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Emotion dysregulation (ED) is prevalent among youth with Attention-Deficit/Hyperactivity Disorder (ADHD) and significantly impacts functioning. Nuanced measurement of ED is central to understanding its role in this disorder and informing treatment approaches. The present study examined the factor structure of the Emotion Regulation Checklist (ERC) among children with ADHD with and without Oppositional Defiant Disorder (ODD). Exploratory factor analysis (EFA) conducted in a sample of 328 youth (mean age = 6.08) with ADHD indicated a four-factor solution, comprised of the following factors: Negative Emotion Lability, Positive Emotion Lability, Socially Appropriate Affect, and Socially Incongruent Affect. The Negative and Positive Emotion Lability subscales assess the reactivity of negatively and positively valenced emotions, respectively. The Socially Appropriate and Socially Incongruent Affect subscales provide an assessment of social-emotional functioning. All subscales discriminated between children with ADHD only and ADHD with co-morbid ODD, such that children with ODD had greater emotional lability and social-emotional difficulties. This revised factor structure of the ERC facilitates a uniquely brief, yet multifaceted and specific, assessment of emotional difficulties in children with ADHD that can inform treatment planning and operationalize emotional reactivity and social-emotional functioning in future research efforts.

Humans are reliant on their caregivers for an extended period of time, offering numerous opportunities for environmental factors, such as parental attitudes and behaviors, to impact brain development. The default mode network is a neural system encompassing the medial prefrontal cortex, posterior cingulate cortex, precuneus, and temporo-parietal junction, which is implicated in aspects of cognition and psychopathology. Delayed default mode network maturation in children and adolescents has been associated with greater general dimensional psychopathology, and positive parenting behaviors have been suggested to serve as protective mechanisms against atypical default mode network development. The current study aimed to extend the existing research by examining whether within- default mode network resting-state functional connectivity would mediate the relation between parental acceptance/warmth and youth psychopathology. Data from the Adolescent Brain and Cognitive Development study, which included a community sample of 9,058 children ages 9-10.9 years, were analyzed to test this prediction. Results from the analysis demonstrated a significant mediation, where greater parental acceptance/warmth predicted greater within- default mode network resting-state functional connectivity, which in turn predicted lower psychopathology. Our study provides preliminary support for the notion that positive parenting traits may reduce the risk for psychopathology in youth through their influence on the default mode network. Due to the cross-sectional nature of this study, we can only draw correlational inference; therefore, these relationships should be tested longitudinally in future investigations.

Among the many impacts of the Coronavirus disease (COVID-19) pandemic, one of the most dramatic was the immediate closure of in-person schooling in March/April 2020 when parents were faced with much greater responsibility in supporting their children's learning. Despite this, few studies have examined parents' own perspectives of this experience. The aims of this preliminary study were to (a) identify challenges, benefits, and useful strategies related to remote learning and (b) examine differences in findings across two countries, between parents of youth with and without attention-deficit/hyperactivity disorder (ADHD), and between parents of children and adolescents. To address these aims, parent responses to open-ended questions on the Home Adjustment to COVID-19 Scale (HACS; Becker, Breaux, et al., 2020) were examined across three studies conducted in the United States and Australia (N = 606, children: 68.5% male, ages 6-17 years). The challenges most frequently expressed by parents included the child's difficulty staying on task (23.8% of parents), lack of motivation (18.3%), remote learning factors (17.8%), and lack of social interaction (14.4%). The most frequently expressed strategy related to using routines and schedules (58.2%) and the biggest benefit was more family time (20.3%). Findings were largely consistent across countries, ADHD status, and age, with a few notable group differences. Given that the most common challenges involved child- (e.g., difficulties with staying on task and motivation), parent- (e.g., balancing remote learning with work responsibilities), and school- (e.g., remote instruction difficulties) related factors, there is a need for improved support across these systems going forward. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

OBJECTIVE: The DSM’s disruptive mood dysregulation disorder (DMDD), characterized by severe, chronic irritability, currently excludes children

