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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]

Aim: Cannabis use is associated with greater likelihood of psychosis. The relationship between attitudes about cannabis and use has not been examined in youth at clinical high‐risk (CHR) for psychosis. Additionally, the shifting legal landscape can provide a valuable context for evaluating use and related attitudes. Methods: This study included 174 participants (44 CHR, 43 healthy control [HC] youth‐parent dyads). Youth completed measures of self‐reported cannabis use confirmed with a urinalysis, self‐perceived risk and perceived peer attitudes. Parents reported attitudes about youth use. Legalization occurred halfway during a 5‐year study in Colorado, providing an opportunity to cross‐sectionally examine its role in use and attitudes. Results: Frequency of youth reporting cannabis use was significantly higher in CHR (69%) than control group (30%). Use in CHR group was associated with higher perceived peer approval (r =.57), increased parental permissiveness (r =.28) and lower self‐perceived risk (r = −.26). Comparing samples participating pre and post‐legalization, use remained stable within each group. Group differences in parental permissiveness shifted; trend toward decrease in permissiveness in CHR group (η2partial =.07) and a significant increase in HCs (η2partial =.16) were observed. Post‐legalization, use in CHR group correlated with higher perceived peer approval (r =.64), lower self‐perceived risk (r = −.51) and higher parental permissiveness (r =.35, trend). Conclusions: Taken together, results indicate a relationship between self and peer/parental attitudes about cannabis and use in youth at CHR for psychosis. These factors are important to consider within the legalization context given the changes in parental attitudes and a stronger association between use and attitudes in this group post‐legalization. [ABSTRACT FROM AUTHOR]

Aim: Poor functioning has become a hallmark of many youth at clinical high‐risk (CHR) of psychosis. Even for those who do not make the transition to psychosis remain troubled by functional deficits and a decline in functioning increases the odds of transitioning to psychosis. There are very few treatment studies that have attempted to improve social and role functioning. The aim of this paper is to describe the methods of a treatment study to address social and role functioning in CHR. Methods: This was a randomized controlled trial of cognitive‐behavioural social skills training (CBSST) versus a supportive therapy. CBSST combines elements of cognitive behaviour therapy (CBT) and social skills training (SST), two evidence‐based treatments for schizophrenia. By adding CBT to SST to target functioning outcomes, SST can be used to train new social skills, and thoughts that interfere with skilled performance in the real world can be addressed using CBT. We developed an adapted version of CBSST, more appropriate for the age range and illness severity of typical CHR individuals, to attempt to show improvements in social and role functioning for these young people. Results: Two hundred and three participants were recruited for this study. Results include initial baseline data. Conclusion: This article describes the baseline methodology of a CHR youth who have difficulties in social and/or role functioning. It is one of the first clinical trials to address this significant problem. [ABSTRACT FROM AUTHOR]

Aim: Childhood Adversity (CA) is strongly linked to psychotic‐like symptoms across the clinical spectrum, though the mechanisms underlying these associations remain poorly understood. Negative cognitive schemas are associated with both CA exposure and psychotic symptoms, highlighting the possibility that cognitive schemas may be a key risk pathway. The purpose of this study was to determine whether negative cognitive schemas mediate the association between CA and specific attenuated psychotic symptoms in a large sample of clinical‐high risk youth. Given the variability in experiences that encompass CA (eg, abuse, neglect and poverty) and attenuated psychotic symptoms (eg, suspiciousness and perceptual abnormalities), we also tested whether these associations differ by CA type (threat vs deprivation) and attenuated positive psychotic symptom domain. Methods: Data were collected from 531 clinical‐high risk youth between 12 and 35 years of age (mean = 18.80, SD = 4.21) who completed a clinical assessment that included the Structured Interview of Prodromal Syndromes (SIPS), Childhood Trauma and Abuse scale and questionnaires on cognitive schemas and depressive symptoms. Results: No direct effects of threat or deprivation exposure on any of the psychotic symptom domains were found. However, there was a unique indirect effect of threat, but not deprivation, on delusional thinking and suspiciousness through negative cognitive schemas about others. Conclusion: Cognitive vulnerability in the form of negative schemas about others may be one mechanism linking childhood threat experiences and attenuated psychotic symptoms. The results underscore the importance of targeting negative schemas in interventions to mitigate psychosis risk. [ABSTRACT FROM AUTHOR]

The objective of the current study was to build predictive models for suicidal ideation in a sample of children aged 9–10 using features previously implicated in risk among older adolescent and adult populations. This case-control analysis utilized baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study, collected from 21 research sites across the United States (N = 11,369). Several regression and ensemble learning models were compared on their ability to classify individuals with suicidal ideation and/or attempt from healthy controls, as assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime Version. When comparing control participants (mean age: 9.92±0.62 years; 4944 girls [49%]) to participants with suicidal ideation (mean age: 9.89±0.63 years; 451 girls [40%]), both logistic regression with feature selection and elastic net without feature selection predicted suicidal ideation with an AUC of 0.70 (CI 95%: 0.70–0.71). The random forest with feature selection trained to predict suicidal ideation predicted a holdout set of children with a history of suicidal ideation and attempt (mean age: 9.96±0.62 years; 79 girls [41%]) from controls with an AUC of 0.77 (CI 95%: 0.76–0.77). Important features from these models included feelings of loneliness and worthlessness, impulsivity, prodromal psychosis symptoms, and behavioral problems. This investigation provided an unprecedented opportunity to identify suicide risk in youth. The use of machine learning to examine a large number of predictors spanning a variety of domains provides novel insight into transdiagnostic factors important for risk classification. [ABSTRACT FROM AUTHOR]

The objective of the study is to describe the development and user acceptance testing of a mobile-based application to monitor daily cannabis use of individuals at clinical high-risk for psychosis. Through participatory co-design, app development was staggered in two phases. In Phase 1 (app development), two focus groups were run to gather information on a) app content, and b) graphic design Participants named the application LooseLeaf, which comprised five features: home screen, inventory, daily questions, calculators, and stats. The application monitored daily cannabis consumption, cannabis-related experiences, other substances, and the perception of their day. In Phase 2 (user acceptance testing), a prototype of the application was debugged and tested by developers. Participants used the app for 1 week. Usability was measured with quantitative and qualitative data about the app through the Mobile Application Rating Scale user-version (uMARS). LooseLeaf received a good overall score in the MARS with the highest rating in esthetics, information, and functionality. In conclusion, co-design through focus groups with youth provided effective feedback for developing LooseLeaf, demonstrating initial acceptability and usability. [ABSTRACT FROM AUTHOR]

Background: Families can play a critical role in the development of psychosis. Adaptability (i.e., flexibility) and cohesion (i.e., emotional bonding) are important markers of family functioning, but have rarely been studied in youth at clinical high risk for developing psychosis (CHR), especially not from a multi-informant perspective.Methods: The current study examined adaptability and cohesion (using youth and mother reports) and clinical symptoms (in youth) among 75 youth at CHR and their mothers (N = 48) and 79 matched healthy controls and their mothers (N = 42).Results: Findings showed that (1) youth at CHR and their mothers reported lower adaptability and cohesion than their healthy control counterparts. (2) All youth reported lower adaptability than mothers, but only youth at CHR (not control youth) reported lower cohesion than their mothers. (3) There were no significant links between CHR youth and mother reports of adaptability and cohesion and clinical symptoms.Conclusions: Findings support existing literature that families with a youth at CHR are at risk for poorer functioning and demonstrate pronounced youth-mother discrepancies with youth at CHR (but not controls) reporting lower emotional bonding than their mothers. Future studies may further probe multi-informant perspectives of family environment as a clinical marker in the clinical high risk state. [ABSTRACT FROM AUTHOR]

