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The two most used semi‐structured psychometric instruments that define criteria for being at clinical high risk (CHR) for psychosis are the Comprehensive Assessment of At‐Risk Mental States (CAARMS) and the Structured Interview for Psychosis‐Risk Syndromes (SIPS). Although very similar there are important differences between these two measures. Developing harmonized psychometric criteria for defining CHR and associated outcomes would be beneficial for future research. This article describes the first step in this process by reporting on a NIMH workshop held in Washington DC, in February 2019 that was attended by experts in the field. The aim of this workshop was to examine the similarities and differences between the two measures and consider how the harmonization process could proceed. [ABSTRACT FROM AUTHOR]

Background: No biological treatment has been firmly established for the at‐risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non‐psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidence questioning both the need and efficacy of specific pharmacological interventions in the ultra‐high risk (UHR) for psychosis group. Methods: Three‐arm randomized controlled trial of 405 patients (135 per arm) aged 12–25 years who meet UHR for psychosis criteria. The study includes a 6‐week lead‐in phase during which 10% of UHR individuals are expected to experience symptom remission. Participants will receive CBD (per oral) at doses 600 or 1000 mg per day (fixed schedule) for 12 weeks. Participants in the third arm of the trial will receive matching placebo capsules. Primary outcome is severity of positive psychotic symptoms as measured by the Comprehensive Assessment of At‐Risk Mental States at 12 weeks. We hypothesize that CBD will be significantly more effective than placebo in improving positive psychotic symptoms in UHR patients. All participants will also be followed up 6 months post baseline to evaluate if treatment effects are sustained. Conclusion: This paper reports on the rationale and protocol of the Cannabidiol for At Risk for psychosis Youth (CanARY) study. This study will test CBD for the first time in the UHR phase of psychotic disorder. [ABSTRACT FROM AUTHOR]

Aims: Psychotic‐like experiences (PLEs) are common in adolescents. Their persistence may confer increased susceptibility to psychotic disorder. The early evolution of transient to persistent PLEs is not well known. This study aimed to investigate the early persistence of PLEs (over 6–12 months) in a community sample of adolescents and examine baseline and longitudinal associations of early persistent PLEs. Methods: Five hundred and ninety Year 10 students were administered the community assessment of psychic experiences (CAPE) to measure PLEs at baseline and at follow up 6–12 months later. Persistent PLEs were defined as those present at or above the 90th centile at both time points. Independent variables of depression, psychological distress and functioning were all measured at both baseline and follow up. Self‐esteem, personality and suicidality were assessed at follow up. Results: The study found 5.1% of participants had early persistent PLEs. Persistence was associated positively with depression and distress at both time points, neuroticism and openness at baseline and suicidality at follow up. Persistence was negatively associated with functioning at both time points, agreeableness at baseline and self‐esteem at follow‐up. Only depression remained significantly associated at both time points when accounting for other variables. Thus, depressive symptoms may account for changes in other domains and be a predictor of early PLEs persistence. Conclusions: These results reinforce the importance of monitoring and assessing PLEs in young people especially when associated with depression. Further research is required to investigate PLE persistence over longer periods with increased measurement intervals. [ABSTRACT FROM AUTHOR]

Aim: Investigating biological processes in at‐risk individuals may help elucidate the aetiological mechanisms underlying psychosis development, refine prediction models and improve intervention strategies. This study examined the associations between sleep disturbances, chronotype, depressive and psychotic symptoms in individuals at ultra‐high risk for psychosis. Methods: A sample of 81 ultra‐high risk patients completed clinical interviews and self‐report assessments of chronotype and sleep during the Neurapro clinical trial. Mixed regression was used to investigate the cross‐sectional associations between symptoms and sleep disturbances/chronotype. Results: Sleep disturbances were significantly associated with increased depressive and attenuated positive psychotic symptoms. Greater preference for eveningness was significantly associated with increased negative symptoms, but not with depressive or attenuated positive psychotic symptoms. Conclusion: Sleep disturbances and chronotype may impact the emerging psychopathology experienced by ultra‐high risk individuals. Further, the preliminary relationship observed between greater preference for eveningness and negative symptoms offers a unique opportunity to treat negative symptoms through chronobiological approaches. [ABSTRACT FROM AUTHOR]