Childhood experiences play a profound role in conferring risk and resilience for brain and behavioral development. However, how different facets of the environment shape neurodevelopment remains largely unknown. Here we sought to decompose heterogeneous relationships between environmental factors and brain structure in 989 school-aged children from the Adolescent Brain Cognitive Development Study. We applied a cross-modal integration and clustering approach called ‘Similarity Network Fusion’, which combined two brain morphometrics (i.e., cortical thickness and myelin-surrogate markers), and key environmental factors (i.e., trauma exposure, neighborhood safety, school environment, and family environment) to identify homogeneous subtypes. Depending on the subtyping resolution, results identified two or five subgroups, each characterized by distinct brain structure-environment profiles. Notably, more supportive caregiving and school environments were associated with increased myelination, whereas less supportive caregiving, higher family conflict and psychopathology, and higher perceived neighborhood safety were observed with increased cortical thickness. These subtypes were highly reproducible and predicted externalizing symptoms and overall mental health problems. Our findings support the theory that distinct environmental exposures differentially influence neurodevelopment. Delineating more precise associations between risk factors, protective factors, and brain development may inform approaches to enhance risk identification and optimize interventions targeting specific experiences.

Emotional lability and sensory sensitivity have been shown to contribute to the overall clinical picture in children with attention deficit hyperactivity disorder (ADHD; Dunn & Bennett, 2002; Sobanski et al., 2010). Further, both of these characteristics have been individually demonstrated to contribute to poorer quality of life, increased functional impairment, and poorer treatment response (Anastopoulos et al., 2010; Boterberg & Warreyn, 2016). However, to date, no study has evaluated the relationship among all three of these factors. The current study hypothesized that increased sensory sensitivity would moderate the relationship between hyperactive/impulsive symptoms of ADHD and emotional lability in youth. Results indicate that heightened sensory sensitivity strengthens the relationship between hyperactive/impulsive symptoms of ADHD and emotional lability in children with three or more clinically impairing ADHD symptoms. This dimensional approach was taken in accordance with growing evidence that even children with sub-threshold ADHD experience significant functional impairment and high rates of sensory sensitivity (Hong et al., 2014). These findings suggest that clinicians treating children with ADHD symptoms and emotional lability should consider assessing for sensory sensitivity as integration of multi-sensory techniques or referral to concurrent occupational therapy may significantly improve treatment outcomes and quality of life for these children and their families.

Introduction: Over the course of the 20th century, there has been a sharp increase in the consumption of saturated fat and refined sugars. This so-called "western diet" (WD) has been extensively linked to biological alterations and associated functional deficits in the hippocampus of animals. However, the effects of a WD on the human hippocampus are less well-characterized. This preliminary study aimed to extend prior animal work by investigating the effects of a WD on hippocampal volume in children. Methods: Twenty-one healthy children (ages 5-9) completed a structural T1-weighted magnetic resonance imaging scan. Bilateral hippocampal volumes (as regions-of-interest) and bilateral amygdala volumes (as medial temporal lobe control regions-of-interest) were calculated. WD variables were derived from the parent-completed Youth/Adolescent Food Frequency Questionnaire. Specifically, variables were calculated as percent of daily calories consumed from sugars, fats, or a combination of these (WD). Results: While the relationships between overall WD consumption and bilateral hippocampal volumes were not significant, increased fat consumption was significantly related to decreased left hippocampal volume. Sugar consumption was not related to hippocampal size. Control region volumes were not related to any diet variables. Discussion: This study is the first to directly link diet-specifically fat consumption-to decreased left hippocampal volume in children. This extends previous work showing smaller left hippocampal volume related to obesity in pediatric samples. Though preliminary, findings represent an important step toward understanding the impact of diet on child brain development.

