[Show abstract][Hide abstract] ABSTRACT: Because the disruptive behavior disorders are highly impairing conditions, it is important to determine if structural variations in brain are associated early in life with these problems among children.
Structural MRI data were acquired from 111 9-11 year olds (58 girls and 53 boys), 43 who met diagnostic criteria for oppositional defiant disorder and/or conduct disorder and 68 healthy controls. Voxel-based morphometry was used to examine associations of behavioral measures with gray matter volumes in whole-brain analyses.
Unlike previous studies, variation in gray matter volume was not found to be associated with a disruptive behavior disorder diagnosis in any brain region at p < .o5 with FWE correction. Nonetheless, an inverse nonlinear association of the number of conduct disorder (CD) symptoms with gray matter volume along the left superior temporal sulcus was significant in the full sample (p < .o5 with FWE correction), with a trend in the right hemisphere (p < 0.001 uncorrected). There also was a trend towards a stronger association of the number of CD symptoms with gray matter volume along the left superior temporal sulcus in girls than boys.
The present findings did not replicate previous findings of reduced gray matter volumes in the anterior insula, amygdala, and frontal cortex in youth with CD, but are consistent with previous findings of reduced gray matter volumes in temporal regions, particularly in girls.
[Show abstract][Hide abstract] ABSTRACT: In this article, we review evidence from recent behavior genetic studies that examined the covariance among common childhood psychopathological conditions and tested specific hypotheses regarding common and broadband-specific underlying features of childhood psychopathology. Specifically, we review the distinction between internalizing and externalizing disorders, the support for the generalist genes and specialist environments model, negative emotionality as a heritable underlying feature common to both internalizing and externalizing disorders, and daring as a heritable broadband-specific underlying feature that distinguishes externalizing disorders from internalizing disorders. We also discuss the implications of research in the search for specific genes that influence childhood psychopathology and suggest avenues for new research.
Child Development Perspectives 12/2014; · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A powerful longitudinal data source, the National Longitudinal Survey of Youth Children data, allows measurement of behavior problems (BP) within a developmental perspective linking them to menarcheal timing (MT). In a preliminary analysis, we evaluate the bivariate relationships between BP measured at different developmental periods and the timing of menarche. Correlations were not consistent with any correlational/causal relationship between BP and MT. In the major part of our study, MT was used to moderate the developmental trajectory of BP, within a genetically-informed design. Girls reaching menarche early had behavior problem variance accounted for by the shared environment; those reaching menarche with average/late timing had behavior problem differences accounted for by genetic variance. Our findings match previous empirical results in important ways, and also extend those results. A theoretical interpretation is offered in relation to a theory linking genetic/shared environmental variance to flexibility and choices available within the family in relation to BP.
[Show abstract][Hide abstract] ABSTRACT: Mental disorders predict future occurrences of both the same disorder (homotypic continuity) and other disorders (heterotypic continuity). Heterotypic continuity is inconsistent with a view of mental disorders as fixed entities. In contrast, hierarchical-dimensional conceptualizations of psychopathology, in which each form of psychopathology is hypothesized to have both unique and broadly shared etiologies and mechanisms, predict both homotypic and heterotypic continuity.
[Show abstract][Hide abstract] ABSTRACT: Background
The best-fitting model of the structure of common psychopathology often includes a general factor on which all dimensions of psychopathology load. Such a general factor would be important if it reflects etiologies and mechanisms shared by all dimensions of psychopathology. Nonetheless, a viable alternative explanation is that the general factor is partly or wholly a result of common method variance or other systematic measurement biases.Methods
To test this alternative explanation, we extracted general, externalizing, and internalizing factor scores using mother-reported symptoms across 5–11 years of age in confirmatory factor analyses of data from a representative longitudinal study of 2,450 girls. Independent associations between the three psychopathology factor scores and teacher-reported criterion variables were estimated in multiple regression, controlling intelligence, and demographic covariates.ResultsThe model including the general factor fit significantly better than a correlated two-factor (internalizing/externalizing) model. The general factor was robustly and independently associated with all measures of teacher-reported school functioning concurrently during childhood and prospectively during adolescence.Conclusions
These findings weaken the hypothesis that the general factor of psychopathology in childhood is solely a measurement artifact and support further research on the substantive meaning of the general factor.
