Little is known about the effect of ethnicity on the response to antipsychotic medication in patients with schizophrenia.

To determine whether ethnicity moderates the response to antipsychotic medication in patients with schizophrenia, and whether this moderation is independent of confounders.

We analysed 18 short-term, placebo-controlled registration trials of atypical antipsychotic medications in patients with schizophrenia (N = 3880). A two-step, random-effects, individual patient data meta-analysis was applied to establish the moderating effect of ethnicity (White versus Black) on symptom improvement according to the Brief Psychiatric Rating Scale (BPRS) and on response, defined as >30% BPRS reduction. These analyses were corrected for baseline severity, baseline negative symptoms, age and gender. A conventional meta-analysis was performed to determine the effect size of antipsychotic treatment for each ethnic group separately.

In the complete data-set, 61% of patients were White, 25.6% of patients were Black and 13.4% of patients were of other ethnicities. Ethnicity did not moderate the efficacy of antipsychotic treatment: pooled β-coefficient for the interaction between treatment and ethnic group was −0.582 (95% CI −2.567 to 1.412) for mean BPRS change, with an odds ratio of 0.875 (95% CI 0.510–1.499) for response. These results were not modified by confounders.

Atypical antipsychotic medication is equally effective in both Black and White patients with schizophrenia. In registration trials, White and Black patients were overrepresented relative to other ethnic groups, limiting the generalisability of our findings.

Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR).

In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview.

At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment.

ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.

Subjective response (SR) to antipsychotic medication is relevant for quality of life, adherence and recovery. Here, we evaluate (1) the extent of variation in SR in patients using a single antipsychotic; (2) the association between subjective and symptomatic response; and (3) predictors of SR.

Open-label, single treatment condition with amisulpride in 339 patients with a first episode of a schizophrenia spectrum disorder, at most minimally treated before inclusion. Patients were evaluated at baseline, before start with amisulpride and after four weeks of treatment with the Subjective Wellbeing under Neuroleptic scale, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale for Schizophrenia.

(1) 26.8% of the patients had a substantial favorable SR, and 12.4% of the patients experienced a substantial dysphoric SR during treatment with amisulpride. (2) Modest positive associations were found between SR and 4 weeks change on symptom subscales (r = 0.268–0.390, p values < 0.001). (3) Baseline affective symptoms contributed to the prediction of subjective remission, demographic characteristics did not. Lower start dosage of amisulpride was associated with a more favorable SR (r = −0.215, p < 0.001).

We conclude that variation in individual proneness for an unfavorable SR is substantial and only modestly associated with symptomatic response. We need earlier identification of those most at risk for unfavorable SR and research into interventions to improve SR to antipsychotic medication in those at risk.

Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status.

We included FEP patients aged 18–64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status.

We examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations.

The higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations.

Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population.

To investigate whether omega-3 polyunsaturated fatty acid (n−3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis.

Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n−3 PUFA levels predicted change in cognitive performance.

The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months.

We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n−3 PUFAs.

The long-term outcome of first-episode schizophrenia needs improvement. Here, we evaluate the effectiveness of 5 years sustained specialist treatment (ST), ST including Parent groups (ST + P) or treatment as usual (TAU) on psychotic relapse and social functioning.

A three condition randomized, parallel assigned, single-blind efficacy trial, in which 198 first-episode psychosis (FEP) patients aged 15–28 years were included. The effect on time to first relapse, first relapse rates, mean number of relapses per patient, and time to the improvement of social functioning were analyzed using Cox regression or ANOVA.

We found no significant differences between treatment conditions in the ITT analysis concerning time to first relapse, nor first relapse rate. Mean number of relapses per patient differed at a trend level between ST, ST + P or TAU conditions, respectively: 0.72; 0.62 or 1.02 (p = 0.069). No evidence was found for differential effect of treatment conditions on social functioning.

Five years sustained ST of FEP nor addition of parent groups increased time to first relapse or reduced first relapse rate, compared to sustained TAU. Indications for favorable effects of parent groups were found on relapses per patient.

Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).

Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.

In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).

Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.

Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.

204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.

Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present.

Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.

We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.

There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).

Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

The high prevalence of smoking in individuals who are at ultra-high risk (UHR) for psychosis is well known and moderate cognitive deficits have also been found in UHR. However, the association between smoking and cognition in UHR is unknown and longitudinal studies are lacking.

A cohort study with 330 UHR individuals and 66 controls was conducted, as part of the European network of national schizophrenia networks studying gene–environment interactions (EU-GEI). At baseline and after 6, 12, and 24 months, smoking behavior was assessed with the Composite International Diagnostic Interview and cognitive functioning with a comprehensive test battery. Linear mixed-effects analyses were used to examine the multicross-sectional and prospective associations between (change in) smoking behavior and cognitive functioning, accounting for confounding variables.

