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Background: Pre-diagnostic stages of psychotic illnesses, including 'clinical high risk' (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis., Methods: Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population., Results: Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa., Conclusion: In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.

Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). FER performance was measured using the Degraded Facial Affect Recognition Task (DFAR). Better FER performance as indicated by higher DFAR-total scores was associated with lifetime regular cannabis use in schizophrenia (B = 1.36, 95% CI 0.02 to 2.69), siblings (B = 2.17, 95% CI 0.79 to 3.56), and HC (B = 3.10, 95% CI 1.14 to 5.06). No associations were found between DFAR-total and current cannabis use. Patients with schizophrenia who started to use cannabis after the age of 16 showed better FER performance than patients who started earlier (B = 2.50, 95% CI 0.15 to 4.84) and non-users (B = 3.72, 95 CI 1.96 to 5.49). Better FER performance was found also in siblings who started to use cannabis after 16 compared to non-users (B = 2.37, 95% CI 0.58 to 4.16), while HC using cannabis performed better than non-users at DFAR-total regardless of the age at onset. Our findings suggest that lifetime regular cannabis use may be associated with better FER regardless of the psychosis risk, but that FER might be moderated by age at first use in people with higher genetic risk. Longitudinal studies may clarify whether there is a cause-and-effect relationship between cannabis use and FER performance in psychotic and non-psychotic samples., Competing Interests: Conflicts of Interest Celso Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Maria Paz Garcia-Portilla has been a consultant to and/or has received honoraria/grants from Angelini, Alianza Otsuka-Lundbeck, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, and SAGE Therapeutics., (Copyright © 2022. Published by Elsevier B.V.)

Background: There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation., Methods: We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 ( n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI ( n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls., Results: The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465)., Conclusions: The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Background: This study attempted to replicate whether a bias in probabilistic reasoning, or 'jumping to conclusions'(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation., Methods: Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses., Results: JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46-5.17 for siblings and aRR: 5.07 CI 95% 4.13-6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67-8.51, and in patients: 2.15 CI 95% 0.94-4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences., Conclusions: These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.

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

Background: Social cognition impairments, such as facial emotion recognition (FER), have been acknowledged since the earliest description of schizophrenia. Here, we tested FER as an intermediate phenotype for psychosis using two approaches that are indicators of genetic risk for schizophrenia: the proxy-genetic risk approach (family design) and the polygenic risk score for schizophrenia (PRS-SCZ)., Methods: The sample comprised 2039 individuals with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). The Degraded Facial Affect Recognition Task (DFAR) was applied to measure the FER accuracy. Schizotypal traits in siblings and HC were assessed using the Structured Interview for Schizotypy-Revised (SIS-R). The PRS-SCZ was trained using the Psychiatric Genomics Consortium results. Regression models were applied to test the association of DFAR with psychosis risk, SIS-R, and PRS-SCZ., Results: The DFAR-total scores were lower in individuals with schizophrenia than in siblings (RR = 0.97 [95% CI 0.97, 0.97]), who scored lower than HC (RR = 0.99 [95% CI 0.99-1.00]). The DFAR-total scores were negatively associated with SIS-R total scores in siblings (B = -2.04 [95% CI -3.72, -0.36]) and HC (B = -2.93 [95% CI -5.50, -0.36]). Different patterns of association were observed for individual emotions. No significant associations were found between DFAR scores and PRS-SCZ., Conclusions: Our findings based on a proxy genetic risk approach suggest that FER deficits may represent an intermediate phenotype for schizophrenia. However, a significant association between FER and PRS-SCZ was not found. In the future, genetic mechanisms underlying FER phenotypes should be investigated trans-diagnostically., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Experience Sampling Method (ESM) is a structured diary technique assessing variations in thoughts, mood, and psychiatric symptoms in everyday life. Research has provided ample evidence for the efficacy of the use of ESM in general psychiatry but its use in forensic psychiatry has been limited. Twenty forensic psychiatric patients participated. The PsyMate™ Device emitted a signal 10 times a day on six consecutive days, at unpredictable moments. After each "beep," the patients completed ESM forms assessing current context, thoughts, positive and negative affect, and psychotic experiences. Stress was measured using the average scores of the stress related items. Compliance rate was high (85% beeps responded). Activity stress was related to more negative affect, lower positive affect, and more psychotic symptoms. This finding was restricted to moments when a team member was present; not when patients were alone or with other patients. ESM can be useful in forensic psychiatry and give insights into the relationships between symptoms and mood in different contexts. In this study activity-related stress was contextualized. These findings can be used to personalize interventions.

Background: Targeting low self-esteem in youth exposed to childhood adversity is a promising strategy for preventing adult mental disorder, but psychological help remains difficult to access and accept for youth, calling for novel, youth-friendly approaches. Mobile Health (mHealth) and, most prominently, ecological momentary interventions (EMIs) provide a unique opportunity to deliver youth-friendly, personalized, real-time, guided self-help interventions. The aim of this study is to investigate the efficacy of a novel, accessible, transdiagnostic ecological momentary intervention for improving self-esteem ('SELFIE') in youth with prior exposure to childhood adversity., Methods/design: In a parallel-group, assessor-blind, multi-center randomized controlled trial, individuals aged 12-26 years with prior exposure to childhood adversity and low self-esteem will be randomly allocated to SELFIE in addition to treatment as usual (TAU) as the experimental condition or the control condition of TAU only, which will include access to all standard health care. SELFIE is a digital guided self-help intervention administered through a smartphone-based app to allow for interactive, personalized, real-time and real-world transfer of intervention components in individuals' daily lives, blended with three training sessions delivered by trained mental health professionals over a 6-week period. Outcomes will be assessed at baseline, post-intervention, and 6-month follow-up by blinded assessors. The primary outcome will be the level of self-esteem as measured with the Rosenberg Self-Esteem Scale (RSES)., Discussion: The current study is the first to establish the efficacy of an EMI focusing on improving self-esteem transdiagnostically in youth exposed to childhood adversity. If this trial provides evidence on the efficacy of SELFIE, it has significant potential to contribute to minimizing the deleterious impact of childhood adversity and, thereby, preventing the development of mental disorder later in life., Trial Registration: Netherlands Trial Register NL7129 (NTR7475 ). Registered on 9 November 2018., (© 2021. The Author(s).)

