Publications by authors named "John M Hettema"

81 Publications

Rates of Incidental Findings in Brain Magnetic Resonance Imaging in Children.

JAMA Neurol 2021 Mar 22. Epub 2021 Mar 22.

Department of Psychiatry, University of Maryland, Baltimore.

Importance: Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings.

Objectives: To determine the overall prevalence of IFs in brain MRI in the nonclinical pediatric population as well as the rates of specific findings and findings for which clinical referral is recommended.

Design, Setting, And Participants: This cohort study was based on the April 2019 release of baseline data from 11 810 children aged 9 to 10 years who were enrolled and completed baseline neuroimaging in the Adolescent Brain Cognitive Development (ABCD) study, the largest US population-based longitudinal observational study of brain development and child health, between September 1, 2016, and November 15, 2018. Participants were enrolled at 21 sites across the US designed to mirror the demographic characteristics of the US population. Baseline structural MRIs were centrally reviewed for IFs by board-certified neuroradiologists and findings were described and categorized (category 1, no abnormal findings; 2, no referral recommended; 3; consider referral; and 4, consider immediate referral). Children were enrolled through a broad school-based recruitment process in which all children of eligible age at selected schools were invited to participate. Exclusion criteria were severe sensory, intellectual, medical, or neurologic disorders that would preclude or interfere with study participation. During the enrollment process, demographic data were monitored to ensure that the study met targets for sex, socioeconomic, ethnic, and racial diversity. Data were analyzed from March 15, 2018, to November 20, 2020.

Main Outcomes And Measures: Percentage of children with IFs in each category and prevalence of specific IFs.

Results: A total of 11 679 children (52.1% boys, mean [SD] age, 9.9 [0.62] years) had interpretable baseline structural MRI results. Of these, 2464 participants (21.1%) had IFs, including 2013 children (17.2%) assigned to category 2, 431 (3.7%) assigned to category 3, and 20 (0.2%) assigned to category 4. Overall rates of IFs did not differ significantly between singleton and twin gestations or between monozygotic and dizygotic twins, but heritability analysis showed heritability for the presence or absence of IFs (h2 = 0.260; 95% CI, 0.135-0.387).

Conclusions And Relevance: Incidental findings in brain MRI and findings with potential clinical significance are both common in the general pediatric population. By assessing IFs and concurrent developmental and health measures and following these findings over the longitudinal study course, the ABCD study has the potential to determine the significance of many common IFs.
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http://dx.doi.org/10.1001/jamaneurol.2021.0306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985817PMC
March 2021

Resting-State Directional Connectivity and Anxiety and Depression Symptoms in Adult Cannabis Users.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 May 7;6(5):545-555. Epub 2020 Oct 7.

Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, Virginia; Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia; Department of Neurology, Virginia Commonwealth University, Richmond, Virginia.

Background: Anxiety and depression symptoms are common among cannabis users and could be a risk factor for cannabis use (CU) disorder. Thus, it is critical to understand the neuronal circuits underlying the associations between CU and these symptoms. Alterations in resting-state functional connectivity within and/or between the default mode network and salience network have been reported in CU, anxiety, and depressive disorders and thus could be a mechanism underlying the associations between CU disorder and anxiety/depression symptoms.

Methods: Using resting-state functional magnetic resonance imaging, effective connectivities (ECs) among 9 major nodes from the default mode network and salience network were measured using dynamic causal modeling in 2 datasets: the Human Connectome Project (28 CU participants and 28 matched non-drug-using control participants) and a local CU study (21 CU participants and 21 matched non-drug-using control participants) in separate and parallel analyses.

Results: Relative to the control participants, right amygdala to left amygdala, anterior cingulate cortex to left amygdala, and medial prefrontal cortex to right insula ECs were greater, and left insula to left amygdala EC was smaller in the CU group. Each of these ECs showed a reliable linear relationship with at least one of the anxiety/depression measures. Most findings on the right amygdala to left amygdala EC were common to both datasets.

Conclusions: Right amygdala to left amygdala and anterior cingulate cortex to left amygdala ECs may be related to the close associations between CU and anxiety/depression symptoms. The findings on the medial prefrontal cortex to right insula and left insula to left amygdala ECs may reflect a compensatory mechanism.
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http://dx.doi.org/10.1016/j.bpsc.2020.09.015DOI Listing
May 2021

An epigenome-wide association study of early-onset major depression in monozygotic twins.

Transl Psychiatry 2020 08 25;10(1):301. Epub 2020 Aug 25.

Virginia Commonwealth University, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA.