Aims: Psychotic‐like experiences (PLE) are sub‐threshold, non‐clinical forms of psychosis which can place an individual at greater risk of development of a psychotic disorder. Subtypes of PLE have also been shown to exist (bizarre experiences, persecutory ideation, perceptual abnormalities and magical thinking). Perceived stress relates to how two individuals may deal with the same objectively stressful event in different ways. The objective of our study was to investigate the extent to which perceived stress is associated with PLE in a community sample of adolescents, whether certain subtypes of PLE correlate more with perceived stress than others and to explore the role of depression with these associations. Methods: A total of 655 students completed the community assessment of psychic experiences (CAPE) and perceived stress scale (PSS). Pearson's correlation was used to investigate the relationship between PSS and CAPE and also between perceived stress and the four subtypes of PLE. Regression then explored the effect of perceived stress on PLE when accounting for depressive symptomatology. Results: Positive correlation was found between PSS and total CAPE (r = 0.405, P = 0.000). Positive significant correlation was also found between PSS and each subtype of PLE, with persecutory ideation correlating the strongest and magical thinking the least. Perceived stress was significantly associated with PLE even after adjusting for depression. Conclusions: We recommend that more regular screening of perceived stress in adolescent populations could lead to earlier recognition of PLE. Early treatment has shown to reduce rates of transition to psychosis, and so could benefit our adolescent community in the future. [ABSTRACT FROM AUTHOR]

The article presents a prospective study focusing on whether youth at high risk of illness progression can be identified by measures of rumination, depression and sleep-wake disturbance. Topics include the use of clinical staging to investigate and identify risk factors for illness progression, and the tendency for common dimensions between rumination and sleep-wake disturbance to indicate illness progression in youth.

Aim: Many young people at ultra‐high risk (UHR) of developing psychosis exhibit marked and persistent impairments in social and occupational functioning. We aimed to explore UHR patients' subjective experiences of these difficulties and their causes. Methods: We conducted semi‐structured interviews with 20 UHR individuals recruited from Early Detection and Intervention Teams in Northwest England. Topics covered included how participants spent their time, their interpersonal relationships, academic and occupational performance, premorbid functioning and clinical treatment. Thematic analysis was used to examine the prevailing themes. Results: The sample included individuals with varying degrees of functional impairment, ranging from mild to severe difficulties in functioning. Analysis of the qualitative data elicited themes around 2 topics: breadth of functional difficulties and subjective reasons for poor functioning. Participants reported a range of impairments in their social and occupational functioning which they attributed to a combination of clinical, cognitive and psychological factors. These included variables previously identified in the quantitative literature such as psychiatric symptoms, adverse life experiences and cognitive deficits. However, our findings also included other factors which have received comparably little attention such as self‐stigmatizing attitudes and dysfunctional metacognitive beliefs. Conclusions: We propose a model that attempts to explain how these variables interact to drive and sustain functional impairment in the UHR population. This will assist in the development of clinical interventions aimed at promoting functional recovery among UHR individuals. [ABSTRACT FROM AUTHOR]

