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.
Cites: Am Psychol. 1989 Feb;44(2):329-352653143
Cites: Arch Gen Psychiatry. 2003 Sep;60(9):929-3712963675
Cites: Arch Gen Psychiatry. 1999 Mar;56(3):223-410078498
Center for Innovation in Mental Health, Academic Unit of Psychology, and Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; New York University Child Study Center, New York, NY, USA; Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK. Electronic address: email@example.com.
Several studies have assessed the possible association between attention deficit hyperactivity disorder (ADHD) and asthma. However, existing evidence is inconclusive as to whether this association remains after controlling for possible important confounders. To fill this knowledge gap, we did a systematic review and meta-analysis, followed by a population-based study.
For the systematic review and meta-analysis, we searched PubMed, PsycINFO, Embase, Embase Classic, Ovid MEDLINE, and Web of Knowledge databases up to Oct 31, 2017, for observational studies allowing estimation of the association between asthma and ADHD. No restrictions to date, language, or article type were applied. Unpublished data were collected from authors of the identified studies. We extracted unadjusted and adjusted odds ratios (ORs) from the identified studies and calculated ORs when they were not reported. We assessed study quality using the Newcastle-Ottawa Scale and study heterogeneity using I2 statistics. A random-effects model was used to calculate pooled ORs. The systematic review is registered with PROSPERO (CRD42017073368). To address the fact that the ORs obtained in the meta-analysis were adjusted for confounders that inevitably varied across studies, we did a population-based study of individuals in multiple national registers in Sweden. We calculated an unadjusted OR and an OR that was simultaneously adjusted for all confounders identified in a directed acyclic graph based on the studies of asthma and ADHD identified in our systematic review.
We identified 2649 potentially eligible citations, from which we obtained 49 datasets including a total of 210?363 participants with ADHD and 3?115?168 without. The pooled unadjusted OR was 1·66 (95% CI 1·22-2·26; I2 =99·47) and the pooled adjusted OR was 1·53 (1·41-1·65; I2 =50·76), indicating a significant association between asthma and ADHD. Possible lack of representativeness of the study population was detected with the Newcastle-Ottawa Scale in 42 of 49 datasets. In the population-based study, we included 1?575?377 individuals born between Jan 1, 1992, and Dec 31, 2006, of whom 259?253 (16·5%) had asthma and 57?957 (3·7%) had ADHD. Asthma was significantly associated with ADHD (OR 1·60, 95% CI 1·57-1·63) in the crude model adjusting for sex and year of birth, and this association remained significant after simultaneous adjustment for all covariates (1·45, 1·41-1·48).
The combined results of the meta-analysis and the population-based study support a significant association between asthma and ADHD, which remained even after simultaneously controlling for several possible confounders in the population-based study. Awareness of this association might help to reduce delay in the diagnosis of both ADHD and asthma.
Swedish Research Council and Shire International GmbH.
Individuals who self-harm may have an increased risk of aggression toward others, but this association has been insufficiently investigated. More conclusive evidence may affect assessment, treatment interventions, and clinical guidelines.
To investigate the association between nonfatal self-harm and violent crime.
This population-based longitudinal cohort study, conducted from January 1, 1997, through December 31, 2013, studied all Swedish citizens born between 1982 and 1998 who were 15 years and older (N?=?1?850?252). Individuals who emigrated from Sweden before the age of 15 years (n?=?104?051) or immigrated to Sweden after the age of 13 years (ie,
Violent criminality is at least moderately heritable, but the mechanisms behind this remain largely unexplained. Height, a highly heritable trait, may be involved but no study has estimated the effect of height on crime while simultaneously accounting for important demographic, biological and other heritable confounders.
We linked nationwide, longitudinal registers for 760 000 men who underwent mandatory military conscription from 1980 through 1992 in Sweden, to assess the association between height and being convicted of a violent crime. We used Cox proportional hazard modelling and controlled for three types of potential confounders: physical characteristics, childhood demographics and general cognitive ability (intelligence).
In unadjusted analyses, height had a moderate negative relationship to violent crime; the shortest of men were twice as likely to be convicted of a violent crime as the tallest. However, when simultaneously controlling for all measured confounders, height was weakly and positively related to violent crime. Intelligence had the individually strongest mitigating effect on the height-crime relationship.
Although shorter stature was associated with increased risk of violent offending, our analyses strongly suggested that this relationship was explained by intelligence and other confounding factors. Hence, it is unlikely that height, a highly heritable physical characteristic, accounts for much of the unexplained heritability of violent criminality.
