Social influences on the relationship between dissociation and psychotic-like experiences.

BACKGROUND: Shame is experienced as a threat to social self, and so activates threat-protective responses. There is evidence that shame has trauma-like characteristics, suggesting it can be understood within the same conceptual framework as trauma and dissociation. Evidence for causal links among trauma, dissociation, and psychosis thus warrant the investigation of how shame may influence causal mechanisms for psychosis symptoms. METHODS: This study tested the interaction between dissociation and shame, specifically external shame (feeling shamed by others), in predicting psychotic-like experiences (PLEs) six months later in a general population sample (N = 314). It also tested if social safeness moderates these effects. A longitudinal, online questionnaire design tested a moderation model (dissociation-shame) and a moderated moderation model (adding social safeness), using multiple regressions with bootstrap procedures. RESULTS: Although there was no direct effect of dissociation on PLEs six months later, there was a significant interaction effect with shame, controlling for PLEs at baseline. There were complex patterns in the directions of effects: For high-shame-scorers, higher dissociation predicted higher PLE scores, but for low-shame-scorers, higher dissociation predicted lower PLE scores. Social safeness was found to significantly moderate these interaction effects, which were unexpectedly more pronounced in the context of higher social safeness. CONCLUSIONS: The results demonstrate evidence for an interaction between dissociation and shame on its impact on PLEs, which manifests particularly for those experiencing higher social safeness. This suggests a potential role of social mechanisms in both the etiology and treatment of psychosis, which warrants further testing in clinical populations.

Investigating associations between self-compassion, self-criticism and psychotic-like experiences.

OBJECTIVES: Dimensional approaches suggest psychotic symptoms exist along a continuum, with psychotic-like experiences (PLEs) being an expression of a non-clinical psychosis phenotype. Existing research indicates self-criticism may contribute to symptom maintenance, frequency and distress, whereas self-compassion may act protectively. Associations between self-criticism, self-compassion and PLEs in the general population have received less attention. The present study sought to investigate these associations. It was hypothesised that PLE endorsement would be associated positively with self-criticism and negatively with self-compassion. DESIGN: Quantitative cross-sectional study. Data collected via an online questionnaire. METHODS: Five hundred thirty-one participants completed the Self-Compassion Scale (Short Form), the Forms of Self-Criticising/Attacking and Self-Reassuring Scale and the Transpersonal Experiences Questionnaire. Individuals with a psychosis-related diagnosis were excluded. The data were analysed using linear regression, accounting for the effects of demographic variables. RESULTS: Self-criticism subtype self-hatred was associated with PLEs. Subtype self-inadequacy was not. No association was found between self-compassion and PLEs. Educational attainment was negatively associated with PLE endorsement. CONCLUSIONS: Self-criticism, but not self-compassion, is associated with PLE endorsement, suggesting they are separate factors with different relationships to PLEs. Further research is needed to confirm the direction of the interaction. Either way, psychological interventions (where needed) could target self-criticism and may be important in assessing psychosis risk.

A brief CBT intervention for depersonalisation-derealisation disorder in psychosis: Results from a feasibility randomised controlled trial.

BACKGROUND AND OBJECTIVES: Depersonalisation/derealisation symptoms are prevalent in psychosis patients, are associated with increased impairment, and may maintain psychosis symptoms. We aimed to establish the feasibility and acceptability of a brief, six session therapy protocol adapted from a Cognitive-Behavioural model of Depersonalisation-Derealisation Disorder (DDD) in participants with psychotic symptoms. METHODS: A single-blind, randomised controlled trial was conducted with a treatment-as-usual control condition. Feasibility and acceptability estimates included rates of referral, acceptance, eligibility, consent, satisfaction and improved skills/knowledge to manage depersonalisation. RESULTS: Twenty-one individuals were recruited to the trial. Results suggest that the intervention was feasible and acceptable to participants and there is some signal of effect on clinical outcomes. LIMITATIONS: There were some challenges in recruitment. Recruitment feasibility estimates from the research register used may not be informative for future trials recruiting directly from teams. CONCLUSIONS: Overall, the results suggest that further investigations would be of interest and recommendations for this are made.

User-Centered Development of STOP (Successful Treatment for Paranoia): Material Development and Usability Testing for a Digital Therapeutic for Paranoia.

