Thomas Frisell

Violent crime runs in families: a total population study of 12.5 million individuals

BACKGROUND Etiological theory and prior research with small or selected samples suggest that interpersonal violence clusters in families. However, the strength and pattern of this aggregation remains mostly unknown. METHOD We investigated all convictions for violent crime in Sweden 1973-2004 among more than 12.5 million individuals in the nationwide Multi-Generation Register, and compared rates of violent convictions among relatives of violent individuals with relatives of matched, non-violent controls, using a nested case-control design. RESULTS We found strong familial aggregation of interpersonal violence among first-degree relatives [e.g. odds ratio (OR)sibling 4.3, 95% confidence interval (CI) 4.2-4.3], lower for more distant relatives (e.g. OR cousin 1.9, 95% CI 1.9-1.9). Risk patterns across biological and adoptive relations provided evidence for both genetic and environmental influences on the development of violent behavior. Familial risks were stronger among women, in higher socio-economic strata, and for early onset interpersonal violence. There were crime-specific effects (e.g. OR sibling for arson 22.4, 95% CI 12.2-41.2), suggesting both general and subtype-specific familial risk factors for violent behavior. CONCLUSIONS The observed familiality should be accounted for in criminological research, applied violence risk assessment, and prevention efforts.

Familial Risks and Heritability of Rheumatoid Arthritis: Role of Rheumatoid Factor/Anti–Citrullinated Protein Antibody Status, Number and Type of Affected Relatives, Sex, and Age

OBJECTIVE To estimate familial aggregation of rheumatoid arthritis (RA) in 3 large population-representative samples and to test if familial aggregation is affected by rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) status, type of relative, sex, and age at onset of RA. METHODS A register-based nested case-control study was performed in the Swedish total population. Data on patients with RA were ascertained through the nationwide Swedish Patient Register (n = 88,639), the clinical Swedish Rheumatology Quality Register (n = 11,519), and the Epidemiological Investigation of Rheumatoid Arthritis case-control study (n = 2,871). Data on first- and second-degree relatives were obtained through the Swedish Multigeneration Register. Familial risks were calculated using conditional logistic regression. RESULTS Consistent across data sources, the familial odds ratio for RA was ∼3 in first-degree relatives of RA patients and 2 in second-degree relatives. Familial risks were similar among siblings, parents, and offspring. Familial aggregation was not modified by sex, but was higher in RA patients with early-onset disease and in RF/ACPA-positive RA patients. The observed familial risks were consistent with a heritability of ∼50% for ACPA-positive RA and ∼20% for ACPA-negative RA. CONCLUSION The pattern of risks suggests that familial factors influence RA in men and women equally and that these factors are of less importance for late-onset RA. Familial factors are more important for seropositive RA, but there is significant familial overlap between seropositive RA and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest that heritability of RA is lower than previously reported, in particular for ACPA-negative RA.

Psychiatric morbidity associated with same-sex sexual behaviour: influence of minority stress and familial factors

BACKGROUND Increased psychiatric morbidity has been widely reported among non-heterosexual individuals (defined as reporting a homosexual/bisexual identity and/or same-sex sexual partners). However, the causes of this psychiatric ill-health are mostly unknown. METHOD We attempted to estimate the influence of minority stress and familial factors on psychiatric disorder among adults with same-sex sexual partners. Self-report data from a 2005 survey of adults (age 20-47 years, n=17,379) in the population-based Swedish Twin Registry were analysed with regression modelling and co-twin control methodology. RESULTS Rates of depression, generalized anxiety disorder (GAD), eating disorders, alcohol dependence and attention deficit hyperactivity disorder (ADHD) were increased among men and women with same-sex sexual experiences. Adjusting for perceived discrimination and hate crime victimization lowered this risk whereas controlling for familial (genetic or environmental) factors in within-twin pair comparisons further reduced or eliminated it. CONCLUSIONS Components of minority stress influence the risk of psychiatric ill-health among individuals with any same-sex sexual partner. However, substantial confounding by familial factors suggests a common genetic and/or environmental liability for same-sex sexual behaviour and psychiatric morbidity.

