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Objective: A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO(2)-induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO(2) are associated with elevated cortisol levels in juvenile offspring.Method: A total of 131 offspring (ages 9-19) of parents with panic disorder, major depression, and no mental disorder underwent CO(2) inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO(2) inhalation.Results: Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO(2) predicted elevated cortisol levels in offspring.Conclusions: As in adults, anxiety response to CO(2) in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses. [ABSTRACT FROM AUTHOR]

Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched extracellular vesicles' (EVs') microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biology. Neuron-enriched EVs' miRNA expression was measured from plasma samples collected from young people using a commercially available microarray platform while alcohol consumption was measured using the Alcohol Use Disorders Identification Test. Linear regression and network analyses were used to identify significantly differentially expressed miRNAs and to characterize the implicated biological pathways, respectively. Compared to alcohol naïve controls, young people reporting high alcohol consumption exhibited significantly higher expression of three neuron-enriched EVs' miRNAs including miR-30a-5p, miR-194-5p, and miR-339-3p, although only miR-30a-5p and miR-194-5p survived multiple test correction. The miRNA-miRNA interaction network inferred by a network inference algorithm did not detect any differentially expressed miRNAs with a high cutoff on edge scores. However, when the cutoff of the algorithm was reduced, five miRNAs were identified as interacting with miR-194-5p and miR-30a-5p. These seven miRNAs were associated with 25 biological functions; miR-194-5p was the most highly connected node and was highly correlated with the other miRNAs in this cluster. Our observed association between neuron-enriched EVs' miRNAs and alcohol consumption concurs with results from experimental animal models of alcohol use and suggests that high rates of alcohol consumption during the adolescent/young adult years may impact brain functioning and development by modulating miRNA expression., (© 2024. The Author(s).)

Salivary alpha amylase (sAA) is a common measure of stress reactivity, primarily reflecting sympathetic nervous system activity. Salivary cortisol is also a reliable, frequently used biomarker of stress and reflects the hypothalamic-pituitary-adrenal (HPA) axis response. This study examined heritability across varying metrics of sAA in response to a social evaluative stressor, the Trier Social Stress Test (TSST). The goal of this study was to estimate genetic and environmental influences on measurements of sAA stress reactivity. Moreover, we evaluated the shared genetic covariation between sAA and cortisol. Participants included twins aged 15-20 years (54% female). We measured alpha amylase and cortisol reactivity to the TSST via serial salivary cortisol samples collected pre- and post-TSST. Modest to moderate heritability estimates (11-64%) were observed across measures purported to capture alpha amylase stress reactivity (peak, area under the curve, baseline-to-peak change). Findings also indicate that sAA baseline and peak are primarily influenced by a shared genetic factor. There was no evidence of shared genetic influences between sAA and cortisol. These findings suggest the genetic control of the HPA and Sympathetic Adreno-Medullar axis are genetically independent of one another despite both playing a role in response to stressors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Although epigenome-wide association studies (EWAS) have been successful in identifying DNA methylation (DNAm) patterns associated with disease states, any further characterization of etiologic mechanisms underlying disease remains elusive. This knowledge gap does not originate from a lack of DNAm-trait associations, but rather stems from study design issues that affect the interpretability of EWAS results. Despite known limitations in predicting the function of a particular CpG site, most EWAS maintain the broad assumption that altered DNAm results in a concomitant change of transcription at the most proximal gene. This study integrated DNAm and gene expression (GE) measurements in two cohorts, the Adolescent and Young Adult Twin Study (AYATS) and the Pregnancy, Race, Environment, Genes (PREG) study, to improve the understanding of epigenomic regulatory mechanisms. CpG sites associated with GE in cis were enriched in areas of transcription factor binding and areas of intermediate-to-low CpG density. CpG sites associated with trans GE were also enriched in areas of known regulatory significance, including enhancer regions. These results highlight issues with restricting DNAm-transcript annotations to small genomic intervals and question the validity of assuming a cis DNAm-GE pathway. Based on these findings, the interpretation of EWAS results is limited in studies without multi-omic support and further research should identify genomic regions in which GE-associated DNAm is overrepresented. An in-depth characterization of GE-associated CpG sites could improve predictions of the downstream functional impact of altered DNAm and inform best practices for interpreting DNAm-trait associations generated by EWAS.