Individuals at ultra-high risk (UHR) of psychosis are characterised by the emergence of attenuated psychotic symptoms and deterioration in functioning. In view of the high non-psychotic comorbidity and low rates of transition to psychosis, the specificity of the UHR status has been called into question. This study aims to (i) investigate if the UHR construct is associated with the genetic liability of schizophrenia or other psychiatric conditions; (ii) examine the ability of polygenic risk scores (PRS) to discriminate healthy controls from UHR, remission and conversion status. PRS was calculated for 210 youths (nUHR = 102, nControl = 108) recruited as part of the Longitudinal Youth at Risk Study (LYRIKS) using nine psychiatric traits derived from twelve large-scale psychiatric genome-wide association studies as discovery datasets. PRS was also examined to discriminate UHR-Healthy control status, and healthy controls from UHR remission and conversion status. Result indicated that schizophrenia PRS appears to best index the genetic liability of UHR, while trend level associations were observed for depression and cross-disorder PRS. Schizophrenia PRS discriminated healthy controls from UHR (R2 = 7.9%, p = 2.59 x 10−3, OR = 1.82), healthy controls from non-remitters (R2 = 8.1%, p = 4.90 x 10−4, OR = 1.90), and converters (R2 = 7.6%, p = 1.61 x 10−3, OR = 1.82), with modest predictive ability. A trend gradient increase in schizophrenia PRS was observed across categories. The association between schizophrenia PRS and UHR status supports the hypothesis that the schizophrenia polygenic liability indexes the risk for developing psychosis. [ABSTRACT FROM AUTHOR]

Objective: Thalamus models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment. Studies to date have provided conflicting findings for structural deficits specific to these nuclei. The authors sought to characterize thalamic structural abnormalities in psychosis and a neurodevelopmental cohort, and to determine whether nuclear volumes were associated with cognitive function.Methods: Thalamic nuclei volumes were tested in a cross-sectional sample of 472 adults (293 with psychosis) and the Philadelphia Neurodevelopmental Cohort (PNC), consisting of 1,393 youths (398 with psychosis spectrum symptoms and 609 with other psychopathologies), using a recently developed, validated method for segmenting thalamic nuclei and complementary voxel-based morphometry. Cognitive function was measured with the Screen for Cognitive Impairment in Psychiatry in the psychosis cohort and the Penn Computerized Neurocognitive Battery in the PNC.Results: The psychosis group had smaller pulvinar, mediodorsal, and, to a lesser extent, ventrolateral nuclei volumes compared with the healthy control group. Youths with psychosis spectrum symptoms also had smaller pulvinar volumes, compared with both typically developing youths and youths with other psychopathologies. Pulvinar volumes were positively correlated with general cognitive function.Conclusions: The study findings demonstrate that smaller thalamic association nuclei represent a neurodevelopmental abnormality associated with psychosis, risk for psychosis in youths, and cognitive impairment. Identifying specific thalamic nuclei abnormalities in psychosis has implications for early detection of psychosis risk and treatment of cognitive impairment in psychosis. [ABSTRACT FROM AUTHOR]

Individuals at ultra-high risk (UHR) for psychosis have an elevated risk of developing psychosis and other psychiatric outcomes. Risk biomarkers can assist in delineating individual risk and allow better prediction of longer-term outcomes. The aim of the present study was to examine if allostatic load (AL), a multisystem index of neuroendocrine, cardiovascular, immune and metabolic dysregulation, is associated with clinical outcomes in youth at UHR for psychosis. AL was measured in 106 participants of the NEURAPRO study (n = 70 female, n = 36 male; mean age 17.21, SD 2.37), a multicentre randomized-controlled trial of long-chain omega-3 polyunsaturated fatty acids versus placebo in people at UHR for psychosis. Psychiatric symptoms and social and occupational functioning were assessed at baseline and 6 and 12 months after study intake. Multivariate linear and logistic regression models were used to test the relationship between AL and clinical outcomes. High AL at baseline was associated with poor social and occupational functioning at 6 months (β = -0.224, p = 0.025) and with more severe manic symptoms at 6 months (β = 0.207, p = 0.026), taking into account relevant covariates including age and smoking status. No significant associations were observed at the 12-month follow-up assessment or with any other clinical outcome measures. Our data provide initial evidence for a link between AL and impaired functioning in individuals at UHR for psychosis. Further studies are needed to evaluate AL as a potential predictor of early treatment response. [ABSTRACT FROM AUTHOR]

Abnormal reward processing is thought to play an important role in the development of psychosis, but relatively few studies have examined reward prediction errors, reinforcement learning (RL), and the reward circuitry that subserves these interconnected processes among individuals at clinical high-risk (CHR) for the disorder. Here, we present behavioral and functional neuroimaging results of two experimental tasks designed to measure overlapping aspects of reward processing among individuals at CHR (n = 22) and healthy controls (n = 19). We found no group differences in response times to positive, negative, or neutral outcome-signaling cues, and no significant differences in brain activation during reward anticipation or receipt. Youth at CHR, however, displayed clear RL impairments, as well as attenuated responses to rewards and blunted prediction error signals in the ventral striatum, dorsal anterior cingulate cortex (dACC), and ventromedial prefrontal cortex (vmPFC). Greater contrasts for cue valence (gain-loss) and outcome magnitude (large-small) in the vmPFC were associated with more severe negative symptoms, and deficits in dACC signaling during RL were associated with more depressive symptoms. Our results provide evidence for RL deficits and abnormal prediction error signaling in the brain's reward circuitry among individuals at CHR, while also suggesting that reward motivation may be relatively preserved at this stage in development. Longitudinal studies, medication-free participants, and comparison of neurobehavioral measures against both healthy and clinical controls are needed to better understand the role of reward system abnormalities in the development of psychosis. [ABSTRACT FROM AUTHOR]

The main goal of the present study was to explore the latent structure of extended psychosis phenotypes in a representative sample of adolescents. Moreover, associations with socio-emotional adjustment, academic achievement, and neurocognition performance across the latent profiles were compared. Participants were 1506 students, 667 males (44.3%), derived from random cluster sampling. Various tools were used to measure psychosis risk, subjective well-being, academic performance, and neurocognition. Based on three psychometric indicators of psychosis risk (schizotypal traits, psychotic-like experiences, and bipolar-like experiences), four latent classes were found: non-risk, low-risk, high reality distortion experiences, and high psychosis liability. The high-risk latent groups scored significantly higher on mental health difficulties, and negative affect, and lower on positive affect and well-being, compared to the two non-risk groups. Moreover, these high-risk groups had a significantly higher number of failed academic subjects compared to the non-risk groups. In addition, no statistically significant differences in efficiency performance were found in the neurocognitive domains across the four latent profiles. This study allows us to improve the early identification of adolescents at risk of serious mental disorder in school settings in order to prevent the incidence and burden associated with these kinds of mental health problems. [ABSTRACT FROM AUTHOR]

