Long-Term Outcomes Associated with Traumatic Brain Injury in Childhood and Adolescence: A Nationwide Swedish Cohort Study of a Wide Range of Medical and Social Outcomes

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of disability and mortality in children and young adults worldwide. It remains unclear, however, how TBI in childhood and adolescence is associated with adult mortality, psychiatric morbidity, and social outcomes. METHODS AND FINDINGS: In a Swedish birth cohort between 1973 and 1985 of 1,143,470 individuals, we identified all those who had sustained at least one TBI (n = 104,290 or 9.1%) up to age 25 y and their unaffected siblings (n = 68,268) using patient registers. We subsequently assessed these individuals for the following outcomes using multiple national registries: disability pension, specialist diagnoses of psychiatric disorders and psychiatric inpatient hospitalisation, premature mortality (before age 41 y), low educational attainment (not having achieved secondary school qualifications), and receiving means-tested welfare benefits. We used logistic and Cox regression models to quantify the association between TBI and specified adverse outcomes on the individual level. We further estimated population attributable fractions (PAF) for each outcome measure. We also compared differentially exposed siblings to account for unobserved genetic and environmental confounding. In addition to relative risk estimates, we examined absolute risks by calculating prevalence and Kaplan-Meier estimates. In complementary analyses, we tested whether the findings were moderated by injury severity, recurrence, and age at first injury (ages 0-4, 5-9, 6-10, 15-19, and 20-24 y). TBI exposure was associated with elevated risks of impaired adult functioning across all outcome measures. After a median follow-up period of 8 y from age 26 y, we found that TBI contributed to absolute risks of over 10% for specialist diagnoses of psychiatric disorders and low educational attainment, approximately 5% for disability pension, and 2% for premature mortality. The highest relative risks, adjusted for sex, birth year, and birth order, were found for psychiatric inpatient hospitalisation (adjusted relative risk [aRR] = 2.0; 95% CI: 1.9-2.0; 6,632 versus 37,095 events), disability pension (aRR = 1.8; 95% CI: 1.7-1.8; 4,691 versus 29,778 events), and premature mortality (aRR = 1.7; 95% CI: 1.6-1.9; 799 versus 4,695 events). These risks were only marginally attenuated when the comparisons were made with their unaffected siblings, which implies that the effects of TBI were consistent with a causal inference. A dose-response relationship was observed with injury severity. Injury recurrence was also associated with higher risks-in particular, for disability pension we found that recurrent TBI was associated with a 3-fold risk increase (aRR = 2.6; 95% CI: 2.4-2.8) compared to a single-episode TBI. Higher risks for all outcomes were observed for those who had sustained their first injury at an older age (ages 20-24 y) with more than 25% increase in relative risk across all outcomes compared to the youngest age group (ages 0-4 y). On the population level, TBI explained between 2%-6% of the variance in the examined outcomes. Using hospital data underestimates milder forms of TBI, but such misclassification bias suggests that the reported estimates are likely conservative. The sibling-comparison design accounts for unmeasured familial confounders shared by siblings, including half of their genes. Thus, residual genetic confounding remains a possibility but will unlikely alter our main findings, as associations were only marginally attenuated within families. CONCLUSIONS: Given our findings, which indicate potentially causal effects between TBI exposure in childhood and later impairments across a range of health and social outcomes, age-sensitive clinical guidelines should be considered and preventive strategies should be targeted at children and adolescents

Violent aggression predicted by multiple pre-adult environmental hits

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention

Towards a more evidence-based risk assessment for people in the criminal justice system: the case of OxRec in the Netherlands

Risk assessment tools are widely used throughout the criminal justice system to assist in making decisions about sentencing, supervision, and treatment. In this article, we discuss several methodological and practical limitations associated with risk assessment tools currently in use. These include variable predictive performance due to the exclusion of important background predictors; high costs, including the need for regular staff training, in order to use many tools; development of tools using suboptimal methods and poor transparency in how they create risk scores; included risk factors being based on dated evidence; and ethical concerns highlighted by legal scholars and criminologists, such as embedding systemic biases and uncertainty about how these tools influence judicial decisions. We discuss the potential that specific predictors, such as living in a deprived neighbourhood, may indirectly select for individuals in racial or ethnic minority groups. To demonstrate how these limitations and ethical concerns can be addressed, we present the example of OxRec, a risk assessment tool used to predict recidivism for individuals in the criminal justice system. OxRec was developed in Sweden and has been externally validated in Sweden and the Netherlands. The advantages of OxRec include its predictive accuracy based on rigorous multivariable testing of predictors, transparent reporting of results and the final model (including how the probability score is derived), scoring simplicity (i.e. without the need for additional interview), and the reporting of a wide range of performance measures, including those of discrimination and calibration, the latter of which is rarely reported but a key metric. OxRec is intended to be used alongside professional judgement, as a support for decision-making, and its performance measures need to be interpreted in this light. The reported calibration of the tool in external samples clearly suggests no systematic overestimation of risk, including in large subgroups

Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression:a Swedish population-based case-control study and sib-pair analysis

BackgroundMany studies have addressed the question of whether mental disorder is associated with creativity, but high-quality epidemiological evidence has been lacking.AimsTo test for an association between studying a creative subject at high school or university and later mental disorder.MethodIn a case–control study using linked population-based registries in Sweden (N = 4 454 763), we tested for associations between tertiary education in an artistic field and hospital admission with schizophrenia (N = 20 333), bipolar disorder (N = 28 293) or unipolar depression (N = 148 365).ResultsCompared with the general population, individuals with an artistic education had increased odds of developing schizophrenia (odds ratio = 1.90, 95% CI = [1.69; 2.12]) bipolar disorder (odds ratio = 1.62 [1.50; 1.75]) and unipolar depression (odds ratio = 1.39 [1.34; 1.44]. The results remained after adjustment for IQ and other potential confounders.ConclusionsStudents of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood.Declaration of interestNone.</jats:sec

Neighborhood influences on violent reoffending risk in released prisoners diagnosed with psychotic disorders

Released prisoners diagnosed with psychotic disorders have elevated rates of violent reoffending risk and their exposure to adverse neighborhood environments may contribute to this risk. We identified all released sentenced prisoners in Sweden between 2003 and 2013 (n=47,226) and followed them up for a median period of 4.4 years. We identified prisoners who had ever been diagnosed with a psychotic disorder (n=3782) or prescribed antipsychotics (n=7366). We examined three neighborhood characteristics: income, proportion of welfare recipients, and crime rate. By fitting generalized mixed-effects and negative binomial regression models and adopting within-individual designs that controlled for all time-invariant unmeasured confounders within each individual, we estimated neighborhood intra-class correlations (ICCs) and associations between specific neighborhood characteristics and violent reoffending. Neighborhood factors explained 13.5% (95% CI: 10.9%-16.6%) of the violent reoffending risk among released prisoners diagnosed with psychotic disorders. This contrasted with 4.3% (95% CI: 3.7%-4.9%) in all released prisoners. However, after controlling for unmeasured confounding, these estimates were not statistically significant (ICCpsychotic disorders=0.9%; 95% CI: -0.8%-2.3%; ICCall prisoners=0.3%; 95% CI: -0.02%-0.6%). Similarly, none of the within-individual correlations between the specific neighborhood factors and violent reoffending were significantly different from zero. We found consistent results when we investigated prisoners with other psychiatric and substance use disorders. These findings suggest that placing released prisoners with psychotic disorders in less deprived neighborhoods might not reduce their violent reoffending risk, which may also apply to other psychiatric disorders. The assessment, treatment and community linkage of high-risk prisoners as a strategy to reduce reoffending needs further research

Neighborhood influences on violent reoffending risk in released prisoners diagnosed with psychotic disorders

Released prisoners diagnosed with psychotic disorders have elevated rates of violent reoffending risk and their exposure to adverse neighborhood environments may contribute to this risk. We identified all released sentenced prisoners in Sweden between 2003 and 2013 (n=47,226) and followed them up for a median period of 4.4 years. We identified prisoners who had ever been diagnosed with a psychotic disorder (n=3782) or prescribed antipsychotics (n=7366). We examined three neighborhood characteristics: income, proportion of welfare recipients, and crime rate. By fitting generalized mixed-effects and negative binomial regression models and adopting within-individual designs that controlled for all time-invariant unmeasured confounders within each individual, we estimated neighborhood intra-class correlations (ICCs) and associations between specific neighborhood characteristics and violent reoffending. Neighborhood factors explained 13.5% (95% CI: 10.9%-16.6%) of the violent reoffending risk among released prisoners diagnosed with psychotic disorders. This contrasted with 4.3% (95% CI: 3.7%-4.9%) in all released prisoners. However, after controlling for unmeasured confounding, these estimates were not statistically significant (ICCpsychotic disorders=0.9%; 95% CI: -0.8%-2.3%; ICCall prisoners=0.3%; 95% CI: -0.02%-0.6%). Similarly, none of the within-individual correlations between the specific neighborhood factors and violent reoffending were significantly different from zero. We found consistent results when we investigated prisoners with other psychiatric and substance use disorders. These findings suggest that placing released prisoners with psychotic disorders in less deprived neighborhoods might not reduce their violent reoffending risk, which may also apply to other psychiatric disorders. The assessment, treatment and community linkage of high-risk prisoners as a strategy to reduce reoffending needs further research