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1.  Stimulant ADHD medication and risk for substance abuse 
Background
There are persistent concerns of long-term effects of stimulant ADHD medication on the development of substance abuse.
Methods
Using Swedish national registers, we studied all individuals born 1960–1998 and diagnosed with ADHD (26,249 men and 12,504 women). We investigated the association between stimulant ADHD medication in 2006 and substance abuse during 2009. Substance abuse was indexed by substance-related death, crime, or hospital visits.
Results
ADHD medication was not associated with increased rate of substance abuse. Actually, the rate during 2009 was 31% lower among those prescribed ADHD medication in 2006, even after controlling for medication in 2009 and other covariates (hazard ratio: 0.69; 95% confidence interval: 0.57–0.84). Also the longer duration of medication, the lower the rate of substance abuse. Similar risk reductions were suggested among children and when investigating the association between stimulant ADHD medication and concomitant short-term abuse.
Conclusions
We found no indication of increased risks of substance abuse among individuals prescribed stimulant ADHD medication; if anything, the data suggested a long-term protective effect on substance abuse. Although stimulant ADHD medication does not seem to increase the risk for substance abuse, clinicians should remain alert to the potential problem of stimulant misuse and diversion in ADHD patients.
doi:10.1111/jcpp.12164
PMCID: PMC4147667  PMID: 25158998
ADHD; Pharmacology; Substance abuse
2.  Suicide after release from prison - a population-based cohort study from Sweden 
The Journal of clinical psychiatry  2014;75(10):1047-1053.
Objective
Released prisoners have high suicide rates compared with the general population, but little is known about risk factors and possible causal pathways. We conducted a population-based cohort study to investigate rates and risk factors for suicide in people previously imprisoned.
Methods
We identified individuals released from prison in Sweden between January 1, 2005 and December 31, 2009 through linkage of national population-based registers. Released prisoners were followed from the day of release until death, emigration, new incarceration, or December 31, 2009. Survival analyses were conducted to compare incidence rates and psychiatric morbidity with non-convicted population controls matched on gender and year of birth.
Results
We identified 38,995 releases among 26,953 prisoners (7.6% females) during 2005-2009. Overall, 127 suicides occurred, accounting for 14% of all deaths after release (n=920). The mean suicide rate was 204 per 100,000 person years yielding an incidence rate ratio of 18.2 (95% CI 13.9-23.8) compared with general population controls. Previous substance use disorder (Hazard Ratio [HR]=2.1, 1.4-3.2), suicide attempt (HR=2.5, 1.7-3.7), and being born in Sweden vs. abroad (HR=2.1, 1.2-3.6) were independent risk factors for suicide after release.
Conclusions
Released prisoners are at high suicide risk and with a slightly different pattern of psychiatric risk factors for suicide compared with the general population. Results suggest appropriate allocation of resources to facilitate transition to life outside prison and increased attention to prisoners with both a previous suicide attempt and substance use disorder.
doi:10.4088/JCP.13m08967
PMCID: PMC4520329  PMID: 25373114
Suicide; Risk factors; Ex-prisoners
3.  The association of maternal diabetes in pregnancy with offspring adiposity into early adulthood: Sibling study in a prospective cohort of 280,866 men from 248,293 families 
Circulation  2011;123(3):258-265.
Background
Maternal diabetes in pregnancy results in greater offspring adiposity at birth. It is unclear whether it is associated with greater adiposity into adulthood, and if so whether this is via intrauterine mechanisms or shared familial characteristics.
Methods and Results
A record linkage prospective cohort study of 280,866 singleton-born Swedish men from 248,293 families was used to explore the intrauterine effect of maternal diabetes on offspring body mass index (BMI) in early adulthood. Maternal diabetes during pregnancy was associated with greater mean BMI at age 18 in their sons. The difference in BMI was similar within brothers and between non-siblings. BMI of men whose mothers had diabetes during their pregnancy was on average 0.94kg/m2 greater (95%CI: 0.35, 1.52) than in their brothers born before their mother was diagnosed with diabetes, after adjustment for birth year, maternal age, parity and education, birthweight, gestational age and age at assessment of BMI. Early-pregnancy BMI was positively associated with son’s BMI between non-siblings, but there was no association within brothers. Adjustment of the maternal diabetes-offspring BMI association for maternal BMI did not alter the association either within brothers or between non-siblings. Results were also robust to sensitivity analyses restricting the within sibling analyses to siblings born within 3 years of each other.
Conclusion
Maternal diabetes has long-term consequences for greater BMI in offspring and this association is likely to be via intrauterine mechanisms and is independent of maternal BMI in early pregnancy.
doi:10.1161/CIRCULATIONAHA.110.980169
PMCID: PMC4440894  PMID: 21220735
Pregnancy diabetes; developmental overnutrition; obesity; epidemiology
4.  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 is 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 offspring ADHD depends on measured and unmeasured selection factors.
