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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]

Background: In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate. Methods: In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers. Results: Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring. Conclusions: ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people. [ABSTRACT FROM AUTHOR]

Dysfunctional metacognitive beliefs are common among people with psychosis. In this meta-analysis we examined whether these are also present in people meeting at-risk mental state (ARMS) criteria. We also explored the relationship between metacognitive beliefs and symptoms in the ARMS group. An electronic database search of Ovid MEDLINE, PsycINFO and Embase from inception until August 2016 was conducted using keyword search terms synonymous with ARMS and metacognition. Eligible studies were original research articles that examined metacognitive beliefs using the Metacognitions Questionnaire (MCQ) among people meeting ARMS criteria. Studies included in the meta-analyses also reported comparison MCQ data acquired from healthy controls, help-seeking individuals, or people with psychotic disorders. Eleven eligible studies were identified, reporting data from six unique ARMS samples. People with ARMS did not differ from those with established psychotic disorders on any MCQ subscale, but they reported significantly more dysfunctional metacognitive beliefs than healthy or help-seeking controls. Maladaptive metacognitive beliefs were associated with a range of symptoms in ARMS individuals, but evidence for associations with specific subthreshold psychotic phenomena was inconsistent. This evidence indicates how valuable assessment and treatment of dysfunctional metacognitive beliefs may be but suggests that specific aspects of methodology should be addressed. [ABSTRACT FROM AUTHOR]

Attempts to identify people at imminent risk of psychotic disorder have been made during the past 20 years. High-risk criteria have been developed, and despite findings of a recent decline in the rate of onset of psychosis associated with these criteria, people identified still have a significantly greater risk, compared with the general population. Intervention studies in this group indicate that psychological treatments and fish oil appear to be just as effective as antipsychotics. Future research should refine risk factors for psychosis and examine outcomes other than psychosis. Research is also needed into what harms and benefits are associated with making the high-risk criteria into a formal diagnosis. [ABSTRACT FROM AUTHOR]

A new approach to understanding severe mental disorders such as schizophrenia is to adopt a clinical staging model. Such a model defines the extent of the illness such that earlier and milder phenomena are distinguished from later, more impairing features. Specifically, a clinical staging model makes three key predictions. First, pathologic measures should be more abnormal in more severe stages. Second, patients who progress between the stages should show change in these same pathologic measures. Finally, treatment should be more effective in the earlier stages, as well as more benign. In this article, we review the evidence for these three predictions from studies of psychotic disorders, with a focus on neuroimaging data. For all three, the balance of evidence supports the predictions of the staging model. However, there are a number of alternative explanations for these findings, including the effects of medication and symptom heterogeneity. [Copyright &y& Elsevier]

Over the last fifteen years attempts have been made to prospectively identify individuals in the prodromal phase of schizophrenia and other psychotic disorders. The 'ultra high risk' approach, based on a combination of known trait and state risk factors, has been the main strategy used. The validation of the ultra high risk criteria led to a series of intervention studies in this population. The aim of this paper is to provide an overview of ultra high risk research. We review studies in this area, focusing on intervention research. Intervention studies have included the use of low dose antipsychotic medication, cognitive therapy, and omega-3 fatty acids. The evidence for specific intervention strategies for this population is moderate and requires replication with larger samples. Recently, it has been proposed to include an adaption of the ultra high risk criteria in the next version of the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). This has raised some controversy in the field. The authors conclude that it would be premature to include the Risk Syndrome in the Diagnostic and Statistical Manual of Mental Disorders at this stage. [ABSTRACT FROM AUTHOR]

Aims: Criteria for identifying people likely to develop a first psychotic episode are now used in many clinical services worldwide. In recent years within these services, there has been an increase in the practice of prescribing antipsychotic medication with the aim of reducing symptoms and preventing onset of full-blown disorder. This practice is based on clinical impression of an incipient psychosis, that is, a clinical judgment that a particular patient may soon progress to full-threshold disorder and may therefore benefit from antipsychotics. However, it is unclear how accurate this clinical impression is. If not accurate it could mean that individuals are receiving antipsychotics unnecessarily. In this study, we investigated the predictive validity of clinical impression of whether ultra high risk patients would develop frank psychosis. Methods: Experienced psychologists rated their clinical impression of incipient psychosis in 168 ultra high risk patients. Ratings were made upon entry to the PACE clinic, a clinical service for ultra high risk patients. Psychosis status over the subsequent 12-month period was established using the Comprehensive Assessment of At Risk Mental States or State medical records. Results: A total of 8.9% of the sample transitioned to psychosis over the 12-month follow-up period. There was a sensitivity of 0.80, specificity of 0.84, positive predictive value (PPV) of 0.32 and negative predictive value (NPV) of 0.98 for the prediction of psychosis using the clinical impression ratings. Conclusions: The results indicate that clinical impression is not sufficient for predicting psychosis outcome in ultra high risk cohorts and that ongoing rigorous research into predictors of outcome in such cohorts is required. The results also caution against the prescription of antipsychotic medication based on clinical impression of incipient psychosis. Future work should address the predictive validity of clinical impression with a larger sample and over a longer follow-up period. [ABSTRACT FROM AUTHOR]

