Automated virtual reality cognitive therapy versus virtual reality mental relaxation therapy for the treatment of persistent persecutory delusions in patients with psychosis (THRIVE): a parallel-group, single-blind, randomised controlled trial in England with mediation analyses.

BACKGROUND: Persecutory delusions are a major psychiatric problem that often do not respond sufficiently to standard pharmacological or psychological treatments. We developed a new brief automated virtual reality (VR) cognitive treatment that has the potential to be used easily in clinical services. We aimed to compare VR cognitive therapy with an alternative VR therapy (mental relaxation), with an emphasis on understanding potential mechanisms of action. METHODS: THRIVE was a parallel-group, single-blind, randomised controlled trial across four UK National Health Service trusts in England. Participants were included if they were aged 16 years or older, had a persistent (at least 3 months) persecutory delusion held with at least 50% conviction, reported feeling threatened when outside with other people, and had a primary diagnosis from the referring clinical team of a non-affective psychotic disorder. We randomly assigned (1:1) patients to either THRIVE VR cognitive therapy or VR mental relaxation, using a permuted blocks algorithm with randomly varying block size, stratified by severity of delusion. Usual care continued for all participants. Each VR therapy was provided in four sessions over approximately 4 weeks, supported by an assistant psychologist or clinical psychologist. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 2 (therapy mid-point), 4 (primary endpoint, end of treatment), 8, 16, and 24 weeks. The primary outcome was persecutory delusion conviction, assessed by the Psychotic Symptoms Rating Scale (PSYRATS; rated 0-100%). Outcome analyses were done in the intention-to-treat population. We assessed the treatment credibility and expectancy of the interventions and the two mechanisms (defence behaviours and safety beliefs) that the cognitive intervention was designed to target. This trial is prospectively registered with the ISRCTN registry, ISRCTN12497310. FINDINGS: From Sept 21, 2018, to May 13, 2021 (with a pause due to COVID-19 pandemic restrictions from March 16, 2020, to Sept 14, 2020), we recruited 80 participants with persistent persecutory delusions (49 [61%] men, 31 [39%] women, with a mean age of 40 years [SD 13, range 18-73], 64 [80%] White, six [8%] Black, one [1%] Indian, three [4%] Pakistani, and six [8%] other race or ethnicity). We randomly assigned 39 (49%) participants assigned to VR cognitive therapy and 41 (51%) participants to VR mental relaxation. 33 (85%) participants who were assigned to VR cognitive therapy attended all four sessions, and 35 (85%) participants assigned to VR mental relaxation attended all four sessions. We found no significant differences between the two VR interventions in participant ratings of treatment credibility (adjusted mean difference -1·55 [95% CI -3·68 to 0·58]; p=0·15) and outcome expectancy (-0·91 [-3·42 to 1·61]; p=0·47). 77 (96%) participants provided follow-up data at the primary timepoint. Compared with VR mental relaxation, VR cognitive therapy did not lead to a greater improvement in persecutory delusions (adjusted mean difference -2·16 [-12·77 to 8·44]; p=0·69). Compared with VR mental relaxation, VR cognitive therapy did not lead to a greater reduction in use of defence behaviours (adjusted mean difference -0·71 [-4·21 to 2·79]; p=0·69) or a greater increase in belief in safety (-5·89 [-16·83 to 5·05]; p=0·29). There were 17 serious adverse events unrelated to the trial (ten events in seven participants in the VR cognitive therapy group and seven events in five participants in the VR mental relaxation group). INTERPRETATION: The two VR interventions performed similarly, despite the fact that they had been designed to affect different mechanisms. Both interventions had high uptake rates and were associated with large improvements in persecutory delusions but it cannot be determined that the treatments accounted for the change. Immersive technologies hold promise for the treatment of severe mental health problems. However, their use will likely benefit from experimental research on the application of different therapeutic techniques and the effects on a range of potential mechanisms of action. FUNDING: Medical Research Council Developmental Pathway Funding Scheme and National Institute for Health and Care Research Oxford Health Biomedical Research Centre.

Body image concerns in patients with persecutory delusions.

