Jean-Paul Selten

Urbanization and psychosis: a study of 1942-1978 birth cohorts in The Netherlands.

BACKGROUND Urban birth is associated with later schizophrenia. This study examined whether this finding is diagnosis-specific and which individuals are most at risk. METHODS All live births recorded between 1942 and 1978 in any of the 646 Dutch municipalities were followed-up through the National Psychiatric Case Register for first psychiatric admission for psychosis between 1970 and 1992 (N = 42115). RESULTS Urban birth was linearly associated with later schizophrenia (incidence rate ratio linear trend (IRR), 1.39; 95% confidence interval (95% CI), 1.36-1.42), affective psychosis (IRR, 1.18; 95% CI, 1.15-1.21) and other psychosis (IRR, 1.27; 95% CI, 1.24-1.30). Individuals born in the highest category of the three-level urban exposure were around twice as likely to develop schizophrenia. Associations were stronger for men and for individuals with early age of onset. The effect of urban birth was also stronger in the more recent birth cohorts. CONCLUSIONS There are quantitative differences between diagnostic categories in the strength of the association between urban birth and later psychiatric disorder. High rates of psychosis in urban areas may be the result of environmental factors associated with urbanization, the effect of which appears to be increasing over successive generations.

Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders: Results From a Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE Inflammatory processes may play a role in the pathophysiology of schizophrenia. The aim of this study was to determine the efficacy of adjuvant treatment with aspirin (acetylsalicylic acid) in schizophrenia spectrum disorders. METHOD This randomized, double-blind, placebo-controlled study was conducted between May 2004 and August 2007. Seventy antipsychotic-treated inpatients and outpatients from 10 psychiatric hospitals in The Netherlands with a DSM-IV-diagnosed schizophrenia spectrum disorder were included. Patients were randomized to adjuvant treatment with aspirin 1000 mg/d or placebo. During a 3-month follow-up, psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Other assessments included cognitive tests and immune function. The primary efficacy outcome was the change in total PANSS score. Secondary outcomes were changes in the PANSS subscales and cognitive test results. RESULTS Mixed-effect models showed a 4.86-point (95% CI, 0.91 to 8.80) and 1.57-point (95% CI, 0.06 to 3.07) larger decrease in the aspirin group compared to the placebo group on the total and positive PANSS score, respectively. Similar but not statistically significant results were observed for the other PANSS subscale scores. Treatment efficacy on total PANSS score was substantially larger in patients with the more altered immune function (P = .018). Aspirin did not significantly affect cognitive function. No substantial side effects were recorded. CONCLUSION Aspirin given as adjuvant therapy to regular antipsychotic treatment reduces the symptoms of schizophrenia spectrum disorders. The reduction is more pronounced in those with the more altered immune function. Inflammation may constitute a potential new target for antipsychotic drug development. TRIAL REGISTRATION controlled-trials.com Identifier: ISRCTN27745631.

The Social Defeat Hypothesis of Schizophrenia: An Update

According to the social defeat (SD) hypothesis, published in 2005, long-term exposure to the experience of SD may lead to sensitization of the mesolimbic dopamine (DA) system and thereby increase the risk for schizophrenia. The hypothesis posits that SD (ie, the negative experience of being excluded from the majority group) is the common denominator of 5 major schizophrenia risk factors: urban upbringing, migration, childhood trauma, low intelligence, and drug abuse. The purpose of this update of the literature since 2005 is to answer 2 questions: (1) What is the evidence that SD explains the association between schizophrenia and these risk factors? (2) What is the evidence that SD leads to sensitization of the mesolimbic DA system? The evidence for SD as the mechanism underlying the increased risk was found to be strongest for migration and childhood trauma, while the evidence for urban upbringing, low intelligence, and drug abuse is suggestive, but insufficient. Some other findings that may support the hypothesis are the association between risk for schizophrenia and African American ethnicity, unemployment, single status, hearing impairment, autism, illiteracy, short stature, Klinefelter syndrome, and, possibly, sexual minority status. While the evidence that SD in humans leads to sensitization of the mesolimbic DA system is not sufficient, due to lack of studies, the evidence for this in animals is strong. The authors argue that the SD hypothesis provides a parsimonious and plausible explanation for a number of epidemiological findings that cannot be explained solely by genetic confounding.

Schizophrenia in Surinamese and Dutch Antillean immigrants to The Netherlands: evidence of an increased incidence.

BACKGROUND Reports of an increased incidence of schizophrenia in Afro-Caribbean immigrants to the UK are a matter of much debate. It is of interest, therefore, that in the 1970s and 1980s many immigrants from Surinam and The Netherlands Antilles have settled in The Netherlands. The purpose of our study was to compare the risk of a first admission for schizophrenia for Surinamese- and Antillean-born persons aged 15-39 years to that for their Dutch-born peers in the period 1983-1992. METHODS We used data from the Dutch psychiatric registry. Age-adjusted relative risks were calculated using Poisson regression analysis. RESULTS The risk for the immigrants was found to be three to four times higher than that for the Dutch-born. Age-adjusted relative risks were significantly higher for male than for female immigrants. CONCLUSIONS The results provide evidence of an increased incidence in these immigrant groups and support similar findings on Afro-Caribbeans in the UK. Migration from Surinam was on such a large scale that selective migration of persons at risk for the disorder is unlikely to account entirely for these findings.