Stress and cannabis use are risk factors for the development of psychosis. We have previously shown that subjects at clinical high risk for psychosis (CHR) exhibit a higher striatal dopamine response to stress compared with healthy volunteers (HV), with chronic cannabis use blunting this response. However, it is unknown if this abnormal dopamine response extends to the prefrontal cortex (PFC). Here, we investigated dorsolateral PFC (dlPFC) and medial PFC (mPFC) dopamine release using [11 C]FLB457 positron emission tomography (PET) and a validated stress task. Thirty-three participants completed two PET scans (14 CHR without cannabis use, eight CHR regular cannabis users [CHR-CUs] and 11 HV) while performing a Sensory Motor Control Task (control scan) and the Montreal Imaging Stress Task (stress scan). Stress-induced dopamine release (ΔBPND ) was defined as percent change in D2/3 receptor binding potential between both scans using a novel correction for injected mass of [11 C]FLB457. ΔBPND was significantly different between groups in mPFC (F(2,30) = 5.40, .010), with CHR-CUs exhibiting lower ΔBPND compared with CHR (.008). Similarly, salivary cortisol response (ΔAUCI ) was significantly lower in CHR-CU compared with CHR (F(2,29) = 5.08, .013; post hoc .018) and positively associated with ΔBPND . Furthermore, CHR-CUs had higher attenuated psychotic symptoms than CHR following the stress task, which were negatively associated with ΔBPND . Length of cannabis use was negatively associated with ΔBPND in mPFC when controlling for current cannabis use. Given the global trend to legalize cannabis, this study is important as it highlights the effects of regular cannabis use on cortical dopamine function in high-risk youth. [ABSTRACT FROM AUTHOR]

Effective social functioning requires a broad range of social communication skills that are impaired in psychosis populations. However, little is known about early childhood (4- to 5-year period) social communication during the premorbid (pre-illness) stage of psychosis. The present study utilized retrospective parent reports to examine total early childhood social communication deficits, as well as deficits in two distinct domains, reciprocal social interaction (social smiling/eye gaze) and communication (social chat/gesture), in youth at clinical high-risk (CHR) for psychosis (ages 13–21; 37.2% female). Furthermore, associations between early childhood social communication and CHR youth's current functioning (social, academic/work), symptoms (positive/negative), and risk for conversion to psychosis were examined. Compared to healthy controls, CHR individuals had greater deficits in total and communication-specific early childhood social communication. Early childhood total, communication, and reciprocal social interaction deficits were associated with worse current functioning and greater current negative symptom severity (amotivation/anhedonia) in CHR youth. Early childhood total and reciprocal social interaction deficits were also associated with increased risk for conversion. These findings inform the field's understanding of the etiology and pathophysiology of psychosis by extending the current developmental literature on premorbid deficits in psychosis populations to specific domains of social behavior in a critical developmental period. [ABSTRACT FROM AUTHOR]

Aim: Few interventions address social cognition or functioning in individuals at clinical risk (CR) for psychosis. Theatre Improvisation Training to Promote Social Cognition (TIPS) is a manualized intervention based on drama therapy. We aim to describe TIPS, evaluate feasibility and acceptability, and present a preliminary investigation of outcomes in a quasi‐experimental design. Methods: Thirty‐six CR participants (15‐25 years) were ascertained from the Philadelphia Neurodevelopmental Cohort. Twenty‐six completed the TIPS protocol: 18 weekly 2‐hour group sessions led by a theatre director and actor‐assistant. Participants engaged in collaborative acting and improvisation exercises. Baseline and follow‐up assessments included the Clinical Assessment Interview for Negative Symptoms (CAINS), Structured Interview for Prodromal Syndromes, Global Assessment of Functioning (GAF) and Penn Computerized Neurocognitive Battery (CNB), which includes social cognitive tests. Acceptability was assessed using focus groups. Preliminary outcomes were compared to CR controls who were not enrolled in the study but completed follow‐up assessments using the same methods. Results: There were no significant differences in baseline demographics, psychosis symptoms, or cognition between those who did and did not complete the protocol. Overall, TIPS was considered feasible and acceptable among CR. Preliminary outcomes suggest that TIPS may be effective in improving positive and negative psychosis‐spectrum symptoms and GAF, but not performance on facial emotion processing. Conclusions: TIPS is a promising and acceptable intervention that may improve symptoms and functioning in CR while providing a framework for participants to develop more empowered and confident ways of relating to others. Larger randomized controlled trials investigating TIPS efficacy are warranted. [ABSTRACT FROM AUTHOR]

Background: In the last 10 years, psychological approaches based on mindfulness techniques have been proposed for the management of psychotic experiences.Method: In this brief review we summarized, to our knowledge for the first time, published studies on mindfulness-based interventions (MBIs) applied to the early phase of major psychoses (affective and non-affective).Results: Despite the great variability in terms of MBIs protocols, available studies on young people at risk to develop or with a first episode of psychosis suggest MBIs as a feasible, well-tolerated and effective approach in ameliorating symptoms, functioning, emotion regulation, and finally reducing the psychological distress associated with the onset of mania and/or psychotic experience.Limitations: The small sample size and inconsistencies between studies in terms of design, MBIs protocols and outcome measures suggest being cautious in interpreting and generalizing results. Moreover, specific guidelines are missing for the adaptation of MBIs to youth at risk of developing affective psychoses.Conclusions: Preliminary findings show that MBIs may be considered a promising adjunctive therapy for the treatment of major psychoses in the early phases of the illness. However, the conduct of further studies in larger samples and with a more rigorous methodology is warranted to confirm the beneficial effect of MBIs in the early stages of major psychoses. [ABSTRACT FROM AUTHOR]

NEURAPRO was a multicenter, placebo-controlled trial of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) in 304 individuals at ultra-high risk for psychotic disorders. The study failed to show benefits of n-3 PUFAs over placebo. Although the randomized controlled trial design is placed at the top of the evidence hierarchy, this methodology has limitations in fish oil randomized controlled trials, as not only is the test agent present in the intervention group, but also n-3 fats are present in the diet and the body tissue of all participants. Analysis of biomarker data (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], n-3 index, EPA+DHA) collected as part of NEURAPRO was conducted on 218 participants with longitudinal biomarker data to determine if n-3 PUFAs measured in erythrocytes at baseline and month 6 predicted clinical outcomes. Increases of the n-3 index, EPA, and DHA predicted less severe psychopathology and better functioning at both follow-up time points. Higher baseline levels and increases of n-3 index also predicted overall clinical improvement at month 6 (n-3 index baseline: adjusted odds ratio [95% confidence interval (CI)] = 1.79 [1.30–2.48]; n-3 PUFA increase: adjusted odds ratio [95% CI] = 1.43 [1.16–1.76]) and at month 12 (n-3 index baseline: adjusted odds ratio [95% CI] = 2.60 [1.71–3.97]; n-3 PUFA increase: adjusted odds ratio [95% CI] = 1.36 [1.06–1.74]). These data suggest that n-3 PUFAs can exert therapeutic effects in ultra-high-risk individuals. This finding has implications for early intervention and treatment guidelines, as n-3 PUFA supplementation can easily and safely be used in a wide variety of settings, from primary care to specialist services. [ABSTRACT FROM AUTHOR]

