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Background: Adolescent antisocial behavior (AB) is a public health concern due to the high financial and social costs of AB on victims and perpetrators. Neural systems involved in reward and loss processing are thought to contribute to AB. However, investigations into these processes are limited: few have considered anticipatory and consummatory components of reward, response to loss, nor whether associations with AB may vary by level of callous-unemotional (CU) traits., Methods: A population-based community sample of 128 predominantly low-income youth (mean age = 15.9 years; 42% male) completed a monetary incentive delay task during fMRI. A multi-informant, multi-method latent variable approach was used to test associations between AB and neural response to reward and loss anticipation and outcome and whether CU traits moderated these associations., Results: AB was not associated with neural response to reward but was associated with reduced frontoparietal activity during loss outcomes. This association was moderated by CU traits such that individuals with higher levels of AB and CU traits had the largest reductions in frontoparietal activity. Co-occurring AB and CU traits were also associated with increased precuneus response during loss anticipation., Conclusions: Findings indicate that AB is associated with reduced activity in brain regions involved in cognitive control, attention, and behavior modification during negative outcomes. Moreover, these reductions are most pronounced in youth with co-occurring CU traits. These findings have implications for understanding why adolescents involved in AB continue these behaviors despite severe negative consequences (e.g. incarceration).

Background: Young people with 22q11.2 deletion syndrome (22q11.2DS) are at high risk for neurodevelopmental disorders. Sleep problems may play a role in this risk but their prevalence, nature and links to psychopathology and cognitive function remain undescribed in this population., Method: Sleep problems, psychopathology, developmental coordination and cognitive function were assessed in 140 young people with 22q11.2DS (mean age = 10.1, s.d. = 2.46) and 65 unaffected sibling controls (mean age = 10.8, s.d.SD = 2.26). Primary carers completed questionnaires screening for the children's developmental coordination and autism spectrum disorder., Results: Sleep problems were identified in 60% of young people with 22q11.2DS compared to 23% of sibling controls (OR 5.00, p < 0.001). Two patterns best-described sleep problems in 22q11.2DS: restless sleep and insomnia. Restless sleep was linked to increased ADHD symptoms (OR 1.16, p < 0.001) and impaired executive function (OR 0.975, p = 0.013). Both patterns were associated with elevated symptoms of anxiety disorder (restless sleep: OR 1.10, p = 0.006 and insomnia: OR 1.07, p = 0.045) and developmental coordination disorder (OR 0.968, p = 0.0023, and OR 0.955, p = 0.009). The insomnia pattern was also linked to elevated conduct disorder symptoms (OR 1.53, p = 0.020)., Conclusions: Clinicians and carers should be aware that sleep problems are common in 22q11.2DS and index psychiatric risk, cognitive deficits and motor coordination problems. Future studies should explore the physiology of sleep and the links with the neurodevelopment in these young people.

Background: We introduce and apply an elegant, contrastive genetic-epidemiological design - Maternal Half-Sibling Families with Discordant Fathers - to clarify cross-generational transmission of genetic risk to alcohol use disorder (AUD), drug abuse (DA) and major depression (MD)., Method: Using Swedish national registries, we identified 73 108 eligible pairs of reared together maternal half-siblings and selected those whose biological fathers were discordant for AUD, DA and MD, and had minimal contact with the affected father. We examined differences in outcome in half-siblings with an affected v. unaffected father., Results: For AUD, DA and MD, the HR (95% confidence intervals) for the offspring of affected v. unaffected fathers were, respectively, 1.72 (1.61; 1.84), 1.55 (1.41; 1.70) and 1.51 (1.40; 1.64). Paternal DA and AUD, but not MD, predicted risk in offspring for attention deficit hyperactivity disorder, conduct disorder, and poor educational performance and attainment. Offspring of affected v. unaffected fathers had poorer pregnancy outcomes, with the effect strongest for DA and weakest for MD. A range of potential biases and confounders were examined and were not found to alter these findings substantially., Conclusion: Reared together maternal half-siblings differ in their paternal genetic endowment, sharing the same mother, family, school and community. They can help clarify the nature of paternal genetic effects and produce results consistent with other designs. Paternal genetic risk for DA and AUD have effects on offspring educational achievement, child and adult psychopathology, and possibly prenatal development. The impact of paternal genetic risk for MD is narrower in scope.

