Childhood behavior problems and adverse economic outcomes: a 30-year population-based study of intergenerational income mobility.

BACKGROUND: The objectives of this study were to (a) assess the associations between early behavioral problems and intergenerational income mobility (i.e., the degree to which income status is transmitted from one generation to the next), (b) verify whether these associations are moderated by child sex, and (c) explore indirect effects of early behavioral problems on income mobility via high school graduation. METHODS: Data were drawn from the Quebec Longitudinal Study of Kindergarten Children (n = 3,020; 49.17% girls). Participants were followed from age 6 to 37 years. Measures included parents' and teachers' ratings of behavioral problems at age 6 years as well as participants' (ages 30-35 years) and their parents' (when participants were aged 10-19 years) income data obtained from tax return records. Regression models were used to predict upward and downward mobility (i.e., increased or decreased income status from one generation to the next) from attention-deficit/hyperactivity problems, conduct/opposition problems, depression/anxiety problems, prosociality, and the quality of children's relationship with their caregiver. Two-way interaction effects between behavioral problems and child sex were examined and indirect effect models including high school graduation as a mediator of these associations were conducted. RESULTS: Despite their higher educational attainment, females had lower incomes and experienced lower upward (but higher downward) income mobility than males. For both females and males, higher levels of attention-deficit/hyperactivity and conduct/opposition problems were associated with decreased odds of upward mobility, whereas higher levels of attention-deficit/hyperactivity were associated with increased odds of downward mobility. Attention-deficit/hyperactivity problems, conduct/opposition problems as well as low prosociality were associated with lower educational attainment (no high school diploma), which in turn was associated with increased odds of downward mobility. CONCLUSIONS: Results highlight the importance of providing intensive support to children with early behavioral problems as a means of improving educational attainment and intergenerational income mobility.

On executive functioning and childcare: The moderating role of parent-child interactions.

Childcare services are widely used by families and thereby exert an important influence on many young children. Yet, little research has examined whether childcare may impact the development of child executive functioning (EF), one of the pillars of cognitive development in early childhood. Furthermore, despite persisting hypotheses that childcare may be particularly beneficial for children who have less access to optimal developmental resources at home, research has yet to address the possibility that putative associations between childcare and EF may vary as a function of family factors. Among a sample of 180 mostly White middle-class families (91 girls), we examined if childcare participation in infancy was related to two aspects of EF (Delay and Conflict) at 3 years, and whether two aspects of maternal parenting behavior (sensitivity and autonomy support) moderated these associations. The results showed positive associations between participation in group-based childcare and Delay EF specifically among children of relatively less autonomy-supportive mothers. These findings suggest that out-of-home childcare services may play a protective role for children exposed to parenting that is less conducive to their executive development. RESEARCH HIGHLIGHTS: Little research has considered effects of childcare in infancy on executive functioning (EF). Long-standing hypothesis that childcare is more beneficial for children exposed to less sensitive and supportive parenting. We test interactions between maternal parenting and childcare participation in infancy in relation to EF at age 3 years. We find positive associations between participation in group-based childcare and Delay EF specifically among children of relatively less autonomy-supportive mothers.

Mechanisms and pathways linking kindergarten behavior problems with mid-life employment earnings for males from low-income neighborhoods.

Childhood behavior problems are associated with reduced labor market participation and lower earnings in adulthood, but little is known about the pathways and mechanisms that explain these associations. Drawing on a 33-year prospective birth cohort of White males from low-income backgrounds (n = 1040), we conducted a path analysis linking participants' teacher-rated behavior problems at age 6 years-that is, inattention, hyperactivity, aggression-opposition, and low prosociality-to employment earnings at age 35-39 years obtained from tax records. We examined three psychosocial mediators at age 11-12 years (academic, behavioral, social) and two mediators at age 25 years (non-high school graduation, criminal convictions). Our findings support the notion that multiple psychosocial pathways-especially low education attainment-link kindergarten behavior problems to lower employment earnings decades later.

Revisiting the childcare-attachment question: under what conditions is childcare participation associated with mother-child attachment security?

Decades have passed since the controversy regarding the putative risks of childcare for mother-child attachment broke out. Yet, some uncertainty remains, as relevant studies have produced inconsistent evidence. Some have proposed that those conflicting findings may be due to the fact that the effects of childcare are conditioned on parenting. Accordingly, this study examined whether relations between childcare participation and mother-child attachment vary according to maternal sensitivity and autonomy support. In this sample of 236 mother-child dyads, there was no indication of main effects of childcare participation on attachment. There were, however, some interactive effects, such that the children who showed the least secure attachment behaviors were those who did not attend childcare and had either less sensitive or less autonomy-supportive mothers. The findings suggest that the effects of childcare on mother-child attachment are best understood in light of the parenting children receive at home.