Background: Despite the long-emphasized role of the family environment in the schizophrenia literature, coping with family stress has been neglected in research on the psychosis risk period.Methods: The sample consisted of 75 youth at clinical high-risk (CHR) for psychosis and 79 matched healthy controls who reported on their use of engagement and disengagement coping strategies in response to stress with parents and perceived social support (i.e., advice availability, family support and strain). Participants were also assessed for clinical symptoms.Results: Individuals at CHR reported similar levels of engagement strategies (e.g., emotion regulation, positive thinking) and more frequent use of disengagement strategies (e.g., avoidance, denial) compared to healthy controls. In individuals at CHR (as well as healthy controls), greater use of engagement strategies predicted greater perceptions of availability of advice support, whereas greater employment of disengagement strategies predicted lower perceived social support from the family and greater family strain. In individuals at CHR (as well as healthy controls), engagement strategies were not linked to any clinical outcomes, whereas disengagement strategies were closely tied to anxiety and depression (but not psychosis symptoms in individuals at CHR).Conclusions: Individuals at CHR appeared to engage the same amount as controls, but disengage more often when coping with family stress; this pattern was linked to perceptions of social support and tied to a putative family environment as well as clinical phenomenology. The findings have implications for targeting interventions for CHR populations during a vulnerable period for stress and social change. [ABSTRACT FROM AUTHOR]

A large body of literature has demonstrated that exercise interventions can improve a broad range of outcomes in people with established schizophrenia, including reducing psychiatric symptoms, increasing cognitive functioning, and improving physical health. Furthermore, these benefits seem just as pronounced in first-episode psychosis. However, there have been few clinical studies to date examining the effects of exercise in those found to be 'at-risk' of psychosis, particularly for those meeting the criteria for 'Clinical High Risk' (CHR) state (a classification which includes both those meeting the 'ultra-high risk for psychosis' criteria and/or those with 'atrisk mental states'). This is surprising, as a proportion of those in the CHR state go on to develop psychotic disorders, and a growing body of evidence suggests that early interventions in this period have significant potential to improve the course of illness. In this article, we shall review the existing literature for i) exercise as an adjunctive intervention for those treated for psychosis; ii) exercise as a standalone intervention in CHR groups; and iii) the rationale and supportive evidence for widescale use of exercise to preserve physical and mental health in those identified as at risk for psychosis. From this, we will put forth how the CHR phase represents an under-researched but highly-suitable timepoint for administering structured exercise interventions, in order to improve physical, psychological and neurocognitive outcomes; while also potentially reducing the odds of transition to full-threshold psychotic disorders. Following this, directions, recommendations and considerations around both the clinical implementation and future research around exercise in CHR individuals will be discussed. [ABSTRACT FROM AUTHOR]

An 8-week mindfulness and compassion program was developed for youth at risk for, or already experiencing, psychosis, based on UK national guidelines for developing interventions. The aim of this paper is to provide a program description and first hand account of a participant's experience. First, mindfulness skills are taught. Next an emotional regulation model is introduced, to help participants understand how psychotic experiences, anxiety and depression contribute to a heightened threat system, and how compassion can help them. The program contains meditations (e.g. breath practice, compassionate friend) and practices for use in daily life (e.g. STOP practice). The second author found mindfulness allowed her to feel and acknowledge her experience and give her emotions the recognition they needed. Being self-compassionate was a new concept, which at times was challenging but helped her realize her emotions were normal and she could manage difficult emotions using soothing practices. Furthermore, being part of a group helped her realize she was not alone. Mindfulness and compassion skills can be helpful for youth with psychotic experiences. A group program can provide a safe place to share experiences and reduce isolation. An evaluation of the program will be the focus of future papers. [ABSTRACT FROM AUTHOR]

Background: Psychotic experiences (PEs) are commonly reported in adolescence and are associated with a range of negative outcomes. Few targets for intervention for PEs have been identified. One potential target is self‐concept: an individual's beliefs about his/her personal attributes. Improvements in self‐concept have been shown to reduce psychotic symptoms in patients with schizophrenia but no study has investigated the relationship between changes in self‐concept and risk of PEs in the general population. We aimed to investigate: (a) the relationship between child and adolescent self‐concept and adolescent PEs; and (b) whether changes in self‐concept between childhood and adolescence were associated with risk of adolescent PEs. Method: Using data from age 9 and age 13 (n = 7,423) of the child cohort (Cohort'98) from the Growing Up in Ireland study we investigated the relationship between self‐concept at age 9 and age 13 and PEs at age 13. PEs were measured using the Adolescent Psychotic Symptoms Screener and self‐concept was measured using the Piers Harris‐II. Using a stratified analysis, we investigated the relationship between change in self‐concept between age 9 and age 13 and the risk of PEs at age 13. Additionally we investigated changes across the six self‐concept subscales. Results: Psychotic experiences were reported by 13% of participants at age 13. 'Very low' self‐concept at age 9 was associated with an increased risk of PEs at age 13 (Adjusted‐OR: 2.74, CI: 1.80–4.19), and 'High' self‐concept at age 9 was associated with a decreased risk of PEs at age 13 (Adjusted‐OR: 0.77, CI: 0.60–0.97). The stratified analysis indicated that improvements in self‐concept reduced the odds of adolescent PEs and decline in self‐concept increased the odds of adolescent PEs. This effect was noted across the majority of the self‐concept subscales. Conclusions: There is a strong relationship between self‐concept and PEs. The antecedents of low self‐concept may be a useful target for preventative psychiatry. Broad‐spectrum interventions targeting self‐concept in childhood may help to reduce the incidence of PEs in adolescence. [ABSTRACT FROM AUTHOR]

Purpose: To investigate to which extent occupational status, and job titles, were associated with types of hospitalisations and psychiatric diagnoses among inpatients of Friuli Venezia Giulia Region, Italy. Methods: Cross-sectional study based on 10 years register data (2008–2017) on 2929 subjects hospitalised in General Hospital Psychiatric Units. Odds ratios (OR) of hospitalisations and psychiatric diagnoses for occupational status and job titles were calculated by logistic regression analysis. Results: Employed were at lower risk of urgent and involuntary hospitalisation. The risk of urgent hospitalisation was higher for affective, organic or other disorders, while all psychiatric diagnoses were at lower risk of involuntary hospitalisation than psychosis. Using white collars as reference category, army showed a higher risk for urgent hospitalisation (OR = 2.3) and affective disorders (OR = 1.9). A higher risk for affective disorders was found in managers (OR = 2.0). Blue collars were at higher risk for alcohol and substance abuse (OR = 1.7). Conclusions: Employment was protective for urgent and involuntary hospitalisations and severe diagnoses. Hospitalisation for affective disorders was more likely in managers, army, and for substances abuse in blue collars. More research is needed to assess the association between specific occupational groups and involuntary hospitalisation. Employment was shown to be a protective factor for both urgent and involuntary hospitalisations and diagnosis of severe mental disorder. Managers, police and military forces were at higher risk of being hospitalised for affective disorders, while blue collars were at higher risk of hospitalisation for alcohol and substances abuse. Future research would benefit from a better analysis on the association between more specific occupational groups and hospitalisation for psychiatric disorders, with a particular focus on involuntary treatment. Further research is needed to compare the risk of hospitalisation for mental disorders in temporary or permanent position, according to recent international changes in labour market and its impact on mental health. [ABSTRACT FROM AUTHOR]