Aim: The effects of nutrient‐based treatments, including adjunctive vitamin or antioxidant supplementation, have been explored extensively in long‐term schizophrenia. However, no systematic evaluation of trials in “first‐episode psychosis” (FEP) has been conducted, despite the potential benefits of using these treatments during the early stages of illness. Therefore, we aimed to review all studies examining efficacy, tolerability and the biological mechanisms of action, of nutrient supplementation in FEP. Methods: A systematic review of electronic databases was conducted from inception to July 2017. All information on feasibility, clinical outcomes and mechanistic findings from nutrient supplementation clinical trials was extracted and systematically synthesized. Results: Eleven studies with a total of 451 patients with FEP (from 8 independent randomized controlled trials) were eligible for inclusion. Six studies examined omega‐3 fatty acids, with inconsistent effects on psychiatric symptoms. However, mechanistic studies found significant improvements in hippocampal neuronal health and brain glutathione. Antioxidants “n‐acetyl cysteine” (n = 1) and vitamin C (n = 2) also improved oxidative status in FEP, which was associated with reduced psychiatric symptoms. No benefits were found for vitamin E (n = 1). Finally, one study trialling the amino acid taurine, showed significant improvements in positive symptoms and psychosocial functioning. Conclusion: There is preliminary evidence that taurine improves outcomes in FEP, whereas effects of omega‐3 and antioxidant vitamins/amino‐acids are inconsistent; perhaps mainly benefitting patients with high levels of oxidative stress. Future studies should evaluate multifaceted dietary and supplementation interventions in FEP; targeting‐specific nutritional deficits and the range of aberrant biological processes implicated in the disorder. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aims of this study were to examine if people with first‐episode psychosis (FEP) are able to continue adhering to exercise after a supervised intervention and to explore if the benefits of exercise can be sustained. Methods: Twenty‐eight persons with FEP took part in a 10‐week exercise intervention that provided each participant with twice‐weekly accompaniment to exercise activities of their own choice, of whom 20 were re‐assessed 6 months after the intervention. Long‐term adherence to exercise was assessed, and measures of psychiatric symptoms, physical health, neurocognition and social functioning were administered at baseline, post‐intervention and 6‐month follow‐up. Results: During the supervised intervention, participants achieved 124.4 min of moderate‐to‐vigorous exercise per week. After 6 months, physical activity levels had decreased significantly (P = 0.025) and only 55% of participants had continued to exercise weekly. Repeated‐measures analysis of variance found that the significant improvements in psychiatric symptoms and social functioning observed immediately after the intervention were maintained at 6 months (P = 0.001). However, post hoc analyses showed that symptomatic reductions were only maintained for those who continued to exercise, whereas symptom scores increased among those who had ceased exercising. Previously observed improvements in waist circumference and verbal memory were lost by 6 months. Conclusion: Long‐term exercise participation is associated with significant benefits for symptoms, cognition and social functioning in FEP. However, adherence to unsupervised exercise is low. Future research should explore the effectiveness of ‘step‐down’ support following supervised interventions, and aim to establish sustainable methods for maintaining regular exercise in order to facilitate functional recovery and maintain physical health. [ABSTRACT FROM AUTHOR]

Abstract: Aim: People with schizophrenia have poor physical health and high rates of premature mortality. Risk factors for later cardiovascular disease are present from an early stage, and recording of these factors is recommended in first‐episode services. However, it is unclear whether cardiometabolic risk factors are monitored prior to first‐episode psychosis. Methods: A retrospective analysis was conducted on case notes of individuals accepted into a specialized early detection service for young people at ultra‐high risk for psychosis. Notes were assessed to determine whether the following physical health measures were recorded: height, weight, body mass index, blood pressure, blood glucose and lipids, physical activity levels, smoking status, substance use and alcohol intake. Results: Forty individuals were deemed at ultra‐high risk for psychosis and accepted into the service. The two measures reported most frequently were whether a person used substances (82.5%) or alcohol (72.5%), but more specific details were not commonly reported. A minority of case files contained information on height (2.5%), weight (7.5%), body mass index (5%), blood glucose (2.5%), smoking status (15%) and physical activity (7.5%). Six case files had no measure of physical health. Conclusions: Physical health and unhealthy lifestyle factors were not assessed routinely in the specialized service. Clear monitoring guidelines should be developed to establish routine assessment of common metabolic risk factors present in this population. [ABSTRACT FROM AUTHOR]

