Association between risk of dementia and very late-onset schizophrenia-like psychosis: a Swedish population-based cohort study.

BACKGROUND: Although the incidence of psychotic disorders among older people is substantial, little is known about the association with subsequent dementia. We aimed to examine the rate of dementia diagnosis in individuals with very late-onset schizophrenia-like psychosis (VLOSLP) compared to those without VLOSLP. METHODS: Using Swedish population register data, we established a cohort of 15 409 participants with VLOSLP matched by age and calendar period to 154 090 individuals without VLOSLP. Participants were born between 1920 and 1949 and followed from their date of first International Classification of Diseases [ICD], Revisions 8-10 (ICD-8/9/10) non-affective psychotic disorder diagnosis after age 60 years old (or the same date for matched participants) until the end of follow-up (30th December 2011), emigration, death, or first recorded ICD-8/9/10 dementia diagnosis. RESULTS: We found a substantially higher rate of dementia in individuals with VLOSLP [hazard ratio (HR): 4.22, 95% confidence interval (95% CI) 4.05-4.41]. Median time-to-dementia-diagnosis was 75% shorter in those with VLOSLP (time ratio: 0.25, 95% CI 0.24-0.26). This association was strongest in the first year following VLOSLP diagnosis, and attenuated over time, although dementia rates remained higher in participants with VLOSLP for up to 20 years of follow-up. This association remained after accounting for potential misdiagnosis (2-year washout HR: 2.22, 95% CI 2.10-2.36), ascertainment bias (HR: 2.89, 95% CI 2.75-3.04), and differing mortality patterns between groups (subdistribution HR: 2.89, 95% CI 2.77-3.03). CONCLUSIONS: Our findings demonstrate that individuals with VLOSLP represent a high-risk group for subsequent dementia. This may be due to early prodromal changes for some individuals, highlighting the importance of ongoing symptom monitoring in people with VLOSLP.

Contact with psychiatric care prior to suicide: are there differences between migrants and the majority population in Sweden? A cohort study of 12 474 persons who died by suicide between 2006 and 2016.

AIMS: The aim of this study was to determine possible differences in psychiatric care contact and the type of contact in the year prior to suicide by migrant status and region of origin compared to Swedish persons. METHODS: A population-based open cohort design, using linked national registers, to study all individuals aged 20-64 years who died by suicide between 1 January 2006 and 31 December 2016 in Sweden (N = 12 474). The primary exposure was migrant status compared to the Swedish majority population in the following categories: non-refugee migrants, refugee migrants and children of migrants. The secondary exposure was region of origin in seven regions: Sweden, other Nordic countries, Europe, Sub-Saharan Africa, the Middle East and North Africa, Asia, the Americas and Oceania. The four outcomes were psychiatric in- and outpatient care, prescribed and purchased psychotropic medication and a variable composing the other variables, all measured the year before death. Logistic regression models adjusted for age, sex, income and marital status estimated the likelihood of psychiatric care utilisation by type of care within the year prior to death by migrant status and region of origin (individually and combined). RESULTS: Out of all who had died by suicide, 81% had had psychiatric care of any type in the year before death by suicide. Among refugees the prevalence of psychiatric care before death by suicide was 88%. Compared with the Swedish reference group, non-refugees and persons from Asia and Sub-Saharan Africa had a lower likelihood of utilising psychiatric care prior to suicide driven by a lower use of prescribed psychotropic medication. Persons from the Middle East and North Africa had a higher likelihood, driven by higher use of psychiatric outpatient care and prescribed psychotropic medication. Non-refugees' likelihood of utilising care before death by suicide was lower within the first 5 years of living in Sweden. CONCLUSION: A large share of those who die by suicide use psychiatric care the year before they die. Non-refugee migrants and persons from Asia and Sub-Saharan Africa have a lower likelihood of utilising psychiatric care prior to suicide compared to Swedish, whereas persons from the Middle East and North Africa have a higher likelihood. Health care and policy makers should consider both migrant status, region of origin and time in the new country for further suicide prevention efforts.

Risk of severe COVID-19 infection in individuals with severe mental disorders, substance use disorders, and common mental disorders.