Background: Anabolic-androgenic steroid (AAS) use is known to be associated with other psychiatric disorders, such as body image disorders, conduct disorder/sociopathy, and other substance use disorders (SUD) - but the causal pathways among these conditions remain poorly delineated., Methods: We created a directed acyclic graph to diagram hypothesized relationships among AAS use and dependence, body image disorder (BID), conduct disorder/sociopathy, and other SUD. Using proportional hazards models, we then assessed potentially causal relationships among these variables, using a dataset of 233 male weightlifters, of whom 102 had used AAS., Results: BID and conduct disorder/sociopathy both strongly contributed to the development of AAS use, but did not appear to contribute further to the progression from AAS use to AAS dependence. Other SUD beginning prior to first AAS use - whether broadly defined or restricted only to opioids - failed to show an effect on AAS use or progression to AAS dependence. Conversely, AAS use contributed significantly to the subsequent first-time development of opioid use disorders but did not significantly increase the risk for first-time development of non-opioid SUD, taken as a whole., Conclusions: Our analysis suggests that AAS use and other SUD are mutually attributable to underlying conduct disorder/sociopathy. SUD do not appear to represent a 'gateway' to subsequent AAS use. AAS use may represent a gateway to subsequent opioid use disorder, but probably not to other SUD.

Background: Low resting heart rate (RHR) is a consistent biological correlate of antisocial behaviour (ASB), however potential mechanisms have been largely unexplored. We hypothesise that lower RHR will be associated with higher ASB levels in mid-adolescence and persistence into adulthood, and that these associations will be explained, in part, by sensation seeking and callous-unemotional traits., Methods: ASB was assessed repeatedly with young people from ages 15 to 21 years in a population-based birth cohort (ALSPAC). A longitudinal trajectory was derived and showed ASB decreasing across adolescence before stabilising in early adulthood. RHR was recorded at age 12 years, and mediators were assessed at age 14 years., Results: After adjusting for socio-demographic confounders, there was evidence for a total effect of RHR on ASB levels in mid-adolescence [b(95% CI) = -0.08 (-0.14 to -0.02)], reflecting 0.08 more types of antisocial activity in the last year per 10 fewer heart beats per minute. This effect was almost entirely explained through sensation seeking [b(95% CI) = -0.06 (-0.08 to -0.04)]. After additionally adjusting for child and parent-related confounders, all effects weakened; however, there was still evidence of an indirect effect of RHR, via sensation seeking, on ASB levels in mid-adolescence [b(95% CI) = -0.01 (-0.03 to -0.003)]. There was no evidence for a total effect of RHR on ASB levels in early adulthood, and weak evidence of an indirect effect, via sensation seeking [b(95% CI) = -0.01 (-0.01 to -0.00)]., Conclusions: Lower RHR in childhood was associated with higher ASB levels in mid-adolescence, indirectly via sensation seeking.

Background: Many preschool-age children meet criteria for psychiatric disorders, and rates approach those observed in later childhood and adolescence. However, there is a paucity of longitudinal research examining the outcomes of preschool diagnoses., Methods: Families with a 3-year-old child (N = 559) were recruited from the community. Primary caregivers were interviewed using the Preschool Age Psychiatric Assessment when children were 3 years old (n = 541), and, along with children, using the Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime Version when children were 9 and 12 years old., Results: Rates of disruptive behavior disorders (DBD) decreased from preschool to middle childhood and early adolescence, whereas rates of attention-deficit/hyperactivity disorder (ADHD) increased. Rates of any psychiatric disorder and depression increased from preschool to early adolescence only. Preschoolers with a diagnosis were over twice as likely to have a diagnosis during later periods. Homotypic continuity was present for anxiety disorders from preschool to middle childhood, for ADHD from preschool to early adolescence, and for DBD through both later time points. There was heterotypic continuity between preschool anxiety and early adolescent depression, and between preschool ADHD and early adolescent DBD. Dimensional symptom scores showed homotypic continuity for all diagnostic categories and showed a number of heterotypic associations as well., Conclusions: Results provide moderate support for the predictive validity of psychiatric disorders in preschoolers. Psychopathology in preschool is a significant risk factor for future psychiatric disorders during middle childhood and early adolescence.

