A qualitative process evaluation of social recovery therapy for enhancement of social recovery in first-episode psychosis (SUPEREDEN3).

BACKGROUND: Many individuals with first-episode psychosis experience severe and persistent social disability despite receiving specialist early intervention. The SUPEREDEN3 trial assessed whether augmenting early intervention in psychosis services with Social Recovery Therapy (SRT) would lead to better social recovery. AIMS: A qualitative process evaluation was conducted to explore implementation and mechanisms of SRT impact from the perspective of SUPEREDEN3 participants. METHOD: A subsample of SUPEREDEN3 trial participants (n = 19) took part in semi-structured interviews, which were transcribed verbatim and analysed thematically. Trial participants were early intervention service users aged 16-35 years with severe and persistent social disability. Both SRT plus early intervention and early intervention alone arm participants were interviewed to facilitate better understanding of the context in which SRT was delivered and to aid identification of mechanisms specific to SRT. RESULTS: The six themes identified were used to generate an explanatory model of SRT's enhancement of social recovery. Participant experiences highlight the importance of the therapist cultivating increased self-understanding and assertively encouraging clients to face feared situations in a way that is perceived as supportive, while managing ongoing symptoms. The sense of achievement generated by reaching targets linked to personally meaningful goals promotes increased self-agency, and generates hope and optimism. CONCLUSIONS: The findings suggest potentially important processes through which social recovery was enhanced in this trial, which will be valuable in ensuring the benefits observed can be replicated. Participant accounts provide hope that, with the right support, even clients who have persistent symptoms and the most severe disability can make a good social recovery.

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.

Measuring adherence in social recovery therapy with people with first episode psychosis.

BACKGROUND: The SUPEREDEN3 study, a phase II randomized controlled trial, suggests that social recovery therapy (SRT) is useful in improving functional outcomes in people with first episode psychosis. SRT incorporates cognitive behavioural therapy (CBT) techniques with case management and employment support, and therefore has a different emphasis to traditional CBT for psychosis, requiring a new adherence tool. AIMS: This paper describes the SRT adherence checklist and content of the therapy delivered in the SUPEREDEN3 trial, outlining the frequency of SRT techniques and proportion of participants who received a full therapy dose. It was hypothesized that behavioural techniques would be used frequently, consistent with the behavioural emphasis of SRT. METHOD: Research therapists completed an adherence checklist after each therapy session, endorsing elements of SRT present. Data from 1236 therapy sessions were reviewed to determine whether participants received full, partial or no therapy dose. RESULTS: Of the 75 participants randomized to receive SRT, 57.3% received a full dose, 24% a partial dose, and 18.7% received no dose. Behavioural techniques were endorsed in 50.5% of sessions, with cognitive techniques endorsed in 34.9% of sessions. CONCLUSIONS: This report describes an adherence checklist which should be used when delivering SRT in both research and clinical practice. As hypothesized, behavioural techniques were a prominent feature of the SRT delivered in SUPEREDEN3, consistent with the behavioural emphasis of the approach. The use of this adherence tool would be considered essential for anyone delivering SRT looking to ensure adherence to the model.

Group-Based Worry Intervention for Persecutory Delusions: an Initial Feasibility Study.

BACKGROUND: A one-to-one cognitive behavioural therapy intervention targeting worry significantly reduces both worry and persecutory delusions (Freeman et al., 2015). AIM: To adapt this intervention for group delivery and conduct a feasibility trial within routine clinical practice. METHOD: Thirteen participants were randomized to a weekly 8-session worry intervention group (n = 7) or wait-list control (n = 6). RESULTS: All but one participant completed measures at all time points. Participants attended an average of six therapy sessions. CONCLUSIONS: Recruitment, retention and therapy uptake were feasible. Observed treatment effects were in the expected direction, but may be diluted compared with one-to-one interventions.

Worry processes in patients with persecutory delusions.