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls., Methods: This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate., Results: ES-SCZ was associated with the GAF dimensions in patients (symptom: B = -1.53, p-value = 0.001; disability: B = -1.44, p-value = 0.001), siblings (symptom: B = -3.07, p-value < 0.001; disability: B = -2.52, p-value < 0.001), and healthy controls (symptom: B = -1.50, p-value < 0.001; disability: B = -1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group., Conclusions: Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

Aims: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum., Methods: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components)., Results: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions., Conclusions: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

Background: Clinical decision aids are used in various medical fields to support patients and clinicians when making healthcare decisions. Few attempts have been made to implement such tools in psychiatry. We developed Treatment E-Assist (TREAT); a routine outcome monitoring based computerized clinical decision aid, which generates personalized treatment recommendations in the care of people with psychotic disorders. The aim of this study is to investigate how TREAT is used and evaluated by clinicians and how this tool can be improved., Methods: Clinicians working with TREAT during a clinical trial were asked to participate in semi-structured interviews. The Unified Theory of Acceptance and Use of Technology (UTAUT) was used as a sensitizing theory to structure a part of the interview questions. The transcripts were analyzed using inductive thematic analysis to uncover the main themes., Results: Thirteen clinicians (mean age: 49) of which eight psychiatrists and five nurse practitioners, participated in this study. Eight clinicians experienced TREAT as beneficial, whereas five experienced no additional benefits. Thematic analysis revealed five themes surrounding usage and evaluation of TREAT, views on TREAT's graphic representation of routine outcome monitoring results, guideline based treatment recommendations, contextual factors, effects on patients and effects on shared decision-making. Performance and effort expectancy were perceived as high by clinicians. The facilitating conditions were optimal and perceived social influence was low., Conclusion: This article presents a qualitative evaluation by clinicians of a computerized clinical decision aid in psychosis care. TREAT was viewed by most clinicians as beneficial during their consultations. The graphic representation of routine outcome monitoring results was well-appreciated and provided input to discuss treatment planning with patients. The treatment recommendations did not change most treatment decisions but supported clinical reasoning. However, some clinicians were unconvinced about TREAT's benefits. The delivery, applicability and the availability of resources require improvement to increase TREAT's efficacy. Not all patients responded well to TREAT but the observed facilitation of shared decision-making is promising. All four predictors of the Unified Theory of Acceptance and Use of Technology were positively evaluated by the majority of clinicians.

Background: First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes., Methods: We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS., Results: In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group., Conclusions: The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene-environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

Objective: To test whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures., Methods: The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily-life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS-S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta-analysis. The analyses were conducted using multilevel mixed-effects tobit regression models., Results: Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. There is novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = -0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress-sensitivity measures., Conclusion: Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotion dysregulation and psychosis proneness., (© 2020 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Identifying variables that influence daily-life fluctuations in auditory verbal hallucinations (AVHs) provides insight into potential mechanisms and targets for intervention. Network analysis, that uses time-series data collected by Experience Sampling Method (ESM), could be used to examine relations between multiple variables over time., Methods: 95 daily voice-hearing individuals filled in a short questionnaire ten times a day for six consecutive days at pseudo-random moments. Using multilevel vector auto-regression, relations between voice-hearing and negative affect, positive affect, uncontrollable thoughts, dissociation, and paranoia were analysed in three types of networks: between-subjects (between persons, undirected), contemporaneous (within persons, undirected), and temporal (within persons, directed) networks. Strength centrality was measured to identify the most interconnected variables in the models., Results: Voice-hearing co-occurred with all variables, while on a 6-day period voice-hearing was only related to uncontrollable thoughts. Voice-hearing was not predicted by any of the factors, but it did predict uncontrollable thoughts and paranoia. All variables showed large autoregressions, i.e. mainly predicted themselves in this severe voice-hearing sample. Uncontrollable thoughts was the most interconnected factor, though relatively uninfluential., Discussion: Severe voice-hearing might be mainly related to mental state factors on the short-term. Once activated, voice-hearing appears to maintain itself. It is important to assess possible reactivity of AVH to triggers at the start of therapy; if reactive, therapy should focus on the triggering factor. If not reactive, Cognitive Behavioural interventions could be used first to reduce the negative effects of the voices. Limitations are discussed., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Initial affective and psychotic reactivity to daily stressors is altered in psychosis, and most notably in early psychosis. In addition to altered initial stress reactivity, results from studies using Experience Sampling Methodology (ESM) and psychophysiological measures indicate that impaired recovery from mild stressors may also be a risk factor for mental illness. The current ESM study investigated affective recovery from daily stressors in chronic psychosis patients (CP; n = 162), individuals at early stages of psychosis (EP; n = 127), and healthy volunteers (HV; n = 220) assessing fluctuations in negative affect (NA), tension, and suspiciousness ten times a day on six consecutive days. Recovery was operationalized for all three variables as the return to baseline (i.e., level at t -1 ) following the first stressful event of a day (i.e., t 0 ). The EP group showed a delayed recovery of NA (t 1 -t 3 : B = 0.185; p = .007 and B = 0.228; p = .002) and suspiciousness (t 1 : B = 0.223; p = .010 and B = 0.291; p = .002) compared to HV and CP, respectively. Delayed recovery was detected for tension as well (t 1 -t 2 : EP > HV: B = 0.242; p = .040 and EP > CP: B = 0.284; p = .023), but contrary to both other momentary states, this effect disappeared when controlling for subsequent stressful events. There were no significant differences in recovery between HV and CP. These results suggest that in EP, stressful daily events have longer-lasting effects on overall negative affect and subclinical psychotic-like experiences. Future studies should incorporate physiological and endocrine measures in order to integrate recovery patterns of the different stress systems., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Whilst childhood trauma (CT) is a known risk factor across the spectrum of psychosis expression, little is known about possible interplay with genetic liability., Methods: The TwinssCan Study collected data in general population twins, focussing on expression of psychosis at the level of subthreshold psychotic experiences. A multilevel mixed-effects linear regression analysis was performed including 745 subjects to assess the interaction between genetic liability and CT. The Symptom Checklist-90 (SCL-90-R) score of the co-twin was used as an indirect measure of genetic liability to psychopathology, while the Childhood Trauma Questionnaire Short-Form (CTQ-SF) was used to assess CT in the domains of physical, emotional and sexual abuse, as well as physical and emotional neglect. The Community Assessment of Psychic Experience (CAPE) questionnaire was used to phenotypically characterize psychosis expression., Results: In the model using the CAPE total score, the interaction between CT and genetic liability was close to statistical significance (χ 2  = 5.6, df = 2, p = 0.06). Analyses of CAPE subscales revealed a significant interaction between CT and genetic liability (χ 2  = 8.8, df = 2, p = 0.012) for the CAPE-negative symptoms subscale, but not for the other two subscales (i.e. positive and depressive)., Conclusion: The results suggest that the impact of CT on subthreshold expression of psychosis, particularly in the negative subdomain, may be larger in the co-presence of significant genetic liability for psychopathology.