Background: To our knowledge, there are no universal screening tools for substance dependence that (1) were developed using a population-based sample, (2) estimate total risk briefly and inexpensively by incorporating a relatively small number of well-established risk factors, and (3) aggregate risk factors using a simple algorithm. We created a universal screening tool that incorporates these features to identify adolescents at risk for persistent substance dependence in adulthood., Method: Participants were members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972-1973 and followed prospectively to age 38 years, with 95% retention. We assessed a small set of childhood and adolescent risk factors: family history of substance dependence, childhood psychopathology (conduct disorder, depression), early exposure to substances, frequent substance use in adolescence, sex, and childhood socioeconomic status. We defined the outcome (persistent substance dependence in adulthood) as dependence on one or more of alcohol, tobacco, cannabis, or hard drugs at ⩾3 assessment ages: 21, 26, 32, and 38 years., Results: A cumulative risk index, a simple sum of nine childhood and adolescent risk factors, predicted persistent substance dependence in adulthood with considerable accuracy (AUC = 0.80)., Conclusions: A cumulative risk score can accurately predict which adolescents in the general population will develop persistent substance dependence in adulthood.

Background: Co-morbid disorders of conduct and emotions can be regarded as childhood antecedents of further negative developments (e.g. manifestation of personality disorders in adulthood). We evaluated a manualized psychodynamic therapy (PDT) for adolescents with these co-morbid disorders., Method: In a randomized controlled trial (RCT), 66 adolescents diagnosed with mixed disorders of conduct and emotions (F92 in ICD-10) were randomly assigned to a manualized in-patient PDT group or a waiting list/treatment-as-usual (WL/TAU) control condition. Diagnoses according to DSM-IV were also documented. Patients were compared using rates of remission as the primary outcome. The Global Severity Index (GSI) and the Strengths and Difficulties Questionnaire (SDQ) were used as secondary measures. Assessments were performed at baseline, post-treatment and at the 6-month follow-up., Results: The sample consisted of severely impaired adolescents with high rates of further co-morbid disorders and academic failure. Patients in the treatment group had a significantly higher rate of remission [odds ratio (OR) 26.41, 95% confidence interval (CI) 6.42-108.55, p < 0.001]. Compared with the control group, the PDT group resulted in significantly better outcomes on the SDQ (p = 0.04) but not the GSI (p = 0.18), with small between-group effect sizes (SDQ: d = 0.38, GSI: d = 0.18). However, the scores of patients treated with PDT were post-treatment no longer significantly different from normative data on the GSI and within the normal range on the SDQ. The effects in the treatment group were stable at follow-up. Furthermore, most patients were reintegrated into educational processes., Conclusion: PDT led to remarkable improvement and furthered necessary preconditions for long-term stabilization. In future, PDT should be compared to other strong active treatments.

Background: Severe youth antisocial behaviour has been associated with increased risk of premature mortality in high-risk samples for many years, and some evidence now points to similar effects in representative samples. We set out to assess the prospective association between adolescent conduct problems and premature mortality in a population-based sample of men and women followed to the age of 65 years., Method: A total of 4158 members of the Medical Research Council National Survey of Health and Development (the British 1946 birth cohort) were assessed for conduct problems at the ages of 13 and 15 years. Follow-up to the age of 65 years via the UK National Health Service Central Register provided data on date and cause of death., Results: Dimensional measures of teacher-rated adolescent conduct problems were associated with increased hazards of death from cardiovascular disease by the age of 65 years in men [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.32], and of all-cause and cancer mortality by the age of 65 years in women (all-cause HR 1.16, 95% CI 1.07-1.25). Adjustment for childhood cognition and family social class did little to attenuate these risks. Adolescent conduct problems were not associated with increased risks of unnatural/substance-related deaths in men or women in this representative sample., Conclusions: Whereas previous studies of high-risk delinquent or offender samples have highlighted increased risks of unnatural and alcohol- or substance abuse-related deaths in early adulthood, we found marked differences in mortality risk from other causes emerging later in the life course among women as well as men.

