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Background There is evidence for a polygenic contribution to psychosis. One targetable mechanism through which polygenic variation may impact on individuals and interact with the social environment is stress sensitization, characterized by elevated reactivity to minor stressors in daily life. The current study aimed to investigate whether stress reactivity is modified by polygenic risk score for schizophrenia (PRS) in cases with enduring non-affective psychotic disorder, first-degree relatives of cases, and controls. Methods We used the experience sampling method to assess minor stressors, negative affect, positive affect and psychotic experiences in 96 cases, 79 first-degree relatives, i.e. siblings, and 73 controls at wave 3 of the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Genome-wide data were collected at baseline to calculate PRS. Results We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWEv. low level of PRS. By contrast, controls with high PRS showed more intense psychotic experiences in response to stress compared to those with low PRS. Conclusions This tentatively suggests that polygenic risk may operate in different ways than previously assumed and amplify reactivity to stress in unaffected individuals but operate as a resilience factor in relatives by attenuating their stress reactivity.

Individuals at clinical risk for psychosis (CHR-P) and persons with a first episode of psychosis (FEP) are up to three-fold more likely to smoke than the general population, respectively1,2. Besides the general well-known consequences of tobacco consumption (lung cancer, COPD, etc.), smoking has also been associated with other profound effects in patients with psychotic disorders and CHR-P individuals. For example, worse psychiatric symptoms3 and an increased risk of relapse4. Besides smoking cigarettes, abuse of cannabis, and other illicit drugs is also common. To improve outcomes, it is essential to gain insight into the patterns of substance abuse in UHR and FEP. Several, non-mutually exclusive explanations of the relationship between smoking and psychosis exist. The shared vulnerability hypothesis5-7 postulates a shared genetic and environmental vulnerability of substance use and psychosis, which explains why patients with psychosis smoke so frequently and heavily compared to healthy controls. The misattribution hypothesis states that substance users experience depressive and anxiety symptoms when withdrawal occurs; these feelings are relieved by substance use thus creating the perception that, for example, smoking has beneficial and relaxing effects. Substance use can also be seen as a dysfunctional coping mechanism to deal with distress and affective symptoms, which are the most common comorbid symptoms in CHR-P8 and FEP9. However, other authors state that nicotine has indeed beneficial effects on symptom severity by stimulation of the acetylcholine receptor and reduce side effects through cyp-induction10,11, also known as self-medication. By contrast, the stress-induction model of smoking proposes that smoking actually causes stress and negative affect12. The aim of this study is to further explore whether substance use is associated with symptomatology, negative affect and stress in CHR-P and FEP. Substance use, symptomatology, negative affect and stress have been assessed with clinical interviews and Experience Sampling Methods (ESM) respectively. We therefore aim to investigate the following research objectives on a between and within-subject level: The objectives are: i. Investigate the associations between baseline substance use (tobacco smoking and cannabis use), and severity and course of symptoms, experienced stress and negative affect as assessed with clinical interviews and aggregated ESM-data over a one year period, while accounting for a-prior defined covariates. ii. Investigate causal effects of smoking on psychotic experiences, negative affect and stress (and vice versa) using a dynamic approach between these outcomes in a moment-to-moment analysis. iii. Explore the moderating role of stress on the smoking-negative affect relationship: since daily stressors are related to both smoking and negative affect, exposure to stress might be an important moderator of the smoking–negative affect relationship.

BACKGROUND: The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach. METHOD: AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time. RESULTS: We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory. CONCLUSION: Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.