Major depression (MD) is a debilitating mental health condition with peak prevalence occurring early in life. Genome-wide examination of DNA methylation (DNAm) offers an attractive complement to studies of allelic risk given it can reflect the combined influence of genes and environment. The current study used monozygotic twins to identify differentially and variably methylated regions of the genome that distinguish twins with and without a lifetime history of early-onset MD. The sample included 150 Caucasian monozygotic twins between the ages of 15 and 20 (73% female; Mage = 17.52 SD = 1.28) who were assessed during a developmental stage characterized by relatively distinct neurophysiological changes. All twins were generally healthy and currently free of medications with psychotropic effects. DNAm was measured in peripheral blood cells using the Infinium Human BeadChip 450 K Array. MD associations with early-onset MD were detected at 760 differentially and variably methylated probes/regions that mapped to 428 genes. Genes and genomic regions involved neural circuitry formation, projection, functioning, and plasticity. Gene enrichment analyses implicated genes related to neuron structures and neurodevelopmental processes including cell-cell adhesion genes (e.g., PCDHA genes). Genes previously implicated in mood and psychiatric disorders as well as chronic stress (e.g., NRG3) also were identified. DNAm regions associated with early-onset MD were found to overlap genetic loci identified in the latest Psychiatric Genomics Consortium meta-analysis of depression. Understanding the time course of epigenetic influences during emerging adulthood may clarify developmental phases where changes in the DNA methylome may modulate individual differences in MD risk.
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http://dx.doi.org/10.1038/s41398-020-00984-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447798PMC
August 2020

Assessing Stakeholder Perceptions of the Utility of Genetic Information for the Clinical Care of Mental Health Disorders: We Have a Will but Need to See the Way.

Adm Policy Ment Health 2021 03;48(2):363-376

Department of Psychology, Virginia Commonwealth University, 806 West Franklin Street, Richmond, VA, 23284, USA.

Academic stakeholders' (primarily mental health researchers and clinicians) practices and attitudes related to the translation of genetic information into mental health care were assessed. A three-part survey was administered at two large, urban universities. Response frequencies were calculated. Participants (N = 64) reported moderate levels of translational practice, adequate levels of genetic knowledge, and variable levels of genetic competence. They held positive attitudes toward translating genetic information about mental health broadly but negative attitudes about the impact that such information would have on specific aspects of care. The current study lays the groundwork for further inquiry into translating genetic information to mental health care.
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http://dx.doi.org/10.1007/s10488-020-01058-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749826PMC
March 2021

Genetic and environmental risk structure of internalizing psychopathology in youth.

Depress Anxiety 2020 06 5;37(6):540-548. Epub 2020 May 5.

Department of Psychiatry, Virginia Institute for Psychiatry and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.

Background: Internalizing disorders (IDs), consisting of syndromes of anxiety and depression, are common, debilitating conditions often beginning early in life. Various trait-like psychological constructs are associated with IDs. Our prior analysis identified a tripartite model of Fear/Anxiety, Dysphoria, and Positive Affect among symptoms of anxiety and depression and the following constructs in youth: anxiety sensitivity, fearfulness, behavioral activation and inhibition, irritability, neuroticism, and extraversion. The current study sought to elucidate their overarching latent genetic and environmental risk structure.

Methods: The sample consisted of 768 juvenile twin subjects ages 9-14 assessed for the nine, abovementioned measures. We compared two multivariate twin models of this broad array of phenotypes.

Results: A hypothesis-driven, common pathway twin model reflecting the tripartite structure of the measures were fit to these data. However, an alternative independent pathway model provided both a better fit and more nuanced insights into their underlying genetic and environmental risk factors.

Conclusions: Our findings suggest a complex latent genetic and environmental structure to ID phenotypes in youth. This structure, which incorporates both clinical symptoms and various psychological traits, informs future phenotypic approaches for identifying specific genetic and pathophysiological mechanisms underlying ID risk.
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http://dx.doi.org/10.1002/da.23024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656112PMC
June 2020

Genome-wide association study of shared liability to anxiety disorders in Army STARRS.

Am J Med Genet B Neuropsychiatr Genet 2020 06 30;183(4):197-207. Epub 2019 Dec 30.

Department of Family Medicine & Public Health, University of California San Diego, La Jolla, California.

