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.

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.

We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWE<0.001). In contrast to our hypotheses, siblings with high PRS reported less intense psychotic experiences in response to momentary stress compared to siblings with low PRS. No differences in magnitude of these associations were observed in cases with high v. 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.

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.

Public health measures to curb SARS-CoV-2 transmission rates may have negative psychosocial consequences in youth. Digital interventions may help to mitigate these effects. We investigated the associations between social isolation, COVID-19-related cognitive preoccupation, worries, and anxiety, objective social risk indicators, and psychological distress, as well as use of, and attitude toward, mobile health (mHealth) interventions in youth.

Data were collected as part of the “Mental Health And Innovation During COVID-19 Survey”—a cross-sectional panel study including a representative sample of individuals aged 16–25 years (N = 666; Mage = 21.3; assessment period: May 5, 2020 to May 16, 2020).

Overall, 38% of youth met criteria for moderate or severe psychological distress. Social isolation worries and anxiety, and objective risk indicators were associated with psychological distress, with evidence of dose–response relationships for some of these associations. For instance, psychological distress was progressively more likely to occur as levels of social isolation increased (reporting “never” as reference group: “occasionally”: adjusted odds ratio [aOR] 9.1, 95% confidence interval [CI] 4.3–19.1, p < 0.001; “often”: aOR 22.2, CI 9.8–50.2, p < 0.001; “very often”: aOR 42.3, CI 14.1–126.8, p < 0.001). There was evidence that psychological distress, worries, and anxiety were associated with a positive attitude toward using mHealth interventions, whereas psychological distress, worries, and anxiety were associated with actual use.

Public health measures during pandemics may be associated with poor mental health outcomes in youth. Evidence-based digital interventions may help mitigate the negative psychosocial impact without risk of viral infection given there is an objective need and subjective demand.

One putative psychological mechanism through which momentary stress impacts on psychosis in individuals with increased liability to the disorder is via affective disturbance. However, to date, this has not been systematically tested. We aimed to investigate whether (i) cross-sectional and temporal effects of momentary stress on psychotic experiences via affective disturbance, and (ii) the reverse pathway of psychotic experiences on stress via affective disturbance were modified by familial liability to psychosis.

The Experience Sampling Method was used in a pooled data set of six studies with three groups of 245 individuals with psychotic disorder, 165 unaffected first-degree relatives, and 244 healthy control individuals to index familial liability. Multilevel moderated mediation models were fitted to investigate indirect effects across groups cross-sectionally and multilevel cross-lagged panel models to investigate temporal effects in the proposed pathways across two measurement occasions.

Evidence on indirect effects from cross-sectional models indicated that, in all three groups, effects of stress on psychotic experiences were mediated by negative affect and, vice versa, effects of psychotic experiences on stress were mediated by negative affect, with all indirect effects being weakest in relatives. Longitudinal modelling of data provided no evidence of temporal priority of stress in exerting its indirect effects on psychotic experiences via affective disturbance or, vice versa.

Our findings tentatively suggest a rapid vicious cycle of stress impacting psychotic experiences via affective disturbances, which does, however, not seem to be consistently modified by familial liability to psychosis.

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.

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.

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.

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.

A growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity.

Using detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder.

CAPsy is population-based first-episode psychosis case–control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments.

We found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence.

Our findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.

It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls.

We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls.

Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat−risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality.

Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.

Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.

We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.

In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.

Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.

Contemporary models of psychosis implicate the importance of affective dysregulation and cognitive factors (e.g. biases and schemas) in the development and maintenance of psychotic symptoms, but studies testing proposed mechanisms remain limited. This study, uniquely using a prospective design, investigated whether the jumping to conclusions (JTC) reasoning bias contributes to psychosis progression and persistence.

Data were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The Composite International Diagnostic Interview and an add-on instrument were used to assess affective dysregulation (i.e. depression, anxiety and mania) and psychotic experiences (PEs), respectively. The beads task was used to assess JTC bias. Time series analyses were conducted using data from T1 and T2 (N = 8666), excluding individuals who reported high psychosis levels at T0.

Although the prospective design resulted in low statistical power, the findings suggest that, compared to those without symptoms, individuals with lifetime affective dysregulation were more likely to progress from low/moderate psychosis levels (state of ‘aberrant salience’, one or two PEs) at T1 to high psychosis levels (‘frank psychosis’, three or more PEs or psychosis-related help-seeking behaviour) at T2 if the JTC bias was present [adj. relative risk ratio (RRR): 3.8, 95% confidence interval (CI) 0.8–18.6, p = 0.101]. Similarly, the JTC bias contributed to the persistence of high psychosis levels (adj. RRR: 12.7, 95% CI 0.7–239.6, p = 0.091).

We found some evidence that the JTC bias may contribute to psychosis progression and persistence in individuals with affective dysregulation. However, well-powered prospective studies are needed to replicate these findings.

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.

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.

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.

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.

Evidence suggests that cannabis use, childhood adversity, and urbanicity, in interaction with proxy measures of genetic risk, may facilitate onset of psychosis in the sense of early affective dysregulation becoming ‘complicated’ by, first, attenuated psychosis and, eventually, full-blown psychotic symptoms.

