Risk of non-affective psychotic disorder and post-traumatic stress disorder by refugee status in Sweden

BACKGROUND: Refugees have different experiences of obtaining a refugee status, however it remains unclear if this affects their risk of psychiatric disorders. The aim of this study was to investigate whether risk for non-affective psychotic disorder (NAPD) and post-traumatic stress disorder (PTSD) differs between quota refugees (resettled from refugee camps) and non-quota refugees (former asylum seekers). METHOD: A register-based cohort with a sample size of 52 561 refugees in Sweden starting 1 January 1997 ending 31 December 2011. EXPOSURE: refugee status (quota or non-quota refugees). Cox regression models estimated adjusted HRs with 95% CIs for NAPD (International Classification of Diseases, Tenth Revision (ICD-10), F20-29) and PTSD (ICD-10, F43.1) by refugee status. RESULTS: There were more non-quota refugees (77.0%) than quota refugees (23.0%). In total we identified 401 cases of NAPD, 1.0% among quota refugees and 0.7% among non-quota refugees, and 1070 cases of PTSD, 1.9% among quota refugees and 2.1% among non-quota refugees. Male quota refugees were at increased risk for NAPD compared with male non-quota refugees (HRmale=1.41, 95% CI 1.09 to 1.82 and HRfemale=0.65, 95% CI 0.42 to 1.00). All quota refugees were at a reduced risk of PTSD compared with non-quota refugees (HR=0.74, 95% CI 0.64 to 0.87). CONCLUSIONS: This study suggests that risk of NAPD and PTSD varies for quota and non-quota refugees, highlighting the possibility that different experiences of the migration process differentiate the risk of psychiatric disorders among refugees

Association of neighbourhood migrant density and risk of non-affective psychosis: a national, longitudinal cohort study

BACKGROUND: Elevated risk of psychotic disorders in migrant groups is a public mental health priority. We investigated whether living in areas of high own-region migrant density was associated with reduced risk of psychotic disorders among migrants and their children, and whether generation status, probable visible minority status, or region-of-origin affected this relationship. METHODS: We used the Swedish registers to identify migrants and their children born between Jan 1, 1982, and Dec 31, 1996, and living in Sweden on or after their 15th birthday. We tracked all included participants from age 15 years or date of migration until emigration, death, or study end (Dec 31, 2016). The outcome was an ICD-10 diagnosis of non-affective psychosis (F20-29). We calculated own-region and generation-specific own-region density within the 9208 small areas for market statistics neighbourhoods in Sweden, and estimated the relationship between density and diagnosis of non-affective psychotic disorders using multilevel Cox proportional hazards models, adjusting for individual confounders (generation status, age, sex, calendar year, lone dwelling, and time since migration [migrants only]), family confounders (family income, family unemployment, and social welfare), and neighbourhood confounders (deprivation index, population density, and proportion of lone dwellings), and using the Akaike information criterion (AIC) to compare model fit. FINDINGS: Of 468 223 individuals included in the final cohort, 4582 (1·0%) had non-affective psychotic disorder. Lower own-region migrant density was associated with increased risk of psychotic disorders among migrants (hazard ratio [HR] 1·05, 95% CI 1·02-1·07 per 5% decrease) and children of migrants (1·03, 1·01-1·06), after adjustment. These effects were stronger for probable visible minority migrants (1·07, 1·04-1·11), including migrants from Asia (1·42, 1·15-1·76) and sub-Saharan Africa (1·28, 1·15-1·44), but not migrants from probable non-visible minority backgrounds (0·99, 0·94-1·04). Among migrants, adding generation status to the measure of own-region density provided a better fit to the data than overall own-region migrant density (AIC 36 103 vs 36 106, respectively), with a 5% decrease in generation-specific migrant density corresponding to a HR of 1·07 (1·04-1·11). INTERPRETATION: Migrant density was associated with non-affective psychosis risk in migrants and their children. Stronger protective effects of migrant density were found for probable visible minority migrants and migrants from Asia and sub-Saharan Africa. For migrants, this risk intersected with generation status. Together, these results suggest that this health inequality is socially constructed. FUNDING: Wellcome Trust, Royal Society, Mental Health Research UK, University College London, National Institute for Health Research, Swedish Research Council, and FORTE

Refugee migration and risk of schizophrenia and other non-affective psychoses: cohort study of 1.3 million people in Sweden.