Patients diagnosed with schizophrenia often report a low quality of life (QoL). The purpose of this study was to investigate whether we could replicate a cross-sectional model by Alessandrini et al. (2016, n = 271) and whether this model predicts QoL later in life. This model showed strong associations between schizophrenia spectrum symptoms and depressive symptoms on QoL, but lacked follow-up assessment. This model was adapted in the current study and the robustness was investigated by using a longitudinal design in which the association between baseline variables (including IQ, depression, schizophrenia spectrum symptoms as well as social functioning) and QoL during 3-years of follow-up was investigated. We included patients with a non-affective psychotic disorder (n = 744) from a prospective naturalistic cohort-study. In the cross-sectional model, with good measure of fit, both depression as well as social functioning was associated with QoL (direct path coefficient -0.28 and 0.41, respectively). Additionally, the severity of schizophrenia spectrum symptoms was highly associated with social functioning (direct path coefficient -0.70). Importantly, the longitudinal model showed good measures of fit, which strengthens the validity of the initial model and highlights that depression prospectively affect QoL while schizophrenia spectrum symptoms prospectively influence QoL via social functioning. The negative, longitudinal impact of a depression on QoL highlights the need to focus on treatment of this co-morbidity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Use of decision aids in mental health care is increasing and will also be introduced in the Dutch mental healthcare system. We describe the context of this development and discuss how decision aids could facilitate evidence-based psychiatry.
AIM: To describe the development of the decision aid TReatment E-Assist (TREAT) in the Dutch mental healthcare system that aims to optimize treatment of people with a psychotic illness.
METHOD: We describe how the TREAT application works and discuss its potential contribution to the treatment of people with a psychotic illness.
RESULTS: In a pilot study TREAT was judged as user friendly and useful. TREAT seemed to increase the integration of ROM-results in treatment and the advice offered new view points for practioners.
CONCLUSION: TREAT is a novel application which combines routine outcome monitoring results with current treatment guidelines and standards of care in order to generate personalised treatment recommendations in the context of a psychiatric treatment trajectory. A multicentre study is being conducted in different provinces in the Netherlands to investigate the effectiveness of TREAT.

