How does genetic liability to suicide attempt (SA), suicide death (SD), major depression (MD), bipolar disorder (BD), schizophrenia (SZ), alcohol use disorder (AUD), and drug use disorder (DUD) impact on risk for SA and SD?

In the Swedish general population born 1932–1995 and followed through 2017 (n = 7 661 519), we calculate family genetic risk scores (FGRS) for SA, SD, MD, BD, SZ, AUD, and DUD. Registration for SA and SD was assessed from Swedish national registers.

In univariate and multivariate models predicting SA, FGRS were highest for SA, AUD, DUD, and MD. In univariate models predicting SD, the strongest FGRS were AUD, DUD, SA, and SD. In multivariate models, the FGRS for SA and AUD were higher in predicting SA while the FGRS for SD, BD, and SZ were higher in predicting SD. Higher FGRS for all disorders significantly predicted both younger age at first SA and frequency of attempts. For SD, higher FGRS for MD, AUD, and SD predicted later age at SD. Mediation of FGRS effects on SA and SD was more pronounced for SD than SA, strongest for AUD, DUD, and SZ FGRS and weakest for MD.

FGRS for both SA and SD and for our five psychiatric disorders impact on risk for SA and SD in a complex manner. While some of the impact of genetic risk factors for psychiatric disorders on risk for SA and SD is mediated through developing the disorders, these risks also predispose directly to suicidal behaviors.

Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association.

We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide.

In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73–2.78 after 1 month of use, and 1.25–1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period.

Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.

Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.

We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.

In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).

AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.

Relapse from drug abuse (DA) is common, but has rarely been studied in general population samples using a wide range of objective predictors.

Using nationwide registries, we ascertained 44 523 subjects first registered for DA between the ages of 15 and 40 in 1998 to 2004 and followed for 8 years. We predicted relapse in subjects defined as a second DA registration. We also predicted DA relapse in relative pairs concordant for DA but discordant for relapse.

In multivariate regression analyses, the strongest predictors for relapse were prior criminal behavior, male sex, being on social welfare, low school achievement, prior alcoholism, and a high-risk father. A risk index trained from these analyses on random split-halves demonstrated a risk ratio of 1.11 [95% confidence intervals (CIs) 1.10–1.11] per decile and an ROC value of 0.70 (0.69–0.71). Co-relative analyses indicated that a modest proportion of this association was causal, with the remainder arising from familial confounders. A developmental structural equation model revealed a complex interviewing of risk pathways to DA with three key mediational hubs: low educational attainment, early age at first registration, and being on social welfare.

In a general population sample, using objective registry information, DA relapse is substantially predictable. However, the identified risk factors may not be valid targets for interventions because many index familial risk and may not impact causally on probability of relapse. Risk for DA relapse may reflect an inter-weaving, over developmental time, of genetic–temperamental vulnerability, indices of externalizing behaviors and social factors reflecting deprivation.

Previous studies have demonstrated that several major psychiatric disorders are influenced by shared genetic factors. This shared liability may influence clinical features of a given disorder (e.g. severity, age at onset). However, findings have largely been limited to European samples; little is known about the consistency of shared genetic liability across ethnicities.

The relationship between polygenic risk for several major psychiatric diagnoses and major depressive disorder (MDD) was examined in a sample of unrelated Han Chinese women. Polygenic risk scores (PRSs) were generated using European discovery samples and tested in the China, Oxford, and VCU Experimental Research on Genetic Epidemiology [CONVERGE (maximum N = 10 502)], a sample ascertained for recurrent MDD. Genetic correlations between discovery phenotypes and MDD were also assessed. In addition, within-case characteristics were examined.

European-based polygenic risk for several major psychiatric disorder phenotypes was significantly associated with the MDD case status in CONVERGE. Risk for clinically significant indicators (neuroticism and subjective well-being) was also associated with case–control status. The variance accounted for by PRS for both psychopathology and for well-being was similar to estimates reported for within-ethnicity comparisons in European samples. However, European-based PRS were largely unassociated with CONVERGE family history, clinical characteristics, or comorbidity.

The shared genetic liability across severe forms of psychopathology is largely consistent across European and Han Chinese ethnicities, with little attenuation of genetic signal relative to within-ethnicity analyses. The overall absence of associations between PRS for other disorders and within-MDD variation suggests that clinical characteristics of MDD may arise due to contributions from ethnicity-specific factors and/or pathoplasticity.

While risk for alcohol use disorder (AUD) is correlated in twins, siblings and parent-offspring pairs, we know little of how this syndrome is transmitted across three generations.

We examined 685 172 individuals born in Sweden from 1980 to 1990 with four grandparents, and both parents alive in 1980. AUD was assessed in all these individuals from nationwide medical, criminal and pharmacy registries.

