Neurodevelopmental disorders and subsequent risk of violent victimization: exploring sex differences and mechanisms.

BACKGROUND: Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood. METHODS: Individuals born in Sweden 1985-1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems. RESULTS: Among 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43-2.70) and females (HR 5.39; 95% CI 4.97-5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06-1.51) and females (HR 1.69; 95% CI 1.21-2.36). CONCLUSIONS: Females with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.

The impact of educational attainment, intelligence and intellectual disability on schizophrenia: a Swedish population-based register and genetic study.

Schizophrenia (SCZ) is highly heterogenous and no subtypes characterizing treatment response or longitudinal course well. Cognitive impairment is a core clinical feature of SCZ and a determinant of poorer outcome. Genetic overlap between SCZ and cognitive traits is complex, with limited studies of comprehensive epidemiological and genomic evidence. To examine the relation between SCZ and three cognitive traits, educational attainment (EDU), premorbid cognitive ability, and intellectual disability (ID), we used two Swedish samples: a national cohort (14,230 SCZ cases and 3,816,264 controls) and a subsample with comprehensive genetic data (4992 cases and 6009 controls). Population-based analyses confirmed worse cognition as a risk factor for SCZ, and the pedigree and SNP-based genetic correlations were comparable. In the genotyped cases, those with high EDU and premorbid cognitive ability tended to have higher polygenetic risk scores (PRS) of EDU and intelligence and fewer rare exonic variants. Finally, by applying an empirical clustering method, we dissected SCZ cases into four replicable subgroups characterized by EDU and ID. In particular, the subgroup with higher EDU in the national cohort had fewer adverse outcomes including long hospitalization and death. In the genotyped subsample, this subgroup had higher PRS of EDU and no excess of rare genetic burdens than controls. In conclusion, we found extensive evidence of a robust relation between cognitive traits and SCZ, underscoring the importance of cognition in dissecting the heterogeneity of SCZ.

Labor epidural analgesia and subsequent risk of offspring autism spectrum disorder and attention-deficit/hyperactivity disorder: a cross-national cohort study of 4.5 million individuals and their siblings.

BACKGROUND: A recent study has suggested that labor epidural analgesia may be associated with increased rates of offspring autism spectrum disorder. Subsequent replication attempts have lacked sufficient power to confidently exclude the possibility of a small effect, and the causal nature of this association remains unknown. OBJECTIVE: This study aimed to investigate the extent to which exposure to labor epidural analgesia is associated with offspring autism spectrum disorder and attention-deficit/hyperactivity disorder following adjustments for unmeasured familial confounding. STUDY DESIGN: We identified 4,498,462 singletons and their parents using the Medical Birth Registers in Finland (cohorts born from 1987-2005), Norway (1999-2015), and Sweden (1987-2011) linked with population and patient registries. These cohorts were followed from birth until they either had the outcomes of interest, emigrated, died, or reached the end of the follow-up (at mean ages 13.6-16.8 years), whichever occurred first. Cox regression models were used to estimate country-specific associations between labor epidural analgesia recorded at birth and outcomes (eg, at least 1 secondary care diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder or at least 1 dispensed prescription of medication used for the treatment of attention-deficit/hyperactivity disorder). The models were adjusted for sex, birth year, birth order, and unmeasured familial confounders via sibling comparisons. Pooled estimates across all the 3 countries were estimated using inverse variance weighted fixed-effects meta-analysis models. RESULTS: A total of 4,498,462 individuals (48.7% female) were included, 1,091,846 (24.3%) of which were exposed to labor epidural analgesia. Of these, 1.2% were diagnosed with autism spectrum disorder and 4.0% with attention-deficit/hyperactivity disorder. On the population level, pooled estimates showed that labor epidural analgesia was associated with increased risk of offspring autism spectrum disorder (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10-1.14, absolute risks, 1.20% vs 1.07%) and attention-deficit/hyperactivity disorder (adjusted hazard ratio, 1.20; 95% confidence interval, 1.19-1.21; absolute risks, 3.95% vs 3.32%). However, when comparing full siblings who were differentially exposed to labor epidural analgesia, the associations were fully attenuated for both conditions with narrow confidence intervals (adjusted hazard ratio [autism spectrum disorder], 0.98; 95% confidence interval, 0.93-1.03; adjusted hazard ratio attention-deficit/hyperactivity disorder, 0.99; 95% confidence interval, 0.96-1.02). CONCLUSION: In this large cross-national study, we found no support for the hypothesis that exposure to labor epidural analgesia causes either offspring autism spectrum disorder or attention-deficit/hyperactivity disorder.