Methods
A total of 811,803individuals 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 offsprings' first five years in life was collected prospectively from the Swedish Integrated Database for Labour Market Research (LISA) 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 (HRQuartile1=2.52; 95% CI, 2.42–2.63; HRQuartile2=1.52; 95% CI, 1.45–1.58; HRQuartile3=1.20; 95% CI, 1.14–1.15). This dose-dependent association decreased after adjustment for measured covariates (HRQuartile1=2.09; 95% CI, 2.00–2.19; HRQuartile2=1.36; 95% CI, 1.30–1.42; HRQuartile3=1.13; 95% CI, 1.08–1.18). Although the association was attenuated in cousin comparisons (HRQuartile1=1.61; 95% CI, 1.40–1.84; HRQuartile2=1.28; 95% CI, 1.12–1.45; HRQuartile3=1.14; 95% CI, 1.01–1.28) and sibling comparison models (HRQuartile1=1.37; 95% CI, 1.07–1.75; HRQuartile2=1.37; 95% CI, 1.12–1.68; HRQuartile3=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 potential causal risk factor for ADHD.
doi:10.1111/jcpp.12140
PMCID: PMC3962802  PMID: 24111650
ADHD; family income; childhood; causality; quasi-experimental approaches
5.  Sexual offending runs in families: A 37-year nationwide study 
Background: Sexual crime is an important public health concern. The possible causes of sexual aggression, however, remain uncertain.
Methods: We examined familial aggregation and the contribution of genetic and environmental factors to sexual crime by linking longitudinal, nationwide Swedish crime and multigenerational family registers. We included all men convicted of any sexual offence (N = 21 566), specifically rape of an adult (N = 6131) and child molestation (N = 4465), from 1973 to 2009. Sexual crime rates among fathers and brothers of sexual offenders were compared with corresponding rates in fathers and brothers of age-matched population control men without sexual crime convictions. We also modelled the relative influence of genetic and environmental factors to the liability of sexual offending.
Results: We found strong familial aggregation of sexual crime [odds ratio (OR) = 5.1, 95% confidence interval (CI) = 4.5–5.9] among full brothers of convicted sexual offenders. Familial aggregation was lower in father-son dyads (OR = 3.7, 95% CI = 3.2–4.4) among paternal half-brothers (OR = 2.1, 95% CI = 1.5–2.9) and maternal half-brothers (OR = 1.7, 95% CI = 1.2–2.4). Statistical modelling of the strength and patterns of familial aggregation suggested that genetic factors (40%) and non-shared environmental factors (58%) explained the liability to offend sexually more than shared environmental influences (2%). Further, genetic effects tended to be weaker for rape of an adult (19%) than for child molestation (46%).
Conclusions: We report strong evidence of familial clustering of sexual offending, primarily accounted for by genes rather than shared environmental influences. Future research should possibly test the effectiveness of selective prevention efforts for male first-degree relatives of sexually aggressive individuals, and consider familial risk in sexual violence risk assessment.
doi:10.1093/ije/dyv029
PMCID: PMC4469797  PMID: 25855722
Crime; sexual; violence; rape; sexual abuse; family relations
6.  Does Population Density and Neighborhood Deprivation Predict Schizophrenia? A Nationwide Swedish Family-Based Study of 2.4 Million Individuals 
Schizophrenia bulletin  2014;41(2):494-502.
People living in densely populated and socially disorganized areas have higher rates of psychiatric morbidity, but the potential causal status of such factors is uncertain. We used nationwide Swedish longitudinal registry data to identify all children born 1967–1989 (n = 2 361 585), including separate datasets for all cousins (n = 1 715 059) and siblings (n = 1 667 894). The nature of the associations between population density and neighborhood deprivation and individual risk for a schizophrenia diagnosis was investigated while adjusting for unobserved familial risk factors (through cousin and sibling comparisons) and then compared with similar associations for depression. We generated familial pedigree structures using the Multi-Generation Registry and identified study participants with schizophrenia and depression using the National Patient Registry. Fixed-effects logistic regression models were used to study within-family estimates. Population density, measured as ln(population size/km2), at age 15 predicted subsequent schizophrenia in the population (OR = 1.10; 95% CI: 1.09; 1.11). Unobserved familial risk factors shared by cousins within extended families attenuated the association (1.06; 1.03; 1.10), and the link disappeared entirely within nuclear families (1.02; 0.97; 1.08). Similar results were found for neighborhood deprivation as predictor and for depression as outcome. Sensitivity tests demonstrated that timing and accumulation effects of the exposures (mean scores across birth, ages 1–5, 6–10, and 11–15 years) did not alter the findings. Excess risks of psychiatric morbidity, particularly schizophrenia, in densely populated and socioeconomically deprived Swedish neighborhoods appear, therefore, to result primarily from unobserved familial selection factors. Previous studies may have overemphasized the etiological importance of these environmental factors.
doi:10.1093/schbul/sbu105
PMCID: PMC4332947  PMID: 25053652
schizophrenia; urbanization; socioeconomic factors; multilevel models; confounding factors; quasiexperimental designs
7.  Offspring psychopathology following preconception, prenatal, and postnatal maternal bereavement stress 
Psychological medicine  2013;44(1):10.1017/S0033291713000780.