Subclinical psychotic experiences are common in the general population and are associated with an increased probability of developing a psychotic disorder (Linscott & Van Os, 2013; McGrath et al., 2015; Morgan et al., 2014). Current evidence has identified enhanced threat anticipation as a putative mechanism through which stress impacts on the formation of psychotic experiences in healthy adults, individuals with an at-risk mental state and patients with a first episode of psychosis (Klippel et al., 2017). The effect of enhanced threat anticipation appears to increase as individuals transition from subclinical psychosis to the formation of a psychotic disorder (Reininghaus et al., 2016). Repeated exposure to adversity may lead individuals to anticipate more unpleasant events from their environment and create an enduring sense of threat, which appeared to be as closely indicative of paranoia as persecutory beliefs (Bentall et al., 2014; Bentall et al., 2009; Morgan, Charalambides, Hutchinson, & Murray, 2010). However, all studies mentioned above investigated adult samples and to date there is no evidence on the role of threat anticipation in the development of psychopathology in adolescents. To address this pressing gap in the literature, the aim of the present project is to investigate the association of i) threat anticipation and ii) childhood adversity with psychopathology in adolescence using cross-sectional data from the first wave of the SIGMA study, a large-scale, longitudinal study of adolescent mental health and development.

In the current study, we aim to examine change in self-compassion and emotion regulation, working alliance, and training frequency as putative therapeutic mechanisms of change in the EMIcompass trial. The EMIcompass trial aims at investigation feasibility, candidate underlying mechanisms and initial signals of efficacy of a novel, transdiagnostic hybrid ecological momentary intervention (EMI) for improving resilience to stress in youth aged 14-25 with current distress, a broad Clinical High At-Risk Mental State (CHARMS) or a fist episode of s severe mental disorder. For a detailed description of the EMIcompass exploratory RCT, please see our published study protocol (Schick et al., 2021). This pre-registration is directly based on the EMIcompass study protocol. The EMIcompass intervention is described in a separate manuscript (Paetzold et al., in preparation). Meta-analytic evidence demonstrates the efficacy of self-compassion interventions for various mental health problems (Ferrari et al., 2019). However, the mechanisms involved remain largely unclear and further research is urgently needed (Ferrari et al., 2019; Kirby, Tellegen, & Steindl, 2017). Besides a change in self-compassion itself, constructs such as improvement in emotion regulation or self-regulation and re-appraisal skills are discussed as putative mechanisms mediating the association (Ferrari et al., 2019). In addition, meta-analytic evidence indicates that training frequency may be a crucial variable: In classic psychotherapeutic settings, an association of homework compliance and outcomes of small to moderate effect size has been reported (Mausbach, Moore, Roesch, Cardenas, & Patterson, 2010). Besides treatment-specific mechanisms, working alliance may also be considered as a putative mechanism of change. Meta-analyses and reviews provide convincing evidence on the association of working alliance and outcomes across different types of therapies and different mental health problems in adults and adolescents (Horvath, Del Re, Flückiger, & Symonds, 2011; Martin, Garske, & Davis, 2000; Murphy & Hutton, 2018; Shirk & Karver, 2003). Baier, Kline, and Feeny (2020) recently reviewed the existing literature on therapeutic alliance as a mediator of change and demonstrated that alliance mediated effects of treatment on therapeutic outcomes in 70% of all studies included. Whereas the role of therapeutic alliance is quite well researched in classic psychotherapeutic settings, a recent review by Henson, Wisniewski, Hollis, Keshavan, and Torous (2019) identified only 5 studies that discuss therapeutic alliance when a mobile application intervention is involved in therapy. To further improve mobile interventions, elucidating mechanisms and processes of change is of crucial importance.

There is evidence for a slower recovery of negative affect (NA) after stressful events in daily life in individuals with early and enduring psychosis compared with healthy controls (Vaessen et al., 2019). We will extend this research by examining trajectories of positive affect (PA) in response to minor stressors in daily life across subclinical and clinical stages of mental disorder. We aim to investigate i) baseline levels of positive affect, ii) reactivity of PA to momentary stress, and iii) positive affective recovery from daily stressors as a momentary mechanism in different stages of mental disorder.

The EMIcompass trial aims at investigation feasibility, candidate underlying mechanisms and initial signals of efficacy of a novel, transdiagnostic hybrid ecological momentary intervention (EMI) for improving resilience to stress in youth aged 14-25 with current distress, a broad Clinical High At-Risk Mental State (CHARMS) or a first episode of s severe mental disorder. In the planned paper, we aim to present the EMIcompass intervention in detail. In addition, we aim to examine whether the intervention is inclusive of all individuals taking part in the intervention. For a detailed description of the EMIcompass exploratory RCT, please see our published study protocol (Schick et al., 2021). This pre-registration is directly based on the EMIcompass study protocol.

