Self-reported suicidal ideation among individuals with first episode psychosis and healthy controls: Findings from the international multicentre EU-GEI study.

INTRODUCTION: Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP. METHODS: In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach. RESULTS: In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation. CONCLUSIONS: This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis. LIMITATIONS: Cross-sectional study design, self-reported questionnaires.

The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study.

AIMS: Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample. METHODS: Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of 'Genetic' models (solely fitted with PRS-SZ), 'Environmental' models (solely fitted with each environmental stressor), 'Independent' models (with PRS-SZ and each environmental factor), and 'Interaction' models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models. RESULTS: There were no genes-environment associations. PRS-SZ was associated with positive dimensions (ß = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension. CONCLUSIONS: This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.

[Referral of a stabilized patient with psychotic disorder to the general practitioner: a pilot study]. / Verwijzing van gestabiliseerde patiënt met psychotische stoornis naar huisarts: kan dat? Een vooronderzoek.

BACKGROUND: In various countries, general practitioners (GPs) play an important role after treatment for non-affective psychotic disorder (NAPD) in mental health care. It is unclear how these patients fare. AIM: To compare the clinical course of patients largely recovered from NAPD and referred to the GP with the course of patients who remain in treatment at mental healthcare. METHOD: In a retrospective cohort study, 20 patients referred to GPs by mental healthcare (GP cohort) were compared to 20 patients who remained in treatment at mental healthcare (MH cohort), matched by age and gender. The clinical course was evaluated with the GPs and the mental healthcare practitioner, respectively. In addition, medication adherence and reasons for referral to the GP and mental healthcare were registered. RESULTS: In the GP cohort more patients (70%) deteriorated than in the MH cohort (5%) (p <0.001). In the MH cohort more patients showed therapeutic compliance (90%) than in the GP cohort (67%) (p = 0.078). After about four years, 65% of the patients in the GP cohort were back in treatment at mental healthcare. Among the 13 patients who were referred to the GP while functioning stably, more patients (54%) deteriorated than their matched counterparts in the MH cohort (8%) (p = 0.034). CONCLUSION: The results confirm that caution is needed in referring patients recovered from non-affective psychotic disorder to the GP.

Mentalization-based treatment for psychotic disorder: a rater-blinded, multi-center, randomized controlled trial.

BACKGROUND: Impaired mentalizing ability - an impaired ability to understand one's own and other people's behavior in terms of mental states - is associated with social dysfunction in non-affective psychotic disorder (NAPD). We tested whether adding mentalization-based treatment for psychotic disorder (MBTp) to treatment as usual (TAU) results in greater improvement in social functioning. METHODS: Multicenter, rater-blinded, randomized controlled trial. Eighty-four patients with NAPD were assigned to TAU or MBTp plus TAU. Patients in the MBTp group received 18 months of MBTp, consisting of weekly group sessions and one individual session per 2 weeks. Social functioning was measured using the Social Functioning Scale. We conducted ANCOVAs to examine the difference between treatment conditions directly after treatment and at 6-month follow-up and performed moderation and mediation analyses. RESULTS: Intention-to-treat analyses showed no significant differences between groups post-treatment (p = 0.31) but revealed the MBTp group to be superior to TAU at follow-up (p = 0.03). Patients in the MBTp group also seemed to perform better on measures of mentalizing ability, although evidence of a mediation effect was limited (p = 0.06). Lastly, MBTp treatment was less effective in chronic patients than in recent-onset patients (p = 0.049) and overall symptoms at baseline were mild, which may have reduced the overall effectiveness of the intervention. CONCLUSION: The results suggest that MBTp plus TAU may lead to more robust improvements in social functioning compared to TAU, especially for patients with a recent onset of psychosis.

Delegating Clozapine Monitoring to Advanced Nurse Practitioners: An Exploratory, Randomized Study to Assess the Effect on Prescription and Its Safety.

To test whether: (1) psychiatrists will prescribe clozapine more often if they can delegate the monitoring tasks to an advanced nurse practitioner (ANP), (2) clozapine monitoring by an ANP is at least as safe as monitoring by a psychiatrist. Patients from 23 Dutch outpatient teams were assessed for an indication for clozapine. ANPs affiliated to these teams were randomized to Condition A: clozapine monitoring by an ANP, or Condition B: monitoring by the psychiatrist. The safety of monitoring was evaluated by determining whether the weekly neutrophil measurements were performed. Staff and patients were blinded regarding the first hypothesis. Of the 173 patients with an indication for clozapine at baseline, only seven in Condition A and four in Condition B were prescribed clozapine (Odds Ratio = 2.24, 95% CI 0.61-8.21; p = 0.225). These low figures affected the power of this study. When we considered all patients who started with clozapine over the 15-month period (N = 49), the Odds Ratio was 1.90 (95% CI 0.93-3.87; p = 0.078). With regard to the safety of the monitoring of the latter group of patients, 71.2% of the required neutrophil measurements were performed in condition A and 67.3% in condition B (OR = 0.98; CI = 0.16-3.04; p = 0.98). Identifying patients with an indication for clozapine does not automatically lead to improved prescription rates, even when an ANP is available for the monitoring. Clozapine-monitoring performed by an ANP seemed as safe as that by a psychiatrist.