Introduction: Auditory verbal hallucinations (AVH) are prevalent experiences that can induce distress and impede social functioning. While most voice hearers benefit from antipsychotic medication or cognitive-behavioural therapy, additional effective interventions are needed to reduce the burden of experiencing AVH. 'Temstem' is an easily accessible and useable smartphone application that was developed by designers in close cooperation with voice hearers and experts. By using language games, Temstem aims to reduce distress and improve social functioning., Methods: This is a single-blind multicentre randomised controlled trial with two arms: 'Temstem+AVH monitoring' versus 'AVH monitoring' (total n=100). Participants are adult patients who suffer daily from AVH and will be recruited in outpatient units. Primary assessment in daily life is made by the Experience Sampling Method (ESM) and daily monitoring with the PsyMate app. During an ESM period of 6 days, participants assess their mental state (including AVH and context) several times a day by filling in short questionnaires. There are three 6-day ESM periods: at baseline (week 0-1), post-treatment (weeks 5-6) and follow-up (weeks 9-10). In addition, during the entire 10-week study period, all participants monitor their AVH two times a day with a short assessment via the PsyMate app. Participants in the Temstem+AVH monitoring condition are provided with the Temstem app from week 1 to 6. Other assessments made at baseline, post-treatment and follow-up are based on questionnaires and a clinical interview., Ethics and Dissemination: The results from this study will provide an evaluation of the effectiveness of Temstem, a non-invasive and easily accessible app for voice hearers, and insight into the determinants of optimal use. Results will be disseminated unreservedly, irrespective of the magnitude or direction of the effects. This study protocol was approved by the Medical Ethics Committee of the VU University Medical Centre (METC number: 2015.435/NL53684.029.15)., Trial Registration Number: ISRCTN75717636; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Cognitive impairments in patients with psychotic disorder have been associated with poor functioning and increased symptom severity. Furthermore, childhood trauma (CT) exposure has been associated with worse cognitive functioning as well as co-occurrence of affective-anxious-psychosis symptoms or a 'mixed phenotype of psychopathology' (MP), which in turn is associated with greater symptom severity, and poor functioning. This study aims to evaluate if cognition could be associated with CT/MP. 532 patients with non-affective psychotic patients were assessed on CT, symptom profile, cognition, functioning, and symptom severity at baseline and 3 and 6-year follow-up. Four subgroups were made according to trauma exposure (CT- or CT+) and presence of a mixed phenotype (MP- or MP+): CT-/MP (n=272), CT-/MP+ (n=157), CT+/MP- (n=49), and CT+/MP+ (n=54). Mixed-effects multilevel regression, linear regression, and Tobit analyses were performed. Patients with both CT and MP showed lower verbal learning and memory than CT-/MP+ individuals (p<0.001). No other significant differences were found among the 4 subgroups. No cognitive decline was found at follow-up, neither in the CT+/MP- nor in CT-/MP- group. Lower cognition was not associated with increased symptom severity or poor functioning at follow-up, neither in the CT+/MP- nor in CT-/MP- group. Although cognitive impairments and CT may be related to clinical or functional features of psychotic disorder, and cognitive functioning could be affected by CT exposure, cognition does not discriminate subgroups of patients stratified by CT exposure and MP., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Subjective well-being (SWB) is associated with treatment adherence and symptom outcome in people with psychotic disorders. Also, it is associated with psychosis susceptibility and it is partly hereditable. The SWN-20 is a widely used tool to assess subjective well-being in patients; it was also found to be suitable for assessing SWB in healthy populations. Yet it is unclear how this retrospectively measured construct may be associated with momentary affective state, which is the proposed underlying mechanism of subjective well-being. This study therefore investigated the ecological validity of the SWN-20 in people at different risk for psychosis. In 63 patients with a psychotic disorder and 61 siblings of patients with a psychotic disorder we assessed whether subjective well-being as measured with the SWN-20, was associated with momentary positive affect, negative affect, reward experience and stress-sensitivity as measured by the experience sample method (ESM). Higher subjective well-being was associated with higher momentary positive affect and lower negative affect, and this association was not conditional on psychosis vulnerability. Subjective well-being was not associated with stress-sensitivity or reward-experience. SWN-20 is an easy-to-use and ecologically valid tool to measure subjective well-being in people with different vulnerability for psychosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Auditory Hallucinations (AH) cause substantial suffering and dysfunction, yet remain poorly understood and modeled. Previous reports have linked AH to increases in negative emotions, suggesting a role for the autonomic nervous system (ANS) in underlying this link. Employing an Experience Sampling Method (ESM) approach, 40 individuals with schizophrenia completed a 36-hour ambulatory assessment of AH and cardiac autonomic regulation. Participants carried mobile electronic devices that prompted them to report 10 times/d the severity of their momentary AH, along with a Holter monitor that continuously recorded their cardiac autonomic regulation. The clocks of the devices and monitors were synchronized, allowing for high time-resolution temporal linking of the AH and concurrent autonomic data. Power spectral analysis was used to determine the relative vagal (parasympathetic) contribution to autonomic regulation during 5 minutes prior to each experience sample. The participants also completed interview-based measures of AH (SAPS; PSYRATS). The ESM-measured severity of AH was significantly correlated with the overall SAPS-indexed AH severity, along with the PSYRATS-indexed AH frequency, duration, loudness, degree of negative content, and associated distress. A mixed-effect regression model indicated that momentary increases in autonomic arousal, characterized by decreases in vagal input, significantly predicted increases in ESM-measured AH severity. Vagal input averaged over the 36-hour assessment displayed a small but significant inverse correlation with the SAPS-indexed AH. The results provide preliminary support for a link between ANS regulation and AH. The findings also underscore the highly dynamic nature of AH and the need to utilize high time-resolution methodologies to investigate AH., (© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Routine Outcome Monitoring (ROM) has become part of the treatment process in mental health care. However, studies have indicated that few clinicians in psychiatry use the outcome of ROM in their daily work. The aim of this study was to explore the degree of ROM use in clinical practice as well as the explanatory factors of this use., Methods: In the Northern Netherlands, a ROM-protocol (ROM-Phamous) for patients with a psychotic disorder has been implemented. To establish the degree of ROM-Phamous use in clinical practice, the ROM results of patients (n=204) were compared to the treatment goals formulated in their treatment plans. To investigate factors that might influence ROM use, clinicians (n=32) were asked to fill out a questionnaire about ROM-Phamous., Results: Care domains that were problematic according to the ROM-Phamous results were mentioned in the treatment plan in 28% of cases on average (range 5-45%). The use of ROM-Phamous in the treatment process varies considerably among clinicians. Most of the clinicians find ROM-Phamous both useful and important for good clinical practice. In contrast, the perceived ease-of-use is low and most clinicians report insufficient time to use ROM-Phamous., Conclusions: More frequent ROM use should be facilitated in clinicians. This could be achieved by improving the fit with clinical routines and the ease-of-use of ROM systems. It is important for all stakeholders to invest in integrating ROM in clinical practice. Eventually, this might improve the diagnostics and treatment of patients in mental health care., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Early social and cognitive alterations in psychotic disorder, associated with familial liability and environmental exposures, may contribute to lower than expected educational achievement. The aims of the present study were to investigate (1) how differences in educational level between parents and their children vary across patients, their healthy siblings, and healthy controls (effect familial liability), and across two environmental risk factors for psychotic disorder: childhood trauma and childhood urban exposure (effect environment) and (2) to what degree the association between familial liability and educational differential was moderated by the environmental exposures., Methods: Patients with a diagnosis of non-affective psychotic disorder (n = 629), 552 non-psychotic siblings and 326 healthy controls from the Netherlands and Belgium were studied. Participants reported their highest level of education and that of their parents. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire-Short Form. Urban exposure, expressed as population density, was rated across five levels., Results: Overall, participants had a higher level of education than their parents. This difference was significantly reduced in the patient group, and the healthy siblings displayed intergenerational differences that were in between those of controls and patients. Higher levels of childhood urban exposure were also associated with a smaller intergenerational educational differential. There was no evidence for differential sensitivity to childhood trauma and childhood urbanicity across the three groups., Conclusion: Intergenerational difference in educational achievements is decreased in patients with psychotic disorder and to a lesser extent in siblings of patients with psychotic disorder, and across higher levels of childhood urban exposure. More research is required to better understand the dynamics between early social and cognitive alterations in those at risk in relation to progress through the educational system and to understand the interaction between urban environment and educational outcomes.

Background: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of childhood trauma increases. Also, any impact of the urban environment on likelihood of exposure to childhood trauma could be stronger in children who later develop psychotic disorder. The aim of this study was twofold: (1) to investigate whether childhood urbanicity moderates the effect of childhood trauma, in a model predicting psychotic disorder; (2) to investigate whether there is an association between the urban environment and childhood trauma and whether this is moderated by genetic liability for psychotic disorder., Methods: Patients with a diagnosis of non-affective psychotic disorder (n = 1119) and 589 healthy controls from the Netherlands and Belgium were studied. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire Short Form. Urban exposure was defined at four levels, considering the population density, using data from Statistics Netherlands and the equivalent database in Belgium., Results: There was a significant interaction between childhood urbanicity on the one hand and childhood trauma on the other, indicating that trauma was significantly associated with psychotic disorder, with increasing odds ratios for higher levels of childhood urbanicity. In addition, there was weak evidence that childhood urbanicity was associated with childhood trauma in the patient group: higher levels of childhood urbanicity were associated with higher trauma scores., Conclusion: The urban environment may moderate the risk-increasing effect of childhood trauma for psychotic disorder and childhood urbanicity may be a risk factor for childhood trauma in individuals who later develop psychotic disorder.