BACKGROUND: Persecutory fears build on feelings of vulnerability that arise from negative views of the self. Body image concerns have the potential to be a powerful driver of feelings of vulnerability. Body image concerns are likely raised in patients with psychosis given the frequent weight gain. We examined for the first-time body esteem - the self-evaluation of appearance - in relation to symptom and psychological correlates in patients with current persecutory delusions. METHODS: One-hundred and fifteen patients with persecutory delusions in the context of non-affective psychosis completed assessments of body image, self-esteem, body mass index (BMI), psychiatric symptoms and well-being. Body esteem was also assessed in 200 individuals from the general population. RESULTS: Levels of body esteem were much lower in patients with psychosis than non-clinical controls (d = 1.2, p < 0.001). In patients, body esteem was lower in women than men, and in the overweight or obese BMI categories than the normal weight range. Body image concerns were associated with higher levels of depression (r = -0.55, p < 0.001), negative self-beliefs (r = -0.52, p < 0.001), paranoia (r = -0.25, p = 0.006) and hallucinations (r = -0.21, p = 0.025). Body image concerns were associated with lower levels of psychological wellbeing (r = 0.41, p < 0.001), positive self-beliefs (r = 0.40, p < 0.001), quality of life (r = 0.23, p = 0.015) and overall health (r = 0.31, p = 0.001). CONCLUSIONS: Patients with current persecutory delusions have low body esteem. Body image concerns are associated with poorer physical and mental health, including more severe psychotic experiences. Improving body image for patients with psychosis is a plausible target of intervention, with the potential to result in a wide range of benefits.

Listening to and Believing Derogatory and Threatening Voices.

BACKGROUND AND HYPOTHESIS: A plausible cause of distress for voice hearers is listening to and believing the threats and criticisms heard. Qualitative research indicates that patients have understandable reasons to listen. This study aimed to develop the understanding of distress using this listening and believing framework. Measures were developed of listening and believing voices and the reasons, and associations with distress tested. STUDY DESIGN: A cross-sectional study of patients hearing derogatory and threatening voices (N = 591). Listening and Believing-Assessment and Listening and Believing-Reasons item pools were completed, and assessments of distress. Exploratory and confirmatory factor analyses and structural equation modeling (SEM) were conducted. STUDY RESULTS: 52% (n = 307) of participants believed their voices most or all the time. Listening and believing had 4 factors: active listening, passive listening, believing, and disregarding. Higher levels of believing, active listening, and particularly passive listening were associated with higher levels of anxiety, depression, and voice distress. Reasons for listening and believing formed 7 factors: to better understand the threat; being too worn down to resist; to learn something insightful; being alone with time to listen; voices trying to capture attention; voices sounding like real people; and voices sounding like known people. Each type of reason was associated with active listening, passive listening, and believing. SEM showed that feeling worn down in particular accounted for listening and believing. Test-retest reliability of measures was excellent. CONCLUSIONS: A framework of listening and believing negative voices has the potential to inform the understanding and treatment of voice distress.

Coronavirus conspiracy beliefs, mistrust, and compliance with government guidelines in England.

BACKGROUND: An invisible threat has visibly altered the world. Governments and key institutions have had to implement decisive responses to the danger posed by the coronavirus pandemic. Imposed change will increase the likelihood that alternative explanations take hold. In a proportion of the general population there may be strong scepticism, fear of being misled, and false conspiracy theories. Our objectives were to estimate the prevalence of conspiracy thinking about the pandemic and test associations with reduced adherence to government guidelines. METHODS: A non-probability online survey with 2501 adults in England, quota sampled to match the population for age, gender, income, and region. RESULTS: Approximately 50% of this population showed little evidence of conspiracy thinking, 25% showed a degree of endorsement, 15% showed a consistent pattern of endorsement, and 10% had very high levels of endorsement. Higher levels of coronavirus conspiracy thinking were associated with less adherence to all government guidelines and less willingness to take diagnostic or antibody tests or to be vaccinated. Such ideas were also associated with paranoia, general vaccination conspiracy beliefs, climate change conspiracy belief, a conspiracy mentality, and distrust in institutions and professions. Holding coronavirus conspiracy beliefs was also associated with being more likely to share opinions. CONCLUSIONS: In England there is appreciable endorsement of conspiracy beliefs about coronavirus. Such ideas do not appear confined to the fringes. The conspiracy beliefs connect to other forms of mistrust and are associated with less compliance with government guidelines and greater unwillingness to take up future tests and treatment.

Comparison of a theoretically driven cognitive therapy (the Feeling Safe Programme) with befriending for the treatment of persistent persecutory delusions: a parallel, single-blind, randomised controlled trial.