Objective: The habenula is a small region in the epithalamus that contributes to the regulation of midbrain dopaminergic circuits implicated in attention-deficit hyperactivity disorder (ADHD). This investigation aims to evaluate the intrinsic functional connectivity (iFC) of the habenula in children with ADHD. Method: A total of 112 children (5-9 years; 75 ADHD, 37 healthy comparisons) completed anatomical and resting-state functional magnetic resonance imaging (MRI) scans. Habenula regions of interest (ROIs) were identified individually on normalized T1-weighted anatomical images. Seed-based iFC analyses and group comparisons were conducted for habenula ROIs, as well as thalamic ROIs to test the specificity of habenula findings. Results: Children with ADHD exhibited reduced habenula–putamen iFC compared with healthy comparisons. Group differences in thalamic iFC showed no overlap with habenular findings. Conclusion: These preliminary findings suggest that habenula–putamen iFC may be disrupted in children with ADHD. Further work is needed to confirm and elucidate the role of this circuit in ADHD pathophysiology.

The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC) imaging in 106 healthy individuals, ages 9–44. Broadly, the dorsal striatum (DS) is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS) is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC) that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns) and dorsal anterior cingulate cortex (dACC) that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents’ unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC–ACC connectivity and hyperactivity, and between aMCC–precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.

Autism spectrum disorder (ASD) is exceptionally heterogeneous in both clinical and physiopathological presentations. Clinical variability applies to ASD-specific symptoms and frequent comorbid psychopathology such as emotional lability (EL). To date, the physiopathological underpinnings of the co-occurrence of EL and ASD are unknown. As a first step, we examined within-ASD inter-individual variability of EL and its neuronal correlates using resting-state functional magnetic resonance imaging (R-fMRI). We analyzed R-fMRI data from 58 children diagnosed with ASD (5-12 years) in relation to the Conners' Parent Rating Scale EL index. We performed both an a priori amygdala region-of-interest (ROI) analysis, and a multivariate unbiased whole-brain data-driven approach. While no significant brain-behavior relationships were identified regarding amygdala intrinsic functional connectivity (iFC), multivariate whole-brain analyses revealed an extended functional circuitry centered on two regions: middle frontal gyrus (MFG) and posterior insula (PI). Follow-up parametric and nonparametric ROI-analyses of these regions revealed relationships between EL and MFG- and PI-iFC with default, salience, and visual networks suggesting that higher-order cognitive and somatosensory processes are critical for emotion regulation in ASD. We did not detect evidence of amygdala iFC underpinning EL in ASD. However, exploratory whole-brain analyses identified large-scale networks that have been previously reported abnormal in ASD. Future studies should consider EL as a potential source of neuronal heterogeneity in ASD and focus on multinetwork interactions.

Despite the success of available medical and psychosocial treatments, a sizable subgroup of individuals with commonly co-occurring disorders, generalized anxiety disorder (GAD) and major depressive disorder (MDD), fail to make sufficient treatment gains thereby prolonging their deficits in life functioning and satisfaction. Clinically, these patients often display temperamental features reflecting heightened sensitivity to underlying motivational systems related to threat/safety and reward/loss (e.g., somatic anxiety) as well as inordinate negative self-referential processing (e.g., worry, rumination). This profile may reflect disruption in two important neural networks associated with emotional/motivational salience (e.g., salience network) and self-referentiality (e.g., default network). Emotion Regulation Therapy (ERT) was developed to target this hypothesized profile and its neurobehavioral markers. In the present study, 22 GAD patients (with and without MDD) completed resting state MRI scans before receiving 16 sessions of ERT. To test study hypotheses, we examined the associations between baseline patterns of intrinsic functional connectivity (iFC) of the insula and of hubs within the default network (anterior and dorsal medial prefrontal cortex [MPFC] and posterior cingulate cortex [PCC]) and treatment-related changes in worry, somatic anxiety symptoms, and decentering. Results suggest that greater treatment linked reductions in worry were associated with iFC clusters in both the insular and parietal cortices. Greater treatment linked gains in decentering, a metacognitive process that involves the capacity to observe items that arise in the mind with healthy psychological distance that is targeted by ERT, was associated with iFC clusters in the anterior and posterior default network. The current study adds to the growing body of research implicating disruptions in the default and salience networks as promising targets of treatment for GAD with and without co-occurring MDD.