Background
Preconception, prenatal, and postnatal maternal stress are 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.
Methods
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 through 2009. Maternal stress was defined as death of a first degree relative during 6 months before conception, across pregnancy, or the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HR) 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 risk of ASD (adjusted HR=1.58, 95% CI: 1.15–2.17) and ADHD (adjusted HR=1.31, 95% CI: 1.04–1.66). First postnatal year stress increased risk for offspring suicide attempt (adjusted HR=1.13, 95% CI: 1.02–1.25) and completed suicide (adjusted HR=1.51, 95% CI: 1.08–2.11). Bereavement stress during the second postnatal year increased risk of ASD (adjusted HR=1.30, 95% CI: 1.09–1.55).
Conclusions
Further research is needed on associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases risk of offspring suicide attempt, completed suicide, and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes.
doi:10.1017/S0033291713000780
PMCID: PMC3766407  PMID: 23591021
stress; preconception; prenatal; postnatal; psychiatric; psychopathology; autism; attention-deficit/hyperactivity disorder; schizophrenia; suicide
8.  Preterm birth and mortality and morbidity: A population-based quasi-experimental study 
JAMA psychiatry (Chicago, Ill.)  2013;70(11):10.1001/jamapsychiatry.2013.2107.
Context
Preterm birth is associated with increased mortality and morbidity. However, previous studies have been unable to rigorously examine whether confounding factors cause these associations rather than the harmful effects of being born preterm.
Objective
To estimate the extent to which the associations between early gestational age and offspring mortality and morbidity were due to confounds by using a quasi-experimental design, the sibling-comparison approach, and controlling for statistical covariates that varied within families.
Design, Setting, and Participants
A population-based cohort study, combining Swedish registries to identify all individuals born in Sweden from 1973–2008 (n=3,300,708 offspring of 1,736,735 mothers) and link them with multiple outcomes.
Main Outcome Measures
Offspring mortality (during infancy and throughout young adulthood) and psychiatric (psychotic or bipolar disorder, autism, ADHD, suicide attempts, substance use, and criminality), academic (failing grades and educational attainment), and social (partnering, parenthood, low income, social welfare benefits) outcomes through 2009.
Results
In the population, there was a dose-response relation between early gestation and the outcome measures. For instance, extreme preterm birth (23–27 weeks of gestation) was associated with infant mortality (OR=288.1, 95% CI=271.7–305.5), autism (HR=3.2, CI=2.6–4.0), low educational attainment (HR=1.7, CI=1.5–2.0), and social welfare benefits (HR=1.3, CI=1.2–1.5) compared to offspring born at term. The associations between early gestation and mortality and psychiatric morbidity generally were robust when comparing differentially exposed siblings and controlling for statistical covariates, whereas the associations with academic and some social problems were greatly or completely attenuated in the fixed effects models.
Conclusions
The mechanisms responsible for the associations between preterm birth and mortality and morbidity are outcome-specific. Associations between preterm birth and mortality and psychiatric morbidity were largely independent of shared familial confounds and measured covariates, consistent with a causal inference. Some associations, particularly predicting suicide attempt, educational attainment, and social welfare benefits were due to confounding factors, however.
doi:10.1001/jamapsychiatry.2013.2107
PMCID: PMC3823714  PMID: 24068297
9.  FAMILY HISTORY OF SCHIZOPHRENIA AND BIPOLAR DISORDER AS RISK FACTORS FOR AUTISM 
Archives of general psychiatry  2012;69(11):1099-1103.
Background
The clinical and etiological relation between autism spectrum disorders (ASD) and schizophrenia is unclear. The degree to which these disorders share a basis in etiology has important implications for clinicians, researchers, and those affected. Our objective was to determine if a family history of schizophrenia and/or bipolar disorder was a risk factor for ASD. We conducted a case-control evaluation of histories of schizophrenia or bipolar disorder in first-degree relatives of probands in three samples, population registers in Sweden, Stockholm County, and Israel. Probands met criteria for ASD, and affection status of parents and siblings for schizophrenia and bipolar disorder were established.
Findings
The presence of schizophrenia in parents was associated with an increased risk for ASD in a Swedish national cohort (odds ratio 2.9, 95% CI 2.5–3.4) and in a Stockholm County cohort (odds ratio 2.9, 95% CI 2.0–4.1). Similarly, schizophrenia in a sibling was associated with an increased risk for ASD in a Swedish national cohort (odds ratio 2.6, 95% CI 2.0–3.2) and in an Israeli conscription cohort (odds ratio 12.1, 95% CI 4.5–32). Bipolar disorder showed a similar pattern of associations but of lesser magnitude.
Interpretation
Findings from these three registers along with consistent findings from a similar study in Denmark suggest that ASD, schizophrenia, and bipolar disorder share common etiological factors.
Funding
Swedish Council for Working Life and Social Research, the Swedish Research Council, and the Beatrice and Samuel A. Seaver Foundation.
doi:10.1001/archgenpsychiatry.2012.730
PMCID: PMC4187103  PMID: 22752149
autism spectrum disorder; schizophrenia; bipolar disorder; family history; genetics; risk factor; exposure; genetic epidemiology
10.  Antipsychotics, mood stabilisers, and risk of violent crime 
Lancet  2014;384(9949):1206-1214.