Objective: Studies conducted in community samples suggest that psychotic-like experiences are common in the general population, leading to suggestions that they are either variations of normal personality or are different expressions of underlying vulnerability to psychotic disorder. Different types of psychotic symptoms may exist, some being normal variants and some having implications for mental health and functioning. The aim of the present study was to determine if different subtypes of psychotic-like experiences could be identified in a community sample of adolescents and to investigate if particular subtypes were more likely to be associated with psychosocial difficulties, that is, distress, depression and poor functioning, than other subtypes. Method: Eight hundred and seventy-five Year 10 students from 34 schools participated in a cross-sectional survey that measured psychotic-like experiences using the Community Assessment of Psychic Experiences; depression using the Centre for Epidemiologic Studies Depression Scale; and psychosocial functioning using the Revised Multidimensional Assessment of Functioning Scale. Factor analysis was conducted to identify any subtypes of psychotic experiences. Results: Four subtypes of psychotic-like experiences were identified: Bizarre Experiences, Perceptual Abnormalities, Persecutory Ideas, and Magical Thinking. Intermittent, infrequent psychotic experiences were common, but frequent experiences were not. Bizarre Experiences, Perceptual Abnormalities and Persecutory Ideas were strongly associated with distress, depression and poor functioning. Magical Thinking was only weakly associated with these variables. Overall these findings may suggest that infrequent psychotic-like experiences are unlikely to be a specific risk factor for onset of a psychotic disorder in community samples. Conclusions: Given that the different subtypes had varying associations with current difficulties it is suggested that not all subtypes confer the same risk for onset of psychotic disorder and poor outcome. Bizarre Experiences, Perceptual Abnormalities and Persecutory Ideas may represent expressions of underlying vulnerability to psychotic disorder, but Magical Thinking may be a normal personality variant. [ABSTRACT FROM AUTHOR]

There is a higher incidence of psychotic disorders in more socially deprived neighbourhoods and a higher risk in migrants living in neighbourhoods of low ethnic density. Yet it is unclear at what stage these neighbourhood environmental factors exert an influence on the risk for psychosis. 166 Ultra high risk for psychosis young people were included in this study. Neighbourhood data were obtained from the Australian Bureau of Statistics. There was a trend for UHR individuals to reside in relatively more deprived areas and there was no association between the rate of identification of UHR migrants and neighbourhood ethnic density. [ABSTRACT FROM AUTHOR]

Abstract: Background: Identification of individuals “prodromal” for schizophrenia and other psychotic disorders relies on criteria that predict onset within a brief period. Previous trials and biological research have been predicated on the view that certain “ultra high risk” (UHR) criteria detect “the prodrome”, but there is a need to test the validity of these criteria. Aim: To assess the predictive validity of the UHR criteria in a clinical population. Method: The presence of UHR criteria was determined in 292 help-seeking individuals. At 2 year follow-up the number of new cases of psychotic disorder was assessed. Results: The criteria significantly predicted onset of psychotic disorder within 2 years. The transition rate of 16% was much lower than in initial cohorts (over 40%). Conclusions: The predictive validity of UHR criteria depends on the sample to which they are applied. Although young help-seekers meeting these criteria are at greater risk of psychotic disorder than those who do not meet them, caution is needed in their management, since a high transition rate can no longer be assumed. [Copyright &y& Elsevier]

The current paper examines a neglected function of ‘ultra high risk’ (UHR) clinics: to detect first-episode psychosis (FEP) mistakenly identified as a prodrome. A clinical audit was conducted of referrals to a UHR service, the Personal Assessment and Crisis Evaluation Clinic, over a 12-month period (April 2005–March 2006). In this audit, 11.4% of the total number of referrals ( n= 149) and 11.9% of those who attended a first appointment were psychotic on referral. These figures indicate that a substantial proportion of individuals thought to be prodromal are in fact suffering FEP. UHR clinics minimize duration of untreated psychosis for FEP patients mistaken as prodromal. [ABSTRACT FROM AUTHOR]

Abstract: Psychotic-like experiences (PLEs) are used to identify individuals considered to be at Ultra High Risk (UHR) of, or prodromal for, psychotic disorder. They are also common in the general population and in clinical samples of non-psychotic individuals. Depression has been found to be an important factor in mediating outcome in those with PLEs in both community and UHR populations. It is associated with increased risk of transition to psychotic disorder in the UHR group, and with need for care in relation to PLEs in community samples. In this study we aimed to examine the 6-month outcome of PLEs in a sample of help-seeking young people aged 15 to 24 years in relation to their level of depression. Subjects (n =140) were assessed at baseline and 6 months for PLEs and depression. PLEs were measured by the Community Assessment of Psychic Experiences (CAPE). Depression was assessed as a continuous measure using the Mood and Anxiety Symptom Questionnaire (MASQ) and categorically according to DSM-IV diagnosis of mood disorder. PLEs reduced in conjunction with an improvement in depression level and with remission of diagnosis of mood disorder. It is important to assess depression in those with PLEs and consider the need for treatment of the comorbid depressive syndrome. This may reduce the risk of worsening of PLEs and transition to psychotic disorder. [Copyright &y& Elsevier]

Abstract: Criteria for identifying individuals at imminent risk for onset of a psychotic disorder, that is “prodromal” for psychosis, have recently been described. The current study set out to test the predictive validity of these criteria in a sample of help-seeking young people aged 15–24 years who were referred to, but not necessarily treated at, a psychiatric service. Ultra High Risk (UHR) status was determined at baseline and psychosis status was assessed at 6 month follow up. Baseline psychosocial functioning was also assessed as a possible predictor of psychosis. In the sample of 292 individuals, 119 (40.7%) met UHR criteria. Of these UHR+ people, 12 became psychotic within 6 months and 107 did not. Only one person not meeting UHR criteria developed psychosis in the follow up period. Sensitivity, specificity, positive predictive value and negative predictive value of UHR+ status for prediction of psychosis were, respectively, 0.923 (95% CI 0.621, 1), 0.616 (95% CI 0.556, 0.673), 0.101 (95% CI 0.056, 0.173) and 0.994 (95% CI 0.963, 1). UHR+ individuals were significantly more likely to become psychotic than UHR− individuals (Odds Ratio 19.3, 95% CI 2.5, 150.5). Low functioning at baseline was associated with psychosis onset in the whole sample and in the UHR group. The transition to psychosis rate was much lower than in previous samples. This may be a due to the sample being a more general one, not identified as possibly “prodromal”. Other potential causes of this reduction in transition are also explored. [Copyright &y& Elsevier]