Journal of Child Psychology and Psychiatry 07/2014; · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serotonergic dysfunctions are implicated in conduct disorder, impulsivity, and aggression. Early adverse experiences increase the risk for these behaviors in adolescents. The authors investigated serotonergic activity in one adolescent male who experienced maternal abandonment and childhood abuse and exhibited severely aggressive sexual offenses. Platelet serotonin (5-HT) concentration, [14C]-5HT uptake kinetics, and plasma prolactin, cortisol response to D,L-fenfluramine (D,L-FEN) were measured. Results showed extremely low 5-HT concentration (2.960.7 ng/108 platelets), [14C]-5HT uptake rate (0.560.04 mM/min/107platelets), undetectable Km and Vmax, and abnormally blunted prolactin, cortisol response to D,L-FEN. These abnormalities in this sexually aggressive adolescent may be a consequence of childhood abuse.
The Journal of neuropsychiatry and clinical neurosciences 07/2014; 26(3):262-270. · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Developmental Origin of Health and Disease (DOHaD) hypothesis is a broad theoretical framework that emphasizes how early risk factors causally influence psychopathology. Researchers have raised concerns about the causal interpretation of statistical associations between early risk factors and later psychopathology because most studies have been unable to rule out the possibility of environmental and genetic confounding. In this article, we illustrate how family-based, quasi-experimental designs can test the DOHaD hypothesis by ruling out alternative hypotheses. We review the logic underlying sibling-comparison, cotwin control, offspring of siblings/twins, adoption, and in vitro fertilization designs. We then present results from studies using these designs focused on broad indices of fetal development (low birth weight and gestational age) and a particular teratogen, smoking during pregnancy. The results provide mixed support for the DOHaD hypothesis for psychopathology, illustrating the critical need to use designs that rule out unmeasured confounding.
Child Development Perspectives 07/2014; · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adolescents with attention deficit/hyperactivity disorder (ADHD) are at an increased risk for substance use but the pathways through which this risk emerges are insufficiently understood. Tobacco, alcohol, and marijuana outcomes were compared between adolescents diagnosed with ADHD in early childhood (N = 113) and demographically similar controls (N = 65). Participants were assessed from age 5 until age 18. A comprehensive history of adolescent substance use was compiled for each participant and growth in ADHD and conduct disorder (CD) were modeled as they related to substance use outcomes. Results indicated that when compared with controls, adolescents with ADHD were more likely to try cigarettes, initiate alcohol use at early ages, and smoke marijuana more frequently. Furthermore, adolescents with ADHD were 4 to 5 times more likely than controls to escalate to heavy cigarette and marijuana use after trying these substances once. Adolescents with ADHD who escalated to heavy use patterns were more likely to display early cigarette use and marked problems with family members, but displayed fewer peer problems. There was evidence of baseline effects (latent intercept, measured at age 5) for both ADHD and CD on substance use outcomes. Furthermore, growth in ADHD symptoms accounted for much of the growth in CD symptoms, and consequently, escalating CD symptoms in childhood (latent slope) were viewed as a mediator of the relationship between ADHD and cigarette and marijuana use. Maternal drinking in early childhood was the strongest predictor of early adolescent alcohol use. These findings are discussed with respect to the role of ADHD in the development of adolescent risk outcomes. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Journal of Abnormal Psychology 05/2014; 123(2):362-374. · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Associations among receptive vocabulary measured at 4-9 years, mother-reported childhood conduct problems at 4-9 years, and self-reported adolescent delinquency at 14-17 years were assessed using data from a prospective study of the offspring of a large U.S. nationally representative sample of women. A novel quasi-experimental strategy was used to rule out family-level confounding by estimating path-analytic associations within families in a sibling comparison design. This allowed simultaneous tests of the direct and indirect effects of receptive vocabulary and childhood conduct problems, and of their joint moderation, on adolescent delinquency without family-level environmental confounding. The significant association of receptive vocabulary with later adolescent delinquency was indirect, mediated by childhood conduct problems. Furthermore, a significant interaction between receptive vocabulary and childhood conduct problems reflected a steeper slope for the predictive association between childhood conduct problems and adolescent delinquency when receptive vocabulary scores were higher. These findings of significant indirect association were qualitatively identical in both population-level and within-family analyses, suggesting that they are not the result of family-level confounds.
