The role of characterisation in everyday voice engagement and AVATAR therapy dialogue.

BACKGROUND: Voices are commonly experienced as communication with a personified 'other' with ascribed attitudes, intentionality and personality (their own 'character'). Phenomenological work exploring voice characterisation informs a new wave of relational therapies. To date, no study has investigated the role of characterisation in behavioural engagement with voices or within psychological therapy for distressing voices. METHODS: Baseline characterisation (the degree to which the voice is an identifiable and characterful entity) of the dominant voice was rated (high, medium or low) using a newly developed coding framework, for n = 60 people prior to starting AVATAR therapy. Associations between degree of characterisation and (i) everyday behavioural engagement with voices (The Beliefs about Voices Questionnaire-Revised; n = 60); and (ii) interaction within avatar dialogue [Session 4 Time in Conversation (participant-avatar); n = 45 therapy completers] were explored. RESULTS: Thirty-three per cent reported high voice characterisation, 42% medium and 25% low. There was a significant association between characterisation and behavioural engagement [H(2) = 7.65, p = 0.022, ɛ2 = 0.130] and duration of participant-avatar conversation [F(2,42) = 6.483, p = 0.004, η2 = 0.236]. High characterisation was associated with increased behavioural engagement compared with medium (p = 0.004, r = 0.34; moderate effect) and low (p = 0.027, r = 0.25; small-moderate effect) with a similar pattern observed for the avatar dialogue [high v. medium: p = 0.008, Hedges' g = 1.02 (large effect); high v. low: p = 0.023, Hedges' g = 1.03 (large effect)]. No differences were observed between medium and low characterisation. DISCUSSION: Complex voice characterisation is associated with how individuals interact with their voice(s) in and out of therapy. Clinical implications and future directions for AVATAR therapy and other relational therapies are discussed.

Relating behaviours and therapeutic actions during AVATAR therapy dialogue: An observational study.

OBJECTIVES: AVATAR therapy is a novel relational approach to working with distressing voices by engaging individuals in direct dialogue with a digital representation of their persecutory voice (the avatar). Critical to this approach is the avatar transition from abusive to conciliatory during the course of therapy. To date, no observational study has examined the moment-to-moment dialogical exchanges of this innovative therapy. We aim to (1) map relating behaviours between participants and their created avatars and (2) examine therapeutic actions delivered within AVATAR dialogue. METHOD: Twenty-five of the fifty-three AVATAR therapy completers were randomly selected from a randomized controlled trial (Craig et al. The Lancet Psychiatry, 5, 2018 and 31). Seventy-five audio recordings of active dialogue from sessions 1 and 4 and the last session were transcribed and analysed using a newly developed coding frame. Inter-rater reliability was good to excellent. RESULTS: Fine-grained analysis of 4,642 observations revealed nuanced communication around relational power and therapeutic activity. Early assertiveness work, reinforced by the therapist, focussed on increasing power and distancing. Participants' submissive behaviours reduced during therapy, but the shift was gradual. Once the transition to a more conciliatory tone took place, the dialogue primarily involved direct communication between participant and avatar, focussing on sense of self and developmental and relational understanding of voices. CONCLUSIONS: AVATAR therapy supports voice-hearers in becoming more assertive towards a digital representation of their abusive voice. Direct dialogue with carefully characterized avatars aims to build the voice-hearers' positive sense of self, supporting the person to make sense of their experiences. PRACTITIONER POINTS: AVATAR therapy enables voice-hearers to engage in face-to-face dialogue with a digital representation ('avatar') of their persecutory voice. Fine-grained analyses showed how relating behaviours and therapeutic actions evolve during active AVATAR therapy dialogue. Carefully characterized avatars and direct therapist input help voice-hearers become more assertive over the avatar, enhance positive sense of self, and support individuals to make sense of their experiences.

The Dunn Worry Questionnaire and the Paranoia Worries Questionnaire: new assessments of worry.

