The impact of study design on schizophrenia incidence estimates: A systematic review of Northern European studies 2008-2019.

The best estimates of the incidence of schizophrenia range more than 25-fold from 3 to 80 per 100,000 person-years. To what extent do differences in study design explain this wide variation? We selected all studies published between 2008-2019 reporting the incidence of schizophrenia in general populations of Northern Europe. We identified 17 estimates covering 85 million person-years and more than 15,000 individual cases. The estimates ranged from 4-72 per 100,000 person-years (median 30; interquartile range 13-41). We classified the estimates in terms of three study design factors (coverage of services, time frame, and diagnostic quality) and two population factors (urbanicity and age). A meta-regression model of the three design factors, using the two population factors as covariates, explained 91% of between-study variation. Studies performed in general psychiatric services reported similar estimates [incidence rate ratio 1.12 (95% confidence interval 0.88 to 1.43)] to those performed in specialized services. But studies applying a cumulative time frame to diagnosis reported fourfold higher estimates [4.04 (3.14 to 5.2)] than those applying a first-contact time frame. And studies based on clinical diagnoses reported lower estimates [0.55 (0.43 to 0.72)] than those based on standardized research diagnoses. The three study design factors by themselves explained 67% of between-study variation. When comparing incidence rates from different populations, distorsions arising from differences in study design can eclipse differences caused by schizophrenia risk factors, such as gender, age or migrant status.

Incidence of schizophrenia among migrants in the Netherlands: a direct comparison of first contact and longitudinal register approaches.

PURPOSE: To estimate the effect of selective sampling on first contact (FC) studies of the relation between migration and schizophrenia. METHODS: We compared the FC method directly with a more inclusive longitudinal psychiatric register (LPR) method, by letting both methods estimate age and sex adjusted incidence rate ratios (IRR) in the population of The Hague aged 20-54 years, for the three largest migrant groups (first and second generation Caribbean, Turkish, and Moroccan) relative to the native Dutch population. RESULTS: Both methods found that the adjusted IRR was higher for migrants than for native Dutch [all migrants IRR = 1.70 (95% Cl 1.30-2.21) for the LPR method and 1.91 (95% Cl 1.15-3.25) for the FC]. The IRR for Moroccans was significantly lower in the LPR [IRR 2.69 (95% 2.10-3.41)] than in the FC study [4.81 (3.41-6.68)]. The FC method was relatively more inclusive for migrants presenting at earlier ages or with shorter durations of prior treatment (DPT) than the native Dutch. This resulted in differential sampling and artificially higher IRRs for Moroccan and, to a lesser extent, Turkish migrants. CONCLUSION: We confirm that the incidence of schizophrenia is raised twofold for migrants compared to nonmigrants. Using the LPR method, however, IRR estimates were less pronounced for most migrant groups than in a high quality FC study conducted in the same population. The FC method may overestimate the risk of schizophrenia for migrant groups who seek first mental health at a relatively younger age, or who present directly with schizophrenia.

Pathways to psychosis: help-seeking behavior in the prodromal phase.

BACKGROUND: Knowledge of pathways to care by help-seeking patients prior to the onset of psychosis may help to improve the identification of at-risk patients. This study explored the history of help-seeking behavior in secondary mental health care services prior to the onset of the first episode of psychosis. METHOD: The psychiatric case register in The Hague was used to identify a cohort of 1753 people in the age range of 18-35 at first contact who developed a psychotic disorder in the period from 1 January 2005 to 31 December 2009. We retrospectively examined the diagnoses made at first contact with psychiatric services. RESULTS: 985 patients (56.2%) had been treated in secondary mental health services prior to the onset of psychosis. The most common disorders were mood and anxiety disorders (N=385 (39.1%)) and substance use disorders (N=211 (21.4%)). Affective psychoses were more often preceded by mood/anxiety disorders, while psychotic disorder NOS was more often preceded by personality disorder or substance abuse. The interval between first contact and first diagnosis of psychosis was approximately 69 months in cases presenting with mood and anxiety disorders and 127 months in cases presenting with personality disorders. DISCUSSION: This study confirms the hypothesis that the majority of patients with psychotic disorders had been help-seeking for other mental disorders in the secondary mental health care prior to the onset of psychosis.

Impact of p53 aberration on the progression of Adult T-cell Leukemia/Lymphoma.

Based on statistical analysis of its age-dependent occurrence, a multi-step carcinogenesis model has been proposed for Adult T-cell Leukemia/Lymphoma (ATLL). We have previously reported that the deletion of the p16 gene is a key event in ATLL progression. In the current study, we report for the first time that the aberrations of p16 and p53 are mutually exclusive in ATLL and either of the two events is sufficient for the ATLL progression. More than half of the patients had one of the two aberrations, and both aberrations emerged as significant markers for a poor prognosis.