[Show abstract][Hide abstract] ABSTRACT: Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4-6 years old. Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods.
Frontiers in Behavioral Neuroscience 01/2014; 8:21. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous research using confirmatory factor analysis to model psychopathology comorbidity has supported the hypothesis of a broad general factor (i.e., a "bifactor"; Holzinger & Swineford, 1937) of psychopathology in children, adolescents, and adults, with more specific higher order internalizing and externalizing factors reflecting additional shared variance in symptoms (Lahey et al., 2012; Lahey, van Hulle, Singh, Waldman, & Rathouz, 2011). The psychological nature of this general factor has not been explored, however. The current study tested a prediction, derived from the spectrum hypothesis of personality and psychopathology, that variance in a general psychopathology bifactor overlaps substantially-at both phenotypic and genetic levels-with the dispositional trait of negative emotionality. Data on psychopathology symptoms and dispositional traits were collected from both parents and youth in a representative sample of 1,569 twin pairs (ages 9-17 years) from Tennessee. Predictions based on the spectrum hypothesis were supported, with variance in negative emotionality and the general factor overlapping substantially at both phenotypic and etiologic levels. Furthermore, stronger correlations were found between negative emotionality and the general psychopathology factor than among other dispositions and other psychopathology factors. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
Journal of Abnormal Psychology 11/2013; 122(4):1142-53. · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Researchers have identified environmental risks that predict subsequent psychological and medical problems. Based on these correlational findings, researchers have developed and tested complex developmental models and have examined biological moderating factors (e.g., gene-environment interactions). In this context, we stress the critical need for researchers to use family-based, quasi-experimental designs when trying to integrate genetic and social science research involving environmental variables because these designs rigorously examine causal inferences by testing competing hypotheses. We argue that sibling comparison, offspring of twins or siblings, in vitro fertilization designs, and other genetically informed approaches play a unique role in bridging gaps between basic biological and social science research. We use studies on maternal smoking during pregnancy to exemplify these principles. (Am J Public Health. Published online ahead of print August 8, 2013: e1-e10. doi:10.2105/AJPH.2013.301252).
American Journal of Public Health 08/2013; · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although advances in neonatal care over the past century have resulted in increased rates of survival among at-risk births, including infants with low birth weight, we have much to learn about psychological outcomes in this population. In particular, despite growing evidence that low birth weight may be associated with an increased risk for Attention-Deficit/Hyperactive Disorder (ADHD) symptoms in childhood, few studies have examined birth weight as a risk factor for disruptive disorders that commonly co-occur with ADHD. In addition, the etiology of the relation between birth weight and these disorders is unknown. The current investigation aimed to better understand these associations in the context of potentially confounding genetic and environmental influences by examining phenotypic associations between birth weight and disruptive disorder symptoms both between families and within families in two independent twin samples (Sample 1: N = 1,676 individuals; Sample 2: N = 4,038 individuals). We found negative associations between birth weight and inattentive, hyperactive-impulsive, and broad externalizing symptoms in both samples. Nonetheless, the overall magnitude of these associations was very small, contributing to less than 1% of the variance in these symptom dimensions. Within-family associations between birth weight and disruptive disorder symptoms did not differ for monozygotic and dizygotic twin pairs, suggesting that nonshared environmental influences rather than common genetic influences are responsible for these associations. Overall, the consistent albeit weak associations between birth weight and disruptive disorder symptoms suggest that low birth weight may not represent a major risk factor in the development of these symptoms. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
