Socioeconomic Disadvantage in Childhood and Later Risk of Schizophrenia and Other Psychoses: National Register-Based Studies

Aim: The aim of this thesis was to analyse the association between various types of indicators of socioeconomic disadvantage in childhood and the risk of later developing schizophrenia and other psychoses. Furthermore, the importance of socioeconomic disadvantage was explored in relation to immigration, school performance, and an indicator of genetic liability for psychosis. Methods: The study populations were based on register linkages of several Swedish registers. They were identified in the Multi-Generation Register and were followed in the National Patient Register regarding admissions for schizophrenia and other psychoses. Exposure of up to seven different indicators of childhood socioeconomic disadvantage (housing, single-parent household, parental socioeconomic classification, parental employment, households receiving social welfare benefits, parental early retirement, and parental education) was obtained via linkage to the national Population and Housing Censuses performed every 5 years between 1960 and 1990, and the Income and Taxation Registers. School performance data was obtained via the School Register. Hazard Ratios were estimated by multivariate Cox proportional hazard models. Results: Five of seven indicators of childhood socioeconomic disadvantage were associated with later risk of schizophrenia and other psychoses (fully adjusted HRs from 1.2 to 1.7) (study I-IV). The risks increased with increasing number of exposures to the different indicators of socioeconomic disadvantage (study I, IV). First and second generation immigrants had increased risks for schizophrenia and other psychoses (HRs 1.4-3.1 and 1.0-2.0 respectively), compared with the Swedish majority population. These risks decreased considerably after adjusting for indicators of socioeconomic disadvantage (study II). In an adoption design (study III) both indicators of genetic liability (HR=4.7) and disadvantaged socioeconomic position (HRs 1.2-2.0) were independently associated with an increased risk for non-affective psychosis. The risk was considerably higher among adoptees exposed to both types of indicators (HRs from 5.7 to 15.0). Synergy indexes were larger than 1 (3.2, 2.6, 1.2). In study IV, risks were increased for schizophrenia (HR=1.9), other non-affective psychoses (HR=3.0), and affective psychoses (HR=2.3) in association with poor average grade, compared with those with a midrange average grade at graduation from compulsory school. Adjustments for socioeconomic position of the family reduced these estimates marginally (schizophrenia: HR=1.7, other non-affective psychoses: HR=2.8, affective psychoses: HR=2.1). Conclusion: The results indicate that socioeconomic disadvantage during childhood or foetal life contributes to the risk of developing schizophrenia and other psychoses. Furthermore, this risk may even be relatively higher in individuals with a genetic liability for psychosis. Thus, influencing the social situation in childhood may have beneficial effects on the occurrence of psychosis. Socioeconomic disadvantage may also contribute to the increased risk of psychoses in immigrants. However, childhood socioeconomic disadvantage did not substantially affect the risk of psychoses associated with low school performance. In summary, there is support for social disadvantage in the aetiology of psychosis. This knowledge may open up for preventive methods on a societal level, perhaps targeting vulnerable groups as immigrants and individuals with genetic liability

Perinatal exposure to traffic-related air pollution and autism spectrum disorders

Background: Studies from the United States indicate that exposure to air pollution in early life is associated with autism spectrum disorders (ASD) in children, but the evidence is not consistent with European data. Objective: We aimed to investigate the association between exposure to air pollution from road traffic and the risk of ASD in children, with careful adjustment for socioeconomic and other confounders. Method: Children born and residing in Stockholm, Sweden, during 1993–2007 with an ASD diagnosis were identified through multiple health registers and classified as cases (n = 5,136). A randomly selected sample of 18,237 children from the same study base constituted controls. Levels of nitrogen oxides (NOx) and particulate matter with diameter ≤ 10 μm (PM10) from road traffic were estimated at residential addresses during mother’s pregnancy and the child’s first year of life by dispersion models. Odds ratios (OR) and 95% confidence intervals (CI) for ASD with or without intellectual disability (ID) were estimated using logistic regression models after conditioning on municipality and calendar year of birth as well as adjustment for potential confounders. Result: Air pollution exposure during the prenatal period was not associated with ASD overall (OR = 1.00; 95% CI: 0.86, 1.15 per 10-μg/m3 increase in PM10 and OR = 1.02; 95% CI: 0.94, 1.10 per 20-μg/m3 increase in NOx during mother’s pregnancy). Similar results were seen for exposure during the first year of life, and for ASD in combination with ID. An inverse association between air pollution exposure and ASD risk was observed among children of mothers who moved to a new residence during pregnancy. Conclusion: Early-life exposure to low levels of NOx and PM10 from road traffic does not appear to increase the risk of ASD.NonePublishe