BACKGROUND: Paranoia is a highly debilitating mental health condition. One novel intervention for paranoia is cognitive bias modification for paranoia (CBM-pa). CBM-pa comes from a class of interventions that focus on manipulating interpretation bias. Here, we aimed to develop and evaluate new therapy content for CBM-pa for later use in a self-administered digital therapeutic for paranoia called STOP ("Successful Treatment of Paranoia"). OBJECTIVE: This study aimed to (1) take a user-centered approach with input from living experts, clinicians, and academics to create and evaluate paranoia-relevant item content to be used in STOP and (2) engage with living experts and the design team from a digital health care solutions company to cocreate and pilot-test the STOP mobile app prototype. METHODS: We invited 18 people with living or lived experiences of paranoia to create text exemplars of personal, everyday emotionally ambiguous scenarios that could provoke paranoid thoughts. Researchers then adapted 240 suitable exemplars into corresponding intervention items in the format commonly used for CBM training and created 240 control items for the purpose of testing STOP. Each item included newly developed, visually enriching graphics content to increase the engagement and realism of the basic text scenarios. All items were then evaluated for their paranoia severity and readability by living experts (n=8) and clinicians (n=7) and for their item length by the research team. Items were evenly distributed into six 40-item sessions based on these evaluations. Finalized items were presented in the STOP mobile app, which was co-designed with a digital health care solutions company, living or lived experts, and the academic team; user acceptance was evaluated across 2 pilot tests involving living or lived experts. RESULTS: All materials reached predefined acceptable thresholds on all rating criteria: paranoia severity (intervention items: ≥1; control items: ≤1, readability: ≥3, and length of the scenarios), and there was no systematic difference between the intervention and control group materials overall or between individual sessions within each group. For item graphics, we also found no systematic differences in users' ratings of complexity (P=.68), attractiveness (P=.15), and interest (P=.14) between intervention and control group materials. User acceptance testing of the mobile app found that it is easy to use and navigate, interactive, and helpful. CONCLUSIONS: Material development for any new digital therapeutic requires an iterative and rigorous process of testing involving multiple contributing groups. Appropriate user-centered development can create user-friendly mobile health apps, which may improve face validity and have a greater chance of being engaging and acceptable to the target end users.

Evaluation of reliability and validity of the Persian version of Peters et al. delusions inventory (PDI-40) in iranian non-clinical and clinical samples.

BACKGROUND: Some individuals may manifest psychotic symptoms that do not fulfill the requisite clinical criteria for a formal diagnosis of psychosis. The assessment of susceptibility to delusions, encompassing both clinical and non-clinical cohorts, frequently makes use of the Peters et al. Delusions Inventory (PDI-40). This study aimed to evaluate the reliability and validity of the Persian version of Peters et al. Delusions Inventory (PDI-40) in Iranian non-clinical and clinical samples. METHODS: The present study employed a cross-sectional, correlational design in 2020. A total of 1402 Iranian participants were recruited for the study, which consisted of three distinct stages. The first stage involved an Exploratory Factor Analysis (EFA) conducted on a non-clinical sample of 512 participants. The second stage comprising different non-clinical sample 764 participants to perform a Confirmatory Factor Analysis (CFA). In the third stage, a clinical sample of 126 psychotic patients was compared to a non-clinical sample. All participants completed the PDI-40, the Community Assessment of Psychotic Experiences (CAPE-42), and the Depression, Anxiety, and Stress Scale (DASS-21). The internal structure of PDI-40 was examined through the analysis of its factor structure using LISREL 8.8. RESULTS: The EFA analysis unveiled nine components within Persian version of PDI-40. The CFA analysis demonstrated an excellent fit of the nine-factor structure of Persian PDI-40 to the data. The total score exhibited high internal reliability, as indicated by Cronbach's alpha coefficient of 0.92. Moreover, Persian PDI-40 exhibited satisfactory evidence of convergent validity, as significant correlations were observed between dimensions of PDI-40 and subscales of CAPE-42 and DASS-21. Lastly, findings indicated that psychotic participants scored higher than non-clinical participants in all components of the PDI-40(p < 0.05). CONCLUSION: Persian version of the PDI-40 demonstrates strong reliability and validity for assessing delusion proneness in both non-clinical and clinical samples in Iran. The observed distinctions between psychotic and non-clinical participants underscore its potential as a valuable tool for discerning delusion proneness in diverse contexts.