Anxiety disorders (ANX), namely generalized anxiety, panic disorder, and phobias, are common, etiologically complex syndromes that show increasing prevalence and comorbidity throughout adolescence and beyond. Few genome-wide association studies (GWAS) examining ANX risk have been published and almost exclusively in individuals of European ancestry. In this study, we phenotyped participants from the Army Study To Assess Risk and Resilience in Servicemembers (STARRS) to approximate DSM-based ANX diagnoses. We factor-analyzed those to create a single dimensional anxiety score for each subject. GWAS were conducted using that score within each of three ancestral groups (EUR, AFR, LAT) and then meta-analyzed across ancestries (N = 16,510). We sought to (a) replicate prior ANX GWAS findings in ANGST; (b) determine whether results extended to other ancestry groups; and (c) meta-analyze with ANGST for increased power to identify novel susceptibility loci. No reliable genome-wide significant SNP associations were detected in STARRS. However, SNPs within the CAMKMT gene located in region 2p21 associated with shared ANX risk in ANGST were replicated in EUR soldiers but not other ancestry groups. Combining EUR STARRS and ANGST (N = 28,950) yielded a more robust 2p21 association signal (p = 9.08x10 ). Gene-based analyses supported three genes within 2p21 and LBX1 on chromosome 10. More powerful ANX genetic studies will be required to identify further loci.
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http://dx.doi.org/10.1002/ajmg.b.32776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210051PMC
June 2020

A major role for common genetic variation in anxiety disorders.

Mol Psychiatry 2020 12 20;25(12):3292-3303. Epub 2019 Nov 20.

King's College London; Social, Genetic and Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, London, UK.

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (n = 25 453, n = 58 113) and an additional analysis of Current Anxiety Symptoms (n = 19 012, n = 58 113). The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant positive genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.
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http://dx.doi.org/10.1038/s41380-019-0559-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237282PMC
December 2020

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study.

Neuroimage 2019 11 12;202:116091. Epub 2019 Aug 12.

National Institute on Drug Abuse, United States.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981278PMC
November 2019

Altered Effective Connectivity of Central Autonomic Network in Response to Negative Facial Expression in Adults With Cannabis Use Disorder.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 01 5;5(1):84-96. Epub 2019 Jun 5.

Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, Virginia; Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia; Department of Neurology, Virginia Commonwealth University, Richmond, Virginia.

Background: Cannabis use is associated with an increased risk of stress-related adverse cardiovascular events. Because brain regions of the central autonomic network largely overlap with brain regions related to the neural response to emotion and stress, the central autonomic network may mediate the autonomic response to negative emotional stimuli. We aimed to obtain evidence to determine whether neural connectivity of the central autonomic network is altered in individuals with cannabis use disorder (CUD) when they are exposed to negative emotional stimuli.

Methods: Effective (directional) connectivity (EC) analysis using dynamic causal modeling was applied to functional magnetic resonance imaging data acquired from 23 subjects with CUD and 23 control subjects of the Human Connectome Project while they performed an emotional face-matching task with interleaving periods of negative-face (fearful/angry) and neutral-shape stimuli. The EC difference (modulatory change) was measured during the negative-face trials relative to the neutral-shape trials.

Results: The CUD group was similar to the control group in nonimaging measures and brain activations but showed greater modulatory changes in left amygdala to hypothalamus EC (positively associated with Perceived Stress Scale score), right amygdala to bilateral fusiform gyri ECs (positively associated with Perceived Stress Scale score), and left ventrolateral prefrontal cortex to bilateral fusiform gyri ECs (negatively associated with Perceived Stress Scale score).

Conclusions: Left amygdala to hypothalamus EC and right amygdala to bilateral fusiform gyri ECs are possibly part of circuits underlying the risk of individuals with CUD to stress-related disorders. Correspondingly, left ventrolateral prefrontal cortex to bilateral fusiform gyri ECs are possibly part of circuits reflecting a protective mechanism.
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http://dx.doi.org/10.1016/j.bpsc.2019.05.013DOI Listing
January 2020

Differential Associations of Distress Tolerance and Anxiety Sensitivity With Adolescent Internalizing Psychopathology.

J Clin Child Adolesc Psychol 2021 Jan-Feb;50(1):97-104. Epub 2019 May 6.

Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University.

Distress tolerance and anxiety sensitivity may differentiate among internalizing disorders, though few studies have examined differential associations of distress tolerance and anxiety sensitivity with depression and anxiety symptoms while adjusting for their intercorrelation. In an adolescent genetic epidemiological sample (ages 15-21), the present study ( = 848, 56.97% female) examined concurrent associations of distress tolerance and anxiety sensitivity with internalizing psychopathology (i.e., symptoms of depression, anxiety, and general stress) at baseline and prospective, predictive associations of baseline distress tolerance and anxiety sensitivity with internalizing psychopathology at 2-year follow-up. In addition, the present study assessed distress tolerance with two laboratory-based tasks, a carbon dioxide challenge and the mirror-tracing task, to distinguish between tolerance of physiological and cognitive distress, respectively. Elevated anxiety sensitivity was broadly associated with elevated symptoms of internalizing psychopathology at baseline and prospectively predicted elevated depression, anxiety, and stress symptoms at 2-year follow-up. Higher tolerance of cognitive distress was associated with lower concurrent anxiety symptoms but not with anxiety symptoms at follow-up. The present results clarify previously mixed findings; during adolescence, anxiety sensitivity showed broad concurrent and prospective associations with internalizing disorder risk whereas distress tolerance, specifically regarding cognitive distress, was associated with only elevated concurrent anxiety symptoms.
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http://dx.doi.org/10.1080/15374416.2019.1602838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832780PMC
May 2019

Heritability, stability, and prevalence of tonic and phasic irritability as indicators of disruptive mood dysregulation disorder.