Summary
Background
Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden.
Methods
We used linked Swedish national registers to study 82 647 patients who were prescribed antipsychotics or mood stabilisers, their psychiatric diagnoses, and subsequent criminal convictions in 2006–09. We did within-individual analyses to compare the rate of violent criminality during the time that patients were prescribed these medications versus the rate for the same patients while they were not receiving the drugs to adjust for all confounders that remained constant within each participant during follow-up. The primary outcome was the occurrence of violent crime, according to Sweden’s national crime register.
Findings
In 2006–09, 40 937 men in Sweden were prescribed antipsychotics or mood stabilisers, of whom 2657 (6·5%) were convicted of a violent crime during the study period. In the same period, 41 710 women were prescribed these drugs, of whom 604 (1·4 %) had convictions for violent crime. Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics (hazard ratio [HR] 0·55, 95% CI 0·47–0·64) and by 24% in patients prescribed mood stabilisers (0·76, 0·62–0·93). However, we identified potentially important differences by diagnosis—mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder. The rate of violence reduction for antipsychotics remained between 22% and 29% in sensitivity analyses that used different outcomes (any crime, drug-related crime, less severe crime, and violent arrest), and was stronger in patients who were prescribed higher drug doses than in those prescribed low doses. Notable reductions in violent crime were also recorded for depot medication (HR adjusted for concomitant oral medications 0·60, 95% CI 0·39–0·92).
Interpretation
In addition to relapse prevention and psychiatric symptom relief, the benefits of antipsychotics and mood stabilisers might also include reductions in the rates of violent crime. The potential effects of these drugs on violence and crime should be taken into account when treatment options for patients with psychiatric disorders are being considered.
Funding
The Wellcome Trust, the Swedish Prison and Probation Service, the Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare.
doi:10.1016/S0140-6736(14)60379-2
PMCID: PMC4165625  PMID: 24816046
11.  Antipsychotics, mood stabilisers, and risk of violent crime 
Lancet  2014;384(9949):1206-1214.
Summary
Background
Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden.
Methods
We used linked Swedish national registers to study 82 647 patients who were prescribed antipsychotics or mood stabilisers, their psychiatric diagnoses, and subsequent criminal convictions in 2006–09. We did within-individual analyses to compare the rate of violent criminality during the time that patients were prescribed these medications versus the rate for the same patients while they were not receiving the drugs to adjust for all confounders that remained constant within each participant during follow-up. The primary outcome was the occurrence of violent crime, according to Sweden's national crime register.
Findings
In 2006–09, 40 937 men in Sweden were prescribed antipsychotics or mood stabilisers, of whom 2657 (6·5%) were convicted of a violent crime during the study period. In the same period, 41 710 women were prescribed these drugs, of whom 604 (1·4 %) had convictions for violent crime. Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics (hazard ratio [HR] 0·55, 95% CI 0·47–0·64) and by 24% in patients prescribed mood stabilisers (0·76, 0·62–0·93). However, we identified potentially important differences by diagnosis—mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder. The rate of violence reduction for antipsychotics remained between 22% and 29% in sensitivity analyses that used different outcomes (any crime, drug-related crime, less severe crime, and violent arrest), and was stronger in patients who were prescribed higher drug doses than in those prescribed low doses. Notable reductions in violent crime were also recorded for depot medication (HR adjusted for concomitant oral medications 0·60, 95% CI 0·39–0·92).
Interpretation
In addition to relapse prevention and psychiatric symptom relief, the benefits of antipsychotics and mood stabilisers might also include reductions in the rates of violent crime. The potential effects of these drugs on violence and crime should be taken into account when treatment options for patients with psychiatric disorders are being considered.
Funding
The Wellcome Trust, the Swedish Prison and Probation Service, the Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare.
doi:10.1016/S0140-6736(14)60379-2
PMCID: PMC4165625  PMID: 24816046
12.  Occupational Complexity and Risk of Parkinson's Disease 
PLoS ONE  2014;9(9):e106676.
Background
The etiology of Parkinson's disease (PD) remains unclear, and environmental risk-factors such as occupation have attracted interest.
Objective
The goal was to investigate occupational complexity in relation to PD.
Methods
We conducted a population-based cohort study based on the Swedish Twin Registry that included 28,778 twins born between 1886 and 1950. We identified 433 PD cases during the study period. Data on occupation were collected from either the 1970 or 1980 Swedish census, and occupational complexity was assessed via a job exposure matrix. Cox proportional hazard regression analyses with age as the underlying time scale were used to assess PD risk as a function of the three domains of occupational complexity: data, people, and things. Sex and smoking were included as covariates. Analyses stratified by twin pair were conducted to test for confounding by familial factors.