A case series study of compassion-focused therapy for distressing experiences in psychosis.

OBJECTIVES: Compassion-focused therapy (CFT) is an evolution-informed biopsychosocial approach that seeks to cultivate attachment and care motivational systems and their psychophysiological regulators. These can counteract some of the harmful effects of social threat, inferiority, shame, self-criticism and depression, which are common in people with psychosis and undermine their well-being, social trust and ability to feel safe. This study aimed to test the acceptability of a novel manualized individual CFT intervention for psychosis (CFTp). DESIGN: A non-concurrent, multiple-baseline, case series design, with three phases: baseline, intervention and follow-up. METHODS: The 26-session CFTp intervention was provided for a sample of eight people with distressing psychotic experiences and a psychosis-related diagnosis. The study aimed to assess acceptability of CFTp and to test clinically reliable improvements while receiving the intervention, compared to a baseline period. RESULTS: Seven of eight participants completed the therapy, and clinically reliable improvements were found at both the single-case and group level of analysis. At the single-case level, over half the participants showed improvements in depression (5/7), stress (5/7), distress (5/7), anxiety (4/7) and voices (3/5). One participant showed a deterioration in anxiety (1/7) and dissociation (1/7). At the group level (n = 7), there were significant improvements in depression, stress, distress, voices and delusions. The improvements in voices, delusions and distress were sustained at 6- to 8-week follow-up, but depression and stress dropped slightly to trend-level improvements. CONCLUSIONS: CFTp is a feasible and acceptable intervention for psychosis, and further investigation is warranted with a randomized controlled trial.

Learning to Discern the Voices of Gods, Spirits, Tulpas, and the Dead.

There are communities in which hearing voices frequently is common and expected, and in which participants are not expected to have a need for care. This paper compares the ideas and practices of these communities. We observe that these communities utilize cultural models to identify and to explain voice-like events-and that there are some common features to these models across communities. All communities teach participants to "discern," or identify accurately, the legitimate voice of the spirit or being who speaks. We also observe that there are roughly two methods taught to participants to enable them to experience spirits (or other invisible beings): trained attention to inner experience, and repeated speech to the invisible other. We also observe that all of these communities model a learning process in which the ability to hear spirit (or invisible others) becomes more skilled with practice, and in which what they hear becomes clearer over time. Practice-including the practice of discernment-is presumed to change experience. We also note that despite these shared cultural ideas and practices, there is considerable individual variation in experience-some of which may reflect psychotic process, and some perhaps not. We suggest that voice-like events in this context may be shaped by cognitive expectation and trained practice as well as an experiential pathway. We also suggest that researchers could explore these common features both as a way to help those struggling with psychosis, and to consider the possibility that expectations and practice may affect the voice-hearing experience.

Detecting anomalous experiences in the community: The Transpersonal Experiences Questionnaire (TEQ).

OBJECTIVES: There is growing recognition of the value of researching anomalous experiences in the general population to aid our understanding of the psychosis continuum. There are key differences in aims, foci and epistemologies of existing measures, with varying utility for specific research designs. This study addresses gaps in the literature by developing a measure of anomalous experiences with utility for longitudinal (time-sensitive) research, and with particular reliability for people towards the upper (high scoring) end of the continuum. METHODS: An online sample was recruited from the general population to provide questionnaire data for two study parts: (A) item selection and (B) psychometric evaluation. For Part A, both classical test theory and item response theory methods were used to select which items to be included from an initial pool of 57, generated from individuals with persistent anomalous experiences. For Part B, psychometric properties of the resulting measure were evaluated using exploratory and confirmatory factor analysis and tests of reliability and validity. RESULTS: Scores were provided by 532 participants, from which a 19-item scale, the Transpersonal Experiences Questionnaire (TEQ), was developed. The TEQ was found to be a unidimensional scale, with satisfactory internal consistency (0.85), good test-retest reliability and convergent validity. CONCLUSIONS: The TEQ can be used as a unidimensional scale to detect anomalous experiences in the general population, with particular reliability for people with higher incidence of these experiences.