AUD was stably transmitted across three generations. Parent-child and grandparent-grandchild tetrachoric correlations equaled +0.25 and +0.12, respectively. Grandchild AUD risk did not vary as a function of the sex of the parent or grandparent. However, from grandparents and parents, transmission to grandchildren was stronger in same-sex than opposite-sex pairs. Compared with a grandchild with unaffected parents and grandparents, risk for AUD with a grandparent but no parent affected, a parent but no grandparent affected or both affected increased approximately 70% and 3 and 4-fold, respectively. Grandchildren with ⩾2 grandparents affected had a 40% greater AUD risk than those with only one affected. Tetrachoric correlations for AUD between offspring and great-aunts/uncles, and aunts/uncles equaled +0.06 and +0.13, respectively.

The transmission of AUD in Sweden across three generations is relatively stable. An orderly pattern of resemblance is seen with correlations declining by approximately 50% between first and second, and second and third-degree relatives. While the transmission of risk from affected male and female relatives does not differ, we find consistent evidence for greater resemblance in same-sex v. opposite-sex across generational pairs of relatives.

DSM-5 includes two conceptualizations of personality disorders (PDs). The classification in Section II is identical to the one found in DSM-IV, and includes 10 categorical PDs. The Alternative Model (Section III) includes criteria for dimensional measures of maladaptive personality traits organized into five domains. The degree to which the two conceptualizations reflect the same etiological factors is not known.

We use data from a large population-based sample of adult twins from the Norwegian Institute of Public Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory that indexes the five domains of the DSM-5 Alternative Model plus a domain explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline, Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the maladaptive personality traits and 10 years previously. Schizoid, Histrionic, Narcissistic, and Dependent PDs were only assessed at the first interview. Biometric models were used to estimate overlap in genetic and environmental risk factors.

When measured concurrently, there was 100% genetic overlap between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial, Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared with the domains. Genetic correlations between the individual domains and PDs ranged from +0.21 to +0.91.

The pathological personality trait domains, which are part of the Alternative Model for classification of PDs in DSM-5 Section III, appears to tap, at an aggregate level, the same genetic risk factors as the DSM-5 Section II classification for most of the PDs.

Prior research consistently demonstrates that neuroticism increases risk for suicidal ideation, but the association between neuroticism and suicidal behavior has been inconsistent. Whereas neuroticism is recommended as an endophenotype for suicidality, the association of neuroticism with attempted suicide warrants clarification. In particular, prior research has not distinguished between correlates of attempted suicide, correlates of suicidal ideation, and correlates of comorbid psychopathology.

The present study used the CONVERGE study, a sample of 5864 women with major depressive disorder (MD) and 5783 women without MD throughout China. Diagnoses, suicidal ideation, and attempted suicide were assessed with the Composite International Diagnostic Interview (CIDI). Neuroticism was assessed with the neuroticism portion of the Eysenck Personality Questionnaire.

Results replicate prior findings on the correlates of suicidal ideation, particularly elevated neuroticism among individuals who report prior suicidal ideation. Moreover, as compared with individuals who reported having experienced only suicidal ideation, neuroticism was associated with decreased likelihood of having attempted suicide.

The association of neuroticism with suicidality is more complicated than has been previously described. Whereas neuroticism increases risk for suicidal ideation, neuroticism may decrease risk for a suicide attempt among individuals with suicidal ideation. These results have implications for the assessment of risk for a suicide attempt among individuals who report suicidal ideation and addresses prior discordant findings by clarifying the association between neuroticism and attempted suicide.

This study seeks to clarify the contribution of temporally stable and occasion-specific genetic and environmental influences on risk for major depression (MD).

Our sample was 2153 members of female–female twin pairs from the Virginia Twin Registry. We examined four personal interview waves conducted over an 8-year period with MD in the last year defined by DSM-IV criteria. We fitted a structural equation model to the data using classic Mx. The model included genetic and environmental risk factors for a latent, stable vulnerability to MD and for episodes in each of the four waves.

The best-fit model was simple and included genetic and unique environmental influences on the latent liability to MD and unique wave-specific environmental effects. The path from latent liability to MD in the last year was constant over time, moderate in magnitude (+0.65) and weaker than the impact of occasion-specific environmental effects (+0.76). Heritability of the latent stable liability to MD was much higher (78%) than that estimated for last-year MD (32%). Of the total unique environmental influences on MD, 13% reflected enduring consequences of earlier environmental insults, 17% diagnostic error and 70% wave-specific short-lived environmental stressors.