Objective: Recognizing the prodrome of a first psychotic episode prospectively creates the opportunity of intervention, which could delay, ameliorate or even prevent onset. Valid criteria and a reliable methodology for identifying possible prodromes are needed. This paper describes an instrument, the Comprehensive Assessment of At-Risk Mental States (CAARMS), which has been designed for such a purpose. It has two functions: (i) to assess psychopathology thought to indicate imminent development of a first-episode psychotic disorder; and (ii) to determine if an individual meets criteria for being at ultra high risk (UHR) for onset of first psychotic disorder. This paper describes the pilot evaluation of the CAARMS. Method: Several methodologies were used to test the CAARMS. First, CAARMS scores in a group of UHR young people and the association between CAARMS scores and the risk of transition to psychotic disorder, were analysed. Second, CAARMS scores in a UHR group were compared to a control group. To assess concurrent validity, CAARMS-defined UHR criteria were compared to the existing criteria for identifying the UHR cohort. To assess predictive validity, the CAARMS-defined UHR criteria were applied to a sample of 150 non-psychotic help-seekers and rates of onset of psychotic disorder at 6-month follow-up determined for the CAARMS-positive (i.e. met UHR criteria) group and the CAARMS-negative (i.e. did not meet UHR criteria) group. The inter-rater reliability of the CAARMS was assessed by using pairs of raters. Results: High CAARMS score in the UHR group was significantly associated with onset of psychotic disorder. The control group had significantly lower CAARMS scores than the UHR group. The UHR criteria assessed by the CAARMS identified a similar group to the criteria measured by existing methodology. In the sample of non-psychotic help-seekers those who were CAARMS-positive were at significantly increased risk of onset of psychotic disorder compared to those who were CAARMS-negative (relative risk of 12.44 (95% CI = 1.5–103.41, p = 0.0025)). The CAARMS had good to excellent reliability. Conclusions: In these preliminary investigations, the CAARMS displayed good to excellent concurrent, discriminant and predictive validity and excellent inter-rater reliability. The CAARMS instrument provides a useful platform for monitoring subthreshold psychotic symptoms for worsening into full-threshold psychotic disorder. [ABSTRACT FROM AUTHOR]

The identification of individuals at high risk of developing a psychotic disorder has long been a goal of clinicians because it is thought that early treatment of this group may prevent onset of the disorder. However, little is known of predictive factors of psychosis, even within a high-risk group. This study followed up 104 young people thought to be at ‘ultra high risk’ for schizophrenia and other psychotic disorders by virtue of having a family history of psychotic disorder combined with some functional decline or the presence of subthreshold or self-limiting psychotic symptoms. All subjects were therefore symptomatic, but not psychotic, at intake. Thirty-six subjects (34.6%) developed frank psychotic symptoms within 12 months.Measures of symptom duration, functioning, disability and psychopathology were made at intake, 6 and 12 months. Poor functioning, long duration of symptoms, high levels of depression and reduced attention were all predictors of psychosis. A combination of family history of psychosis, a recent significant decrease in functioning and recent experience of subthreshold psychotic symptoms was also predictive of psychosis. Combining highly predictive variables yielded a method of psychosis prediction at 12 months with good positive predictive value (80.8%), negative predictive value (81.8%) and specificity (92.6%) and moderate sensitivity (60.0%).Within our symptomatic high-risk group, therefore, it appears possible to identify those individuals who are at particularly high risk of developing a psychotic disorder such as schizophrenia. Given the very high PPV and low false positive rate with this two-step process, it may be justifiable to target these individuals for intensive monitoring of mental state and even low-dose neuroleptic medication or other biological and psychosocial treatments depending on clinical condition. This indicated prevention approach could be further developed and preventive strategies in the psychoses refined. [Copyright &y& Elsevier]

Intervention in the prodromal phase of schizophrenia and related psychoses may result in attenuation, delay or even prevention of the onset of psychosis in some individuals. However, a “prodrome” is difficult to recognise prospectively because of its nonspecific symptoms.This study set out to recruit and follow up subjects at high risk of transition to psychosis with the aim of examining the predictive power for psychosis onset of certain mental state and illness variables.Symptomatic individuals with either a family history of psychotic disorder, schizotypal personality disorder, subthreshold psychotic symptoms or brief transient psychotic symptoms were assessed and followed up monthly for 12 months or until psychosis onset.Twenty of 49 subjects (40.8%) developed a psychotic disorder within 12 months. Some highly significant predictors of psychosis were found: long duration of prodromal symptoms, poor functioning at intake, low-grade psychotic symptoms, depression and disorganization. Combining some predictive variables yielded a strategy for psychosis prediction with good sensitivity (86%), specificity (91%) positive predictive value (80%) and negative predictive value (94%) within 6 months.This study illustrates that it is possible to recruit and follow up individuals at ultra high risk of developing psychosis within a relatively brief follow-up period. Despite low numbers some highly significant predictors of psychosis were found. The findings support the development of more specific preventive strategies targeting the prodromal phase for some individuals at ultra high risk of schizophrenia. [Copyright &y& Elsevier]

Background: The prevalence of psychosis has been shown to be disproportionately high amongst sexual and gender minority individuals. However, there is currently little consideration of the unique needs of this population in mental health treatment, with LGBTQA+ individuals facing barriers in accessing timely and non-stigmatising support for psychotic experiences. This issue deserves attention as delays to help-seeking and poor engagement with treatment predict worsened clinical and functional outcomes for people with psychosis. The present protocol describes the methodology for a scoping review which will aim to identify barriers and facilitators faced by LGBTQA+ individuals across the psychosis spectrum in help-seeking and accessing mental health support. Methods: A comprehensive search strategy will be used to search Medline, PsycINFO, Embase, Scopus, LGBTQ+ Source, and grey literature. Original studies of any design, setting, and publication date will be included if they discuss barriers and facilitators to mental health treatment access and engagement for LGBTQA+ people with experiences of psychosis. Two reviewers will independently screen titles/abstracts and full-text articles for inclusion in the review. Both reviewers will then extract the relevant data according to pre-determined criteria, and study quality will be assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Key data from included studies will be synthesised in narrative form according to the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews. Discussion: The results of this review will provide a comprehensive account of the current and historical barriers and facilitators to mental healthcare faced by LGBTQA+ people with psychotic symptoms and experiences. It is anticipated that the findings from this review will be relevant to clinical and community services and inform future research. Findings will be disseminated through publication in a peer-reviewed journal and presented at conferences. Scoping review registration: This protocol is registered in Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/AT6FC). [ABSTRACT FROM AUTHOR]