Results
High occupational complexity with data and people was associated with increased risk overall (Hazard Ratio [HR] = 1.07, 95% confidence interval [CI] 1.02–1.14, and HR = 1.10, 95% CI 1.01–1.21, respectively), and in men (HR = 1.08, 95% CI 1.01–1.16, and HR = 1.15, 95% CI 1.03–1.28, respectively). Complexity with things was not associated with risk of PD. When the analyses were stratified by twin pair, the HRs for occupational complexity with data and people were attenuated in men.
Conclusions
High complexity of work with data and people is related to increased risk of PD, particularly in men. The attenuation of risk observed in the twin pair-stratified analyses suggests that the association may partly be explained by familial factors, such as inherited traits contributing to occupational selection or other factors shared by twins.
doi:10.1371/journal.pone.0106676
PMCID: PMC4157797  PMID: 25198429
13.  Parental Socioeconomic Status, Childhood Asthma and Medication Use – A Population-Based Study 
PLoS ONE  2014;9(9):e106579.
Background
Little is known about how parental socioeconomic status affects offspring asthma risk in the general population, or its relation to healthcare and medication use among diagnosed children.
Methods
This register-based cohort study included 211,520 children born between April 2006 and December 2008 followed until December 2010. Asthma diagnoses were retrieved from the National Patient Register, and dispensed asthma medications from the Prescribed Drug Register. Parental socioeconomic status (income and education) were retrieved from Statistics Sweden. The associations between parental socioeconomic status and outcomes were estimated by Cox proportional hazard regression.
Results
Compared to the highest parental income level, children exposed to all other levels had increased risk of asthma during their first year of life (e.g. hazard ratio, HR 1.19, 95% confidence interval, CI 1.09–1.31 for diagnosis and HR 1.17, 95% CI 1.08–1.26 for medications for the lowest quintile) and the risk was decreased after the first year, especially among children from the lowest parental income quintile (HR 0.84, 95% CI 0.77–0.92 for diagnosis, and HR 0.80, 95% CI 0.74–0.86 for medications). Further, compared to children with college-educated parents, those whose parents had lower education had increased risk of childhood asthma regardless of age. Children with the lowest parental education had increased risk of an inpatient (HR 2.07, 95% CI 1.61–2.65) and outpatient (HR 1.32, 95% CI 1.18–1.47) asthma diagnosis. Among diagnosed children, those from families with lower education used fewer controller medications than those whose parents were college graduates.
Conclusions
Our findings indicate an age-varying association between parental income and childhood asthma and consistent inverse association regardless of age between parental education and asthma incidence, dispensed controller medications and inpatient care which should be further investigated and remedied.
doi:10.1371/journal.pone.0106579
PMCID: PMC4154738  PMID: 25188036
14.  Teenage childbirth and young adult criminal convictions: A quasi-experimental study of criminal outcomes for teenage mothers 
Journal of criminal justice  2013;41(5):318-323.
Purpose
Teenage childbirth is associated with poor psychosocial outcomes for teen mothers. One example is that teen mothers have higher rates of antisocial behavior. The extant research has not been able to determine if teenage motherhood is independently associated with criminal behavior, or if the association is due to selection factors associated with both teenage childbirth and criminal behavior.
Methods
We used longitudinal data from Swedish national registers and sibling-comparisons (both full- and half-siblings) to identify the extent to which there is an independent association between teenage childbirth and mothers’ likelihood of criminal conviction between ages 20-30, or if the association is confounded by familial (including genetic or environmental) factors that make sisters similar.
Results
Women who began childbearing as teenagers were more likely to be convicted of a crime in young adulthood compared to women who delayed childbearing. When sisters were compared, the association between teenage childbirth and criminal convictions disappeared. Multivariate behavior genetic analyses suggest genetic and shared environmental account for the association.
Conclusions
The statistical association between teenage childbirth and early adulthood criminal convictions is confounded by genetic and shared environmental factors that influence both the likelihood of teenage childbirth and risk of early adulthood criminal conviction.
PMCID: PMC3769799  PMID: 24039311
Teenage mothers; teenage childbirth; criminality
15.  Fetal and Maternal Genes’ Influence on Gestational Age in a Quantitative Genetic Analysis of 244,000 Swedish Births 
American Journal of Epidemiology  2013;178(4):543-550.
Although there is increasing evidence that genetic factors influence gestational age, it is unclear to what extent this is due to fetal and/or maternal genes. In this study, we apply a novel analytical model to estimate genetic and environmental contributions to pregnancy history records obtained from 165,952 Swedish families consisting of offspring of twins, full siblings, and half-siblings (1987–2008). Results indicated that fetal genetic factors explained 13.1% (95% confidence interval (CI): 6.8, 19.4) of the variation in gestational age at delivery, while maternal genetic factors accounted for 20.6% (95% CI: 18.1, 23.2). The largest contribution to differences in the timing of birth were environmental factors, of which 10.1% (95% CI: 7.0, 13.2) was due to factors shared by births of the same mother, and 56.2% (95% CI: 53.0, 59.4) was pregnancy specific. Similar models fit to the same data dichotomized at clinically meaningful thresholds (e.g., preterm birth) resulted in less stable parameter estimates, but the collective results supported a model of homogeneous genetic and environmental effects across the range of gestational age. Since environmental factors explained most differences in the timing of birth, genetic studies may benefit from understanding the specific effect of fetal and maternal genes in the context of these yet-unidentified factors.
doi:10.1093/aje/kwt005
PMCID: PMC3736752  PMID: 23568591
environment; fetal genes; gestational age; maternal genes; preterm birth; twins
16.  The impact of neighbourhood deprivation on adolescent violent criminality and substance misuse: A longitudinal, quasi-experimental study of the total Swedish population 
Background A number of studies suggest associations between neighbourhood characteristics and criminality during adolescence and young adulthood. However, the causality of such neighbourhood effects remains uncertain.