Cognitive bias modification for paranoia (CBM-pa): a randomised controlled feasibility study in patients with distressing paranoid beliefs.

BACKGROUND: Cognitive Bias Modification for paranoia (CBM-pa) is a novel, theory-driven psychological intervention targeting the biased interpretation of emotional ambiguity associated with paranoia. Study objectives were (i) test the intervention's feasibility, (ii) provide effect size estimates, (iii) assess dose-response and (iv) select primary outcomes for future trials. METHODS: In a double-blind randomised controlled trial, sixty-three outpatients with clinically significant paranoia were randomised to either CBM-pa or an active control (text reading) between April 2016 and September 2017. Patients received one 40 min session per week for 6 weeks. Assessments were given at baseline, after each interim session, post-treatment, and at 1- and 3-months post-treatment. RESULTS: A total of 122 patients were screened and 63 were randomised. The recruitment rate was 51.2%, with few dropouts (four out of 63) and follow-up rates were 90.5% (1-month) and 93.7% (3-months). Each session took 30-40 min to complete. There was no statistical evidence of harmful effects of the intervention. Preliminary data were consistent with efficacy of CBM-pa over text-reading control: patients randomised to the intervention, compared to control patients, reported reduced interpretation bias (d = -0.48 to -0.76), improved symptoms of paranoia (d = -0.19 to -0.38), and lower depressed and anxious mood (d = -0.03 to -0.29). The intervention effect was evident after the third session. CONCLUSIONS: CBM-pa is feasible for patients with paranoia. A fully powered randomised control trial is warranted.

Multisite randomised controlled trial of trauma-focused cognitive behaviour therapy for psychosis to reduce post-traumatic stress symptoms in people with co-morbid post-traumatic stress disorder and psychosis, compared to treatment as usual: study protocol for the STAR (Study of Trauma And Recovery) trial.

BACKGROUND: People with psychosis have high rates of trauma, with a post-traumatic stress disorder (PTSD) prevalence rate of approximately 15%, which exacerbates psychotic symptoms such as delusions and hallucinations. Pilot studies have shown that trauma-focused (TF) psychological therapies can be safe and effective in such individuals. This trial, the largest to date, will evaluate the clinical effectiveness of a TF therapy integrated with cognitive behaviour therapy for psychosis (TF-CBTp) on post-traumatic stress symptoms in people with psychosis. The secondary aims are to compare groups on cost-effectiveness; ascertain whether TF-CBTp impacts on a range of other meaningful outcomes; determine whether therapy effects endure; and determine acceptability of the therapy in participants and therapists. METHODS: Rater-blind, parallel arm, pragmatic randomised controlled trial comparing TF-CBTp + treatment as usual (TAU) to TAU only. Adults (N = 300) with distressing post-traumatic stress and psychosis symptoms from five mental health Trusts (60 per site) will be randomised to the two groups. Therapy will be manualised, lasting 9 months (m) with trained therapists. We will assess PTSD symptom severity (primary outcome); percentage who show loss of PTSD diagnosis and clinically significant change; psychosis symptoms; emotional well-being; substance use; suicidal ideation; psychological recovery; social functioning; health-related quality of life; service use, a total of four times: before randomisation; 4 m (mid-therapy); 9 m (end of therapy; primary end point); 24 m (15 m after end of therapy) post-randomisation. Four 3-monthly phone calls will be made between 9 m and 24 m assessment points, to collect service use over the previous 3 months. Therapy acceptability will be assessed through qualitative interviews with participants (N = 35) and therapists (N = 5-10). An internal pilot will ensure integrity of trial recruitment and outcome data, as well as therapy protocol safety and adherence. Data will be analysed following intention-to-treat principles using generalised linear mixed models and reported according to Consolidated Standards of Reporting Trials-Social and Psychological Interventions Statement. DISCUSSION: The proposed intervention has the potential to provide significant patient benefit in terms of reductions in distressing symptoms of post-traumatic stress, psychosis, and emotional problems; enable clinicians to implement trauma-focused therapy confidently in this population; and be cost-effective compared to TAU through reduced service use. TRIAL REGISTRATION: ISRCTN93382525 (03/08/20).

The digital divide: factors impacting on uptake of remote therapy in a South London psychological therapy service for people with psychosis.

