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Background: Both maternal and, separately, paternal mental illness are associated with diminished academic attainment among children. However, the differential impacts of diagnostic type and degree of parental burden (e.g. one v. both parents affected) on these functional outcomes are unknown. Methods: Using the Swedish national patient (NPR) and multi-generation (MGR) registers, 2 226 451 children (1 290 157 parental pairs), born 1 January 1973–31 December 1997, were followed through 31 December 2013. Diagnostic status of all cohort members was defined for eleven psychiatric disorders, and families classed by exposure: (1) parents affected with any disorder, (2) parents affected with a disorder group (e.g. neuropsychiatric disorders), and (3) parents affected with a specific disorder (e.g. ADHD). Pairs were further defined as 'unaffected,' 'single-affected,', or 'dual-affected.' Among offspring, the study evaluated fulfillment of four academic milestones, from compulsory (primary) school through University (college). Sensitivity analyses considered the impact of child's own mental health, as well as parental education, on main effects. Results: Marked reductions in the odds of achievement were observed, emerging at the earliest levels of schooling for both single-affected [adjusted odds ratio (aOR), 0.50; 95% CI 0.49–0.51] and dual-affected (aOR 0.29, 95% CI 0.28–0.30) pairs and persisting thereafter [aOR range (single), 0.52–0.65; aOR range (dual), 0.30–0.40]. This pattern was repeated for analyses within diagnosis/diagnostic group. Main results were robust to adjustment for offspring mental health and parent education level. Conclusions: Parental mental illness is associated with profound reductions in educational attainment in the subsequent generation, with children from dual-affected families at uniquely high risk. [ABSTRACT FROM AUTHOR] more...

Background: The authors sought to clarify the impact of spousal psychiatric disorders of differing severity [major depression or anxiety disorders (DAD) v. bipolar disorder or nonaffective psychosis (BPN)] on proband risk for alcohol use disorder (AUD) during marriage. Methods: In a Swedish cohort (N = 744 628), associations between spousal DAD and BPN and proband AUD were estimated with Cox proportional hazards; associations between parental AUD, proband premarital AUD, and spousal lifetime DAD and BPN were estimated with logistic regression; and whether spousal DAD or BPN causally increased risk for AUD was evaluated with frailty models. Results: Spousal premarital DAD, spousal marital-onset DAD, and spousal BPN (premarital or marital-onset) were associated with proband AUD during marriage [hazard ratios (HR) range 1.44–3.72]. Those with a parental or premarital history of AUD (v. without) were more likely to marry a spouse with DAD or BPN (odds ratios 1.22–2.77). Moving from an unaffected first spouse to a DAD-affected second spouse increased AUD risk in males (HR 2.90). Moving from an unaffected first spouse to a BPN-affected second spouse increased AUD risk (HRmales 3.96; HRfemales 5.64). Moving to an unaffected second spouse from a DAD-affected first spouse decreased AUD risk, with stronger evidence in females compared to males (HRmales 0.59; HRfemales 0.28). Conclusions: Associations between spousal DAD or BPN and proband AUD reflect both selection and causal effects. Marriage to a BPN-affected spouse has a particularly strong effect on AUD risk, with more modest effects for spousal DAD. [ABSTRACT FROM AUTHOR] more...

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. [ABSTRACT FROM AUTHOR] more...

Background: Individuals diagnosed with psychiatric disorders who are prescribed antipsychotics have lower rates of violence and crime but the differential effects of specific antipsychotics are not known. We investigated associations between 10 specific antipsychotic medications and subsequent risks for a range of criminal outcomes. Methods: We identified 74 925 individuals who were ever prescribed antipsychotics between 2006 and 2013 using nationwide Swedish registries. We tested for five specific first-generation antipsychotics (levomepromazine, perphenazine, haloperidol, flupentixol, and zuclopenthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, risperidone, and aripiprazole). The outcomes included violent, drug-related, and any criminal arrests and convictions. We conducted within-individual analyses using fixed-effects Poisson regression models that compared rates of outcomes between periods when each individual was either on or off medication to account for time-stable unmeasured confounders. All models were adjusted for age and concurrent mood stabilizer medications. Results: The relative risks of all crime outcomes were substantially reduced [range of adjusted rate ratios (aRRs): 0.50–0.67] during periods when the patients were prescribed antipsychotics v. periods when they were not. We found that clozapine (aRRs: 0.28–0.44), olanzapine (aRRs: 0.46–0.72), and risperidone (aRRs: 0.53–0.64) were associated with lower arrest and conviction risks than other antipsychotics, including quetiapine (aRRs: 0.68–0.84) and haloperidol (aRRs: 0.67–0.77). Long-acting injectables as a combined medication class were associated with lower risks of the outcomes but only risperidone was associated with lower risks of all six outcomes (aRRs: 0.33–0.69). Conclusions: There is heterogeneity in the associations between specific antipsychotics and subsequent arrests and convictions for any drug-related and violent crimes. [ABSTRACT FROM AUTHOR] more...