J Child Psychol Psychiatry 2019 09 17;60(9):1032-1041. Epub 2019 Apr 17.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.

Background: Little is known about genetic and environmental influences on the components of disruptive mood dysregulation disorder (DMDD), tonic irritability (i.e., irritable mood) and phasic irritability (i.e., temper outbursts). This study examined prevalence, stability, and heritability of tonic irritability, phasic irritability, and a DMDD proxy (pDMDD) based on DSM-5 criteria.

Methods: pDMDD was derived using data from clinical interviews of parents and their twins (N = 1,431 twin pairs), ages 8-17, participating in Waves 1 and 2 of the Virginia Twin Study of Adolescent Behavioral Development. Biometrical modeling was used to compare a common pathway model (CPM) and an independent pathway model (IPM), and heritability estimates were obtained for pDMDD using the symptoms of irritable mood (tonic irritability; DMDD Criterion D), intense temper outbursts (phasic irritability; DMDD Criterion A), and frequent temper outbursts (phasic irritability; DMDD Criterion C).

Results: Lifetime prevalence of pDMDD was 7.46%. The stability of DMDD symptoms and the pDMDD phenotype across approximately one year were moderate (.30-.69). A CPM was a better fit to the data than an IPM. Phasic irritability loaded strongly onto the pDMDD latent factor (.89-.96) whereas tonic irritability did not (.28). Genetic influences accounted for approximately 59% of the variance in the latent pDMDD phenotype, with the remaining 41% of the variance due to unique environmental effects. The heritability of tonic irritability (54%) was slightly lower than that of frequent and intense temper (components of phasic irritability; 61% and 63%, respectively).

Conclusions: Compared to tonic irritability, phasic irritability appears to be slightly more stable and heritable, as well as a stronger indicator of the latent factor. Furthermore, environmental experiences appear to play a substantial role in the development of irritability and DMDD, and researchers should seek to elucidate these mechanisms in future work.
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http://dx.doi.org/10.1111/jcpp.13062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692198PMC
September 2019

Quantifying Dispositional Fear as Threat Sensitivity: Development and Initial Validation of a Model-Based Scale Measure.

Assessment 2020 04 4;27(3):533-546. Epub 2019 Apr 4.

Florida State University, Tallahassee, FL, USA.

The Research Domain Criteria initiative aims to reorient the focus of psychopathology research toward biobehavioral constructs that cut across different modalities of measurement, including self-report and neurophysiology. Constructs within the Research Domain Criteria framework are intentionally transdiagnostic, with the construct of "acute threat," for example, broadly relevant to clinical problems and associated traits involving fearfulness and stress reactivity. A potentially valuable referent for research on the construct of acute threat is a structural model of fear/fearlessness questionnaires known to predict variations in physiological threat reactivity as indexed by startle potentiation. The aim of the current work was to develop an efficient, item-based scale measure of the general factor of this structural model for use in studies of dispositional threat sensitivity and its relationship to psychopathology. A self-report scale consisting of 44 items from a conceptually relevant, nonproprietary questionnaire was first developed in a sample of 1,307 student participants, using the general factor of the fear/fearlessness model as a direct referent. This new Trait Fear scale was then evaluated for convergent and discriminant validity with measures of personality and psychopathology in a separate sample ( = 213) consisting of community adults and undergraduate students. The strong performance of the scale in this criterion-validation sample suggests that it can provide an effective means for indexing variations along a dispositional continuum of fearfulness reflecting variations in sensitivity to acute threat.
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http://dx.doi.org/10.1177/1073191119837613DOI Listing
April 2020

The genetic underpinnings of callous-unemotional traits: A systematic research review.

Neurosci Biobehav Rev 2019 05 25;100:85-97. Epub 2019 Feb 25.

Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, 800 E. Leigh St., Suite 100, Box 980126, Richmond, VA, 23298, USA.

Background: Callous-unemotional (CU) traits represent the affective features of psychopathy used to delineate youth at high risk for externalizing pathology. The genetic etiology CU traits is not currently well-understood.

Methods: The current review surveyed the literature for studies on the genetic underpinnings of CU traits and integrated information from 39 genetic studies.

Results: The results from 24 studies with quantitative data suggest that the heritability for CU traits is likely between 36-67%. A majority of the 16 molecular genetic studies focused on candidate genes in the serotonin and oxytocin systems with results that have not been well replicated. Although two genome-wide association studies have been conducted, no genome-wide significant loci have been discovered.