Aim Recent research has indicated that preventative intervention is likely to benefit patients 'at-risk' for psychosis, both in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. The strong preliminary results for the effectiveness of omega-3 polyunsaturated fatty acids ( PUFAs), coupled with the falling transition rate in ultra high-risk ( UHR) samples, mean that further study of such benign, potentially neuroprotective interventions is clinically and ethically required. Employing a multicentre approach, enabling a large sample size, this study will provide important information with regard to the use of omega-3 PUFAs in the UHR group. Methods This trial is a 6-month, double-blind, randomized placebo-controlled trial of 1.4 g day−1 omega-3 PUFAs in UHR patients aged between 13 and 40 years. The primary hypothesis is that UHR patients receiving omega-3 PUFAs plus cognitive-behavioural case management ( CBCM) will be less likely to transition to psychosis over a 6-month period compared to treatment with placebo plus CBCM. Secondary outcomes will examine symptomatic and functional changes, as well as examine if candidate risk factors predict response to omega-3 PUFA treatment in the UHR group. Conclusion This is the protocol of the NeuraproE study. Utilizing a large sample, results from this study will be important in informing indicated prevention strategies for schizophrenia and other psychotic disorders, which may be the strongest avenue for reducing the burden, stigmatization, disability and economic consequences of these disorders. [ABSTRACT FROM AUTHOR]

Aim The duration of untreated psychosis ( DUP) refers to the period of time between the emergence of psychotic symptoms and the initiation of appropriate clinical treatment. Prolonged DUP is associated with a range of adverse consequences, including more severe illness course, cognitive deficits and poor functioning. Problems with recognition of illness and in seeking help contribute to DUP, but another major cause of prolonged DUP is delays within secondary mental health services. In an attempt to reduce these delays, National Health Service England and the Department of Health have set new targets to improve access to early intervention services which will come into effect in April 2016. Given this background, we aimed to examine the DUP and pathways to care of new patients entering an early intervention service. We also examined whether they were receiving National Institute for Health and Care Excellence (NICE) concordant treatment. This will enable us to establish a baseline so that the impact of the new targets can be determined and to assess the degree of change that will be required to implement these. Methods De-identified electronic records of 165 patients accepted into the service over a 12-month period were analysed. Results Median DUP was 6 months. There was a median of 2 contacts prior to service entry. Community Mental Health Teams were the largest source of referrals. Conclusions The majority of patients had a DUP exceeding the international target of 3 months. The findings appear to support previous evidence that this may be partially attributable to significant delays within the mental health care system. [ABSTRACT FROM AUTHOR]

Aim US authorities have recommended 'black-box' warnings for antidepressants because of the increased risk of suicidality for individuals up to age 25. There is thus a clinical and ethical imperative to provide effective treatment for youth depression with an acceptable risk-benefit balance. Long-chain omega-3 polyunsaturated fatty acids ( PUFAs) play an important role in a range of physiological processes in living organisms. Supplementation with omega-3 PUFAs has been shown to have a range of beneficial effects on both physical and mental health, and results of previous trials suggest that omega-3 PUFAs may be a safe and effective treatment for depression. However, conclusions from these trials have been limited by their relatively small sample sizes. Methods This trial will test the effectiveness of a 12-week parallel group, double-blind, randomized, placebo-controlled trial of 1.4 g day−1 omega-3 PUFAs in help seeking 15- to 25-year-olds ( N = 400) presenting with major depressive disorder. The primary hypothesis is that young people will show greater improvement of depressive symptoms after 12 weeks of treatment with omega-3 PUFAs plus cognitive behavioural case management compared with treatment with placebo plus cognitive behavioural case management. Conclusion Because of using a large sample, results from this study will provide the strongest evidence to date to inform the use of omega-3 PUFAs as first-line therapy in young people presenting with major depressive disorder. The study also heralds an important step towards indicated prevention of persistent depression, which may reduce the burden, stigmatization, disability and economic consequences of this disorder. [ABSTRACT FROM AUTHOR]