Labeling terms for high-risk state for psychosis, such as 'ultra-high risk' (UHR), 'attenuated psychosis syndrome' (APS), and 'at-risk mental state' (ARMS), have been criticized for their potential to lead to stigma. Hence, mental health service users in Melbourne recently proposed new terms illustrating the at-risk concept ['pre-diagnosis stage' (PDS), 'potential of developing a mental illness' (PDMI), and 'disposition for developing a mental illness' (DDMI)]. We aimed at testing the suitability of these existing and new terms in the clinical settings of early psychiatric intervention in Japan. At two centers of early intervention (Toyama and Tokyo), a questionnaire on the understanding and opinion of high-risk terminology was administered to 62 high-risk patients, 44 caregivers, and 64 clinicians. The questionnaire contained the existing and new terms, where the term ARMS was translated into two different Japanese terms ARMS-psychosis and ARMS- kokoro. Participants' opinion on the disclosure of high-risk status was also obtained. ARMS- kokoro was most preferred, least stigmatizing, and best explaining the patients' difficulties for all groups, while UHR and other terms including the Japanese word 'psychosis' (i.e., APS and ARMS-psychosis) were not preferred. New labeling terms were generally not well received. All groups preferred full disclosure of high-risk terms by the psychiatrist with or without the presence of family members. The term ARMS- kokoro was commonly accepted as a favorable labeling term for the high-risk state for psychosis in Japan. However, another translation ARMS-psychosis was considered stigmatizing, demonstrating the importance of appropriate translation of high-risk terminology into local languages. • Existing terms for psychosis high-risk status may lead to stigma. • Patients, family members, and clinicians were surveyed about high-risk terms. • ARMS- kokoro was most preferred and least stigmatizing among high-risk terms. • Ultra-high risk and other terms including 'psychosis' were not preferred. [ABSTRACT FROM AUTHOR]

Background: Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders.Methods: This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups.Results: Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups.Conclusion: These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis. [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]

• Active neuroinflammation may contribute to the onset of schizophrenia. • Anti-inflammatory treatments in the at-risk mental state could reduce risk of onset. • Minocycline and omega-3, neither alone nor together, reduced transition to psychosis. • Omega-3 supplementation improved nonpsychotic general and transdiagnostic symptoms. Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. 10,173 help-seeking individuals aged 16–35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. The study was funded by the Stanley Research Medical Institute. [ABSTRACT FROM AUTHOR]

Objectives: Childhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorders, there is evidence that trauma is associated with an admixture of affective, anxiety and psychotic symptoms in adults. Given that early onset of mental disorder and trauma exposure herald poor outcomes, it is important to examine trauma prevalence rates in youth mental health services and to determine whether this trauma-related clustering is present in help-seeking young people. Methods: We used data from the Transitions Study, a longitudinal investigation of young people attending headspace youth mental health services in Australia between January 2011 and August 2012. Participants were 775 young people aged 12–25. Childhood trauma was assessed using the Childhood Trauma Questionnaire. Multinomial regression was used to assess whether reported childhood trauma was more strongly associated with the co-occurrence of depression, anxiety, mania and psychosis symptoms than with any one in isolation. Results: Approximately 84% of participants reported some form of abuse (emotional: 68%; physical: 32%; sexual: 22%) or neglect (emotional: 65%; physical: 46%). Exposure to multiple trauma types was common. Childhood trauma was significantly associated with each symptom domain. More severe childhood trauma was more strongly associated with the co-occurrence of symptoms than with any one symptom domain in isolation, such that more severely trauma-exposed young people were more likely to experience increased symptom clustering. Conclusions: Childhood trauma is pervasive in youth mental health services and associated with a symptom profile that cuts across traditional diagnostic boundaries. [ABSTRACT FROM AUTHOR]

Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute's Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treated with a combination of atypical antipsychotic drugs commonly used to treat psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorder), and differential gene expression was analysed. Biological pathways with an increased gene expression included circadian rhythm and vascular endothelial growth factor signalling, while the adherens junction and cell cycle pathways were transcriptionally downregulated. The Connectivity Map (CMap) analysis screen highlighted drugs that affect global gene expression in a similar manner to these psychiatric disorder treatments, including several other antipsychotic drugs, confirming the utility of this approach. The CMap screen specifically identified metergoline, an ergot alkaloid currently used to treat seasonal affective disorder, as a drug of interest. In mice, metergoline dose-dependently reduced MK-801- or methamphetamine-induced locomotor hyperactivity confirming the potential of metergoline to treat positive symptoms of schizophrenia in an animal model. Metergoline had no effects on prepulse inhibition deficits induced by MK-801 or methamphetamine. Taken together, metergoline appears a promising drug for further studies to be repurposed as a treatment for schizophrenia and possibly other psychiatric disorders. [ABSTRACT FROM AUTHOR]

Psychotic symptoms are typically measured using clinical ratings, but more objective and sensitive metrics are needed. Hence, we will assess thought disorder using the Research Domain Criteria (RDoC) heuristic for language production, and its recommended paradigm of "linguistic corpus-based analyses of language output". Positive thought disorder (e.g., tangentiality and derailment) can be assessed using word-embedding approaches that assess semantic coherence, whereas negative thought disorder (e.g., concreteness, poverty of speech) can be assessed using part-of-speech (POS) tagging to assess syntactic complexity. We aim to establish convergent validity of automated linguistic metrics with clinical ratings, assess normative demographic variance, determine cognitive and functional correlates, and replicate their predictive power for psychosis transition among at-risk youths. This study will assess language production in 450 English-speaking individuals in Australia and Canada, who have recent onset psychosis, are at clinical high risk (CHR) for psychosis, or who are healthy volunteers, all well-characterized for cognition, function and symptoms. Speech will be elicited using open-ended interviews. Audio files will be transcribed and preprocessed for automated natural language processing (NLP) analyses of coherence and complexity. Data analyses include canonical correlation, multivariate linear regression with regularization, and machine-learning classification of group status and psychosis outcome. This prospective study aims to characterize language disturbance across stages of psychosis using computational approaches, including psychometric properties, normative variance and clinical correlates, important for biomarker development. SPEAK will create a large archive of language data available to other investigators, a rich resource for the field. [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]

