Despite evidence of associations between glucocorticoid treatment and adverse psychiatric and suicidal behaviour outcomes, large-scale observational evidence for serious outcomes is lacking.

To assess the risk of psychiatric and suicidal behaviour outcomes during glucocorticoid treatment.

Using Swedish population registers, we identified 1 105 964 individuals aged 15–54 years who collected a glucocorticoid prescription in oral form between 2006 and 2020. We investigated associations with a range of psychiatric outcomes: unplanned specialist healthcare contacts due to depressive, bipolar, anxiety or schizophrenia-spectrum disorders; and deaths by suicide or unplanned specialist healthcare contacts due to self-harm (‘suicidal behaviour’). We estimated hazard ratios from Cox proportional hazards models in a medication-only cohort by comparing outcome rates during and outside treated periods within individuals. We further identified individuals with an autoimmune or gastrointestinal autoimmune disorder diagnosis and compared hazards of the outcomes between those who did and did not initiate a glucocorticoid using a target trial emulation approach.

We found increased risks for psychiatric outcomes, with within-individual hazard ratios ranging from 1.08 (95% CI, 1.00–1.16) for depressive disorders to 1.23 (95% CI, 1.12–1.36) for bipolar disorder and 1.25 (95% CI, 1.20–1.31) for anxiety disorders. We found no clear association with suicidal behaviour (hazard ratio: 1.06; 95% CI, 0.96–1.17). These findings were similar when stratified by age and gender. Within-individual associations were attenuated in those diagnosed with an autoimmune disorder. The risk of anxiety and bipolar disorder outcomes appeared particularly elevated in the first weeks of treatment. Absolute rates were modestly elevated during treatment, and higher in those with a history of psychiatric disorders.

Glucocorticoid treatment is associated with elevated risks of serious psychiatric outcomes, including the onset and relapse of common psychiatric disorders. Individuals with psychiatric histories may require additional monitoring during glucocorticoid treatment.

Shared genetic risk between schizophrenia (SCZ) and bipolar disorder (BD) is well-established, yet the extent to which they share environmental risk factors remains unclear. We compare the associations between environmental exposures during childhood/prior to disorder onset with the risk of developing SCZ and BD.

We conducted a Swedish register-based nested case–control study using 4184 SCZ cases and 18 681 BD cases diagnosed 1988–2013. Cases were matched to five controls by birth year, birth region, and sex. Conditional logistic regression was used to estimate incidence rate ratios (IRR) for SCZ and BD for each exposure (severe childhood infections, adverse childhood experiences (ACEs), substance use disorders (SUDs), urban birth/longest residence).

All SUD types were associated with very high risk (IRR 4.9–25.5), and all forms of ACEs with higher risk (IRR 1.5–4.3) for both disorders. In the mutually adjusted models, ACEs demonstrated slightly higher risk for BD (SCZ IRR 1.30, 1.19-1.42; BD IRR 1.49, 1.44–1.55), while for SUD, risk was higher for SCZ (SCZ IRR 9.43, 8.15–10.92; BD IRR 5.50, 5.15–5.88). Infections were associated with increased risk of BD (IRR 1.21, 1.17–1.26) but not SCZ. Urban birth and urban longest residence were associated with higher risk of SCZ (IRR 1.19, 1.03–1.37), while only the combination of urban birth and rural longest residence showed higher risk for BD (IRR 1.24, 1.13–1.35).

There were both shared and unique environmental risk factors: SUDs and ACEs were risk factors for both disorders, while infections were more strongly associated with BD and urbanicity with SCZ.

Both maternal and, separately, paternal mental illness are associated with diminished academic attainment among children. However, the differential impacts of diagnostic type and degree of parental burden (e.g. one v. both parents affected) on these functional outcomes are unknown.