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. [ABSTRACT FROM AUTHOR] more...

BackgroundGiven the frequency with which families change residences, the effects of childhood relocations have gained increasing research attention. Many researchers have demonstrated that childhood relocations are associated with a variety of adverse outcomes. However, drawing strong causal claims remains problematic due to uncontrolled confounding factors.MethodWe utilized longitudinal, population-based Swedish registers to generate a nationally representative sample of offspring born 1983–1997 (n = 1 510 463). Using Cox regression and logistic regression, we examined the risk for numerous adverse outcomes after childhood relocation while controlling for measured covariates. To account for unmeasured genetic and environmental confounds, we also compared differentially exposed cousins and siblings.ResultsIn the cohort baseline model, each annual relocation was associated with risk for the adverse outcomes, including suicide attempt [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.19–1.20]. However, when accounting for offspring and parental covariates (HR 1.08, 95% CI 1.07–1.09), as well as genetic and environmental confounds shared by cousins (HR 1.07, 95% CI 1.05–1.09) and siblings (HR 1.00, 95% CI 0.97–1.04), the risk for suicide attempt attenuated. We found a commensurate pattern of results for severe mental illness, substance abuse, criminal convictions, and low academic achievement.ConclusionsPrevious research may have overemphasized the independent association between relocations and later adverse outcomes. The results suggest that the association between childhood relocations and suicide attempt, psychiatric problems, and low academic achievement is partially explained by genetic and environmental confounds correlated with relocations. This study demonstrates the importance of using family-based, quasi-experimental designs to test plausible alternate hypotheses when examining causality. [ABSTRACT FROM PUBLISHER] more...

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.. [ABSTRACT FROM PUBLISHER] more...

BackgroundOffspring of patients with schizophrenia exhibit poorer school performance compared with offspring of non-schizophrenic parents. We aimed to elucidate the mechanisms behind this association.MethodWe linked longitudinal national population registers in Sweden and compared school performance among offspring of schizophrenic parents with offspring of non-schizophrenic parents (1 439 215 individuals with final grades from compulsory school 1988–2006). To investigate the mechanisms, we studied offspring of schizophrenic patients and controls within the same extended families. We investigated genetic effects by stratifying analyses of parent–child associations according to genetic relatedness (half-cousins, full cousins and half-siblings). Environmental effects were investigated by comparing school performance of offspring of schizophrenic fathers and of schizophrenic mothers, respectively, and by stratifying the analyses according to environmental relatedness while controlling genetic relatedness (paternal and maternal half-cousins, paternal and maternal half-siblings).ResultsOffspring of parents with schizophrenia had poorer overall school performance than unrelated offspring of non-schizophrenic parents (−0.31 s.d.). Variability in genetic relatedness greatly moderated the strength of the within-family association (β=−0.23 within exposure-discordant half-cousins, β=−0.13 within exposure-discordant full cousins, β=0.04 within exposure-discordant half-siblings), while no evidence was found that the environment affected offspring school performance.ConclusionsGenetic factors account for poorer school performance in children of parents with schizophrenia. This supports that cognitive deficits found in individuals with schizophrenia and their relatives might be genetically inherited. Early detection of prodromal signs and impaired functioning of offspring of patients with schizophrenia could lead to earlier and better tailored interventions. [ABSTRACT FROM PUBLISHER] more...