Background: Maternal experience of childhood maltreatment and maternal antenatal depression are both associated with offspring childhood maltreatment and offspring adjustment problems. We have investigated the relative impact of maternal childhood maltreatment and exposure to depression in utero on offspring maltreatment and psychopathology., Method: The sample included 125 families from the South London Child Development Study. A prospective longitudinal design was used. Data on maternal childhood maltreatment, maternal antenatal depression (36 weeks of pregnancy), offspring childhood maltreatment (age 11 years) and offspring adolescent antisocial behaviour and depression (ages 11 and 16 years) were obtained from parents and offspring through clinical interview., Results: Mothers who experienced childhood maltreatment were significantly more likely to be depressed during pregnancy [odds ratio (OR) 10.00]. Offspring of mothers who experienced only childhood maltreatment or only antenatal depression were no more at risk of being maltreated or having psychopathology; however, offspring of mothers who experienced both maternal childhood maltreatment and antenatal depression were exposed to significantly greater levels of childhood maltreatment and exhibited significantly higher levels of adolescent antisocial behaviour compared with offspring not so exposed. Furthermore, maternal childhood maltreatment accounted for a significant proportion of the variance in offspring childhood maltreatment in only those offspring exposed to depression in utero., Conclusions: Maternal childhood maltreatment and maternal antenatal depression are highly associated. The co-occurrence of both insults significantly increases the risk of offspring adversity. The antenatal period is an optimum period to identify vulnerable women and to provide interventions.

Background: Population data on conduct disorder (CD) symptoms can help determine whether hypothesized subtypes of CD are sufficiently disparate in their familial, psychiatric and life course correlates to distinguish separate diagnostic entities., Method: Latent class analysis (LCA) of CD symptoms occurring before age 15 was conducted in a national sample of adults aged 18-44 years from the National Epidemiological Study of Alcohol and Related Conditions. Associations of latent class membership with parental behavior problems, onset of psychiatric disorders and anti-social behaviors after age 15, adolescent life events (e.g. high school drop-out), and past-year life events (e.g. divorce/separation, bankruptcy) were estimated., Results: LCA identified a no-CD class with low prevalence of all symptoms, three intermediate classes - deceit/theft, rule violations, aggression - and a severe class. The prevalence of CD, according to DSM-IV criteria, was 0% in the no-CD class, between 13.33% and 33.69% in the intermediate classes and 62.20% in the severe class. Latent class membership is associated with all the familial, psychiatric and life course outcomes examined. Among the intermediate classes, risk for subsequent mood/anxiety disorders and anti-social behavior was higher in the deceit/theft and aggressive classes than in the rule violations class. However, risk for adolescent life events is highest in the rule violations class., Conclusions: CD symptoms tend to occur in a partially ordered set of classes in the general population. Prognostically meaningful distinctions can be drawn between classes, but only at low levels of symptoms.

Background: Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations., Method: A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds., Results: In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20-1.93] and conduct disorder (CD; HR 2.27, CI 1.31-3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00-1.94). Logistic regression analysis suggested that the parental depression-offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63-3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95-6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses., Conclusions: The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Background: Although mental disorders have been shown to predict subsequent substance disorders, it is not known whether substance disorders could be cost-effectively prevented by large-scale interventions aimed at prior mental disorders. Although experimental intervention is the only way to resolve this uncertainty, a logically prior question is whether the associations of mental disorders with subsequent substance disorders are strong enough to justify mounting such an intervention. We investigated this question in this study using simulations to estimate the number of substance disorders that might be prevented under several hypothetical intervention scenarios focused on mental disorders., Method: Data came from the National Comorbidity Survey Replication (NCS-R), a nationally representative US household survey that retrospectively assessed lifetime history and age of onset of DSM-IV mental and substance disorders. Survival analysis using retrospective age-of-onset reports was used to estimate associations of mental disorders with subsequent substance dependence. Simulations based on the models estimated effect sizes in several hypothetical intervention scenarios., Results: Although successful intervention aimed at mental disorders might prevent some proportion of substance dependence, the number of cases of mental disorder that would have to be treated to prevent a single case of substance dependence is estimated to be so high that this would not be a cost-effective way to prevent substance dependence (in the range 76-177 for anxiety-mood disorders and 40-47 for externalizing disorders)., Conclusions: Treatment of prior mental disorders would not be a cost-effective way to prevent substance dependence. However, prevention of substance dependence might be considered an important secondary outcome of interventions for early-onset mental disorders.