Both genetic influences on MD and MD heritability are stable over middle adulthood. However, the largest influence on last-year MD is short-lived environmental effects. As predicted by genetic theory, the heritability of MD is increased substantially by measurement at multiple time points largely through the reduction of the effects of measurement error and short-term environmental risk factors.

Marriage is associated with a reduced rate of criminal recidivism, but the underlying mechanisms have only partly been elucidated. We seek to clarify the nature of the association between marriage and recidivism and how that relationship may be moderated as a function of gender, deviance of spouse, a history of violence and familial risk.

We utilise a longitudinal cohort design consisting of Swedish men (n = 239 328) and women (n = 72 280), born between 1958 and 1986, who were convicted of at least one crime before age 20 and were not married prior to age 20. The analyses used Cox regression with marriage as a time-dependent covariate. We also perform co-relative analyses in sibling and first cousin pairs.

Marriage after a first crime substantially reduces risk of recidivism in both males (hazard ratio (HR) with key covariates and 95% confidence intervals 0.55, 0.53–0.57) and females (HR = 0.38, 0.34–0.42), although the effect is stronger in females. Marriage to a deviant spouse increases recidivism rates in males. In males, a history of violent criminality and high familial risk, respectively, decrease and increase sensitivity to the protective effect of marriage on recidivism. Consistent with a causal effect of marriage on recidivism, marriage was associated with a decline in risk for criminal relapse comparable with that in the population in both male–male sibling pairs (raw HR = 0.53, 0.45–0.62) and cousin pairs (HR = 0.55, 0.47, 0.65) concordant for prior convictions.

The protective effect of marriage on risk for criminal recidivism is likely largely causal and is of importance in both males and females. Those at high familial risk for criminal behaviour are more sensitive to the protective effects of marriage.

Although there is robust evidence linking childhood adversities (CAs) and an increased risk for psychotic experiences (PEs), little is known about whether these associations vary across the life-course and whether mental disorders that emerge prior to PEs explain these associations.

We assessed CAs, PEs and DSM-IV mental disorders in 23 998 adults in the WHO World Mental Health Surveys. Discrete-time survival analysis was used to investigate the associations between CAs and PEs, and the influence of mental disorders on these associations using multivariate logistic models.

Exposure to CAs was common, and those who experienced any CAs had increased odds of later PEs [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.9–2.6]. CAs reflecting maladaptive family functioning (MFF), including abuse, neglect, and parent maladjustment, exhibited the strongest associations with PE onset in all life-course stages. Sexual abuse exhibited a strong association with PE onset during childhood (OR 8.5, 95% CI 3.6–20.2), whereas Other CA types were associated with PE onset in adolescence. Associations of other CAs with PEs disappeared in adolescence after adjustment for prior-onset mental disorders. The population attributable risk proportion (PARP) for PEs associated with all CAs was 31% (24% for MFF).

Exposure to CAs is associated with PE onset throughout the life-course, although sexual abuse is most strongly associated with childhood-onset PEs. The presence of mental disorders prior to the onset of PEs does not fully explain these associations. The large PARPs suggest that preventing CAs could lead to a meaningful reduction in PEs in the population.

Worldwide 350 million people suffer from major depression, with the majority of cases occurring in low- and middle-income countries. We examined the patterns, correlates and care-seeking behaviour of adults suffering from major depressive episode (MDE) in China.

A nationwide study recruited 512 891 adults aged 30–79 years from 10 provinces across China during 2004–2008. The 12-month prevalence of MDE was assessed by the Modified Composite International Diagnostic Interview-short form. Logistic regression yielded adjusted odds ratios (ORs) of MDE associated with socio-economic, lifestyle and health-related factors and major stressful life events.

Overall, 0.7% of participants had MDE and a further 2.4% had major depressive symptoms. Stressful life events were strongly associated with MDE [adjusted OR 14.7, 95% confidence interval (CI) 13.7–15.7], with a dose–response relationship with the number of such events experienced. Family conflict had the highest OR for MDE (18.9, 95% CI 16.8–21.2) among the 10 stressful life events. The risk of MDE was also positively associated with rural residency (OR 1.5, 95% CI 1.4–1.7), low income (OR 2.3, 95% CI 2.1–2.4), living alone (OR 2.6, 95% CI 2.3–3.0), smoking (OR 1.4, 95% CI 1.3–1.6) and certain other mental disorders (e.g. anxiety, phobia). Similar, albeit weaker, associations were observed with depressive symptoms. Among those with MDE, about 15% sought medical help or took psychiatric medication, 15% reported having suicidal ideation and 6% reported attempting suicide.

Among Chinese adults, the patterns and correlates of MDE were generally consistent with those observed in the West. The low rates of seeking professional help and treatment highlight the great gap in mental health services in China.