Triarchic traits as risk versus protective factors for ADHD symptomatology: A prospective longitudinal investigation.

Attention-deficit/hyperactivity disorder (ADHD) symptoms are associated with myriad adverse outcomes, including interpersonal difficulties, but factors that moderate the developmental course and functional impact of ADHD over time are not well understood. The present study evaluated developmental contributions of the triarchic neurobehavioral traits (boldness, meanness, and disinhibition) to ADHD symptomatology and its subdimensions from adolescence to young adulthood. Participants were twins and triplets assessed at ages 14, 17, and 19 (initial N = 1,185, 51.2% female). Path analyses using negative binomial regression revealed that boldness at age 14 was associated with more ADHD symptoms cross-sectionally (especially hyperactivity/impulsivity), but fewer symptoms (especially inattention) at age 19 in the prospective analysis. Notably, inclusion of interpersonal problems at ages 14 and 17 as covariates reduced the latter effect to nonsignificant. Disinhibition concurrently and prospectively predicted higher levels of ADHD symptoms, including both subdimensions, and the prospective effects were partially mediated by greater social impairment at age 17. Meanness prospectively (but not concurrently) predicted higher levels of hyperactivity/impulsivity symptoms. Sex moderated certain associations of meanness and disinhibition with ADHD symptoms. These findings highlight how fundamental neurobehavioral traits shape both psychopathology and adaptive outcomes in the developmental course of ADHD.

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts.

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Pursuing the developmental aims of the triarchic model of psychopathy: Creation and validation of triarchic scales for use in the USC: RFAB longitudinal twin project.

The triarchic model was advanced as an integrative, trait-based framework for investigating psychopathy using different assessment methods and across developmental periods. Recent research has shown that the triarchic traits of boldness, meanness, and disinhibition can be operationalized effectively in youth, but longitudinal research is needed to realize the model's potential to advance developmental understanding of psychopathy. We report on the creation and validation of scale measures of the triarchic traits using questionnaire items available in the University of Southern California Risk Factors for Antisocial Behavior (RFAB) project, a large-scale longitudinal study of the development of antisocial behavior that includes measures from multiple modalities (self-report, informant rating, clinical-diagnostic, task-behavioral, physiological). Using a construct-rating and psychometric refinement approach, we developed triarchic scales that showed acceptable reliability, expected intercorrelations, and good temporal stability. The scales showed theory-consistent relations with external criteria including measures of psychopathy, internalizing/externalizing psychopathology, antisocial behavior, and substance use. Findings demonstrate the viability of measuring triarchic traits in the RFAB sample, extend the known nomological network of these traits into the developmental realm, and provide a foundation for follow-up studies examining the etiology of psychopathic traits and their relations with multimodal measures of cognitive-affective function and proneness to clinical problems.

Developmental Trajectories of Delinquent and Aggressive Behavior: Evidence for Differential Heritability.

The developmental course of antisocial behavior is often described in terms of qualitatively distinct trajectories. However, the genetic etiology of various trajectories is not well understood. We examined heterogeneity in the development of delinquent and aggressive behavior in 1532 twin youth using four waves of data collection, spanning ages 9-10 to 16-18. A latent class growth analysis was used to uncover relevant subgroups. For delinquent behavior, three latent classes emerged: Non-Delinquent, Low-Level Delinquent, and Persistent Delinquent. Liability for persistent delinquency had a substantial genetic origin (heritability = 67%), whereas genetic influences were negligible for lower-risk subgroups. Three classes of aggressive behavior were identified: Non-Aggressive, Moderate, and High. Moderate heritability spanned the entire continuum of risk for aggressive behavior. Thus, there are differences between aggressive behavior and non-aggressive delinquency with respect to heterogeneity of etiology. We conclude that persistent delinquency represents an etiologically distinct class of rule-breaking with strong genetic roots.

Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer.

BACKGROUND: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC through unknown mechanisms. METHODS: Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq. RESULTS: These studies reveal novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage. Analysis of clinical samples demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair deficiency. CONCLUSIONS: These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOC.

Genetic and environmental influences on disinhibition, boldness, and meanness as assessed by the triarchic psychopathy measure in 19-20-year-old twins.