Background: Relational models of psychopathology propose that symptoms are dynamically connected and hypothesize that genetic and environmental influences moderate the strength of these symptom connections. Previous findings suggest that the interplay between hallucinations and delusions may play a crucial role in the development of psychotic disorder. The current study examined whether the connection between hallucinations and delusions is impacted by proxy genetic and environmental risk factors., Methods: Hallucinations and delusions at baseline and at 3-year follow-up were assessed in a sample of 1054 healthy siblings and 918 parents of 1109 patients with psychosis, and in 589 healthy controls (no familial psychosis risk). Environmental factors assessed were cannabis use, childhood trauma, and urbanicity during childhood. Logistic regression analyses tested whether familial psychosis risk predicted increased risk of delusions, given presence of hallucinations. Moderating effects of environmental factors on the hallucination-delusion association were tested in a similar fashion, restricted to the control and sibling groups., Results: The risk of delusions, given hallucinations, was associated with proxy genetic risk: 53% in parents, 47% in siblings, and 36% in controls. The hallucination-delusion association was stronger in those reporting cannabis use (risk difference: 32%) and childhood trauma (risk difference: 15%) although not all associations were statistically conclusive (respectively: p = .037; p = .054). A directionally similar but nonsignificant effect was found for urb anicity during childhood (risk difference: 14%, p =.357)., Conclusion: The strength of the connection between delusions and hallucinations is associated with familial and environmental risks for psychotic disorder, suggesting that specific symptom connections in the early psychosis psychopathology network are informative of underlying mechanisms., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Stereotype awareness--or an individual's perception of the degree to which negative beliefs or stereotypes are held by the public--is an important factor mediating public stigma, self-stigma and their negative consequences. Research is required to assess how individuals become more sensitive to perceive stereotypes, pointing the way to therapeutic options to reduce its negative effects and increase stigma resilience. Because perception and interpretation can be guided by belief systems, and childhood trauma (CT) is reported to impact such beliefs, CT is explored in relation to stereotype awareness (SA) in persons with psychosis, their siblings and controls., Method: Data from the GROUP project (Genetic Risk and Outcome of Psychosis) were analyzed. SA was measured by devaluation scales which assess a respondent's perception of the degree to which stereotypes about people with mental illness and about their families are held by the public. CT was measured using the Childhood Trauma Questionnaire (short form)., Results: In patients, symptoms of disorganization and emotional distress were associated with SA about people with mental illness. In siblings, schizotypal features were associated with both types of SA (more schizotypy = more SA). In both patients and siblings, CT was associated with both types of SA (more CT = more SA), independent of symptoms (patients) or schizotypy (siblings)., Conclusion: CT in people with psychosis and their siblings may sensitize to SA. Thus, CT may not only impact on risk for illness onset, it may also increase SA associated with mental illness, potentially interfering with the recovery process. CT-induced SA may indicate a heightened sensitivity to threat, which may also impact psychopathology.

Purpose: Psychosis is associated with urban upbringing, and increased emotional reactivity is associated with psychosis. The aim of this study was to examine to what degree urban upbringing impacts emotional reactivity, and how this may be relevant for psychotic disorder and familial risk of psychotic disorder., Methods: Patients with a diagnosis of non-affective psychotic disorder (n = 57), 59 first degree relatives of patients and 75 healthy comparison subjects were studied with the experience sampling method (a random time sampling technique to assess affective experience in relation to fluctuating stressors in the flow of daily life), to measure a change in negative affect in relation to subjective stress. Urban exposure was defined at 5 levels, considering the population density and the number of moves between birth and the 15th birthday, using data from the Dutch Central Bureau of Statistics and the equivalent database in Belgium., Results: Multilevel random regression analyses showed that urban upbringing was consistently and strongly associated with a reduced increase in negative affect in relation to SS in adulthood in a dose-response fashion in all three groups. Regression coefficients in the patient group decreased from 0.148 (p < 0.001) in the lowest urbanicity level to 0.094 (p < 0.001) in the highest urbanicity level., Conclusion: The findings suggest that urban upbringing may occasion "habituation" rather than "sensitization" across groups, which may or may not be relevant for the onset of psychotic disorder.

Purpose: Factor mixture analysis (FMA) and item response mixture models in the general population have shown that the psychosis phenotype has four classes. This study attempted to replicate this finding in help-seeking people accessing mental health services for symptoms of non-psychotic mental disorders., Methods: All patients (18-35 years old) referred for non-psychotic mental health problems to the secondary mental healthcare service in The Hague between February 2008 to February 2010 (N = 3,694), were included. Patients completed the Prodromal Questionnaire (PQ). Hybrid latent class analysis was applied to explore the number, size and symptom profiles of the classes., Results: The FMA resulted in four classes. Class 1 (N = 1,039, 28.1%) scored high on conceptual disorganization, inattention and mood disorder. Patients in Class 2 (N = 619, 16.8%) endorsed almost all PQ-items, were more often screened as being psychotic or at high risk of developing psychosis, without care takers noticing. In Class 3 (N = 1,747, 47.3%) perplexity, paranoia and negative symptoms were more prevalent. Patients were more often at high risk of developing psychosis. Class 4 (N = 286, 7.7%) represented the 'normative' group with low probabilities for all items., Discussion: The results support the hypothesis that a representation in four classes of psychotic-like experiences can also be applied in a help-seeking population.

Introduction: Stigma is an important environmental risk factor for a variety of outcomes in schizophrenia. In order to understand and remediate its effects, research is required to assess how stigma experiences are processed at the level of the individual. To this end, stereotype awareness (SA) with respect to people with mental illness and their families was explored in persons with psychotic disorder., Method: Data from the Dutch Genetic Risk and OUtcome of Psychosis project (GROUP) were analyzed. SA was measured using scales that assess a respondent's perception of common opinions about people with a mental illness and their families., Results: People with higher level of self-esteem were less aware of stereotypes about patients and families. People with more severe psychopathology reported more awareness of stereotypes about families, not about patients., Conclusion: Enhancing psychological resources, by increasing self-esteem and the ability to cope with symptoms, can be targeted to diminish stereotype threat and improve stigma resilience. Interventions can be tailored to individual differences to increase their impact. Furthermore, in order to diminish detrimental consequences of negative stereotypes, mental health professionals, health educators and experts by experience can inform the public about mental illness and stigma.