OBJECTIVES: Worry may be common in patients with paranoia and a contributory causal factor in the occurrence of the delusions. A number of psychological mechanisms have been linked to the occurrence of worry in emotional disorders but these are yet to be investigated in psychosis. The primary aim of the study was to test the links between five main worry mechanisms - perseverative thinking, catastrophizing, stop rules, metacognitive beliefs, and intolerance of uncertainty - and the cognitive style of worry in patients with persecutory delusions. METHOD: One hundred and fifty patients with persecutory delusions completed assessments of paranoia, worry, and worry mechanisms. RESULTS: Worry in patients with psychosis was associated with the following: a perseverative thinking style, an 'as many as can' stop rule, a range of metacognitive beliefs (cognitive confidence, worry as uncontrollable and the need to control thoughts), and intolerance of uncertainty. Higher levels of worry were associated with higher levels of paranoia. There was also evidence that intolerance of uncertainty and the metacognitive belief concerning the need to control thoughts were independently associated with paranoia. CONCLUSIONS: Worry in patients with persecutory delusions may well be understood by similar underlying mechanisms as worry in emotional disorders. This supports the use of interventions targeting worry, suitably modified, for patients with psychosis. PRACTITIONER POINTS: Worry is a significant concern for patients with paranoia Worry in paranoia is likely to be caused by similar mechanisms as worry in emotional disorders The results support the recent trial findings that standard techniques for treating worry in anxiety, suitably modified, are applicable for patients with paranoia LIMITATIONS: The findings are limited by the self-report nature of measures and by the study design which precludes any assumptions about the direction of causality between the psychological mechanisms and worry.

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.

How do individuals with persecutory delusions bring worry to a close? An interpretive phenomenological analysis.

BACKGROUND: Worry is a significant problem for individuals with paranoia, leading to delusion persistence and greater levels of distress. There are established theories concerning processes that maintain worry but little has been documented regarding what brings worry to a close. AIMS: The aim was to find out what patients with persecutory delusions report are the factors that bring a worry episode to an end. METHOD: Eight patients with persecutory delusions who reported high levels of worry participated. An open-ended semi-structured interview technique and IPA qualitative analysis was employed to encourage a broad elaboration of relevant constructs. RESULTS: Analyses revealed one theme that captured participants' detailed descriptions of their experience of worry and five themes that identified factors important for bringing worry episodes to a close: natural drift, distraction, interpersonal support, feeling better, and reality testing. CONCLUSIONS: Patients with persecutory delusions report worry being uncontrollable and distressing but are able to identify ways that a period of worry can stop. The present study suggests that building on individuals' distraction techniques, reality testing ability and their social support network could be of benefit. Research is needed to identify the most effective means of bringing paranoid worries to an end.

Depersonalization in patients with persecutory delusions.

Delusions are, in part, attempts to explain confusing anomalous experience. Depersonalization, a key subset of anomalous experience, has been little studied in relation to persecutory delusions. The aims of this study were to assess the presence of depersonalization in patients with persecutory delusions and to examine associations with levels of paranoia and worry. Fifty patients with a current persecutory delusion completed measures of depersonalization, psychotic symptoms, and worry. Depersonalization experiences were common: 30 patients (60%) each reported at least 10 different depersonalization symptoms occurring often. A greater number of depersonalization experiences were associated with higher levels of paranoia and worry. The positive association of worry and paranoia became nonsignificant when controlling for depersonalization. Overall, depersonalization may be common in patients with persecutory delusions and is associated with the severity of paranoia. The results are consistent with the view that worry may cause depersonalization experiences that contribute to the occurrence of paranoid thoughts.

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.

One Health assessment of persistent organic chemicals and PFAS for consumption of restored anadromous fish.