Ader, L., Schick, A., Reininghaus, U. (2021, January 15). Positive affective recovery in daily life as a momentary mechanism across subclinical and clinical stages of mental disorder. Retrieved from osf.io/qp3bv. doi: 10.17605/OSF.IO/QP3BV

For a detailed description of the study, please see our published study protocol (Schick et al., 2021). This preregistration includes the Statistical Analysis Plan (see sections 21-25) for this exploratory randomized controlled trial, which must be read and considered in conjunction with the published study protocol (Schick et al., 2021). Elevated stress reactivity is one of the most widely studied mechanisms underlying psychotic and affective mental health problems. Thus, targeting stress reactivity in youth is a promising indicated and translational preventive strategy for adverse mental health outcomes later in life and for improving resilience. Compassion-Focused Interventions (CFIs) offer a wide range of innovative therapeutic techniques particularly amenable to being implemented as an Ecological Momentary Intervention (EMI) to enable youth to access interventions in a given moment and context in daily life. The aim of the EMIcompass trial is to investigate the feasibility, candidate underlying mechanisms and initial signals of efficacy of a novel, transdiagnostic, hybrid EMI for improving resilience to stress in youth aged 14-25 with current distress, a broad Clinical High At-Risk Mental State (CHARMS) or a first episode of a severe mental disorder. Sections of this pre-registration are taken from the EMIcompass study protocol (please refer to Schick et al., (2021) for further details). For further information on the EMIcompass intervention, please refer to Paetzold et al. (2019). The present preregistration focuses on the main hypotheses that will be tested and reported in the first manuscript. In subsequent preregistration reports, we will elaborate on the analysis plan for other papers.

For a detailed description of the study, please see our published study protocol (1). This preregistration includes the Statistical Analysis Plan (see sections 21-25) for this multicenter randomized controlled trial, which must be read and considered in conjunction with the published study protocol (1). 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 the SELFIE trial is to investigate the efficacy of a novel, accessible, transdiagnostic ecological momentary intervention for improving self-esteem (‘SELFIE’) in youth aged 12-26 years with prior exposure to childhood adversity. (Preliminary remarks) Sections of this pre-registration are taken from the SELFIE study protocol (please refer to Daemen, Postma (1) for further details). The present preregistration focuses on the main hypotheses on primary and secondary outcomes at 6-month follow-up that will be tested and reported in the first manuscript. In addition, we will report the statistical analysis plan for hypotheses relating to outcomes at 18-month and 24-month follow-up, which will be reported in a subsequent manuscript. The statistical analysis plan for hypotheses relating to hypotheses on cost effectiveness and cost utility will be described in a subsequent preregistration report.

Affective reactivity to daily stressors are increased in individuals in the early stages of psychosis. Studies in psychosis patients and healthy individuals at increased psychosis risk show altered neural reactivity to stress in limbic (i.e., hippocampus [HC] and amygdala), prelimbic (i.e., ventromedial prefrontal cortex [vmPFC] and ventral anterior cingulate cortex [vACC]), and salience areas (i.e., anterior insula [AI]). We investigated whether a similar pattern of neural reactivity is present in early psychosis individuals and if brain activity in these regions is associated with daily-life stress reactivity.Twenty-nine early psychosis individuals (11 clinical high risk and 18 first-episode psychosis) completed a stress task in conjunction with functional MRI. All participants also provided experience sampling methodology (ESM) data on momentary affect and stressful activities in their everyday environment. Multilevel regression models were used to estimate if daily-life stress reactivity was moderated by activity in (pre)limbic and salience areas.Task-induced stress was associated with increased activation of the right AI and decreased activation in the vmPFC, vACC, and HC. Task-induced changes in vmPFC and vACC activity were associated with affective stress reactivity, whereas changes in HC and amygdala activity were associated with higher overall stress levels.These preliminary results suggest region-specific roles in affective and psychotic daily-life stress reactivity in early psychosis. The observed pattern suggests that chronic stress plays a role in neural stress reactivity. Direct comparison with a control group should elucidate whether these findings reflect a neural basis for an affective pathway to psychosis.

Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2010-241909, Purpose: The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. Methods: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case–control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. Conclusions: This resource constitutes the largest and most extensive incidence and case–control study of psychosis ever conducted.

Additional file 4: Overview of participants in the qualitative study.

Additional file 3: Online survey.

Additional file 2: Interview topic guide–expert interviews.

Additional file 5: COREQ-Checklist.

BACKGROUND: Individuals diagnosed with schizophrenia are often assigned other psychiatric diagnoses during their lives. The significance of changing diagnosis has not been widely studied. AIMS: Our aim was to examine the association between diagnostic change and later outcome. METHODS: Individuals' diagnostic history, clinical and social outcomes were extracted from the AESOP-10 study, a 10-year follow-up of first episode psychosis cases. The association between outcome and different patterns of diagnosis over time were assessed using linear or logistic regression. RESULTS: Individuals always diagnosed with schizophrenia (n = 136) had worse clinical and social outcomes at follow-up than those never diagnosed with schizophrenia (n = 163), being more likely to be symptomatic, unemployed, single, and socially isolated. There was no difference in outcome between individuals always diagnosed with schizophrenia and those changing to a diagnosis of schizophrenia (n = 60), and no difference in outcome between individuals never diagnosed with schizophrenia, and those changing from a diagnosis of schizophrenia (n = 44). CONCLUSIONS: Individuals always and never diagnosed with schizophrenia had different outcomes. In cases of diagnostic instability participants had similar outcomes to those always assigned the diagnosis they changed to irrespective of initial diagnosis.

Im Zuge der Anerkennung psychischer Gesundheit als wesentlicher Bestandteil der Bevölkerungsgesundheit wird am Robert Koch-Institut eine Mental Health Surveillance (MHS) für Deutschland aufgebaut. Ziel der MHS ist die kontinuierliche Berichterstattung relevanter Kennwerte zum Zweck einer evidenzbasierten Planung und Evaluation von Public-Health- Maßnahmen. Zur Entwicklung eines Indikatorensets für die erwachsene Bevölkerung wurden potenzielle Indikatoren durch eine systematische Literaturrecherche identifiziert und in einem strukturierten Konsentierungsprozess durch internationale und nationale Expertinnen und Experten beziehungsweise Stakeholder ausgewählt. Das finale Set enthält 60 Indikatoren, die ein mehrdimensionales Public-Health-Rahmenkonzept psychischer Gesundheit in vier Handlungsfeldern abbilden. Im fünften Handlungsfeld „Gesundheitsförderung und Prävention“ besteht Bedarf der Indikatorenentwicklung. Die pilotierte Methodik erwies sich als praktikabel. Diskutiert werden Stärken und Limitationen der Recherche und Definition von Indikatoren, der Umfang des Indikatorensets sowie die partizipative Entscheidungsfindung. Nächste Schritte zur Etablierung der MHS bestehen in der Operationalisierung von Indikatoren und der Erweiterung unter anderem auf das Kindes- und Jugendalter. Bei gesicherter Datenverfügbarkeit wird die MHS zum Wissen über die Gesundheit der Bevölkerung beitragen und die gezielte Förderung psychischer Gesundheit sowie die Verringerung der Krankheitslast psychischer Störungen unterstützen.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.

Epidemiological studies suggest that the observed association between urbanicity and psychosis may be explained in part by social deprivation, reduced social capital affecting cohesion and trust, and minority group and ethnic density effects, which in turn may represent aspects of “social defeat.” In addition, urbanicity is also associated with pollution, noise, and lack of green space, which may negatively impact a range of health outcomes. This chapter reviews the neuroimaging literature on brain function, structure, and connectivity in relation to urbanicity. Research in patients with psychosis has mostly shown associations of urbanicity with brain functioning, rather than structure or connectivity. Neuroimaging research in healthy individuals may support altered social stress processing as a possible explanatory mechanism. Altered reward processing associated with urbanicity may provide an explanation for the possible influence of urban environments on dopamine dysregulation and the pathogenesis of psychosis. Mentalizing and sensory gating deficits may also mediate some of the negative effects of the city on mental health. A sustained effort toward exact replication is required to further develop this promising field.