Prenatal exposure to maternal depression is common and puts offspring at risk for developing a range of neuropsychiatric disorders. Despite its prevalence and adverse associations, neurobiological processes by which prenatal maternal depression (PMD) confers risk remain poorly understood. Maternal mood and fetal behavior were assessed between 34 and 37 gestational weeks. Using resting-state functional magnetic resonance imaging (fMRI) and diffusion MRI, we examined functional and structural connectivity within amygdala–prefrontal circuits in 64 infants (mean age=5.8±1.7 weeks) with (n=20) and without (n=44) in utero exposure to PMD. Resting fMRI and diffusion MRI both indicated atypical amygdala–prefrontal connectivity in PMD-exposed infants: Resting fMRI indicated increased inverse, or negative, functional connectivity between the amygdala and the dorsal prefrontal cortex (PFC), bilaterally, and diffusion MRI indicated decreased structural connectivity between the right amygdala and the right ventral PFC. Spectral dynamic causal modeling supported these findings suggesting altered amygdala–PFC effective (or directed) connectivity in PMD-exposed infants. Last, path analyses supported a mechanistic account relating PMD to a third-trimester fetal behavior: PMD alters amygdala–PFC connectivity, which in turn, is associated with an increase in fetal heart rate reactivity to in utero perturbation. These data suggest that the maturation and coordination of central and peripheral physiology are altered by prenatal exposure to maternal depression. To the best of our knowledge, this is the first study to directly associate infant MRI measures with a behavior—fetal heart rate response, and supports hypotheses that PMD-associated variations in the development of amygdala–PFC circuits are relevant for future neurobehavioral maturation.

Deficits in emotion processing, a known clinical feature of major depressive disorder (MDD), have been widely investigated using emotional face paradigms and neuroimaging. However, most studies have not accounted for the high inter-subject variability of symptom severity. Similarly, only sparse research has focused on MDD in adolescence, early in the course of the illness. Here we sought to investigate neural responses to emotional faces using both categorical and dimensional analyses with a focus on anhedonia, a core symptom of MDD associated with poor outcomes. Nineteen medication-free depressed adolescents and 18 healthy controls (HC) were scanned during presentation of happy, sad, fearful, and neutral faces. ANCOVAs and regressions assessed group differences and relationships with illness and anhedonia severity, respectively. Findings included a group by valence interaction with depressed adolescents exhibiting decreased activity in the superior temporal gyrus (STG), putamen and premotor cortex. Post-hoc analyses confirmed decreased STG activity in MDD adolescents. Dimensional analyses revealed associations between illness severity and altered responses to negative faces in prefrontal, cingulate, striatal, and limbic regions. However, anhedonia severity was uniquely correlated with responses to happy faces in the prefrontal, cingulate, and insular regions. Our work highlights the need for studying specific symptoms dimensionally in psychiatric research.

In light of the current controversy about whether severe temper outbursts are diagnostic of mania in young children, we conducted a study to characterize such children, focusing on mania and other mood disorders, emotion regulation, and parental psychiatric history.Study participants included 51 5-9-year-old children with frequent, impairing outbursts (probands) and 24 non-referred controls without outbursts. Parents completed a lifetime clinical interview about their child, and rated their child's current mood and behavior. Teachers completed a behavior rating scale. To assess emotion regulation, children were administered the Balloons Game, which assesses emotion expressivity in response to frustration, under demands of high and low regulation. Parental lifetime diagnoses were ascertained in blind clinical interviews.No child had bipolar disorder, bipolar disorder not otherwise specified (NOS), or major depression (MDD). The most prevalent disorder was oppositional defiant disorder (88.2%), followed by attention-deficit/hyperactivity disorder (74.5%), anxiety disorders (49.0%), and non-MDD depressive disorders (33.3%). Eleven probands (21.6%) met criteria for severe mood dysregulation. During the Balloons Game, when there were no demands for self-regulation, children with severe outbursts showed reduced positive expressivity, and also showed significant deficits in controlling negative facial expressions when asked to do so. Anxiety disorders were the only diagnoses significantly elevated in probands' mothers.Overall, young children with severe temper outbursts do not present with bipolar disorder. Rather, disruptive behavior disorders with anxiety and depressive mood are common. In children with severe outbursts, deficits in regulating emotional facial expressions may reflect deficits controlling negative affect. This work represents a first step towards elucidating mechanisms underlying severe outbursts in young children.