Journal of Abnormal Psychology 07/2013; · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several researchers have suggested that the nature of the covariation between internalizing and externalizing disorders may be understood better by examining the associations between temperament or personality and these disorders. The present study examined neuroticism as a potential common feature underlying both internalizing and externalizing disorders and novelty seeking as a potential broad-band specific feature influencing externalizing disorders alone. Participants were 12- to 18-year-old twin pairs (635 monozygotic twin pairs and 691 dizygotic twin pairs; 48 % male and 52 % female) recruited from the Colorado Center for Antisocial Drug Dependence. Genetic and nonshared environmental influences shared in common with neuroticism influenced the covariation among distinct internalizing disorders, the covariation among distinct externalizing disorders, and the covariation between internalizing and externalizing disorders. Genetic influences shared in common with novelty seeking influenced the covariation among externalizing disorders and the covariation between major depressive disorder and externalizing disorders, but not the covariation among internalizing disorders or between anxiety disorders and externalizing disorders. Also, after accounting for genetic and environmental influences shared in common with neuroticism and novelty seeking, there were no significant common genetic or environmental influences among the disorders examined, suggesting that the covariance among the disorders is sufficiently explained by neuroticism and novelty seeking. We conclude that neuroticism is a heritable common feature of both internalizing disorders and externalizing disorders, and that novelty seeking is a heritable broad-band specific factor that distinguishes anxiety disorders from externalizing disorders.
Journal of Abnormal Child Psychology 03/2013; · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Prediction of antisocial behavior is important, given its adverse impact on both the individuals engaging in antisocial behavior and society. Additional research identifying early predictors of future antisocial behavior, or antisocial propensity, is needed. The present study tested the hypothesis that both concern for others and active disregard for others in distress in toddlers and young children predict antisocial behavior during middle childhood and adolescence. Methods: A representative sample of same-sex twins (N = 956) recruited in Colorado was examined. Mother-rated and researcher-observed concern and disregard for others assessed at age 14-36 months were examined as predictors of parent- (age 4-12), teacher- (age 7-12), and self-reported (age 17) antisocial behavior. Results: Observed disregard for others predicted antisocial behavior assessed by three different informants (parents, teachers, and self), including antisocial behavior assessed 14 years later. It also predicted a higher order antisocial behavior factor (β = .58, p < .01) after controlling for observed concern for others. Mother-rated disregard for others predicted parent-reported antisocial behavior. Contrary to predictions, neither mother-rated nor observed concern for others inversely predicted antisocial behavior. Results of twin analyses suggested that the covariation between observed disregard for others and antisocial behavior was due to shared environmental influences. Conclusions: Disregard for others in toddlerhood/early childhood is a strong predictor of antisocial behavior in middle childhood and adolescence. The results suggest the potential need for early assessment of disregard for others and the development of potential interventions.
Journal of Child Psychology and Psychiatry 02/2013; 54(2):157-166. · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CONTEXT Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy (SDP) causes increased risk of substance use/problems in offspring. OBJECTIVE To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design. DESIGN We used 2 separate samples from the United States and Sweden. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding. SETTING Offspring of a representative sample of women in the United States (sample 1) and the total Swedish population born during the period from January 1, 1983, to December 31, 1995 (sample 2). PATIENTS OR OTHER PARTICIPANTS Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n = 6904) and all offspring born in Sweden during the 13-year period (n = 1 187 360). MAIN OUTCOME MEASURES Self-reported adolescent alcohol, cigarette, and marijuana use and early onset (before 14 years of age) of each substance (sample 1) and substance-related convictions and hospitalizations for an alcohol- or other drug-related problem (sample 2). RESULTS The same pattern emerged for each index of substance use/problems across the 2 samples. At the population level, maternal SDP predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (hazard ratio [HR]moderate, 1.32 [95% CI, 1.22-1.43]; HRhigh, 1.33 [1.17-1.53]) to a narcotics-related conviction (HRmoderate, 2.23 [2.14-2.31]; HRhigh, 2.97 [2.86-3.09]). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant. CONCLUSIONS The association between maternal SDP and offspring substance use/problems is likely due to familial background factors, not a causal influence, because siblings have similar rates of substance use and problems regardless of their specific exposure to SDP.