Background: Previous studies have documented associations between mental and physical health problems in cross-sectional studies, yet little is known about these relationships over time or the specificity of these associations. The aim of the current study was to examine the relationship between mental health problems in childhood at age 8 years and physical disorders in adulthood at ages 18-23 years., Method: Multiple logistic regression analyses were used to examine the relationship between childhood mental health problems, reported by child, parent and teacher, and physical disorders diagnosed by a physician in early adulthood., Results: Significant linkages emerged between childhood mental health problems and obesity, atopic eczema, epilepsy and asthma in early adulthood. Specifically, conduct problems in childhood were associated with a significantly increased likelihood of obesity and atopic eczema; emotional problems were associated with an increased likelihood of epilepsy and asthma; and depression symptoms at age 8 were associated with an increased risk of asthma in early adulthood., Conclusions: Our findings provide the first evidence of an association between mental health problems during childhood and increased risk of specific physical health problems, mainly asthma and obesity, during early adulthood, in a representative sample of males over time. These data suggest that behavioral and emotional problems in childhood may signal vulnerability to chronic physical health problems during early adulthood.

Background: There is increasing evidence that certain environmental factors can modify genetic effects. This is an important area of investigation as such work will help to guide the development of new intervention programs. In this paper, we address whether rural environments moderate the genetic influence on adolescent substance use and rule-breaking behavior (i.e. externalizing psychopathology)., Method: Over 1200 Minnesotan 17-year-old twins were classified as either urban or rural. Externalizing behavior was operationalized as the use and abuse of alcohol and drugs along with symptoms of conduct, oppositional defiant, and antisocial personality disorders. Biometric factor modeling estimated whether the relative contribution of genetic and shared environmental factors varied from urban to rural settings., Results: Residency effects reached statistical significance in the male sample only. In urban environments, externalizing behavior was substantially influenced by genetic factors, but in rural environments, shared environmental factors became more influential. This was apparent at both the individual-variable and factor levels., Conclusions: These findings suggest a gene-environment interaction in the development of male adolescents' problem behaviors, including substance use. The results fit within an expanding literature demonstrating both the contextual nature of the heritability statistic and how certain environments may constrain the expression of genetic tendencies.

Background: A better understanding of the long-term scope and impact of the co-morbidity with oppositional defiant disorder (ODD) and conduct disorder (CD) in attention deficit hyperactivity disorder (ADHD) youth has important clinical and public health implications., Method: Subjects were assessed blindly at baseline (mean age=10.7 years), 1-year (mean age=11.9 years), 4-year (mean age=14.7 years) and 10-year follow-up (mean age=21.7 years). The subjects' lifetime diagnostic status of ADHD, ODD and CD by the 4-year follow-up were used to define four groups (Controls, ADHD, ADHD plus ODD, and ADHD plus ODD and CD). Diagnostic outcomes at the 10-year follow-up were considered positive if full criteria were met any time after the 4-year assessment (interval diagnosis). Outcomes were examined using a Kaplan-Meier survival function (persistence of ODD), logistic regression (for binary outcomes) and negative binomial regression (for count outcomes) controlling for age., Results: ODD persisted in a substantial minority of subjects at the 10-year follow-up. Independent of co-morbid CD, ODD was associated with major depression in the interval between the 4-year and the 10-year follow-up. Although ODD significantly increased the risk for CD and antisocial personality disorder, CD conferred a much larger risk for these outcomes. Furthermore, only CD was associated with significantly increased risk for psychoactive substance use disorders, smoking, and bipolar disorder., Conclusions: These longitudinal findings support and extend previously reported findings from this sample at the 4-year follow-up indicating that ODD and CD follow a divergent course. They also support previous findings that ODD heralds a compromised outcome for ADHD youth grown up independently of the co-morbidity with CD.