Background: For the purpose of diagnosis, psychopathology can be represented as categories of mental disorder, symptom dimensions or symptom networks. Also, psychopathology can be assessed at different levels of temporal resolution (monthly episodes, daily fluctuating symptoms, momentary fluctuating mental states). We tested the diagnostic value, in terms of prediction of treatment needs, of the combination of symptom networks and momentary assessment level., Method: Fifty-seven patients with a psychotic disorder participated in an ESM study, capturing psychotic experiences, emotions and circumstances at 10 semi-random moments in the flow of daily life over a period of 6 days. Symptoms were assessed by interview with the Positive and Negative Syndrome Scale (PANSS); treatment needs were assessed using the Camberwell Assessment of Need (CAN)., Results: Psychotic symptoms assessed with the PANSS (Clinical Psychotic Symptoms) were strongly associated with psychotic experiences assessed with ESM (Momentary Psychotic Experiences). However, the degree to which Momentary Psychotic Experiences manifested as Clinical Psychotic Symptoms was determined by level of momentary negative affect (higher levels increasing probability of Momentary Psychotic Experiences manifesting as Clinical Psychotic Symptoms), momentary positive affect (higher levels decreasing probability of Clinical Psychotic Symptoms), greater persistence of Momentary Psychotic Experiences (persistence predicting increased probability of Clinical Psychotic Symptoms) and momentary environmental stress associated with events and activities (higher levels increasing probability of Clinical Psychotic Symptoms). Similarly, the degree to which momentary visual or auditory hallucinations manifested as Clinical Psychotic Symptoms was strongly contingent on the level of accompanying momentary paranoid delusional ideation. Momentary Psychotic Experiences were associated with CAN unmet treatment needs, over and above PANSS measures of psychopathology, similarly moderated by momentary interactions with emotions and context., Conclusion: The results suggest that psychopathology, represented as an interactome at the momentary level of temporal resolution, is informative in diagnosing clinical needs, over and above traditional symptom measures.

Background: FK506 binding protein 5 (FKBP5) has repeatedly been shown to be a critical determinant of post-traumatic stress disorder (PTSD) and depression following childhood trauma., Aims: To examine the role of FKBP5-trauma interactions in the partly stress-related psychosis phenotype., Method: In 401 general population twins, four functional polymorphisms were examined in models of psychosis and cortisol, and followed up in models of psychosis in three samples at different familial liability (175 controls, 200 unaffected siblings and 195 patients with a psychotic disorder)., Results: The most consistent finding was an interaction between childhood trauma and rs9296158/rs4713916 on psychotic symptoms and cortisol in the twin sample, combined with a directionally similar interaction in siblings (rs4713916) and patients (rs9296158), A-allele carriers at both polymorphisms being most vulnerable to trauma., Conclusions: Trauma may increase the risk of psychosis through enduring changes in the cortisol feedback loop, similar to that for PTSD, suggesting comparable biological mechanisms for psychosis across diagnostic boundaries.

Psychotic disorders are thought to represent altered neural function. However, research has failed to map diagnostic categories to alterations in neural networks. It is proposed that the basic unit of psychotic psychopathology is the moment-to-moment expression of subtle anomalous experiences of subclinical psychosis, and particularly its tendency to persist from moment-to-moment in daily life, under the influence of familial, environmental, emotional and cognitive factors.In a general population twin sample (n = 579) and in a study of patients with psychotic disorder (n = 57), their non-psychotic siblings (n = 59) and unrelated controls (n = 75), the experience sampling paradigm (ESM; repetitive, random sampling of momentary mental states and context) was applied. We analysed, in a within-person prospective design, (i) transfer of momentary anomalous experience at time point (t-1) to time point (t) in daily life, and (ii) moderating effects of negative affect, positive affect, daily stressors, IQ and childhood trauma. Additionally, (iii) familial associations between persistence of momentary anomalous experience and psychotic symptomatology were investigated. Higher level of schizotypy in the twins (but not higher level of psychotic symptoms in patients) predicted more persistence of momentary anomalous experience in daily life, both within subjects and across relatives. Persistence of momentary anomalous experience was highest in patients, intermediate in their siblings and lowest in controls. In both studies, persistence of momentary anomalous experience was moderated by higher levels of negative affect, daily stressors and childhood trauma (only in twins), and by lower levels of positive affect. The study of alterations in the moment-to-moment transfer of subtle anomalous experience of psychosis, resulting in their persistence, helps to explain why psychotic and emotional dysregulation tend to cluster in a single phenotype such as schizophrenia, and how familial and environmental risks increase the risk of expression of psychosis from, first, subtle momentary anomalous experience to, second, observable clinical symptoms.

Background: Deficits in emotion processing are thought to underlie the key negative symptoms flat affect and anhedonia observed in psychotic disorders. This study investigated emotional experience and social behavior in the realm of daily life in a sample of patients with schizophrenia and schizoaffective disorder, stratified by level of negative symptoms., Methods: Emotional experience and behavior of 149 patients with schizophrenia and schizoaffective disorder and 143 controls were explored using the Experience Sampling Method., Results: Patients reported lower levels of positive and higher levels of negative affect compared with controls. High negative symptom patients reported similar emotional stability and capacity to generate positive affect as controls, whereas low negative symptom patients reported increased instability. All participants displayed roughly comparable emotional responses to the company of other people. However, in comparison with controls, patients showed more social withdrawal and preference to be alone while in company, particularly the high negative symptom group., Conclusions: This study revealed no evidence for a generalized hedonic deficit in patients with psychotic spectrum disorders. Lower rather than higher levels of negative symptoms were associated with a pattern of emotional processing which was different from healthy controls.

Aims: To study the systematic assessment of need for care and clinical parameters for use in treatment plans in patients diagnosed with severe mental illness., Methods: The Cumulative Needs for Care Monitor (CNCM) includes various validated instruments, such as the Camberwell Assessment of Need. A Markov-type cost-effectiveness model (health care perspective, 5-year time horizon) was used to compare CNCM with care as usual (CAU). Two studies were used to determine model parameters: a before–after study (n = 2155) and a matched-control study (n = 937)., Results: The CNCM may lead to a gain in psychiatric functioning according to the models. CNCM patients remain in (outpatient) care, while CAU patients drop out more frequently. There is only a small difference in inpatient care. As a result, average costs per patient in the CNCM group are between €2809 (before–after model) and €5251 (matched-control model) higher. The iCER was between €45 127 and €57 839 per life year without psychiatric dysfunction gained., Conclusions: CNCM may be only cost-effective when willingness to pay for a life year without psychiatric dysfunction is higher than €45 000. However, this result is highly sensitive to the level of psychiatric dysfunctioning in patients who do not receive care.

