Identifying risk factors involved in the common versus specific liabilities to substance use: A genetically informed approach.

Individuals most often use several rather than one substance among alcohol, cigarettes or cannabis. This widespread co-occurring use of multiple substances is thought to stem from a common liability that is partly genetic in origin. Genetic risk may indirectly contribute to a common liability to substance use through genetically influenced mental health vulnerabilities and individual traits. To test this possibility, we used polygenic scores indexing mental health and individual traits and examined their association with the common versus specific liabilities to substance use. We used data from the Avon Longitudinal Study of Parents and Children (N = 4218) and applied trait-state-occasion models to delineate the common and substance-specific factors based on four classes of substances (alcohol, cigarettes, cannabis and other illicit substances) assessed over time (ages 17, 20 and 22). We generated 18 polygenic scores indexing genetically influenced mental health vulnerabilities and individual traits. In multivariable regression, we then tested the independent contribution of selected polygenic scores to the common and substance-specific factors. Our results implicated several genetically influenced traits and vulnerabilities in the common liability to substance use, most notably risk taking (bstandardised = 0.14; 95% confidence interval [CI] [0.10, 0.17]), followed by extraversion (bstandardised = -0.10; 95% CI [-0.13, -0.06]), and schizophrenia risk (bstandardised = 0.06; 95% CI [0.02, 0.09]). Educational attainment (EA) and body mass index (BMI) had opposite effects on substance-specific liabilities such as cigarette use (bstandardised-EA = -0.15; 95% CI [-0.19, -0.12]; bstandardised-BMI = 0.05; 95% CI [0.02, 0.09]) and alcohol use (bstandardised-EA = 0.07; 95% CI [0.03, 0.11]; bstandardised-BMI = -0.06; 95% CI [-0.10, -0.02]). These findings point towards largely distinct sets of genetic influences on the common versus specific liabilities.

Multi-Polygenic Score Approach to Identifying Individual Vulnerabilities Associated With the Risk of Exposure to Bullying.

Importance: Exposure to bullying is a prevalent experience with adverse consequences throughout the life span. Individual vulnerabilities and traits, such as preexisting mental health problems, may be associated with increased likelihood of experiencing bullying. Identifying such individual vulnerabilities and traits is essential for a better understanding of the etiology of exposure to bullying and for tailoring effective prevention. Objective: To identify individual vulnerabilities and traits associated with exposure to bullying in childhood and adolescence. Design, Setting, and Participants: For this study, data were drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort study. The initial ALSPAC sample consisted of 14 062 children born to women residing in Avon, United Kingdom, with an expected date of delivery between April 1, 1991, and December 31, 1992. Collection of the ALSPAC data began in September 6, 1990, and the last follow-up assessment of exposure to bullying was conducted when participants were 13 years of age. Data analysis was conducted from November 1, 2017, to January 1, 2019. Exposures: The polygenic score approach was used to derive genetic proxies that indexed vulnerabilities and traits. A total of 35 polygenic scores were computed for a range of mental health vulnerabilities (eg, depression) and traits related to cognition (eg, intelligence), personality (eg, neuroticism), and physical measures (eg, body mass index), as well as negative controls (eg, osteoporosis). Main Outcomes and Measures: Single and multi-polygenic score regression models were fitted to test the association between indexed traits and exposure to bullying. Children completed the Bullying and Friendship Interview Schedule at the ages of 8, 10, and 13 years. A mean score of exposure to bullying across ages was used as the main outcome. Results: A total of 5028 genotyped individuals (2481 boys and 2547 girls) with data on exposure to bullying were included. Among the 35 initially included polygenic scores, 11 were independently associated with exposure to bullying; no significant association was detected for the 24 remaining scores. In multivariable analyses, 5 polygenic scores were associated with exposure to bullying; the largest associations were present for genetic risk relating to mental health vulnerabilities, including diagnosis of depression (standardized b = 0.065; 95% CI, 0.035-0.095) and attention-deficit/hyperactivity disorder (standardized b = 0.063; 95% CI, 0.035-0.091), followed by risk taking (standardized b = 0.041; 95% CI, 0.013-0.069), body mass index (standardized b = 0.036; 95% CI, 0.008-0.064), and intelligence (standardized b = -0.031; 95% CI, -0.059 to 0.003). Conclusion and Relevance: Using the multi-polygenic score approach, the findings implicate preexisting mental health vulnerabilities as risk factors for exposure to bullying. A mechanistic understanding of how these vulnerabilities link to exposure of bullying is important to inform prevention strategies.