Objective: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur, with elevated rates of both disorders in lesbian, gay, or bisexual (LGB) samples. Few studies have compared the strength of PTSD-AUD associations between LGB and heterosexual individuals or evaluated the role of nontraumatic LGB discrimination in these relationships among sexual minorities., Method: The current study utilized nationally representative epidemiological data ( N = 29,646) to (a) examine whether associations between lifetime trauma endorsement/PTSD and lifetime alcohol dependence (AD) differ as a function of sexual minority status and (b) evaluate the role of LGB-specific discrimination in trauma/PTSD and AD associations among LGB individuals., Results: Logistic regression analyses showed the association between lifetime trauma endorsement and lifetime AD was significantly greater in magnitude for LGB individuals (odds ratio [ OR ] = 2.17) compared to heterosexual individuals ( OR = 1.32; Z = 2.51, p < .05). The magnitude of the association between lifetime PTSD and lifetime AD was not greater in the LGB subsample ( OR = 2.11) than the heterosexual subsample ( OR = 1.71; Z = 0.63, p > .05), after controlling for trauma endorsement. Among the LGB subsample, logistic regression analyses did not support a significant main effect for LGB discrimination nor an interaction between trauma endorsement and nontraumatic LGB discrimination, nor between PTSD and nontraumatic LGB discrimination, on lifetime AD ( p s > .05)., Conclusions: LGB individuals demonstrate stronger associations between lifetime trauma endorsement and AD, relative to heterosexual counterparts; however, this association may not be accounted for or moderated by nontraumatic LGB discrimination. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Multiple psychiatric disorders are associated with difficulties in facial emotion recognition. However, generalized anxiety disorder may be associated with more accurate recognition of others' emotional expressions, particularly expressions of happiness and fear, which index safety and threat. Children aged 9-14 from a community sample (N = 601) completed a facial emotion labeling task. Children's symptoms of depressive and anxiety syndromes were assessed by self- and parent-report. Elevated symptoms of generalized anxiety disorder were associated with more accurate facial emotion recognition (β = 0.16, p = 0.007), specifically recognition of happiness (β = 0.17, p = 0.002) and fear (β = 0.15, p = 0.006). Elevated depressive symptoms were associated with less accurate facial emotion recognition (β = -0.12, p = 0.018), specifically happiness (β = -0.15, p = 0.002). Elevated symptoms of separation anxiety disorder were also associated with less accurate facial emotion recognition (β = -0.16, p = 0.003), specifically happiness (β = -0.15, p = 0.006) and fear (β = -0.15, p = 0.005), which highlights the importance of distinguishing between anxiety syndromes. Results held when adjusting for child age and sex. Evidence that symptoms of generalized anxiety disorder are associated with more accurate recognition of happiness and fear is consistent with theories of heightened social vigilance and support a transdiagnostic role of facial emotion recognition that may inform the psychosocial development of youth with anxiety and depressive symptoms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Maternal age is an established predictor of preterm birth independent of other recognized risk factors. The use of chronological age makes the assumption that individuals age at a similar rate. Therefore, it does not capture interindividual differences that may exist due to genetic background and environmental exposures. As a result, there is a need to identify biomarkers that more closely index the rate of cellular aging. One potential candidate is biological age (BA) estimated by the DNA methylome. This study investigated whether maternal BA, estimated in either early and/or late pregnancy, predicts gestational age at birth. BA was estimated from a genome-wide DNA methylation platform using the Horvath algorithm. Linear regression methods assessed the relationship between BA and pregnancy outcomes, including gestational age at birth and prenatal perceived stress, in a primary and replication cohort. Prenatal BA estimates from early pregnancy explained variance in gestational age at birth above and beyond the influence of other recognized preterm birth risk factors. Sensitivity analyses indicated that this signal was driven primarily by self-identified African American participants. This predictive relationship was sensitive to small variations in the BA estimation algorithm. Benefits and limitations of using BA in translational research and clinical applications for preterm birth are considered., (© 2021. The Author(s).)

