Hicks, B.M., Bernat,E.M., Malone, S.M., Iacono, W.G., Patrick, C.J., Krueger, R.F. & McGue, M. (2007) Genes Mediate the Association between P3 Amplitude and Externalizing Disorders. Psychophysiology, 44, 98-105.
Reduced P3 amplitude has been consistently linked to a spectrum of externalizing disorders. Utilizing data from a large sample of adolescent male twins (N51196), we used biometric modeling to assess the genetic and environmental contributions to the association between reduced P3 amplitude and a general vulnerability to externalizing disorders. Externalizing vulnerability was indexed by a composite of symptoms of conduct disorder, adult antisocial behavior, and alcohol, nicotine, and drug dependence. The sample included two independent age cohorts, providing an internal replication of the findings. For the best-fitting model, genetic influences alone accounted for the association between P3 amplitude and externalizing disorders, with an estimated genetic correlation of rg5 _.22. Results replicated across the two age cohorts and demonstrate that reduced P3 amplitude is a marker of the biological vulnerability to externalizing disorders.
Patrick, C.J., Bernat, E.M, Malone, S.M., Iacono, W.G., Krueger, R.F. & McGue, M. (2006). P300 Amlitude as an Indicator of Externalizing in Adolescent Males. Psychophysiology, 43, 84-92.
Reduced P300 amplitude is reliably found in individuals with a personal or family history of alcohol problems. However, alcoholism is part of a broader externalizing spectrum that includes other substance use and antisocial disorders. We hypothesized that reduced P300 is an indicator of the common factor that underlies disorders within this spectrum. Community males (N5969) were assessed at age 17 in a visual oddball task. Externalizing was defined as the common factor underlying symptoms of alcohol dependence, drug dependence, nicotine dependence, conduct disorder, and adult antisocial behavior. A robust association was found between reduced P300 amplitude and the externalizing factor, and this relation accounted for links between specific externalizing disorders and P300. Our findings indicate that reduced P300 amplitude is an indicator of the broad neurobiological vulnerability that underlies disorders within the externalizing spectrum.
Blonigen, D.M., Hicks, B.M., Krueger, R.F., Patrick, C.J. & Iacono, W.G. (2005). Psychopathic Personality Traits: Heritability and Genetic Overlap with Internalizing and Externalizing Psychopathology. Psychological Medicine, 35, 637-648.
Background. Little research has examined genetic and environmental contributions to psychopathic personality traits. Additionally, no studies have examined etiological connections between psychopathic traits and the broad psychopathological domains of internalizing (mood and anxiety) and externalizing (antisocial behavior, substance abuse). The current study was designed to fill these gaps in the literature.
Method. Participants were 626 pairs of 17-year-old male and female twins from the community. Psychopathic traits were indexed using scores on the Multidimensional Personality Questionnaire (MPQ). Symptoms of internalizing and externalizing psychopathology were obtained via structured clinical interviews. Structural equation modeling was used to estimate genetic and environmental influences on psychopathic personality traits as well as the degree of genetic overlap between these traits and composites of internalizing and externalizing.
Results. Twin analyses revealed signi.cant genetic in.uence on distinct psychopathic traits (Fearless Dominance and Impulsive Antisociality). Moreover, Fearless Dominance was associated with reduced genetic risk for internalizing psychopathology, and Impulsive Antisociality was associated with increased genetic risk for externalizing psychopathology.
Conclusions. These results indicate that di.erent psychopathic traits as measured by the MPQ show distinct genetically based relations with broad dimensions of DSM psychopathology.
Burt, S.A., McGue, M., Krueger, R.F. & Iacono, W.G. (2005). How are parent-child conflict and childhood externalizing symptoms related over time? Results from a genetically informative cross-lagged study. Development and Psychopatholgy, 17, 145-165.
The present study attempted to determine the direction and etiology of the robust relationship between childhood externalizing (EXT) symptoms and parent–child conflict using a genetically informative longitudinal model and data from the ongoing Minnesota Twin Family Study. Participants consisted of 1,506 same-sex twins assessed at ages 11 and 14, and their parents. The relationship between EXT and parent–child conflict from ages 11 to 14 was examined within a biometrical cross-lagged design. The results revealed three primary findings: first, the stability of conflict and externalizing over time is largely, although not solely, a result of genetic factors. Second, there appears to be a bidirectional relationship between conflict and EXT over time, such that both conflict and EXT at 11 independently predict the other 3 years later. Finally, the results are consistent with the notion that parent–child conflict partially results from parental responses to their child’s heritable externalizing behavior, while simultaneously contributing to child externalizing via environmental mechanisms. These results suggest a “downward spiral” of interplay between parent–child conflict and EXT, and offer confirmation of a (partially) environmentally mediated effect of parenting on child behavior.
Burt, S.A., McGue, M., Krueger, R.F. & Iacono, W.G. (2005). Sources of covariation among the child-externalizing disorders: informant effects and the shared environment. Psychological Medicine, 35, 1133-1144.
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.
Hicks, B.M., Krueger, R.F., Iacono, W.G., McGue, M, & Patrick, C.J. (2004). Family transmission and heritability of externalizing disorders: A twin-family study. Archives of General Psychiatry, 61, 922-928.
Background: Antisocial behavior and substance dependence disorders exact a heavy financial and human cost on society. A better understanding of the mechanisms of familial transmission for these “externalizing” disorders is necessary to better understand their etiology and to help develop intervention strategies.
Objectives: To determine the extent to which the family transmission of externalizing disorders is due to a general vs a disorder-specific vulnerability and, owing to the genetically informative nature of our data, to estimate the heritable vs environmental nature of these transmission effects.