Familial clustering of suicide risk: A total population study of 11.4 million individuals

Background Research suggests that suicidal behaviour is aggregated in families. However, due to methodological limitations, including small sample sizes, the strength and pattern of this aggregation remains uncertain. Method We examined the familial clustering of completed suicide in a Swedish total population sample. We linked the Cause of Death and Multi-Generation Registers and compared suicide rates among relatives of all 83 951 suicide decedents from 1952–2003 with those among relatives of population controls. Results Patterns of familial aggregation of suicide among relatives to suicide decedents suggested genetic influences on suicide risk; the risk among full siblings (odds ratio 3.1, 95% confidence interval 2.8–3.5, 50% genetic similarity) was higher than that for maternal half-siblings (1.7, 1.1–2.7, 25% genetic similarity), despite similar environmental exposure. Further, monozygotic twins (100% genetic similarity) had a higher risk than dizygotic twins (50% genetic similarity) and cousins (12.5% genetic similarity) had higher suicide risk than controls. Shared (familial) environmental influences were also indicated; siblings to suicide decedents had a higher risk than offspring (both 50% genetically identical but siblings having a more shared environment, 3.1, 2.8–3.5 v. 2.0, 1.9–2.2), and maternal half-siblings had a higher risk than paternal half-siblings (both 50% genetically identical but the former with a more shared environment). Although comparisons of twins and half-siblings had overlapping confidence intervals, they were supported by sensitivity analyses, also including suicide attempts. Conclusions Familial clustering of suicide is primarily influenced by genetic and also shared environmental factors. The family history of suicide should be considered when assessing suicide risk in clinical settings or designing and administering preventive interventions.

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients

Many JC virus antibody‐positive relapsing–remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy.

TNF inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis: a nationwide cohort study

Objective To investigate the risk of breast cancer recurrence in rheumatoid arthritis (RA)—patients with tumour necrosis factor inhibitor (TNFi) treatment and a history of breast cancer, taking several breast cancer, comorbidity and RA-related prognostic factors into account. Methods 143 female TNFi-treated patients (1999–2010) with RA and a history of breast cancer before start of TNFi were identified through register linkages, and matched 1:1 from a cohort of 1598 comparable biologics-naive individuals. 120 TNFi-treated and 120 matched biologics-naive individuals with a history of equally recent/distant breast cancer met the eligibility criteria and comprised the final study population. The primary outcome was first recurrence of breast cancer. Through register-linkages and chart review, individuals were followed until 2011. HRs for recurrence were calculated using Cox regression. Results The median time from breast cancer diagnosis until TNFi-treatment/start of follow-up was 9.4 years. Modest differences in breast cancer characteristics and/or treatment among TNFi-treated and biologics-naive individuals were noted at time of breast cancer diagnosis. Median follow-up from TNFi start was 4.9 years (4.6 years among biologics-naive). Among the TNFi-treated, 9 developed a breast cancer recurrence (crude incidence rate 15/1000 person-years) during follow-up, compared with 9 among the matched biologics-naive (16/1000 person-years). The adjusted corresponding HR was 1.1 (95% CI 0.4 to 2.8). Conclusions Among patients with RA and a history of breast cancer, those who started TNFi-treatment did not experience more breast cancer recurrences than patients with RA treated otherwise. The generalisability of our findings to women with a very recent or a poor prognosis of breast cancer remains unknown.

Maternal body mass index during early pregnancy, gestational weight gain, and risk of autism spectrum disorders: Results from a Swedish total population and discordant sibling study

Background: Prenatal environmental factors such as maternal adiposity may influence the risk of offspring autism spectrum disorders (ASD), though current evidence is inconsistent. The objective of this study was to assess the relationship of parental BMI and gestational weight gain (GWG) with risk of offspring ASD in a population-based cohort study using family-based study designs. Methods: The cohort was based in Stockholm County, Sweden, including 333 057 individuals born 1984–2007, of whom 6420 were diagnosed with an ASD. We evaluated maternal body mass index (BMI) at first antenatal visit, GWG and paternal BMI at the time of conscription into the Swedish military as exposures using general estimating equation (GEE) models with logit link. Results: At the population level, maternal overweight/obesity was associated with increased risk of offspring ASD [odds ratio (OR)25 ≤ BMI < 30 1.31, 95% confidence interval = 1.21–1.41; ORBMI ≥ 30 1.94, 1.72–2.17], as was paternal underweight (ORBMI < 18.5, 1.19, 1.06–1.33) and obesity (ORBMI ≥ 30 1.47, 1.12–1.92) in mutually adjusted models. However, in matched sibling analyses, the relationship between elevated maternal BMI and ASD risk was not apparent. GWG had a U-shaped association with offspring ASD at the population level (ORinsufficient 1.22, 1.07–1.40; ORexcessive 1.23, 1.08–1.40). Matched sibling analyses were suggestive of elevated risk with excessive GWG (ORinsufficient 1.12, 0.68–1.84; ORexcessive 1.48, 0.93–2.38). Conclusions: Whereas population-level results suggested that maternal BMI was associated with ASD, sibling analyses and paternal BMI analyses indicate that maternal BMI may also be a proxy marker for other familial risk factors. Evidence is stronger for a direct link between GWG and ASD risk.

Is the Association between General Cognitive Ability and Violent Crime Caused by Family-Level Confounders?

Background Research has consistently found lower cognitive ability to be related to increased risk for violent and other antisocial behaviour. Since this association has remained when adjusting for childhood socioeconomic position, ethnicity, and parental characteristics, it is often assumed to be causal, potentially mediated through school adjustment problems and conduct disorder. Socioeconomic differences are notoriously difficult to quantify, however, and it is possible that the association between intelligence and delinquency suffer substantial residual confounding. Methods We linked longitudinal Swedish total population registers to study the association of general cognitive ability (intelligence) at age 18 (the Conscript Register, 1980–1993) with the incidence proportion of violent criminal convictions (the Crime Register, 1973–2009), among all men born in Sweden 1961–1975 (N = 700,514). Using probit regression, we controlled for measured childhood socioeconomic variables, and further employed sibling comparisons (family pedigree data from the Multi-Generation Register) to adjust for shared familial characteristics. Results Cognitive ability in early adulthood was inversely associated to having been convicted of a violent crime (β = −0.19, 95% CI: −0.19; −0.18), the association remained when adjusting for childhood socioeconomic factors (β = −0.18, 95% CI: −0.18; −0.17). The association was somewhat lower within half-brothers raised apart (β = −0.16, 95% CI: −0.18; −0.14), within half-brothers raised together (β = −0.13, 95% CI: (−0.15; −0.11), and lower still in full-brother pairs (β = −0.10, 95% CI: −0.11; −0.09). The attenuation among half-brothers raised together and full brothers was too strong to be attributed solely to attenuation from measurement error. Discussion Our results suggest that the association between general cognitive ability and violent criminality is confounded partly by factors shared by brothers. However, most of the association remains even after adjusting for such factors.

Hospital Admission With Infection During Childhood and Risk for Psychotic Illness—A Population-based Cohort Study

A growing body of literature suggests that exposure to infections, particularly maternal infections, during pregnancy confers risk for later development of psychotic disorder. Though brain development proceeds throughout childhood and adolescence, the influence of infections during these ages on subsequent psychosis risk is insufficiently examined. The aim of this study was to investigate the potential association between infections during childhood and nonaffective psychoses in a large population-based birth cohort with follow up long enough to include peak incidence of nonaffective psychosis. We included all individuals born in Sweden between 1973 and 1985, (N = 1172879), with follow up on first time inpatient care with nonaffective psychosis from age 14 years until 2006, (N = 4638). Following adjustment for differences in sex, socioeconomic status, family history of psychosis, and hospital admissions involving noninfectious, nonpsychiatric care, we observed a small but statistically significant association between hospital admissions for infections, in general, throughout childhood (0-13 years) and a later diagnosis of nonaffective psychosis, hazard ratio (HR) = 1.10 (95% CI 1.03-1.18), and this association seemed to be driven by bacterial infection, HR = 1.23 (95% CI 1.08-1.40). Bacterial infections and central nervous system infections during preadolescence (10-13 years) conferred the strongest risk, HR 1.57 (95% CI 1.21-2.05) and HR 1.96 (95% CI 1.05-3.62), respectively. Although preadolescence appeared to be a vulnerable age period, and bacterial infection the most severe in relation to psychosis development, the present findings can also indicate an increased susceptibility to hospital admission for infections among children who will later develop nonaffective psychosis due to social or familial/genetic factors.

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.