OBJECTIVE:  To determine whether refugees are at elevated risk of schizophrenia and other non-affective psychotic disorders, relative to non-refugee migrants from similar regions of origin and the Swedish-born population. DESIGN:  Cohort study of people living in Sweden, born after 1 January 1984 and followed from their 14th birthday or arrival in Sweden, if later, until diagnosis of a non-affective psychotic disorder, emigration, death, or 31 December 2011. SETTING:  Linked Swedish national register data. PARTICIPANTS:  1 347 790 people, including people born in Sweden to two Swedish-born parents (1 191 004; 88.4%), refugees (24 123; 1.8%), and non-refugee migrants (132 663; 9.8%) from four major refugee generating regions: the Middle East and north Africa, sub-Saharan Africa, Asia, and Eastern Europe and Russia. MAIN OUTCOME MEASURES:  Cox regression analysis was used to estimate adjusted hazard ratios for non-affective psychotic disorders by refugee status and region of origin, controlling for age at risk, sex, disposable income, and population density. RESULTS:  3704 cases of non-affective psychotic disorder were identified during 8.9 million person years of follow-up. The crude incidence rate was 38.5 (95% confidence interval 37.2 to 39.9) per 100 000 person years in the Swedish-born population, 80.4 (72.7 to 88.9) per 100 000 person years in non-refugee migrants, and 126.4 (103.1 to 154.8) per 100 000 person years in refugees. Refugees were at increased risk of psychosis compared with both the Swedish-born population (adjusted hazard ratio 2.9, 95% confidence interval 2.3 to 3.6) and non-refugee migrants (1.7, 1.3 to 2.1) after adjustment for confounders. The increased rate in refugees compared with non-refugee migrants was more pronounced in men (likelihood ratio test for interaction χ(2) (df=2) z=13.5; P=0.001) and was present for refugees from all regions except sub-Saharan Africa. Both refugees and non-refugee migrants from sub-Saharan Africa had similarly high rates relative to the Swedish-born population. CONCLUSIONS:  Refugees face an increased risk of schizophrenia and other non-affective psychotic disorders compared with non-refugee migrants from similar regions of origin and the native-born Swedish population. Clinicians and health service planners in refugee receiving countries should be aware of a raised risk of psychosis in addition to other mental and physical health inequalities experienced by refugees

Suicide risk in people with post-traumatic stress disorder: a cohort study of 3.1 million people in Sweden

BACKGROUND: It is unclear whether post-traumatic stress disorder [PTSD] is associated with suicide risk in the general population, whether this differs by sex, or what the population impact of PTSD is for suicide. METHODS: We constructed a nationwide cohort of all people living in Sweden, born 1973-1997, followed from their 14th birthday (or immigration, if later) until suicide, other death, emigration or 31 December 2016. We used Cox proportional hazards regression to estimate hazard ratios [HR], and calculated the population impact of PTSD on suicide. We included sensitivity analyses to explore effects of outcome and exposure definitions, and to account for potential competing risks. RESULTS: Of 3,177,706 participants, 22,361 (0•7%) were diagnosed with PTSD, and 6,319 (0•2%) died by suicide over 49•2 million person-years. Compared with women and men without PTSD, suicide rates were 6•74 (95%CI: 5•61-8•09) and 3•96 (95%CI: 3•12-5•03) times higher in those with PTSD, respectively, after sociodemographic adjustment. Suicide rates remained elevated in women (HR: 2•61; 95%CI: 2•16-3•14) and men (HR: 1•67; 95%CI: 1•31-2•12) after adjustment for previous psychiatric conditions; attenuation was driven by previous non-fatal suicide attempts. Findings were insensitive to definitions or competing risks. If causal, 1•6% (95%CI: 1•2-2•1) of general population suicides could be attributed to PTSD, and up to 53.7% (95%CI: 46.1-60.2) in people with PTSD. LIMITATIONS: Residual confounding remains possible due to depressive and anxiety disorders diagnosed in primary care but unrecorded in these registers. CONCLUSIONS: Clinical guidelines for the management of people with PTSD should recognise increased suicide risk

Inequalities in Psychiatric Service Use and Mortality by Migrant Status Following a First Diagnosis of Psychotic Disorder: A Swedish Cohort Study of 1.3M People