Comment In: Int J Epidemiol. 2014 Jun;43(3):639-4425050434
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.
Differences in cardiovascular autonomic activity between individuals with psychiatric disorders and healthy controls have been observed, but whether cardiovascular autonomic abnormalities are associated with subsequent psychiatric disorders is unknown.
To investigate whether differences in cardiac autonomic function as indexed by resting heart rate and blood pressure are associated with psychiatric disorders during the lifetime of men in Sweden.
We conducted a longitudinal register-based study of Swedish men whose resting heart rate (n?=?1?039?443) and blood pressure (n?=?1?555?979) were measured at military conscription at a mean (SD) age of 18.3 (0.6) years during the period from 1969 to 2010, with register-based follow-up data available until the end of 2013. Analyses were performed from November 18, 2015, to June 9, 2016.
Dates of inpatient/outpatient diagnoses of anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, depressive disorders, bipolar disorder, schizophrenia, and substance use disorders and convictions for violent crimes, between 1973 and 2013, were obtained from nationwide registers. Adjustments were made for height, weight, body mass index, cardiorespiratory fitness, cognitive ability, and socioeconomic covariates.
After adjustment for covariates, Cox regression models with up to 45 years of follow-up data showed that men (mean [SD] age of 18.3 [0.6] years at conscription) with resting heart rates above 82 beats per minute had a 69% (95% CI, 46%-94%) increased risk for obsessive-compulsive disorder, a 21% (95% CI, 11%-33%) increased risk for schizophrenia, and an 18% (95% CI, 13%-22%) increased risk for anxiety disorders compared with men with resting heart rates below 62 beats per minute. Similar associations were observed with systolic/diastolic blood pressure. In contrast, lower resting heart rate and lower systolic blood pressure were associated with substance use disorders and violent criminality.
Our results suggest that for men, differences in heart rate and blood pressure in late adolescence are associated with lifetime major psychiatric disorders, with higher levels associated with obsessive-compulsive disorder, schizophrenia, and anxiety disorders and lower levels associated with substance use disorders and violent behavior. Differences in autonomic nervous system functioning may predate or represent an early marker of psychiatric disorders.
Bipolar disorder (BPD) shares genetic components with other psychiatric disorders; however, uncertainty remains about where in the psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the familial aggregation of BPD and co-aggregation between BPD and schizophrenia, depression, anxiety disorders, attention-deficit hyperactivity disorder, drug abuse, personality disorders, and autism spectrum disorders.
A population-based cohort was created by linking several Swedish national registers. A total of 54,723 individuals with BPD were identified among 8,141,033 offspring from 4,149,748 nuclear families. The relative risk of BPD in relatives and the co-occurrence of other psychiatric disorders in patients with BPD and their relatives were compared to those of matched-population controls. Structural equation modeling was used to estimate the heritability and tetrachoric correlation.
The familial risks for relatives of BPD probands were 5.8-7.9 in first-degree relatives, and decreased with genetic distance. Co-occurrence risks for other psychiatric disorders were 9.7-22.9 in individuals with BPD and 1.7-2.8 in full siblings of BPD probands. Heritability for BPD was estimated at 58%. The correlations between BPD and other psychiatric disorders were considerable (0.37-0.62) and primarily due to genetic effects. The correlation with depression was the highest (0.62), and was 0.44 for schizophrenia.
The high familial risks provide evidence that genetic factors play an important role in the etiology of BPD, and the shared genetic determinants suggest pleiotropic effects across different psychiatric disorders. Results also indicate that BPD is in both the mood and psychotic spectra, but possibly more closely related to mood disorders.
Attention-Deficit/Hyperactivity Disorder (ADHD) frequently co-occurs with externalizing disorders, but a clear understanding of the etiologic underpinnings is hampered by the limited understanding of the codevelopment of the traits from childhood into early adulthood.
Using a birth cohort of 2600 twins, the Swedish Twin study of Child and Adolescent Development study, assessed at ages 8-9, 13-14, 16-17, and 19-20, we investigated the codevelopment of ADHD and externalizing behavior from childhood to adulthood. The analyses examined ADHD-like and externalizing traits, as rated by twins and their parents using the Attention Problems scale and Externalizing scale of the Child Behavior Checklist, and estimated cross-lagged effects (one trait at one time-point predicting the other at the next). The covariation between the traits were decomposed into stable (effects carried over from the prior time-points) and innovative (new effects for each time-point) sources; each source was further decomposed into additive genetics, shared and nonshared environment.