In recent years, there has been much debate regarding the most appropriate diagnostic classification of children exhibiting emotion dysregulation in the form of irritability and severe temper outbursts. Most recently, this has resulted in the addition of a new diagnosis, Disruptive Mood Dysregulation Disorder (DMDD) in the DSM 5. The impetus for including this new disorder was to reduce the number of diagnoses that these children would typically receive; however, there is concern that it has only complicated matters rather than simplifying them. For example, a recent epidemiologic study shows that DMDD cannot be differentiated from oppositional defiant disorder (ODD) based on symptoms alone. Thus, these children are an ideal population in which to apply RDoC constructs in order to obtain greater clarity in terms of underlying processes and ultimately, inform nosology and appropriate interventions. The aim of this article is to provide a foundation for future research by examining extant theoretical and empirical evidence for the role of four key RDoC constructs in DMDD.

Adolescents engage in a wide range of risky behaviors that their older peers shun, and at an enormous cost. Despite being older, stronger, and healthier than children, adolescents face twice the risk of mortality and morbidity faced by their younger peers. Are adolescents really risk-seekers or does some richer underlying preference drive their love of the uncertain? To answer that question, we used standard experimental economic methods to assess the attitudes of 65 individuals ranging in age from 12 to 50 toward risk and ambiguity. Perhaps surprisingly, we found that adolescents were, if anything, more averse to clearly stated risks than their older peers. What distinguished adolescents was their willingness to accept ambiguous conditions—situations in which the likelihood of winning and losing is unknown. Though adults find ambiguous monetary lotteries undesirable, adolescents find them tolerable. This finding suggests that the higher level of risk-taking observed among adolescents may reflect a higher tolerance for the unknown. Biologically, such a tolerance may make sense, because it would allow young organisms to take better advantage of learning opportunities; it also suggests that policies that seek to inform adolescents of the risks, costs, and benefits of unexperienced dangerous behaviors may be effective and, when appropriate, could be used to complement policies that limit their experiences.

When a linear model is chosen by searching for the best subset among a set of candidate predictors, a fixed penalty such as that imposed by the Akaike information criterion may penalize model complexity inadequately, leading to biased model selection. We study resampling-based information criteria that aim to overcome this problem through improved estimation of the effective model dimension. The first proposed approach builds upon previous work on bootstrap-based model selection. We then propose a more novel approach based on cross-validation. Simulations and analyses of a functional neuroimaging data set illustrate the strong performance of our resampling-based methods, which are implemented in a new R package.

Studies of cognitive reappraisal have demonstrated that reinterpreting a stimulus can alter emotional responding, yet few studies have examined the durable effects associated with reinterpretation-based emotion regulation strategies. Evidence for the enduring effects of emotion regulation may be found in clinical studies that use cognitive restructuring (CR) techniques in cognitive-behavioral therapy (CBT) to alleviate anxiety. These techniques are based on cognitive theories of anxiety that suggest these disorders arise from biased cognitions; therefore, changing a person's thoughts will elicit durable changes in an individual's emotional responses. Despite the considerable success of CBT for anxiety disorders, durable effects associated with emotion regulation have not been thoroughly examined in the context of a laboratory paradigm. The goal of this study was to determine whether CR, a technique used in CBT and similar to cognitive reappraisal, could attenuate conditioned fear responses, and whether the effect would persist over time (24 hr). We conditioned participants using images of snakes or spiders that were occasionally paired with a mild shock to the wrist while we obtained subjective fear reports and electrodermal activity (EDA). After conditioning, half of the participants were randomly assigned to CR training aimed at decreasing their emotional response to the shock and the conditioned stimuli, while the other half received no such training. All participants returned 24 hr later to repeat the conditioning session. Compared with control participants, CR participants demonstrated a reduction in fear and EDA across sessions. These findings suggest that CR has durable effects on fear responding.