Supplemental material, sj-docx-1-asm-10.1177_10731911211015355 for Development of the Thought Disorder Measure for the Hierarchical Taxonomy of Psychopathology by David C. Cicero, Katherine G. Jonas, Michael Chmielewski, Elizabeth A. Martin, Anna R. Docherty, Jonathan Berzon, John D. Haltigan, Ulrich Reininghaus, Avshalom Caspi, Rachael G. Graziolplene and Roman Kotov in Assessment

The work was supported by Guarantors of Brain post-doctoral clinical fellowship to DQ; Clinician Scientist Medical Research Council fellowship (project reference MR/M008436/1) to MDF; Heisenberg professorship from the German Research Founda- tion (grant no. 389624707) to UR; the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (Project EU-GEI). The Brazilian study was funded by the São Paulo Research Foundation under grant number 2012/0417-0., Quattrone D., Reininghaus U., Richards A.L., Tripoli G., Ferraro L., Quattrone A., Marino P., Rodriguez V., Spinazzola E., Gayer-Anderson C., Jongsma H.E., Jones P.B., La Cascia C., La Barbera D., Tarricone I., Bonora E., Tosato S., Lasalvia A., Szöke A., Arango C., Bernardo M., Bobes J., Del Ben C.M., Menezes P.R., Llorca P.-M., Santos J.L., Sanjuán J., Arrojo M., Tortelli A., Velthorst E., Berendsen S., de Haan L., Rutten B.P.F., Lynskey M.T., Freeman T.P., Kirkbride J.B., Sham P.C., O’Donovan M.C., Cardno A.G., Vassos E., van Os J., Morgan C., Murray R.M., Lewis C.M., Di Forti M., Hubbard K., Beards S., Stilo S.A., Parellada M., Fraguas D., Castro M.R., Andreu-Bernabeu Á., López G., Matteis M., González E., Durán-Cutilla M., Díaz-Caneja C.M., Cuadrado P., Rodríguez Solano J.J., Carracedo A., Costas J., Sánchez E., Amoretti S., Lorente-Rovira E., Garcia-Portilla P., Jiménez-López E., Franke N., van Dam D., Termorshuizen F., van der Ven E., Messchaart E., Leboyer M., Schürhoff F., Jamain S., Baudin G., Ferchiou A., Pignon B., Richard J.-R., Charpeaud T., Tronche A.-M., Frijda F., Marrazzo G., Sideli L., Sartorio C., Seminerio F., Loureiro C.M., Shuhama R., Ruggeri M., Bonetto C., Cristofalo D., Berardi D., Seri M., D’Andrea G.

Background Older individuals are at increased risk of a severe and lethal course of COVID-19. They have typically been advised to practice particularly restrictive social distancing (‘cocooning’), which has sparked much debate on the consequences for their mental wellbeing. We aimed to provide evidence by conducting a representative survey among the German old population during COVID-19 lockdown. Methods A computer-assisted standardized telephone interview was conducted in a randomly selected and representative sample of the German old age population (n = 1005; age ≥ 65 years) during the first lockdown in April 2020. Assessments included sociodemographic factors, aspects of the personal life situation during lockdown, attitudes towards COVID-19, and standardized screening measures on depression, anxiety, somatization, overall psychological distress (Brief Symptom Inventory/BSI-18) and loneliness (UCLA 3-item loneliness scale). Sampling-weighted descriptive statistics and multiple multivariable regression analyses were conducted. Results Participants were M = 75.5 (SD = 7.1) years old; 56.3% were women. At data collection, COVID-19 lockdown had been in force for M = 28.0 (SD = 4.8) days. Overall, older individuals were worried about COVID-19, but supportive of the lockdown. Mean BSI-18 scores were 1.4 for depression, 1.6 for anxiety and 2.2 for somatization as well as 5.1 for global psychological distress. These figures did not indicate worse mental wellbeing, given normative values established by studies before the pandemic (2.0, 1.6, 2.4, 6.0, respectively). The prevalence of loneliness was 13.1%, which also fell within a range of estimates reported by studies before the pandemic. There were only few significant associations of aspects of the personal life situation during lockdown and attitudes towards COVID-19 with mental wellbeing. Resilience explained a large amount of variance. Conclusions In the short-term, the mental wellbeing of the German old age population was largely unaltered during COVID-19 lockdown, suggesting resilience against the challenging pandemic situation. Our results refute common ageist stereotypes of “the weak and vulnerable older adults” that were present during the pandemic. Long-term observations are needed to provide robust evidence. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-020-01889-x.