Perinatal exposure to traffic-related air pollution and autism spectrum disorders

Background: Studies from the United States indicate that exposure to air pollution in early life is associated with autism spectrum disorders (ASD) in children, but the evidence is not consistent with European data. Objective: We aimed to investigate the association between exposure to air pollution from road traffic and the risk of ASD in children, with careful adjustment for socioeconomic and other confounders. Method: Children born and residing in Stockholm, Sweden, during 1993–2007 with an ASD diagnosis were identified through multiple health registers and classified as cases (n = 5,136). A randomly selected sample of 18,237 children from the same study base constituted controls. Levels of nitrogen oxides (NOx) and particulate matter with diameter ≤ 10 μm (PM10) from road traffic were estimated at residential addresses during mother’s pregnancy and the child’s first year of life by dispersion models. Odds ratios (OR) and 95% confidence intervals (CI) for ASD with or without intellectual disability (ID) were estimated using logistic regression models after conditioning on municipality and calendar year of birth as well as adjustment for potential confounders. Result: Air pollution exposure during the prenatal period was not associated with ASD overall (OR = 1.00; 95% CI: 0.86, 1.15 per 10-μg/m3 increase in PM10 and OR = 1.02; 95% CI: 0.94, 1.10 per 20-μg/m3 increase in NOx during mother’s pregnancy). Similar results were seen for exposure during the first year of life, and for ASD in combination with ID. An inverse association between air pollution exposure and ASD risk was observed among children of mothers who moved to a new residence during pregnancy. Conclusion: Early-life exposure to low levels of NOx and PM10 from road traffic does not appear to increase the risk of ASD.Swedish Research Council for Health, Working Life and Welfare (FORTE), 2012-0573, 2015-00289Swedish Research Council, 2011-3060Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS)Swedish Innovation Agency (VINNOVA), 259-2012-24Swedish Research Council, Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM), 340-2013-5867HKH Kronprinsessan Lovisas förening for barnasjukvårdStrategic Research Program in Epidemiology at Karolinska InstitutetPublishe

Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots.

In the present study, we tested whether there were proteomic differences in blood between schizophrenia patients after the initial onset of the disorder and controls; and whether those differences were also present at birth among neonates who later developed schizophrenia compared to those without a psychiatric admission. We used multiple reaction monitoring mass spectrometry to quantify 77 proteins (147 peptides) in serum samples from 60 first-onset drug-naive schizophrenia patients and 77 controls, and 96 proteins (152 peptides) in 892 newborn blood-spot (NBS) samples collected between 1975 and 1985. Both serum and NBS studies showed significant alterations in protein levels. Serum results revealed that Haptoglobin and Plasma protease C1 inhibitor were significantly upregulated in first-onset schizophrenia patients (corrected P < 0.05). Alpha-2-antiplasmin, Complement C4-A and Antithrombin-III were increased in first-onset schizophrenia patients (uncorrected P-values 0.041, 0.036 and 0.013, respectively) and also increased in newborn babies who later develop schizophrenia (P-values 0.0058, 0.013 and 0.044, respectively). We also tested whether protein abundance at birth was associated with exposure to an urban environment during pregnancy and found highly significant proteomic differences at birth between urban and rural environments. The prediction model for urbanicity had excellent predictive performance in both discovery (area under the receiver operating characteristic curve (AUC) = 0.90) and validation (AUC = 0.89) sample sets. We hope that future biomarker studies based on stored NBS samples will identify prognostic disease indicators and targets for preventive measures for neurodevelopmental conditions, particularly those with onset during early childhood, such as autism spectrum disorder