BACKGROUND: The Triarchic Psychopathy Measure (TriPM) provides Disinhibition, Boldness, and Meanness scales for assessing the three trait domains of the triarchic model. Here we examined the genetic and environmental etiology of these three domains, including evaluation of potential sex differences. METHODS: A total of 1016 men and women ages 19-20 years were drawn from the University of Southern California Risk Factors for Antisocial Behavior twin study. RESULTS: Scores for the three TriPM scales were correlated to differing degrees, with the strongest phenotypic correlation between Disinhibition and Meanness. No sex differences were found in the genetic and environmental influences underlying these three domains, suggesting that the same genes and life experiences contribute to these traits in young men and women. For TriPM Disinhibition and Boldness, genetic factors explained about half or less of the variance, with the rest of the variance being explained by non-shared environmental factors. For TriPM Meanness, on the other hand, genetic, shared environmental, and non-shared environmental factors accounted for the variance. The phenotypic correlation between Disinhibition and Meanness was explained in part by common genes (26%), with the remainder attributable about equally to common shared (39%), and non-shared environmental influences (35%). CONCLUSIONS: These findings contribute to our understanding of psychopathic personality traits by demonstrating the importance of heritable factors for disinhibition and boldness facets of psychopathy, and the importance of shared environmental influences for the meanness facet.

Quality Improvement Initiative to Reduce Pediatric Intensive Care Unit Noise Pollution With the Use of a Pediatric Delirium Bundle.

OBJECTIVES:: Noise pollution in pediatric intensive care units (PICU) contributes to poor sleep and may increase risk of developing delirium. The Environmental Protection Agency (EPA) recommends <45 decibels (dB) in hospital environments. The objectives are to assess the degree of PICU noise pollution, to develop a delirium bundle targeted at reducing noise, and to assess the effect of the bundle on nocturnal noise pollution. METHODS:: This is a QI initiative at an academic PICU. Thirty-five sound sensors were installed in patient bed spaces, hallways, and common areas. The pediatric delirium bundle was implemented in 8 pilot patients (40 patient ICU days) while 108 non-pilot patients received usual care over a 28-day period. RESULTS:: A total of 20,609 hourly dB readings were collected. Hourly minimum, average, and maximum dB of all occupied bed spaces demonstrated medians [interquartile range] of 48.0 [39.0-53.0], 52.8 [48.1-56.2] and 67.0 [63.5-70.5] dB, respectively. Bed spaces were louder during the day (10AM to 4PM) than at night (11PM to 5AM) (53.5 [49.0-56.8] vs. 51.3 [46.0-55.3] dB, P < 0.01). Pilot patient rooms were significantly quieter than non-pilot patient rooms at night (n=210, 45.3 [39.7-55.9]) vs. n=1841, 51.2 [46.9-54.8] dB, P < 0.01). The pilot rooms compliant with the bundle had the lowest hourly nighttime average dB (44.1 [38.5-55.5]). CONCLUSIONS:: Substantial noise pollution exists in our PICU, and utilizing the pediatric delirium bundle led to a significant noise reduction that can be perceived as half the loudness with hourly nighttime average dB meeting the EPA standards when compliant with the bundle.

Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies.

Marijuana is one of the most commonly used drugs in the United States, and use during adolescence--when the brain is still developing--has been proposed as a cause of poorer neurocognitive outcome. Nonetheless, research on this topic is scarce and often shows conflicting results, with some studies showing detrimental effects of marijuana use on cognitive functioning and others showing no significant long-term effects. The purpose of the present study was to examine the associations of marijuana use with changes in intellectual performance in two longitudinal studies of adolescent twins (n = 789 and n = 2,277). We used a quasiexperimental approach to adjust for participants' family background characteristics and genetic propensities, helping us to assess the causal nature of any potential associations. Standardized measures of intelligence were administered at ages 9-12 y, before marijuana involvement, and again at ages 17-20 y. Marijuana use was self-reported at the time of each cognitive assessment as well as during the intervening period. Marijuana users had lower test scores relative to nonusers and showed a significant decline in crystallized intelligence between preadolescence and late adolescence. However, there was no evidence of a dose-response relationship between frequency of use and intelligence quotient (IQ) change. Furthermore, marijuana-using twins failed to show significantly greater IQ decline relative to their abstinent siblings. Evidence from these two samples suggests that observed declines in measured IQ may not be a direct result of marijuana exposure but rather attributable to familial factors that underlie both marijuana initiation and low intellectual attainment.

Epigenomics of mammary gland development.