Objective: The interplay between genetic and environmental factors on risk for psychotic illness remains poorly understood. The aim of this study was to estimate independent and combined effects of familial liability for schizophrenia and exposure to obstetric complications on risk for developing psychotic illness, covarying with exposure to other environmental stressors. Methods: This whole-population birth cohort study used record linkage across Western Australian statewide data collections (midwives, psychiatric, hospital admissions, child protection, mortality) to identify liveborn offspring (n = 1046) born 1980–1995 to mothers with schizophrenia, comparing them to offspring of mothers with no recorded psychiatric history (n = 298,370). Results: Both maternal schizophrenia and pregnancy complications were each significantly associated with psychotic illness in offspring, with no interaction. Non-obstetric environmental stressors significantly associated with psychotic illness in offspring included the following: being Indigenous; having a mother who was not in a partnered relationship; episodes of disrupted parenting due to hospitalisation of mother, father or child; abuse in childhood; and living in areas of greatest socioeconomic disadvantage and with elevated rates of violent crime. Adjustment for these other environmental stressors reduced the hazard ratio for maternal schizophrenia substantially (from hazard ratio: 5.7, confidence interval: 4.5–7.2 to hazard ratio: 3.5, confidence interval: 2.8–4.4), but not the estimate for pregnancy complications (hazard ratio: 1.1, confidence interval: 1.0–1.2). The population attributable fraction for maternal schizophrenia was 1.4 and for pregnancy complications was 2.1. Conclusion: Our finding of a substantial decrease in risk of psychotic illness associated with familial liability for psychosis following adjustment for other environmental stressors highlights potentially modifiable risk factors on the trajectory to psychotic illness and suggests that interventions that reduce or manage exposure to these risks may be protective, despite a genetic liability. [ABSTRACT FROM AUTHOR]

Aim: The aims of this study are: (a) to determine the incidence of postoperative delirium (POD) among surgical intensive care unit (ICU) patients in China and identify risk factors, especially, which are modifiable and have value for developing a prediction model; (b) to develop and validate a prediction model of delirium to recognize high‐risk patients in surgical ICUs; (c) to investigate the short‐ and long‐term outcomes of delirious patients and identify the predictors of patient outcomes. Design: A single‐centre prospective cohort study. Methods: Patients will be enrolled from three surgical ICUs in a tertiary teaching hospital. Delirium assessment and perioperative data will be collected throughout the hospitalization. Delirious patients will be followed up for 2 years. The study was approved by the ethics committee in May 2018 and was funded by the clinical research grant from Zhongshan hospital, Fudan University, Shanghai. Discussion: Developing POD can be a burden to patients both for the short‐ and long‐term period. Due to the lack of effective treatments for POD, prevention remains the best strategy. This study will provide an effective tool for early screening of high‐risk patients of POD and provide a better understanding of the aetiology and outcome of delirium. Impact: In clinical practice, a prediction model will offer an effective tool for ICU nurses to assess high‐risk patients, which can support them to implement preventive strategies at the early stages to targeted patients. The follow‐up results will help us better understand the impact of delirium on patients' long‐term outcome. [ABSTRACT FROM AUTHOR]

Childhood adversity is among the strongest risk factors for psychosis-spectrum disorders, though the nature and specificity of the biological mechanisms underlying this association remains unclear. Previous research reveals overlaps in the volumetric alterations observed in both adversity-exposed individuals and in psychosis-spectrum populations, highlighting the possibility that deviations in corticolimbic gray matter development may be one mechanism linking adversity and psychosis. Given that childhood adversity encompasses a wide range of adverse experiences, there is also a critical need to examine whether these different types of experiences have unique effects on corticolimbic regions. This study examined the association between childhood adversity and cortical, hippocampal, and amygdalar volume in a large sample of youth at clinical-high risk (CHR) for psychosis. We utilized a novel differentiated adversity approach that distinguishes exposures along dimensions of threat (e.g., abuse) and deprivation (e.g., poverty, neglect) to test for differential associations. Participants were drawn from the North American Prodromal Longitudinal Study (NAPLS) and completed an MRI scan and a retrospective assessment of childhood adversity at baseline. We found that deprivation exposure, but not threat, was uniquely associated with smaller cortical volume and smaller right hippocampal volume in CHR youth. These associations were masked in a generalized risk model that utilized a total adversity score. The findings suggest that deprivation exposures during childhood contribute to the subtle volumetric reductions observed in clinical high-risk samples and highlight the importance of disentangling different dimensions of adversity. [ABSTRACT FROM AUTHOR]

Importance: In most patients, a prodromal period precedes the onset of schizophrenia. Although clinical criteria for identifying the psychosis risk syndrome (PRS) show promising predictive validity, assessment of neurophysiologic abnormalities in at-risk individuals may improve clinical prediction and clarify the pathogenesis of schizophrenia.Objective: To determine whether P300 event-related potential amplitude, which is deficient in schizophrenia, is reduced in the PRS and associated with clinical outcomes.Design, Setting, and Participants: Auditory P300 data were collected as part of the multisite, case-control North American Prodrome Longitudinal Study (NAPLS-2) at 8 university-based outpatient programs. Participants included 552 individuals meeting PRS criteria and 236 healthy controls with P300 data. Auditory P300 data of participants at risk who converted to psychosis (n = 73) were compared with those of nonconverters who were followed up for 24 months and continued to be symptomatic (n = 135) or remitted from the PRS (n = 90). Data were collected from May 27, 2009, to September 17, 2014, and were analyzed from December 3, 2015, to May 1, 2019.Main Outcomes and Measures: Baseline electroencephalography was recorded during an auditory oddball task. Two P300 subcomponents were measured: P3b, elicited by infrequent target stimuli, and P3a, elicited by infrequent nontarget novel stimuli.Results: This study included 788 participants. The PRS group (n = 552) included 236 females (42.8%) (mean [SD] age, 19.21 [4.38] years), and the healthy control group (n = 236) included 111 females (47.0%) (mean [SD] age, 20.44 [4.73] years). Target P3b and novelty P3a amplitudes were reduced in at-risk individuals vs healthy controls (d = 0.37). Target P3b, but not novelty P3a, was significantly reduced in psychosis converters vs nonconverters (d = 0.26), and smaller target P3b amplitude was associated with a shorter time to psychosis onset in at-risk individuals (hazard ratio, 1.45; 95% CI, 1.04-2.00; P = .03). Participants with the PRS who remitted had baseline target P3b amplitudes that were similar to those of healthy controls and greater than those of converters (d = 0.51) and at-risk individuals who remained symptomatic (d = 0.41).Conclusions and Relevance: In this study, deficits in P300 amplitude appeared to precede psychosis onset. Target P3b amplitudes, in particular, may be sensitive to clinical outcomes in the PRS, including both conversion to psychosis and clinical remission. Auditory target P3b amplitude shows promise as a putative prognostic biomarker of clinical outcome in the PRS. [ABSTRACT FROM AUTHOR]

Negative symptoms are recognized as a fundamental feature of schizophrenia throughout the disease course. Epigenetic alterations in the oxytocin receptor gene (OXTR) may be a key mechanism involved in social-emotional disturbances of schizophrenia. Here, we investigated OXTR methylation and its association with clinical and brain network connectivity phenotypes of negative symptoms, particularly anhedonia-asociality, in individuals with recent-onset schizophrenia (ROS) and at ultrahigh risk (UHR) for psychosis. Sixty-four ROS (39 women), 46 UHR (19 women), and 98 healthy individuals (52 women) participated in this study. OXTR methylation was quantified using the pyrosequencing method. A subset of participants (16 ROS, 23 UHR, and 33 healthy controls [HCs]) underwent a 5.5-minute resting-state functional magnetic resonance imaging to determine the relationship between OXTR methylation and the striatal-amygdala network functional connectivity (FC) underlying anhedonia-asociality. Both men and women with ROS and UHR showed significantly decreased OXTR methylation compared to HCs. In women with ROS and UHR, decreased OXTR methylation showed a significant correlation with increased anhedonia-asociality. FC of the striatal-amygdala network, positively associated with the severity of anhedonia-asociality, showed an inverse correlation with OXTR methylation. This study suggests that epigenetic alterations of OXTR , which can be detected before the development of full-blown psychosis, confer susceptibility to schizophrenia and play a crucial role in the manifestation of anhedonia-asociality, particularly in women. [ABSTRACT FROM AUTHOR]