BACKGROUND: The cognitive process of worry, which keeps negative thoughts in mind and elaborates the content, contributes to the occurrence of many mental health disorders. Our principal aim was to develop a straightforward measure of general problematic worry suitable for research and clinical treatment. Our secondary aim was to develop a measure of problematic worry specifically concerning paranoid fears. METHODS: An item pool concerning worry in the past month was evaluated in 250 non-clinical individuals and 50 patients with psychosis in a worry treatment trial. Exploratory factor analysis and item response theory (IRT) informed the selection of scale items. IRT analyses were repeated with the scales administered to 273 non-clinical individuals, 79 patients with psychosis and 93 patients with social anxiety disorder. Other clinical measures were administered to assess concurrent validity. Test-retest reliability was assessed with 75 participants. Sensitivity to change was assessed with 43 patients with psychosis. RESULTS: A 10-item general worry scale (Dunn Worry Questionnaire; DWQ) and a five-item paranoia worry scale (Paranoia Worries Questionnaire; PWQ) were developed. All items were highly discriminative (DWQ a = 1.98-5.03; PWQ a = 4.10-10.7), indicating small increases in latent worry lead to a high probability of item endorsement. The DWQ was highly informative across a wide range of the worry distribution, whilst the PWQ had greatest precision at clinical levels of paranoia worry. The scales demonstrated excellent internal reliability, test-retest reliability, concurrent validity and sensitivity to change. CONCLUSIONS: The new measures of general problematic worry and worry about paranoid fears have excellent psychometric properties.

Self-Confidence and Paranoia: An Experimental Study Using an Immersive Virtual Reality Social Situation.

BACKGROUND: Paranoia may build directly upon negative thoughts about the self. There have been few direct experimental tests of this hypothesis. AIMS: The aim of the study was to test the immediate effects of manipulating self-esteem in individuals vulnerable to paranoia. METHOD: A two condition cross-over experimental test was conducted. The participants were 26 males reporting paranoid ideation in the past month. Each participant experienced a neutral immersive virtual reality (VR) social environment twice. Before VR participants received a low self-confidence manipulation or a high self-confidence manipulation. The order of manipulation type was randomized. Paranoia about the VR avatars was assessed. RESULTS: The low self-confidence manipulation, relative to the high self-confidence manipulation, led to significantly more negative social comparison in virtual reality and higher levels of paranoia. CONCLUSIONS: Level of self-confidence affects the occurrence of paranoia in vulnerable individuals. The clinical implication is that interventions designed to improve self-confidence may reduce persecutory ideation.

The Perseverative Thinking Questionnaire in Patients with Persecutory Delusions.

BACKGROUND: Ruminative negative thinking has typically been considered as a factor maintaining common emotional disorders and has recently been shown to maintain persecutory delusions in psychosis. The Perseverative Thinking Questionnaire (PTQ) (Ehring et al., 2011) is a transdiagnostic measure of ruminative negative thinking that shows promise as a "content-free" measure of ruminative negative thinking. AIMS: The PTQ has not previously been studied in a psychosis patient group. In this study we report for the first time on the psychometric properties of Ehring et al.'s PTQ in such a group. METHOD: The PTQ was completed by 142 patients with current persecutory delusions and 273 non-clinical participants. Participants also completed measures of worry and paranoia. A confirmatory factor analysis was performed on the clinical group's PTQ responses to assess the factor structure of the measure. Differences between groups were used to assess criterion reliability. RESULTS: A three lower-order factor structure of the PTQ (core characteristics of ruminative negative thinking, perceived unproductiveness, and capturing mental capacity) was replicated in the clinical sample. Patients with persecutory delusions were shown to experience significantly higher levels of ruminative negative thinking on the PTQ than the general population sample. The PTQ demonstrated high internal reliability. CONCLUSIONS: This study did not include test-retest data, and did not compare the PTQ against a measure of depressive rumination but, nevertheless, lends support for the validity of the PTQ as a measure of negative ruminative thinking in patients with psychosis.

Targeting Recovery in Persistent Persecutory Delusions: A Proof of Principle Study of a New Translational Psychological Treatment (the Feeling Safe Programme).