BACKGROUND: Restoration efforts have led to the return of anadromous fish, potential source of food for the Penobscot Indian Nation, to the previously dammed Penobscot River, Maine. OBJECTIVE: U.S. Environmental Protection Agency (EPA), Penobscot Indian Nation's Department of Natural Resources (PINDNR), and Agency for Toxic Substances and Disease Registry (ATSDR), measured contaminants in six species of anadromous fish. Fish tissue concentrations were then used, along with exposure parameters, to evaluate potential human and aquatic-dependent wildlife risk. METHODS: PINDNR collected, filleted, froze, and shipped fish for analysis of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dioxins/furans, and per- and polyfluoroalkyl substances (PFAS). Contaminant levels were compared to reference doses (where possible) and wildlife values (WVs). RESULTS: Chemical concentrations ranged from 6.37 nanogram per gram (ng/g) wet weight (ww) in American Shad roe to 100 ng/g ww in Striped Bass for total PCBs; 0.851 ng/g ww in American Shad roe to 5.92 ng/g ww in large Rainbow Smelt for total PBDEs; and 0.037 ng/g ww in American Shad roe to 0.221 ng/g ww in Striped Bass for total dioxin/furans. PFAS concentrations ranged between 0.38 ng/g ww of PFBA in Alewife to 7.86 ng/g ww of PFUnA in Sea Lamprey. Dioxin/furans and PFOS levels indicated that there are potential human health risks. The WV for mink for total PCBs (72 ng/g) was exceeded in Striped Bass and the WV for Kestrel for PBDEs (8.7 ng/g) was exceeded in large Rainbow Smelt. Mammalian wildlife consuming Blueback Herring, Striped Bass, and Sea Lamprey may be at risk based on PFOS WVs from Canada. IMPACT: Anadromous fish returning to the Penobscot River potentially could represent the restoration of a major component of tribal traditional diet. However, information about contaminant levels in these fish is needed to guide the tribe about consumption safety. Analysis of select species of fish and risk calculations demonstrated the need for a protective approach to consumption for both humans and wildlife. This project demonstrates that wildlife can also be impacted by contamination of fish and their risks can be as great or greater than those of humans. A One Health approach addresses this discrepancy and will lead to a healthier ecosystem.

Correlates of perceptual distortions in clinical and non-clinical populations using the Cardiff Anomalous Perceptions Scale (CAPS): associations with anxiety and depression and a re-validation using a representative population sample.

Although the literature on hallucinations in psychiatric patients shows clear links with anxiety and depression, associations of affect with a wider array of anomalous perceptual experiences have been much less studied. This study investigated patients with psychosis (N=29) and a non-clinical population (N=193) using the Cardiff Anomalous Perceptions Scale (CAPS), a measure of perceptual distortion and associated distress, intrusiveness and frequency; along with measures of depression, anxiety and worry. The study also allowed a re-validation of the CAPS in a more representative sample of the UK population. Moderate, reliable correlations with depression, anxiety and worry were found in the non-clinical population with the association being stronger in psychotic patients. The study re-confirmed that anomalous perceptual experiences are common in the general population and that a significant minority (11.9%) have higher levels than the mean of psychotic patients. Scale reliability and validity were also re-confirmed, and the CAPS score was found to be unrelated to age or gender in either sample. As in the original study, factor analysis produced a three-factor solution, although factor theme was not fully replicated: as before, a cluster of first-rank symptoms emerged, but with equivocal evidence for a temporal lobe factor and no replication of a 'chemosensation' component.

Risks from mercury in anadromous fish collected from Penobscot River, Maine.

Levels of total mercury were measured in tissue of six species of migratory fish (alewife, American shad, blueback herring, rainbow smelt, striped bass, and sea lamprey), and in roe of American shad for two consecutive years collected from the Penobscot River or its estuary. The resultant mercury levels were compared to reference doses as established in the U.S. Environmental Protection Agency (EPA) Integrated Risk Information System and wildlife values. Mercury concentrations ranged from 4 µg/kg ww in roe to 1040 µg/kg ww in sea lamprey. Sea lamprey contained the highest amounts of mercury for both seasons of sampling. Current health advisories are set at sufficient levels to protect fishers from harmful consumption of the fish for mercury alone, except for sea lamprey. Based upon published wildlife values for mink, otter, and eagle, consumption of rainbow smelt, striped bass, or sea lamprey poses a risk to mink; striped bass and sea lamprey to otter; and sea lamprey to eagle. For future consideration, the resultant data may serve as a reference point for both human health and wildlife risk assessments for the consumption of anadromous fish. U.S. EPA works with federally recognized Tribes across the nation greatly impacted by restrictions on sustenance fishing, to develop culturally sensitive risk assessments.

Isolation and characterisation of amphotericin B analogues and truncated polyketide intermediates produced by genetic engineering of Streptomyces nodosus.