Adolescents hearing non-existent voices may be at risk for psychosis, but the prevalence of voice-hearing (VH) in the general population complicates clinical interpretations. Differentiating between VH with and without distress may aid treatment decisions in psychosis services, but understanding the differences between these two phenomena as they present in the normal adolescent population is necessary to validate this differentiation. The present study compared VH with and without distress in 10,346 adolescents in relation to clinical characteristics, known risk factors, predictors and psychosocial moderators of psychosis. A population-based cohort of Norwegian 16–19 years old adolescents completed a comprehensive web-based questionnaire, including two questions from the extended Launay-Slade Hallucinations Scale: (1) I often hear a voice speaking my thoughts aloud and (2) I have been troubled by hearing voices in my head. Adolescents reporting no VH, non-distressing VH or distressing VH were compared on 14 psychosocial and clinical variables. A multinomial regression model showed that non-disturbing voices were predicted by better school grades, social dysfunction, distractibility, affective symptoms and experience of trauma, while the disturbing voices were predicted by the experience of bullying and trauma, perceived negative self-worth and self-efficacy, less family support, dysregulation of activation, distractibility, self-harm and anxiety. Hearing voices without distress versus being distressed by the voices is related to different constellations of psychosocial variables, suggesting that they represent two separate groups of adolescents. The findings validate the emphasis on distress in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Current methods to identify people with psychosis risk involve administration of specialized tools such as the Structured Interview for Psychosis-Risk Syndromes (SIPS), but these methods have not been widely adopted. Validation of a more multipurpose assessment tool—such as the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS)—may increase the scope of identification efforts. Methods: We assessed the correspondence between SIPS-determined clinical high risk/early psychosis (CHR/early psychosis) status and K-SADS psychosis screen (child and parent reports and their combination) in a sample of 147 help-seeking individuals aged 12–25. Detailed classification results are reported. Results: Both the child and parent interviews on the K-SADS psychosis screen were strongly predictive of CHR/early psychosis status, although parent reports contributed no significant additional information beyond child reports. Across informants, the presence of either subthreshold hallucinations or subthreshold delusions was highly suggestive of CHR/early psychosis status as determined by SIPS interview (78% (child) and 74% (parent) accuracy). Conclusions: Subthreshold scores on the two-item K-SADS psychosis screen may be good indicators of the presence or absence of early signs of psychosis. The option of using a non-specialized assessment such as the K-SADS as a staged approach to assess for CHR/early psychosis status could increase rates of early psychosis screening and treatment. [ABSTRACT FROM AUTHOR]

The article offers causal factors related to attenuated psychosis syndrome. It focuses about schizophrenia that typically features delusions, hallucinations and aberrant thought patterns and also mentions symptoms of schizophrenia with emotional changes and changes in perception and beliefs that have preceded the onset of their first psychotic episode.

Since the 1990s, facilities for individuals at putative risk for psychosis have mushroomed and within a very short time have become part of the standard psychiatric infrastructure in many countries. The idea of preventing a severe mental disorder before its exacerbation is laudable, and early data indeed strongly suggested that the sooner the intervention, the better the outcome. In this paper, the authors provide four reasons why they think that early detection or prodromal facilities should be renamed and their treatment targets reconsidered. First, the association between the duration of untreated psychosis and outcome is empirically established but has become increasingly weak over the years. Moreover, its applicability to those who are considered at risk remains elusive. Second, instruments designed to identify future psychosis are prone to many biases that are not yet sufficiently controlled. None of these instruments allows an even remotely precise prognosis. Third, the rate of transition to psychosis in at-risk patients is likely lower than initially thought, and evidence for the success of early intervention in preventing future psychosis is promising but still equivocal. Perhaps most importantly, the treatment is not hope-oriented. Patients are more or less told that schizophrenia is looming over them, which may stigmatize individuals who will never, in fact, develop psychosis. In addition self-stigma has been associated with suicidality and depression. The authors recommend that treatment of help-seeking individuals with mental problems but no established diagnosis should be need-based, and the risk of psychosis should be de-emphasized as it is only one of many possible outcomes, including full remission. Prodromal clinics should not be abolished but should be renamed and restructured. Such clinics exist, but the transformation process needs to be facilitated. [ABSTRACT FROM AUTHOR]

Background: As efforts intensify to intervene early among those at risk for psychosis, examination of the relationship between presenting psychopathology and long-term functional outcome may guide treatment decision-making and offer a means to prevent or reduce chronic disability.Methods: Data were collected through the Early Detection and Intervention for the Prevention of Psychosis Program (EDIPPP), a multisite national trial testing the efficacy of an early intervention for youth at risk of developing psychosis. Participants were followed prospectively and completed comprehensive evaluations at 6, 12, and 24 months, including the Structured Interview for Prodromal Syndromes (SIPS) and the Global Social and Role Functioning Scales. The present analyses included 327 participants and examined the relationships between baseline symptoms and longitudinal global social and role functioning using a linear mixed modeling approach.Results: Higher baseline negative symptoms and deteriorated thought process predicted worse social and role functioning in the follow-up period. The effect of negative symptoms on social functioning, however, was moderated by positive symptoms, and the relationship between positive symptoms and social functioning changed over time. Baseline positive symptoms, distress, and level of symptom severity were not predictors of either social or role functioning.Conclusions: Baseline negative symptoms and thought disorder appear to predict functional outcome for up to two years among adolescents and young adults at risk for psychosis. Developing effective interventions to target these symptoms may be critical to promote functional recovery among those experiencing attenuated symptoms or a first episode of psychosis. [ABSTRACT FROM AUTHOR]

A cohort study examining patients who were initiated to methylphenidate treatment between the ages of 12 and 30 has found no evidence of increased risk of psychosis in this group as a result of methylphenidate initiation. The study's findings contradict a prevalent view that methylphenidate increases the risk of psychotic events in young people and should be avoided in patients with a history of psychotic illness. Study results were published online June 17 in Lancet Psychiatry. [ABSTRACT FROM AUTHOR]

Background: Much research attention has been given to the high rates of psychosis diagnosed in the Black community. However, little has been heard about possible reasons for this from Black African and Caribbean mental health service users themselves. Aims: To determine how Black African and Caribbean service users perceive and explain these apparent differences. Methods: We conducted four focus groups between 2014 and 2015 with 35 participants from the Black African and Black Caribbean community in Lambeth and Southwark, South East London, diagnosed with a psychotic illness. Recruitment was through a local voluntary sector organization and other community contacts. Results: Each group described an elevated risk of psychosis in their community and explanations followed the following themes, with increased rates due to: (a) an accumulation of stressors due to disadvantaged ethnic minority status, (b) further disadvantage due to inequitable experiences of mental health services, (c) an absence of community support and (d) a double stigma: as a result of external discrimination, due to ethnicity, and internal stigma about mental illness from within the Black community itself. Conclusions: Black mental health service users attributed an elevated risk of psychosis in their community to an accumulation of stressors directly related to ethnic minority status. [ABSTRACT FROM AUTHOR]