OBJECTIVE: To evaluate the risk of severe COVID-19 in individuals with severe mental disorders, substance use disorders, and common mental disorders in the total adult population of Region Stockholm (N = 1,516,270), and to explore possible underlying mechanisms to the increased risk. METHODS: In this prospective cohort study, we examined the risk of hospitalization and treatment in an intensive care unit (ICU) with COVID-19, and death from COVID-19 for individuals with mental disorders. Associations were step by step adjusted for (1) sociodemographic/economic factors, (2) indicators of virus exposure, (3) somatic conditions, and (4) psychopharmacological treatment. RESULTS: In model 1 (adjusted for age, sex and living in a care home for elderly people), people with a mental disorder had increased risks for inpatient care (HR = 1.5), ICU care (HR = 1.5), and mortality (HR = 1.4) from COVID-19. There was an increased risk of dying from COVID-19 in all subgroups of mental disorders, particularly in people with a severe mental disorder (HR = 1.9). Different covariates had different effects on the association depending on the outcome and on sex, age, or psychiatric diagnosis of the participants. CONCLUSION: People with mental disorders have an increased risk of severe COVID-19, including mortality. The increased risk was partly explained by the examined covariates.

Migrant status and risk of compulsory admission at first diagnosis of psychotic disorder: a population-based cohort study in Sweden.

BACKGROUND: Minority ethnic and migrant groups face an elevated risk of compulsory admission for mental illness. There are overlapping cultural, socio-demographic, and structural explanations for this risk that require further investigation. METHODS: By linking Swedish national register data, we established a cohort of persons first diagnosed with a psychotic disorder between 2001 and 2016. We used multilevel mixed-effects logistic modelling to investigate variation in compulsory admission at first diagnosis of psychosis across migrant and Swedish-born groups with individual and neighbourhood-level covariates. RESULTS: Our cohort included 12 000 individuals, with 1298 (10.8%) admitted compulsorily. In an unadjusted model, being a migrant [odds ratio (OR) 1.48; 95% confidence interval (CI) 1.26-1.73] or child of a migrant (OR 1.27; 95% CI 1.10-1.47) increased risk of compulsory admission. However after multivariable modelling, region-of-origin provided a better fit to the data than migrant status; excess risk of compulsory admission was elevated for individuals from sub-Saharan African (OR 1.94; 95% CI 1.51-2.49), Middle Eastern and North African (OR 1.46; 95% CI 1.17-1.81), non-Nordic European (OR 1.27; 95% CI 1.01-1.61), and mixed Swedish-Nordic backgrounds (OR 1.33; 95% CI 1.03-1.72). Risk of compulsory admission was greater in more densely populated neighbourhoods [OR per standard deviation (s.d.) increase in the exposure: 1.12, 95% CI 1.06-1.18], an effect that appeared to be driven by own-region migrant density (OR per s.d. increase in exposure: 1.12; 95% CI 1.02-1.24). CONCLUSIONS: Inequalities in the risk of compulsory admission by migrant status, region-of-origin, urban living and own-region migrant density highlight discernible factors which raise barriers to equitable care and provide potential targets for intervention.

Trends in psychiatric diagnoses, medications and psychological therapies in a large Swedish region: a population-based study.

BACKGROUND: Health services utilization for mental health disorders is reported to increase sharply in many countries. The aim of this study was to report trends in all aspects of mental health care utilization in a total population sample. METHODS: Repeated cross-sectional register study of the Stockholm Region (VAL) including both primary and secondary care. Trends in the proportion of adults in the total population of Stockholm Region with a recorded ICD-10 psychiatric diagnosis or psychological therapy during 2007-2017 as well as claims of psychiatric medication from 2011 were calculated. RESULTS: The proportion of adults utilizing any mental health care increased from 13.2% in 2011 to 16.1% in 2017. In 2017, 49.3% were treated in primary care, 32.2% in secondary care and 18.5% were jointly managed. The increase was most pronounced in younger adults. Women were more likely to receive mental health care than men in all ages. Medication decreased from 71.0 to 67.7%, while psychological therapy increased from 33.1 to 37.6%. The use of psychiatric medication increased with age while psychological therapy decreased. All time trends were statistically significant (p < .0001). CONCLUSION: Care for mental health disorders has been increasing mainly in primary care and was delivered to one in seven adult individuals in 2017. Interventions are needed to address the growing burden of mental health disorders while avoiding overtreatment.

