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This study uses novel approaches to examine genetic and environmental influences shared between childhood behavioral inhibition (BI) and symptoms of preadolescent anxiety disorders. Three hundred and fifty-two twin pairs aged 9–13 and their mothers completed questionnaires about BI and anxiety symptoms. Biometrical twin modeling, including a direction-of-causation design, investigated genetic and environmental risk factors shared between BI and social, generalized, panic and separation anxiety. Social anxiety shared the greatest proportion of genetic (20%) and environmental (16%) variance with BI with tentative evidence for causality. Etiological factors underlying BI explained little of the risk associated with the other anxiety domains. Findings further clarify etiologic pathways between BI and anxiety disorder domains in children.

OBJECTIVE: Childhood irritability exhibits significant theoretical and empirical associations with depression and anxiety syndromes. The current study used the twin design to parse genetic and environmental contributions to these relationships. METHOD: Children aged 9–14 from 374 twin pairs were assessed for irritability and symptoms of depression, generalized anxiety, panic, social phobia, and separation anxiety using dimensional self-report instruments. Multivariate structural equation modeling decomposed the correlations between these syndromes into genetic and environmental components to examine shared and specific risk domains. RESULTS: Irritability had significant associations with each internalizing symptom domain. Genetic contributions to irritability are moderately correlated with genetic risk for symptoms of depression, generalized anxiety, and separation anxiety with weaker overlap with the other anxiety syndromes. Familial and specific environmental risk factors explained covariation among syndromes and indicated potential syndrome-specific risk. CONCLUSIONS: There is substantial overlap among the genetic and environmental factors that influence individual differences in irritability and those that increase liability for depression and anxiety symptoms in children. These findings deepen the current understanding of childhood internalizing risk factors and provide important implications for syndrome prediction and susceptibility gene discovery efforts.

Background Internalizing disorders (IDs), consisting of the syndromes of anxiety and depression, are common, debilitating conditions often having onsets in adolescence. Scientists have developed dimensional self-report instruments that assess putative negative valence system (NVS) trait-like constructs as complimentary phenotypes to clinical symptoms. These include various measures that index temperamental predispositions to IDs and correlate with neural substrates of fear, anxiety, and affective regulation. This study sought to elucidate the overarching structure of putative NVS traits and their relationship to early manifestations of ID symptomatology. Methods The sample consisted of 768 juvenile twin subjects ages 9–13. Together with ID symptoms, extant validated instruments were chosen to assess a broad spectrum of NVS traits: anxiety sensitivity, irritability, fearfulness, behavioral activation and inhibition, and neuroticism and extraversion. Exploratory and confirmatory factor analyses (EFA/CFA) were used to investigate the latent structure of the associations among these different constructs and ID symptoms. Bifactor modeling in addition to standard correlated-factor analytic approaches were applied. Results Factor analyses produced a primary tripartite solution comprising anxiety/fear, dysphoria, and positive affect among all these measures. Competing DSM-like correlated factors and an RDoC-like NVS bifactor structure provided similar fit to these data. Conclusions Our findings support the conceptual organization of a tripartite latent internalizing domain in developing children. This structure includes both clinical symptoms and a variety of self-report dimensional traits currently in use by investigators. These various constructs are, therefore, most informatively investigated using an inclusive, integrated approach.

Fear and anxiety are conceptualized as responses to acute or potential threat, respectively. Adult twin studies found substantial interplay between genetic and environmental factors influencing fear disorders (phobias) and anxiety disorders. Research in children, however, has largely examined these factors independently. Thus, there exists a substantial knowledge gap regarding the underlying etiologic structure of these closely-related constructs during development. Symptom counts for five fear (criticism, the unknown, death, animal, medical) and four anxiety (generalized, panic, separation, social) dimensions were obtained for 373 twin pairs ages 9-14. Multivariate twin modeling was performed to elucidate the genetic and environmental influences distributed amongst these dimensions. The best fitting model contained one genetic, two familial environmental, and two unique environmental factors shared between fear and anxiety symptoms plus dimension-specific genetic and unique environmental factors. Although several environmental factors were shared between fear and anxiety dimensions, one latent factor accounted for genetic influences across both domains. While adult studies find somewhat distinct etiological differences between anxiety and phobic disorders, the current results suggest that their relative genetic and environmental influences are not as clearly demarcated in children. These etiological distinctions are more nuanced, likely contributing to the highly diffuse symptom patterns seen during development.

