Children born to older fathers are at higher risk to develop severe psychopathology (e.g., schizophrenia and bipolar disorder), possibly because of increased de novo mutations during spermatogenesis with older paternal age. Because severe psychopathology is correlated with antisocial behavior, we examined possible associations between advancing paternal age and offspring violent offending. Interlinked Swedish national registers provided information on fathers' age at childbirth and violent criminal convictions in all offspring born from 1958 to 1979 (N = 2,359,921). We used ever committing a violent crime and number of violent crimes as indices of violent offending. The data included information on multiple levels; we compared differentially exposed siblings in within-family analyses to rigorously test causal influences. In the entire population, advancing paternal age predicted offspring violent crime according to both indices. Congruent with a causal effect, this association remained for rates of violent crime in within-family analyses. However, in within-family analyses, we found no association with ever committing a violent crime, suggesting that factors shared by siblings (genes and environment) confounded this association. Life-course persistent criminality has been proposed to have a partly biological etiology; our results agree with a stronger biological effect (i.e., de novo mutations) on persistent violent offending.
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Posttraumatic stress disorder (PTSD) has been associated with impaired educational performance. Previous studies on the disorder could not control for important measured and unmeasured confounders.
To prospectively investigate the association between PTSD and objective indicators of educational attainment across the life span, controlling for familial factors shared by full siblings, psychiatric comorbidity, and general cognitive ability.
This population-based cohort study included 2?244?193 individuals born in Sweden between January 1, 1973, and December 31, 1997, who were followed-up until December 31, 2013. Clusters of full siblings were used to account for familial factors. Data analyses were conducted between December 2018 and May 2020.
International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of PTSD in the Swedish National Patient Register.
Eligibility to access upper secondary education after finishing compulsory education, finishing upper secondary education, starting a university degree, and finishing a university degree.
Of the final cohort of 2?244?193 individuals (1?151?414 [51.3%] men) included in the analysis, 1?425?326 were assessed for finishing compulsory education (919 with PTSD), 2?001?944 for finishing upper secondary education (2013 with PTSD), and 1?796?407 and 1?356?741 for starting and finishing a university degree (2243 and 2254 with PTSD, respectively). Posttraumatic stress disorder was associated with lower odds of achieving each of the educational milestones during the study period, including 82% lower odds of finishing compulsory education (adjusted odds ratio [aOR], 0.18; 95% CI, 0.15-0.20), 87% lower odds of finishing upper secondary education (aOR, 0.13; 95% CI, 0.12-0.14), 68% lower odds of starting a university degree (aOR, 0.32; 95% CI, 0.28-0.35), and 73% lower odds of finishing a university degree (aOR, 0.27; 95% CI, 0.23-0.31). Estimates in the sibling comparison were attenuated (aOR range, 0.22-0.53) but remained statistically significant. Overall, excluding psychiatric comorbidities and adjusting for the successful completion of the previous milestone and general cognitive ability did not statistically significantly alter the magnitude of the associations.
Posttraumatic stress disorder was associated with educational impairment across the life span, and the associations were not entirely explained by shared familial factors, psychiatric comorbidity, or general cognitive ability. This finding highlights the importance of implementing early trauma-informed interventions in schools and universities to minimize the long-term socioeconomic consequences of academic failure in individuals with PTSD.