Amphotericin B is a powerful but toxic drug used against fungal infections and leishmaniases. These diseases would be treated more effectively if non-toxic amphotericin derivatives could be produced on a large scale at low cost. Genetic manipulation of the amphotericin B producer, Streptomyces nodosus, has previously led to the detection and partial characterisation of 8-deoxyamphotericin B, 16-descarboxyl-16-methyl-amphotericin B, 15-deoxy-16-descarboxyl-16-methyl-15-oxo-amphotericin B, 7-oxo-amphotericin B and pentaene analogues. Here we report improved production and purification protocols that have allowed detailed chemical analyses of these compounds. The polyketide synthase product 8-deoxy-16-descarboxyl-16-methyl-amphoteronolide B was identified for the first time. In addition, the ketoreductase 10 domain of the polyketide synthase was specifically inactivated by targeted gene replacement. The resulting mutants produced truncated polyketide intermediates as linear polyenyl-pyrones.

Insomnia and paranoia.

Insomnia is a potential cause of anxiety, depression, and anomalies of experience; separate research has shown that anxiety, depression and anomalies of experience are predictors of paranoia. Thus insomnia may contribute to the formation and maintenance of persecutory ideation. The aim was to examine for the first time the association of insomnia symptoms and paranoia in the general population and the extent of insomnia in individuals with persecutory delusions attending psychiatric services. Assessments of insomnia, persecutory ideation, anxiety, and depression were completed by 300 individuals from the general population and 30 individuals with persecutory delusions and a diagnosis of non-affective psychosis. Insomnia symptoms were clearly associated with higher levels of persecutory ideation. Consistent with the theoretical understanding of paranoia, the association was partly explained by the presence of anxiety and depression. Moderate or severe insomnia was present in more than 50% of the delusions group. The study provides the first direct evidence that insomnia is common in individuals with high levels of paranoia. It is plausible that sleep difficulties contribute to the development of persecutory ideation. The intriguing implication is that insomnia interventions for this group could have the added benefit of lessening paranoia.

Jumping to conclusions and paranoid ideation in the general population.

An association of a 'jumping to conclusions' (JTC) reasoning style and delusions has been repeatedly found. The data-gathering bias has been particularly implicated with higher levels of delusional conviction in schizophrenia. For the first time the symptom, psychological and social correlates of jumping to conclusions are examined in a large general population sample. This is based upon the recognition that delusional ideation in non-clinical populations is on a continuum of severity with delusions in psychosis. Two hundred individuals completed a probabilistic reasoning task and assessments of paranoid ideation, intellectual functioning, affective symptoms, anomalies of experience, cognitive flexibility, illicit drug use, social support, and trauma. The jumping to conclusions reasoning bias was found in 20% of the non-clinical sample. JTC was strongly associated with higher levels of conviction in paranoid thoughts and the occurrence of perceptual anomalies, but not with the presence of affective symptoms. The results indicate that jumping to conclusions is a reasoning bias specifically associated with levels of delusional conviction, and is not a product of generally high levels of distress and affect. The association of jumping to conclusions with the types of anomalies of experience seen in psychotic disorders is intriguing, and consistent with recent dopamine dysregulation theories and the importance of reasoning to perception. The study is a further illustration of the need to consider the dimensions of delusional experience separately.

Responsibility beliefs and persecutory delusions.

Recent research implicates cognitive processes traditionally linked to anxiety disorders in the maintenance of paranoia. Responsibility beliefs have traditionally been associated with OCD, and recent research suggests they may be transdiagnostic. The present study reports the first data on responsibility beliefs in individuals with persecutory delusions. 30 people with persecutory delusions completed measures of psychotic symptoms and responsibility beliefs. Participants were also asked to identify who they held responsible for their persecution. Quantitative data on responsibility beliefs were compared with 29 matched non-clinical control participants, and with published data from patients with OCD and anxiety disorders. People with persecutory delusions identified a number of different entities responsible for harm. The persecutory delusions group had higher responsibility beliefs than those with OCD, anxiety disorders and nonclinical controls. The results suggest that responsibility beliefs are a facet of the phenomenology of persecutory beliefs. Cognitive-behavioural therapy for psychosis might usefully draw from OCD interventions and focus on responsibility beliefs, perhaps especially in Bad Me paranoia.

The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis.

BACKGROUND: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. METHODS: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251. FINDINGS: Between March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (-2·22, -2·98 to -1·45, Cohen's d=0·19; p<0·0001), and hallucinations (-1·58, -1·98 to -1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported. INTERPRETATION: To our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision. FUNDING: Wellcome Trust.

Negative cognitions about the self in patients with persecutory delusions: An empirical study of self-compassion, self-stigma, schematic beliefs, self-esteem, fear of madness, and suicidal ideation.