Using the Swedish national patient (NPR) and multi-generation (MGR) registers, 2 226 451 children (1 290 157 parental pairs), born 1 January 1973–31 December 1997, were followed through 31 December 2013. Diagnostic status of all cohort members was defined for eleven psychiatric disorders, and families classed by exposure: (1) parents affected with any disorder, (2) parents affected with a disorder group (e.g. neuropsychiatric disorders), and (3) parents affected with a specific disorder (e.g. ADHD). Pairs were further defined as ‘unaffected,’ ‘single-affected,’, or ‘dual-affected.’ Among offspring, the study evaluated fulfillment of four academic milestones, from compulsory (primary) school through University (college). Sensitivity analyses considered the impact of child's own mental health, as well as parental education, on main effects.

Marked reductions in the odds of achievement were observed, emerging at the earliest levels of schooling for both single-affected [adjusted odds ratio (aOR), 0.50; 95% CI 0.49–0.51] and dual-affected (aOR 0.29, 95% CI 0.28–0.30) pairs and persisting thereafter [aOR range (single), 0.52–0.65; aOR range (dual), 0.30–0.40]. This pattern was repeated for analyses within diagnosis/diagnostic group. Main results were robust to adjustment for offspring mental health and parent education level.

Parental mental illness is associated with profound reductions in educational attainment in the subsequent generation, with children from dual-affected families at uniquely high risk.

Intellectual disability (ID) is associated with violent and sexual offending and victimization, but the importance of neuropsychiatric comorbidity and severity of disability remains unclear.

In a register-based cohort study of people born in Sweden 1980–1991 (n = 1 232 564), we investigated associations of mild and moderate/severe ID with any, violent and sexual crimes, and with assault victimization, stratified by comorbid autism and attention deficit hyperactivity disorder (ADHD). We defined ID by attendance at a special school or registered diagnosis and obtained data on criminal convictions and injuries or deaths due to assaults from nationwide registers until end of 2013.

Compared to people without ID, autism or ADHD, men and women with mild or moderate/severe ID and comorbid ADHD had elevated risks of violent crimes [range of hazard ratios (HRs) 4.4–10.4] and assault victimization (HRs 2.0–7.7). Women with mild ID without comorbidities or with comorbid autism also had elevated risks of violent crimes and victimization (HRs 1.8–4.6) compared to women without ID, autism or ADHD. The relative risks of sexual offending and victimization were elevated in men and women with ID without comorbidities (HRs 2.6–12.7). The highest risks for sexual offending in men (HRs 9.4–11.0) and for sexual assault victimization in women (HRs 11.0–17.1) related to ID and comorbid ADHD.

The elevated risk of violent offending and assault victimization in people with ID is largely explained by comorbid ADHD, whereas ID is independently associated with sexual crimes and victimization, even though absolute risks are low.

Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood.

Individuals born in Sweden 1985–1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems.

Among 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43–2.70) and females (HR 5.39; 95% CI 4.97–5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06–1.51) and females (HR 1.69; 95% CI 1.21–2.36).

Females with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.

Familial co-aggregation studies of eating disorders (EDs) and schizophrenia reveal shared genetic and environment factors, yet their etiological and clinical relationship remains unclear. We evaluate the influence of schizophrenia family history on clinical outcomes of EDs.

We conducted a cohort evaluation of the association between family history of schizophrenia and ED clinical features, psychiatric comorbidities, and somatic and mental health burden in individuals born in Sweden 1977–2003 with anorexia nervosa (AN) or other EDs (OED: bulimia nervosa, binge-eating disorder, and ED not otherwise specified).

Of 12 424 individuals with AN and 20 716 individuals with OED, 599 (4.8%) and 1118 (5.4%), respectively, had a family history of schizophrenia (in up to third-degree relatives). Among individuals with AN, schizophrenia in first-degree relatives was significantly associated with increased comorbid attention-deficit/hyperactivity disorder (ADHD) [HR(95% CI) 2.26 (1.27–3.99)], substance abuse disorder (SUD) [HR (95% CI) 1.93 (1.25–2.98)], and anxiety disorders [HR (95% CI) 1.47 (1.08–2.01)], but higher lowest illness-associated body mass index (BMI) [1.14 kg/m2, 95% CI (0.19–2.10)]. Schizophrenia in any relative (up to third-degree) in AN was significantly associated with higher somatic and mental health burden, but lower ED psychopathology scores [−0.29, 95% CI (−0.54 to −0.04)]. Schizophrenia in first-degree relatives in individuals with OED was significantly associated with increased comorbid ADHD, obsessive-compulsive disorder, SUD, anxiety disorders, somatic and mental health burden, and suicide attempts.