Few quantitative behavior genetic studies have examined why psychopathology is associated with suicide attempt (SA) and self-harm (SH) in adolescence. The present study analyzed data from the Child and Adolescent Twin Study in Sweden to examine the extent to which genetic and environmental factors explain SA/SH and its association with psychopathology in childhood, an often-cited risk factor of subsequent SA/SH. When children were 9 or 12 years old (n = 30,444), parents completed the Autism-Tics, AD/HD and other Comorbidities Inventory (Larson et al., 2010) regarding their children's psychiatric problems as part of an ongoing, longitudinal study. At age 18 years (n = 10,269), adolescents completed self-report questionnaires, including SA/SH assessments. In a bifactor model of childhood psychopathology, a general factor of psychopathology was a statistically significant predictor of adolescent SA/SH at a higher magnitude (ß, 0.25, 95% confidence interval [CI; 0.15, 0.34] for suicide attempt), as compared with specific factors of inattention, impulsivity, oppositional behavior, and anxiety/emotion symptoms. Quantitative genetic modeling indicated that the additive genetic influences on the general factor accounted for the association with each outcome (ß, 0.24, 95% CI [0.13, 0.34] for suicide attempt). The results remained virtually identical when we fit a higher order factors model. Two additional outcomes demonstrated comparable results. The results extend current literature by revealing the shared genetic overlap between general psychopathology during childhood and adolescent SA/SH. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Several recent population-based studies have linked exposure to maternal smoking during pregnancy to increased risk of severe mental illness in offspring (eg, bipolar disorder, schizophrenia). It is not yet clear, however, whether this association results from causal teratogenic effects or from confounding influences shared by smoking and severe mental illness.
To examine the association between smoking during pregnancy and severe mental illness in offspring, adjusting for measured covariates and unmeasured confounding using family-based designs.
This study analyzed population register data through December 31, 2013, for a cohort of 1 680 219 individuals born in Sweden from January 1, 1983, to December 31, 2001. Associations between smoking during pregnancy and severe mental illness in offspring were estimated with adjustment for measured covariates. Cousins and siblings who were discordant on smoking during pregnancy and severe mental illness were then compared, which helped to account for unmeasured genetic and environmental confounding by design.
Maternal self-reported smoking during pregnancy, obtained from antenatal visits.
Severe mental illness, with clinical diagnosis obtained from inpatient and outpatient visits and defined using International Classification of Diseases codes for bipolar disorder and schizophrenia spectrum disorders.
Of the 1 680 219 offspring included in the analysis, 816 775 (48.61%) were female. At the population level, offspring exposed to moderate and high levels of smoking during pregnancy had greater severe mental illness rates than did unexposed offspring (moderate smoking during pregnancy: hazard ratio [HR], 1.25; 95% CI, 1.19-1.30; high smoking during pregnancy: HR, 1.51; 95% CI, 1.44-1.59). These associations decreased in strength with increasing statistical and methodologic controls for familial confounding. In sibling comparisons with within-family covariates, associations were substantially weaker and nonsignificant (moderate smoking during pregnancy: HR, 1.09; 95% CI, 0.94-1.26; high smoking during pregnancy: HR, 1.14; 95% CI, 0.96-1.35). The pattern of associations was consistent across subsets of severe mental illness disorders and was supported by further sensitivity analyses.
This population- and family-based study failed to find support for a causal effect of smoking during pregnancy on risk of severe mental illness in offspring. Rather, these results suggest that much of the observed population-level association can be explained by measured and unmeasured factors shared by siblings.
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 to 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 non-violent 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 non-violent 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 non-violent 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 also target risk factors influencing all offspring of teenage mothers.
Induction of labor is a frequently performed obstetrical intervention. It would thus be of great concern if reported associations between labor induction and offspring risk of autism spectrum disorders (ASD) reflected causal influence.
To assess the associations of labor induction with ASD, comparing differentially exposed relatives (siblings and cousins discordant for induction).
Follow-up of all live births in Sweden between 1992 and 2005, defined in the Medical Birth Register. The register was linked to population registers of familial relations, inpatient and outpatient visits, and education records. Diagnoses of ASD were from 2001 through 2013, and data were analyzed in the 2015-2016 year.
Induction of labor.
Autism spectrum disorders identified by diagnoses from inpatient and outpatient records between 2001 and 2013. Hazard ratios (HRs) quantified the association between labor induction and offspring ASD. In addition to considering a wide range of measured confounders, comparison of exposure-discordant births to the same woman allowed additional control for all unmeasured factors shared by siblings.