Objectives: Alterations in thalamocortical anatomical connectivity, specifically the connection between the orbitofrontal cortex and thalamus, have been frequently reported in schizophrenia and are suggested to contribute to the pathophysiology of schizophrenia. The connectivity of the thalamocortical white matter in unaffected relatives of schizophrenia patients was compared to that of healthy controls. Methods: The unaffected relative group was defined as asymptomatic family members who had at least one first-degree relative with schizophrenia and one or more other affected first- to third-degree relatives. A total of 35 unaffected relatives and 34 healthy controls underwent diffusion-weighted and T1-weighted magnetic resonance imaging to examine the white matter connectivity between the thalamus and orbitofrontal cortex using probabilistic tractography. Results: After controlling for age and sex, the unaffected relatives exhibited significantly reduced fractional anisotropy values for the left thalamo-orbitofrontal tract compared to that of healthy controls, F (1, 65) = 6.93, p = 0.011, effect size partial η2 = 0.10. However, there was no association between the Genetic Liability Score and fractional anisotropy in the left thalamo-orbitofrontal tracts. Conclusion: Our findings in the unaffected relatives of schizophrenia patients, which are in line with the alterations reported in schizophrenia, first-episode psychosis and clinical high risk for psychosis, highlight a possible genetic contribution to the proposed biomarker of altered thalamocortical connectivity. [ABSTRACT FROM AUTHOR]

Background: In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors. Methods: In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models. Results: A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (β = −0.09, t = −3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F 11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (β = 0.09, t = 3.04, p = 0.002). Conclusions: In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD. [ABSTRACT FROM AUTHOR]

Objective: The aim of this retrospective study was to review and report short-term and mid-term outcomes of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension at our institute in the recent 2 years and to describe perfusion strategy. Methods: A total of 58 consecutive patients with chronic thromboembolic pulmonary hypertension underwent pulmonary endarterectomy under deep hypothermia circulatory arrest with an established perfusion practice between November 2015 and December 2017. Peri-operative data and patients' outcome were retrospectively analyzed. Results: Mean pulmonary artery pressure was decreased (49 (40-56) mmHg vs 27 (20-31) mmHg, p < 0.001), and pulmonary vascular resistance (724 (538-1108) vs 206 (141-284) dyn second cm−5, p < 0.001) improved significantly after surgery. In-hospital mortality was 1.7% and postoperative complication rate was 27.6%. Antipsychotic medication of olanzapine was prescribed for 36 patients (62.1%), which was independently related to total deep hypothermic circulatory arrest time, postoperative blood potassium concentration, and hematocrit. The majority of patients recovered uneventfully with good mid-term cardiac function (New York Heart Association I-II: 98.1%) and neurological outcome (Glasgow Outcome Scale—Extended Upper Good Recovery: 74.1% and Lower Good Recovery: 20.3%). Mid-term neurological outcome was associated with post–pulmonary endarterectomy antipsychotic medication. Conclusion: Short-term and mid-term outcome after pulmonary endarterectomy was comparable to high-volume centers. Incidence of post–pulmonary endarterectomy delirium was relatively high and associated with mid-term neurological outcome. Total deep hypothermic circulatory arrest time, postoperative blood potassium concentration, and hematocrit were independent risk factors of postoperative olanzapine medication. More efforts and further research are required to optimize the neuroprotection of perfusion practice. [ABSTRACT FROM AUTHOR]

Identification of neurophysiological abnormalities associated with schizophrenia that predate and predict psychosis onset may improve clinical prediction in the psychosis risk syndrome (PRS) and help elucidate the pathogenesis of schizophrenia. Amplitude reduction of the P300 event-related potential component reflects attention-mediated processing deficits and is among the most replicated biological findings in schizophrenia, making it a candidate biomarker of psychosis risk. The relative extent to which deficits in P300 amplitudes elicited by auditory and visual oddball stimuli precede psychosis onset during the PRS and predict transition to psychosis, however, remains unclear. Forty-three individuals meeting PRS criteria, 19 schizophrenia patients, and 43 healthy control (HC) participants completed baseline electroencephalography recording during separate auditory and visual oddball tasks. Two subcomponents of P300 were measured: P3b, elicited by infrequent target stimuli, and P3a, elicited by infrequent nontarget novel stimuli. Auditory and visual target P3b and novel P3a amplitudes were reduced in PRS and schizophrenia participants relative to HC participants. In addition, baseline auditory and visual target P3b, but not novel P3a, amplitudes were reduced in 15 PRS participants who later converted to psychosis, relative to 18 PRS non-converters who were followed for at least 22 months. Furthermore, target P3b amplitudes predicted time to psychosis onset among PRS participants. These results suggest that P300 amplitude deficits across auditory and visual modalities emerge early in the schizophrenia illness course and precede onset of full psychosis. Moreover, target P3b may represent an important neurophysiological vulnerability marker of the imminence of risk for psychosis. [ABSTRACT FROM AUTHOR]

Background: Migration is a risk factor for psychoses but risks within the large South Asian communities of West Yorkshire are not known. Aim: To estimate the risk of psychosis in the Pakistani, Bangladeshi and Indian populations in West Yorkshire as compared with British White population. Method: We used data from Early Intervention for Psychosis services on 15-35 year-olds diagnosed with first episode psychosis in 2013-2015 and local census data to calculate risks. Results: Compared with the British White population, the Pakistani population had a significantly higher risk of first episode psychosis (RR 1.31, 95% CI 1.09, 1.58). The smaller Bangladeshi population showed a similar, but non-significant, trend (RR 1.50, 95% CI 0.89, 2.53). In contrast, the Indian population had a significantly lower risk (RR 0.51, 95% CI 0.33, 0.79). Conclusion: Variable risk of psychosis among south Asian ethnic groups in West Yorkshire needs further research. [ABSTRACT FROM AUTHOR]

Aim: Schizophrenia is a highly stigmatized disorder. Identification of youth at high risk for psychosis has the potential for improved outcomes. However, identifying youth at risk could subject them to increased public stigma. Using an experimental vignette design, this study examined relative levels of public stigma elicited by the labels "schizophrenia," "clinical high risk (CHR)," "attenuated psychotic symptoms syndrome (APSS)," a label implying normative adolescent development ("a bad breakup"), and a no‐label control condition. Methods: Ninety‐six undergraduates (age: 18.8 + 1.1, range: 18‐22) read a vignette describing an adolescent experiencing symptoms typical of CHR for psychosis. The vignette label (APSS, CHR, schizophrenia, a bad breakup or no label) was counterbalanced between participants. Participants answered questions assessing stigma toward the individual and their prior knowledge of and familiarity with psychosis. Results: Overall stigma did not differ across conditions. Only ratings of personal responsibility were higher for the breakup label than the schizophrenia label (P < .05). More prior knowledge about, and higher familiarity with, psychotic symptoms predicted lower overall stigma. Conclusion: We did not find that schizophrenia, CHR or APSS labels elicited elevated stigma in this sample relative to the control labels. This may reflect relatively low levels of mental health stigma in the group studied, a new finding inconsistent with earlier work. Greater levels of knowledge about and familiarity with psychosis were associated with lower stigma. These findings reinforce the potential for mental health awareness campaigns to reduce stigma but also raise questions about factors contributing to lower rates of stigma. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that cannabis use, childhood adversity, and urbanicity, in interaction with proxy measures of genetic risk, may facilitate onset of psychosis in the sense of early affective dysregulation becoming 'complicated' by, first, attenuated psychosis and, eventually, full-blown psychotic symptoms. Methods: Data were derived from three waves of the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The impact of environmental risk factors (cannabis use, childhood adversity, and urbanicity) was analyzed across severity levels of psychopathology defined by the degree to which affective dysregulation was 'complicated' by low-grade psychotic experiences ('attenuated psychosis' – moderately severe) and, overt psychotic symptoms leading to help-seeking ('clinical psychosis' – most severe). Familial and non-familial strata were defined based on family history of (mostly) affective disorder and used as a proxy for genetic risk in models of family history × environmental risk interaction. Results: In proxy gene–environment interaction analysis, childhood adversity and cannabis use, and to a lesser extent urbanicity, displayed greater-than-additive risk if there was also evidence of familial affective liability. In addition, the interaction contrast ratio grew progressively greater across severity levels of psychosis admixture (none, attenuated psychosis, clinical psychosis) complicating affective dysregulation. Conclusion: Known environmental risks interact with familial evidence of affective liability in driving the level of psychosis admixture in states of early affective dysregulation in the general population, constituting an affective pathway to psychosis. There is interest in decomposing family history of affective liability into the environmental and genetic components that underlie the interactions as shown here. [ABSTRACT FROM AUTHOR]