Background: Historically, gene X environment examinations in psychotic disorders have employed candidate gene methods and environmental determinants impacting on similar biological mechanisms. However, genome wide association studies (GWAS) show that many variants associated with schizophrenia have a modest effect size on risk. In this respect, it is unclear whether the effect of cannabis on psychosis phenotypes is modified by a few genes, e.g. those involved in dopamine signalling, or by the overall genetic susceptibility to schizophrenia. Indeed, candidate gene approaches might be complementary to GWAS to test gene X cannabis interaction. We aimed to investigate the interactive effects of cannabis use on variants in DRD2 gene on: 1) the risk of developing first episode psychosis (FEP); and 2) the frequency of positive symptoms at FEP. We undertook a replication study of previous Gene X Cannabis interactions for DRD2 (rs1076560); further, we tested interactions between cannabis use and any SNP associated with schizophrenia within DRD2 gene in the last Psychiatric Genomics Consortium (PGC) GWAS. Methods: We genotyped ∼830 FEP patients and ∼1200 controls recruited across six countries as part of the large EUGEI study. OPerational CRITeria system and Cannabis Experience Questionnaire were used for evaluating psychopathology and patterns of cannabis use. Dimensions of psychopathology, which included a specific dimension of positive symptoms, were estimated using multidimensional item response modelling in Mplus. We tested for an interaction between risk allele count and daily cannabis use on: 1) the risk of psychotic disorder in the case-control study; 2) the positive symptom dimension in the case-only sample. Only one SNP in DRD2 was significantly associated with schizophrenia in the PGC study, so we tested for interaction with rs2514218, in addition to rs1076560. These regression models, conducted in STATA 14, were adjusted for age, gender, ethnicity, 10 principal components (PC) for population stratification and SNP-environment and SNP-PC interaction terms. Results were corrected for multiple testing of four SNPs (p

Background\ud The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.\ud \ud Method\ud This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.\ud \ud Results\ud A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.\ud \ud Conclusions\ud Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.

Additional file 1.

Subjective quality of life (SQOL) is an established patient-reported outcome in psychosis. However, current self-report measures of SQOL may be affected by recall bias and may not fully capture dynamic changes in SQOL over time. This study aimed to examine the ecological validity of self-reported and momentary assessment measures of SQOL, and their association with emotional experience, social interaction and activity in real life, in both patients with psychotic disorder (n = 56) and controls (n = 71). Self-reported QOL was assessed with the WHO-QOL, momentary QOL and real life experiences were assessed with the Experience Sampling Method (ESM). Results show that both measures were significantly associated in patients and controls, and associations with emotional experience were most relevant, momentary QOL being a stronger predictor than self-reported QOL. The association between momentary QOL and negative affect was stronger in patients than in controls. Overall, momentary QOL was more consistently associated with affect, social interaction and activity, while self-reported QOL displayed a more narrow association with mostly affect. Concluding, concurrent assessment of self-reported QOL and momentary QOL showed that momentary QOL may enhance the ecological validity of SQOL measurement. Experience sampling research may broaden our perspective on SQOL and its associations with real life functioning.

Background. The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment. Method. This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions. Results. A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions. Conclusions. Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.

BACKGROUND: The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment. METHOD: This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions. RESULTS: A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions. CONCLUSIONS: Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.