Aim The 'ultra-high-risk' criteria identify a clinical population at substantially increased risk for progressing to schizophrenia and other psychotic disorders. Although a number of clinical variables predictive of transition to psychotic disorder have been identified within this population, the predictive value of the level of distress associated with attenuated psychotic symptoms has not yet been examined. This was the aim of the present study. Method The level of distress (0-100) associated with attenuated psychotic symptoms was recorded for 70 ultra-high-risk ( UHR) patients using the Comprehensive Assessment of At-Risk Mental State ( CAARMS). Transition to psychosis was assessed over a 16-month follow-up period. Results Of the 70 UHR patients, 15 transitioned to psychosis (21.4%). Of the four CAARMS subscales measuring attenuated positive symptoms, Perceptual Abnormalities was rated as the most distressing. There were no differences in CAARMS scales rated as the most distressing between those who transitioned to psychosis and those who did not. There was also no association between higher levels of distress associated with attenuated psychotic symptoms and transition to psychosis. Conclusion Although the findings require replication, they indicate that the degree of distress associated with attenuated psychotic symptoms should not be used as a criterion for enriching UHR samples for risk of frank psychotic disorder. [ABSTRACT FROM AUTHOR]

Aim On the basis of applying 'ultra-high-risk' ( UHR) criteria, initially high rates of transition to psychosis were reported. However, a decline in transition to psychosis has been observed in recent years. The current descriptive paper aims to investigate if this drop in transition rate may be due to potential changes in patterns of referral to a large UHR clinic. Methods One hundred fifty young people who were referred to the Personal Assessment and Crisis Evaluation ( PACE) Clinic in Melbourne, Australia, between August 2000 and July 2004 were included. Their referral pathways were assessed using a semistructured interview. Results were compared with a similar study of a cohort referred to the same clinic between 1995 and 1996. Results The mean number of contacts prior to referral to the PACE Clinic was 1.93 (standard deviation ( SD) = 1.15), and the average time between symptom onset and referral to PACE was 46.5 weeks ( SD = 57.4). In comparison with the earlier cohort (mean = 2.36; SD = 1.32), our results indicate a lower number of contacts ( Cohen's d = 0.35, r = 0.17). Furthermore, participants in the current study were referred twice as fast to the PACE Clinic. Conclusions Increasing awareness of UHR symptoms among professionals and in the general population seems to have resulted in faster referral of young people to specialized mental health services. The global drop in transition rate might be due to a change in referral pathways to UHR services. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side‐effect profile) of lithium in a sample of young people identified at ultra‐high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU).Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side‐effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes.Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side‐effect assessment indicated that lithium was well‐tolerated. 64% (n = 16) of participants in the lithium group were lithium‐adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time.With a side‐effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Exercise can improve psychiatric symptoms, neurocognitive functioning and physical health in schizophrenia. However, the effects in early psychosis have not been explored. This study aimed to assess the feasibility of an exercise intervention for early psychosis and to determine if it was associated with changes in physical and mental health. Methods: Thirty‐one patients with first‐episode psychosis (FEP) were recruited from early intervention services to a 10‐week exercise intervention. The intervention group received individualized training programmes, aiming to achieve ≥90 min of moderate‐to‐vigorous activity each week, using exercise programmes tailored to individual preferences and needs. A comparison FEP sample from the same services (n = 7) received treatment as usual. Results: Rates of consent and retention in the exercise group were 94% and 81%, respectively. Participants achieved an average of 107 min of moderate‐to‐vigorous exercise per week. Positive and Negative Syndrome Scale total scores reduced by 13.3 points after 10 weeks of exercise, which was significantly greater than the treatment as usual comparison group (P = 0.010). The greatest differences were observed in negative symptoms, which reduced by 33% in the intervention group (P = 0.013). Significant improvements were also observed in psychosocial functioning and verbal short‐term memory. Increases in cardiovascular fitness and processing speed were positively associated with the amounts of exercise achieved by participants. Conclusion: Individualized exercise training could provide a feasible treatment option for improving symptomatic, neurocognitive and metabolic outcomes in FEP. [ABSTRACT FROM AUTHOR]

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS)., Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences., Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS., Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)