Objective Youth with psychiatric disorders distinguished by irritability, including depression and associated trait neuroticism, show deficits in the ability to recognize facial expressions of emotion, particularly happiness. However, the contribution of genetic and environmental factors to this ability remains unknown. The present study examined this trait in twins to assess the genetic and environmental influences on face-emotion recognition abilities and their association with irritability, neuroticism, and depression. Method Child and adolescent twins (N = 957 from 496 families) 9 to 17 years old rated their irritability (on the Affective Reactivity Index), neuroticism (on the Junior Eysenck Personality Questionnaire), and depression (on the Short Mood and Feelings Questionnaire) and completed a face-emotion labeling task. Faces depicting anger, disgust, fear, happiness, sadness, and surprise were morphed with a neutral face, yielding 10 levels of increasing emotional expressivity. Biometrical twin analyses evaluated contributions of genetic and environmental factors to the etiology of face-emotion recognition and its association with irritability, neuroticism, and depression. Results Recognition of each emotion was heritable; common and specific sets of genetic factors influenced all emotions and individual emotions, respectively. Irritability, neuroticism, and depression were modestly and negatively correlated with emotion recognition, particularly the recognition of happiness. For irritability and neuroticism, this correlation appeared largely due to genetic factors. Conclusion This study maps genetic and environmental contributions to face-emotion recognition and its association with irritability, neuroticism, and depression. Findings implicate common genetic factors in deficits regarding the recognition of happiness associated with irritability and neuroticism in childhood and adolescence.

Research in community and clinical samples has documented elevated rates of cannabis use and cannabis use disorders (CUDs) among individuals with trauma exposure and posttraumatic stress disorder (PTSD). However, there is a lack of research investigating relations between, and correlates of, trauma and cannabis phenotypes in epidemiologic samples. The current study examined associations between trauma (i.e., lifetime trauma exposure and PTSD) and cannabis phenotypes (i.e., lifetime cannabis use and CUD) in a nationally representative sample. Participants were individuals who participated in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,396; 52.4% women; age, M = 48.0 years, SD = 16.9). Lifetime DSM-IV Criterion A trauma exposure was significantly associated with lifetime cannabis use (OR = 1.215) but was only marginally associated with CUD (OR = 0.997). Within the trauma-exposed sample, lifetime PTSD showed a significant association with CUD (OR = 1.217) but was only marginally associated with lifetime cannabis use (OR = 0.992). Partially consistent with hypotheses, lifetime trauma was associated with greater odds of lifetime cannabis use, whereas PTSD was associated with greater odds of CUD. Longitudinal research investigating patterns of onset of these events/disorders is needed.

Objective Hypersensitivity to carbon dioxide (CO 2 )-enriched air may be a promising risk marker for anxiety disorders. Among adult and adolescent samples, heterogeneity in distress response to the CO 2 challenge task indexes three underlying classes of individuals, which distinguish between sustained and acute threat response as markers for internalizing disorders, broadly, and anxiety disorders, specifically. The present study examines latent classes in children's response to the CO 2 challenge task to clarify the association of CO 2 hypersensitivity with anxiety and internalizing symptomatology in childhood. Method Healthy children from a community twin sample (N = 538; 9-13 years) rated anxious distress every 2 minutes while breathing air enriched to 7.5% CO 2 for 8 minutes. Latent growth mixture modeling evaluated potential classes of individuals with characteristic trajectories of distress during the task to clarify the association with internalizing disorder symptoms and related traits (e.g., anxiety sensitivity, irritability). Results While all participants reported increased distress during the task, inter-individual heterogeneity in distress indexed three underlying classes: a consistently low class ("low"), a consistently high class ("high"), and participants who demonstrated markedly increased acute distress ("acute"). Compared to the low class, the high class reported greater internalizing psychopathology, whereas membership in the acute class was associated with experiencing a panic-like event during the task. Conclusion As in older individuals, three distinct trajectories emerged to capture inter-individual heterogeneity in children's distress during the CO 2 challenge task. These classes were distinguished by clinical validators that reinforce the association of CO 2 hypersensitivity and internalizing disorder phenotypes in children.