BACKGROUND: Remote therapy promises a cost-effective way of increasing delivery of psychological-therapy in underserved populations. However, research shows a "digital divide", with some groups experiencing digital exclusion. AIMS: To assess whether technology, accessibility, and demographic factors influence remote therapy uptake among individuals with psychosis, and whether demographic factors are associated with digital exclusion. METHODS: Remote therapy uptake and demographics were assessed in people (n = 51) within a psychology-led service for psychosis, using a survey of access to digital hardware, data and private space. RESULTS: The majority of individuals had access to digital devices, but 29% did not meet minimum requirements for remote therapy. Nineteen (37%) individuals declined remote therapy. Those who accepted were significantly younger and more likely to have access to technology than those who declined. The mean age of those with access to smartphones and large screen devices was younger than those without access. CONCLUSIONS: A subgroup of people with psychosis face barriers to remote therapy and a significant minority are digitally excluded. Older age is a key factor influencing remote therapy uptake, potentially related to less access to digital devices. Services must minimize exclusion through provision of training, hardware and data, whilst promoting individual choice.

Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

The effects of voice content on stress reactivity: A simulation paradigm of auditory verbal hallucinations.

OBJECTIVES: Psychosis is associated with increased subjective and altered endocrine and autonomic nervous system stress-reactivity. Psychosis patients often experience auditory verbal hallucinations, with negative voice content being particularly associated with distress. The present study developed a voice-simulation paradigm and investigated the effect of simulated voices with neutral and negative content on psychophysiological stress-reactivity, and the effect of mindful voice-appraisals on stress-reactivity. METHOD: Eighty-four healthy participants completed the Montreal Imaging Stress Task with simultaneous presentation of one of three randomly allocated auditory stimuli conditions: negative voices, neutral voices or non-voice ambient sounds. Subjective stress-levels and mindful voice-appraisals were assessed using questionnaire measures, and cortisol and α-amylase levels were measured using saliva samples. RESULTS: ANOVA revealed a significant effect of condition on subjective stress-levels (p = .002), but not cortisol (p = .63) or α-amylase (p = .73). Post-hoc analyses showed that negative voices increased subjective stress-levels relative to neutral voices (p = .002) and ambient sounds (p = .01), which did not differ from each other (p = .41). Mindful voice-appraisals were associated with less distress across conditions (p = .003), although negative voices were also associated with less mindful appraisals (p < .001). CONCLUSIONS: Negative voice content, rather than voices or auditory stimuli per se, is linked to greater subjective but not physiological stress-reactivity. Mindful appraisals may partially moderate this effect. These findings highlight the importance of voice content for the impact of voice-hearing, and highlight the potential value of mindfulness training to treat voice distress in psychosis.

Associations between responses to voices, distress and appraisals during daily life: an ecological validation of the cognitive behavioural model.

BACKGROUND: Cognitive models propose that behavioural responses to voices maintain distress by preventing disconfirmation of negative beliefs about voices. We used Experience Sampling Methodology (ESM) to examine the hypothesized maintenance role of behavioural responses during daily life. METHOD: Thirty-one outpatients with frequent voices completed a smartphone-based ESM questionnaire 10 times a day over 9 days, assessing voice-related distress; resistance and compliance responses to voices; voice characteristics (intensity and negative content); appraisals of voice dominance, uncontrollability and intrusiveness. RESULTS: In line with predictions, behavioural responses were associated with voice appraisals (dominance and uncontrollability), but not voice characteristics. Greater resistance and compliance were reported in moments of increased voice distress, but these associations did not persist after controlling for concurrent voice appraisals and characteristics. Voice distress was predicted by appraisals, and, unexpectedly, also by voice characteristics. As predicted, compliance and resistance were related to increases in distress at subsequent timepoints, whilst antecedent voice appraisals and characteristics had no such effect. Compliance, but not resistance, additionally predicted subsequent increases in voice uncontrollability. In both cases, the reverse models showed no association, indicating directional effects of responses on subsequent distress, and of compliance on uncontrollability appraisals. CONCLUSIONS: These results provide support for the cognitive model by suggesting that momentary behavioural and emotional responses to voices are associated with concurrent negative voice appraisals. Findings suggest that behavioural responses may be driven by voice appraisals, rather than directly by distress, and may in turn maintain voice appraisals and associated distress during the course of daily life.