Psychiatric comorbidity and risk of premature mortality and suicide among those with chronic respiratory diseases, cardiovascular diseases, and diabetes in Sweden: A nationwide matched cohort study of over 1 million patients and their unaffected siblings.

BACKGROUND: Persons with noncommunicable diseases have elevated rates of premature mortality. The contribution of psychiatric comorbidity to this is uncertain. We aimed to determine the risks of premature mortality and suicide in people with common noncommunicable diseases, with and without psychiatric disorder comorbidity. METHODS AND FINDINGS: We used nationwide registries to study all individuals born in Sweden between 1932 and 1995 with inpatient and outpatient diagnoses of chronic respiratory diseases (n = 249,825), cardiovascular diseases (n = 568,818), and diabetes (n = 255,579) for risks of premature mortality (≤age 65 years) and suicide until 31 December 2013. Patients diagnosed with either chronic respiratory diseases, cardiovascular diseases, or diabetes were compared with age and sex-matched population controls (n = 10,345,758) and unaffected biological full siblings (n = 1,119,543). Comorbidity with any psychiatric disorder, and by major psychiatric categories, was examined using diagnoses from patient registers. Associations were quantified using stratified Cox regression models that accounted for time at risk, measured sociodemographic factors, and unmeasured familial confounders via sibling comparisons. Within 5 years of diagnosis, at least 7% (range 7.4% to 10.8%; P < 0.001) of patients with respiratory diseases, cardiovascular diseases, or diabetes (median age at diagnosis: 48 to 54 years) had died from any cause, and 0.3% (0.3% to 0.3%; P < 0.001) had died from suicide, 25% to 32% of people with these medical conditions had co-occurring lifetime diagnoses of any psychiatric disorder, most of which antedated the medical diagnosis. Comorbid psychiatric disorders were associated with higher all-cause mortality (15.4% to 21.1%) when compared to those without such conditions (5.5% to 9.1%). Suicide mortality was also elevated (1.2% to 1.6% in comorbid patients versus 0.1% to 0.1% without comorbidity). When we compared relative risks with siblings without noncommunicable diseases and psychiatric disorders, the comorbidity with any psychiatric disorder was associated with substantially increased mortality rates (adjusted HR range: aHRCR = 7.2 [95% CI: 6.8 to 7.7; P < 0.001] to aHRCV = 8.9 [95% CI: 8.5 to 9.4; P < 0.001]). Notably, comorbid substance use disorders were associated with a higher mortality rate (aHR range: aHRCR = 8.3 [95% CI: 7.6 to 9.1; P < 0.001] to aHRCV = 9.9 [95% CI: 9.3 to 10.6; P < 0.001]) than depression (aHR range: aHRCR = 5.3 [95% CI: 4.7 to 5.9; P < 0.001] to aHRCV = 7.4 [95% CI: 7.0 to 7.9; P < 0.001]), but risks of suicide were similar for these 2 psychiatric comorbidities. One limitation is that we relied on secondary care data to assess psychiatric comorbidities, which may have led to missing some patients with less severe comorbidities. Residual genetic confounding is another limitation, given that biological full siblings share an average of half of their cosegregating genes. However, the reported associations remained large even after adjustment for shared and unmeasured familial confounders. CONCLUSIONS: In this longitudinal study of over 1 million patients with chronic health diseases, we observed increased risks of all-cause and suicide mortality in individuals with psychiatric comorbidities. Improving assessment, treatment, and follow-up of people with comorbid psychiatric disorders may reduce the risk of mortality in people with chronic noncommunicable diseases.

Increased schizophrenia family history burden and reduced premorbid IQ in treatment-resistant schizophrenia: a Swedish National Register and Genomic Study.