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]

Background: Preventing psychotic disorders and effective treatment in first-episode psychosis are key priorities for the National Institute for Health and Care Excellence. This review assessed the evidence base for the cost-effectiveness of health and social care interventions for people at risk of psychosis and for first-episode psychosis. Methods: Electronic searches were conducted using the PsycINFO, MEDLINE and Embase databases to identify relevant published full economic evaluations published before August 2020. Full-text English-language studies reporting a full economic evaluation of a health or social care intervention aiming to reduce or prevent symptoms in people at risk of psychosis or experiencing first-episode psychosis were included. Screening, data extraction, and critical appraisal were performed using pre-specified criteria and forms based on the NHS Economic Evaluation Database (EED) handbook and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist for economic evaluations. The protocol was registered on the PROSPERO database (CRD42018108226). Results were summarised qualitatively. Results: Searching identified 1,628 citations (1,326 following the removal of duplications). After two stages of screening 14 studies met the inclusion criteria and were included in the review. Interventions were varied and included multidisciplinary care, antipsychotic medication, psychological therapy, and assertive outreach. Evidence was limited in the at-risk group with only four identified studies, though all interventions were found to be cost-effective with a high probability (> 80%). A more substantial evidence base was identified for first-episode psychosis (11 studies), with a focus on early intervention (7/11 studies) which again had positive conclusions though with greater uncertainty. Conclusions: Study findings generally concluded interventions were cost-effective. The evidence for the population who are at-risk of psychosis was limited, and though there were more studies for the population with first-episode psychosis, limitations of the evidence base (including generalisability and heterogeneity across the methods used) affect the certainty of conclusions. [ABSTRACT FROM AUTHOR]

Abstract: A shallow olfactory sulcus has been reported in schizophrenia, possibly reflecting abnormal forebrain development during early gestation. However, it remains unclear whether this anomaly exists prior to the onset of psychosis and/or differs according to illness stage. In the current study, magnetic resonance imaging was used to investigate the length and depth of the olfactory sulcus in 135 ultra high-risk (UHR) individuals [of whom 52 later developed psychosis (UHR-P) and 83 did not (UHR-NP)], 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, and 87 healthy controls. While there was no group difference in the length of the sulcus, UHR-P subjects had significantly shallower olfactory sulcus at baseline as compared with UHR-NP and control subjects. The depth of this sulcus became increasingly more superficial as one moved from UHR-P subjects to FEP patients to chronic schizophrenia patients. Finally, the depth of the olfactory sulcus in the UHR-P subjects was negatively correlated with the severity of negative symptoms. These findings suggest that the altered depth of the olfactory sulcus, which exists before psychosis onset, could be predictive of transition to psychosis, but also suggest ongoing changes of the sulcus morphology during the course of the illness. [Copyright &y& Elsevier]

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]

Aim Disturbance in the basic sense of self has previously been found to characterize schizophrenia spectrum disorders and to predict onset of psychosis in the ultra-high-risk population. The current study examined basic self-disturbance in a first-episode psychosis (FEP) population. We hypothesized that basic self-disturbance would be more prominent in cases with a schizophrenia spectrum disorder compared to those with other psychoses. Method Sixteen FEP patients from Orygen Youth Health, Melbourne, were recruited to the study. Participants were assessed using the Examination of Anomalous Self-Experience and the Structured Clinical Interview for DSM- IV. Results Basic self-disturbance scores were significantly higher in patients with a schizophrenia spectrum diagnosis ( n = 8) compared to patients with other psychotic diagnoses ( n = 8). Conclusions The findings are consistent with previous work indicating that the disturbance of the basic sense of self is more characteristic of schizophrenia spectrum psychosis than other psychoses. This may have implications for early diagnosis, clinical formulation and intervention. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Studies conducted in community samples indicate that psychotic-like experiences (PLEs) are common in the general population; it has been suggested that such experiences are either variations in normal personality or different expressions of vulnerability to psychotic disorders. The aim of this study was to determine whether different subtypes of PLEs could be identified in a community sample of adolescents and young adults, and to investigate whether particular subtypes of PLEs were more likely to be associated with psychosocial difficulties, i.e. distress, depression and poor functioning, than other subtypes. Method: 1882 students from high schools and universities participated in a cross-sectional multisite survey that measured i) PLEs using the Positive Scale of the Community Assessment of Psychic Experiences (CAPE), ii) depression and distress using the CAPE Depression and Distress Subscales, and iii) functioning using the General Health Questionnaire-12. Factor analysis was conducted to identify any subtypes of PLEs. Results: Four subtypes of PLEs were identified: bizarre experiences (BE), perceptual abnormalities (PA), persecutory ideas (PI) and grandiosity (GR). Intermittent, infrequent psychotic experiences were common, whereas frequent experiences were not. BE and PI were strongly associated with distress, depression and poor functioning. PA and GR were associated with these variables to a lesser degree. Conclusions: Different subtypes of PLEs were identified in this large sample, confirming the findings of our previous studies. These subtypes seem to have different psychopathological meaning and may therefore indicate different levels of risk of severe psychiatric disorders, which suggests it is misleading to define PLEs as a homogenous entity. [Copyright &y& Elsevier]