BACKGROUND: Many patients do not respond adequately to current pharmacological or psychological treatments for psychosis. Persistent persecutory delusions are common in clinical services, and cause considerable patient distress and impairment. Our aim has been to build a new translational personalized treatment, with the potential for wide use, that leads to high rates of recovery in persistent persecutory delusions. We have been developing, and evaluating individually, brief modular interventions, each targeting a key causal factor identified from our cognitive model. These modules are now combined in "The Feeling Safe Programme". AIMS: To test the feasibility of a new translational modular treatment for persistent persecutory delusions and provide initial efficacy data. METHOD: 12 patients with persistent persecutory delusions in the context of non-affective psychosis were offered the 6-month Feeling Safe Programme. After assessment, patients chose from a personalized menu of treatment options. Four weekly baseline assessments were carried out, followed by monthly assessments. Recovery in the delusion was defined as conviction falling below 50% (greater doubt than certainty). RESULTS: 11 patients completed the intervention. One patient withdrew before the first monthly assessment due to physical health problems. An average of 20 sessions (SD = 4.4) were received. Posttreatment, 7 out of 11 (64%) patients had recovery in their persistent delusions. Satisfaction ratings were high. CONCLUSIONS: The Feeling Safe Programme is feasible to use and was associated with large clinical benefits. To our knowledge this is the first treatment report focused on delusion recovery. The treatment will be tested in a randomized controlled trial.

The effect of paranoia on the judging of harmful events.

OBJECTIVE: Social psychological research has indicated that intentional harm may be perceived as causing greater damage than unintentional harm. It has been proposed that this harm magnification is a consequence of a need to blame, condemn and punish ("blame motivation"). The objective of the current study was to replicate these findings and to test whether such judgements about harmful events are associated with the level of an individual's paranoia. METHOD: Three hundred adults read a scenario in which a head of a company causes a reduction in employees' pay. Participants were randomly allocated to versions in which the outcome of the executive's action was intended or unintended. Ratings were made of intent, harm caused and blame motivation. Participants also completed assessments of paranoia and anxiety. RESULTS: Intentional harm was judged as causing worse outcomes than unintentional harm, explaining a small amount of variance in harm scores. Paranoia moderated judgements of intent and blame motivation but not the degree of harm caused; high paranoia, relative to low paranoia, was associated with the unintentional scenario generating higher attributions of intent and blame and the intentional scenario generating lower attributions of intent and blame. Anxiety levels did not affect judgements. CONCLUSIONS: The study supports the theory that there is a reasoning bias that magnifies the consequences of intentional harm relative to unintentional harm. In the initial judgement about intent, people with paranoia are less accurate in their use of contextual information.

Persecutory delusions and psychological well-being.

PURPOSE: Persecutory delusions are one of the key problems seen in psychotic conditions. The aim of the study was to assess for the first time the levels of psychological well-being specifically in patients with current persecutory delusions. METHOD: One hundred and fifty patients with persecutory delusions in the context of a diagnosis of non-affective psychosis, and 346 non-clinical individuals, completed the Warwick-Edinburgh Mental Well-Being Scale and symptom assessments. RESULTS: Well-being scores were much lower in the persecutory delusions group compared with the non-clinical control group. 47 % of the persecutory delusions group scored lower than two standard deviations below the control group mean score. Within the patient group, psychological well-being was negatively associated with depression, anxiety, and hallucinations. In both groups, lower levels of well-being were associated with more severe paranoia. CONCLUSIONS: Levels of psychological well-being in patients with current persecutory delusions are strikingly low. This is likely to arise from the presence of affective symptoms and psychotic experiences. Measurement of treatment change in positive mental health for patients with psychosis is recommended.

Comparing Gender Congruency in Nonsurgical versus Postsurgical Top Surgery Patients: A Prospective Survey Study.