Risk avoidance is a hallmark of psychopathological conditions such as anxiety disorders. Yet few studies have examined its neural basis. The present work sought to identify the neural correlates of risk avoidance. While functional MRI scans were acquired, healthy adults ( N = 23) played a Wheel of Fortune game during which they chose to bet or pass on each of 104 proposed gamble trials. Participants also completed the Cognitive Appraisal of Risky Events (CARE, Fromme et al., 1997 ), a self-report measure of “real world” risky behavior. As expected, decision-making was associated with activation, as measured by increased BOLD responses, of the striatum, insula, anterior cingulate cortex, dorsolateral prefrontal cortex, and parietal lobe. Risk avoidance during probabilistic trials (percent of trials passed) was significantly correlated with precuneus and striatal responses to trials with a certain outcome (No-Risk). Similarly, “real world” risk avoidance, as measured by the CARE, was significantly correlated with precuneus activity during No-Risk trials. Collectively, these data suggest that precuneus and striatal responses to decision-making under certainty represent putative neural markers of risk avoidance in the laboratory and in the “real world.” Further, they underline the need to extend neuroimaging research on risk avoidance, and associated anxiety disorders, to posterior cortical regions.

Aggression is widely observed in children with attention deficit/hyperactivity disorder (ADHD) and has been frequently linked to frustration or the unsatisfied anticipation of reward. Although animal studies and human functional neuroimaging implicate altered reward processing in aggressive behaviors, no previous studies have documented the relationship between fronto-accumbal circuitry—a critical cortical pathway to subcortical limbic regions—and aggression in medication-naive children with ADHD. To address this, we collected behavioral measures and parental reports of aggression and impulsivity, as well as structural and diffusion MRI, from 30 children with ADHD and 31 healthy controls (HC) (mean age, 10±2.1 SD). Using grey matter morphometry and probabilistic tractography combined with multivariate statistical modeling (partial least squares regression and support vector regression), we identified anomalies within the fronto-accumbal circuit in childhood ADHD, which were associated with increased aggression. More specifically, children with ADHD showed reduced right accumbal volumes and frontal-accumbal white matter connectivity compared with HC. The magnitude of the accumbal volume reductions within the ADHD group was significantly correlated with increased aggression, an effect mediated by the relationship between the accumbal volume and impulsivity. Furthermore, aggression, but not impulsivity, was significantly explained by multivariate measures of fronto-accumbal white matter connectivity and cortical thickness within the orbitofrontal cortex. Our multi-modal imaging, combined with multivariate statistical modeling, indicates that the fronto-accumbal circuit is an important substrate of aggression in children with ADHD. These findings suggest that strategies aimed at probing the fronto-accumbal circuit may be beneficial for the treatment of aggressive behaviors in childhood ADHD.