Background: Hallucinations are a core feature of psychosis, often causing considerable distress. Reported prevalence ranges from 70% for auditory hallucinations (AHs) to 30% for visual hallucinations (VHs) and 4% for hallucinations in the tactile domain. AHs have been studied extensively but studies on VHs are scarce. The current study investigated the phenomenology of VHs and AHs in the realm of daily life, by analyzing their prevalence, course and co-occurrence over a 6-day period and their temporal relation to emotions and delusions., Methods: The ESM, a structured diary technique, was used to investigate hallucinatory experiences in the context of daily life in a pooled data-set of 184 participants (71% males) with psychosis spectrum disorders, which were recruited from mental health facilities in the south of the Netherlands and Belgium. All self-assessments were rated on 7-point Likert scales. VHs were defined using participants' scores on the item "I see phenomena". AHs were measured using the item "I hear voices"., Results: Overall, 73 participants (40%) reported hallucinations. Ten participants reported VHs only, 38 reported both VHs and AHs, and 25 participants reported AHs only. AHs co-occurred with VHs in 40% of the hallucinatory moments. Patients with both VHs and AHs reported higher levels of negative affect, lower levels of positive affect and higher delusional intensity than non-hallucinating patients. Increased delusional intensity preceded the onset of hallucinatory episodes, whereas increases in positive or negative affect did not., Discussion: These results show that VHs are common in patients with psychosis spectrum disorders and often co-occur with AHs in time. Furthermore delusional ideation may precede hallucinatory episodes in the realm of daily life, rather than result from a hallucination and affective dysregulation might not play a primary role in hallucination onset., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: The associations of two types of childhood trauma (abuse and neglect) with psychosis symptom domains were investigated in subjects with psychotic illness, high psychosis vulnerability, and average psychosis vulnerability., Method: Childhood trauma was assessed with the Childhood Trauma Questionnaire. Symptoms were assessed with the Positive and Negative Syndrome Scale in the patients (N=272) and with the Structured Interview for Schizotypy-Revised in the patients' siblings (N=258), and healthy comparison subjects (N=227)., Results: Childhood trauma was associated with psychotic disorder in a dose-response fashion in the comparison of patients and healthy subjects (adjusted odds ratio=4.53, 95% CI=2.79-7.35). The comparison of siblings and healthy subjects suggested that siblings shared a degree of trauma with the patients (adjusted odds ratio=1.61, 95% CI=0.95-2.61), but the patient-sibling comparison indicated much greater exposure in patients than in siblings (adjusted odds ratio=2.60, 95% CI=1.78-3.78). Childhood abuse but not neglect was associated with positive but not negative symptoms in a dose-response fashion in all three groups. There was no evidence for moderation by sex., Conclusions: Discordance in psychotic illness across related individuals can be traced to differential exposure to trauma. The association between trauma and psychosis is apparent across different levels of illness and vulnerability to psychotic disorder, suggesting true association rather than reporting bias, reverse causality, or passive gene-environment correlation. Positive psychotic symptoms in vulnerable individuals may arise as a consequence of the level and frequency of exposure to abuse rather than neglect, suggesting symptom-specific and exposure-specific underlying mechanisms.

Cognition has been studied extensively in schizophrenia in Western countries. Far less research is devoted, however, to cognitive functioning in brief psychotic disorder and schizophreniform disorder. Moreover, few studies have been performed in third world countries. In this study, we want to fill this gap by comparing the cognitive functioning of three groups of ambulant, first-episode patients with a non-affective psychosis in the Democratic Republic of Congo. To test if cognitive dysfunction is a core symptom of psychosis in an African population, 153 healthy control subjects are compared with a sample of 68 patients with brief psychotic disorder, 50 patients with schizophreniform disorder, and 70 patients with schizophrenia in a cross-sectional study on several distinctive cognitive domains including verbal, visual, and working memory, attention, visuomotor control, motor speed, verbal fluency, and executive functions. In addition, these three groups of patients are compared among themselves on these cognitive domains. Results indicate that patients perform significantly worse than healthy controls on all cognitive domains with cognitive deficits being most pronounced in verbal and working memory, attention, motor speed, and executive functions. No major differences were found, however, between the three patient groups., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

Background: Psychosis has been repeatedly suggested to be affected by increases in stress and arousal. However, there is a dearth of evidence supporting the temporal link between stress, arousal, and psychosis during "real-world" functioning. This paucity of evidence may stem from limitations of current research methodologies. Our aim is to the test the feasibility and validity of a novel methodology designed to measure concurrent stress and arousal in individuals with psychosis during "real-world" daily functioning., Method: Twenty patients with psychosis completed a 36-hour ambulatory assessment of stress and arousal. We used experience sampling method with palm computers to assess stress (10 times per day, 10 AM → 10 PM) along with concurrent ambulatory measurement of cardiac autonomic regulation using a Holter monitor. The clocks of the palm computer and Holter monitor were synchronized, allowing the temporal linking of the stress and arousal data. We used power spectral analysis to determine the parasympathetic contributions to autonomic regulation and sympathovagal balance during 5 minutes before and after each experience sample., Results: Patients completed 79% of the experience samples (75% with a valid concurrent arousal data). Momentary increases in stress had inverse correlation with concurrent parasympathetic activity (ρ = -.27, P < .0001) and positive correlation with sympathovagal balance (ρ = .19, P = .0008). Stress and heart rate were not significantly related (ρ = -.05, P = .3875)., Conclusion: The findings support the feasibility and validity of our methodology in individuals with psychosis. The methodology offers a novel way to study in high time resolution the concurrent, "real-world" interactions between stress, arousal, and psychosis. The authors discuss the methodology's potential applications and future research directions.

Background: Little is known about the experiential dynamics of the interaction between cannabis and vulnerability to psychosis., Aims: To examine the effects of cannabis on psychotic symptoms and mood in patients with psychosis and healthy controls., Method: Patients with a psychotic disorder (n = 42) and healthy controls (n = 38) were followed in their daily lives using a structured time-sampling technique., Results: Daily life cannabis use predicted subsequent increases in positive affect and in patients, but not in controls, decreases in negative affect. In patients, but not in controls, cannabis use predicted increased levels of hallucinatory experiences. Mood-enhancing properties of cannabis were acute, whereas psychosis-inducing effects were sub-acute. There was no direct evidence for self-medication effects in daily life., Conclusions: Patients with psychosis are more sensitive to both the psychosis-inducing and mood-enhancing effects of cannabis. The temporal dissociation between acute rewarding effects and sub-acute toxic influences may be instrumental in explaining the vicious circle of deleterious use in these patients.