Background: Gender dysphoria can result in reduced quality of life. Treatments include hormone replacement therapy (HRT) and gender-affirming surgery. Our study compared congruency, satisfaction, and discrimination in patients who underwent top surgery and HRT versus HRT alone. We hypothesized improved outcomes in top surgery patients but that lack of access is a common barrier. Methods: Transgender and nonbinary subjects who underwent at least 6 months of HRT were recruited and answered questions on gender congruency, discrimination, and barriers to care. Surgical patients were asked about postoperative satisfaction using the BREAST-Q. A Mann-Whitney test compared survey responses between study arms. Results: One hundred twelve eligible subjects completed the survey. Surgical subjects answered significantly more positively (P < 0.001) on all questions regarding gender congruency. The greatest difference was observed in how subjects' physical bodies represented their gender identity, where the surgery group rated higher on the five-point Likert scale by 2.0 points (P < 0.001). Surgical patients also reported less violence, verbal abuse, and discrimination (P < 0.003). Within the hormone arm, 87.1% stated desire for surgery and 62.5% declared barriers to surgery, with cost and insurance coverage representing the most common barriers. Finally, surgical subjects reported high satisfaction on the BREAST-Q, scoring more than 3.0 in all categories of breast augmentation and more than 2.6 for breast reduction on a four-point Likert scale. Conclusions: Top surgery, in addition to HRT, significantly improves gender congruency and decreases discrimination and abuse, compared with HRT alone. Unfortunately, barriers including cost and lack of insurance continue to be obstacles for care.

Spontaneous Rupture of the Extensor Pollicis Longus Tendon: A Systematic Review.

BACKGROUND: Extensor pollicis longus (EPL) rupture and tenosynovitis of the third dorsal compartment is often described in association with a history of rheumatoid arthritis or in the setting of a distal radius fracture. However, the literature suggests multiple other potential factors that may lead to a seemingly spontaneous rupture. METHODS: We performed a systematic review following guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search consisted of headings and keywords related to tendon injuries, tendinopathy, hand surgery, tendon transfer, and injections, as published in reports and studies. Citations were screened by title and abstract against predetermined inclusion and exclusion criteria by 2 independent reviewers, with a third reviewer resolving discrepancies. To be eligible, articles had to meet the following inclusion criterion: describe cases of spontaneous EPL rupture or tenosynovitis of the third dorsal compartment. The exclusion criterion was any history of distal radius fracture or rheumatoid arthritis. RESULTS: We identified 29 articles that met the inclusion criterion. CONCLUSIONS: A myriad of prodromal events or predisposing factors ultimately led to EPL rupture or tenosynovitis of the third compartment. Methods of reconstruction described included primary repair, tendon grafting, and tendon transfer techniques; all with generally good outcomes. These results highlight the inherent fragility of this tendon and support the historical recommendation for early release of the EPL tendon in the setting of tenosynovitis of the third dorsal compartment.

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.

Gut feelings, deliberative thought, and paranoid ideation: a study of experiential and rational reasoning.

Rapid intuitive hunches or gut feelings may be a compelling source of evidence for paranoid ideas. Conversely, a failure to apply effortful analytic thinking may contribute to the persistence of such thoughts. Our main aim was to examine for the first time the associations of persecutory thinking with experiential and rational thinking styles. Five hundred individuals recruited from the general population completed self-report assessments of current persecutory ideation, general reasoning styles and personality traits. Persecutory ideation was independently associated with greater use of experiential reasoning and less use of rational reasoning. The correlations were small. Persecutory ideation was also positively associated with neuroticism and negatively correlated with extraversion, agreeableness and conscientiousness. There was no evidence of an interaction between neuroticism and experiential reasoning in the prediction of paranoia, but high experiential reasoning in the context of low rational reasoning was particularly associated with persecutory ideation. Overall, the study provides rare evidence of self-reported general reasoning styles being associated with delusional ideation. Perceived reliance on intuition is associated with paranoid thinking, while perceived reliance on deliberation is associated with fewer such thoughts. The dual process theory of reasoning may provide a framework to contribute to the understanding of paranoid thinking.

A Technical Guide for Sciatic Nerve Targeted Muscle Reinnervation in a Transfemoral Amputee.