Perinatal and early-life factors associated with stable and unstable trajectories of psychopathic traits across childhood.

BACKGROUND: This study aimed to identify perinatal and early-life factors associated with trajectories of psychopathic traits across childhood. METHODS: Participants were 1631 children (51.5% girls) from the Quebec Longitudinal Study of Child Development. A wide range of perinatal and early-life factors were assessed from pregnancy to age 2.5 years using medical files and mothers' reports. Psychopathic traits were assessed via teachers' reports at ages 6, 7, 8, 10, and 12 years. Latent class growth analyses and multinomial logistic regressions controlling for child sex were conducted. Two-way interaction effects between perinatal/early-life factors and child sex were explored. RESULTS: Four trajectories of psychopathic traits were identified: High-stable (4.48%), Increasing (8.77%), Decreasing (11.46%), and Low-stable (75.29%). A few perinatal factors and most child-level and family-level early-life factors significantly increased the odds of following the High-stable v. the Low-stable trajectory. Higher levels of psychotropic exposures during pregnancy, socioeconomic adversity, child's physical aggression, child's opposition, mother's depressive symptoms, and hostile parenting increased the likelihood of following the Increasing instead of the Low-stable trajectory. Higher socioeconomic adversity, mother's depressive symptoms, and inconsistent parenting were associated with membership to the High-stable instead of the Decreasing trajectory. Most associations were not moderated by child sex. CONCLUSIONS: These results shed light on the perinatal and early-life factors that are associated with specific pathways of psychopathic traits during childhood and suggest that different factors could be targeted to prevent the exacerbation (v. low and stable levels) or the stability at high levels (v. attenuation) of these traits.

Mental health comorbidities following peer victimization across childhood and adolescence: a 20-year longitudinal study.

BACKGROUND: Peer victimization is associated with a wide range of mental health problems in youth, yet few studies described its association with mental health comorbidities. METHODS: To test the association between peer victimization timing and intensity and mental health comorbidities, we used data from 1216 participants drawn from the Quebec Longitudinal Study of Child Development, a population-based birth cohort. Peer victimization was self-reported at ages 6-17 years, and modeled as four trajectory groups: low, childhood-limited, moderate adolescence-emerging, and high-chronic. The outcomes were the number and the type of co-occurring self-reported mental health problems at age 20 years. Associations were estimated using negative binomial and multinomial logistic regression models and adjusted for parent, family, and child characteristics using propensity score inverse probability weights. RESULTS: Youth in all peer victimization groups had higher rates of co-occurring mental health problems and higher likelihood of comorbid internalizing-externalizing problems [odds ratios ranged from 2.06, 95% confidence interval (CI) 1.52-2.79 for childhood-limited to 4.34, 95% CI 3.15-5.98 for high-chronic victimization] compared to those in the low victimization group. The strength of these associations was highest for the high-chronic group, followed by moderate adolescence-emerging and childhood-limited groups. All groups also presented higher likelihood of internalizing-only problems relative to the low peer victimization group. CONCLUSIONS: Irrespective of timing and intensity, self-reported peer victimization was associated with mental health comorbidities in young adulthood, with the strongest associations observed for high-chronic peer victimization. Tackling peer victimization, especially when persistent over time, could play a role in reducing severe and complex mental health problems in youth.

Medical conditions and Attention-Deficit/Hyperactivity Disorder symptoms from early childhood to adolescence.

The comorbidity between physical and mental health conditions is challenging and frequently goes unrecognized in practice. Associations between Attention-Deficit/Hyperactivity Disorder (ADHD) and physical conditions have been reported in youth. However, prior research failed to: (1) address the patterns of associations in early childhood, middle childhood, and adolescence within the same population sample; (2) consider a large set of physical disorders at the same time; (3) take confounders into account. Our goal was to assess the associations between ADHD symptoms and a broad set of physical conditions across developmental periods. This birth cohort study (n = 2057) is the first to explore the associations between ADHD and a wide range of medical conditions by encompassing the whole early development from 5 months to 17 years in the same sample and relying on innovative network analyses. We found significant associations between ADHD symptoms and several physical conditions, some of which were observed in early childhood, middle childhood, and adolescence (e.g., asthma, sleep problems) or were confounded by socioeconomic status or psychiatric comorbidities (e.g., body mass index, dental caries). The study calls for an effective integrated care model encompassing mental and general healthcare across the developmental period.

Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.

Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development.

BACKGROUND: Peer victimisation has been associated with depressive symptoms during adolescence, however not all peer victimised adolescents will exhibit such symptoms. This study tested whether having a genetic predisposition to developing depression increased the risk of experiencing depressive symptoms in peer victimised youth. To date, no study has explored such gene-environment interaction using a polygenic risk score for depression (PRS-depression) in the context of peer victimisation and depressive symptoms in adolescence. METHODS: The sample included 748 participants born in 1997/98 from the Quebec Longitudinal Study of Child Development with genotype data and prospectively collected information on peer victimisation (12-13 years) obtained from both self- and teacher-reports, as well as self-reported depressive symptoms (15-17 years). The PRS-depression was based on the genome-wide association meta-analysis of broad depression by Howard et al. (2019). RESULTS: Self- and teacher-reported peer victimisation in early adolescence were both associated with depressive symptoms in adolescence (ß = 0.34, p < .001; ß = 0.14, p = .001 respectively), and this association remained significant when accounting for PRS-depression (ß = 0.33, p < .001; ß = 0.13, p = .002 respectively). PRS-depression was independently associated with depressive symptoms, but there was no significant PRS-depression by peer victimisation interaction (self-reported and teacher-reported). PRS-depression was correlated with self-reported, but not teacher-reported, peer victimisation. CONCLUSIONS: Our findings suggested that a partial measure of an individual's genetic predisposition to depression, as measured by PRS-depression, and being exposed to peer victimisation (self- and teacher-reported) were independently associated with depressive symptoms in adolescence. Furthermore, PRS-depression did not exacerbate the risk of depressive symptoms among adolescents who had been peer victimised. Lastly, we found evidence of a gene-environment correlation between PRS-depression and self-reported peer victimisation. Future studies are needed to replicate this finding and to further understand the role of genetic predispositions in experiencing depressive symptoms following peer victimisation.

Do more hours in center-based care cause more externalizing problems? A cross-national replication study.

Whether high quantities of center-based care cause behavior problems is a controversial question. Studies using covariate adjustment for selection factors have detected relations between center care and behavior problems, but studies with stronger internal validity less often find such evidence. We examined whether within-child changes in hours in center-based care predicted changes in externalizing problems in toddlers and preschoolers (N = 10,105; 49% female; data collection 1993-2012) in seven studies, including from Germany, Netherlands, Norway, two from Canada and two from the U.S. Race/ethnicity data were only collected in the United States (57% and 80% White; 42% and 13% African-American; 1.2% and 5% Latinx). Meta-analyses showed no association (r = .00, p = .88) between hours in center-based care and externalizing problems.

Adolescents' internalizing symptoms predict dating violence victimization and perpetration 2 years later.

The aim of this longitudinal study was to examine bidirectional associations of adolescents' internalizing symptoms with dating violence victimization and perpetration. We conducted secondary analyses of the Québec Longitudinal Study of Child Development data (n = 974). Each adolescent completed items from the Conflict Tactics Scale (at ages 15 and 17 years) to assess psychological, physical, and sexual dating violence victimization and perpetration in the past 12 months. Adolescents' symptoms of depression and general anxiety in the past 12 months were self-reported (at ages 15 and 17 years) using The Mental Health and Social Inadaptation Assessment for Adolescents. There were concurrent associations of adolescents' internalizing symptoms with dating violence victimization and perpetration. Internalizing symptoms at age 15 years were positively associated with dating violence victimization and perpetration 2 years later in both males and females, even after adjusting for baseline characteristics. However, neither dating violence victimization nor perpetration at age 15 years was associated with internalizing symptoms 2 years later. For males and females, internalizing symptoms put adolescents at risk for future dating violence victimization and perpetration. Interventions that target internalizing symptoms may have the potential to decrease subsequent dating violence.

Behaviors in kindergarten are associated with trajectories of long-term welfare receipt: A 30-year population-based study.