The analysis suggested that externalizing traits in middle childhood (age 8-9) predicted ADHD-like traits in early adolescence (age 13-14), whereas the reverse association was nonsignificant. In contrast, ADHD-like traits in lateadolescence (age 16-17) predicted externalizing traits in early adulthood (age 19-20). The correlation between ADHD-like and externalizing traits increased over time. At all time-points, innovative sources contributed substantially to maintained comorbidity. Genetic effects explained 67% of the covariation at each time-point; importantly, nearly 50% of these effects were innovative.
This study challenges the belief that ADHD generally precedes externalizing behaviors; rather, change in the etiologic factors across the development is the rule. The effects were due to both new genetic and environmental factors emerging up to young adulthood. Clinicians and researchers needs to consider complex etiologic and developmental models for the comorbidity between ADHD and externalizing behaviors.
Cites: Biol Psychiatry. 2005 Jun 1;57(11):1313-2315950004
Cites: Dev Psychopathol. 2005 Winter;17(1):145-6515971764
To investigate the association in males between cognitive ability in late adolescence and subsequent substance misuse-related events, and to study the underlying genetic and environmental correlations.
A population-based longitudinal study with three different family-based designs. Cox proportional hazards models were conducted to investigate the association at the individual level. Bivariate quantitative genetic modelling in (1) full brothers and maternal half-brothers, (2) full brothers reared together and apart and (3) monozygotic and dizygotic twin brothers was used to estimate genetic and environmental correlations.
Register-based study in Sweden.
The full sample included 1 402 333 Swedish men born 1958-91 and conscripted at mean age 18.2 [standard deviation (SD)?=?0.5] years. A total of 1 361 066 men who had no substance misuse events before cognitive assessment at mandatory military conscription were included in the Cox regression models, with a follow-up time of up to 35.6?years.
Cognitive ability was assessed at conscription with the Swedish Enlistment Battery. Substance misuse events included alcohol- and drug-related court convictions, medical treatments and deaths, available from governmental registries.
Lower cognitive ability in late adolescence predicted an increased risk for substance misuse events [hazard ratio (HR) for a 1-stanine unit decrease in cognitive ability: 1.29, 95% confidence interval (CI)?=?1.29-1.30]. The association was somewhat attenuated within clusters of full brothers (HR?=?1.21, 95% CI?=?1.20-1.23). Quantitative genetic analyses indicated that the association was due primarily to genetic influences; the genetic correlations ranged between -0.39 (95% CI?=?-0.45, -0.34) and -0.52 (95% CI -0.55, -0.48) in the three different designs.
Shared genetic influences appear to underlie the association between low cognitive ability and subsequent risk for substance misuse events among Swedish men.
There is a strong genetic component in prostate cancer development with an estimated heritability of 58%. In addition, recent epidemiological assessments show a familial component in prostate cancer-specific survival, which could be due to either common genetics or environment. In this study we sought to estimate the heritability of prostate cancer-specific survival by studying brothers and father-son pairs in Sweden.
We used linkage records from three Swedish national registers: the Multi-Generation Register, the Cancer Register, and the Cause of Death Register. One thousand seven hundred twenty-eight brother pairs and 6,444 father-son pairs, where both family members were diagnosed with prostate cancer, were followed for prostate cancer mortality. By assuming that (i) brothers on average share 50% of their segregating alleles and 100% environment and (ii) fathers and sons share 50% of their segregating alleles and no environment, we implemented a model including influences of additive genetics (heritability), shared environment and non-shared environment for survival data. A conditional likelihood estimation procedure was developed to fit the model. Data simulation was applied to validate model assumptions.
In a model that adjusted for age at diagnosis and calendar period, the estimated heritability of prostate cancer-specific survival was 0.10 (95% CI?=?0.00-0.20) that was borderline significantly different from zero (P?=?0.057). The shared environment component was not significantly different from zero with a point estimate of 0.00 (95% CI?=?0.00-0.13). Simulation studies and sensitivity analysis revealed that the estimated heritability component was robust, whereas the shared environmental component may be underestimated.
Heritability of prostate cancer-specific survival is considerably lower than for prostate cancer incidence. This supports a hypothesis that susceptibility of disease and progression of disease are separate mechanisms that involve different genes. Further assessment of the genetic basis of prostate cancer-specific survival is warranted. Prostate 77:900-907, 2017. ? 2017 Wiley Periodicals, Inc.