Which outcome domains are important in palliative care and when? An international expert consensus workshop, using the nominal group technique

© The Author(s) 2019. Background: When capturing patient-level outcomes in palliative care, it is essential to identify which outcome domains are most important and focus efforts to capture these, in order to improve quality of care and minimise collection burden. Aim: To determine which domains of palliative care are most important for measurement of outcomes, and the optimal time period over which these should be measured. Design: An international expert consensus workshop using nominal group technique. Data were analysed descriptively, and weighted according to ranking (1–5, lowest to highest priority) of domains. Participants’ rationales for their choices were analysed thematically. Setting/participants: In all, 33 clinicians and researchers working globally in palliative care outcome measurement participated. Two groups (n = 16; n = 17) answered one question each (either on domains or optimal timing). This workshop was conducted at the 9th World Research Congress of the European Association for Palliative Care in 2016. Results: Participants’ years of experience in palliative care and in outcome measurement ranged from 10.9 to 14.7 years and 5.8 to 6.4 years, respectively. The mean scores (weighted by rank) for the top-ranked domains were ‘overall wellbeing/quality of life’ (2.75), ‘pain’ (2.06), and ‘information needs/preferences’ (2.06), respectively. The palliative measure ‘Phase of Illness’ was recommended as the preferred measure of time period over which the domains were measured. Conclusion: The domains of ‘overall wellbeing/quality of life’, ‘pain’, and ‘information needs/preferences’ are recommended for regular measurement, assessed using ‘Phase of Illness’. International adoption of these recommendations will help standardise approaches to improving the quality of palliative care

Attention and distraction in children with learning disabilities

Note:Two experiments assessed the development of attention and resistance to distraction in normal and learning disabled children using a reaction time task. Learning disabled children had slower reaction times than normal children on all aspects of the task and were relatively less able to sustain attention, but did not differ from normal children in the ability to attend selectively to relevant information in the presence of distraction. Increasing the attentional demands of the task affected the performance of normal children to a greater extent than that of the learning disabled children, suggesting that the two groups may be employing different attentional strategies. The poorer performance of the learning disabled children, coupled with the lack of developmental interactions, suggests that their attentional problem may be due to a deficit rather than a developmental lag. The results also suggest that the deficit is at a basic level of attention, rather than at a higher level, such as selective attention.Le développement de l'attention et de la résistance à la distraction fut étudié au cours de deux expériences de temps de réaction impliquant des enfants normaux et des enfants ayant des troubles d'apprentissage. Ces cerniers ont produit, pour toutes les conditions d'attention, des temps de réaction plus longs que ceux des enfants normaux, ils avaient aussi relativement plus de difficulté à garder une attention soutenue, mais ils ne se distinguaient pas des enfants normaux pour ce qui est de porter sélectivement attention à l'information pertinente en présence de distracteurs. L’augmentation du fardeau d'attention exigé par la tâche s'avère affecter davantage le rendement des enfants normaux que de ceux ayant des troubles d'apprentissage, ce qui suggère que les deux groupes appliquent possiblement des stratégies d'attention différentes. L'infériorité de rendement des enfants ayant des troubles d’apprentissage et la constatation que cette infériorité ne varie pas avec le groupe d’âge suggèrent un déficit plutôt qu'un retard de développement comme facteur responsable du problème d'attention. Les résultats suggèrent de plus que le déficit se situerait à un niveau élémentaire du processus d'attention plutôt qu'à un niveau élevé, tel la selectivité