This study examines the link between behavior in kindergarten and adult-life welfare receipt. Teacher-rated behavioral assessments were obtained for inattention, hyperactivity, aggression-opposition, anxiety, and prosociality when children (n=2960) were aged 5-6 years and linked to their tax return records from age 18-35 years. We used group-based based trajectory modeling to identify distinct trajectories of welfare receipt and multinomial logistic regression models to examine the association between behaviors and trajectory group membership. The child's sex, IQ, and family background were adjusted for. Four trajectories of welfare receipt were identified: low (n = 2,390, 80.7%), declining (n = 260, 8.8%), rising (n = 150, 5.2%), and chronic (n = 160, 5.4%). Relative to the low trajectory, inattention and aggression-opposition at age 6 years were associated with increased risk of following a declining, rising, and chronic trajectory of welfare receipt, independent of hyperactivity and anxiety. Prosocial behaviors were independently associated with a lower risk of following a chronic trajectory. This study shows that kindergarten children exhibiting high inattention and aggression-opposition and low prosocial behaviors may be at increased risk of long-term welfare receipt in adulthood. The implications for early screening, monitoring, and prevention are discussed.

Association between ADHD symptoms and illicit stimulants use following 1 year among French university students of the i-Share cohort.

PURPOSE: Although attention deficit hyperactivity disorder (ADHD) has been associated with illicit stimulants use, less is known about their prospective association in university students. We aimed to examine the association between ADHD symptoms at inclusion and illicit stimulants use following 1 year among university students. METHODS: The i-Share cohort recruited French students from February 2013 to July 2020. The study included 4270 participants. The Adult ADHD Self-Report Scale (ASRS) was used to evaluate ADHD symptoms at inclusion. Illicit stimulants use was assessed at inclusion and 1 year after inclusion. Multivariable logistic regressions were conducted to assess the association between ADHD symptoms at inclusion and illicit stimulants use following 1 year. RESULTS: High levels of ADHD symptoms at inclusion were associated with a greater probability of illicit stimulants use following 1 year (adjusted OR: 2.42 (1.51-3.8)). The adjusted odds ratio was 2.7 (1.08-7.84) among participants who had used illicit stimulant at least once (continuation) and 2.25 (1.04-4.37) among participants who had never used illicit stimulants at inclusion (initiation). CONCLUSION: High levels of ADHD symptoms are a feature that may promote both initiation and continuation of illicit stimulants use among university students. Our findings suggest that university students with high levels of ADHD symptoms may benefit from screening to help identify those at risk of illicit stimulants use.

Childhood psychopathic traits and mental health outcomes in adolescence: compensatory and protective effects of positive relationships with parents and teachers.

We identified mental health outcomes associated with specific developmental trajectories of psychopathic traits across childhood and tested whether positive relationships with parents and teachers have compensatory or protective effects. Participants were 1401 children (52.82% girls) from the Quebec Longitudinal Study of Child Development with available data on teacher-reported psychopathic traits (ages 6-12 years) and self-reported mental health outcomes (ages 15-17 years). Parents and teachers reported their levels of positive relationship with the child (ages 6-8 and 10-12 years). Trajectories of psychopathic traits (High-stable, Increasing, Decreasing, and Low-stable) were included as predictors of mental health outcomes (e.g., conduct disorder, anxiety) in structural equation models controlling for child sex, family SES, and earlier psychopathology. Compensatory effects were tested via main effects of positive relationships and protective effects were tested via their interactive effects with trajectories memberships. When compared to the Low-stable trajectory of psychopathic traits, the High-stable, Increasing, and Decreasing trajectories were associated with distinct sets of mental health outcomes, with children from the Increasing trajectory being at higher risk for both externalizing and internalizing psychopathology. Positive relationships with parents and teachers only partially compensated for these effects. Findings suggest that clinicians cannot expect the detrimental effects associated with psychopathic traits to be entirely prevented by children's positive relationships with parents and/or teachers. This study reinforces the importance of providing intensive preventive interventions to elementary school children with high levels of psychopathic traits to prevent the long-term negative consequences associated with these traits.

Longitudinal impact of psychosocial status on children's mental health in the context of COVID-19 pandemic restrictions.