Data were derived from three waves of the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The impact of environmental risk factors (cannabis use, childhood adversity, and urbanicity) was analyzed across severity levels of psychopathology defined by the degree to which affective dysregulation was ‘complicated’ by low-grade psychotic experiences (‘attenuated psychosis’ – moderately severe) and, overt psychotic symptoms leading to help-seeking (‘clinical psychosis’ – most severe). Familial and non-familial strata were defined based on family history of (mostly) affective disorder and used as a proxy for genetic risk in models of family history × environmental risk interaction.

In proxy gene–environment interaction analysis, childhood adversity and cannabis use, and to a lesser extent urbanicity, displayed greater-than-additive risk if there was also evidence of familial affective liability. In addition, the interaction contrast ratio grew progressively greater across severity levels of psychosis admixture (none, attenuated psychosis, clinical psychosis) complicating affective dysregulation.

Known environmental risks interact with familial evidence of affective liability in driving the level of psychosis admixture in states of early affective dysregulation in the general population, constituting an affective pathway to psychosis. There is interest in decomposing family history of affective liability into the environmental and genetic components that underlie the interactions as shown here.

The jumping to conclusions (JTC) reasoning bias and decreased working memory performance (WMP) are associated with psychosis, but associations with affective disturbances (i.e. depression, anxiety, mania) remain inconclusive. Recent findings also suggest a transdiagnostic phenotype of co-occurring affective disturbances and psychotic experiences (PEs). This study investigated whether JTC bias and decreased WMP are associated with co-occurring affective disturbances and PEs.

Data were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). Trained interviewers administered the Composite International Diagnostic Interview (CIDI) at three time points in a general population sample (N = 4618). The beads and digit-span task were completed to assess JTC bias and WMP, respectively. CIDI was used to measure affective disturbances and an add-on instrument to measure PEs.

Compared to individuals with neither affective disturbances nor PEs, the JTC bias was more likely to occur in individuals with co-occurring affective disturbances and PEs [moderate psychosis (1–2 PEs): adjusted relative risk ratio (RRR) 1.17, 95% CI 0.98–1.41; and high psychosis (3 or more PEs or psychosis-related help-seeking behaviour): adjusted RRR 1.57, 95% CI 1.19–2.08], but not with affective disturbances and PEs alone, whereas decreased WMP was more likely in all groups. There was some evidence of a dose–response relationship, as JTC bias and decreased WMP were more likely in individuals with affective disturbances as the level of PEs increased or help-seeking behaviour was reported.

The findings suggest that JTC bias and decreased WMP may contribute to a transdiagnostic phenotype of co-occurring affective disturbances and PEs.

The incidence of psychotic disorders is elevated in some minority ethnic populations. However, we know little about the outcome of psychoses in these populations.

To investigate patterns and determinants of long-term course and outcome of psychoses by ethnic group following a first episode.

ÆSOP-10 is a 10-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.

There 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.

These findings suggest ethnic disparities in the incidence of psychoses extend, for some groups, to worse outcomes in multiple domains.

In recent years, the Kraepelinian dichotomy has been challenged in light of evidence on shared genetic and environmental factors for schizophrenia and bipolar disorder, but empirical efforts to identify a transdiagnostic phenotype of psychosis remain remarkably limited.

To investigate whether schizophrenia spectrum and bipolar disorder lie on a transdiagnostic spectrum with overlapping non-affective and affective psychotic symptoms.

Multidimensional item-response modelling was conducted on symptom ratings of the OPerational CRITeria (OPCRIT) system in 1168 patients with schizophrenia spectrum and bipolar disorder.

A bifactor model with one general, transdiagnostic psychosis dimension underlying affective and non-affective psychotic symptoms and five specific dimensions of positive, negative, disorganised, manic and depressive symptoms provided the best model fit and diagnostic utility for categorical classification.

Our findings provide support for including dimensional approaches into classification systems and a directly measurable clinical phenotype for cross-disorder investigations into shared genetic and environmental factors of psychosis.

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.

To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences.

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.

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).

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.

There are calls to use patient-reported outcomes (PROs) routinely across mental health services. However, the use of PROs in patients with psychosis has been questioned.

To examine the concepts and measures of four widely used PROs: treatment satisfaction, subjective quality of life, needs for care and the quality of the therapeutic relationship.

We conducted a literature search of academic databases on concepts, characteristics and psychometric properties of the four PROs in patients with psychosis.

Although numerous concepts and measures have been published, evidence on the methodological quality of existing PROs is limited. Measures designed to assess distinct PROs showed a considerable conceptual, operational and empirical overlap, and some of them also included specific aspects. The impact of symptoms and cognitive deficits appears unlikely to be of clinical significance.

The popularity of PROs has not been matched with progress in their conceptualisation and measurement. Based on current evidence, some recommendations can be made. Distinct and short measures with clinical relevance and sufficient psychometric properties should be preferred. Future research should optimise the validity and measurement precision of PROs, while reducing assessment burden.