Differentiation of stem cells into highly specialised cells requires gene expression changes brought about by remodelling of the chromatin architecture. During this lineage-commitment process, the majority of DNA needs to be packaged into inactive heterochromatin, allowing only a subset of regulatory elements to remain open and functionally required genes to be expressed. Epigenetic mechanisms such as DNA methylation, post-translational modifications to histone tails, and nucleosome positioning all potentially contribute to the changes in higher order chromatin structure during differentiation. The mammary gland is a particularly useful model to study these complex epigenetic processes since the majority of its development is postnatal, the gland is easily accessible, and development occurs in a highly reproducible manner. Inappropriate epigenetic remodelling can also drive tumourigenesis; thus, insights into epigenetic remodelling during mammary gland development advance our understanding of breast cancer aetiology. We review the current literature surrounding DNA methylation and histone modifications in the developing mammary gland and its implications for breast cancer.

Long-Term Ambient Temperature and Externalizing Behaviors in Adolescents.

The climate-violence relationship has been debated for decades, and yet most of the supportive evidence has come from ecological or cross-sectional analyses with very limited long-term exposure data. We conducted an individual-level, longitudinal study to investigate the association between ambient temperature and externalizing behaviors of urban-dwelling adolescents. Participants (n = 1,287) in the Risk Factors for Antisocial Behavior Study, in California, were examined during 2000-2012 (aged 9-18 years) with repeated assessments of their externalizing behaviors (e.g., aggression, delinquency). Ambient temperature data were obtained from the local meteorological information system. In adjusted multilevel models, aggressive behaviors significantly increased with rising average temperatures (per 1°C increment) in the preceding 1, 2, or 3 years (respectively, ß = 0.23, 95% confidence interval (CI): 0.00, 0.46; ß = 0.35, 95% CI: 0.06, 0.63; or ß = 0.41, 95% CI: 0.08, 0.74), equivalent to 1.5-3.0 years of delay in age-related behavioral maturation. These associations were slightly stronger among girls and families of lower socioeconomic status but greatly diminished in neighborhoods with more green space. No significant associations were found with delinquency. Our study provides the first individual-level epidemiologic evidence supporting the adverse association of long-term ambient temperature and aggression. Similar approaches to studying meteorology and violent crime might further inform scientific debates on climate change and collective violence.

Heritability and Longitudinal Stability of Planning and Behavioral Disinhibition Based on the Porteus Maze Test.

The Porteus Maze Test (PMT) provides measures of planning and behavioral disinhibition. The PMT was administered to 941 twins during Wave 1 (9-10 years) and 320 twins during Wave 2 (11-13 years). Participants were drawn from the University of Southern California Risk Factors for Antisocial Behavior Study (RFAB). Heritability of behavioral disinhibition, determined by PMT Q-Score, were 33% at Wave 1 and 52% at Wave 2. For planning, determined by Test Age, heritability was 53% at Wave 1; at Wave 2, the non-shared environment was important in boys, whereas genetic influences were important in girls. Both indices were modestly stable (r = 0.52; r = 0.37). A common genetic factor influenced both indices, respectively, at the two time points, with no 'new' genetic variance at Wave 2; the non-shared environment was time-specific. Thus, both genetic and non-shared environmental influences are important for behavioral disinhibition (Q-Score) and planning (Test Age).

Neural correlates of proactive and reactive aggression in adolescent twins.

Verbal and physical aggression begin early in life and steadily decline thereafter in normal development. As a result, elevated aggressive behavior in adolescence may signal atypical development and greater vulnerability for negative mental and health outcomes. Converging evidence suggests that brain disturbances in regions involved in impulse control, emotional regulation, and sensation seeking may contribute to heightened aggression. However, little is known regarding the neural mechanisms underlying subtypes of aggression (i.e., proactive and reactive aggression) and whether they differ between males and females. Using a sample of 106 14-year-old adolescent twins, this study found that striatal enlargement was associated with both proactive and reactive aggression. We also found that volumetric alterations in several frontal regions including smaller middle frontal and larger orbitofrontal cortex were correlated with higher levels of aggression in adolescent twins. In addition, cortical thickness analysis showed that thickness alterations in many overlapping regions including middle frontal, superior frontal, and anterior cingulate cortex and temporal regions were associated with aggression in adolescent twins. Results support the involvement of fronto-limbic-striatal circuit in the etiology of aggression during adolescence. Aggr. Behav. 43:230-240, 2017. © 2016 Wiley Periodicals, Inc.

Psychopathic personality development from ages 9 to 18: Genes and environment.