Discussion: There is some evidence to suggest that the serotonin and oxytocin systems may play a role in CU traits; however, there is currently not enough evidence to implicate specific genetic mechanisms. The authors encourage researchers to continue to apply the most up-to-date and relevant methodology, specifically collaborations and consortiums using genome-wide and polygenic methods.
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http://dx.doi.org/10.1016/j.neubiorev.2019.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756755PMC
May 2019

Genetic underpinnings of callous-unemotional traits and emotion recognition in children, adolescents, and emerging adults.

J Child Psychol Psychiatry 2019 06 18;60(6):638-645. Epub 2019 Feb 18.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.

Background: Callous-Unemotional (CU) and psychopathic traits are consistently associated with impaired recognition of others' emotions, specifically fear and sadness. However, no studies have examined whether the association between CU traits and emotion recognition deficits is due primarily to genetic or environmental factors.

Methods: The current study used data from 607 Caucasian twin pairs (N = 1,214 twins) to examine the phenotypic and genetic relationship between the Inventory of Callous-Unemotional Traits (ICU) and facial emotion recognition assessed via the laboratory-based Facial Expression Labeling Task (FELT).

Results: The uncaring/callous dimension of the ICU was significantly associated with impaired recognition of happiness, sadness, fear, surprise, and disgust. The unemotional ICU dimension was significantly associated with improved recognition of surprise and disgust. Total ICU score was significantly associated with impaired recognition of sadness. Significant genetic correlations were found for uncaring/callous traits and distress cue recognition (i.e. fear and sadness). The observed relationship between uncaring/callous traits and deficits in distress cue recognition was accounted for entirely by shared genetic influences.

Conclusions: The results of the current study replicate previous findings demonstrating impaired emotion recognition among youth with elevated CU traits. We extend these findings by replicating them in an epidemiological sample not selected or enriched for pathological levels of CU traits. Furthermore, the current study is the first to investigate the genetic and environmental etiology of CU traits and emotion recognition, and results suggest genetic influences underlie the specific relationship between uncaring/callous traits and distress cue (fear/sadness) recognition in others.
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http://dx.doi.org/10.1111/jcpp.13018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520193PMC
June 2019

The genetic and environmental structure of fear and anxiety in juvenile twins.

Am J Med Genet B Neuropsychiatr Genet 2019 04 1;180(3):204-212. Epub 2019 Feb 1.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.

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.
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http://dx.doi.org/10.1002/ajmg.b.32714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414251PMC
April 2019

The Genetic and Environmental Relationship Between Childhood Behavioral Inhibition and Preadolescent Anxiety.

Twin Res Hum Genet 2019 02 30;22(1):48-55. Epub 2019 Jan 30.

Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University,Richmond, VA,USA.

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.
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http://dx.doi.org/10.1017/thg.2018.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449201PMC
February 2019

Fear-potentiated startle response as an endophenotype: Evaluating metrics and methods for genetic applications.

Psychophysiology 2019 05 4;56(5):e13325. Epub 2019 Jan 4.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.

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, 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 preadolescent twins (N = 569 from 320 twin pairs, M = 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 = 0.59) and heritability of the overall SR (h = 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 makes 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 codependency can be disentangled.
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http://dx.doi.org/10.1111/psyp.13325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454577PMC
May 2019

A Developmental Twin Study of Emotion Recognition and Its Negative Affective Clinical Correlates.

J Am Acad Child Adolesc Psychiatry 2018 12 29;57(12):925-933.e3. Epub 2018 Sep 29.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.

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.
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http://dx.doi.org/10.1016/j.jaac.2018.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036262PMC
December 2018

Confirmatory factor structure and psychometric properties of the Multidimensional Peer Victimization Scale.

J Psychopathol Behav Assess 2018 Dec 14;40(4):725-735. Epub 2018 Apr 14.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, 800 E Leigh St., Suite 101, P.O. Box 980126, Richmond, VA, 23298, USA.

The Multidimensional Peer Victimization Scale (MPVS; Mynard & Joseph, 2000) is a 16-item self-report scale that captures peer victimization across four dimensions: physical victimization, verbal victimization, social manipulation, and attacks on property. Performance of the scale has not been evaluated among older adolescents. We examined the factor structure, internal consistency reliability, and performance of the scale in two separate epidemiological U.S. samples representing different age groups: 9-14 year olds (N=610) and 15-17 year olds (N=524). The four-factor structure of the scale was affirmed in both samples, however; there was not metric invariance by gender in the younger age group. The scale and its subscales were found to have good internal consistency. Expected relationships between the MPVS and measures of irritability, anxiety, and depression were affirmed. Results support continued use of the MPVS among child and adolescent samples.
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http://dx.doi.org/10.1007/s10862-018-9678-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221199PMC
December 2018

A Population-Based Twin Study of Childhood Irritability and Internalizing Syndromes.