Emerging research suggests that the prevalence of child and adolescent mental health problems has increased considerably during the COVID-19 crisis. However, there have been few longitudinal studies on children's mental health issues according to their social determinants in this context, especially in Europe. Our aim was to investigate the association between family socioeconomic status (SES) and children' mental health during the period of school closure due to COVID-19. Longitudinal data came from 4575 children aged 8-9 years old in 2020 and participating in the ELFE population-based birth cohort that focuses on children's health, development and socialization. Parents completed the Strengths and Difficulties Questionnaire (SDQ) when children were (a) 5 years of age and (b) 9 years of age, which corresponded to the period of school closure due to the COVID-19 pandemic in France. We retrieved data from the ELFE cohort collected on children from birth to age 5 years (birth, 1 year, 2 years, 3,5 years and 5 years). Socioeconomic status (SES) was measured based on information obtained when the child was 5 years old. Data were analyzed using multinomial logistic regression models. Children's elevated levels of symptoms of Attention-deficit/Hyperactivity disorder (ADHD) during the period of school closure were significantly associated with prior low family SES (aOR 1.26, 95% CI 1.08-1.48). Children's elevated symptoms of hyperactivity/inattention and of emotional symptoms were associated with decline in income during the COVID crisis (respectively, aOR 1.38, 95% CI 1.16-1.63 and aOR 1.23, 95% CI 1.01-1.51). Moreover, when testing interactions, a low prior SES was significantly associated with a higher risk of emotional symptoms aOR 1.54 (1.07-2.21), only for children whose families experienced a decline in income, while gender, parental separation and prior mental health difficulties were not associated. This study underlines the impact of the financial crisis related to the COVID-19 epidemic on children's mental health. Both pre-existing family SES before lockdown and more proximal financial difficulties during the COVID crisis were negatively associated with children's psychological difficulties during the period of school closure. The pandemic appears to exacerbate mental health problems in deprived children whose families suffer from financial difficulties.

Developmental Patterns of Gambling Participation and Substance use Throughout Adolescence in a Population Birth Cohort.

This study investigated adolescents' single and co-occurring developmental patterns of gambling participation and substance use and their association with gambling and substance use-related issues at age 17, controlling for confounders. Multiple assessments from age 12 to 17 were conducted in a population-based cohort (N=1594, 51.2% boys). Latent growth modeling was used to analyze developmental patterns and Generalized linear models to examine their association with age-17 gambling and substance use-related problems, types and variety of activities, and substance abuse. Results revealed six developmental patterns, including Low- or Non-substance Users or Gamblers (24.2% sample), two trajectory-classes of Later-Onset Increasing (to a moderate level) substance users, either with or without gambling participation (7.8% and 45.5%, respectively), two trajectory-classes of Early-Onset Increasing (to a higher level) substance users, either with or without gambling participation (6.2% and 12.7%, respectively), and a smaller trajectory-class of Slow-Increasing Substance Users and Early-Onset Gamblers, declining to non-gambling after age 13 (3.6%). Gambling participation and substance use did not appear to influence each other with regard to their onset and course throughout adolescence, and to age-17 types and variety of gambling activities or substances used, problems related to gambling participation or substance use, or substance abuse. These findings are consistent with the addictive syndrome model and with both common and individualized approaches to prevention and treatment for adolescent gamblers or substance users.

Childhood Overeating and Disordered Eating From Early Adolescence to Young Adulthood: A Longitudinal Study on the Mediating Role of BMI, Victimization and Desire for Thinness.

Eating disorders have early origins, and there could be a continuum between childhood eating behaviors, such as overeating, and long-term disordered eating, but this remains to be shown. BMI, desire for thinness and peer victimization could influence this continuum, but their interactions are unknown. To fill this gap, the study used data from the Quebec Longitudinal Study of Child Development (N = 1511; 52% girls), in which 30.9% of youth presented a trajectory associated with high disordered eating from 12 to 20 years. The results support an indirect association between overeating at age 5 and disordered eating trajectories, with different mediation processes observed between boys and girls. The findings underscore the importance of promoting healthy body images and eating behaviors among youths.

Maternal depressive symptoms and children's academic performance: sex differences in the mediating role of school experiences.

BACKGROUND: Maternal depressive symptoms (MDSs) are negatively associated with children's academic performance, with stronger effects sometimes reported in boys. However, few studies have tested the mechanisms of this association. We examined the mediating role of school engagement and peer victimization in this association and tested for sex differences. METHODS: Participants were 1173 families from a population-based longitudinal Canadian study. MDSs were self-reported annually using the Centre for Epidemiologic Studies Depression Scale (child's age: 5 months to 5 years). Data on mediators (peer victimization, cognitive, behavioral, and emotional school engagement) were reported annually from ages 6-10 by multiple informants including children, parents, and teachers using items from validated scales. Mathematics, reading, and writing exam scores at age 12 were obtained from standardized exams administered by Québec's Ministry of Education and Teaching. Structural equation modeling was used to test mediation by school experiences in boys and girls. RESULTS: Exposure to MDSs was negatively associated with mathematics, reading, and writing scores in girls and with mathematics only in boys. Cognitive and behavioral engagement significantly mediated the association between MDSs and mathematics, reading, and writing scores in girls. There were no significant mediators for boys. CONCLUSIONS: Prevention and intervention strategies aiming to improve school engagement might be beneficial for daughters of mothers experiencing depressive symptoms. Further research is needed to replicate these findings and to identify the mechanisms explaining this association in boys.

