HTA programme (project number 13/154/04) and in Australia by the National Heath and Medical Research Council (APP1095879). The research will be published in full in the HTA. This study is supported by NHS Research Scotland, through the Chief Scientist Office and the NHS Scotland Mental Health Network. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. MA-J is supported by an Investigator Grant (APP1177235) from the National Health and Medical Research Council and a Dame Kate Campbell Fellowship from The University of Melbourne. MB and SS are supported by NIHR Applied Research Centre (ARC) West Midlands. SA is supported by a Cremore Research Fellowship, donated to the University of Glasgow. This independent research study was funded by the UK NIHR-HTA. The views expressed in this publication are those of the authors and not necessarily of the NHS, the National Institute for Health Research, or the UK Department of Health and Social Care. The study sponsors and funders were not involved in the study design; collection, management, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication. We would like to thank health and care providers in Scotland and Australia who contributed to the study and of course to all the service users and their supporters who participated in this research. We sincerely hope we have met your expectations in taking part. We would like to acknowledge and recognise the contribution of members of the research team not listed as authors. These include Imogen Bell, Emily Castagnini, Andrea Clark, Amy Hood, Maria Lambrou, Casey Lynch, Casey McCrae, Ishani Majmudar, Claire Matrunola, Giada Micolucci, Sophie Norman, Lesley Smith, Suzy Syrett, David Thomson, Helen Whitehill, and Alison Wilson Kay. We also express our gratitude to our Study Steering Committee members: Prof David Kingdon (Chair), Prof Daniel Freeman (independent member), Prof Fiona Lobban (independent member), David Kavanagh (independent member), and Graham Morgan (Independent Public and Patient Involvement Representative). We also express our gratitude to our Data Monitoring and Ethics Committee members: Prof Emmanuelle Peters (Chair), Dr Alison Brabban (Independent Clinician), Prof Rod Taylor (Independent Statistician), and Prof Greg Murray (Independent Statistician). Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licensePeer reviewe

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse : the EMPOWER feasibility cluster RCT

Funding Information: Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879). Funding Information: The research reported in this issue of the journal was funded by the HTA programme as project number 13/154/04. The contractual start date was in April 2016. The draft report began editorial review in September 2019 and was accepted for publication in March 2020. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Funding Information: Declared competing interests of authors: Andrew I Gumley reports personal fees from the University of Manchester, the University of Exeter and the British Association for Behavioural & Cognitive Psychotherapies (BABCP) (Accrington, UK), and other interests with NHS Education for Scotland outside the submitted work. John Ainsworth reports other interests with Affigo CIC (Manchester, UK) outside the submitted work. Sandra Bucci is a director of Affigo CIC, a not-for-profit social enterprise company spun out of the University of Manchester in December 2015 to enable access to social enterprise funding and to promote ClinTouch, a symptom-monitoring app, to the NHS and public sector. Andrew Briggs reports personal fees from Bayer (Leverkusen, Germany), Merck Sharp & Dohme (Kenilworth, NJ, USA), Janssen Pharmaceutica (Beerse, Belgium), Novartis (Basel, Switzerland), SWORD Health (Porto, Portugal), Amgen Inc. (Thousand Oaks, CA, USA) and Daiichi Sankyo (Tokyo, Japan) outside the submitted work. John Farhall reports grants from the National Health and Medical Research Council (Australia) during the conduct of the study and other interests with Melbourne Health (NorthWestern Mental Health, Parkville, VIC, Australia) outside the submitted work. Shôn Lewis reports grants from the Medical Research Council, non-financial support from Affigo CIC and personal fees from XenZone plc (Manchester, UK) outside the submitted work. Cathy Mihalopoulos reports grants from National Health and Medical Research Council (Australia) during the conduct of the study. John Norrie reports grants from the University of Aberdeen and the University of Edinburgh during the conduct of the study and declares membership of the following NIHR boards: CPR Decision Making Committee (2016), HTA Commissioning Board (2010–16), HTA Commissioning Sub-Board (EOI) (2012–16), HTA Funding Boards Policy Group (2016), HTA General Board (2016–19), HTA Post-Board funding teleconference (2016–19), NIHR CTU Standing Advisory Committee (2017–present), NIHR HTA and EME Editorial Board (2014–19) and Pre-exposure Prophylaxis Impact Review Panel (2017–present). Paul French is a member of the HTA Mental Health Prioritisation Panel (2017–present). Chris Williams reports grants from NIHR during the conduct of the study (HTA 10/104/34 BEAT-IT: a randomised controlled trial comparing a behavioural activation treatment for depression in adults with learning disabilities with attention control; NIHR multicentre RCT of a group psychological intervention for postnatal depression in British mothers of South Asian Origin: RP-PG-0514-20012: Integrated therapist and online CBT for depression in primary care); other from Five Areas Ltd (Clydebank, UK) outside the submitted work; and that he has twice been president of the British Association for Behavioural & Cognitive Psychotherapies, the lead body for cognitive–bahavioural therapy in the UK. This body aims to advocate use of evidence-based delivery of cognitive–bahavioural therapy. Publisher Copyright: © Queen’s Printer and Controller of HMSO 2022.Peer reviewedPublisher PD

Early Signs Monitoring to Prevent Relapse in Psychosis and Promote Well-Being, Engagement, and Recovery:Protocol for a Feasibility Cluster Randomized Controlled Trial Harnessing Mobile Phone Technology Blended With Peer Support

BACKGROUND: Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions. OBJECTIVE: This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial. METHODS: We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants' own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support. RESULTS: Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation. CONCLUSIONS: The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15058

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

BACKGROUND: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. OBJECTIVE: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? DESIGN: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. SETTINGS: Glasgow, UK, and Melbourne, Australia. PARTICIPANTS: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. INTERVENTIONS: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. MAIN OUTCOME MEASURES: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. RESULTS: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. LIMITATIONS: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. CONCLUSIONS: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. FUTURE WORK: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). TRIAL REGISTRATION: This trial is registered as ISRCTN99559262. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879)