Objective: Recent years have witnessed widespread interest in the early phase of psychotic disorders. The most widely used approach to identify individuals in the prodromal phase is the ultra-high risk (UHR) approach, which combines known trait and state risk factors for psychotic disorder. The Personal Assessment and Crisis Evaluvation Clinic introduced the Comprehensive Assessment of At Risk Mental States (CAARMS) in order to assess UHR status. A training DVD and manual in the use of the CAARMS was recently developed in order to assist with UHR identification. The current paper reports the outcome of a series of training workshops with mental health professionals based around this DVD. The research aim was to investigate whether the training workshops assisted mental health professionals in their confidence and ability to accurately identify UHR cases and distinguish these from non-UHR and first-episode psychosis (FEP) cases. Method: A total of 137 mental health workers participated in the training sessions across eight training sites. The training sessions consisted of four modules: theoretical background; rating written vignettes for UHR, non-UHR or FEP status; viewing and discussing the CAARMS Training DVD; and re-rating matched written vignettes for UHR, non-UHR or FEP status. Results: Participants' confidence in identifying UHR cases and in using the CAARMS increased as a result of the workshop. Participants' ability to correctly identify UHR-positive cases did not improve as a result of the workshop. This may have been the result of a ceiling effect due to the baseline ability to identify UHR-positive cases being high. But there was a trend for participants' ability to correctly identify UHR-negative cases to improve as a result of the workshop. Conclusions: UHR training workshops are a valuable means of increasing mental health workers' confidence in identifying UHR patients. Future UHR training programmes with experienced mental health professionals should pay particular attention to the correct identification of UHR-negative cases. [ABSTRACT FROM AUTHOR]

Background: The association between cannabis use and the development of a first psychotic episode was studied in a group of 100 young people identified as being at very high risk for the onset of psychosis. Method: The ‘ultra’ high risk cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-two per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of cannabis use by participants in the year prior to enrolment in the study was assessed at intake. Results: Cannabis use or dependence in the year prior to recruitment to this study was not associated with a heightened risk of developing psychosis over the following 12-month period and therefore did not appear to contribute to the onset of a psychotic disorder. Conclusion: The results of this study suggest that cannabis use may not play an integral role in the development of psychosis in a high-risk group. While this study does not support a role for cannabis in the development of first-episode psychosis, we cannot conclude that cannabis use should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study (the low level of cannabis use in the current sample, the lack of monitoring of cannabis use after intake) suggest that it may be premature to dismiss cannabis use as a risk factor for the development of psychosis and further research is urged in this area. [ABSTRACT FROM AUTHOR]

Over a quarter of a century ago, the formulation of the "at risk mental state" and operational criteria to prospectively identify individuals at "clinical" or "ultra-high risk" (UHR) for psychosis created a global wave of research momentum aimed at predicting and preventing first-episode psychosis. A substantial number of randomized controlled trials (RCTs) were conducted to determine if transition to psychosis could be delayed or even prevented. The efficacy of a range of interventions was examined, with standard meta-analyses clearly indicating that these could at least delay transition for 1-2 years and that outcomes improve. Recently, network meta-analyses have attempted to identify the most effective intervention. These highlighted the fact that no one form of intervention is superior to the rest, a finding interpreted in such a way as to create doubts concerning the value of intervening. These doubts have been reinforced by a subsequent Cochrane review which judged the quality of the evidence as low or very low. Here, we report a narrative review of findings from RCTs and meta-analyses on the efficacy of interventions in UHR. We also critique the network meta-analyses and the Cochrane review, and indicate that many of the trials were of the highest possible quality for such research, and were published in top ranked psychiatry journals, which demand such quality. Although outcomes vary, and the UHR group is clearly heterogeneous, we highlight the clinical benefits of psychosocial treatment. The next generation of clinical trials seek to elucidate the optimal type, duration and sequence of interventions. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma, particularly sexual abuse, has been associated with transition to psychosis in individuals at "ultra-high risk" (UHR). This study investigated whether the effects of various forms of childhood trauma on transition to psychosis are mediated by cortical thickness and surface area abnormalities.Methods: This prospective study used data from 62 UHR individuals from a previous (PACE 400) cohort study. At follow-up, 24 individuals had transitioned to psychosis (UHR-T) and 38 individuals had not transitioned (UHR-NT). Student-t/Mann-Whitney-U tests were performed to assess morphological differences in childhood trauma (low/high) and transition. Mediation analyses were conducted using regression and bootstrapping techniques.Results: UHR individuals with high sexual trauma histories presented with decreased cortical thickness in bilateral middle temporal gyri and the left superior frontal gyrus compared to those with low sexual trauma. Participants with high physical abuse had increased cortical thickness in the right middle frontal gyrus compared to those with low physical abuse. No differences were found for emotional abuse or physical/emotional neglect. Reduced cortical thickness in the right middle temporal gyrus and increased surface area in the right cingulate were found in UHR-T compared to UHR-NT individuals. Sexual abuse had an indirect effect on transition to psychosis, where decreased cortical thickness in the right middle temporal gyrus was a mediator.Conclusions: Results suggest that childhood sexual abuse negatively impacted on cortical development of the right temporal gyrus, and this heightened the risk of transition to psychosis in our sample. Further longitudinal studies are needed to precisely understand this link. [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]

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 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]

Emerging evidence suggests young people at ultra-high risk for psychosis (UHR) are also at-risk for poor physical health, and display high rates of modifiable cardiometabolic risk factors. However, before we can develop effective interventions there is a need to understand factors affecting lifestyle choices in the UHR group. We conducted semi-structured qualitative interviews with 20 UHR individuals (50% male; mean age 21.7), 5 parents (4 mothers, 1 father), and 6 clinicians from early intervention services in the Northwest of England to identify barriers and facilitators to living a healthy lifestyle, including achieving regular exercise, eating well and refraining from excessive substance use. Thematic analysis revealed the main barriers to living a healthy lifestyle related to psychiatric symptoms, beliefs about self, social withdrawal and practical considerations such as accessibility and cost. Provision of social support and promoting autonomy emerged as the two main themes which would facilitate a healthy lifestyle. Promoting physical health in people with emerging symptoms of psychosis is an important, yet neglected area of mental health practice and warrants further investigation. UHR individuals experience numerous barriers to living a healthy lifestyle, and interventions should focus primarily on targeting autonomous motivation and providing social support to facilitate this change. [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]