Quasi-experimental evidence on short- and long-term consequences of bullying victimization: A meta-analysis.

Exposure to bullying victimization is associated with a wide-range of short and long-term adverse outcomes. However, the extent to which these associations reflect a causal influence of bullying victimization remains disputed. Here, we aimed to provide the most stringent evidence regarding the consequences of bullying victimization by meta-analyzing all relevant quasi-experimental (QE) studies. Multilevel random effects models and metaregression were employed to (a) estimate the pooled QE-adjusted effect size (Cohen d) for bullying victimization on outcomes and to (b) evaluate potential sources of heterogeneity. A total of 16 studies were included. We derived 101 QE-estimates from three different methods (twin design, fixed effects analysis, and propensity score matching) for three pools of outcomes (internalizing symptoms, externalizing symptoms, academic difficulties). QE-adjusted effects were small for internalizing symptoms (dadjusted = 0.27, 95% CI [0.05, 0.49]), and smaller for externalizing symptoms (dadjusted = 0.15, 95% CI [0.10, 0.21]) and academic difficulties (dadjusted = 0.10, 95% CI [0.06, 0.13]). Accounting for a shared rater effect between the exposure and the outcome further reduced the effect for internalizing (dnonshared rater = 0.14, 95% CI [0.05, 0.23]) and externalizing symptoms (dnonshared rater = 0.06, 95% CI [0.01, 0.11]). Finally, the adverse effects declined in the long-term, most markedly for internalizing symptoms (dlong-term = 0.06, 95% CI [-0.01, 0.13]). Based on the most stringent evidence available to date, findings indicate that bullying victimization may causally impact children's wellbeing in the short-term, especially anxiety and depression levels. The reduction of adverse effects over time highlights the potential for resilience in individuals who have experienced bullying. Secondary preventive interventions in bullied children should therefore focus on resilience and address children's preexisting vulnerabilities. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Concurrent and Longitudinal Contribution of Exposure to Bullying in Childhood to Mental Health: The Role of Vulnerability and Resilience.

Importance: Exposure to bullying is associated with poor mental health. However, the degree to which observed associations reflect direct detrimental contributions of exposure to bullying to mental health remains uncertain, as noncausal relationships may arise from genetic and environmental confounding (eg, preexisting vulnerabilities). Determining to what extent exposure to bullying contributes to mental health is an important concern, with implications for primary and secondary interventions. Objective: To characterize the concurrent and longitudinal contribution of exposure to bullying to mental health in childhood and adolescence using a twin differences design to strengthen causal inference. Design, Setting, and Participants: Participants were drawn from the Twins Early Development Study, a population-based cohort recruited from population records of births in England and Wales between January 1, 1994, and December 31, 1996. Data collection took place when the participants were between 11 and 16 years of age from December 1, 2005, to January 31, 2013. Data analysis was conducted from January 1, 2016, to June 20, 2017. Exposures: Participants completed the Multidimensional Peer-Victimization Scale at 11 and 14 years of age. Main Outcomes and Measures: Mental health assessments at 11 and 16 years of age included anxiety, depression, hyperactivity and impulsivity, inattention, conduct problems, and psychotic-like experiences (eg, paranoid thoughts or cognitive disorganization). Results: The 11 108 twins included in the final sample (5894 girls and 5214 boys) were a mean age of 11.3 years at the first assessment and 16.3 years at the last assessment. The most stringent twin differences estimates (monozygotic) were consistent with causal contribution of exposure to bullying at 11 years to concurrent anxiety, depression, hyperactivity and impulsivity, inattention, and conduct problems. Effects decreased over time; that is, substantial concurrent contributions to anxiety (ß = 0.27; 95% CI, 0.22-0.33) persisted for 2 years (ß = 0.12; 95% CI, 0.04-0.20) but not 5 years. Direct contributions to paranoid thoughts and cognitive disorganization persisted for 5 years. Conclusions and Relevance: This study is the largest to date to characterize the contribution of exposure to bullying in childhood to mental health using a twin differences design and multi-informant, multiscale data. Stringent evidence of the direct detrimental contribution of exposure to bullying in childhood to mental health is provided. Findings also suggest that childhood exposure to bullying may partly be viewed as a symptom of preexisting vulnerabilities. Finally, the dissipation of effects over time for many outcomes highlights the potential for resilience in children who were bullied. In addition to programs that aim to reduce exposure to bullying, interventions may benefit from addressing preexisting vulnerabilities and focus on resilience.