The full cohort included 1?362?950 births, of which 22?077 offspring (1.6%) were diagnosed with ASD by ages 8 years through 21 years. In conventional models of the full cohort, associations between labor induction and offspring ASD were attenuated but remained statistically significant after adjustment for measured potential confounders (HR, 1.19; 95% CI, 1.13-1.24). When comparison was made within siblings whose births were discordant with respect to induction, thus accounting for all environmental and genetic factors shared by siblings, labor induction was no longer associated with offspring ASD (HR, 0.99; 95% CI, 0.88-1.10).
In this nationwide sample of live births we observed no association between induction of labor and offspring ASD within sibling comparison. Our findings suggest that concern for ASD should not factor into the clinical decision about whether to induce labor.
To our knowledge, the association of obsessive-compulsive disorder (OCD) and academic performance has not been objectively quantified.
To investigate the association of OCD with objectively measured educational outcomes in a nationwide cohort, adjusting for covariates and unmeasured factors shared between siblings.
This population-based birth cohort study included 2?115?554 individuals who were born in Sweden between January 1, 1976, and December 31, 1998, and followed up through December 31, 2013. Using the Swedish National Patient Register and previously validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, we identified persons with OCD; within the cohort, we identified 726?198 families with 2 or more full siblings, and identified 11?482 families with full siblings discordant for OCD. Data analyses were conducted from October 1, 2016, to September 25, 2017.
The study evaluates the following educational milestones: eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, finishing a university degree, and finishing postgraduate education.
Of the 2?115?554 individuals in the cohort, 15?120 were diagnosed with OCD (59% females). Compared with unexposed individuals, those with OCD were significantly less likely to pass all core and additional courses at the end of compulsory school (adjusted odds ratio [aOR] range, 0.35-0.60) and to access a vocational or academic program in upper secondary education (aOR, 0.47; 95% CI, 0.45-0.50 and aOR, 0.61; 95% CI, 0.58-0.63, for vocational and academic programs, respectively). People with OCD were also less likely to finish upper secondary education (aOR, 0.43; 95% CI, 0.41-0.44), start a university degree (aOR, 0.72; 95% CI, 0.69-0.75), finish a university degree (aOR, 0.59; 95% CI, 0.56-0.62), and finish postgraduate education (aOR, 0.52; 95% CI, 0.36-0.77). The results were similar in the sibling comparison models. Individuals diagnosed with OCD before age 18 years showed worse educational attainment across all educational levels compared with those diagnosed at or after age 18 years. Exclusion of patients with comorbid neuropsychiatric disorders, psychotic, anxiety, mood, substance use, and other psychiatric disorders resulted in attenuated estimates, but patients with OCD were still impaired across all educational outcomes.
Obsessive-compulsive disorder, particularly when it has an early onset, is associated with a pervasive and profound decrease in educational attainment, spanning from compulsory school to postgraduate education.
To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors.
A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins).
A total of 3?004?401 people born in Sweden between 1951 and 1998.
The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses.
In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI) = 4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI = -0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI = 5.17-5.18; grades: 0.09, 95% CI = 0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI = 4.15-4.20; grades: -0.83, 95% CI = -0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI = 4.59-4.60; grades: -0.38, 95% CI = -0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors.
There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.
Perinatal complications may increase the risk of obsessive-compulsive disorder (OCD). Previous reports were based on small, retrospective, specialist clinic-based studies that were unable to rigorously control for unmeasured environmental and genetic confounding.
To prospectively investigate a wide range of potential perinatal risk factors for OCD, controlling for unmeasured factors shared between siblings in the analyses.
This population-based birth cohort study included all 2?421?284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1?403?651 families in the cohort, differentially exposed siblings from the 743?885 families with siblings were evaluated; of these, 11?592 families included clusters of full siblings that were discordant for OCD. Analysis of the data was conducted from January, 26, 2015, to September, 5, 2016.
Perinatal data were collected from the Swedish Medical Birth Register and included maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age (for preterm birth), birth weight, birth weight in relation to gestational age, 5-minute Apgar score, and head circumference.
Previously validated OCD codes (International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish National Patient Register.
