Psychosis Endophenotypes: A Gene-Set-Specific Polygenic Risk Score Analysis.

BACKGROUND AND HYPOTHESIS: Endophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes. STUDY DESIGN: We computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score. STUDY RESULTS: After correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: -1.15 µV; 95% CI: -1.70 to -0.59 µV; P = 6 × 10-5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores. CONCLUSIONS: Our finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models.

Experiences of frontline healthcare workers and their views about support during COVID-19 and previous pandemics: a systematic review and qualitative meta-synthesis.

BACKGROUND: Healthcare workers across the world have risen to the demands of treating COVID-19 patients, potentially at significant cost to their own health and wellbeing. There has been increasing recognition of the potential mental health impact of COVID-19 on frontline workers and calls to provide psychosocial support for them. However, little attention has so far been paid to understanding the impact of working on a pandemic from healthcare workers' own perspectives or what their views are about support. METHODS: We searched key healthcare databases (Medline, PsychINFO and PubMed) from inception to September 28, 2020. We also reviewed relevant grey literature, screened pre-print servers and hand searched reference lists of key texts for all published accounts of healthcare workers' experiences of working on the frontline and views about support during COVID-19 and previous pandemics/epidemics. We conducted a meta-synthesis of all qualitative results to synthesise findings and develop an overarching set of themes and sub-themes which captured the experiences and views of frontline healthcare workers across the studies. RESULTS: This review identified 46 qualitative studies which explored healthcare workers' experiences and views from pandemics or epidemics including and prior to COVID-19. Meta-synthesis derived eight key themes which largely transcended temporal and geographical boundaries. Participants across all the studies were deeply concerned about their own and/or others' physical safety. This was greatest in the early phases of pandemics and exacerbated by inadequate Personal Protective Equipment (PPE), insufficient resources, and inconsistent information. Workers struggled with high workloads and long shifts and desired adequate rest and recovery. Many experienced stigma. Healthcare workers' relationships with families, colleagues, organisations, media and the wider public were complicated and could be experienced concomitantly as sources of support but also sources of stress. CONCLUSIONS: The experiences of healthcare workers during the COVID-19 pandemic are not unprecedented; the themes that arose from previous pandemics and epidemics were remarkably resonant with what we are hearing about the impact of COVID-19 globally today. We have an opportunity to learn from the lessons of previous crises, mitigate the negative mental health impact of COVID-19 and support the longer-term wellbeing of the healthcare workforce worldwide.

Participants' experience of approach bias modification training with transcranial Direct Current Stimulation as a combination treatment for binge eating disorder.

OBJECTIVE: This study explored participants' experience of approach bias modification training (ABM) with transcranial Direct Current Stimulation (tDCS) for binge eating disorder (BED) within a randomised controlled trial (RCT). A subset of participants who completed the RCT were interviewed to attain feedback on treatment experience and outcomes. METHOD: 15 participants with BED who completed the RCT were recruited, using purposive sampling. Participants received six sessions of concurrent ABM training with either real or sham tDCS. Semi-structured interviews relating to study experience and treatment outcomes were conducted and data were analysed thematically. RESULTS: The combined ABM and tDCS intervention was deemed acceptable and worthwhile by participants interviewed across both intervention groups. Negative preconceptions of tDCS were an initial deterrent to study participation for some, yet the brain stimulation experience was found to be tolerable. Minor and transient sensations and side effects attributed to tDCS were reported by most participants during and after stimulation, in addition to less pleasant aspects of ABM training, with no significant adverse effects reported by interviewees. Positive outcomes were described by participants across both intervention groups, relating to changes in BED symptoms and to broader beneficial effects on associated cognitive and emotional factors. Two participants experienced a shift in autonomy, attributed to tDCS and the combined intervention respectively. CONCLUSIONS: Adults with symptoms of BED found concurrent ABM and tDCS sessions to be acceptable, despite initial apprehension about the safety of tDCS. Findings are relevant to the neuroethics literature and may inform science communication strategies on neuromodulation treatments.

Experiences of mental health professionals supporting front-line health and social care workers during COVID-19: qualitative study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is having a well-documented impact on the mental health of front-line health and social care workers (HSCWs). However, little attention has been paid to the experiences of, and impact on, the mental health professionals who were rapidly tasked with supporting them. AIMS: We set out to redress this gap by qualitatively exploring UK mental health professionals' experiences, views and needs while working to support the well-being of front-line HSCWs during the COVID-19 pandemic. METHOD: Mental health professionals working in roles supporting front-line HSCWs were recruited purposively and interviewed remotely. Transcripts of the interviews were analysed by the research team following the principles of reflexive thematic analysis. RESULTS: We completed interviews with 28 mental health professionals from varied professional backgrounds, career stages and settings across the UK. Mental health professionals were motivated and driven to develop new clinical pathways to support HSCWs they perceived as colleagues and many experienced professional growth. However, this also came at some costs, as they took on additional responsibilities and increased workloads, were anxious and uncertain about how best to support this workforce and tended to neglect their own health and well-being. Many were professionally isolated and were affected vicariously by the traumas and moral injuries that healthcare workers talked about in sessions. CONCLUSIONS: This research highlights the urgent need to consider the mental well-being, training and support of mental health professionals who are supporting front-line workers.