Background: Conduct disorder (CD) is a relatively common disorder of childhood and adolescence in the USA with substantial associated morbidity, yet little has been published on CD among Asians and Native Hawaiian/Pacific Islanders (NH/PI) in the USA., Method: We used the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) to examine the prevalence and correlates of retrospectively reported CD within Asians and NH/PI (18 years and older). We also completed logistic regressions to explore factors associated with CD within Asians (n=1093) and, separately, NH/PI (n=139) and to explain racial differences in CD prevalence., Results: Asians were about a third as likely [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.22-0.58] whereas NH/PI were about two and half times more likely (OR 2.6, 95% CI 1.31-5.06) to have had CD compared with Caucasian respondents. Within Asians and NH/PI, CD was strongly associated with adult antisocial behavior, substance use and affective disorders. Demographic factors, the age that subjects came to the USA, measures of family environment and family history could not explain the observed differences in prevalence of CD for NH/PI relative to Caucasians., Conclusions: Asian and NH/PI youth with CD represent a subgroup of Asian youth at very high risk for a number of serious psychiatric disorders. Further investigation is needed to explain the high CD prevalence among NH/PI.

Background: Conduct disorder (CD) prior to age 15 has been associated with an increased risk of aggressive behaviour and crime among men with schizophrenia. The present study aimed to replicate and extend this finding in a clinical sample of severely mentally ill men and women., Method: We examined a cohort of in-patients with severe mental illness in one mental health trust. A total of 205 men and women participated, average age 38.5 years. CD was diagnosed using a structured diagnostic tool. Alcohol and illicit drug use, aggressive behaviour and victimization were self-reported. Information on convictions was extracted from official criminal records. Analyses controlled for age and sex., Results: CD prior to age 15 was associated with an increased risk of assault over the lifespan [odds ratio (OR) 3.98, 95% confidence interval (CI) 1.87-8.44)], aggressive behaviour in the 6 months prior to interview (OR 2.66, 95% CI 1.24-5.68), and convictions for violent crimes (OR 3.19, 95% CI 1.46-6.97) after controlling for alcohol and illicit drug use. The number of CD symptoms present prior to age 15 significantly increased the risk of serious assaults over the lifespan, aggressive behaviour in the past 6 months, and violent crime after controlling for alcohol and illicit drug use., Conclusions: Men and women with severe mental illness who have a history of CD by mid-adolescence are at increased risk for aggressive behaviour and violent crime. These patients are easily identifiable and may benefit from learning-based treatments aimed at reducing antisocial behaviour. Longitudinal, prospective investigations are needed to understand why CD is more common among people with than without schizophrenia.

Background: Conduct disorder (CD) and peer deviance (PD) both powerfully predict future externalizing behaviors. Although levels of CD and PD are strongly correlated, the causal relationship between them has remained controversial and has not been examined by a genetically informative study., Method: Levels of CD and PD were assessed in 746 adult male-male twin pairs at personal interview for ages 8-11, 12-14 and 15-17 years using a life history calendar. Model fitting was performed using the Mx program., Results: The best-fit model indicated an active developmental relationship between CD and PD including forward transmission of both traits over time and strong causal relationships between CD and PD within time periods. The best-fit model indicated that the causal relationship for genetic risk factors was from CD to PD and was constant over time. For common environmental factors, the causal pathways ran from PD to CD and were stronger in earlier than later age periods., Conclusion: A genetically informative model revealed causal pathways difficult to elucidate by other methods. Genes influence risk for CD, which, through social selection, impacts on the deviance of peers. Shared environment, through family and community processes, encourages or discourages adolescent deviant behavior, which, via social influence, alters risk for CD. Social influence is more important than social selection in childhood, but by late adolescence social selection becomes predominant. These findings have implications for prevention efforts for CD and associated externalizing disorders.