The genetic and environmental etiology of individual differences was examined in initial level and change in psychopathic personality from ages 9 to 18 years. A piecewise growth curve model, in which the first change score (G1) influenced all ages (9-10, 11-13, 14-15, and 16-18 years) and the second change score (G2) only influenced ages 14-15 and 16-18 years, fit the data better did than the standard single slope model, suggesting a turning point from childhood to adolescence. The results indicated that variations in levels and both change scores were mainly due to genetic (A) and nonshared environmental (E) influences (i.e., AE structure for G0, G1, and G2). No sex differences were found except on the mean values of level and change scores. Based on caregiver ratings, about 81% of variance in G0, 89% of variance in G1, and 94% of variance in G2 were explained by genetic factors, whereas for youth self-reports, these three proportions were 94%, 71%, and 66%, respectively. The larger contribution of genetic variance and covariance in caregiver ratings than in youth self-reports may suggest that caregivers considered the changes in their children to be more similar as compared to how the children viewed themselves.

Genetic covariance between psychopathic traits and anticipatory skin conductance responses to threat: Evidence for a potential endophenotype.

The genetic architecture of the association between psychopathic traits and reduced skin conductance responses (SCRs) is poorly understood. By using 752 twins aged 9-10 years, this study investigated the heritability of two SCR measures (anticipatory SCRs to impending aversive stimuli and unconditioned SCRs to the aversive stimuli themselves) in a countdown task. The study also investigated the genetic and environmental sources of the covariance between these SCR measures and two psychopathic personality traits: impulsive/disinhibited (reflecting impulsive-antisocial tendencies) and manipulative/deceitful (reflecting the affective-interpersonal features). For anticipatory SCRs, 27%, 14%, and 59% of the variation was due to genetic, shared environmental, and nonshared environmental effects, respectively, while the percentages for unconditioned SCRs were 44%, 2%, and 54%. The manipulative/deceitful (not impulsive/disinhibited) traits were negatively associated with both anticipatory SCRs (r = -.14, p < .05) and unconditioned SCRs (r = -.17, p < .05) in males only, with the former association significantly accounted for by genetic influences (r g = -.72). Reduced anticipatory SCRs represent a candidate endophenotype for the affective-interpersonal facets of psychopathic traits in males.

The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer.

BACKGROUND: Acquired resistance to Tamoxifen remains a critical problem in breast cancer patient treatment, yet the underlying causes of resistance have not been fully elucidated. Abberations in the Wnt signalling pathway have been linked to many human cancers, including breast cancer, and appear to be associated with more metastatic and aggressive types of cancer. Here, our aim was to investigate if this key pathway was involved in acquired Tamoxifen resistance, and could be targeted therapeutically. METHODS: An in vitro model of acquired Tamoxifen resistance (named TamR) was generated by growing the estrogen receptor alpha (ER) positive MCF7 breast cancer cell line in increasing concentrations of Tamoxifen (up to 5 uM). Alterations in the Wnt signalling pathway and epithelial to mesenchymal transition (EMT) in response to Tamoxifen and treatment with the Wnt inhibitor, IWP-2 were measured via quantitative RT-PCR (qPCR) and TOP/FOP Wnt reporter assays. Resistance to Tamoxifen, and effects of IWP-2 treatment were determined by MTT proliferation assays. RESULTS: TamR cells exhibited increased Wnt signalling as measured via the TOP/FOP Wnt luciferase reporter assays. Genes associated with both the ß-catenin dependent (AXIN2, MYC, CSNK1A1) and independent arms (ROR2, JUN), as well as general Wnt secretion (PORCN) of the Wnt signalling pathway were upregulated in the TamR cells compared to the parental MCF7 cell line. Treatment of the TamR cell line with human recombinant Wnt3a (rWnt3a) further increased the resistance of both MCF7 and TamR cells to the anti-proliferative effects of Tamoxifen treatment. TamR cells demonstrated increased expression of EMT markers (VIM, TWIST1, SNAI2) and decreased CDH1, which may contribute to their resistance to Tamoxifen. Treatment with the Wnt inhibitor, IWP-2 inhibited cell proliferation and markers of EMT. CONCLUSIONS: These data support the role of the Wnt signalling pathway in acquired resistance to Tamoxifen. Further research into the mechanism by which activated Wnt signalling inhibits the effects of Tamoxifen should be undertaken. As a number of small molecules targeting the Wnt pathway are currently in pre-clinical development, combinatorial treatment with endocrine agents and Wnt pathway inhibitors may be a useful therapeutic option in the future for a subset of breast cancer patients.

Medical record validation of maternal recall of pregnancy and birth events from a twin cohort.