Background Data on the reliability and validity of assessments for irritability, particularly behavioral paradigms, are limited. This study examined the test-retest reliability and validity of a frustration paradigm (the Affective Posner 2 task) and two irritability measures [the Affective Reactivity Index (ARI) and Child Behavior Checklist (CBCL) irritability]. Methods Participants were 109 youth from a general population sample of twins (aged 9–14 years). Participants completed two visits that were 2–4 weeks apart. At both visits, participants completed the Affective Posner 2 task and self-reported their irritability using the ARI. Parents reported their child's irritability using the ARI and completed the CBCL. Results The Affective Posner 2 task demonstrated good test-retest reliability, with intraclass correlations (ICCs) ranging from .44 to .78. The task effectively evoked negative affect (frustration and unhappiness) at both test and retest, demonstrating its construct validity. Moreover, self-rated frustration and unhappiness during the frustration components of the task correlated positively with self-reported but not parent-reported irritability, providing modest support for convergent validity. Parent- and child-reports of the ARI and parent-reports of the CBCL irritability measure showed excellent test-retest reliability, with ICCs ranging from .88 to .90. Limitations The sample consists of mostly twins aged 9–14 years from the communities. Thus, results may not generalize to non-twin samples or clinical samples outside of this age range. Conclusions The Affective Posner 2 paradigm and the ARI and CBCL irritability scales may be useful tools for longitudinal or treatment research on irritability.

The modulation of the startle response (SR) by threatening stimuli (fear-potentiated startle; FPS), is a proposed endophenotype for disorders of the fearful-fearlessness spectrum. FPS has failed to show evidence of heritability, raising concerns. However, the metrics used to index FPS – and, importantly, other conditional phenotypes that are dependent on a baseline – may not be suitable for the approaches used in genetic epidemiology studies. Here we evaluated multiple metrics of FPS in a population-based sample of pre-adolescent twins (N = 569 from 320 twin pairs, M(age) = 11.4) who completed a fear-conditioning paradigm with airpuff-elicited SR on two occasions (~1 month apart). We applied univariate and multivariate biometric modeling to estimate the heritability of FPS using several proposed standardization procedures. This was extended with data simulations to evaluate biases in heritability estimates of FPS (and similar metrics) under various scenarios. Consistent with previous studies, results indicated moderate test-retest reliability (r = .59) and heritability of the overall SR (h(2) = 34%) but poor reliability and virtually no unique genetic influences on FPS when considering a raw or standardized differential score that removes baseline SR. Simulations demonstrated that the use of differential scores introduces bias in heritability estimates relative to jointly analyzing baseline SR and FPS in a multivariate model. However, strong dependency of FPS on baseline levels make unique genetic influences virtually impossible to detect regardless of methodology. These findings indicate that FPS and other conditional phenotypes may not be well-suited to serve as endophenotypes unless such co-dependency can be disentangled.

The Twin Study of Negative Valence Emotional Constructs is a multi-site study designed to examine the relationship between a broad selection of potential measures designed to assess putative endophenotypes for negative valence systems (NVS) and early symptoms of internalizing disorders (IDs). In this article, we describe the sample characteristics, data collection protocols, and measures used. Pre-adolescent Caucasian twin pairs were recruited through the Mid-Atlantic Twin Registry; data collection began in February of 2013. Enrolled twins completed various dimensional self-report measures along with cognitive, emotional, and psychophysiological tasks designed to assess NVS function. Parents also completed surveys about their twins and themselves. In addition, a subset of the twins also participated in a neuroimaging protocols. Data collection is in the final stages, and preliminary analyses are underway. The findings will potentially expand our understanding of the mechanisms by which genetic and environmental factors contribute to individual differences in NVS phenotypes and provide new insights into underlying risk factors for IDs.

Callous-unemotional (CU) traits comprise the core symptoms of psychopathy, yet no study has estimated the heritability of CU traits in a community sample of children using an instrument designed solely to assess CU traits. The current study uses data from 339 twin pairs aged 9-14 to examine the reliability and heritability of the parent-report Inventory of Callous-unemotional Traits (ICU) at two assessments approximately 3 weeks apart. Time-specific measurement error was taken into account to obtain a more accurate estimate of the heritability reflecting the latent liability to CU traits. Test-retest reliability was 0.84 and heritability at visit 1 was 39%. The heritability of the latent liability to CU traits was 47%. This latent liability contributed 79% of the variance in ICU score at visit 1 and visit 2. This is the first study to account for measurement error while examining the heritability of CU traits, furthering our understanding of psychopathy in children.