We observed different patterns of ED-related outcomes, psychiatric comorbidity, and illness burden in individuals with EDs with and without family histories of schizophrenia and provide new insights into the diverse manifestations of EDs.

There is evidence that autism spectrum disorders (ASDs) co-occur with bipolar disorder (BD) relatively frequently. Individuals with BD often report symptoms of mania and hypomania during adolescence, prior to the age of onset for BD. It is unknown whether these symptoms are associated with ASDs. We examined whether diagnoses of ASDs and autistic traits were associated with hypomania in a large, population-based Swedish twin sample.

Parental structured interviews assessed autistic traits, and were used to assign screening diagnoses of ASDs, when twins were aged 9 or 12 (N = 13 533 pairs). Parents then completed questionnaires assessing hypomania when the twins were aged 15 and 18 (N = 3852 pairs at age 15, and 3013 pairs at age 18). After investigating the phenotypic associations between these measures, we used the classical twin design to test whether genetic and environmental influences on autistic traits influence variation in adolescent hypomania.

Autistic traits and ASD diagnoses in childhood were associated with elevated scores on the measures of adolescent hypomania. Twin analyses indicated that 6–9% of the variance in hypomania was explained by genetic influences that were shared with autistic traits in childhood. When repeating these analyses for specific autistic trait domains, we found a stronger association between social interaction difficulties and hypomania than for other autistic trait domains.

These results indicate a genetic link between autistic traits and hypomania in adolescence. This adds to the growing evidence base of genetic factors associated with ASDs showing links with psychiatric outcomes across childhood and into adulthood.

Individuals diagnosed with psychiatric disorders who are prescribed antipsychotics have lower rates of violence and crime but the differential effects of specific antipsychotics are not known. We investigated associations between 10 specific antipsychotic medications and subsequent risks for a range of criminal outcomes.

We identified 74 925 individuals who were ever prescribed antipsychotics between 2006 and 2013 using nationwide Swedish registries. We tested for five specific first-generation antipsychotics (levomepromazine, perphenazine, haloperidol, flupentixol, and zuclopenthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, risperidone, and aripiprazole). The outcomes included violent, drug-related, and any criminal arrests and convictions. We conducted within-individual analyses using fixed-effects Poisson regression models that compared rates of outcomes between periods when each individual was either on or off medication to account for time-stable unmeasured confounders. All models were adjusted for age and concurrent mood stabilizer medications.

The relative risks of all crime outcomes were substantially reduced [range of adjusted rate ratios (aRRs): 0.50–0.67] during periods when the patients were prescribed antipsychotics v. periods when they were not. We found that clozapine (aRRs: 0.28–0.44), olanzapine (aRRs: 0.46–0.72), and risperidone (aRRs: 0.53–0.64) were associated with lower arrest and conviction risks than other antipsychotics, including quetiapine (aRRs: 0.68–0.84) and haloperidol (aRRs: 0.67–0.77). Long-acting injectables as a combined medication class were associated with lower risks of the outcomes but only risperidone was associated with lower risks of all six outcomes (aRRs: 0.33–0.69).

There is heterogeneity in the associations between specific antipsychotics and subsequent arrests and convictions for any drug-related and violent crimes.

Socioeconomic factors can affect healthcare management.

The aim was to investigate if patient educational attainment is associated with management of bipolar disorder.

We included patients with bipolar disorder type 1 (n = 4289), type 2 (n = 4020) and not otherwise specified (n = 1756), from the Swedish National Quality Register for Bipolar Disorder (BipoläR). The association between patients’ educational level and pharmacological and psychological interventions was analysed by binary logistic regression. We calculated odds ratios after adjusting for demographic and clinical variables.