Design: We used structural equation modeling to simultaneously estimate the general and specific transmission effects of 4 externalizing disorders: conduct disorder, adult antisocial behavior, alcohol dependence, and drug dependence.
Setting: Participants were recruited from the community and were interviewed in a university laboratory.
Participants: The sample consisted of 542 families participating in the Minnesota Twin Family Study. All families included 17-year-old twins and their biological mother and father.
Main Outcome Measures: Symptom counts of conduct disorder, the adult criteria for antisocial personality disorder, alcohol dependence, and drug dependence.
Results: Transmission of a general vulnerability to all the externalizing disorders accounted for most familial resemblance. This general vulnerability was highly heritable (h2=0.80). Disorder-specific vulnerabilities were also detected for conduct disorder, alcohol dependence, and drug dependence.
Conclusions: The mechanism underlying the familial transmission of externalizing disorders is primarily a highly heritable general vulnerability. This general vulnerability or common risk factor should be the focus of research regarding the etiology and treatment of externalizing disorders.
Arch Gen Psychiatry. 2004;61:922-928
King, S.M., Iacono, W.G. & McGue, M. (2004). Childhood Externalizing and Internalizing Psychopathology in Prediction of Early Substance Use. Addiction, 99, 1548-1559.
Aims: To examine the prospective relationships between childhood externalizing and internalizing disorders and substance use in early adolescence.
Design: Longitudinal, community-based study of twins (aged 11 at intake; aged 14 at follow-up).
Setting and participants: The sample was composed of twins participating in the Minnesota Twin Family Study, an epidemiological sample of twins and their families representative of the state population of Minnesota. A total of 699 twin girls and 665 twin boys participated at both time-points.
Measurements: Twins participated in in-person, life-time diagnostic assessments of the following childhood DSM III-R externalizing and internalizing disorders at age 11: conduct disorder, oppositional defiant disorder, attention deficit hyperactivity disorder, major depressive disorder and in addition, for girls only, overanxious disorder and separation anxiety disorder. At ages 11 and 14, substance use and abuse were assessed.
Findings: Externalizing psychopathology predicted having tried alcohol, nicotine and cannabis by age 14 as well as regular and advanced experience with these substances. Internalizing disorders showed weak effects, with only major depression at age 11 showing a significant relationship with substance use at age 14.
Conclusion: The results suggest that externalizing psychopathology is a robust prospective predictor of a variety of early onset substance use behaviors and is systematically related to degree of substance use involvement. The results also suggest that depression may predict initiation of licit substance use in early adolescence.
Iacono, W.G., Malone, S & McGue, M. (2003). Substance Use Disorders, Externalizing Psychopathologies, and P300 Event Related Potential Amplitude. International Journal of Psychophysiology, 48, 147-178.
We hypothesize the existence of an inherited predisposition for a spectrum of behaviors and traits characterized by behavioral disinhibition. This externalizing spectrum includes childhood disruptive disorders, antisocial behavior, substance use disorders, personality traits related to behavioral under control, and the precocious expression of problem behavior. We further hypothesize that a genetically influenced central nervous system diathesis underlies this spectrum and is reflected in reduced P300 amplitude in a visual oddball event-related potential task. A review of evidence bearing on the model is derived from findings from the Minnesota Twin Family Study, a population-based, longitudinal investigation of twin youth. These findings indicate that the collection of attributes related to behavioral disinhibition is familial, heritable, and interrelated. Evidence supporting P3 amplitude reduction (P3-AR) as an index of genetic vulnerability for this externalizing spectrum includes its association with (a) familial risk for substance use and antisocial personality disorders, (b) diagnoses of childhood disruptive disorders and substance use disorders, (c) early onset of undersocialized behavior, and (d) quantitative phenotypes related to externalizing problems. In addition, the development of substance use disorders over a 3-year period is associated with P3-AR measured prior to their expression. These findings suggest that P3-AR indexes one aspect of the genetic diathesis for a spectrum of externalizing problem behavior.
©2003 Elsevier Science B.V. All rights reserved.
Malone, S.M., Iacono, W.G., McGue, M. (2002). Drinks of the father: Father’s maximum number of drinks consumed predicts externalizing disorders, substance use, and substance use disorders in preadolescent and adolescent offspring. Alcoholism: Clinical & Experimental Research, 26, 1823-1832.
Background: The maximum number of drinks consumed in 24 hr seems to be an interesting phenotype related to alcoholism. The goal of the present study was to determine in an epidemiologic sample whether this measure of drinking history in fathers predicted externalizing behavioral disorders, substance use, and substance abuse in preadolescent and adolescent offspring and whether any such associations would be independent of paternal alcohol dependence diagnoses.
Methods: Subjects were male and female twins from both age cohorts of the Minnesota Twin Family Study, a population-based longitudinal study, and were approximately 11 or 17 years of age, respectively, upon study enrollment. In both age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder served as outcome measures. In addition, measures of lifetime substance use and of the presence of symptoms of substance abuse were derived for the 11-year-old cohort when subjects were approximately 14 years old and diagnoses of substance abuse were derived for the older cohort at age 17. An extension of logistic regression using generalized estimating equations served to assess whether paternal maximum alcohol consumption predicted filial outcome measures.
Results: Paternal maximum alcohol consumption was consistently associated with conduct disorder, substance use, and substance abuse or dependence in male and female offspring. These associations were not mediated by a primary effect of paternal alcoholism.
Conclusions: Paternal maximum alcohol consumption was uniquely associated with those offspring characteristics most reliably found in adolescent children of alcoholic parents. This phenotype might supplement DSM diagnoses of alcohol dependence to reduce the number of false positives in genetic research.