IMPORTANCE Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. OBJECTIVES To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. DESIGN, SETTING, AND PARTICIPANTS An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catchment areas), Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6 catchment areas), and Brazil (1 catchment area) with a first episode of nonorganic psychotic disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33) confirmed by the Operational Criteria Checklist. Denominator populations were estimated using official national statistics. EXPOSURES Age, sex, and racial/ethnic minority status were treated as a priori confounders. Latitude, population density, percentage unemployment, owner-occupied housing, and single-person households were treated as catchment area-level exposures. MAIN OUTCOMES AND MEASURES Incidence of nonorganic psychotic disorders (ICD-10 codes F20-F33), nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10 codes F30-F33) confirmed by the Operational Criteria Checklist. RESULTS A total of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile range, 23.0-41.0 years]) with incident cases of psychotic disorders were identified during 12.9 million person-years at risk (crude incidence, 21.4 per 100 000 person-years; 95%CI, 19.4-23.4 per 100 000 person-years). A total of 2183 patients (78.7%) had nonaffective psychotic disorders. After direct standardization for age, sex, and racial/ethnic minority status, an 8-fold variation was seen in the incidence of all psychotic disorders, from 6.0 (95%CI, 3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95%CI, 37.3-55.0) per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic minority groups (incidence rate ratio, 1.6; 95%CI, 1.5-1.7), were highest for men 18 to 24 years of age, and were lower in catchment areas with more owner-occupied homes (incidence rate ratio, 0.8; 95%CI, 0.7-0.8). Similar patterns were observed for nonaffective psychoses; a lower incidence of affective psychoses was associated with higher area-level unemployment (incidence rate ratio, 0.3; 95%CI, 0.2-0.5). CONCLUSIONS AND RELEVANCE This study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses.

IMPORTANCE Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. OBJECTIVES To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. DESIGN, SETTING, AND PARTICIPANTS An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catchment areas), Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6 catchment areas), and Brazil (1 catchment area) with a first episode of nonorganic psychotic disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33) confirmed by the Operational Criteria Checklist. Denominator populations were estimated using official national statistics. EXPOSURES Age, sex, and racial/ethnic minority status were treated as a priori confounders. Latitude, population density, percentage unemployment, owner-occupied housing, and single-person households were treated as catchment area-level exposures. MAIN OUTCOMES AND MEASURES Incidence of nonorganic psychotic disorders (ICD-10 codes F20-F33), nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10 codes F30-F33) confirmed by the Operational Criteria Checklist. RESULTS A total of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile range, 23.0-41.0 years]) with incident cases of psychotic disorders were identified during 12.9 million person-years at risk (crude incidence, 21.4 per 100 000 person-years; 95%CI, 19.4-23.4 per 100 000 person-years). A total of 2183 patients (78.7%) had nonaffective psychotic disorders. After direct standardization for age, sex, and racial/ethnic minority status, an 8-fold variation was seen in the incidence of all psychotic disorders, from 6.0 (95%CI, 3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95%CI, 37.3-55.0) per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic minority groups (incidence rate ratio, 1.6; 95%CI, 1.5-1.7), were highest for men 18 to 24 years of age, and were lower in catchment areas with more owner-occupied homes (incidence rate ratio, 0.8; 95%CI, 0.7-0.8). Similar patterns were observed for nonaffective psychoses; a lower incidence of affective psychoses was associated with higher area-level unemployment (incidence rate ratio, 0.3; 95%CI, 0.2-0.5). CONCLUSIONS AND RELEVANCE This study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses.

Background. A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diagnoses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an incidence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change.Method. Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables associated with change were examined using logistic regression and likelihood ratio tests.Results. Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder anddrug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years. Many variables were associated with change to schizophrenia but few with overall change in diagnosis. Conclusions. Diagnoses other than schizophrenia should to be regarded as potentially provisional.