BACKGROUND: There is a large clinical need for improved treatments for patients with persecutory delusions. We aimed to test whether a new theoretically driven cognitive therapy (the Feeling Safe Programme) would lead to large reductions in persecutory delusions, above non-specific effects of therapy. We also aimed to test treatment effect mechanisms. METHODS: We did a parallel, single-blind, randomised controlled trial to test the Feeling Safe Programme against befriending with the same therapists for patients with persistent persecutory delusions in the context of non-affective psychosis diagnoses. Usual care continued throughout the duration of the trial. The trial took place in community mental health services in three UK National Health Service trusts. Participants were included if they were 16 years or older, had persecutory delusions (as defined by Freeman and Garety) for at least 3 months and held with at least 60% conviction, and had a primary diagnosis of non-affective psychosis from the referring clinical team. Patients were randomly assigned to either the Feeling Safe Programme or the befriending programme, using a permuted blocks algorithm with randomly varying block size, stratified by therapist. Trial assessors were masked to group allocation. If an allocation was unmasked then the unmasked assessor was replaced with a new masked assessor. Outcomes were assessed at 0 months, 6 months (primary endpoint), and 12 months. The primary outcome was persecutory delusion conviction, assessed within the Psychotic Symptoms Rating Scale (PSYRATS; rated 0-100%). Outcome analyses were done in the intention-to-treat population. Each intervention was provided individually over 6 months. This trial is registered with the ISRCTN registry, ISRCTN18705064. FINDINGS: From Feb 8, 2016, to July 26, 2019, 130 patients with persecutory delusions (78 [60%] men; 52 [40%] women, mean age 42 years [SD 12·1, range 17-71]; 86% White, 9% Black, 2% Indian; 2·3% Pakistani; 2% other) were recruited. 64 patients were randomly allocated to the Feeling Safe Programme and 66 patients to befriending. Compared with befriending, the Feeling Safe Programme led to significant end of treatment reductions in delusional conviction (-10·69 [95% CI -19·75 to -1·63], p=0·021, Cohen's d=-0·86) and delusion severity (PSYRATS, -2·94 [-4·58 to -1·31], p<0·0001, Cohen's d=-1·20). More adverse events occurred in the befriending group (68 unrelated adverse events reported in 20 [30%] participants) compared with the Feeling Safe group (53 unrelated adverse events reported in 16 [25%] participants). INTERPRETATION: The Feeling Safe Programme led to a significant reduction in persistent persecutory delusions compared with befriending. To our knowledge, these are the largest treatment effects seen for patients with persistent delusions. The principal limitation of our trial was the relatively small sample size when comparing two active treatments, meaning less precision in effect size estimates and lower power to detect moderate treatment differences in secondary outcomes. Further research could be done to determine whether greater effects could be possible by reducing the hypothesised delusion maintenance mechanisms further. The Feeling Safe Programme could become the recommended psychological treatment in clinical services for persecutory delusions. FUNDING: NIHR Research Professorship and NIHR Oxford Health Biomedical Research Centre.

Anticipatory pleasure in current psychosis: Cognitive and emotional correlates.

Anticipation of pleasure - a key aspect of hedonic experience - is a motivating factor for engaging in activities. Low levels of anticipatory pleasure and activity are found in individuals with psychosis. Cognitive factors (e.g., working memory and IQ) have been a focus of explanation for anticipation of pleasure in psychosis. However, cognitive factors do not fully account for such difficulties. It is plausible that emotional factors (e.g., depression, self-beliefs) also contribute. We examined anticipatory pleasure in relation to cognitive and emotional processes in patients with current psychosis. 128 patients with persecutory delusions in the context of non-affective psychosis completed assessments of anticipatory pleasure, cognitive functioning, emotional processes, and activity. Lower anticipatory pleasure was significantly associated with depression, insomnia, negative-self beliefs, suicidal ideation, poorer psychological wellbeing, and paranoia-related avoidance. There were no significant associations with working memory, physical activity, or meaningful activity.  Emotional factors may play a more significant role than cognitive difficulties in the experience of anhedonia in psychosis. However, the cross-sectional design precludes causal inferences. Future research should examine whether, for example, improving self-concept or reducing paranoia-related avoidance leads to improvement in anticipatory pleasure in patients with psychosis.

The weeks before 100 persecutory delusions: the presence of many potential contributory causal factors.