Archives of general psychiatry 11/2012; 69(11):1140-50. · 12.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is likely that all complex behaviors and diseases result from interactions between genetic vulnerabilities and environmental factors. Accurately identifying such gene-environment interactions is of critical importance for genetic research on health and behavior. In a previous article we proposed a set of models for testing alternative relationships between a phenotype (P) and a putative moderator (M) in twin studies. These include the traditional bivariate Cholesky model, an extension of that model that allows for interactions between M and the underling influences on P, and a model in which M has a non-linear main effect on P. Here we use simulations to evaluate the type I error rates, power, and performance of the Bayesian Information Criterion under a variety of data generating mechanisms and samples sizes (n = 2,000 and n = 500 twin pairs). In testing the extension of the Cholesky model, false positive rates consistently fell short of the nominal Type I error rates ([Formula: see text]). With adequate sample size (n = 2,000 pairs), the correct model had the lowest BIC value in nearly all simulated datasets. With lower sample sizes, models specifying non-linear main effects were more difficult to distinguish from models containing interaction effects. In addition, we provide an illustration of our approach by examining possible interactions between birthweight and the genetic and environmental influences on child and adolescent anxiety using previously collected data. We found a significant interaction between birthweight and the genetic and environmental influences on anxiety. However, the interaction was accounted for by non-linear main effects of birthweight on anxiety, verifying that interaction effects need to be tested against alternative models.
[Show abstract][Hide abstract] ABSTRACT: This chapter reviews what is currently known about the developmental precursors to conduct disorder (CD). Specifically, it summarizes current findings on the potential developmental relations between attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) on the one hand, and CD on the other hand. Although ODD appears to be a developmental precursor to CD in both girls and boys, the existing evidence suggests that not all children who meet criteria for CD first exhibit a significant number of ODD behaviors. If childhood ODD is a developmental precursor to CD for some boys but not others, it should be possible eventually to identify the factors that govern the developmental progression from ODD to CD. If the findings reviewed in this chapter are correct in suggesting that ODD behaviors play the role of a developmental precursor to CD, how might this happen? We briefly advance one view in this chapter that is consistent with the existing data: ODD is characterized by frequently occurring behaviors that are defined in broad terms, that is, whereas CD behaviors refer to specific law-violating acts, ODD is defined in terms of broad tendencies to respond angrily. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
[Show abstract][Hide abstract] ABSTRACT: The patterns of comorbidity among prevalent mental disorders in adults lead them to load on "externalizing," "distress," and "fears" factors. These factors are themselves robustly correlated, but little attention has been paid to this fact. As a first step in studying the implications of these interfactor correlations, we conducted confirmatory factor analyses on diagnoses of 11 prevalent Diagnostic and Statistical Manual of Mental Disorders (4th ed.) mental disorders in a nationally representative sample. A model specifying correlated externalizing, distress, and fears factors fit well, but an alternative model was tested in which a "general" bifactor was added to capture what these disorders share in common. There was a modest but significant improvement in fit for the bifactor model relative to the 3-factor oblique model, with all disorders loading strongly on the bifactor. Tests of external validity revealed that the fears, distress, and externalizing factors were differentially associated with measures of functioning and potential risk factors. Nonetheless, the general bifactor accounted for significant independent variance in future psychopathology, functioning, and other criteria over and above the fears, distress, and externalizing factors. These findings support the hypothesis that these prevalent forms of psychopathology have both important common and unique features. Future studies should determine whether this is because they share elements of their etiology and neurobiological mechanisms. If so, the existence of common features across diverse forms of prevalent psychopathology could have important implications for understanding the nature, etiology, and outcomes of psychopathology. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
Journal of Abnormal Psychology 07/2012; · 4.86 Impact Factor