There are approximately 2 million people living with the loss of a major limb in America. It is estimated that 95% of these will have some form of pain associated with their amputation. Phantom limb pain, related to symptomatic neuromas, contributes to amputation morbidity and can be difficult to treat. Studies have shown that targeted muscle reinnervation (TMR), by giving symptomatic neuromas "somewhere to go and something to do," can be an effective therapy. However, a large proportion of surgeons still treat symptomatic neuromas by burying them in nearby tissue. Methods: We treated a patient with previous above-the-knee amputation, complicated by a symptomatic neuroma, with TMR. We identified and described nine steps to the procedure. Our description is accompanied by illustrative, intraoperative photographs and technical pearls. Results: This article provides a description of TMR technique involving a neuroma of the sciatic nerve and its branches, to treat an above-the-knee amputation, with the aim of making this approach more accessible. At 9-month follow-up, the patient had active firing of the recipient muscles with donor nerve stimulation indicating successful reinnervation. The patient continued to report stump pain, but with intermittent pain-free days. Conclusions: TMR has proven potential as a therapy for amputation-related, neuropathic pain. With this technical guide to TMR, surgeons should feel more comfortable adding this technique to their armamentarium, to be utilized either at the time of amputation or as a secondary measure.

'Stop sign' position for subclavian ultrasound: a single-blinded observational study of subclavian vein dimensions.

OBJECTIVE: Right subclavian vein (SCV) dimensions were evaluated on ultrasound and whether these change when the right upper limb is in a neutral position compared with the 'stop sign' position (shoulder abducted and externally rotated to 90°, elbow flexed to 90°), and when patients were positioned 30° head-up compared with lying supine. METHODS: Images of transverse and longitudinal views of the right SCV in patients ≥18 years, presenting with a range of conditions to a Regional Hospital Emergency Department, were recorded by two physicians in a randomly assigned, nonsequential order and measured blinded. Data were analysed with paired Student's t tests. N = 62. RESULTS: Primary outcome: cross-sectional area (CSA) of the right SCV in transverse images. SECONDARY OUTCOMES: depth of SCV to skin and diameter of SCV on longitudinal images. There was no significant difference in CSA of the SCV in supine patients when the arm was in the stop sign position compared with neutral (mean CSA: 1.20 ± 0.42 and 1.15 ± 0.39 cm, respectively; P = 0.3). In patients positioned 30° head-up, the stop sign position significantly increased CSA from 0.65 ± 0.33 to 1.00 ± 0.38 cm (P < 0.0001). CONCLUSIONS: Utilizing the stop sign position does not change SVC dimensions when patients are supine, however, may improve dimensions when lying supine is contraindicated.

Automated psychological therapy using virtual reality (VR) for patients with persecutory delusions: study protocol for a single-blind parallel-group randomised controlled trial (THRIVE).

BACKGROUND: Persecutory delusions are a major psychiatric problem and are associated with a wide range of adverse outcomes. Our theoretical model views these delusions as unfounded threat beliefs which persist due to defence behaviours (e.g. avoidance) that prevent disconfirmatory evidence being processed. The treatment implications are that patients need to (1) go into feared situations and (2) not use defence behaviours. This enables relearning of safety and hence paranoia diminution. However, this is very difficult for patients due to their severe anxiety. A solution is to use virtual reality (VR) social situations, which are graded in difficulty and which patients find much easier to enter. We have now automated the provision of cognitive therapy within VR using an avatar coach, so that a therapist is not required and the treatment is scalable. In the THRIVE trial, the automated VR cognitive treatment will be tested against a VR control condition. It will contribute to our wider programme of work developing VR for patients with psychosis. METHODS: Patients with persistent persecutory delusions in the context of non-affective psychosis will be randomised (1:1) to the automated VR cognitive treatment or VR mental relaxation (control condition). Each VR treatment will comprise approximately four sessions of 30 min. Standard care will remain as usual in both groups. Assessments will be carried out at 0, 2, 4 (post treatment), 8, 16, and 24 weeks by a researcher blind to treatment allocation. The primary outcome is degree of conviction in the persecutory delusion (primary endpoint 4 weeks). Effect sizes will be re-established by an interim analysis of 30 patients. If the interim effect size suggests that the treatment is worth pursuing (d > 0.1), then the trial will go on to test 90 patients in total. Secondary outcomes include real world distress, activity levels, suicidal ideation, and quality of life. Mediation will also be tested. All main analyses will follow the intention-to-treat principle. The trial is funded by the Medical Research Council Developmental Pathway Funding Scheme. DISCUSSION: The trial will provide the first test of automated cognitive therapy within VR for patients with psychosis. The treatment is potentially highly scalable for treatment services. TRIAL REGISTRATION: ISRCTN, ISRCTN12497310 . Registered on 14 August 2018.