Background: Research on the overlap between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) in males has provided useful information on the etiology, correlates, course, and nosology of this co-morbid condition. However, it is unclear how these results extend to females. Our aim was to examine the predictors, clinical characteristics, and functional outcome of CD in a sample of female youth with and without ADHD., Method: We conducted a blind, 5-year prospective longitudinal study of girls with (n=140) and without (n=122) ADHD, aged 6-18 years at baseline. At the 5-year follow-up, 123 (88%) and 112 (92%) of the ADHD and control children respectively were reassessed at a mean age of 16.7 years. Psychiatric disorders were assessed using blind structured diagnostic interviews., Results: Baseline ADHD was a significant risk factor for lifetime CD throughout childhood and adolescence [hazard ratio (HR) 5.8, 95% confidence interval (CI) 2.9-11.5, p<0.001]. Among ADHD girls, childhood-onset (<12 years) CD was predicted by paternal antisocial personality disorder (ASPD), while adolescent-onset CD (12 years) was predicted by family conflict. In addition, lifetime CD significantly predicted academic, psychiatric and sexual behavior problems in girls with ADHD at follow-up., Conclusions: ADHD is a significant risk factor for CD in girls. CD is associated with increased risk for academic, psychiatric and sexual behavior problems compared to ADHD girls without CD. Given that the therapeutic approaches indicated by ADHD and CD differ, these findings highlight the importance of improved efforts aimed at early identification and treatment of CD in girls with ADHD.

Background: Prior research indicates that conduct disorder (CD) is associated with a range of co-morbid mental disorders. However, the actual prevalence, subtypes and patterns of co-morbidity of DSM-IV-defined CD in the general US population remains unknown., Method: Retrospective assessment of CD and other DSM-IV disorders was conducted using fully structured diagnostic interviews among a nationally representative sample of respondents (n=3199) in the National Comorbidity Survey Replication (NCS-R)., Results: The estimated lifetime prevalence of CD in the US is 9.5% (12.0% among males and 7.1% among females), with a median age-of-onset of 11.6 (0.2) years. Latent class analysis (LCA) identified five CD subtypes characterized by rule violations, deceit/theft, aggression, severe covert behaviors, and pervasive CD symptoms. A dose-response relationship was revealed between CD subtype severity and risk of subsequent disorders. Results also indicated that CD typically precedes mood and substance use disorders, but most often occurs after impulse control and anxiety disorders. Although both active and remitted CD is associated with increased risk of the subsequent first onset of other mental disorders, remitted CD is associated with significantly lower risk of subsequent disorders., Conclusions: CD is prevalent and heterogeneous in the US population, and more severe subtypes and the presence of active CD are associated with higher risk of co-morbid disorders. Future prospective studies using general population samples will further inform the nature and course of this disorder.

Background: Research has documented high levels of co-morbidity among childhood externalizing disorders, but its etiology remains in dispute. Specifically, although all behavior genetic studies of the etiology of the co-occurrence of attention deficit-hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) agree that genetic factors are important, differences exist across studies in the relative weight assigned to genetic, shared environmental factors (i.e. factors that increase similarity among family members), and non-shared environmental factors (i.e. factors that decrease similarity among family members). Because heritability estimates can vary across informants, we used a biometric informant-effects model to determine whether these discrepancies were a function of systematic differences in maternal and child informant reports of ADHD, CD, and ODD., Method: We studied 1782 11-year-old twins from the Minnesota Twin Family Study. Symptom counts for each disorder were obtained from interviews administered to twins and their mothers. We fit a model that allowed us to examine, both across and within informants, the genetic and environmental contributions to the co-occurrence among ADHD, CD, and ODD., Results: The results revealed that the co-occurrence among the disorders common to maternal and child informant reports was influenced largely by shared environmental forces. Genetic factors also contributed, though their impact was only marginally significant. In contrast, the co-occurrence unique to each informant was influenced exclusively by either genetic or non-shared environmental factors., Conclusions: Such findings offer additional evidence that shared environmental factors are important to the co-morbidity among ADHD, CD, and ODD, and highlight the necessity of considering informant effects when drawing conclusions about the origins of co-morbidity from analyses of genetically informative data.