Association between preeclampsia and attention-deficit hyperactivity disorder: a population-based and sibling-matched cohort study.

OBJECTIVE: To examine the association between preeclampsia and attention-deficit hyperactivity disorder (ADHD), using a large Swedish-based registry cohort. METHODS: This study comprised 2 047 619 children, with 114 934 (5.6%) cases of ADHD. Preeclampsia was based on two alternate definitions: (i) preeclampsia (using ICD-9/ICD-10) and (ii) preeclampsia and small for gestational age (SGA) combined. ADHD was determined in one of two ways: (i) if a diagnosis of ADHD was present in the National Patient Register or (ii) if an individual was in receipt of ADHD medication in the Prescribed Drug Register. Multivariate Cox proportional hazards regression analysis allowed adjustment for several perinatal/sociodemographic factors. Sibling-matched analysis further controlled for shared genetic and familial confounding. RESULTS: In the adjusted Cox model, preeclampsia was associated with an increase in likelihood of ADHD (HR: 1.15, 95% CI: 1.12, 1.19). The HR for preeclampsia and those born SGA was 1.43 (95% CI: 1.31, 1.55) in the adjusted model, compared to those unexposed to preeclampsia/SGA. The sibling-matched analysis did not materially change these associations (HR: 1.13, 95% CI: 1.05, 1.22) and 1.55 (95% CI: 1.28, 1.88). CONCLUSIONS: Exposure to preeclampsia or preeclampsia/SGA was associated with ADHD, independent of genetic/familial factors shared by siblings. However, it is important to note that sibling-matched analysis can only adjust for factors that are constant between pregnancies; therefore, residual confounding cannot be ruled out. Further research is needed to explore modifiable risk factors and identify those most-at-risk babies following delivery.

Mental health service use, depression, panic disorder and life events among Swedish young adults in 2000 and 2010: a repeated cross-sectional population study in Stockholm County, Sweden.

AIMS: The use of specialised psychiatric services for depression and anxiety has increased steadily among young people in Sweden during recent years. It is not known to what extent this service use is due to an increase in psychiatric morbidity, or whether other adversities explain these trends. The aim of this study is to examine if there is increased use of psychiatric services among young adults in Sweden between 2000 and 2010, and if so, to what extent this increase is associated with differences in depression, anxiety and negative life events. METHODS: This is a repeated cross-sectional study of 20-30-year old men and women in Stockholm County in 2000 and 2010 (n = 2590 and n = 1120). Log-binomial regression analyses were conducted to compare the prevalence of service use, depression and panic disorder between the two cohorts. Self-reported life events were entered individually and as a summary index, and entered as potential mediators. Different effects of life events on service use were examined through interaction analysis. We report prevalence proportion ratios (PPR) with 95% confidence intervals. RESULTS: Specialised psychiatric service use, but also depression and panic disorder was more common in the younger cohort (current service use 2.4 and 5.0%). The younger cohort did not report more life events overall or among those with depression or anxiety. Neither depression, panic disorder nor life events could explain the increased use of psychiatric services in the younger cohort (Fully adjusted model PPR = 1.70, 1.20-2.40 95% CI). There was no significant interaction between cohort and life events in predicting psychiatric service use. CONCLUSION: This study provides initial support for an increase in service use among young adults compared with 10 years earlier. The increased service use cannot be explained with increasing worse life situations.

Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden.

Although many studies indicate the interplay of genetic and environmental factors in the etiology of autism spectrum disorder (ASD), our limited understanding of the underlying mechanisms hampers the development of effective ways of detecting and preventing the disorder. Recent studies support the hypothesis that prenatal androgen exposure contributes to the development of ASD. This would suggest that maternal polycystic ovary syndrome (PCOS), a condition associated with excess androgens, would increase the risk of ASD in the offspring. We conducted a matched case-control study nested within the total population of Sweden (children aged 4-17 who were born in Sweden from 1984 to 2007). The sample consisted of 23 748 ASD cases and 208 796 controls, matched by birth month and year, sex and region of birth. PCOS and ASD were defined from ICD codes through linkage to health-care registers. Maternal PCOS increased the odds of ASD in the offspring by 59%, after adjustment for confounders (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.34-1.88). The odds of offspring ASD were further increased among mothers with both PCOS and obesity, a condition common to PCOS that is related to more severe hyperandrogenemia (OR 2.13, 95% CI 1.46-3.10). Risk estimates did not differ between sexes. In conclusion, children of women with PCOS appear to have a higher risk of developing ASD. This finding awaits confirmation, and exploration of potentially underlying mechanisms, including the role of sex steroids in the etiology of ASD.