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 effects of cannabidiol on persecutory ideation and anxiety in a high trait paranoid group.

BACKGROUND: Previous studies have suggested that cannabidiol has anxiolytic and antipsychotic properties, raising hopes that cannabidiol will translate to the psychiatric clinic. Cannabidiol may be particularly useful for anxiety and paranoia in those at-risk of major mental illness. METHODS: Immersion in a controlled 3D virtual-reality scenario was used to assay persecutory ideation and anxiety in a sample of non-clinical volunteers ( n=32) pre-selected for high paranoid traits. Participants were randomised to receive oral cannabidiol (600 mg) or placebo 130 min prior to entering virtual-reality. Well-validated rating scales were used to assay persecutory thinking and anxiety. Salivary cortisol concentration, heart rate and blood pressure were measured over the course of the experimental session. RESULTS: Immersion in the virtual-reality session elicited anxiety as indexed by the Beck's anxiety inventory ( p<0.005), and increased cortisol concentration ( p=0.05), heart rate ( p<0.05) and systolic blood pressure ( p<0.05). However, cannabidiol had no impact upon any of these effects, except for a strong trend to increase anxiety ( p=0.09). Cannabidiol had no effect on persecutory ideation as assayed by the Community Assessment of Psychic Experiences questionnaire or the State Social Paranoia Scale. CONCLUSIONS: In contrast to previous studies, there was no evidence of any benefits of cannabidiol on anxiety or persecutory ideation in healthy volunteers with high trait paranoia. However, a larger sample will be required for a definitive study.

The patient experience of sleep problems and their treatment in the context of current delusions and hallucinations.

OBJECTIVES: There is increasing recognition that sleep problems are common in patients with psychosis, that they exacerbate delusions and hallucinations and should be a treatment target. The aim of this study was to gain a patient perspective on the nature of sleep problems in psychosis and experience of treatment. DESIGN: A qualitative, semi-structured interview-based study to explore patient accounts of sleep problems and associated psychological treatment. METHODS: Ten patients with recent delusions and hallucinations, who had experienced sleep problems and received psychological treatment during a clinical trial (the Better Sleep Trial), were interviewed. Responses were analysed using interpretative phenomenological analysis. RESULTS: Patients reported experiencing problems of getting to sleep, staying asleep, too much sleep, nightmares, and erratic sleep patterns. These sleep problems caused emotional distress, fatigue, and reduction in daytime activities. Worry and psychotic experiences disturbed sleep, while consequent tiredness meant that patients coped poorly with voices and persecutory fears. Treatment for sleep problems was viewed very positively and considered to have wide-ranging impacts. CONCLUSIONS: Sleep disturbance is a major problem for patients with psychosis, which should be treated more often in services using evidence-based interventions. PRACTITIONER POINTS: Psychological interventions for sleep problems are valued by patients with psychosis. Patients with current distressing psychotic experiences report wide-ranging benefits from a brief psychological intervention for sleep problems.

Genetic moderation of the effects of cannabis: catechol-O-methyltransferase (COMT) affects the impact of Δ9-tetrahydrocannabinol (THC) on working memory performance but not on the occurrence of psychotic experiences.