A high proportion of those with schizophrenia experience treatment non-response, placing them at higher risk for mortality and suicide attempts, compared to treatment responders. The clinical, social, and economic burden of treatment-resistant schizophrenia (TRS) are substantial. Previous genomic and epidemiological studies of TRS were often limited by sample size or lack of comprehensive genomic data. We aimed to systematically understand the clinical, demographic, and genomic correlates of TRS using epidemiological and genetic epidemiological modelling in a Swedish national population sample (n = 24,706) and then in a subgroup with common variant genetic risk scores, rare copy-number variant burden, and rare exonic burden (n = 4936). Population-based analyses identified increasing schizophrenia family history to be significantly associated with TRS (highest quartile of familial burden vs. lowest: adjusted odds ratio (aOR): 1.31, P = 4.8 × 10-8). In males, a decrease of premorbid IQ of one standard deviation was significantly associated with greater risk of TRS (minimal aOR: 0.94, P = 0.002). In a subset of cases with extensive genomic data, we found no significant association between the genetic risk scores of four psychiatric disorders and two cognitive traits with TRS (schizophrenia genetic risk score: aOR = 1.07, P = 0.067). The association between copy number variant and rare variant burden measures and TRS did not reach the pre-defined statistical significance threshold (all P ≥ 0.005). In conclusion, direct measures of genomic risk were not associated with TRS; however, premorbid IQ in males and schizophrenia family history were significantly correlated with TRS and points to new insights into the architecture of TRS.

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.

Associations between individual antipsychotics and the risk of arrests and convictions of violent and other crime: a nationwide within-individual study of 74 925 persons.

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.

Familial confounding affected the associations between maternal smoking during pregnancy and offspring speech and language, scholastic and coordination disorders.

AIM: This study examined the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders in offspring, using sibling and population controls. METHODS: National Finnish registers were used to identify all 690 654 singletons born between 1996 and 2007 and any cases diagnosed with speech and language, scholastic, coordination and mixed developmental disorders by the end of 2012. Cases were compared to population controls, biological full-siblings and maternal half-siblings born during the same period. Conditional logistic regression was used to assess any associations between smoking during pregnancy and the selected developmental disorders. RESULTS: Prenatal smoking was higher in the mothers of the 27 297 cases (21.7%) than the 99 876 population controls (14.5%). The adjusted odds ratio for smoking throughout pregnancy, and any diagnosis of speech and language, scholastic, coordination or mixed developmental disorders, was 1.29 (95% confidence interval 1.24-1.34). However, when we compared a subsample of 15 406 cases and their 20 657 siblings, the association was no longer statistically significant (odds ratio 1.09, 95% confidence interval 0.98-1.21). CONCLUSION: The sibling comparisons suggested that the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders were confounded by familial factors shared by differentially exposed siblings.

Predictive validity of parent- and self-rated ADHD symptoms in adolescence on adverse socioeconomic and health outcomes.

There is scarcity of research investigating the validity of self-report of attention deficit hyperactivity disorder (ADHD) symptoms compared to other informants, such as parents. This study aimed to compare the predictive associations of ADHD symptoms rated by parents and their children across adolescence on a range of adverse socioeconomic and health outcomes in early adulthood. Parent- and self-rated ADHD symptoms were assessed in 2960 individuals in early (13-14 years) and late adolescence (16-17 years). Logistic regression analyses were used to compare the associations between parent- and self-rated ADHD symptoms at both time points and adverse life outcomes in young adulthood obtained from Swedish national registries. Both parent- and self-ratings of ADHD symptoms were associated with increased risk for adverse outcomes, although associations of parent-ratings were more often statistically significant and were generally stronger (OR = 1.12-1.49, p < 0.05) than self-ratings (OR = 1.07-1.17, p < 0.05). After controlling for the other informant, parent-ratings of ADHD symptoms in both early and late adolescence significantly predicted academic and occupational failure, criminal convictions and traffic-related injuries, while self-ratings of ADHD symptoms only in late adolescence predicted substance use disorder and academic failure. Our findings suggest that both parent- and self-ratings of ADHD symptoms in adolescence provides valuable information on risk of future adverse socioeconomic and health outcomes, however, self-ratings are not valuable once parent-ratings have been taken into account in predicting most outcomes. Thus, clinicians and researchers should prioritize parent-ratings over self-ratings.

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.

The association between childhood autistic traits and adolescent psychotic experiences is explained by general neuropsychiatric problems.