Risk of non-affective psychotic disorder or bipolar disorder in autism spectrum disorder: a longitudinal register-based study in the Netherlands.

BACKGROUND: Individuals with autism spectrum disorder (ASD) appear to be at increased risk of non-affective psychotic disorder (NAPD) and bipolar disorder (BD). However, most previous studies examined the co-occurrence of ASD and NAPD or BD, ignoring possible diagnostic bias and selection bias. We used longitudinal data from Dutch psychiatric case registers to assess the risk of NAPD or BD among individuals with ASD, and compared the results to those obtained for the Dutch population in earlier studies. METHODS: Individuals with ASD (n = 17 234) were followed up between 16 and 35 years of age. Kaplan-Meier estimates were used to calculate the risk of NAPD or BD. We conducted separate analyses to reduce possible bias, including an analysis among individuals diagnosed with ASD before age 16 years (n = 8337). RESULTS: Of the individuals with ASD, 23.50% (95% confidence interval 21.87-25.22) were diagnosed with NAPD and 3.79% (3.06-4.69) with BD before age 35 years. The corresponding figures for the general population were 0.91% (0.63-1.28) and 0.13% (0.08-0.20). Risk estimates were substantially lower, but still higher than general population estimates, when we restricted our analyses to individuals diagnosed with ASD before age 16, with 1.87% (1.33-2.61) being diagnosed with NAPD and 0.57% (0.21-1.53) with BD before age 25 years. The corresponding figures for the general population were 0.63% (0.44-0.86) and 0.08% (0.05-0.12). CONCLUSIONS: Individuals with ASD are at increased risk of NAPD or BD. This is likely not the result of diagnostic or selection bias.

Mentalizing impairment as a mediator between reported childhood abuse and outcome in nonaffective psychotic disorder.

Reported childhood abuse has been linked to the severity of clinical symptoms and social dysfunction in non-affective psychotic disorder. Impaired mentalizing ability may be one of the mechanisms accounting for this effect. This study examined whether impaired mentalizing mediates the effect of reported childhood abuse on positive symptoms, negative symptoms, and social dysfunction. Eighty-seven patients with non-affective psychotic disorder were examined. Reported childhood abuse was measured using the Childhood Experience of Care and Abuse interview. Additionally, the Social Functioning Scale and the Positive and Negative Syndrome Scale were used. The Hinting Task was used to measure mentalizing impairment. Reported childhood abuse was significantly related to the severity of positive and negative symptoms, not to social dysfunction. Reported childhood abuse was also related to mentalizing impairment. Mentalizing impairment was related to negative symptoms, but not to positive symptoms or social dysfunction. Mentalizing impairment accounted for 40% of the association between reported childhood abuse and negative symptoms, indicating partial mediation. A sensitivity analysis revealed that the mediating effect was only observed in those who reported fairly severe childhood abuse.

Evidence of an excessive gender gap in the risk of psychotic disorder among North African immigrants in Europe: a systematic review and meta-analysis.

PURPOSE: Epidemiological studies in the Netherlands have reported an excessive gender gap in the risk for non-affective psychotic disorder (NAPD) among immigrants from Morocco with a higher risk elevation in males compared to females. We examined the consistency of these findings and their generalizability to immigrants from the Maghreb (Mauritania, Morocco, Algeria, Tunisia and Libya) in other European countries. METHODS: Systematic review and meta-analysis. Medline, PsychINFO and EMBASE databases were searched for publications in the period from January 1970 to April 2014. We included incidence and prevalence studies of non-affective psychotic disorder (NAPD) among migrants from the Maghreb in Europe and studies of subclinical psychotic symptoms (SPS) in representative samples. A meta-analysis was performed on the subgroup of incidence studies. RESULTS: Five incidence and three prevalence studies of NAPD, and two prevalence studies of SPS, conducted in the Netherlands (n=7), Belgium (n=1), France (n=1) and Italy (n=1) met our inclusion criteria. Across all research designs, the risks of NAPD and SPS were consistently increased among male, not female immigrants from the Maghreb. The meta-analysis of incidence studies of NAPD yielded male-to-female risk ratios of 5.1 [95 % confidence interval (CI) 3.1-8.4] for migrants from the Maghreb, 2.0 (95 % CI 1.6-2.5) for other migrant groups, and 1.8 (95 % CI 1.3-2.5) for non-migrant Europeans. CONCLUSIONS: The marked gender gap in psychosis risk among migrants from the Maghreb appears a consistent finding, foremost among the Moroccan-Dutch. The small number of studies limits the strength of conclusions that can be drawn about countries other than the Netherlands. Achievement-expectation mismatch, social marginalization and an increased prevalence of illicit drug use are possible explanations.