Background: The jumping to conclusions (JTC) reasoning bias and decreased working memory performance (WMP) are associated with psychosis, but associations with affective disturbances (i.e. depression, anxiety, mania) remain inconclusive. Recent findings also suggest a transdiagnostic phenotype of co-occurring affective disturbances and psychotic experiences (PEs). This study investigated whether JTC bias and decreased WMP are associated with co-occurring affective disturbances and PEs. Methods: Data were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). Trained interviewers administered the Composite International Diagnostic Interview (CIDI) at three time points in a general population sample (N = 4618). The beads and digit-span task were completed to assess JTC bias and WMP, respectively. CIDI was used to measure affective disturbances and an add-on instrument to measure PEs. Results: Compared to individuals with neither affective disturbances nor PEs, the JTC bias was more likely to occur in individuals with co-occurring affective disturbances and PEs [moderate psychosis (1–2 PEs): adjusted relative risk ratio (RRR) 1.17, 95% CI 0.98–1.41; and high psychosis (3 or more PEs or psychosis-related help-seeking behaviour): adjusted RRR 1.57, 95% CI 1.19–2.08], but not with affective disturbances and PEs alone, whereas decreased WMP was more likely in all groups. There was some evidence of a dose–response relationship, as JTC bias and decreased WMP were more likely in individuals with affective disturbances as the level of PEs increased or help-seeking behaviour was reported. Conclusion: The findings suggest that JTC bias and decreased WMP may contribute to a transdiagnostic phenotype of co-occurring affective disturbances and PEs. [ABSTRACT FROM AUTHOR]

Background: Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis. Methods: In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe. Results: There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls. Conclusions: A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms. [ABSTRACT FROM AUTHOR]

The clinical significance and the prognostic value of clinical high risk (CHR) for psychosis, while substantially corroborated in adults, remains less firmly established in children and early adolescents. This follow-up study, developed within the Reggio Emilia At Risk Mental States project, is meant to contribute to the reduction of such lacuna, and has two main aims: (1) to characterize the clinical profile of help seekers [stratified in non-CHR, CHR and first episode psychosis (FEP)] referred to child–adolescent mental health services; and (2) to monitor the cumulative transition rate from CHR to FEP in adolescents at the follow-up of 12 and 24 months. 112 adolescents (aged 13–18 years) were assessed with the Comprehensive Assessment of At-Risk Mental States and the Schizophrenia Proneness Instrument, Child and Youth version. 51 subjects met CHR criteria (45.5% of the sample) and 33 subjects met FEP criteria (29.5%) at baseline. The criterial transition rate from CHR to FEP was 7% over 12 months and 13% over 24 months; higher rates of cumulative transition were detected when also functional transition (indexed by the consensual introduction of antipsychotic medication by the treating clinical staff) was considered. The identification of CHR for psychosis in help-seeking adolescents is feasible and clinically relevant. Studies conducted in real world, publicly funded components of the national health system, should take into consideration not only criterial, psychometric transition, but also functional equivalents of transition. [ABSTRACT FROM AUTHOR]

Background: There are concerns that antipsychotics may be used inappropriately in adults with intellectual disability for problem behaviours in the absence of a diagnosed mental health condition. The aim was to examine the prevalence and patterns of antipsychotic use and their association with problem behaviours and mental health conditions in older adults with intellectual disability. Methods: Cross‐sectional data were drawn from Wave 2 (2013/2014) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS‐TILDA). Medication data were available for 95.6% (n = 677). Those who reported antipsychotic use and reported psychotic or other mental health conditions and those who reported problem behaviours were compared. Results: In total, 45.1% (n = 305) had antipsychotics, and of those with antipsychotic use and diagnosis information (n = 282), 25.9% (73) had a psychotic disorder. 58% of those exposed to antipsychotics reported problem behaviours. Conclusion: Reported use of antipsychotics significantly exceeded reported doctor's diagnosis of psychotic conditions in this study. [ABSTRACT FROM AUTHOR]

Cannabis legalization has led to significant health consequences, particularly to patients in emergency departments and hospitals in Colorado. The most concerning include psychosis, suicide, and other substance abuse. Deleterious effects on the brain include decrements in complex decision-making, which may not be reversible with abstinence. Increases in fatal motor vehicle collisions, adverse effects on cardiovascular and pulmonary systems, inadvertent pediatric exposures, cannabis contaminants exposing users to infectious agents, heavy metals, and pesticides, and hash-oil burn injuries in preparation of drug concentrates have been documented. Cannabis dispensary workers ("budtenders") without medical training are giving medical advice that may be harmful to patients. Cannabis research may offer novel treatment of seizures, spasticity from multiple sclerosis, nausea and vomiting from chemotherapy, chronic pain, improvements in cardiovascular outcomes, and sleep disorders. Progress has been slow due to absent standards for chemical composition of cannabis products and limitations on research imposed by federal classification of cannabis as illegal. Given these factors and the Colorado experience, other states should carefully evaluate whether and how to decriminalize or legalize non-medical cannabis use. [West J Emerg Med. [ABSTRACT FROM AUTHOR]

Bullying is an adverse childhood experience that is more common among youth with special needs and is associated with increased psychopathology throughout the lifespan. Individuals with chromosome 22q11.2 deletion syndrome (22q) represent one group of special needs youth who are at increased risk for bullying due to co-occurring genetically-mediated developmental, physical, and learning difficulties. Furthermore, individuals with 22q are at increased risk for developing psychotic disorders such as schizophrenia. However, there is a paucity of research exploring the impact of bullying on individuals with 22q and the possible impact this has on risk for psychosis in this population. To explore this relationship using existing research the goals of the review are: (i) to explore the nature of bullying among youth with special needs, and (ii) to discuss its potential role as a specific risk factor in the development of adverse outcomes, including psychosis symptoms. We reviewed the relationship between bullying and its short and long-term effects on the cognitive, social, and developmental functioning of typically developing individuals and those with special needs. We propose an interactive relationship between trauma, stress, and increased psychosis risk among youth with 22q with a history of bullying. The early childhood experience of trauma in the form of bullying promotes an altered developmental trajectory that may elevate the risk for maladaptive functioning and subsequent psychotic disorders, particularly in youth with genetic vulnerabilities. Therefore, we conclude the experience of bullying among individuals with 22q should be more closely examined. [ABSTRACT FROM AUTHOR]

Background: Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms. Method: In a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids [(Δ9 -tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites)] were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency [Severity of Dependence Scale (SDS), DSM-IV-TR] and acute psychotic-like symptoms [Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS)]. Results: Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS. Conclusions: Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes. [ABSTRACT FROM AUTHOR]