The current study examined bidirectional relations between anxious symptoms and two forms of peer victimization (i.e., overt and relational) within an underrepresented sample of urban adolescents during key transition periods (i.e., elementary to middle school; middle school to high school) and the following 2 years. A predominantly African American sample (91%) of 358 adolescents (56% female, mean age = 12.10 years) living in low-income urban areas were assessed annually across 4 years. Using self-report measures, adolescents reported on their past year experiences of anxiety and peer victimization. Longitudinal path analyses tested progressively complex models for each type of victimization. Anxious symptoms predicted both overt and relational victimization at the time of transition (Wave 1 to Wave 2) and the following year (Wave 2 to Wave 3). Furthermore, whereas previous levels of victimization and future anxious symptoms were positively correlated over time, only relational victimization at Wave 1 predicted anxious symptoms at Wave 2. Prior levels of each construct were the strongest predictor of future outcomes (e.g., anxious symptoms at Wave 1 predicting anxious symptoms at Wave 2). Overall, there was little support for bidirectional relations between anxiety symptoms and peer victimization. Intervention and prevention programs seeking to reduce peer victimization or anxiety should start by targeting the symptom/behavior of interest. Interventions that target anxious thoughts and feelings during these key transition times in adolescence should be assessed as areas of priority.

Introduction: As the use of electronic cigarette (EC) continues to rise in the United States, especially among adolescents and young adults, it is necessary to better understand the factors associated with EC initiation. Specifically, it is unclear how genetic and environmental contributions influence the initiation of EC. Furthermore, the degree to which genetic and environmental influences are shared between EC initiation and conventional cigarette (CC) initiation is unknown., Methods: A sample of young adult twins ages 15-20 (N = 858 individuals; 421 complete twin pairs) was used to estimate the genetic and environmental influences on the liability of initiation unique to EC and CC as well as the degree to which these factors are shared between the two. Approximately 24% of participants initiated the use of EC, 19% initiated the use of CC, and 11% initiated the dual use., Results: Combined contributions of additive genetic and shared environmental influences were significant for CC (ACC = 0.19 [95% confidence interval {CI} = 0-0.79], p = 0.57; CCC = 0.42 [95% CI = 0-0.70], p = 0.13) and EC (AEC = 0.25 [95% CI = 0-0.83, p = 0.44; CEC = 0.42 [95% CI = 0-0.73], p = 0.12), whereas unique environmental influences were significant (ECC = 0.39 [95% CI = 0.18-0.57], p < 0.001; EEC = 0.32 [95% CI = 0.14-0.56], p < 0.001). Results also demonstrated a significant overlap of the unique environmental (rE = 0.87, p < 0.001) and familial influences contributing to correlation between the two phenotypes in the bivariate analysis., Conclusions: These preliminary results suggest that both genes and environmental influences are potential drivers of EC initiation among adolescents and young adults., Implications: This article is the first to use a sample of twin to estimate the contributions of genetic and environmental influences toward EC initiation and estimate the potential for overlapping influences with CC initiation. This study has implications for future debate about the etiology of EC and CC use with respect to potential overlapping genetic and environmental influences., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Individuals vary in their response to psychological and physiological stressors, and this reactivity can be captured using measures of cortisol. Previous research suggests cortisol reactivity is under some degree of genetic control; however, the measures used have varied widely. This study (N = 524) examined potential differences in heritability across varying cortisol metrics of stress reactivity following the Trier Social Stress Test (TSST) and whether these measures are genetically or environmentally interrelated. Participants included twins aged 15-20 years (56% female). Cortisol reactivity to the TSST was assessed via serial salivary cortisol samples collected pre- and post-TSST. Modest to moderate heritability estimates (12% [95CI: 1-36%] - 45% [95CI: 16-69%]) were observed across measures purported to capture stress reactivity (peak, area under the curve [AUC], baseline-to-peak change). Findings also demonstrate both shared and unique genetic and environmental influences between baseline cortisol and cortisol reactivity. Minimal to no additional genetic innovations above and beyond the contributions of peak cortisol were found for other measures of cortisol reactivity such as AUC. This study is one of the largest twin-based samples to examine the heritability of cortisol reactivity, and results suggest that simpler measures of cortisol reactivity demonstrate higher heritability compared to more complex measurements., (Copyright © 2021. Published by Elsevier Ltd.)

Neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyper-activity disorder (ADHD), represent a group of conditions that manifest early in child development and produce impairments across multiple domains of functioning. Although a number of pharmacological and psychosocial treatments exist to improve the symptoms associated with these syndromes, treatment advances have lagged. The Precision Medicine Initiative was launched with the goal of revolutionizing medicine by progressing beyond the historical one-size-fits-all approach. In this review, we evaluate current research efforts to personalize treatments for ASD and ADHD. Most pharmacogenetic testing has focused on the cytochrome P450 enzyme family with a particular focus on CYP2D6 and CYP2C19, which are genes that produce an enzyme that acts as a key metabolizer of many prescribed medications. This article provides an update on the state of the field of pharmacogenetics and "therapy-genetics" in the context of ASD and ADHD, and it also encourages clinicians to follow US Food and Drug Administration recommendations regarding pharmacogenetic testing.