Comparing cohort incidence of schizophrenia with that of bipolar disorder and affective psychosis in individuals born in Stockholm County 1955-1967.

BACKGROUND: Perinatal factors are associated with increased risk for both schizophrenia and bipolar disorder. Improvements in obstetric and maternal healthcare and positive socioeconomic development in Sweden from the 1950s onwards could be expected to affect incidence estimates. However, commonly incidence rates are calculated during a specific year, i.e. time of diagnosis, which mirrors proximal precipitating risk factors. To examine whether incidence estimates are compatible with the hypothesis of an impact of perinatal exposures on the risk of the different disorders we here instead calculate incidence rates for consecutive birth cohorts born between 1955 and 1967. We hypothesized that schizophrenia incidence would be more affected compared to bipolar disorder and other affective psychoses since most perinatal risk factors are more pronounced in schizophrenia aetiology. METHOD: Birth cohorts of individuals born in Sweden and resident in Stockholm (N = 2,16,322), were followed in The National Patient Register regarding incident inpatient episodes Incident cases/10,000 person-years and birth cohort were calculated. Linear regression was used to estimate change in incidence rate. RESULTS: We found stable birth cohort-based incidence estimates for bipolar disorder and other affective psychoses, but a continuous reduction in incidence estimates for schizophrenia as well as other non-affective psychoses in subsequent birth cohorts from 1955 to 1967. CONCLUSIONS: The consecutive birth cohort-based incidence estimates unveiled patterns that are compatible with the hypothesis of an impact of early life exposures decreasing over time, in the aetiology of schizophrenia, whereas this pattern is less apparent in affective psychoses..

Influence of maternal infections on neonatal acute phase proteins and their interaction in the development of non-affective psychosis.

Although primary infections with Toxoplasma gondii or herpes viruses during pregnancy are established teratogens, chronic maternal infections with these pathogens are considered far less serious. However, such chronic infections have been associated with neuropsychiatric disorders in the offspring. The risks of non-affective psychoses, including schizophrenia, in offspring associated with these exposures during pregnancy have not been completely defined. We used data from neonatal dried blood samples from 199 cases of non-affective psychosis and 525 matched controls (born 1975-1985). We measure immunoglobulin G antibodies directed at T. gondii, cytomegalovirus and herpes simplex virus type-1 and -2, as well as levels of nine acute phase proteins (APPs). We assessed the interaction between maternal antibodies and neonatal APP in terms of risk of non-affective psychosis. Among controls, maternal exposure to T. gondii or cytomegalovirus, but not to the other herpes viruses, was associated with significantly higher levels of neonatal APPs. Among cases, none of the maternal exposures were associated with any significant change in APPs. We observed increased RR for non-affective psychosis associated with maternal infection with T. gondii (odds ratio 2.1, 95% confidence interval 1.1-4.0) or cytomegalovirus (1.7, 0.9-3.3) only among neonates with low APP levels. These findings suggest that chronic maternal infection with T. gondii or cytomegalovirus affect neonatal markers of innate immunity. Deficient fetal immune responses in combination with maternal chronic infections may contribute to subsequent risk for psychosis. A greater understanding of the maternal-fetal immunological interplay may ultimately lead to preventive strategies toward neuropsychiatric disorders.

Do eating disorders in parents predict eating disorders in children? Evidence from a Swedish cohort.