It is unclear whether inequalities in mental healthcare and mortality following the onset of psychosis exist by migrant status and region-of-origin. We investigated whether (1) mortality (including by major causes of death); (2) first admission type (inpatient or outpatient); (3) in-patient length of stay (LOS) at first diagnosis for psychotic disorder presentation, and; (4) time-to-readmission for psychotic disorder differed for refugees, non-refugee migrants, and by region-of-origin. We established a cohort of 1 335 192 people born 1984-1997 and living in Sweden from January 1, 1998, followed from their 14th birthday or arrival to Sweden, until death, emigration, or December 31, 2016. People with ICD-10 psychotic disorder (F20-33; N = 9399) were 6.7 (95% confidence interval [95%CI]: 5.9-7.6) times more likely to die than the general population, but this did not vary by migrant status (P = .15) or region-of-origin (P = .31). This mortality gap was most pronounced for suicide (adjusted hazard ratio [aHR]: 12.2; 95% CI: 10.4-14.4), but persisted for deaths from other external (aHR: 5.1; 95%CI: 4.0-6.4) and natural causes (aHR: 2.3; 95%CI: 1.6-3.3). Non-refugee (adjusted odds ratio [aOR]: 1.4, 95%CI: 1.2-1.6) and refugee migrants (aOR: 1.4, 95%CI: 1.1-1.8) were more likely to receive inpatient care at first diagnosis. No differences in in-patient LOS at first diagnosis were observed by migrant status. Sub-Saharan African migrants with psychotic disorder were readmitted more quickly than their Swedish-born counterparts (adjusted sub-hazard ratio [sHR]: 1.2; 95%CI: 1.1-1.4). Our findings highlight the need to understand the drivers of disparities in psychosis treatment and the mortality gap experienced by all people with disorder, irrespective of migrant status or region-of-origin

Suicide risk among refugees compared with non-refugee migrants and the Swedish-born majority population

BACKGROUND: It has been hypothesised that refugees have an increased risk of suicide. AIMS: To investigate whether risk of suicide is higher among refugees compared with non-refugee migrants from the same areas of origin and with the Swedish-born population, and to examine whether suicide rates among migrants converge to the Swedish-born population over time. METHOD: A population-based cohort design using linked national registers to follow 1 457 898 people born between 1 January 1970 and 31 December 1984, classified by migrant status as refugees, non-refugee migrants or Swedish-born. Participants were followed from their 16th birthday or date of arrival in Sweden until death, emigration or 31 December 2015, whichever came first. Cox regression models estimated adjusted hazard ratios for suicide by migrant status, controlling for age, gender, region of origin and income. RESULTS: There were no significant differences in suicide risk between refugee and non-refugee migrants (hazard ratio 1.28, 95% CI 0.93-1.76) and both groups had a lower risk of suicide than Swedish born. During their first 5 years in Sweden no migrants died by suicide; however, after 21-31 years their suicide risk was equivalent to the Swedish-born population (hazard ratio 0.94, 95% CI 0.79-1.22). After adjustment for income this risk was significantly lower for migrants than the Swedish-born population. CONCLUSIONS: Being a refugee was not an additional risk factor for suicide. Our findings regarding temporal changes in suicide risk suggest that acculturation and socioeconomic deprivation may account for a convergence of suicide risk between migrants and the host population over time. DECLARATION OF INTEREST: None

Family networks during migration and risk of non-affective psychosis: A population-based cohort study

OBJECTIVE: The determinants of increased psychosis risk among immigrants remain unclear. Given ethnic density may be protective, we investigated whether the presence of immediate family, or "family networks", at time of immigration was associated with risk of non-affective psychosis. METHODS: We followed a cohort of migrants (n = 838,717) to Sweden, born 1968-1997, from their 14th birthday, or earliest immigration thereafter, until diagnosis of non-affective psychosis (ICD-9/ICD-10), emigration, death, or 2011. Using record linkage, we measured family network as the presence of adult first-degree relatives immigrating with the cohort participant or already residing in Sweden. We used Cox proportional hazards regression to examine whether risk varied between those migrating with family, migrating to join family, or migrating alone. RESULTS: Migrating with immediate family was associated with increased psychosis risk amongst males compared to males who did not migrate with family (adjusted Hazard Ratio [aHR]: 1.16, 95% CI: 1.00-1.34). Migrating with family did not increase risk among females (aHR: 0.91, 95% CI: 0.78-1.07); similar observations were observed for males who immigrated to join family (aHR: 1.35, 95% CI: 1.21-1.51). In contrast, females who migrated alone were at increased risk compared to females who did not migrate alone (aHR: 1.31, 95% CI: 1.11-1.54). CONCLUSION: Family networks at the time of immigration were associated with differential patterns of non-affective psychotic disorders for males and females. These results suggest sex-specific differences in the perceived role of family networks during the migration process