Testing Ødegaard's selective migration hypothesis: a longitudinal cohort study of risk factors for non-affective psychotic disorders among prospective emigrants.

BACKGROUND: The selection hypothesis posits that the increased rates of psychosis observed among migrants are due to selective migration of people who are predisposed to develop the disorder. To test this hypothesis, we examined whether risk factors for psychosis are more prevalent among future emigrants. METHOD: A cohort of 49,321 Swedish military conscripts was assessed at age 18 years on cannabis use, IQ, psychiatric diagnosis, social adjustment, history of trauma and urbanicity of place of upbringing. Through data linkage we examined whether these exposures predicted emigration out of Sweden. We also calculated the emigrants' hypothetical relative risk compared with non-emigrants for developing a non-affective psychotic disorder. RESULTS: Low IQ [odds ratio (OR) 0.5, 95% confidence interval (95% CI) 0.3-0.9] and 'poor social adjustment' (OR 0.4, 95% CI 0.2-0.8) were significantly less prevalent among prospective emigrants, whereas a history of urban upbringing (OR 2.3, 95% CI 1.4-3.7) was significantly more common. Apart from a non-significant increase in cannabis use among emigrants (OR 1.6, 95% CI 0.8-3.1), there were no major group differences in any other risk factors. Compared to non-emigrants, hypothetical relative risks for developing non-affective psychotic disorder were 0.7 (95% CI 0.4-1.2) and 0.8 (95% CI 0.7-1.0), respectively, for emigrants narrowly and broadly defined. CONCLUSIONS: This study adds to an increasing body of evidence opposing the selection hypothesis.

Social disorganization of neighborhoods and incidence of psychotic disorders: a 7-year first-contact incidence study.

BACKGROUND: Environmental factors such as urban birth and ethnic minority position have been related to risk for psychotic disorders. There is some evidence that not only individual, but also neighborhood characteristics influence this risk. The aim of this study was to investigate social disorganization of neighborhoods and incidence of psychotic disorders. METHOD: The research was a 7-year first-contact incidence study of psychotic disorders in The Hague. Neighborhood characteristics included continuous, dichotomous and cumulative measures of socio-economic level, residential mobility, ethnic diversity, proportion of single person households, voter turnout, population density and crime level. Using multilevel Poisson regression analysis, incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of psychotic disorders were calculated for the indicators of neighborhood social disorganization. RESULTS: A total of 618 incident cases were identified. Neighborhood socio-economic level and residential mobility had the strongest association with incidence of psychotic disorders [individual-level adjusted Wald χ2 1 = 13.03 (p = 0.0003) and 5.51 (p = 0.02), respectively]. All but one (proportion of single person households) of the dichotomous neighborhood indicators were significantly associated with a higher IRR. The cumulative degree of neighborhood social disorganization was strongly and linearly associated with the incidence of psychotic disorders (trend test, Wald χ2 5 = 25.76, p = 0.0001). The IRR in neighborhoods with the highest degree of social disorganization was 1.95 (95% CI 1.38-2.75) compared with the lowest disorganization category. CONCLUSIONS: The findings suggest that the risk for developing a psychotic disorder is higher for people living in socially disorganized environments. Longitudinal studies are needed to investigate causality.

Psychotic reactions to daily life stress and dopamine function in people with severe hearing impairment.

BACKGROUND: Minor stresses measured in daily life have repeatedly been associated with increased momentary psychotic experiences, both in individuals with psychotic disorders and in persons who are genetically at an increased risk for these disorders. Severe hearing impairment (SHI) is an environmental risk factor for psychotic disorder, possibly due to the experience of social exclusion. The aim of the current study is to investigate whether people with SHI exhibit higher levels of psychotic reactivity to social stressors in daily life than normal-hearing controls and whether this reactivity is associated with decreased baseline dopamine (DA) D2/3 receptor availability and/or elevated DA release following a dexamphetamine challenge. METHOD: We conducted an experience sampling study in 15 young adults with SHI and 19 matched normal-hearing controls who had previously participated in a single photon emission computed tomography study measuring DA D2/3 receptor availability and DA release in response to dexamphetamine. RESULTS: The association between social stress and momentary psychotic experiences in daily life was stronger among SHI participants than among normal-hearing controls. Interactions between social stress and baseline striatal DA D2/3 receptor availability or DA release were not significant in multilevel models of momentary psychotic experiences including age, sex and tobacco use. CONCLUSIONS: While both elevated striatal DA release and elevated psychotic stress reactivity have been found in the same population defined by an environmental risk factor, SHI, their inter-relationship cannot be established. Further research is warranted to clarify the association between biological and psychological endophenotypes and psychosis risk.