Incidence of schizophrenia among ethnic minorities in the Netherlands : A four-year first-contact study

There is only one previous report on the first-contact incidence of schizophrenia among immigrants in the Netherlands, which was based on a small number of cases, particularly for second generation immigrants. We conducted another two-year first-contact incidence study in the same geographical area, combined the data of both studies and compared risks over all four years. The incidence of schizophrenia was increased for all first generation non-Western immigrants. The risk was particularly high for second generation immigrants: the age- and gender-adjusted incidence rate ratio was 5.8 (95% CI, 2.9-11.4) for Moroccans, 2.9 (1.6-5.0) for Surinamese, 2.3 (1.0-5.4) for Turks, and 3.5 (1.8-6.8) for immigrants from other non-Western countries.

Migration and schizophrenia.

Purpose of review An exploration of the evidence that a history of migration is a risk factor for schizophrenia and an evaluation of those studies that seek an explanation for this. Recent findings A meta-analysis found an increased risk for schizophrenia among first-generation and second-generation migrants and found a particularly high risk for migrants from countries where the majority of the population was Black. The latter finding was confirmed and extended by a large first-contact incidence study in the UK, which found excessive risks for schizophrenia and mania in the African–Caribbean and black–African sections of the population. A very high risk of schizophrenia has also been reported for Moroccan males in the Netherlands. The explanation for these findings is uncertain. Social adversity, racial discrimination, family dysfunction, unemployment and poor housing conditions have been proposed as contributing factors. According to one hypothesis, the chronic experience of social defeat disturbs dopamine function in the brain. Summary A personal or family history of migration is a high risk factor for schizophrenia and there is now strong evidence against selective migration as the explanation. There is an increasing interest in the impact of social stressors on brain functioning and on the pathogenesis of schizophrenia.

Hypothesis: social defeat is a risk factor for schizophrenia?

The increased schizophrenia risks for residents of cities with high levels of competition and for members of disadvantaged groups (for example migrants from low- and middle-income countries, people with low IQ, hearing impairments or a history of abuse) suggest that social factors are important for aetiology. Dopaminergic dysfunctioning is a key mechanism in pathogenesis. This editorial is a selective literature review to delineate a mechanism whereby social factors can disturb dopamine function in the brain. Experiments with rodents have shown that social defeat leads to dopaminergic hyperactivity and to behavioural sensitisation, whereby the animal displays an enhanced behavioural and dopamine response to dopamine agonists. Neuroreceptor imaging studies have demonstrated the same phenomena in patients with schizophrenia who had never received antipsychotics. In humans, the chronic experience of social defeat may lead to sensitisation (and/or increased baseline activity) of the mesolimbic dopamine system and thereby increase the risk for schizophrenia.

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.

Treatment adherence therapy in people with psychotic disorders: randomised controlled trial

BACKGROUND Interventions to improve adherence to treatment in people with psychotic disorders have produced inconclusive results. We developed a new treatment, treatment adherence therapy (TAT), whose intervention modules are tailored to the reasons for an individuals non-adherence. AIMS To examine the effectiveness of TAT with regard to service engagement and medication adherence in out-patients with psychotic disorders who engage poorly. METHOD Randomised controlled study of TAT v. treatment as usual (TAU) in 109 out-patients. Most outcome measurements were performed by masked assessors. We used intention-to-treat multivariate analyses (Dutch Trial Registry: NTR1159). RESULTS Treatment adherence therapy v. TAU significantly benefited service engagement (Cohens d = 0.48) and medication adherence (Cohens d = 0.43). Results remained significant at 6-month follow-up for medication adherence. Near-significant effects were also found regarding involuntary readmissions (1.9% v. 11.8%, P = 0.053). Symptoms and quality of life did not improve. CONCLUSIONS Treatment adherence therapy helps improve engagement and adherence, and may prevent involuntary admission.

Psychotic illness after prenatal exposure to the 1953 Dutch Flood Disaster

We tested the hypothesis that maternal stress during pregnancy increases the risk of non-affective psychosis for the child. The concept of non-affective psychosis includes the ICD categories schizophrenic disorder, paranoid state and other non-organic psychosis. Data from the Dutch Psychiatric Registry were examined for an effect of the Flood Disaster of 1 February 1953. On this day, a gale caused a flood in the South-west of The Netherlands and 1835 people perished. Our study concerned the 19 villages where mortality exceeded 0.25%. The risk of non-affective psychosis for the cohort born in the period February-October 1953 was compared to the risks for the cohorts born in the corresponding periods of the previous and subsequent 2 years. The relative risk of non-affective psychosis for those exposed during gestation was 1.8 [95% Confidence Interval (CI): 0.9-3.5]. Thus, our study failed to demonstrate a significant association between prenatal exposure to maternal stress and risk of non-affective psychosis. The possible explanations for this finding are discussed.