OBJECTIVE: We investigated whether parental eating disorders (ED) predict ED in children, using a large multigeneration register-based sample. METHOD: We used a subset of the Stockholm Youth Cohort born 1984-1995 and resident in Stockholm County in 2001-2007 (N = 286,232), The exposure was a diagnosed eating disorder in a parent; the outcome was any eating disorder diagnosis in their offspring, given by a specialist clinician, or inferred from an appointment at a specialist eating disorder clinic. A final study sample of 158,697 (55.4%) had data on these variables and confounding factors and contributed a total of 886,241 person years to the analysis. RESULTS: We found good evidence in support of the hypothesis that ED in either parent are independently associated with ED in their female children (HR 1.97 (95% CI: 1.17-3.33), P = 0.01) and that ED in mothers are independently associated with ED in their female children (HR 2.35 (95% CI: 1.39-3.97) P = 0.001). Numbers were too low to permit separate analysis of ED in parents and their male children. CONCLUSION: Eating disorders in parents were associated with ED in children. This study adds to our knowledge about the intergenerational transmission of ED, which will help identify high-risk groups and brings about the possibility of targeted prevention.

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.

Oestrus synchronization treatment induces histomorphological changes on the uterine tube epithelium of the gilt.

The aim of this study was to determine the histomorphological changes that occurred in response to two treatments for oestrus synchronization in three different regions of the gilt's uterine tubes epithelium: the ampulla (AMP), ampulla-isthmic junction (AIJ) and isthmus (IST). Nine prepuberal gilts were divided into three groups (n = 3): (1) eCG 400 IU and hCG 200 IU (eCG/hCG), (2) progesterone agonist (P4) and (3) control group. The number of secretory cells (stained with periodic acid-Schiff reaction or PAS-positive cells) decreased in the AMP in the P4 treated group when compared to the control group, whereas, no difference was observed in the number of PAS-negative cells in the AMP of the three groups. A significant decrease in the number of PAS-positive cells was observed in the AIJ and IST of the P4 treated group when compared to the eCG/hCG and control groups. An increase in the number of PAS-negative cells was observed in the AIJ and IST in the P4 treated group. The epithelium height in the AMP and AIJ was increased in the eCG/hCG group when compared to the control and P4 groups. In this last group, we observed a reduced height compared with the other two groups for the AIJ. In the IST, there were no significant changes in the epithelium height of the control or the other two groups (eCG/hCG and P4). The epithelial cells of the P4 treated group had the least amount of cytoplasmic granules and the lowest intensity of PAS staining in the AMP, AIJ and IST. Animals treated with eCG/hCG showed an intermediate number of cytoplasmic granules and intensity in all regions evaluated. These data show that P4 treatment for synchronization induces a significant (P < 0.001) decrease of PAS-positive cells and staining intensity of cytoplasmic granules in the different regions studied and an increased number of PAS-negative cells in the AIJ and IST epithelium. Moreover, eCG/hCG treatment increased the height of the epithelium in the AMP and AIJ, while in this last region, the P4 treatment decreased the epithelium height. These results show that synchronization treatments with P4 and in a smaller proportion with eCG/hCG can modify the amount of PAS-positive and PAS-negative cells, and the epithelium height. This has influence in the secretory activity of the epithelium and possibly alters the fluid microenvironment of the gilt's uterine tube. The biological impact of regional variations in the epithelial cells of the gilt's uterine tube needs further investigation to understand the implications that the reproductive processes can have in the uterine tube.

Prognosis of schizophrenia in persons with and without a history of cannabis use.

BACKGROUND: The aim of the study was to determinate whether schizophrenia patients with a history of cannabis use have a different prognosis, with regards to readmission and hospital duration, compared with those without a history of cannabis use. METHOD: The present investigation was a cohort study of 50,087 Swedish men with data on cannabis use at the ages of 18-20 years. A total of 357 cases of schizophrenia were identified from in-patient care and followed up from 1973 to 2007. RESULTS: Schizophrenia patients with a history of cannabis use had a higher median duration of first hospital episode (59 days v. 30 days). Patients with a history of cannabis use had a higher median rate of readmission (10 times v. four times). Also, total number of hospital days was higher in patients with a history of cannabis use compared with those without (547 days v. 184 days). Patients with a history of cannabis use had an increased odds of having more than 20 hospital readmissions compared with non-users [3.1, 95% confidence interval (CI) 1.3-7.3] as well as an increased odds of hospital admission lasting more than 2 years (2.4, 95% CI 1.1-7.4) after controlling for diagnosis of personality disorders, family socio-economic position, IQ score, civil status, place of residence, risky use of alcohol and use of other drugs. Patients with a history of cannabis use were less likely to have paranoid schizophrenia compared with never users (8% v. 17%) in the first admission. CONCLUSIONS: Schizophrenia patients with a history of cannabis use had a significantly higher burden of lifetime in-patient care than non-cannabis users. Not only does cannabis increase the risk of schizophrenia, but also our findings indicate that the course and prognosis of schizophrenia may be more severe than schizophrenia cases in general.

Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study.

OBJECTIVE: To examine the risk of psychosis associated with severe bereavement stress during the antenatal and postnatal period, between conception to adolescence, and with different causes of death. DESIGN: Population based cohort study. SETTING: Swedish national registers including births between 1973 and 1985 and followed-up to 2006. PARTICIPANTS: In a cohort of 1,045,336 Swedish births (1973-85), offspring born to mothers exposed to severe maternal bereavement stress six months before conception or during pregnancy, or exposed to loss of a close family member subsequently from birth to 13 years of age were followed until 2006. Admissions were identified by linkage to national patient registers. MAIN OUTCOME MEASURES: Crude and adjusted odds ratios for all psychosis, non-affective psychosis, and affective psychosis. RESULTS: Maternal bereavement stress occurring preconception or during the prenatal period was not associated with a significant excess risk of psychosis in offspring (adjusted odds ratio, preconception 1.24, 95% confidence interval 0.96 to 1.62; first trimester 0.95, 0.58 to 1.56; second trimester 0.79, 0.46 to 1.33; third trimester 1.14, 0.78 to 1.66). Risks increased modestly after exposure to the loss of a close family member from birth to adolescence for all psychoses (adjusted odds ratio 1.17, 1.04 to 1.32). The pattern of risk was generally similar for non-affective and affective psychosis. Thus estimates were higher after death in the nuclear compared with extended family but remained non-significant for prenatal exposure; the earlier the exposure to death in the nuclear family occurred in childhood (all psychoses: adjusted odds ratio, birth to 2.9 years 1.84, 1.41 to 2.41; 3-6.9 years 1.47, 1.16 to 1.85; 7-12.9 years 1.32, 1.10 to 1.58) and after suicide. Following suicide, risks were especially higher for affective psychosis (birth to 2.9 years 3.33, 2.00 to 5.56; 6.9 years 1.84, 1.04 to 3.25; 7-12.9 years 2.68, 1.84 to 3.92). Adjustment for key confounders attenuated but did not explain associations with risk. CONCLUSIONS: Postnatal but not prenatal bereavement stress in mothers is associated with an increased risk of psychosis in offspring. Risks are especially high for affective psychosis after suicide in the nuclear family, an effect that is not explained by family psychiatric history. Future studies are needed to understand possible sources of risk and resilience so that structures can be put in place to support vulnerable children and their families.

Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress.

BACKGROUND: Preconception, prenatal and postnatal maternal stress is associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt and completed suicide. METHOD: Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992-2000 for childhood outcomes and 2,155,221 offspring born 1973-1997 for adult outcomes with follow-up to 2009. Maternal stress was defined as death of a first-degree relative during (a) the 6 months before conception, (b) pregnancy or (c) the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HRs) in unadjusted and adjusted analyses. RESULTS: Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third-trimester prenatal stress increased the risk of ASD [adjusted HR (aHR) 1.58, 95% confidence interval (CI) 1.15-2.17] and ADHD (aHR 1.31, 95% CI 1.04-1.66). First postnatal year stress increased the risk of offspring suicide attempt (aHR 1.13, 95% CI 1.02-1.25) and completed suicide (aHR 1.51, 95% CI 1.08-2.11). Bereavement stress during the second postnatal year increased the risk of ASD (aHR 1.30, 95% CI 1.09-1.55). CONCLUSIONS: Further research is needed regarding associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases the risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases the risk of offspring suicide attempt, completed suicide and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes.

School performance and the risk of suicide attempts in young adults: a longitudinal population-based study.