Higher education was associated with increased likelihood of receiving psychotherapy (adjusted odds ratio 1.34, 95% CI 91.22–1.46) and psychoeducation (adjusted odds ratio 1.18, 95% CI 1.07–1.46), but with lower likelihood of receiving first-generation antipsychotics (adjusted odds ratio 0.76, 95% CI 0.62–0.94) and tricyclic antidepressants (adjusted odds ratio 0.76, 95% CI 0.59–0.97). Higher education was also associated with lower risk for compulsory in-patient care (adjusted odds ratio 0.79, 95% CI 0.67–0.93).

Pharmacological and psychological treatment of bipolar disorder differ depending on patients’ educational attainment. The reasons for these disparities remain to be explained.

Previous research indicates that body dysmorphic disorder (BDD) is associated with risk of suicidality. However, studies have relied on small and/or specialist samples and largely focussed on adults, despite these difficulties commonly emerging in youth. Furthermore, the aetiology of the relationship remains unknown.

Two independent twin samples were identified through the Child and Adolescent Twin Study in Sweden, at ages 18 (N = 6027) and 24 (N = 3454). Participants completed a self-report measure of BDD symptom severity. Young people and parents completed items assessing suicidal ideation/behaviours. Logistic regression models tested the association of suicidality outcomes with: (a) probable BDD, classified using an empirically derived cut-off; and (b) continuous scores of BDD symptoms. Bivariate genetic models examined the aetiology of the association between BDD symptoms and suicidality at both ages.

Suicidal ideation and behaviours were common among those with probable BDD at both ages. BDD symptoms, measured continuously, were linked with all aspects of suicidality, and associations generally remained significant after adjusting for depressive and anxiety symptoms. Genetic factors accounted for most of the covariance between BDD symptoms and suicidality (72.9 and 77.7% at ages 18 and 24, respectively), but with significant non-shared environmental influences (27.1 and 22.3% at ages 18 and 24, respectively).

BDD symptoms are associated with a substantial risk of suicidal ideation and behaviours in late adolescence and early adulthood. This relationship is largely explained by common genetic liability, but non-shared environmental effects are also significant and could provide opportunities for prevention among those at high-risk.

Although attention-deficit hyperactivity disorder (ADHD) is classified as a neurodevelopmental disorder in the latest diagnostic manuals, it shows phenotypic and genetic associations of similar magnitudes across neurodevelopmental, externalising and internalising disorders.

To investigate if ADHD is aetiologically more closely related to neurodevelopmental than externalising or internalising disorder clusters, after accounting for a general psychopathology factor.

Full and maternal half-sibling pairs (N = 774 416), born between 1980 and 1995, were identified from the Swedish Medical Birth and Multi-Generation Registers, and ICD diagnoses were obtained from the Swedish National Patient Register. A higher-order confirmatory factor analytic model was fitted to examine associations between ADHD and a general psychopathology factor, as well as a neurodevelopmental, externalising and internalising subfactor. Quantitative genetic modelling was performed to estimate the extent to which genetic, shared and non-shared environmental effects influenced the associations with ADHD.

ADHD was significantly and strongly associated with all three factors (r = 0.67–0.75). However, after controlling for a general psychopathology factor, only the association between ADHD and the neurodevelopmental-specific factor remained moderately strong (r = 0.43, 95% CI = 0.42–0.45) and was almost entirely influenced by genetic effects. In contrast, the association between ADHD and the externalising-specific factor was smaller (r = 0.25, 95% CI = 0.24–0.27), and largely influenced by non-shared environmental effects. There remained no internalising-specific factor after accounting for a general factor.

Findings suggest that ADHD comorbidity is largely explained by genetically influenced general psychopathology, but the strong link between ADHD and other neurodevelopmental disorders is also substantially driven by unique genetic influences.

To describe characteristics of self-identified popular diet followers and compare mean BMI across these diets, stratified by time following diet.

Cross-sectional, web-based survey administered in 2015.

Non-localised, international survey.

Self-selected followers of popular diets (n 9019) were recruited to the survey via social media and email announcements by diet community leaders, categorised into eight major diet groups.