Depression onset during and after pregnancy is prevalent and associated with significant implications for maternal, child, and family health. Although environmental risk factors important to the expression of pregnancy-related depression are well known, knowledge of the genetic underpinning is limited. Given the joint contribution of environmental and genetic factors to depression risk liability, DNA methylation presents itself as an ideal biomarker to investigate basic mechanisms and opportunities for translational research to care for pregnancy-related depression health outcomes. This article is an introduction to DNA methylation and its potential to serve as a marker of depression risk during pregnancy and the postpartum. This commentary discusses current clinical uses of DNA methylation-based testing and how it may be applied to perinatal depression clinical care and management., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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 ( N = 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.

DNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The foetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behaviour of individual genes. The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation.

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.

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.

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., (© 2020 Wiley Periodicals, Inc.)

Background: Perinatal depressive symptoms have been linked to adverse maternal and infant health outcomes. The etiology associated with perinatal depressive psychopathology is poorly understood, but accumulating evidence suggests that understanding inter-individual differences in DNA methylation (DNAm) patterning may provide insight regarding the genomic regions salient to the risk liability of perinatal depressive psychopathology., Results: Genome-wide DNAm was measured in maternal peripheral blood using the Infinium MethylationEPIC microarray. Ninety-two participants (46% African-American) had DNAm samples that passed all quality control metrics, and all participants were within 7 months of delivery. Linear models were constructed to identify differentially methylated sites and regions, and permutation testing was utilized to assess significance. Differentially methylated regions (DMRs) were defined as genomic regions of consistent DNAm change with at least two probes within 1 kb of each other. Maternal age, current smoking status, estimated cell-type proportions, ancestry-relevant principal components, days since delivery, and chip position served as covariates to adjust for technical and biological factors. Current postpartum depressive symptoms were measured using the Edinburgh Postnatal Depression Scale. Ninety-eight DMRs were significant (false discovery rate < 5%) and overlapped 92 genes. Three of the regions overlap loci from the latest Psychiatric Genomics Consortium meta-analysis of depression., Conclusions: Many of the genes identified in this analysis corroborate previous allelic, transcriptomic, and DNAm association results related to depressive phenotypes. Future work should integrate data from multi-omic platforms to understand the functional relevance of these DMRs and refine DNAm association results by limiting phenotypic heterogeneity and clarifying if DNAm differences relate to the timing of onset, severity, duration of perinatal mental health outcomes of the current pregnancy or to previous history of depressive psychopathology.

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., (© 2019 Association for Child and Adolescent Mental Health.)

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., (© 2019 Association for Child and Adolescent Mental Health.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Posttraumatic stress disorder (PTSD) often co-occurs with panic disorder (PD), with some etiological models positing a causal role of panic reactivity in PTSD onset; however, data addressing the temporal ordering of these conditions are lacking. The aim of this study was to examine the bi-directional associations between PD and PTSD in a nationally representative, epidemiologic sample of trauma-exposed adults., Methods: Participants were community-dwelling adults (62.6% women; M age  = 48.9, SD 16.3) with lifetime DSM-IV PTSD criterion A trauma exposure drawn from the 2001/2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and re-interviewed in 2004/5 (N = 12,467). Cox discrete-time proportional hazards models with time-varying covariates were used to investigate the bi-directional associations between lifetime PD and PTSD, accounting for demographic characteristics, trauma load, and lifetime history of major depression, generalized anxiety disorder, and social anxiety disorder., Results: PD was significantly associated with subsequent onset of PTSD (HR 1.210, 95%CI = 1.207-1.214, p < .001), and PTSD was significantly associated with onset of PD (HR 1.601, 95% CI 1.597-1.604, p < .001). The association between PTSD and subsequent PD was stronger in magnitude than that between PD and subsequent PTSD (Z = - 275.21, p < .01). Men evidenced stronger associations between PD and PTSD compared to women., Conclusions: Results were consistent with a bidirectional pathway of risk, whereby PD significantly increased risk for the development of PTSD, and PTSD significantly increased risk for PD. Given the association between PTSD and subsequent PD, particularly among men, clinicians may consider supplementing PTSD treatment with panic-specific interventions, such as interoceptive exposure, to prevent or treat this disabling comorbidity.

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 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 = 0.59) 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 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., (© 2019 Society for Psychophysiological Research.)

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., (© 2019 Wiley Periodicals, Inc.)

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 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.

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., Competing Interests: Conflict of Interest: Meridith L. Eastman declares that she has no conflict of interest. Ashlee A. Moore declares that she has no conflict of interest. Jennifer Cecilione declares that she has no conflict of interest. John M. Hettema declares that he has no conflict of interest. Roxann Roberson-Nay declares that she has no conflict of interest. Conflict of interest: The authors each declare that they have no conflict of interest.

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., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

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.

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 2 ) appeared consistent across intervals within each metric with the following estimates (collapsed across time intervals): mean IBI (h 2  = 0.36-0.46), SDNN (h 2  = 0.23-0.30), RMSSD (h 2  = 0.36-0.39), CVI (h 2  = 0.37-0.42), CSI (h 2  = 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.

Purpose: The goal of the Pregnancy, Race, Environment, Genes study was to understand how social and environmental determinants of health (SEDH), pregnancy-specific environments (PSE) and biological processes influence the timing of birth and account for the racial disparity in preterm birth. The study followed a racially diverse longitudinal cohort throughout pregnancy and included repeated measures of PSE and DNA methylation (DNAm) over the course of gestation and up to 1 year into the postpartum period., Participants: All women were between 18 and 40 years of age with singleton pregnancies and no diagnosis of diabetes or indication of assisted reproductive technology. Both mother and father had to self-identify as either African-American (AA) or European-American (EA). Maternal peripheral blood samples along with self-report questionnaires measuring SEDH and PSE factors were collected at four pregnancy visits, and umbilical cord blood was obtained at birth. A subset of participants returned for two additional postpartum visits, during which additional questionnaires and maternal blood samples were collected. The pregnancy and postpartum extension included n=240 (AA=126; EA=114) and n=104 (AA=50; EA=54), respectively., Findings to Date: One hundred seventy-seven women (AA=89, EA=88) met full inclusion criteria out of a total of 240 who were initially enrolled. Of the 63 participants who met exclusion criteria after enrolment, 44 (69.8%) were associated with a medical reason. Mean gestational age at birth was significantly shorter for the AA participants by 5.1 days (M=272.5 (SD=10.5) days vs M=277.6 (SD=8.3))., Future Plans: Future studies will focus on identifying key environmental factors that influence DNAm change across pregnancy and account for racial differences in preterm birth., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Major depression during the peripartum (MDP) period carries significant public health impact due to the potential adverse effects on maternal, infant, and family outcomes., Methods: As part of a larger longitudinal study, this cross-sectional observational study sought to build upon the current literature on the prevalence and predictors of depression in the early second trimester of pregnancy, as related to generally accepted risk factors and other less explored risk factors., Results: The findings from this study suggest that in this sample of 230 black and white women at ∼14 weeks gestation, ∼19% endorsed depressive symptoms and that the most important predictors of depression in pregnancy were a preconception history of a mental health issue (e.g., lifetime depressive episode) and perceived stress. Other relevant predictors were pregnancy-related anxiety, income, and stressful life events., Conclusion/clinical Relevance: It is important for clinicians not only to screen for MDP during prenatal visits by asking about current depressive, stress, and anxiety symptoms but also to identify patients at risk for MDP by asking simple questions about history of preconception/lifetime episodes of depression and stressful life events. Given the variance accounted for by lifetime depression, additional research into how clinicians may approach this important topic is warranted. For example, checklists given in the waiting room may be less likely to elicit endorsement compared with conversations aimed to normalize the range of depressive histories that may have relevance to obstetric health.

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.

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, ((c) 2017 APA, all rights reserved).)

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 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 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; age 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: 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 2 challenge task. These classes were distinguished by clinical validators that reinforce the association of CO 2 hypersensitivity and internalizing disorder phenotypes in children., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Panic disorder is characterized by sudden, repeated, and unexpected attacks of intense fear and overwhelming anxiety about when another attack may strike. Patients with panic disorder and healthy individuals with a history of panic attacks show a hypersensitivity to unpredictable threats, suggesting a possible link between panic and sustained anxiety. The purpose of this study was to determine the degree to which induced symptoms of panic relate to fear and anxiety, as well as activity in the neural systems that mediate and regulate these affective states. Psychological and physiological symptoms of panic were assessed during an 8-min 7.5% CO 2 challenge task. Psychological, physiological, and neural symptoms of fear and anxiety were measured during two sessions (one psychophysiology and one functional magnetic resonance imaging where subjects experienced several blocks of no threat (N), predictable shock (P), and unpredictable shock (U; NPU threat task). We used a principle component analysis to characterize panic susceptibility (PS), and found that PS significantly predicted dorsolateral prefrontal cortex (dlPFC) activity to the unpredictable cue during the NPU threat task. When examining the weighted beta coefficients from this analysis, we observed that self-reported fear/anxiety during the CO 2 challenge negatively loaded onto dlPFC activity during the NPU task. Consistent with this observation, dlPFC activity during the unpredictable cue was also negatively correlated with anxiety during the NPU sessions. Together, these results suggest that panic symptoms and anxiety are regulated by the same prefrontal cognitive control system.

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., (© 2017 Association for Child and Adolescent Mental Health.)

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., (© 2017 Wiley Periodicals, Inc.)

Objective: Posttraumatic stress disorder (PTSD) and alcohol dependence (AD) frequently co-occur; however, epidemiologic studies of temporal associations between PTSD and AD are limited. The aims of this study were (a) to investigate the bidirectional associations between PTSD and AD and (b) to examine demographic and clinical correlates of order-of-onset among individuals with PTSD and AD., Method: Participants were 11,103 adults (60.6% women; Mage = 48.7 years, SD = 15.9) from the National Epidemiologic Survey on Alcohol and Related Conditions who endorsed lifetime alcohol consumption and DSM-IV PTSD Criterion A trauma exposure (American Psychiatric Association, 2000). Cox proportional hazards models with time-dependent covariates were used to evaluate bidirectional associations between PTSD and AD. Sex differences were assessed using stratified analyses., Results: After adjusting for demographic, trauma, and alcohol characteristics, PTSD was associated with greater likelihood of subsequent AD (hazard ratio [HR] = 1.359, 95% CI = 1.357-1.362), and AD was associated with greater likelihood of subsequent PTSD (HR = 1.274, 95% CI = 1.271-1.277). Bidirectional associations between PTSD and AD were stronger for women compared with men. Among individuals with PTSD and AD, initial onset of PTSD was associated with younger age of first potentially traumatic event. Initial onset of AD was associated with earlier initiation of alcohol use, earlier onset of heavy alcohol use, family history of alcohol problems, and history of generalized anxiety disorder and social anxiety disorder for women but not men. Initial AD was associated with lifetime panic disorder for men and women., Conclusions: Etiology of PTSD and AD is heterogeneous, and order of onset may reflect differing risk pathways. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Although breathing CO 2 -enriched air reliably increases anxiety, there is debate concerning the nature and specificity of CO 2 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 2 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 2 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 2 challenge. Three distinct response profiles emerged, which clarifies the manifestation of CO 2 hypersensitivity in anxiety disorders with strong, though not unique, associations with panic-relevant traits., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The course of conduct disorder (CD) is heterogeneous. Moffitt proposed the heuristic of life course persistent (LCP) and adolescence limited (AL) to differentiate etiologically distinct forms of antisocial behavior (AB), each with distinct predictors and consequences, although a few studies have assessed this demarcation within the context of CD. The objective of this study was to apply Moffitt's taxonomy in a nationally representative US sample to investigate the prevalence, predictors, and outcomes of LCP and AL CD., Methods: Data come from the Collaborative Psychiatric Epidemiology Studies, a set of population-based nationally representative cross-sectional surveys (N = 20,130). Predictors included harsh discipline, maternal and paternal closeness, poverty in childhood, history of learning disability, parental deviance, and nativity. Outcomes included substance use, employment status, education attainment, marital status, income level, and self-rated mental and physical health., Results: The prevalence of LCP and AL CD was 0.5 and 4.6%, respectively, for females, and 1.9 and 5.1%, respectively, for males. Low childhood SES [Odds Ratio (OR) = 3.49], lack of maternal closeness (OR = 2.50), and history of harsh discipline (OR = 2.17) increased odds of LCP group membership. The LCP group had higher odds of developing substance use disorders (OR = 2.00) relative to AL., Conclusions: LCP CD is more strongly influenced by childhood environment and confers increased odds for substance use problems in adulthood relative to AL CD.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)