Exploring the causal nature of neighborhood influences on violent criminality, substance misuse and psychiatric morbidity

Individuals who live in socioeconomically deprived neighborhoods, particularly in urban settings, experience elevated risk of being convicted of violent criminality, to engage in substance misuse and to be diagnosed with psychiatric disorders. The causal nature of these associations is questioned in the literature because previous studies have insufficiently accounted for genetic and environmental risks shared within families. The aim of the dissertation was therefore to explore the etiological relevance of neighborhoods in these traits by combining quasi-experimental, family-based research designs with nationwide Swedish registry data. In Studies I and II, we investigated the associations between residence in deprived neighborhoods and family income during childhood on subsequent risks of being convicted of violent offences and to engage in substance misuse. We found that biological full-siblings who had been differentially exposed to deprived neighborhoods, due to residential relocations between their birthdays, or to family income, due to the parents’ career trajectories, did not differ from one another in terms of their risks for being convicted or to engage in substance misuse. In Study III, we studied the associations between neighborhood deprivation and population density on later risks of being diagnosed with schizophrenia. Biological full-siblings who had been differentially exposed to the different neighborhood conditions did not differ from one another in terms of their risks of schizophrenia. In Study IV, we used quantitative genetic models that compared biological full and half-siblings to understand the etiology of social drift in schizophrenia. We found that the heritability of living in deprived neighborhoods was 60 percent. Schizophrenia patients were more likely to live in deprived neighborhoods but this was due to common genetic influences. In conclusion, we found that familial risks simultaneously explained parental selection into high-risk neighborhoods as well as their offspring’s increased risks of adverse outcomes. Methodologically, these studies emphasize the importance of accounting for unobserved familial confounders in epidemiological studies of socioeconomic status and later behavioral and psychiatric outcomes. Substantively, the findings indicate that efficient prevention efforts to decrease the rates of the examined outcomes must consider a broader range of familial and individual risks than merely socioeconomic and demographic measures, at least in the Swedish context

Risk of Subjection to Violence and Perpetration of Violence in Persons With Psychiatric Disorders in Sweden

Importance Key outcomes for persons with psychiatric disorders include subjection to violence and perpetration of violence. The occurrence of these outcomes and their associations with psychiatric disorders need to be clarified. Objective To estimate the associations of a wide range of psychiatric disorders with the risks of subjection to violence and perpetration of violence. Design, Setting, and Participants A total of 250 419 individuals born between January 1, 1973, and December 31, 1993, were identified to have psychiatric disorders using Swedish nationwide registers. Premorbid subjection to violence was measured since birth. The patients were matched by age and sex to individuals in the general population (n = 2504 190) and to their full biological siblings without psychiatric disorders (n = 194 788). The start date for the patients and control groups was defined as the discharge date of the first psychiatric episode. The participants were censored either when they migrated, died, experienced the outcome of interest, or reached the end of the study period on December 31, 2013. Data were analyzed from January 15 to September 14, 2019. Exposures Patients with common psychiatric disorders (eg, schizophrenia, bipolar disorder, depression, and anxiety) were differentiated using a hierarchical approach. Patients with personality disorders and substance use disorders were also included. Main Outcomes and Measures Subjection to violence was defined as an outpatient visit (excluding a primary care visit), inpatient episode, or death associated with any diagnosis of an injury that was purposefully inflicted by other persons. Perpetration of violence was defined as a violent crime conviction. Stratified Cox regression models were fitted to account for the time at risk, a range of sociodemographic factors, a history of violence, and unmeasured familial confounders (via sibling comparisons). Results Among 250 419 patients (55.4% women), the median (interquartile range) age at first diagnosis ranged from 20.0 (17.4-24.0) years for alcohol use disorder to 23.7 (19.9-28.8) years for anxiety disorder. Compared with 2504 190 matched individuals without psychiatric disorders from the general population, patients with psychiatric disorders were more likely to be subjected to violence (7.1 [95% CI, 6.9-7.2] vs 1.0 [95% CI, 0.9-1.0] per 1000 person-years) and to perpetrate violence (7.5 [95% CI, 7.4-7.6] vs 0.7 [95% CI, 0.7-0.7] per 1000 person-years). In the fully adjusted models, patients with psychiatric disorders were 3 to 4 times more likely than their siblings without psychiatric disorders to be either subjected to violence (adjusted hazard ratio [aHR], 3.4 [95% CI, 3.2-3.6]) or to perpetrate violence (aHR, 4.2 [95% CI, 3.9-4.4]). Diagnosis with any of the specific disorders was associated with higher rates of violent outcomes, with the sole exception of schizophrenia, which was not associated with the risk of subjection to violence. Conclusions and Relevance In this study, persons with psychiatric disorders were 3 to 4 times more likely than their siblings without psychiatric disorders to have been subjected to violence or to have perpetrated violence after the onset of their conditions. The risks of both outcomes varied by specific psychiatric diagnosis, history of violence, and familial risks. Clinical interventions may benefit from targeted approaches for the assessment and management of risk of violence in people with psychiatric disorders.Peer reviewe

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

Background: Low socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviors but the causal mechanisms are questioned. Aims: To investigate if the associations between childhood family income and subsequent adolescent criminality and substance misuse are explained by unobserved familial risk factors. Method: Swedish population-based quasi-experimental, family-based study following cohorts born 1989-1993 (ntotal=529,428; ncousins=262,816; nsiblings=217,035) from their 15th birthday up until the end of 2009. Results: Children of parents in the lowest income quintile experienced a seven-fold increased hazard rate of being convicted of violent criminality compared to peers in the highest quintile (HR=6.84, 95% CI: 6.28-7.44). This association was entirely accounted for by unobserved familial risk factors (HR=0.99; 95% CI: 0.46-2.13). Similar pattern of effects was found for substance misuse. Conclusions: There are no associations between childhood family income and subsequent violent criminality and substance misuse once unobserved familial risk factors are adjusted for.The Swedish Council for Working Life and Social ResearchThe Swedish Research CouncilThe National Institute of Child Health and Human DevelopmentAccepte

Associations between individual antipsychotics and the risk of arrests and convictions of violent and other crime : a nationwide within-individual study of 74925 persons

Background Individuals diagnosed with psychiatric disorders who are prescribed antipsycho-tics 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. Method 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 zuclo-penthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, ris-peridone, 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.Peer reviewe

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

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.</p

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 (ASD). 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 To investigate the extent to which exposure to labor epidural analgesia is associated with offspring ASD and attention-deficit/hyperactivity disorder (ADHD) 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 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 (e.g., at least one secondary care diagnosis of ASD and ADHD or at least one dispensed prescription of medication used for the treatment of ADHD). The models were adjusted for sex, birth year, birth order, and unmeasured familial confounders via sibling-comparisons. Pooled estimates across all three 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 ASD and 4.0% with ADHD. On the population level, pooled estimates showed that labor epidural analgesia was associated with increased risk of offspring ASD (adjusted hazard ratio, aHR=1.12; 95% CI: 1.10-1.14, absolute risks: 1.20% vs. 1.07%) and ADHD (aHR=1.20; 1.19-1.21; 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 (aHRASD=0.98; 0.93-1.03; aHRADHD=0.99; 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 ASD or ADHD.Peer reviewe

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.Peer reviewe