Background: In previous studies of subthreshold conditions, co-morbidity has been largely ignored. The purpose was to examine rates of co-morbidity among subthreshold disorders and between subthreshold and full-syndrome disorders for the major non-psychotic classes of disorders from DSM-IV., Method: Participants came from the Oregon Adolescent Depression Project (mean age=16.6 years; females=52.1%). On the basis of a diagnostic interview (K-SADS), participants were assigned to eight subthreshold disorders (MDD, bipolar, eating, anxiety, alcohol use, substance use, conduct, ADHD)., Results: Of the 1704 adolescents in the analyses, 52.5% had at least one subthreshood disorder. Of those, 40.0% had also experienced a co-morbid subthreshold condition, and 29.9% of those had a second co-morbid subthreshold condition. Of those with a subthreshold, 36.4% also had a full syndrome. The subthreshold forms of externalizing disorders were co-morbid with each other. As expected, subthreshold anxiety was co-morbid with subthreshold MDD but subthreshold anxiety was also co-morbid with subthreshold alcohol, conduct, and ADHD. The pattern of co-morbidities was nearly identical for males and females., Conclusions: The hypotheses that externalizing disorders would be co-morbid with other externalizing disorders and that internalizing disorders would be co-morbid with other internalizing disorders was partially supported. Co-morbidities between subthreshold disorders and between subthreshold disorders and full syndrome should impact future research and clinical practice. The assessment of subthreshold disorders needs to include the assessment of other subthreshold and full-syndrome conditions.

Background: Major depressive disorder (MDD) is highly co-morbid with other Axis I disorders, which commonly precede its onset. We sought to determine the level and periods of risk for MDD posed by prior or co-occurring psychiatric disorders., Method: Using retrospective data from a longitudinal, population-based sample of 2926 male and 1929 female adult twin subjects, we predicted the hazard rates for MDD from a Cox proportional hazards model with same-year or prior onsets of co-morbid Axis I disorders as time-dependent covariates., Results: All axis I disorders studied (generalized anxiety disorder, panic disorder, phobia, alcohol dependence, psychoactive substance use disorders and conduct disorder) significantly predicted increased risk for developing MDD. The highest hazard rates occurred for MDD onsets that co-occurred with those of the co-morbid disorder. However, the risk for onset of MDD subsequent to that of prior disorders is also significantly increased and remains relatively unchanged over time. Although the risk for onset of MDD is significantly higher in women than men, this was not explained by gender differences in prior disorder prevalence or increased sensitivity in women to the effects of prior disorders on risk for depression., Conclusions: Prior psychiatric disorders are significant risk factors for the development of MDD, independent of the length of the intervening period between the onset of the first disorder and that of MDD.

Background: The aims of this research were to examine the associations between the personality trait of neuroticism in adolescence and later psychotic symptoms, taking into account potential confounding factors., Method: Data were gathered over the course of a longitudinal study of a birth cohort of New Zealand born young people (N=1265). Over the course of the study, data were gathered on: (a) neuroticism at age 14; (b) psychotic symptoms predominantly subclinical, assessed on the Symptom Checklist (SCL-90), at ages 18 and 21; (c) a range of potential confounding factors including measures of childhood adversity and co-morbid mental disorders., Results: Young people in the highest quartile of neuroticism at age 14 had rates of psychotic symptoms that were two to three times higher than those in the lowest quartile. After statistical adjustment for confounding factors, including childhood adversity and co-morbid mental disorders, the association between neuroticism and later psychotic symptoms reduced but remained statistically significant (P<0.05). After adjustment for confounding, young people with high levels of neuroticism had rates of psychotic symptoms that were between 1.5 to 1.8 times higher than those with low levels of neuroticism., Conclusions: Early neuroticism may be a precursor to the onset of psychotic symptoms. The mechanisms underlying this association are unclear, but may relate to overlapping features between prodromal phases of psychosis and items that measure neuroticism.