J Clin Child Adolesc Psychol 2020 Jul-Aug;49(4):524-534. Epub 2018 Oct 30.

Department of Psychiatry, Virginia Commonwealth University.

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. Children ages 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. 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. 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.
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http://dx.doi.org/10.1080/15374416.2018.1514612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491264PMC
November 2020

Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths.

Am J Psychiatry 2019 01 19;176(1):67-76. Epub 2018 Oct 19.

From the Department of Health and Human Services, Emotion and Development Branch and Scientific and Statistical Computing Core, NIMH, Bethesda, Md.; the Department of Psychiatry and the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond; the Department of Psychology, Wellesley College, Wellesley, Mass.; the University of Colorado School of Medicine, Aurora, Colo.; the Department of Medicine, Stanford University, Stanford, Calif.; the Departments of Psychology and Neuroscience, University of North Carolina at Chapel Hill; Emory University School of Medicine, Atlanta; the Department of Psychology, University of California at Los Angeles; and University of Michigan Medical School, Ann Arbor.

Objective: Childhood irritability is a common, impairing problem with changing age-related manifestations that predict long-term adverse outcomes. However, more investigation of overall and age-specific neural correlates is needed. Because youths with irritability exhibit exaggerated responses to frustrating stimuli, the authors used a frustration functional MRI (fMRI) paradigm to examine associations between irritability and neural activation and tested the moderating effect of age.

Method: The authors studied a transdiagnostic sample of 195 youths with varying levels of irritability (disruptive mood dysregulation disorder, N=52; anxiety disorder, N=42; attention deficit hyperactivity disorder, N=40; and healthy volunteers, N=61). Irritability was measured by parent and child reports on the Affective Reactivity Index. The fMRI paradigm was a cued-attention task differentiating neural activity in response to frustration (rigged feedback) from activity during attention orienting in the trial following frustration.

Results: Whole-brain activation analyses revealed associations with irritability during attention orienting following frustration. Irritability was positively associated with frontal-striatal activation, specifically in the dorsolateral prefrontal cortex, inferior frontal gyrus, and caudate. Age moderated the association between irritability and activation in some frontal and posterior regions (the anterior cingulate cortex, medial frontal gyrus, cuneus, precuneus, and superior parietal lobule [F=19.04-28.51, df=1, 189, partial eta squared=0.09-0.13]). Specifically, higher irritability was more strongly related to increased activation in younger youths compared with older youths.

Conclusions: Following frustration, levels of irritability correlated with activity in neural systems mediating attention orienting, top-down regulation of emotions, and motor execution. Although most associations were independent of age, dysfunction in the anterior cingulate cortex and posterior regions was more pronounced in young children with irritability.
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http://dx.doi.org/10.1176/appi.ajp.2018.18040491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408218PMC
January 2019

Age-Related Differences in the Structure of Genetic and Environmental Contributions to Types of Peer Victimization.

Behav Genet 2018 11 21;48(6):421-431. Epub 2018 Sep 21.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA, 23298-0126, USA.

The goal of the present investigation was to clarify and compare the structure of genetic and environmental influences on different types (e.g., physical, verbal) of peer victimization experienced by youth in pre-/early adolescence and mid-/late adolescence. Physical, verbal, social, and property-related peer victimization experiences were assessed in two twin samples (306 pairs, ages 9-14 and 294 pairs, ages 15-20). Cholesky decompositions of individual differences in victimization were conducted, and independent pathway (IP) and common pathway (CP) twin models were tested in each sample. In the younger sample, a Cholesky decomposition best described the structure of genetic and environmental contributors to peer victimization, with no evidence that common additive genetic or environmental factors influence different types of peer victimization. In the older sample, common environmental factors influenced peer victimization types via a general latent liability for peer victimization (i.e., a CP model). Whereas the pre-/early adolescent sample demonstrated no evidence of a shared genetic and environmental structure for different types of peer victimization, the mid-/late adolescent sample demonstrates the emergence of an environmentally-driven latent liability for peer victimization across peer victimization types.
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http://dx.doi.org/10.1007/s10519-018-9923-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233884PMC
November 2018

Resting Heart Rate Variability (HRV) in Adolescents and Young Adults from a Genetically-Informed Perspective.

Behav Genet 2018 09 11;48(5):386-396. Epub 2018 Jul 11.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, 800 E. Leigh St, Biotech One, Suite 101, Richmond, VA, 23219, USA.