Studies suggest associations between childhood autistic traits and adolescent psychotic experiences. However, recent research suggests that a general neuropsychiatric problems factor predicts adverse outcomes better than specific diagnostic entities. To examine if the alleged association between autistic traits and psychotic experiences could rather be explained by a general neuropsychiatric problems factor comprising symptoms of ADHD, tic disorder, developmental coordination disorder, and learning disorder, we conducted a prospective cohort study based on the Child and Adolescent Twin Study in Sweden. In addition, we examined the genetic and environmental influences on the associations. A total of 9,282 twins with data on childhood autistic traits and other neuropsychiatric problems, and follow-up data on psychotic experiences at ages 15 and/or 18 years were included. First, psychotic experiences were regressed on autistic traits and second, the general neuropsychiatric problems factor was added to the model. Auditory hallucinations were analyzed separately from the other psychotic experiences. Finally, twin analyses were employed to disentangle genetic from environmental influences in the observed associations. Replicating prior research, significant associations were found between autistic traits in childhood and auditory hallucinations at ages 15 and 18. However, after controlling for the general neuropsychiatric problems factor, the associations between autistic traits and auditory hallucinations disappeared, whereas the association between the general neuropsychiatric problems factor and auditory hallucinations persisted after controlling for autistic traits. Twin analyses revealed that the association between the general neuropsychiatric problems factor and auditory hallucinations was driven by shared genetic influences. © 2015 Wiley Periodicals, Inc.

Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide.

BACKGROUND: Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant. Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important. We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm. METHODS: Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009. We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009. We also used a Bayesian approach to look at clustering of people who self-harmed. Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed. FINDINGS: 139,195 self-harm incidents were recorded in 26,510 individual prisoners between 2004 and 2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year. Self-harm rates were more than ten times higher in female prisoners than in male inmates. Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17,307 episodes. In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor. Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11-0·18). 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm. Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide. INTERPRETATION: The burden of self-harm in prisoners is substantial, particularly in women. Self-harm in prison is associated with subsequent suicide in this setting. Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons. FUNDING: Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health.

Childhood family income, adolescent violent criminality and substance misuse: quasi-experimental total population study.

BACKGROUND: Low socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviours but the causal mechanisms are questioned. Aims To investigate whether childhood family income predicts subsequent violent criminality and substance misuse and whether the associations are in turn explained by unobserved familial risk factors. METHOD: Nationwide Swedish quasi-experimental, family-based study following cohorts born 1989-1993 (n(total) = 526 167, n(cousins) = 262 267, n(siblings) = 216 424) between the ages of 15 and 21 years. RESULTS: Children of parents in the lowest income quintile experienced a seven-fold increased hazard rate (HR) of being convicted of violent criminality compared with peers in the highest quintile (HR = 6.78, 95% CI 6.23-7.38). This association was entirely accounted for by unobserved familial risk factors (HR = 0.95, 95% CI 0.44-2.03). Similar pattern of effects was found for substance misuse. CONCLUSIONS: There were no associations between childhood family income and subsequent violent criminality and substance misuse once we had adjusted for unobserved familial risk factors.

Family income in early childhood and subsequent attention deficit/hyperactivity disorder: a quasi-experimental study.

BACKGROUND: Studies have found negative associations between socioeconomic position and attention deficit/hyperactivity disorder (ADHD), but it remains unclear if this association is causal. The aim of this study was to determine the extent to which the association between family income in early childhood and subsequent ADHD depends on measured and unmeasured selection factors. METHODS: A total of 811,803 individuals born in Sweden between 1992 and 2000 were included in this nationwide population-based cohort study. Diagnosis of ADHD was assessed via the Swedish national Patient Register and the Swedish Prescribed Drug Register. Annual family income during offspring's first 5 years in life was collected prospectively from the Swedish Integrated Database for Labour Market Research and divided into quartiles by (lower) family disposable income. We predicted ADHD from family income while controlling for covariates and also comparing differently exposed cousins and siblings to control for unmeasured familial confounding. RESULTS: The crude analyses suggested that children exposed to lower income levels were at increased risk for ADHD (HRQ uartile1  = 2.52; 95% CI, 2.42-2.63; HRQ uartile2  = 1.52; 95% CI, 1.45-1.58; HRQ uartile3  = 1.20; 95% CI, 1.14-1.15). This dose-dependent association decreased after adjustment for measured covariates (HRQ uartile1  = 2.09; 95% CI, 2.00-2.19; HRQ uartile2  = 1.36; 95% CI, 1.30-1.42; HRQ uartile3  = 1.13; 95% CI, 1.08-1.18). Although the association was attenuated in cousin comparisons (HRQ uartile1  = 1.61; 95% CI, 1.40-1.84; HRQ uartile2  = 1.28; 95% CI, 1.12-1.45; HRQ uartile3  = 1.14; 95% CI, 1.01-1.28) and sibling comparison models (HRQ uartile1  = 1.37; 95% CI, 1.07-1.75; HRQ uartile2  = 1.37; 95% CI, 1.12-1.68; HRQ uartile3  = 1.23; 95% CI, 1.04-1.45), it remained statistically significant across all levels of decreased disposable family income. CONCLUSIONS: Our results indicated that low family income in early childhood was associated with increased likelihood of ADHD. The link remained even after controlling for unmeasured selection factors, highlighting family income in early childhood as a marker of causal factors for ADHD.