BACKGROUND: Poor school performance is strongly associated with attempted suicide, but the mechanisms underlying this association are uncertain. We examined this relationship and the extent to which it is explained by (i) adult health behaviours and (ii) social conditions. Furthermore, we examined the potential modifying role of previous suicidal thoughts in the relationship. METHOD: We conducted a longitudinal cohort study of 6146 individuals aged 18-33 years, recruited in 2002 and 2006 in Stockholm and resurveyed in 2007 and 2010 respectively. We estimated the risk of reported lifetime suicide attempts at follow-up among individuals without a history of suicide attempts at baseline and in relation to compulsory school-leaving grades, controlling for possible confounders and mediators. RESULTS: There were 91 cases of self-reported suicide attempts during the follow-up (5-year incidence of 1.5%). ORs ranged from 3.35 [95% confidence interval (CI) 1.88-5.96] for those in the lowest grade quartile to 2.60 (95% CI 1.48-4.57) and 1.76 (95% CI 0.99-3.13) for those in the second and third quartiles respectively. The relationship between school performance and risk of suicide attempts did not differ by sex. Adult health behaviours and social conditions marginally attenuated, but did not explain, the relationship. The gradient varied with baseline history of suicidal thoughts, and was found only among individuals without such a history. CONCLUSIONS: Poor school performance was found to predict suicide attempts among young adults without a history of suicidal thoughts. Adult health behaviours and social conditions did not explain this relationship. Instead, other factors linked with poor school performance, such as poor coping ability, may increase the risk of suicide attempts.

Individual- and area-level influence on suicide risk: a multilevel longitudinal study of Swedish schoolchildren.

BACKGROUND: Characteristics related to the areas where people live have been associated with suicide risk, although these might reflect aggregation into these communities of individuals with mental health or social problems. No studies have examined whether area characteristics during childhood are associated with subsequent suicide, or whether risk associated with individual characteristics varies according to childhood neighbourhood context. METHOD: We conducted a longitudinal study of 204,323 individuals born in Sweden in 1972 and 1977 with childhood data linked to suicide (n = 314; 0.15%) up to age 26-31 years. Multilevel modelling was used to examine: (i) whether school-, municipality- or county-level characteristics during childhood are associated with later suicide, independently of individual effects, and (ii) whether associations between individual characteristics and suicide vary according to school context (reflecting both peer group and neighbourhood effects). RESULTS: Associations between suicide and most contextual measures, except for school-level gender composition, were explained by individual characteristics. There was some evidence of cross-level effects of individual- and school-level markers of ethnicity and deprivation on suicide risk, with qualitative interaction patterns. For example, having foreign-born parents increased the risk for individuals raised in areas where they were in a relative minority, but protected against suicide in areas where larger proportions of the population had foreign-born parents. CONCLUSIONS: Characteristics that define individuals as being different from most people in their local environment as they grow up may increase suicide risk. If robustly replicated, these findings have potentially important implications for understanding the aetiology of suicide and informing social policy.

Neonatal levels of acute phase proteins and later risk of non-affective psychosis.

Mounting evidence suggests that immune disturbances in early life may be implicated in the etiology of non-affective psychoses. Our aim was to assess the levels of neonatal acute phase proteins (APPs), central to innate immune function as well as central nervous system development, in neonatal dried blood spots and their association with later risk of non-affective psychoses. This case-control study included 196 individuals with a verified register-based diagnosis of non-affective psychosis and 502 controls matched on age, sex and hospital of birth. Concentrations of nine different APPs were measured in eluates from dried blood spots using a bead-based multiplex assay. Odds ratios (OR) for non-affective psychoses were calculated for log(2)-transformed (continuous) as well as tertiles of APP concentrations. In continuous analysis, higher concentrations of two APPs, tissue plasminogen activator (tPA; OR: 0.90, 95% confidence interval (CI): 0.85-0.96) and serum amyloid P (SAP; OR: 0.88, 95% CI: 0.78-0.99) were protective in terms of risk of non-affective psychosis. These relationships were not affected by the addition of covariates relevant to maternal health, pregnancy and delivery to the model. Tertile analysis confirmed a protective relationship for higher levels of tPA and SAP, as well as for procalcitonin (highest tertile OR: 0.54, 95% CI:0.32-0.91). Our results suggest that persons who develop non-affective psychoses have lower levels of certain APPs at the time of birth. These differences may render individuals more susceptible to infectious diseases or cause deficiencies in pathways critical for neurodevelopment.