Reduced heart rate variability (HRV) is associated with cardiac morbidity, mortality, and negative psychopathology. Most research concerning genetic influences on HRV has focused on adult populations, with fewer studies investigating the developmental period of adolescence and emerging adulthood. The current study estimated the genetic and environmental contributions to resting HRV in a sample of twins using various HRV time domain metrics to assess autonomic function across two different time measurement intervals (2.5- and 10-min). Five metrics of resting HRV [mean interbeat interval (IBI), the standard deviation of normal IBIs (SDNN), root square mean of successive differences between IBIs (RMSSD), cardiac vagal index (CVI), and cardiac sympathetic index (CSI)] were assessed in 421 twin pairs aged 14-20 during a baseline electrocardiogram. This was done for four successive 2.5-min intervals as well as the overall 10-min interval. Heritability (h) appeared consistent across intervals within each metric with the following estimates (collapsed across time intervals): mean IBI (h = 0.36-0.46), SDNN (h = 0.23-0.30), RMSSD (h = 0.36-0.39), CVI (h = 0.37-0.42), CSI (h = 0.33-0.46). Beyond additive genetic contributions, unique environment also was an important influence on HRV. Within each metric, a multivariate Cholesky decomposition further revealed evidence of genetic stability across the four successive 2.5-min intervals. The same models showed evidence for both genetic and environmental stability with some environmental attenuation and innovation. All measures of HRV were moderately heritable across time, with further analyses revealing consistent patterns of genetic and environmental influences over time. This study confirms that in an adolescent sample, the time interval used (2.5- vs. 10-min) to measure HRV time domain metrics does not affect the relative proportions of genetic and environmental influences.
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http://dx.doi.org/10.1007/s10519-018-9915-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345603PMC
September 2018

Genetic and Environmental Contributions of Negative Valence Systems to Internalizing Pathways.

Twin Res Hum Genet 2018 02;21(1):12-23

Department of Psychiatry,Virginia Commonwealth University,Richmond,Virginia,USA.

The genetic and environmental contributions of negative valence systems (NVS) to internalizing pathways study (also referred to as the Adolescent and Young Adult Twin Study) was designed to examine varying constructs of the NVS as they relate to the development of internalizing disorders from a genetically informed perspective. The goal of this study was to evaluate genetic and environmental contributions to potential psychiatric endophenotypes that contribute to internalizing psychopathology by studying adolescent and young adult twins longitudinally over a 2-year period. This report details the sample characteristics, study design, and methodology of this study. The first wave of data collection (i.e., time 1) is complete; the 2-year follow-up (i.e., time 2) is currently underway. A total of 430 twin pairs (N = 860 individual twins; 166 monozygotic pairs; 57.2% female) and 422 parents or legal guardians participated at time 1. Twin participants completed self-report surveys and participated in experimental paradigms to assess processes within the NVS. Additionally, parents completed surveys to report on themselves and their twin children. Findings from this study will help clarify the genetic and environmental influences of the NVS and their association with internalizing risk. The goal of this line of research is to develop methods for early internalizing disorder risk detection.
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http://dx.doi.org/10.1017/thg.2017.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884079PMC
February 2018

Clinical Correlates of Carbon Dioxide Hypersensitivity in Children.

J Am Acad Child Adolesc Psychiatry 2017 Dec 27;56(12):1089-1096.e1. Epub 2017 Sep 27.

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond.

Objective: Hypersensitivity to carbon dioxide (CO)-enriched air may be a promising risk marker for anxiety disorders. Among adult and adolescent samples, heterogeneity in distress response to the CO challenge task indexes 3 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 challenge task to clarify the association of CO hypersensitivity with anxiety and internalizing symptomatology in childhood.

Method: Healthy children from a community twin sample (N = 538; age 9-13 years) rated anxious distress every 2 minutes while breathing air enriched to 7.5% CO 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: Although all participants reported increased distress during the task, interindividual heterogeneity in distress indexed 3 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, 3 distinct trajectories emerged to capture interindividual heterogeneity in children's distress during the CO challenge task. These classes were distinguished by clinical validators that reinforce the association of CO hypersensitivity and internalizing disorder phenotypes in children.
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http://dx.doi.org/10.1016/j.jaac.2017.09.423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762134PMC
December 2017

Anxiety symptoms and children's eye gaze during fear learning.

J Child Psychol Psychiatry 2017 Nov 24;58(11):1276-1286. Epub 2017 Jul 24.

Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

Background: The eye region of the face is particularly relevant for decoding threat-related signals, such as fear. However, it is unclear if gaze patterns to the eyes can be influenced by fear learning. Previous studies examining gaze patterns in adults find an association between anxiety and eye gaze avoidance, although no studies to date examine how associations between anxiety symptoms and eye-viewing patterns manifest in children. The current study examined the effects of learning and trait anxiety on eye gaze using a face-based fear conditioning task developed for use in children.