Social isolation and psychosis: an investigation of social interactions and paranoia in daily life.

Social isolation has been suggested to foster paranoia. Here we investigate whether social company (i.e., being alone vs. not) and its nature (i.e., stranger/distant vs. familiar other) affects paranoia differently depending on psychosis risk. Social interactions and paranoid thinking in daily life were investigated in 29 patients with clinically stable non-affective psychotic disorders, 20 first-degree relatives, and 26 controls (n = 75), using the experience sampling method (ESM). ESM was completed up to ten times daily for 1 week. Patients experienced marginally greater paranoia than relatives [b = 0.47, p = 0.08, 95% CI (- 0.06, 1.0)] and significantly greater paranoia than controls [b = 0.55, p = 0.03, 95% CI (0.5, 1.0)], but controls and relatives did not differ [b = 0.07, p = 0.78, 95% CI (- 0.47, 0.61)]. Patients were more often alone [68.5% vs. 44.8% and 56.2%, respectively, p = 0.057] and experienced greater paranoia when alone than when in company [b = 0.11, p = 0.016, 95% CI (0.02, 0.19)]. In relatives this was reversed [b = - 0.17, p < 0.001, 95% CI (- 0.28, - 0.07)] and in controls non-significant [b = - 0.02, p = 0.67, 95% CI (- 0.09, 0.06)]. The time-lagged association between being in social company and subsequent paranoia was non-significant and paranoia did not predict the likelihood of being in social company over time (both p's = 0.68). All groups experienced greater paranoia in company of strangers/distant others than familiar others [X2(2) = 4.56, p = 0.03] and being with familiar others was associated with lower paranoia over time [X2(2) = 4.9, p = 0.03]. Patients are frequently alone. Importantly, social company appears to limit their paranoia, particularly when being with familiar people. The findings stress the importance of interventions that foster social engagement and ties with family and friends.

You read my mind: fMRI markers of threatening appraisals in people with persistent psychotic experiences.

Anomalous perceptual experiences are relatively common in the general population. Evidence indicates that the key to distinguishing individuals with persistent psychotic experiences (PEs) with a need for care from those without is how they appraise their anomalous experiences. Here, we aimed to characterise the neural circuits underlying threatening and non-threatening appraisals in people with and without a need for care for PEs, respectively. A total of 48 participants, consisting of patients with psychosis spectrum disorder (clinical group, n = 16), non-need-for-care participants with PEs (non-clinical group, n = 16), and no-PE healthy control participants (n = 16), underwent functional magnetic resonance imaging while completing the Telepath task, designed to induce an anomalous perceptual experience. Appraisals of the anomalous perceptual experiences were examined, as well as functional brain responses during this window, for significant group differences. We also examined whether activation co-varied with the subjective threat appraisals reported in-task by participants. The clinical group reported elevated subjective threat appraisals compared to both the non-clinical and no-PE control groups, with no differences between the two non-clinical groups. This pattern of results was accompanied by reduced activation in the superior and inferior frontal gyri in the clinical group as compared to the non-clinical and control groups. Precuneus activation scaled with threat appraisals reported in-task. Resilience in the context of persistent anomalous experiences may be explained by intact functioning of fronto-parietal regions, and may correspond to the ability to contextualise and flexibly evaluate psychotic experiences.

Networks underpinning emotion: A systematic review and synthesis of functional and effective connectivity.

Existing models of emotion processing are based almost exclusively on brain activation data, yet make assumptions about network connectivity. There is a need to integrate connectivity findings into these models. We systematically reviewed all studies of functional and effective connectivity employing tasks to investigate negative emotion processing and regulation in healthy participants. Thirty-three studies met inclusion criteria. A quality assessment tool was derived from prominent neuroimaging papers. The evidence supports existing models, with primarily limbic regions for salience and identification, and frontal areas important for emotion regulation. There was mixed support for the assumption that regulatory influences on limbic and sensory areas come predominantly from prefrontal areas. Rather, studies quantifying effective connectivity reveal context-dependent dynamic modulatory relationships between occipital, subcortical, and frontal regions, arguing against purely top-down regulatory theoretical models. Our quality assessment tool found considerable variability in study design and tasks employed. The findings support and extend those of previous syntheses focused on activation studies, and provide evidence for a more nuanced view of connectivity in networks of human emotion processing and regulation.