BACKGROUND: The period before the formation of a persecutory delusion may provide causal insights. Patient accounts are invaluable in informing this understanding. AIMS: To inform the understanding of delusion formation, we asked patients about the occurrence of potential causal factors - identified from a cognitive model - before delusion onset. METHOD: A total of 100 patients with persecutory delusions completed a checklist about their subjective experiences in the weeks before belief onset. The checklist included items concerning worry, images, low self-esteem, poor sleep, mood dysregulation, dissociation, manic-type symptoms, aberrant salience, hallucinations, substance use and stressors. Time to reach certainty in the delusion was also assessed. RESULTS: Most commonly it took patients several months to reach delusion certainty (n = 30), although other patients took a few weeks (n = 24), years (n = 21), knew instantly (n = 17) or took a few days (n = 6). The most frequent experiences occurring before delusion onset were: low self-confidence (n = 84); excessive worry (n = 80); not feeling like normal self (n = 77); difficulties concentrating (n = 77); going over problems again and again (n = 75); being very negative about the self (n = 75); images of bad things happening (n = 75); and sleep problems (n = 75). The average number of experiences occurring was high (mean 23.5, s.d. = 8.7). The experiences clustered into six main types, with patients reporting an average of 5.4 (s.d. = 1.0) different types. CONCLUSIONS: Patients report numerous different experiences in the period before full persecutory delusion onset that could be contributory causal factors, consistent with a complex multifactorial view of delusion occurrence. This study, however, relied on retrospective self-report and could not determine causality. DECLARATION OF INTEREST: None.

The comments of voices on the appearance of patients with psychosis: 'the voices tell me that I am ugly'.

BACKGROUND: There are high rates of obesity and low self-esteem in patients with psychosis. The occurrence of negative voice content directly about appearance is therefore plausible. Derogatory comments about appearance are likely to be distressing, increase depression and contribute to social withdrawal. AIMS: To systematically assess the occurrence of voice content regarding appearance and identify correlates. METHOD: Sixty patients experiencing verbal auditory hallucinations at least once a week in the context of non-affective psychosis completed a measure assessing positive and negative voice content about appearance. They also completed assessments about body image, self-esteem, psychiatric symptoms and well-being. RESULTS: Fifty-five (91.7%) participants reported hearing voices comment on their appearance. A total of 54 (90%) patients reported negative voice content about their appearance with 30 (50%) patients experienced negative appearance comments on a daily basis. The most common negative comment was 'the voices tell me that I am ugly' (n = 48, 80%). There were 39 (65%) patients who reported positive voice content on appearance. The most frequent positive comment was 'I look as nice as other people' (n = 26, 43.3%). Negative voice content about appearance was associated with body image concerns, paranoia, voice hearing severity, depression, worry, negative self-beliefs and safety-seeking behaviours. Positive appearance voice content was associated with greater body esteem and well-being and lower levels of depression and insomnia. CONCLUSIONS: Voice content about appearance is very common for patients seen in clinical services. Negative voice content may reflect - and subsequently reinforce - negative beliefs about one's appearance, low self-esteem, worry and paranoia. DECLARATION OF INTEREST: None.

Suicidal ideation and behaviour in patients with persecutory delusions: Prevalence, symptom associations, and psychological correlates.

BACKGROUND: To determine the prevalence of suicidal ideation and behaviour - and their correlates - in patients with persecutory delusions. METHODS: 110 patients with persecutory delusions in the context of non-affective psychosis were assessed for suicidal thoughts and behaviours over the past month. Symptom and psychological assessments were also completed. RESULTS: The severity of suicidal ideation was: no suicidal ideation (n = 26, 23.6%); wish to be dead (n = 21, 19.1%); nonspecific active suicidal thoughts (n = 14, 12.7%); suicidal thoughts with methods but no intent (n = 29, 26.4%); suicidal thoughts with intent but no specific plan (n = 13, 11.8%); and suicidal intent with plan (n = 7, 6.4%). In the past month, five patients (4.5%) had made an actual, interrupted, or aborted suicide attempt. The severity of suicidal ideation was associated with higher levels of depression, paranoia, hallucinations, anger, insomnia, negative beliefs about the self and others, pessimism, worry, and delusion safety-seeking behaviours and lower levels of psychological well-being and reward responsiveness. Severity of ideation was not associated with cannabis or alcohol use, working memory, pain, or meaningful activity levels. CONCLUSIONS: Patients with persecutory delusions are typically in a severe state of psychological stress, and at risk of suicide, as indicated by very high levels of suicidal ideation. This exploratory study also identifies correlates of suicidal ideation that could be investigated in causal research designs.