Perinatal adversity profiles and suicide attempt in adolescence and young adulthood: longitudinal analyses from two 20-year birth cohort studies.

BACKGROUND: We aimed to identify groups of children presenting distinct perinatal adversity profiles and test the association between profiles and later risk of suicide attempt. METHODS: Data were from the Québec Longitudinal Study of Child Development (QLSCD, N = 1623), and the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5734). Exposures to 32 perinatal adversities (e.g. fetal, obstetric, psychosocial, and parental psychopathology) were modeled using latent class analysis, and associations with a self-reported suicide attempt by age 20 were investigated with logistic regression. We investigated to what extent childhood emotional and behavioral problems, victimization, and cognition explained the associations. RESULTS: In both cohorts, we identified five profiles: No perinatal risk, Poor fetal growth, Socioeconomic adversity, Delivery complications, Parental mental health problems (ALSPAC only). Compared to children with No perinatal risk, children in the Poor fetal growth (pooled estimate QLSCD-ALSPAC, OR 1.89, 95% CI 1.04-3.44), Socioeconomic adversity (pooled-OR 1.42, 95% CI 1.08-1.85), and Parental mental health problems (OR 1.74, 95% CI 1.27-2.40), but not Delivery complications, profiles were more likely to attempt suicide. The proportion of this effect mediated by the putative mediators was larger for the Socioeconomic adversity profile compared to the others. CONCLUSIONS: Perinatal adversities associated with suicide attempt cluster in distinct profiles. Suicide prevention may begin early in life and requires a multidisciplinary approach targeting a constellation of factors from different domains (psychiatric, obstetric, socioeconomic), rather than a single factor, to effectively reduce suicide vulnerability. The way these factors cluster together also determined the pathways leading to a suicide attempt, which can guide decision-making on personalized suicide prevention strategies.

A genetically informed study on the association of cannabis, alcohol, and tobacco smoking with suicide attempt.

Use of substances such as cannabis, alcohol, and tobacco, has been associated with increased risk of suicide attempt in several observational studies. However, establishing whether these associations are causal is challenging when using observational designs. To evaluate the potential causal contributions of cannabis use, alcohol use, and tobacco smoking to suicide attempt, we applied two-sample Mendelian randomization, an instrumental variable approach using single-nucleotide polymorphisms (SNPs) as instrumental variables for three exposures: lifetime cannabis use (yes/no; 42 instrument SNPs; GWAS sample size [N] = 162,082), alcohol use (drinks-per-week; 53 instrument SNPs; N = 941,280), and tobacco smoking (initiation, yes/no; 156 instrument SNPs; N = 1,232,091; heaviness; 27 instrument SNPs; N = 337,334). The main outcome was suicide attempt measured from hospital records (N = 50,264). All data come from publicly available summary statistics of genome-wide association studies of participants of European ancestry. We found evidence supporting a possible causal role of cannabis (OR = 1.18; 95% CI = 1.01-1.37, P = 0.032), alcohol (OR = 1.95; 95% CI = 1.15-3.32, P = 0.013), and smoking (initiation, OR = 1.90; 95% CI = 1.54-2.34, P < 0.001; heaviness, OR = 2.13; 95% CI = 1.13-3.99; P = 0.019) on suicide attempt. Using multivariable Mendelian randomization, we found that only cannabis showed a direct pathway to suicide attempt (P = 0.001), suggesting that the effect of alcohol and smoking was mediated by the other substance use phenotypes. No evidence was found for reverse causation, i.e., associations of suicide attempt on cannabis (P = 0.483), alcohol (P = 0.234), smoking initiation (P = 0.144), and heaviness (P = 0.601). In conclusion, evidence from this quasi-experimental study based on genetic data from large-scale GWASs are consistent with a causal role of cannabis, alcohol, and tobacco smoking on suicide attempt.