Methods We followed all children born in Sweden from 1975–1989 who lived in its three largest cities by the age of 15 years and for whom complete information was available about individual and contextual factors (N = 303 465). All biological siblings were identified in the sample (N = 179 099). Generalized linear mixed-effects models were used to assess the effect of neighbourhood deprivation on violent criminality and substance misuse between the ages of 15 and 20 years, while taking into account the cross-classified data structure (i.e. siblings in the same families attending different schools and living in different neighbourhoods at age 15).
Results In the crude model, an increase of 1 SD in neighbourhood deprivation was associated with a 57% increase in the odds of being convicted of a violent crime (95% CI 52%–63%). The effect was greatly attenuated when adjustment was made for a number of observed confounders (OR 1.09, 95% CI 1.06–1.11). When we additionally adjusted for unobserved familial confounders, the effect was no longer present (OR 0.96, 95% CI 0.84–1.10). Similar results were observed for substance misuse. The results were not due to poor variability either between neighbourhoods or within families.
Conclusions We found that the adverse effect of neighbourhood deprivation on adolescent violent criminality and substance misuse in Sweden was not consistent with a causal inference. Instead, our findings highlight the need to control for familial confounding in multilevel studies of criminality and substance misuse.
doi:10.1093/ije/dyt066
PMCID: PMC3780994  PMID: 24062294
Violence; substance-related disorders; residence characteristics; socio-economic factors; multi-level analysis; confounding factors
17.  Does attention deficit hyperactivity disorder share etiologic factors with bipolar disorder and schizophrenia? 
BACKGROUND
ADHD is associated with bipolar disorder and schizophrenia, and it has been suggested that combined bipolar disorder/ADHD is etiologically distinct from the pure disorders.
AIM
To clarify if ADHD shares genetic and environmental factors with bipolar disorder and schizophrenia.
METHODS
By linking longitudinal Swedish national registers, we identified 61,187 ADHD probands and their first and second-degree relatives and matched them with non-ADHD controls and their corresponding relatives. Conditional logistic regression was used to determine risks for bipolar disorder and schizophrenia in relatives of probands vs. controls.
RESULTS
First-degree relatives of ADHD probands were at increased risk of both bipolar disorder (ORs from 1.84 to 2.54 for parents, offspring and full siblings) and schizophrenia (ORs from 1.71 to 2.22 for parents, offspring and full siblings). The risk of bipolar disorder and schizophrenia among second-degree relatives were substantially lower than among full-siblings.
CONCLUSIONS
These findings suggest that co-occurring ADHD and bipolar disorder and ADHD plus schizophrenia are due to shared genetic factors, rather than representing completely etiologically distinct sub-syndromes.
doi:10.1192/bjp.bp.112.120808
PMCID: PMC3730113  PMID: 23703314
ADHD; Bipolar disorder; Schizophrenia; Comorbidity; Family study
18.  Maternal stress and infant mortality: The importance of the preconception period 
Psychological science  2013;24(7):1309-1316.
Although preconception and prenatal maternal stress are associated with adverse birth and childhood outcomes, the relation to infant mortality remains uncertain. We used logistic regression to study infant mortality risk following maternal stress within a population-based sample of offspring born in Sweden from 1973 to 2008 (N= 3,055,361). Preconception (6-0 months before conception) and prenatal (conception to birth) stress was defined as death of a first-degree relative of the mother. A total of 20,651 offspring were exposed to preconception stress, 26,731 to prenatal stress, and 8,398 cases of infant mortality were identified. Preconception stress increased the risk of infant mortality independent of measured covariates (adjusted OR=1.53; 95% CI=1.25–1.88) and the association was timing-specific and robust across low-risk groups. Prenatal stress did not increase risk of infant mortality (adjusted OR=1.05; 95% CI=0.84–1.30). The period immediately before conception may be a sensitive developmental period influencing risk for infant mortality.
doi:10.1177/0956797612468010
PMCID: PMC3713176  PMID: 23653129
Preconception; prenatal; maternal stress; bereavement; infant mortality
19.  Suicide, Fatal Injuries, and Other Causes of Premature Mortality in Patients With Traumatic Brain Injury 
JAMA psychiatry  2014;71(3):326-333.
IMPORTANCE
Longer-term mortality in individuals who have survived a traumatic brain injury (TBI) is not known.
OBJECTIVES
To examine the relationship between TBI and premature mortality, particularly by external causes, and determine the role of psychiatric comorbidity.