At baseline, 53% of UHR and 27% of controls smoked tobacco. Smoking UHR and controls did not significantly differ from nonsmoking counterparts on the tested cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, or reasoning/problem solving) across different assessment times. Neither smoking cessation nor initiation was associated with a significant change in cognitive functioning in UHR.

No associations were found between smoking and cognitive impairment in UHR nor in controls. However, the fact that one in every two UHR individuals report daily use of tobacco is alarming. Our data suggest that UHR have fewer cognitive impairments and higher smoking cessation rates compared to patients with first-episode psychosis found in literature. Implications to promote smoking cessation in the UHR stage need further investigation.

The Netherlands has few financial barriers to access mental healthcare. However, in 2012, a sharp rise in co-payments was introduced.

We tested whether these increased co-payments coincided with less guideline-recommended continuous out-patient psychiatric care and more crisis interventions for patients with bipolar disorder.

A retrospective longitudinal cohort study on a health insurance registry was performed to examine trends, and deviations from these trends, in the healthcare received by patients with bipolar disorder. Deviations of trends were tested by time-series analyses (autoregressive integrated moving average). Subsequently, the relationship between significant deviations of trends and rise in co-payments was examined. Outcome measures were the level of standard out-patient care (out-patient psychiatric care and/or medication), crisis psychiatric care and somatic care.

The cohort comprised 3210 patients. During follow-up, the use of psychiatric care decreased and somatic care increased. The high rise in co-payments from 2012 onward coincided with decreases in standard out-patient care and increases in medication-only treatment, crisis psychiatric care and somatic care. Crisis intervention was highest when patients received only bipolar disorder medication. Patients receiving continuous standard out-patient care (62%) had less crisis intervention compared with the other patients.

Our data suggest that the rise of co-payments decreased guideline-recommended continuous out-patient psychiatric care among patients with bipolar disorder, and increased crisis psychiatric care.

Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.

We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case−control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.

Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91–1.59) for any discrimination and 1.79 (95% CI 1.19–1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12–2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65–3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).

Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.

This meta-analysis on peripheral blood compounds in drug-naïve first-episode patients with either schizophrenia or major depressive disorder (MDD) examined which compounds change following psychopharmacological treatment.

The Embase, PubMed and PsycINFO databases were systematically searched for longitudinal studies reporting measurements of blood compounds in drug-naïve first-episode schizophrenia or MDD.

For this random-effects meta-analysis, we retrieved a total of 31 studies comprising 1818 schizophrenia patients, and 14 studies comprising 469 MDD patients. Brain-derived neurotrophic factor (BDNF) increased following treatment in schizophrenia (Hedges' g (g): 0.55; 95% confidence interval (CI) 0.39–0.70; p < 0.001) and MDD (g: 0.51; CI 0.06–0.96; p = 0.027). Interleukin (IL)-6 levels decreased in schizophrenia (g: −0.48; CI −0.85 to −0.11; p = 0.011), and for MDD a trend of decreased IL-6 levels was observed (g: −0.39; CI −0.87 to 0.09; p = 0.115). Tumor necrosis factor alpha (TNFα) also decreased in schizophrenia (g: −0.34; CI −0.68 to −0.01; p = 0.047) and in MDD (g: −1.02; CI −1.79 to −0.25; p = 0.009). Fasting glucose levels increased only in schizophrenia (g: 0.26; CI 0.07–0.44; p = 0.007), but not in MDD. No changes were found for C-reactive protein, IL-1β, IL-2 and IL-4.

Psychopharmacological treatment has modulating effects on BDNF and TNFα in drug-naïve first-episode patients with either schizophrenia or MDD. These findings support efforts for further research into transdiagnostic preventive strategies and augmentation therapy for those with immune dysfunctions.

Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.

We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case–control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models.

In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06–2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02–3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03–1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672–2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose–response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06–96.47, p = 0.007).

The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.

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.

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.

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.

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.

Psychosis is associated with a reasoning bias, which manifests as a tendency to ‘jump to conclusions’. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes.

In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A ‘beads’ task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point.

There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ.

In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.

In Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: ‘minorities’). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population).

The European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of Diseases, 10th edition, codes F20–F33) from 13 sites.

The standardized incidence rates for minorities, combined into one category, varied from 12.2 in Valencia to 82.5 per 100 000 in Paris. These rates were generally high at sites with high rates for the reference population, and low at sites with low rates for the reference population. IRRs for minorities (combined into one category) varied from 0.70 (95% CI 0.32–1.53) in Valencia to 2.47 (95% CI 1.66–3.69) in Paris (test for interaction: p = 0.031). At most sites, IRRs were higher for persons from non-Western countries than for those from Western countries, with the highest IRRs for individuals from sub-Saharan Africa (adjusted IRR = 3.23, 95% CI 2.66–3.93).

Incidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.