Cannabis use can induce cognitive impairments and psychotic experiences. A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val(158)Met) appears to influence the immediate cognitive and psychotic effects of cannabis, or ∆(9)-tetrahydrocannabinol (THC), its primary psychoactive ingredient. This study investigated the moderation of the impact of experimentally administered THC by COMT. Cognitive performance and psychotic experiences were studied in participants without a psychiatric diagnosis, using a between-subjects design (THC vs. placebo). The effect of COMT Val(158)Met genotype on the cognitive and psychotic effects of THC, administered intravenously in a double-blind, placebo-controlled manner to 78 participants who were vulnerable to paranoia, was examined. The results showed interactive effects of genotype and drug group (THC or placebo) on working memory, assayed using the Digit Span Backwards task. Specifically, THC impaired performance in COMT Val/Val, but not Met, carriers. In contrast, the effect of THC on psychotic experiences, measured using the Community Assessment of Psychic Experiences (CAPE) positive dimension, was unaffected by COMT genotype. This study is the largest to date examining the impact of COMT genotype on response to experimentally administered THC, and the first using a purely non-clinical cohort. The data suggest that COMT genotype moderates the cognitive, but not the psychotic, effects of acutely administered THC.

Efficacy of cognitive behavioural therapy for sleep improvement in patients with persistent delusions and hallucinations (BEST): a prospective, assessor-blind, randomised controlled pilot trial.

BACKGROUND: Sleep disturbance occurs in most patients with delusions or hallucinations and should be treated as a clinical problem in its own right. However, cognitive behavioural therapy (CBT)-the best evidence-based treatment for insomnia-has not been tested in this patient population. We aimed to pilot procedures for a randomised trial testing CBT for sleep problems in patients with current psychotic experiences, and to provide a preliminary assessment of potential benefit. METHODS: We did this prospective, assessor-blind, randomised controlled pilot trial (Better Sleep Trial [BEST]) at two mental health centres in the UK. Patients (aged 18-65 years) with persistent distressing delusions or hallucinations in the context of insomnia and a schizophrenia spectrum diagnosis were randomly assigned (1:1), via a web-based randomisation system with minimisation to balance for sex, insomnia severity, and psychotic experiences, to receive either eight sessions of CBT plus standard care (medication and contact with the local clinical team) or standard care alone. Research assessors were masked to group allocation. Assessment of outcome was done at weeks 0, 12 (post-treatment), and 24 (follow-up). The primary efficacy outcomes were insomnia assessed by the Insomnia Severity Index (ISI) and delusions and hallucinations assessed by the Psychotic Symptoms Rating Scale (PSYRATS) at week 12. We did analysis by intention to treat, with an aim to provide confidence interval estimation of treatment effects. This study is registered with ISRCTN, number 33695128. FINDINGS: Between Dec 14, 2012, and May 22, 2013, and Nov 7, 2013, and Aug 26, 2014, we randomly assigned 50 patients to receive CBT plus standard care (n=24) or standard care alone (n=26). The last assessments were completed on Feb 10, 2015. 48 (96%) patients provided follow-up data. 23 (96%) patients offered CBT took up the intervention. Compared with standard care, CBT led to reductions in insomnia in the large effect size range at week 12 (adjusted mean difference 6.1, 95% CI 3.0-9.2, effect size d=1.9). By week 12, nine (41%) of 22 patients receiving CBT and one (4%) of 25 patients receiving standard care alone no longer had insomnia, with ISI scores lower than the cutoff for insomnia. The treatment effect estimation for CBT covered a range from reducing but also increasing delusions (adjusted mean difference 0.3, 95% CI -2.0 to 2.6) and hallucinations (-1.9, -6.5 to 2.7). Three patients, all in the CBT group, had five adverse events, although none were regarded as related to study treatment. INTERPRETATION: Our findings show that CBT for insomnia might be highly effective for improving sleep in patients with persistent delusions or hallucinations. A larger, suitably powered phase 3 study is now needed to provide a precise estimate of the effects of CBT for sleep problems, both on sleep and psychotic experiences. FUNDING: Research for Patient Benefit Programme, National Institute for Health Research.