There has been growing awareness of the high prevalence of negative cognitions about the self in patients with persecutory delusions, and it has been proposed that paranoid fears build upon these perceived vulnerabilities. This study aimed to investigate for the first time a wide range of different conceptualisations of the negative self, and to examine associations with suicidal ideation, in patients with persecutory delusions. Twenty-one patients with persecutory delusions and twenty-one non-clinical individuals completed measures relating to negative self cognitions. The delusions group also completed a measure of suicidal ideation. It was found that the patients with persecutory delusions had low self-compassion, low self-esteem, increased fears of being mad, beliefs of inferiority to others, negative self-schemas, and low positive self-schemas when compared to the non-clinical control group. The effect sizes (Cohen's d) were large, and the different conceptualisations of negative self cognitions were highly associated with one another. Self-stigma did not differ between the two groups. Furthermore, suicidal ideation was highly associated with low self-compassion, low self-esteem, fears of madness, and negative self-schema but not self-stigma. This study shows marked negative self cognitions in patients with persecutory delusions. These are likely to prove targets of clinical interventions, with patient preference most likely determining the best conceptualisation of negative self cognitions for clinicians to use.

Effects of cognitive behaviour therapy for worry on persecutory delusions in patients with psychosis (WIT): a parallel, single-blind, randomised controlled trial with a mediation analysis.

BACKGROUND: Worry might be a contributory causal factor in the occurrence of persecutory delusions in patients with psychotic disorders. Therefore we postulated that reducing worry with cognitive behaviour therapy (CBT) would reduce persecutory delusions. METHODS: For our two-arm, assessor-blinded, randomised controlled trial (Worry Intervention Trial [WIT]), we recruited patients aged 18-65 years with persistent persecutory delusions but non-affective psychosis from two centres: the Oxford Health National Health Service (NHS) Foundation Trust (Oxford, UK) and the Southern Health NHS Foundation Trust (Southampton, UK). The key inclusion criteria for participants were a score of at least 3 on the Psychotic Symptoms Rating Scale (PSYRATS) denoting a current persecutory delusion; that the delusion had persisted for at least 3 months; a clinical diagnosis of schizophrenia, schizoaffective disorder, or delusional disorder; and a clinically significant level of worry. We randomly assigned (1:1) eligible patients, using a randomly permuted block procedure with variable block sizes and division by four strata, to either six sessions of worry-reduction CBT intervention done over 8 weeks added to standard care (the CBT-intervention group), or to standard care alone (the control group). The assessors were masked to patient allocations and did their assessments at week 0 (baseline), 8 weeks (end of treatment), and 24 weeks, follow-up. The primary outcomes were worry measured by the Penn State Worry Questionnaire (PSWQ) and delusions measured by the PSYRATS-delusion scale; we did the analyses in the intention-to-treat population, and also did a planned mediation analysis. This trial is registered with the ISRCTN Registry (number ISRCTN23197625) and is closed to new participants. FINDINGS: From Nov 1, 2011, to Sept 9, 2013, we recruited 150 eligible participants and randomly assigned 73 to the CBT intervention group, and 77 to the control group. 143 patients (95%) provided primary outcome follow-up data. Compared with standard care alone, at 8 weeks the CBT intervention significantly reduced worry (mean difference 6·35 [SE 1·56] PSWQ units, 95% CI 3·30-9·40; p<0·001) and persecutory delusions (2·08 [SE 0·73] PSYRATS units, 95% CI 0·64-3·51; p=0·005). The reductions were maintained to 24 weeks follow-up. The mediation analysis suggested that the change in worry accounted for 66% of the change in delusion. No patients died or were admitted to secure units during our study. Six suicide attempts (two in the CBT intervention group, and four in the control group) and two serious violent incidents (one in each group) were noted, but no adverse events were deemed related to the treatments or the assessments. INTERPRETATION: To our knowledge, this is the first large trial focused on persecutory delusions. We have shown that long-standing delusions were significantly reduced by a brief intervention targeted on worry, although the limitations for our study include no determination of the key elements within the intervention. Our results suggest that worry might cause paranoia, and that worry intervention techniques might be a beneficial addition to the standard treatment of psychosis. FUNDING: Efficacy and Mechanism Evaluation programme, which is a UK Medical Research Council and National Institute of Health Research partnership.