DESIGN, SETTING, AND PATIENTS
We studied all persons born in 1954 or later in Sweden who received inpatient and outpatient International Classification of Diseases-based diagnoses of TBI from 1969 to 2009 (n = 218 300). We compared mortality rates 6 months or more after TBI to general population controls matched on age and sex (n = 2 163 190) and to unaffected siblings of patients with TBI (n = 150 513). Furthermore, we specifically examined external causes of death (suicide, injury, or assault). We conducted sensitivity analyses to investigate whether mortality rates differed by sex, age at death, severity (including concussion), and different follow-up times after diagnosis.
MAIN OUTCOMES AND MEASURES
Adjusted odds ratios (AORs) of premature death by external causes in patients with TBI compared with general population controls.
RESULTS
Among those who survived 6 months after TBI, we found a 3-fold increased odds of mortality (AOR, 3.2; 95% CI, 3.0-3.4) compared with general population controls and an adjusted increased odds of mortality of 2.6 (95% CI, 2.3-2.8) compared with unaffected siblings. Risks of mortality from external causes were elevated, including for suicide (AOR, 3.3; 95% CI, 2.9-3.7), injuries (AOR, 4.3; 95% CI, 3.8-4.8), and assault (AOR, 3.9; 95% CI, 2.7-5.7). Among those with TBI, absolute rates of death were high in those with any psychiatric or substance abuse comorbidity (3.8% died prematurely) and those with solely substance abuse (6.2%) compared with those without comorbidity (0.5%).
CONCLUSIONS AND RELEVANCE
Traumatic brain injury is associated with substantially elevated risks of premature mortality, particularly for suicide, injuries, and assaults, even after adjustment for sociodemographic and familial factors. Current clinical guidelines may need revision to reduce mortality risks beyond the first few months after injury and address high rates of psychiatric comorbidity and substance abuse.
doi:10.1001/jamapsychiatry.2013.3935
PMCID: PMC4058552  PMID: 24430827
20.  The association between teenage motherhood and poor offspring outcomes: A national cohort study across 30 years 
Teenage motherhood is associated with poor offspring outcomes but these associations may be influenced by offspring birth year because of substantial social changes in recent decades. Existing research also has not examined whether these associations are due to the specific effect of mother’s age at childbirth or factors shared by siblings in a family. We used a population-based cohort study in Sweden comprising all children born from 1960–1989 (N=3,162,239), and a subsample of siblings differentially exposed to maternal teenage childbearing (N=485,259) to address these limitations. We examined the effect of teenage childbearing on offspring violent and nonviolent criminal convictions, poor academic performance, and substance-related problems. Population-wide, teenage childbearing was associated with offspring criminal convictions, poor academic performance, and substance-related problems. The magnitude of these associations increased over time. Comparisons of differentially exposed siblings indicated no within-family association between teenage childbearing and offspring violent and nonviolent criminal convictions or poor academic performance, although offspring born to teenage mothers were more likely to experience substance-related problems than their later-born siblings. Being born to a teenage mother in Sweden has become increasingly associated with negative outcomes across time, but the nature of this association may differ by outcome. Teenage childbearing may be associated with offspring violent and nonviolent criminal convictions and poor academic performance because of shared familial risk factors but may be causally associated with offspring substance-related problems. The findings suggest that interventions to improve offspring outcomes should delay teenage childbearing and target risk factors influencing all offspring of teenage mothers.
doi:10.1017/thg.2013.23
PMCID: PMC3657321  PMID: 23632141
Teenage childbearing; teenage motherhood; criminal behavior; substance use; academic attainment; academic achievement
22.  Why Does Early Sexual Intercourse Predict Subsequent Maladjustment? Exploring Potential Familial Confounds 
Objective
Previous studies have found an association between early age at first sexual intercourse and subsequent psychosocial maladjustment. Using a quasi-experimental approach, we examined the extent to which this observed association may be due to familial confounds not explored in prior research.
Methods
Using a population-based cohort of Swedish adult twins (ages 19–47; N = 12,126), we examined the nature of the association between early sexual intercourse (i.e., first intercourse occurring before age 16) and various outcomes reflecting psychosocial health, including substance use, depression, criminal convictions, and adolescent childbearing. We used two methods—discordant-twin analyses and bivariate twin modeling—to estimate the extent to which genetic and environmental confounds explained observed associations.
Results
Individuals who engaged in early intercourse were at greater risk for most of the adverse psychosocial health outcomes measured in this study. Twin pairs discordant for engaging in early intercourse, however, did not differ significantly in their risk for psychosocial maladjustment. Our results indicated that early age at first sexual intercourse and subsequent psychosocial maladjustment may be associated due to familial factors shared by twins.
Conclusion
Early intercourse may be associated with poor psychosocial health largely due to shared familial influences rather than through a direct causal connection. Effective and efficient interventions, therefore, should address other risk factors common to both early intercourse and poor psychosocial health.
doi:10.1037/a0028922
PMCID: PMC3664184  PMID: 22708520
adolescence; sexual behavior; sex-education programs; behavior genetics
23.  Testing Putative Causal Associations of Risk Factors for Early Intercourse in the Study of Twin Adults: Genes and Environment (STAGE) 
Archives of sexual behavior  2012;42(1):35-44.