Background: Psychotic disorders are associated with high rates of sustained unemployment, however, little is known about the long-term employment outcome of people at ultra-high risk (UHR) of developing psychosis. We sought to investigate the long-term unemployment rate and baseline predictors of employment status at follow-up in a large UHR cohort.Method: 268 UHR patients recruited from the Personal Assessment and Crisis Evaluation clinic in Melbourne, Australia were followed-up over 2-14years after initial presentation to the service. Individuals in no form of employment or education were classed as unemployed. Logistic regression analyses were used to examine predictors of employment outcome.Results: A high rate of unemployment was present at follow-up in this UHR sample (23%). At baseline, those who were unemployed at follow-up had a longer duration of untreated illness, more severe negative symptoms, lower IQ, poorer social and occupational functioning and reported more childhood trauma than the employed group. At follow-up, unemployed individuals exhibited significantly more severe symptoms on all measures and were more likely to have been diagnosed with a mood, anxiety, psychotic or substance use disorder. Childhood trauma and the duration of untreated illness at baseline were significant independent predictors of employment status at follow-up in the multivariate analyses.Conclusions: Nearly a quarter of this UHR sample was unemployed at long-term follow-up. The duration of untreated illness and the effects of childhood trauma are potentially modifiable risk factors for long-term employment outcome in this group. Vocational support may be beneficial for many UHR patients presenting to services. [ABSTRACT FROM AUTHOR]

Objective: Social and role functioning are compromised for the majority of individuals at ultra-high risk of psychosis, and it is important to identify factors that contribute to this functional decline. This study aimed to investigate social cognitive abilities, which have previously been linked to functioning in schizophrenia, as potential factors that impact social, role and global functioning in ultra-high risk patients. Method: A total of 30 ultra-high risk patients were recruited from an established at-risk clinical service in Melbourne, Australia, and completed a battery of social cognitive, neurocognitive, clinical and functioning measures. We examined the relationships between all four core domains of social cognition (emotion recognition, theory of mind, social perception and attributional style), neurocognitive, clinical and demographic variables with three measures of functioning (the Global Functioning Social and Role scales and the Social and Occupational Functioning Assessment Scale) using correlational and multiple regression analyses. Results: Performance on a visual theory of mind task (visual jokes task) was significantly correlated with both concurrent role (r = 0.425, p = 0.019) and global functioning (r = 0.540, p = 0.002). In multivariate analyses, it also accounted for unique variance in global, but not role functioning after adjusting for negative symptoms and stress. Social functioning was not associated with performance on any of the social cognition tasks. Conclusion: Among specific social cognitive abilities, only a test of theory of mind was associated with functioning in our ultra-high risk sample. Further longitudinal research is needed to examine the impact of social cognitive deficits on long-term functional outcome in the ultra-high risk group. Identifying social cognitive abilities that significantly impact functioning is important to inform the development of targeted intervention programmes for ultra-high risk individuals. [ABSTRACT FROM AUTHOR]

Objective: Physical activity (PA) improves health outcomes in people with schizophrenia. It is unclear how much PA people with schizophrenia undertake and what influences PA participation. We conducted a meta-analysis to investigate PA levels and predictors in people with schizophrenia.Method: Major databases were searched from inception till 02/2016 for articles measuring PA (self-report questionnaire (SRQ) or objective measure (e.g. accelerometer)) in people with schizophrenia, including first episode psychosis (FEP). A random effects meta-analysis and meta-regression analysis were conducted.Results: 35 studies representing 3453 individuals with schizophrenia (40.0years; 64.0% male) were included. Engagement in light PA was 80.44min (95% CI 68.32-92.52, n=2658), 47.1min moderate-vigorous PA (95% CI 31.5-62.8, n=559) and 1.05min (95% CI 0.48-1.62, n=2533) vigorous PA per day. People with schizophrenia engaged in significantly less moderate (hedges g=-0.45, 95% CI -0.79 to -0.1, p=0.01) and vigorous PA (g=-0.4, 95% CI -0.60 to -0.18) versus controls. Higher light to moderate, but lower vigorous PA levels were observed in outpatients and in studies utilizing objective measures versus SRQ. 56.6% (95% CI 45.8-66.8, studies=12) met the recommended 150min of moderate physical activity per week. Depressive symptoms and older age were associated with less vigorous PA in meta-regression analyses.Conclusions: Our data confirm that people with schizophrenia engage in significantly less moderate and vigorous PA versus controls. Interventions aiming to increase PA, regardless of intensity are indicated for people with schizophrenia, while specifically increasing moderate-vigorous PA should be a priority given the established health benefits. [ABSTRACT FROM AUTHOR]

Introduction: Two thirds of individuals identified as ultra-high risk (UHR) for psychosis do not transition to psychosis over the medium to long-term (non-transition; UHR-NT). Nevertheless, many of these individuals have persistent attenuated psychotic symptoms (APS). The current study examined whether there were differences in baseline grey matter volume (i.e. at initial identification as UHR) in UHR-NT individuals whom had APS compared to those without APS (No-APS) at medium to long-term follow-up.Methods: Participants were help-seeking individuals who were identified as being at UHR for psychosis between 2 and 12years previously (mean=7.5). The sample consisted of 109 participants who underwent a Magnetic Resonance Imaging scan at baseline and who had not been observed to develop a psychotic disorder over the follow-up period (UHR-NT). Using voxel-based morphometry, baseline grey matter volume (GMV) was compared between participants with (N=30) and without (N=79) APS at follow-up.Results: At baseline, the APS and No-APS groups were clinically indistinguishable. At follow-up, the APS group had significantly worse symptoms and impaired functioning. Individuals with APS had reduced baseline GMV in frontal, temporal, posterior and cingulate regions compared to those without APS at follow-up. Reduced GMV was associated with more severe positive, negative and depressive symptoms and lower global functioning in the combined UHR-NT cohort. These associations were independent of later APS outcome.Discussion: This study found that differences in regional GMV are discernible at an early stage of UHR and may be specific to individuals who have APS and psychopathology at follow-up. Our findings suggest that lower GMV at baseline may confer neurobiological risk for later APS and/or increased psychopathology while the absence of these structural abnormalities might be protective. [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]