Predicting suicide risk in 137,112 people with severe mental illness in Finland: external validation of the Oxford Mental Illness and Suicide tool (OxMIS).

Oxford Mental Illness and Suicide tool (OxMIS) is a standardised, scalable, and transparent instrument for suicide risk assessment in people with severe mental illness (SMI) based on 17 sociodemographic, criminal history, familial, and clinical risk factors. However, alongside most prediction models in psychiatry, external validations are currently lacking. We utilised a Finnish population sample of all persons diagnosed by mental health services with SMI (schizophrenia-spectrum and bipolar disorders) between 1996 and 2017 (n = 137,112). To evaluate the performance of OxMIS, we initially calculated the predicted 12-month suicide risk for each individual by weighting risk factors by effect sizes reported in the original OxMIS prediction model and converted to a probability. This probability was then used to assess the discrimination and calibration of the OxMIS model in this external sample. Within a year of assessment, 1.1% of people with SMI (n = 1475) had died by suicide. The overall discrimination of the tool was good, with an area under the curve of 0.70 (95% confidence interval: 0.69-0.71). The model initially overestimated suicide risks in those with elevated predicted risks of >5% over 12 months (Harrell's Emax = 0.114), which applied to 1.3% (n = 1780) of the cohort. However, when we used a 5% maximum predicted suicide risk threshold as is recommended clinically, the calibration was excellent (ICI = 0.002; Emax = 0.005). Validating clinical prediction tools using routinely collected data can address research gaps in prediction psychiatry and is a necessary step to translating such models into clinical practice.

Physical injuries as triggers for self-harm: a within-individual study of nearly 250 000 injured people with a major psychiatric disorder.

BACKGROUND: Although there is robust evidence for several factors which may precipitate self-harm, the contributions of different physical injuries are largely unknown. OBJECTIVE: To examine whether specific physical injuries are associated with risks of self-harm in people with psychiatric disorders. METHODS: By using population and secondary care registers, we identified all people born in Finland (1955-2000) and Sweden (1948-1993) with schizophrenia-spectrum disorder (n=136 182), bipolar disorder (n=68 437) or depression (n=461 071). Falls, transport-related injury, traumatic brain injury and injury from interpersonal assault were identified within these subsamples. We used conditional logistic regression models adjusted for age and calendar month to compare self-harm risk in the week after each injury to earlier weekly control periods, which allowed us to account for unmeasured confounders, including genetics and early environments. FINDINGS: A total of 249 210 individuals had been diagnosed with a psychiatric disorder and a physical injury during the follow-up. The absolute risk of self-harm after a physical injury ranged between transport-related injury and injury from interpersonal assault (averaging 17.4-37.0 events per 10 000 person-weeks). Risk of self-harm increased by a factor of two to three (adjusted OR: 2.0-2.9) in the week following a physical injury, as compared with earlier, unexposed periods for the same individuals. CONCLUSIONS: Physical injuries are important proximal risk factors for self-harm in people with psychiatric disorders. CLINICAL IMPLICATIONS: Mechanisms underlying the associations could provide treatment targets. When treating patients with psychiatric illnesses, emergency and trauma medical services should actively work in liaison with psychiatric services to implement self-harm prevention strategies.