Psychophysiological stress-reactivity in clinical and non-clinical voice-hearers.

BACKGROUND: Psychosis is associated with dysregulation of psychophysiological stress-reactivity, including in subjective, autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) parameters. AIMS: This study investigated whether dysregulated psychophysiological stress-reactivity is specifically associated with auditory verbal hallucinations (AVHs) or psychosis more generally by comparing voice-hearers with and without a need for care. METHOD: Clinical (n = 20) and non-clinical voice-hearers (n = 23), as well as a healthy control group with no voices (n = 23), were compared on HPA and ANS responses, and subjective reactivity, to a psychophysiological stress paradigm, the socially evaluative cold pressor test. RESULTS: Measures of HPA function in both clinical and non-clinical voice-hearers diverged from non-voice-hearing controls. Clinical participants showed a blunted peak response compared to both non-clinical groups (p = 0.02), whilst non-clinical voice-hearers showed, at trend-level, reduced cortisol levels during stress exposure compared to both clinical voice-hearers (p = 0.07) and healthy controls (p = 0.07), who unexpectedly did not differ from each other (p = 0.97). Clinical participants showed greater subjective stress levels than both non-clinical groups (p < 0.001), as well as greater anticipatory stress (p = 0.001) and less recovery. There were no differences between groups on parameters of the ANS (all p > 0.05). CONCLUSIONS: Dysregulated psychophysiological stress-function is present in clinical voice-hearers, and partially discriminates them from non-clinical voice-hearers. Overall, the present findings identified specific potential psychophysiological markers of risk and resilience in auditory verbal hallucinations and need for care.

Optimising AVATAR therapy for people who hear distressing voices: study protocol for the AVATAR2 multi-centre randomised controlled trial.

BACKGROUND: AVATAR therapy is a novel intervention targeting distressing auditory verbal hallucinations (henceforth 'voices'). A digital simulation (avatar) of the voice is created and used in a three-way dialogue between participant, avatar and therapist. To date, therapy has been delivered over 6 sessions, comprising an initial phase, focusing on standing up to a hostile avatar, and a second phase in which the avatar concedes and focus shifts to individualised treatment targets, including beliefs about voices. The first fully powered randomised trial found AVATAR therapy resulted in a rapid and substantial fall in voice frequency and associated distress that was superior to supportive counselling at 12 weeks. The main objective of this AVATAR2 trial is to test the efficacy of two forms of AVATAR therapy in reducing voice-related distress: AVATAR-brief (standardised focus on exposure, assertiveness and self-esteem) and AVATAR-extended (phase 1 mirroring AVATAR-brief augmented by a formulation-driven phase 2). Secondary objectives include the examination of additional voice, wellbeing and mood outcomes, the exploration of mediators and moderators of therapy response, and examining cost-effectiveness of both forms of therapy compared with usual treatment (TAU). METHODS: This multi-site parallel group randomised controlled trial will independently randomise 345 individuals to receive AVATAR-brief (6 sessions) plus TAU or AVATAR-extended (12 sessions) plus TAU or TAU alone (1:1:1 allocation). Participants will be people with a diagnosis of schizophrenia spectrum and other psychotic disorders who have heard distressing voices for more than 6 months. The primary outcome is the PSYRATS Auditory Hallucinations Distress dimension score at 16 and 28 weeks, conducted by blinded assessors. Statistical analysis will follow the intention-to-treat principle and data will be analysed using linear mixed models. Mediation and moderation analyses using contemporary causal inference methods will be conducted as secondary analyses. Service costs will be calculated, and cost-effectiveness assessed in terms of quality-adjusted life years accrued. DISCUSSION: This study will clarify optimal therapy delivery, test efficacy in a multi-site study and enable the testing of the AVATAR software platform, therapy training and provision in NHS settings. TRIAL REGISTRATION: ISRCTN registry ISRCTN55682735 . Registered on 22 January 2020. The trial is funded by the Wellcome Trust (WT).

The Early Youth Engagement in first episode psychosis (EYE-2) study: pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement.

BACKGROUND: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium-long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. METHOD: The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14-35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. DISCUSSION: The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. TRIAL REGISTRATION: ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.