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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.

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.

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.

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.