Sexual minority status and psychotic symptoms: findings from the Netherlands Mental Health Survey and Incidence Studies (NEMESIS).

BACKGROUND: Ethnic minority position is associated with increased risk for psychotic outcomes, which may be mediated by experiences of social exclusion, defeat and discrimination. Sexual minorities are subject to similar stressors. The aim of this study is to examine whether sexual minorities are at increased risk for psychotic symptoms and to explore mediating pathways. METHOD: A cross-sectional survey was performed assessing cumulative incidence of psychotic symptoms with the Composite International Diagnostic Interview in two separate random general population samples (NEMESIS-1 and NEMESIS-2). Participants were sexually active and aged 18-64 years (n = 5927, n = 5308). Being lesbian, gay or bisexual (LGB) was defined as having sexual relations with at least one same-sex partner during the past year. Lifetime experience of any psychotic symptom was analysed using logistic regression, adjusted for gender, educational level, urbanicity, foreign-born parents, living without a partner, cannabis use and other drug use. RESULTS: The rate of any psychotic symptom was elevated in the LGB population as compared with the heterosexual population both in NEMESIS-1 [odds ratio (OR) 2.56, 95% confidence interval (CI) 1.71-3.84] and NEMESIS-2 (OR 2.30, 95% CI 1.42-3.71). Childhood trauma, bullying and experience of discrimination partly mediated the association. CONCLUSIONS: The finding that LGB orientation is associated with psychotic symptoms adds to the growing body of literature linking minority status with psychosis and other mental health problems, and suggests that exposure to minority stress represents an important mechanism.

An incidence study of diagnosed autism-spectrum disorders among immigrants to the Netherlands.

OBJECTIVE: To estimate the risk of developing autism-spectrum disorder (ASD) in children born to immigrants as compared with children of Dutch-born parents. METHOD: Retrospective, population-based cohort study of all live births (n = 106 953) between 1998 and 2007 in a circumscribed geographical region in the Netherlands. Cohort members were linked to the Psychiatric Case Register to identify diagnosed cases. RESULTS: A total of 518 cases of ASD were identified, including 150 children with autism and 368 children with Asperger syndrome or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). Children born to migrants from developing countries were at significantly lower risk of ASD [rate ratio (RR) = 0.6, 95% confidence interval (CI) 0.5-0.9] than children of Dutch-born parents. Within the ASD group, the risk for the subgroup with Asperger syndrome and PDD-NOS was reduced (RR = 0.4, 95% CI 0.3-0.6), whereas that for narrowly defined autism was non-significantly increased (RR = 1.4, 95% CI 0.9-2.4). Migrant groups did not differ in age at diagnosis. CONCLUSION: The results echo Swedish findings indicating a reversal of risk gradient in children of parents from developing countries, specifically a decreased risk for high-functioning and increased risk for low-functioning autism.

Childhood bullying and the association with psychosis in non-clinical and clinical samples: a review and meta-analysis.

BACKGROUND: Approximately 11% of schoolchildren are bullied on a regular basis. It has been argued that continuous exposure to stress is related to the development of psychotic symptoms. The current study sought to investigate whether being bullied in childhood is related to the development of psychotic symptoms. METHOD: A search of PubMed, PsycINFO and EMBASE was conducted. The reference lists of included papers were searched to identify other eligible papers. A meta-analysis was performed on a subgroup of studies. RESULTS: We found four clinical and 10 general population studies that met inclusion criteria. The results of the clinical studies were mixed. However, the results of the non-clinical studies provided more consistent evidence that school bullying is related to the development of non-clinical psychotic symptoms. Stronger associations were found with increased frequency and severity and longer duration of being bullied. We performed a meta-analysis on seven population-based studies, yielding unadjusted and adjusted odds ratios (ORs) of 2.7 [95% confidence interval (CI) 2.1-3.6] and 2.3 (95% CI 1.5-3.4) respectively. CONCLUSIONS: Although there is some evidence of an association between bullying and psychosis in clinical samples, the research is too sparse to draw any firm conclusions. However, population-based non-clinical studies support the role of bullying in the development of psychotic symptoms later in life. These findings are consistent with findings of an increased risk of psychotic symptoms among those exposed to other types of abuse.