Background Investigation of aberrant large-scale brain networks offers novel insight into the role these networks play in diverse psychiatric disorders such as schizophrenia. Although studies report altered functional brain connectivity in participants at ultra-high risk (UHR) for psychosis, it is unclear whether these alterations extend to structural brain networks. Methods Whole-brain structural covariance patterns of 133 participants at UHR for psychosis (51 of whom subsequently developed psychosis) and 65 healthy control (HC) subjects were studied. Following data preprocessing (using VBM8 toolbox), the mean signal in seed regions relating to specific networks (visual, auditory, motor, speech, semantic, executive control, salience, and default-mode) were extracted, and voxel-wise analyses of covariance were conducted to compare the association between whole-brain signal and each seed region for UHR and HC individuals. The UHR participants who transitioned to psychosis were compared with the UHR participants who did not. Results Significantly reduced structural covariance was observed in the UHR sample compared with the HC sample for the default-mode network, and increased covariance was observed for the motor and executive control networks. When the UHR participants who transitioned to psychosis were compared with the UHR participants who did not, aberrant structural covariance was observed in the salience, executive control, auditory, and motor networks. Conclusions Whole-brain structural covariance analyses revealed subtle changes of connectivity of the default-mode, executive control, salience, motor, and auditory networks in UHR individuals for psychosis. Although we found significant differences, these are small changes and tend to reflect largely intact structural networks. [ABSTRACT FROM AUTHOR]

Objective Despite social environmental factors such as deprivation, urbanicity, migration and adversity being established risk factors for psychotic disorders, there is a paucity of knowledge on the influence of social environmental risk factors in the UHR population. Firstly, we aimed to investigate the association between social deprivation and risk of transition and secondly, we aimed to investigate the association between migration status and the risk of transition. Method UHR individuals at the Personal Assessment and Crisis Evaluation (PACE) service in Melbourne were included. Social deprivation as assessed according to postal code area of residence was obtained from census data and Cox regression analysis was used to calculate hazard ratios. Results A total of 219 UHR individuals were included and over the median follow-up time of 4.8 years, 32 individuals (14.6%) were known to have transitioned to a psychotic disorder. 8.8% of UHR individuals were first generation migrants and 41.9% were second generation migrants. The level of social deprivation was not associated with the risk of transition (p = 0.83). Similarly, first or second generation migrants did not have an increased risk of transition to psychosis (p = 0.84). Conclusions Despite being established risk factors for psychotic disorders, social deprivation and migrant status have not been found to increase the risk of transition in a UHR population. [ABSTRACT FROM AUTHOR]

Background Transition to psychotic disorder has been the traditional outcome of interest for research in the at-risk mental state (ARMS). However, there is growing recognition that individuals with ARMS may function poorly regardless of whether they develop psychosis. We aimed to review the literature to determine whether there are specific factors associated with, or predictive of, functional impairment in the ARMS population. Method An electronic database search of MEDLINE, PsycINFO and Embase from inception until May 2014 was conducted using keyword search terms synonymous with the at-risk mental state and functioning. Eligible studies were original peer-reviewed English language research articles with populations that met validated at-risk diagnostic criteria and examined the cross-sectional or longitudinal association between any variable and a measure of functioning. Results Seventy-two eligible studies were identified. Negative symptoms and neurocognitive impairment were associated with poor functioning in cross-sectional studies. Negative and disorganised symptoms, neurocognitive deficits and poor functioning at baseline were predictive of poor functional outcome in longitudinal studies. Positive symptoms were unrelated to functioning in both cross-sectional and longitudinal studies. Functional disability was persistent and resistant to current treatments. Conclusions Negative and disorganised symptoms and cognitive deficits pre-date frank psychotic symptoms and are risk factors for poor functioning. This is consistent with a subgroup of ARMS individuals potentially having neurodevelopmental schizophrenia. Treatments aimed at improving functioning must be considered a priority on par with preventing transition to psychosis in the development of future interventions in the ARMS group. [ABSTRACT FROM AUTHOR]

Abstract: Three types of orbitofrontal cortex (OFC) sulcogyral patterns have been identified in the general population. The distribution of these three types has been found to be altered in individuals at genetic risk of psychosis, and in patients with first episode psychosis (FEP) and chronic schizophrenia. This study aims at establishing whether altered OFC sulcogyral patterns were present in a large cohort of individuals at ultra high risk (UHR) for psychosis. OFC pattern type was classified and the number of posterior and intermediate sulci present on the surface of the OFC was counted. OFC sulcogyral type and the number of sulci were compared between controls (n=58) and UHR participants who transitioned (n=49) versus those who did not transition (n=77) to psychosis. Finally, the relationship between sulcogyral type and number of sulci with intellectual quotient (IQ), symptom severity and social functioning of UHR individuals was explored. In line with other studies conducted in chronic schizophrenia and FEP, UHR individuals who later transitioned to psychosis showed a reduced incidence of the Type I OFC on the right hemisphere compared to controls (χ2 =19.847, p<0.001). These highly consistent results point towards the protective effect of possessing a Type I OFC in the right hemisphere. Furthermore, OFC sulcus counts revealed that controls presented with a higher number of posterior (right hemisphere; χ2 =11.658, p=0.003) and intermediate sulci (left: χ2 =6.643, p=0.036; right: χ2 =11.726, p=0.020) when compared to UHR individuals. However, no associations between OFC types or sulcus count and IQ, symptoms and functioning were observed. [Copyright &y& Elsevier]