Post-traumatic stress disorder and the risk of violent crime conviction in Sweden: a nationwide, register-based cohort study.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been linked to violent crime in veteran populations. However, whether there is a link between PTSD and violent crime in the general population is not known. This study aimed to investigate the hypothesised association between PTSD and violent crime in the Swedish general population and to investigate the extent to which familial factors might explain this association using unaffected sibling control individuals. METHODS: This nationwide, register-based cohort study assessed individuals born in Sweden in 1958-93 for eligibility for inclusion. Individuals who died or emigrated before their 15th birthday, were adopted, were twins, or whose biological parents could not be identified were excluded. Participants were identified and included from the National Patient Register (1973-2013), the Multi-Generation Register (1932-2013), the Total Population Register (1947-2013), and the National Crime Register (1973-2013). Participants with PTSD were matched (1:10) with randomly selected control individuals from the population without PTSD by birth year, sex, and county of residence in the year of PTSD diagnosis for the matched individual. Each participant was followed up from the date of matching (ie, the index person's first PTSD diagnosis) until violent crime conviction or until being censored at emigration, death, or Dec 31, 2013, whichever occurred first. Stratified Cox regressions were used to estimate the hazard ratio of time to violent crime conviction ascertained from national registers in individuals with PTSD compared with control individuals. To account for familial confounding, sibling analyses were conducted, comparing the risk of violent crime in a subsample of individuals with PTSD with their unaffected full biological siblings. FINDINGS: Of 3 890 765 eligible individuals, 13 119 had a PTSD diagnosis (9856 [75·1%] of whom were female and 3263 [24·9%] of whom were male), were matched with 131 190 individuals who did not, and were included in the matched cohort. 9114 individuals with PTSD and 14 613 full biological siblings without PTSD were also included in the sibling cohort. In the sibling cohort, 6956 (76·3%) of 9114 participants were female and 2158 (23·7%) were male. Cumulative incidence of violent crime convictions after 5 years was 5·0% (95% CI 4·6-5·5) in individuals diagnosed with PTSD versus 0·7% (0·6-0·7) in individuals without PTSD. At the end of follow-up (median follow-up time 4·2 years, IQR 2·0-7·6), cumulative incidence was 13·5% (11·3-16·6) versus 2·3% (1·9-2·6). Individuals with PTSD had a significantly higher risk of violent crime than the matched control population in the fully-adjusted model (hazard ratio [HR] 6·4, 95% CI 5·7-7·2). In the sibling cohort, the risk of violent crime was also significantly higher in the siblings with PTSD (3·2, 2·6-4·0). INTERPRETATION: PTSD was associated with increased risk of violent crime conviction, even after controlling for familial effects shared by siblings and in the absence of SUD or a history of violent crime. Although our results might not be generalisable to less severe or undetected PTSD, our study could inform interventions that aim to reduce violent crime in this vulnerable population. FUNDING: None.

Long-term Health and Social Outcomes in Children and Adolescents Placed in Out-of-Home Care.

Importance: Children who are placed in out-of-home care may have poorer outcomes in adulthood, on average, compared with their peers, but the direction and magnitude of these associations need clarification. Objective: To estimate associations between being placed in out-of-home care in childhood and adolescence and subsequent risks of experiencing a wide range of social and health outcomes in adulthood following comprehensive adjustments for preplacement factors. Design, Setting, and Participants: This cohort and cosibling study of all children born in Finland between 1986 and 2000 (N = 855 622) monitored each person from their 15th birthday either until the end of the study period (December 2018) or until they migrated, died, or experienced the outcome of interest. Cox and Poisson regression models were used to estimate associations with adjustment for measured confounders (from linked population registers) and unmeasured familial confounders (using sibling comparisons). Data were analyzed from October 2020 to August 2021. Exposures: Placement in out-of-home care up to age 15 years. Main Outcomes and Measures: Through national population, patient, prescription drug, cause of death, and crime registers, 16 specific outcomes were identified across the following categories: psychiatric disorders; low socioeconomic status; injuries and experiencing violence; and antisocial behaviors, suicidality, and premature mortality. Results: A total of 30 127 individuals (3.4%) were identified who had been placed in out-of-home care for a median (interquartile range) period of 1.3 (0.2-5.1) years and 2 (1-3) placement episodes before age 15 years. Compared with their siblings, individuals who had been placed in out-of-home care were 1.4 to 5 times more likely to experience adverse outcomes in adulthood (adjusted hazard ratio [aHR] for those with a fall-related injury, 1.40; 95% CI, 1.25-1.57 and aHR for those with an unintentional poisoning injury, 4.79; 95% CI, 3.56-6.43, respectively). The highest relative risks were observed for those with violent crime arrests (aHR, 4.16; 95% CI, 3.74-4.62; cumulative incidence, 24.6% in individuals who had been placed in out-of-home care vs 5.1% in those who had not), substance misuse (aHR, 4.75; 95% CI, 4.25-5.30; cumulative incidence, 23.2% vs 4.6%), and unintentional poisoning injury (aHR 4.79; 95% CI, 3.56-6.43; cumulative incidence, 3.1% vs 0.6%). Additional adjustments for perinatal factors, childhood behavioral problems, and traumatic injuries, including experiencing violence, did not materially change the findings. Conclusions and Relevance: Out-of-home care placement was associated with a wide range of adverse outcomes in adulthood, which persisted following adjustments for measured preplacement factors and unmeasured familial factors.