Adverse childhood experiences and substance use have been identified as potential causal risk factors for early-onset sexual intercourse. While it is possible that exposure to these risk factors directly increases the likelihood of engaging in early intercourse, an alternative explanation is that observed associations between these variables are due to shared familial confounds. These unmeasured confounds may increase the likelihood of being exposed to these risk factors and of engaging in early intercourse. Participants drawn from a population-based study of Swedish adult twins (ages 19–47 years; N = 12,126) reported on their history of exposure to early physical and sexual trauma, cigarette use, and cannabis use. We investigated the nature of the association between these risk factors and young age at first intercourse, using a comparison of twins differentially exposed to each risk factor. When compared to non-exposed, unrelated individuals, participants who reported adverse childhood experiences or who engaged in early cigarette use or cannabis use were more likely to engage in early intercourse. However, co-twin comparisons indicated that observed associations between these risk factors and early intercourse may be due to familial factors shared within twin pairs, and risk factor exposure may not lead directly to early intercourse. Our results suggest that preventing trauma exposure or preventing or delaying adolescents’ cigarette smoking or cannabis use may not effectively delay intercourse onset; instead, other aspects of the adolescent’s environment should be addressed.
doi:10.1007/s10508-012-9947-1
PMCID: PMC3473173  PMID: 22441771
adolescence; sexual behavior; substance use; child abuse; co-twin comparison; behavioral genetics
24.  Medication for Attention Deficit-Hyperactivity Disorder and Criminality 
The New England journal of medicine  2012;367(21):2006-2014.
Background
Attention deficit hyperactivity disorder (ADHD) is a common disorder that is associated with criminal behavior. Pharmacological treatment is available for ADHD and may reduce the risk of criminality
Methods
We gathered information on all individuals with a diagnosis of ADHD (N=25,656), their pharmacological treatment, and subsequent criminal convictions in Sweden during 2006 to 2009 using Swedish national registers. We used stratified Cox regression analyses to compare the rate of criminality while on ADHD medication, compared with the rate for the same individual while off medication.
Results
Compared to non-medication periods, the criminality rate while on medication was significantly decreased by 32% (stratified Cox Regression hazard ratio: 0.68; 95 % confidence interval: 0.63-0.73) for men and 41% (hazard ratio: 0.59; 95 % confidence interval: 0.50-0.70) for women. The rate reduction remained between 17-46% in sensitivity analyses among males, including different exposures (e.g., type of treatment – stimulant and non-stimulant) and outcomes (e.g., type of crime - less severe, violent, and substance-related conviction).
Conclusions
We found statistically significant associations between ADHD medication and criminality in within-individual comparisons, with lower rates of criminality observed during periods on treatment. These findings raise the possibility that medication treatment reduces the risk of criminality among patients with ADHD.
doi:10.1056/NEJMoa1203241
PMCID: PMC3664186  PMID: 23171097
25.  Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study 
Lancet  2013;382(9905):1646-1654.
Summary
Background
Epilepsy is associated with high rates of premature mortality, but the contribution of psychiatric comorbidity is uncertain. We assessed the prevalence and risks of premature mortality from external causes such as suicide, accidents, and assaults in people with epilepsy with and without psychiatric comorbidity.
Methods
We studied all individuals born in Sweden between 1954 and 2009 with inpatient and outpatient diagnoses of epilepsy (n=69 995) for risks and causes of premature mortality. Patients were compared with age-matched and sex-matched general population controls (n=660 869) and unaffected siblings (n=81 396). Sensitivity analyses were done to investigate whether these odds differed by sex, age, seizure types, comorbid psychiatric diagnosis, and different time periods after epilepsy diagnosis.
Results
6155 (8.8%) people with epilepsy died during follow-up, at a median age of 34·5 (IQR 21·0–44·0) years with substantially elevated odds of premature mortality (adjusted odds ratio [aOR] of 11·1 [95% CI 10·6–11·6] compared with general population controls, and 11·4 [10·4–12·5] compared with unaffected siblings). Of those deaths, 15·8% (n=972) were from external causes, with high odds for non-vehicle accidents (aOR 5·5, 95 % CI 4·7–6·5) and suicide (3·7, 3·3–4·2). Of those who died from external causes, 75·2% had comorbid psychiatric disorders, with strong associations in individuals with co-occurring depression (13·0, 10·3–16·6) and substance misuse (22·4, 18·3–27·3), compared with patients with no epilepsy and no psychiatric comorbidity.
Interpretation
Reducing premature mortality from external causes of death should be a priority in epilepsy management. Psychiatric comorbidity plays an important part in the premature mortality seen in epilepsy. The ability of health services and public health measures to prevent such deaths requires review.
Funding
Wellcome Trust, the Swedish Prison and Probation Service, and the Swedish Research Council.
doi:10.1016/S0140-6736(13)60899-5
PMCID: PMC3899026  PMID: 23883699

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