Background: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.Method: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.Results: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.Conclusions: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

BACKGROUND: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.METHOD: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.RESULTS: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.CONCLUSIONS: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

BackgroundThe incidence of psychotic disorders is elevated in some minority ethnic populations. However, we know little about the outcome of psychoses in these populations.AimTo investigate patterns and determinants of long-term course and outcome of psychoses by ethnic group following a first episode.MethodÆSOP-10 is a ten-year follow-up of an ethnically diverse cohort of 532 individuals with first-episode psychosis identified in the UK. Information was collected, at baseline, on clinical presentation and neurodevelopmental and social factors and, at follow-up, on course and outcome.ResultsThere was evidence that, compared with white British, black Caribbean patients experienced worse clinical, social, and service use outcomes, and black African patients experienced worse social and service use outcomes. There was evidence that baseline social disadvantage contributed to these disparities.ConclusionThese findings suggest ethnic disparities in the incidence of psychoses extend, for some groups, to worse outcomes in multiple domains.

Background There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. Aims To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. Method Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. Results There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). Conclusions Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors.

While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ(2) = 6.3, P = 0.044), activities (χ(2) = 6.7, P = 0.036), and areas (χ(2) = 9.4, P = 0.009) and enhanced threat anticipation (χ(2) = 9.3, P = 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ(2) = 5.7, P = 0.058) and aberrantly salient experiences (χ(2) = 12.3, P = 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder.

It has long been held that schizophrenia and other psychotic disorders have a predominately poor course and outcome. We have synthesized information on mortality, clinical and social outcomes from the AESOP-10 multicenter study, a 10-year follow-up of a large epidemiologically characterized cohort of 557 people with first-episode psychosis. Symptomatic remission and recovery were more common than previously believed. Distinguishing between symptom and social recovery is important given the disparity between these; even when symptomatic recovery occurs social inclusion may remain elusive. Multiple factors were associated with an increased risk of mortality, but unnatural death was reduced by 90% when there was full family involvement at first contact compared with those without family involvement. These results suggest that researchers, clinicians and those affected by psychosis should countenance a much more optimistic view of symptomatic outcome than was assumed when these conditions were first described.

Background Recent estimates suggest around 14% of 11-16-year-olds in England have a mental health problem. However, we know very little about the extent and nature of mental health problems among diverse groups in densely populated inner cities, where contexts and experiences may differ from the national average. Aims To estimate the extent and nature of mental health problems in inner-city London, overall and by social group, using data from our school-based accelerated cohort study of adolescent mental health, REACH (Resilience, Ethnicity and AdolesCent Mental Health). Methods Self-report data on mental health (general mental health, depression, anxiety, self-harm) were analysed (n, 4353; 11-14yrs, 85% BAME). Mixed models were used to estimate weighted prevalences and adjusted risks of each type of problem, overall and by gender, cohort, ethnic group, and free school meals (FSM) status. Results The weighted prevalence of mental health problems was 18.6% (95% CI 16.4-20.8). Each type of mental health problem was more common among girls compared with boys (adjusted risk ratios [adjRR]: mental health problems, 1.33 [95% CI: 1.18-1.48]; depression, 1.52 [1.30-1.73]; anxiety, 2.09 [1.58-2.59], self-harm, 1.40 [1.06-1.75]). Gender differences were more pronounced in older cohorts compared with the youngest. Mental health problems (1.28 [1.05-1.51]) and self-harm (1.29 [1.02-1.56]) – but not depression or anxiety – were more common among those receiving (vs. not receiving) FSM. There were many similarities, with some variations, by ethnic group. Conclusions Adolescent mental health problems and self-harm are common in inner-city London. Gender differences in mental health problems may emerge during early adolescence.

BackgroundThe incidence of psychotic disorders is elevated in some minority ethnic populations. However, we know little about the outcome of psychoses in these populations.AimTo investigate patterns and determinants of long-term course and outcome of psychoses by ethnic group following a first episode.MethodÆSOP-10 is a ten-year follow-up of an ethnically diverse cohort of 532 individuals with first-episode psychosis identified in the UK. Information was collected, at baseline, on clinical presentation and neurodevelopmental and social factors and, at follow-up, on course and outcome.ResultsThere was evidence that, compared with white British, black Caribbean patients experienced worse clinical, social, and service use outcomes, and black African patients experienced worse social and service use outcomes.There was evidence that baseline social disadvantage contributed to these disparities.ConclusionThese findings suggest ethnic disparities in the incidence of psychoses extend, for some groups, to worse outcomes in multiple domains.

Additional file 1. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist.