Accumulating evidence suggests that many psychiatric disorders etiologically represent the extreme end of dimensionally distributed features rather than distinct entities. The extent to which this applies to eating disorders (EDs) is unknown.

We investigated if there is similar etiology in (a) the continuous distribution of the Eating Disorder Inventory-2 (EDI-2), (b) the extremes of EDI-2 score, and (c) registered ED diagnoses, in 1481 female twin pairs at age 18 years (born 1992–1999). EDI-2 scores were self-reported at age 18. ED diagnoses were identified through the Swedish National Patient Register, parent-reported treatment and/or self-reported purging behavior of a frequency and duration consistent with DSM-IV criteria. We differentiated between anorexia nervosa (AN) and other EDs.

The heritability of the EDI-2 score was 0.65 (95% CI 0.61–0.68). The group heritabilities in DeFries–Fulker extremes analyses were consistent over different percentile-based extreme groups [0.59 (95% CI 0.37–0.81) to 0.65 (95% CI 0.55–0.75)]. Similarly, the heritabilities in liability threshold models were consistent over different levels of severity. In joint categorical-continuous models, the twin-based genetic correlation was 0.52 (95% CI 0.39–0.65) between EDI-2 score and diagnoses of other EDs, and 0.26 (95% CI 0.08–0.42) between EDI-2 score and diagnoses of AN. The non-shared environmental correlations were 0.52 (95% CI 0.32–0.70) and 0.60 (95% CI 0.38–0.79), respectively.

Our findings suggest that some EDs can partly be conceptualized as the extreme manifestation of continuously distributed ED features. AN, however, might be more distinctly genetically demarcated from ED features in the general population than other EDs.

Anorexia nervosa and bulimia nervosa are two severe eating disorders associated with high premature mortality, suicidal risk and serious medical complications. Transition between anorexia nervosa and bulimia nervosa over the illness course and familial co-aggregation of the two eating disorders imply aetiological overlap. However, genetic and environmental liabilities to the overlap are poorly understood. Quantitative genetic research using clinical diagnosis is needed.

We acquired a clinical diagnosis of anorexia nervosa (prevalence = 0.90%) and bulimia nervosa (prevalence = 0.48%) in a large population-based sample (N = 782 938) of randomly selected full-sisters and maternal half-sisters born in Sweden between 1970 and 2005. Structural equation modelling was applied to quantify heritability of clinically diagnosed anorexia nervosa and bulimia nervosa and the contributions of genetic and environmental effects on their overlap.

The heritability of clinically diagnosed anorexia nervosa and bulimia nervosa was estimated at 43% [95% confidence interval (CI) (36–50%)] and 41% (31–52%), respectively, in the study population, with the remaining variance explained by variance in unique environmental effects. We found statistically significant genetic [0.66, 95% CI (0.49–0.82)] and unique environmental correlations [0.55 (0.43–0.66)] between the two clinically diagnosed eating disorders; and their overlap was about equally explained by genetic and unique environmental effects [co-heritability 47% (35–58%)].

Our study supports shared mechanisms for anorexia nervosa and bulimia nervosa and extends the literature from self-reported behavioural measures to clinical diagnosis. The findings encourage future molecular genetic research on both eating disorders and emphasize clinical vigilance for symptom fluctuation between them.

Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors.

We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis.

Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse.

Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression.

The immune system has been suggested to be associated with neuropsychiatric disorders; for example, elevated levels of cytokines and the inflammation-related transcription factor nuclear factor kappa-B (NF-κB) have been reported in individuals with autism spectrum disorder (ASD). The aim of this study was to investigate possible associations between autistic-like traits (ALTs) and single nucleotide polymorphisms (SNPs) in NFKB1 (encoding a subunit of the NF-κB protein complex) and NF-κB inhibitor-like protein 1 (NFKBIL1).

The study was conducted in a cohort from the general population: The Child and Adolescent Twin Study in Sweden (CATSS, n = 12 319, 9–12 years old). The subjects were assessed by the Autism-Tics, ADHD, and Other Comorbidities Inventory. Five SNPs within the two genes were genotyped (NFKBIL1: rs2857605, rs2239707, rs2230365 and rs2071592; NFKB1: rs4648022).

We found significant associations for two SNPs in NFKBIL1: rs2239707 showed a significant distribution of genotype frequencies in the case-control analysis both for all individuals combined and in boys only, and rs2230365 was significantly associated with the ALTs-module language impairment in boys only. Furthermore, we found nominal association in the case-control study for rs2230365, replicating earlier association between this SNP and ASD in an independent genome-wide association study.

The shown associations between polymorphisms in NFKBIL1 and ALTs are supporting an influence of the immune system on neuropsychiatric symptoms.

Maternal smoking during pregnancy (MSDP) has been linked to offspring's externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence.

Data came from four prospective twin cohorts – Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study – who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9–10; 12; 14–15 and 16–18.

MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression.

Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents’ aggressive behaviour.

Body dysmorphic disorder (BDD) usually begins during adolescence but little is known about the prevalence, etiology, and patterns of comorbidity in this age group. We investigated the prevalence of BDD symptoms in adolescents and young adults. We also report on the relative importance of genetic and environmental influences on BDD symptoms, and the risk for co-existing psychopathology.

Prevalence of BDD symptoms was determined by a validated cut-off on the Dysmorphic Concerns Questionnaire (DCQ) in three population-based twin cohorts at ages 15 (n = 6968), 18 (n = 3738), and 20–28 (n = 4671). Heritability analysis was performed using univariate model-fitting for the DCQ. The risk for co-existing psychopathology was expressed as odds ratios (OR).

The prevalence of clinically significant BDD symptoms was estimated to be between 1 and 2% in the different cohorts, with a significantly higher prevalence in females (1.3–3.3%) than in males (0.2–0.6%). The heritability of body dysmorphic concerns was estimated to be 49% (95% CI 38–54%) at age 15, 39% (95% CI 30–46) at age 18, and 37% (95% CI 29–42) at ages 20–28, with the remaining variance being due to non-shared environment. ORs for co-existing neuropsychiatric and alcohol-related problems ranged from 2.3 to 13.2.

Clinically significant BDD symptoms are relatively common in adolescence and young adulthood, particularly in females. The low occurrence of BDD symptoms in adolescent boys may indicate sex differences in age of onset and/or etiological mechanisms. BDD symptoms are moderately heritable in young people and associated with an increased risk for co-existing neuropsychiatric and alcohol-related problems.

Clinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however, their design often limits generalisation to routine clinical practice.

To estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder.

We used national registers to identify 35022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine and olanzapine treatment from 2006 to 2009. The main outcome was psychiatric hospital admissions. We used stratified cox regression to compare periods on and off medication within the same individual.

Medication with lithium, valproate, lamotrigine, olanzapine and quetiapine was associated with reduced rates of admission to hospital. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode.

Our findings complement results from randomised controlled trails, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice.

Mortality has been suggested to be increased in autism spectrum disorder (ASD).

To examine both all-cause and cause-specific mortality in ASD, as well as investigate moderating role of gender and intellectual ability.

Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27 122, diagnosed between 1987 and 2009) compared with gender-, age- and county of residence-matched controls (n = 2 672 185).

During the observed period, 24 358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38–2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analysed diagnostic categories. Mortality and patterns for cause-specific mortality were partly moderated by gender and general intellectual ability.

Premature mortality was markedly increased in ASD owing to a multitude of medical conditions.

Violence risk assessment in schizophrenia relies heavily on criminal history factors.

To investigate which criminal history factors are most strongly associated with violent crime in schizophrenia.

A total of 13 806 individuals (8891 men and 4915 women) with two or more hospital admissions for schizophrenia were followed up for violent convictions. Multivariate hazard ratios for 15 criminal history factors included in different risk assessment tools were calculated. The incremental predictive validity of these factors was estimated using tests of discrimination, calibration and reclassification.

Over a mean follow-up of 12.0 years, 17.3% of men (n=1535) and 5.7% of women (n=281) were convicted of a violent offence. Criminal history factors most strongly associated with subsequent violence for both men and women were a previous conviction for a violent offence; for assault, illegal threats and/or intimidation; and imprisonment. However, only a previous conviction for a violent offence was associated with incremental predictive validity in both genders following adjustment for young age and comorbid substance use disorder.

Clinical and actuarial approaches to assess violence risk can be improved if included risk factors are tested using multiple measures of performance.