Risk of schizophrenia, schizoaffective, and bipolar disorders by migrant status, region of origin, and age-at-migration: a national cohort study of 1.8 million people

BACKGROUND: We assessed whether the risk of various psychotic disorders and non-psychotic bipolar disorder (including mania) varied by migrant status, a region of origin, or age-at-migration, hypothesizing that risk would only be elevated for psychotic disorders. METHODS: We established a prospective cohort of 1 796 257 Swedish residents born between 1982 and 1996, followed from their 15th birthday, or immigration to Sweden after age 15, until diagnosis, emigration, death, or end of 2011. Cox proportional hazards models were used to model hazard ratios by migration-related factors, adjusted for covariates. RESULTS: All psychotic disorders were elevated among migrants and their children compared with Swedish-born individuals, including schizophrenia and schizoaffective disorder (adjusted hazard ratio [aHR]migrants: 2.20, 95% CI 1.96-2.47; aHRchildren : 2.00, 95% CI 1.79-2.25), affective psychotic disorders (aHRmigrant1.42, 95% CI 1.25-1.63; aHRchildren: 1.22 95% CI 1.07-1.40), and other non-affective psychotic disorders (aHRmigrant: 1.97, 95% CI 1.81-2.14; aHRchildren: 1.68, 95% CI 1.54-1.83). For all psychotic disorders, risks were generally highest in migrants from Africa (i.e. aHRschizophrenia: 5.24, 95% CI 4.26-6.45) and elevated at most ages-of-migration. By contrast, risk of non-psychotic bipolar disorders was lower for migrants (aHR: 0.58, 95% CI 0.52-0.64) overall, and across all ages-of-migration except infancy (aHR: 1.20; 95% CI 1.01-1.42), while risk for their children was similar to the Swedish-born population (aHR: 1.00, 95% CI 0.93-1.08). CONCLUSIONS: Increased risk of psychiatric disorders associated with migration and minority status may be specific to psychotic disorders, with exact risk dependent on the region of origin

Can subtle changes in gene expression be consistently detected with different microarray platforms?

Background: The comparability of gene expression data generated with different microarray platforms is still a matter of concern. Here we address the performance and the overlap in the detection of differentially expressed genes for five different microarray platforms in a challenging biological context where differences in gene expression are few and subtle. Results: Gene expression profiles in the hippocampus of five wild-type and five transgenic δC-doublecortin-like kinase mice were evaluated with five microarray platforms: Applied Biosystems, Affymetrix, Agilent, Illumina, LGTC home-spotted arrays. Using a fixed false discovery rate of 10% we detected surprising differences between the number of differentially expressed genes per platform. Four genes were selected by ABI, 130 by Affymetrix, 3,051 by Agilent, 54 by Illumina, and 13 by LGTC. Two genes were found significantly differentially expressed by all platforms and the four genes identified by the ABI platform were found by at least three other platforms. Quantitative RT-PCR analysis confirmed 20 out of 28 of the genes detected by two or more platforms and 8 out of 15 of the genes detected by Agilent only. We observed improved correlations between platforms when ranking the genes based on the significance level than with a fixed statistical cut-off. We demonstrate significant overlap in the affected gene sets identified by the different platforms, although biological processes were represented by only partially overlapping sets of genes. Aberrances in GABA-ergic signalling in the transgenic mice were consistently found by all platforms. Conclusion: The different microarray platforms give partially complementary views on biological processes affected. Our data indicate that when analyzing samples with only subtle differences in gene expression the use of two different platforms might be more attractive than increasing the number of replicates. Commercial two-color platforms seem to have higher power for finding differentially expressed genes between groups with small differences in expression