This study aims to assess the validity of maternal recall for several perinatal variables 8-10 years after pregnancy in a twin sample. Retrospective information was collected 8-10 years after the delivery event in a cohort of mothers from the University of Southern California Twin Study (N = 611) and compared with medical records for validity analysis. Recall of most variables showed substantial to perfect agreement (κ = 0.60-1.00), with notable exceptions for specific medical problems during pregnancy (κ ≤ 0.40) and substance use when mothers provided continuous data (e.g., number of cigarettes per day; r ≤ 0.24). With the exception of delivery method, neonatal intensive care unit admission, birth weight, neonatal information, and post-delivery complications were also recalled with low accuracy. For mothers of twins, maternal recall is generally a valid measure for perinatal variables 10 years after pregnancy. However, caution should be taken regarding variables such as substance use, medical problems, birth length, and post-delivery complications.

The Southern California Twin Register at the University of Southern California: III.

The Southern California Twin Register at the University of Southern California (USC) was initiated in 1984 and continues to provide an important resource for studies investigating genetic and environmental influences on human behavior. This article provides an update on the current register and its potential for future twin studies using recruitment through school district databases and voter records. An overview is also provided for an ongoing longitudinal twin study investigating the development of externalizing psychopathology from childhood to young adulthood, the USC Study of Risk Factors for Antisocial Behavior. Characteristics of the twins and their families are presented, including recruitment and participation rates, as well as attrition analyses and a summary of key findings to date.

The genetic and environmental etiology of decision-making: a longitudinal twin study.

The present study examined the genetic and environmental etiology of decision-making (Iowa Gambling Task; Bechara, Damásio, Damásio, & Anderson, 1994), in a sample of twins at ages 11-13, 14-15, and 16-18 years. The variance across five 20-trial blocks could be explained by a latent "decision-making'' factor within each of the three times of IGT administration. This latent factor was modestly influenced by genetic factors, explaining 35%, 20% and 46% of the variance within each of the three times of IGT administration. The remaining variance was explained by the non-shared environment (65%, 80% and 54%, respectively). Block-specific non-shared environmental influences were also observed. The stability of decision-making was modest across development. Youth showed a trend to choose less risky decks at later ages, suggesting some improvement in task performance across development. These findings contribute to our understanding of decision-making by highlighting the particular importance of each person's unique experiences on individual differences.

Psychopathic Personality and Negative Parent-to-Child Affect: A Longitudinal Cross-lag Twin Study.

PURPOSE: Previous studies that have explored the relationship between parenting style and children's antisocial behavior have generally found significant bidirectional effects, whereby parenting behaviors influence their child's antisocial outcomes, but a child's behaviors also lead to changes in parenting style. METHODS: The present study investigated the genetic and environmental underpinnings of the longitudinal relationship between negative parent-to-child affect and psychopathic personality in a sample of 1,562 twins. Using a biometrical cross-lag analysis, bidirectional effects were investigated across two waves of assessment when the twins were ages 9-10 and 14-15, utilizing both caregiver and youth self-reports. RESULTS: Results demonstrated that negative parental affects observed at ages 9-10 influenced the child's later psychopathic personality at ages 14-15, based on both caregiver and youth self-reports. For these 'parent-driven effects', both genetic and non-shared environmental factors were important in the development of later psychopathic personality during adolescence. There were additional 'child-driven effects' such that children's psychopathic personality at ages 9-10 influenced negative parent-to-child affect at ages 14-15, but only within caregiver reports. CONCLUSIONS: Thus, children's genetically influenced psychopathic personality seemed to evoke parental negativity at ages 14-15, highlighting the importance of investigating bidirectional effects in parent-child relationships to understand the development of these traits.

Aggression and Rule-breaking: Heritability and stability of antisocial behavior problems in childhood and adolescence.

PURPOSE: This twin study examined the structure of genetic and environmental influences on aggression and rule-breaking in order to examine change and stability across the span of childhood to mid-adolescence. METHODS: Behavioral assessments were conducted at two time points: age 9-10 years and 14-15 years. Using behavioral genetics biometric modeling, the longitudinal structure of influences was investigated. RESULTS: Aggression and rule-breaking were found to be influenced by a latent common factor of antisocial behavior (ASB) within each wave of data collection. The childhood-age common factor of ASB was influenced by 41% genetics, 40% shared environment and 19% nonshared environment. In adolescence, 41% of influences on the common factor were novel and entirely genetic, while the remainder of influences were stable across time. Additionally, both aggression and rule-breaking within each wave were found to have unique influences not common across subscales or across waves, highlighting specificity of influences on different problem behaviors at both ages. CONCLUSIONS: This research sheds light on the commonality of influences on etiology of different forms of antisocial behavior, and suggests future directions for research into intervention for antisocial behavior problems in youth, such as investigation of adolescence-specific environmental influences on the development of antisocial behavior problems.