Methods: Participants were 82 youth from a general population sample of twins (aged 9-13 years), exhibiting a range of anxiety symptoms. Participants underwent a fear conditioning paradigm where the conditioned stimuli (CS+) were two neutral faces, one of which was randomly selected to be paired with an aversive scream. Eye tracking, physiological, and subjective data were acquired. Children and parents reported their child's anxiety using the Screen for Child Anxiety Related Emotional Disorders.

Results: Conditioning influenced eye gaze patterns in that children looked longer and more frequently to the eye region of the CS+ than CS- face; this effect was present only during fear acquisition, not at baseline or extinction. Furthermore, consistent with past work in adults, anxiety symptoms were associated with eye gaze avoidance. Finally, gaze duration to the eye region mediated the effect of anxious traits on self-reported fear during acquisition.

Conclusions: Anxiety symptoms in children relate to face-viewing strategies deployed in the context of a fear learning experiment. This relationship may inform attempts to understand the relationship between pediatric anxiety symptoms and learning.
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http://dx.doi.org/10.1111/jcpp.12749DOI Listing
November 2017

Latent structure of negative valence measures in childhood.

Depress Anxiety 2017 08 22;34(8):742-751. Epub 2017 May 22.

Department of Psychiatry, Virginia Institute for Psychiatry and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.

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.
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http://dx.doi.org/10.1002/da.22656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542863PMC
August 2017

Clinical characteristics of latent classes of CO hypersensitivity in adolescents and young adults.

Behav Res Ther 2017 Jun 30;93:95-103. Epub 2017 Mar 30.

Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, 800 E Leigh Street, Suite 101, Richmond, VA, USA. Electronic address:

Although breathing CO-enriched air reliably increases anxiety, there is debate concerning the nature and specificity of CO hypersensitivity to panic risk and panic disorder versus anxiety disorders and related traits broadly, particularly among adolescents and emerging adults. The present study sought to clarify the association of CO hypersensitivity with internalizing conditions and symptoms among adolescents and young adults. Participants (N = 628) self-reported anxiety levels every 2 min while breathing air enriched to 7.5% CO for 8 min. Growth mixture models were used to examine the structure of anxiety trajectories during the task and the association of each trajectory with dimensional and diagnostic assessments of internalizing disorders. Three distinct trajectories emerged: overall low (low), overall high (high), and acutely increased anxiety (acute). Compared to the low class, the acute class reported elevated neuroticism, anxiety sensitivity, and stress whereas the high class reported elevated anxiety symptoms, depression symptoms, neuroticism, anxiety sensitivity, and increased likelihood of an anxiety disorder diagnosis. Moreover, the acute and high classes reported experiencing a panic-like event at a higher rate than the low class while participants in the high class terminated the task prematurely at a higher rate. The present study clarifies the nature of response to CO challenge. Three distinct response profiles emerged, which clarifies the manifestation of CO hypersensitivity in anxiety disorders with strong, though not unique, associations with panic-relevant traits.
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http://dx.doi.org/10.1016/j.brat.2017.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502686PMC
June 2017

Test-retest reliability of the facial expression labeling task.

Psychol Assess 2017 Dec 23;29(12):1537-1542. Epub 2017 Feb 23.

Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University.

Recognizing others' emotional expressions is vital for socioemotional development; impairments in this ability occur in several psychiatric disorders. Further study is needed to map the development of this ability and to evaluate its components as potential transdiagnostic endophenotypes. Before doing so, however, research is required to substantiate the test-retest reliability of scores of the face emotion identification tasks linked to developmental psychopathology. The current study estimated test-retest reliability of scores of one such task, the facial expression labeling task (FELT) among a sample of twin children (N = 157; ages 9-14). Participants completed the FELT at two visits two to five weeks apart. Participants discerned the emotion presented of faces depicting six emotions (i.e., happiness, anger, sadness, fear, surprise, and disgust) morphed with a neutral face to provide 10 levels of increasing emotional expressivity. The present study found strong test-retest reliability (Pearson r) of the FELT scores across all emotions. Results suggested that data from this task may be effectively analyzed using a latent growth curve model to estimate overall ability (i.e., intercept; r's = 0.76-0.85) and improvement as emotions become clearer (i.e., linear slope; r's = 0.69-0.83). Evidence of high test-retest reliability of this task's scores informs future developmental research and the potential identification of transdiagnostic endophenotypes for child psychopathology. (PsycINFO Database Record
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http://dx.doi.org/10.1037/pas0000439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568997PMC
December 2017

Test-retest reliability and validity of a frustration paradigm and irritability measures.

J Affect Disord 2017 Apr 23;212:38-45. Epub 2017 Jan 23.

Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

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.
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http://dx.doi.org/10.1016/j.jad.2017.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049456PMC
April 2017