Of 2?421?284 individuals included in the cohort, 17?305 persons were diagnosed with OCD. Of these, 7111 were men (41.1%). The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years. An increased risk for OCD remained after controlling for shared familial confounders and measured covariates (including sex, year of birth, maternal and paternal age at birth, and parity), for smoking 10 or more cigarettes per day during pregnancy (hazard ratio [HR], 1.27; 95% CI, 1.02-1.58), breech presentation (HR, 1.35; 95% CI, 1.06-1.71), delivery by cesarean section (HR, 1.17; 95% CI, 1.01-1.34), preterm birth (HR, 1.24; 95% CI, 1.07-1.43), birth weight 1501 to 2500 g (HR, 1.30; 95% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08; 95% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95% CI, 1.05-1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95% CI, 1.07-2.09). Gestational age and birth weight followed inverse dose-response associations, whereby an increasingly higher risk for OCD was noted in children with a shorter gestational age and lower birth weight. We also observed a dose-response association between the number of perinatal events and increased OCD risk, with HRs ranging from 1.11 (95% CI, 1.07-1.15) for 1 event to 1.51 (95% CI, 1.18-1.94) for 5 or more events.
A range of perinatal risk factors is associated with a higher risk for OCD independent of shared familial confounders, suggesting that perinatal risk factors may be in the causal pathway to OCD.
A previous register-based study reported elevated all-cause mortality in attention-deficit/hyperactivity disorder (ADHD), but cause-specific risks and the potential associations of psychiatric comorbidities remain unknown.
To investigate the all-cause and cause-specific mortality risks in ADHD and to explore the potential role of psychiatric comorbidities.
This prospective cohort study used Swedish national registers to identify 2 675 615 individuals born in Sweden from January 1, 1983, through December 31, 2009, as the study population, among whom 86 670 individuals (3.2%) received a diagnosis of ADHD during follow-up. Follow-up was completed December 31, 2013, and data were analyzed from October 2018 through March 2019.
Attention-deficit/hyperactivity disorder identified by first clinical diagnosis or first prescription of ADHD medications as recorded in Swedish registers. Clinical diagnosis of psychiatric comorbidity was available in the National Patient Register.
All-cause and cause-specific mortalities and hazard ratios (HRs) using Cox proportional hazards regression models.
In the overall cohort of 2 675 615 individuals, 1 374 790 (51.4%) were male (57 919 with an ADHD diagnosis) and 1 300 825 (48.6%) were female (28 751 with an ADHD diagnosis). Mean (SD) age at study entry was 6.4 (5.6) years. During follow-up, 424 individuals with ADHD and 6231 without ADHD died, resulting in mortality rates of 11.57 and 2.16 per 10 000 person-years, respectively. The association was stronger in adulthood (HR, 4.64; 95% CI, 4.11-5.25) compared with childhood (HR, 1.41; 95% CI, 0.97-2.04) and increased substantially with the number of psychiatric comorbidities with ADHD (HR for individuals with only ADHD, 1.41 [95% CI, 1.01-1.97]; HR for those with =4 comorbidities, 25.22 [95% CI, 19.60-32.46]). In adulthood, when adjusting for early-onset psychiatric comorbidity, the association between ADHD and risk of death due to natural causes was attenuated substantially and was no longer statistically significant (HR, 1.32; 95% CI, 0.94-1.85). When adjusting for later-onset psychiatric disorders, the association was attenuated to statistical nonsignificance for death due to suicide (HR, 1.13; 95% CI, 0.88-1.45) but remained statistically significant for death caused by unintentional injury (HR, 2.14; 95% CI, 1.71-2.68) or other external causes (HR, 1.75; 95% CI, 1.23-2.48).
Psychiatric comorbidity appears to play an important role in all-cause and cause-specific mortality risks in ADHD. In adulthood, early-onset psychiatric comorbidity contributed primarily to the association with death due to natural causes, whereas later-onset psychiatric comorbidity mainly influenced death due to unnatural causes, including suicide and unintentional injury. These findings suggest that health care professionals should closely monitor specific psychiatric comorbidities in individuals with ADHD to identify high-risk groups for prevention efforts.