Background: Psychotic disorders are a serious mental health problem. Intervention before the onset of psychosis might result in delaying the onset, reducing the impact or even preventing the first episode of psychosis. This study explores the effectiveness of cognitive behavioural therapy (CBT) in targeting cognitive biases that are involved in the formation of delusions in persons with an ultra-high risk for developing psychosis. A single blind randomised controlled trial compares CBT with treatment as usual in preventing or delaying the onset of psychosis., Method/design: All help seeking patients aged 14 to 35 years referred to the mental health services in three regions in the Netherlands are pre-screened with the Prodromal Questionnaire during a period of two years. Patients with a score of 18 or more on the sub-clinical positive symptoms items (45 items in total) will be assessed with the Comprehensive Assessment of At Risk Mental State (CAARMS). In a different pathway to care model all referrals from the mental health services in Amsterdam to the specialized psychosis clinic of the Academic Medical Centre in Amsterdam are also assessed with the CAARMS. The primary outcome is the transition rate to psychosis according to the CAARMS-criteria. Group differences will be analysed with chi-square tests and survival analyses., Discussion: CBT is a highly tolerated treatment. The psycho-educational CBT approach may prove to be a successful strategy since most people with an At Risk Mental State (ARMS) are distressed by odd disturbing experiences. Giving explanations for and normalising these experiences may reduce the arousal (distress) and therefore may prevent people from developing a catastrophic delusional explanation for their odd experiences and thus prevent them from developing psychosis.Screening the entire help-seeking population referred to community mental health services with a two-stage strategy, as compared with traditional referral to a specialist clinical psychosis centre, might detect more ultra-high-risk (UHR) patients. This type of screening could be implemented in mental health care as routine screening. The trial is registered at Current Controlled trials as trial number ISRCTN21353122.

There is an expanding interest to study psychosis in the realm of daily life. The study of the person in the context of daily life may provide a powerful addition to more conventional and cross-sectional research strategies in the study of psychosis. This article first discusses the nature of experience sampling research in psychosis and demonstrates the feasibility and validity of studies using the experience sampling method (ESM) in this patient group. Second, the article presents a review of all ESM research in psychosis with a special focus on (a) the phenomenology, (b) the etiology, and (c) psychological models of psychosis. Variability over time and the dynamic interplay with the environment were found to be essential features of the positive symptoms of psychosis, whereas behavioral patterns as well as self-reported affect in daily life reality might be essential when studying negative symptomatology. ESM contributes to a better understanding of the interplay between psychotic experiences and environmental features, such as stress or cannabis exposure. Finally, the study of symptomatic variability may fuel new research into psychological models and treatment of psychosis and the study of the person-environment interplay may foster new Gene x Environment interaction studies.

Objective: The aim of this study was to examine whether proneness to subjective cognitive failure (cognitive based mistakes) increases the risk for the development of symptoms of psychosis and to what degree any association was familial., Methods: At baseline, the Cognitive Failure Questionnaire (CFQ) and the Community Assessment of Psychic Experiences (CAPE) questionnaire were administered in a general population sample of genetically related individuals (n = 755). Individuals scoring high (>75th percentile) or average on the CAPE (between 40th and 60th percentile) (n = 488) were reinterviewed with the CAPE and Structured Interview for Schizotypy-Revised (SIS-R) at follow-up (mean interval = 7.7 months, SD = 4.8 months)., Results: Cross-trait, within-relative analysis showed a significant association between the CFQ and the negative dimension, assessed with both the CAPE and SIS-R, whereas no association was found between the CFQ and the positive dimension. Cross-trait, between-relative analyses showed no association between the CFQ in one relative and any of the dimensions of the subclinical psychosis phenotype in the other relative., Conclusion: Proneness to subjective cognitive failure possibly contributes to the development or persistence of negative symptoms and can be seen as potential risk factor for negative symptoms of psychosis. This overlap is due to individual effects rather than familial liability.

Objective: A functional polymorphism in the catechol-o-methyltransferase gene (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted., Method: The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25)., Results: Carriers of the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability., Conclusion: The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.

A systematic review of all reported incidence and prevalence studies of population rates of subclinical psychotic experiences reveals a median prevalence rate of around 5% and a median incidence rate of around 3%. A meta-analysis of risk factors reveals associations with developmental stage, child and adult social adversity, psychoactive drug use, and also male sex and migrant status. The small difference between prevalence and incidence rates, together with data from follow-up studies, indicates that approximately 75-90% of developmental psychotic experiences are transitory and disappear over time. There is evidence, however, that transitory developmental expression of psychosis (psychosis proneness) may become abnormally persistent (persistence) and subsequently clinically relevant (impairment), depending on the degree of environmental risk the person is additionally exposed to. The psychosis proneness-persistence-impairment model considers genetic background factors impacting on a broadly distributed and transitory population expression of psychosis during development, poor prognosis of which, in terms of persistence and clinical need, is predicted by environmental exposure interacting with genetic risk.

There is evidence that the normally transitory developmental expression of psychosis (psychosisproneness) may first of all become abnormally persistent (persistence) and later on become clinically relevant (impairment), depending on the amount of environmental risk to which the person is exposed. According to the psychosis-proneness-persistence impairment model, genetic background factors can impact on a transitory expression of psychosis. Whether or not this will lead to a poor prognosis in terms of persistence and clinical need will depend on the interaction between environmental exposure and genetic risk.

Objective: Previous research has suggested that going along with psychotic symptoms (symptomatic coping) is less effective than other coping strategies with psychotic symptoms. This pilot study aims to validate such findings using a momentary assessment strategy of coping with stress in daily life., Method: Patients with psychosis (n = 35) were studied with the Experience Sampling Method (ESM; a structured diary technique) to assess coping with stress in daily life. This was analysed in relation to coping with psychotic symptoms using a previously validated interview (Maastricht Assessment of Coping Strategies)., Results: Symptomatic and non-symptomatic coping were negatively associated with each other. Symptomatic coping was negatively associated with the level of coping in daily life, whereas a positive association was apparent for non-symptomatic coping. Non-symptomatic coping, but not symptomatic coping, predicted appraisals of distress associated with psychotic symptoms., Conclusion: Effective coping may be associated with the tendency to develop conscious appraisals of distress associated with psychotic symptoms.