General linear models were used to compare mean BMI among (1) short-term (<1 year) and long-term (≥1 year) followers within diet groups and (2) those identifying as ‘try to eat healthy’ (TTEH) to all other diet groups, stratified by time following the specific diet. Participants were 82 % female, 93 % White and 96 % non-Hispanic. Geometric mean BMI was lower (P < 0·05 for all) among longer-term followers (≥1 year) of whole food, plant-based (WFPB), vegan, whole food and low-carb diets compared with shorter-term followers. Among those following their diet for 1–5 years (n 4067), geometric mean BMI (kg/m2) were lower (P < 0·05 for all) for all groups compared with TTEH (26·4 kg/m2): WFPB (23·2 kg/m2), vegan (23·5 kg/m2), Paleo (24·6 kg/m2), vegetarian (25·0 kg/m2), whole food (24·6 kg/m2), Weston A. Price (23·5 kg/m2) and low-carb (24·7 kg/m2).

Our findings suggest that BMI is lower among individuals who made active decisions to adhere to a specific diet, particularly more plant-based diets and/or diets limiting highly processed foods, compared with those who simply TTEH. BMI is also lower among individuals who follow intentional eating plans for longer time periods.

Genetically informed studies have provided mixed findings as to what extent parental substance misuse is associated with offspring substance misuse and antisocial behavior due to shared environmental and genetic factors.

We linked data from nationwide registries for a cohort of 2 476 198 offspring born in Sweden 1958–1995 and their parents. Substance misuse was defined as International Classification of Diseases diagnoses of alcohol/drug use disorders or alcohol/drug-related criminal convictions. Quantitative genetic offspring-of-siblings analyses in offspring of monozygotic and dizygotic twin, full-sibling, and half-sibling parents were conducted.

Both maternal and paternal substance misuse were robustly associated with offspring substance misuse [maternal adjusted hazard ratio (aHR) = 1.83 (95% confidence interval (CI) 1.80–1.87); paternal aHR = 1.96 (1.94–1.98)] and criminal convictions [maternal aHR = 1.56 (1.54–1.58); paternal aHR = 1.66 (1.64–1.67)]. Additive genetic effects explained 42% (95% CI 25–56%) and 46% (36–55%) of the variance in maternal and paternal substance misuse, respectively, and between 36 and 44% of the variance in substance misuse and criminality in offspring. The associations between parental substance misuse and offspring outcomes were mostly due to additive genetic effects, which explained 54–85% of the parent-offspring covariance. However, both nuclear and extended family environmental factors also contributed to the associations, especially with offspring substance misuse.

Our findings from a large offspring-of-siblings study indicate that shared genetic influences mostly explain the associations between parental substance misuse and both offspring substance misuse and criminality, but we also found evidence for the contribution of environmental factors shared by members of nuclear and extended families.

Many psychiatric disorders show gender differences in prevalence. Recent studies suggest that female patients diagnosed with anxiety and depression carry more genetic risks related to attention-deficit hyperactivity disorder (ADHD) compared with affected males.

In this register-based study, we aimed to test whether female patients who received clinical diagnoses of anxiety, depressive, bipolar and eating disorders are at higher familial risk for ADHD and other neurodevelopmental disorders, compared with diagnosed male patients.

We analysed data from a record-linkage of several Swedish national registers, including 151 025 sibling pairs from 103 941 unique index individuals diagnosed with anxiety, depressive, bipolar or eating disorders, as well as data from 646 948 cousin pairs. We compared the likelihood of having a relative diagnosed with ADHD/neurodevelopmental disorders in index males and females.

Female patients with anxiety disorders were more likely than affected males to have a brother with ADHD (odd ratio (OR) = 1.13, 95% CI 1.05–1.22). Results for broader neurodevelopmental disorders were similar and were driven by ADHD diagnoses. Follow-up analyses revealed similar point estimates for several categories of anxiety disorders, with the strongest effect observed for agoraphobia (OR = 1.64, 95% CI 1.12–2.39). No significant associations were found in individuals with depressive, bipolar or eating disorders, or in cousins.

These results provide modest support for the possibility that familial/genetic risks for ADHD may show gender-specific phenotypic expression. Alternatively, there could be gender-specific biases in diagnoses of anxiety and ADHD. These factors could play a small role in the observed gender differences in prevalence of ADHD and anxiety.

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.