Severe, chronic irritable mood in children has long presented achallenge to pediatric psychiatry becauseof its poor diagnostic specificity and its inclusion in numerous mood, anxiety, and disruptive behavior disorders (1). A consequence has been the frequent diagnosis of bipolar disorder in children with chronically irritable mood, thus redefining bipolar disorder in early life as a nonepisodic syndrome. It is likely that this diagnostic approach has contributed to the dramatic rise in the rate of pediatric visits for bipolar disorder in the United States, from an estimated 25 per 100,000 in 1994–95 to 1,003 per 100,000 in 2002–2003 (2). Approximately 60% of medical visits with this diagnosis result in treatment with polypharmacy, and 48% include an atypical antipsychotic. While antipsychotics ameliorate symptoms of mania in bipolar disorder (3) as well as aggression and irritability in autism (4), they have not been tested in other children with chronic irritability and severe outbursts. Thus, this clinical trend has caused concern about improper diagnosis and treatment. In the 1990s, efforts to better characterize adolescents with chronic irritability resulted in the delineation of a broad phenotype named “severe mood dysregulation” (5). In contrast to bipolar disorder, severe mood dysregulation is defined by nonepisodic irritability, exaggerated emotional reactivity, and hyperarousal. Severe mood dysregulation and bipolar disorder differ with regard to familial aggregation (6), physiological responses to frustration (7), and neural responses to social stimuli (8). Reanalysis of longitudinal data from the Great Smoky Mountains Study foundassociationsbetweenseveremooddysregulationand later depression (9). The relationship between early chronic irritability and later depressive disorders is consistent with findings that irritability symptoms in childhood (i.e., loses temper, easily annoyed) predict later depression (10–12). These findings provided the foundation for the diagnosis of disruptive mood dysregulation disorder (DMDD) and its placement among the DSM-5 depressive disorders, which emphasizes the disorder’s mood component and its distinction from the bipolar disorders. The core feature of DMDD is “chronic, severe persistent irritability” accompanied by severe temper outbursts, at least three times per week, that are out of proportion to provocation and inconsistent with developmental level. Symptoms are pervasive in the sense that they characterize the child’s comportment across multiple settings. The minimum duration of symptoms is 1 year (without interruption exceeding 3 months), with onset by age 10. These symptoms are consistent with those of severe mood dysregulation, with one exception: severe mood dysregulation includes symptoms of hyperarousal, which are not included in DMDD. The diagnosis is not applied before age 6 or after age 18 (an age range that approximates that of children in studies of severe mood dysregulation), if there is more than 1 day of manic or hypomanic symptoms, or if the symptoms are explained by another disorder. These clinical criteria indicate that DMDD, correctly, is not designed to include all children with severe outbursts. For example, in a cohort of 5- to 9-year-olds with a long history of frequent, severe temper outbursts (13), we found that half did not meet criteria for DMDD because they failed to exhibit chronic irritability.

Behavioral inhibition (BI) is a temperament identified early in life that is associated with increased risk for anxiety disorders. Amygdala hyperresponsivity, found both in behaviorally inhibited and anxious individuals, suggests that amygdala dysfunction may represent a marker of anxiety risk. However, broader amygdala networks have not been examined in individuals with a history of childhood BI. This study uses resting state fMRI to assess amygdala intrinsic functional connectivity (iFC) in 38 healthy young adults (19 with a history of BI, 19 with no history of BI) selected from a longitudinal study. Centromedial, basolateral, and superficial amygdala iFCs were compared between groups and examined in relation to self-report measures of anxiety. Group differences were observed in amygdala iFC with prefrontal cortex, striatum, anterior insula, and cerebellum. Adults characterized with BI in childhood endorsed greater state anxiety prior to entering the scanner, which was associated with several of the group differences. Findings support enduring effects of BI on amygdala circuitry, even in the absence of current psychopathology.

Item does not contain fulltext OBJECTIVE: A substantial proportion of children with attention-deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits manifesting as chronic irritability, severe temper outbursts, and aggression. The amygdala is implicated in emotion regulation, but its connectivity and relation to emotion regulation in ADHD has yet to be explored. The purpose of this study was to examine the relationship between intrinsic functional connectivity (iFC) of amygdala circuits and emotion regulation deficits in youth with ADHD. METHOD: Bilateral amygdala iFC was examined using functional magnetic resonance imaging in 63 children with ADHD, aged 6 to 13 years. First, we examined the relationship between amygdala IFC and parent ratings of emotional lability (EL) in children with ADHD. Second, we compared amygdala iFC across subgroups of children with ADHD and high EL (n = 18), ADHD and low EL (n = 20), and typically developing children (TDC), all with low EL (n = 19). RESULTS: Higher EL ratings were associated with greater positive iFC between the amygdala and rostral anterior cingulate cortex in youth with ADHD. EL scores were also negatively associated with iFC between bilateral amygdala and posterior insula/superior temporal gyrus. Patterns of amygdala-cortical iFC in ADHD participants with low EL were not different from the comparison group, and the effect sizes for these comparisons were smaller than those for the trend-level differences observed between the high-EL and TDC groups. CONCLUSIONS: In children with ADHD and a range of EL, deficits in emotion regulation were associated with altered amygdala-cortical iFC. When comparing groups that differed on ADHD status but not EL, differences in amygdala iFC were small and nonsignificant, highlighting the specificity of this finding to emotional deficits, independent of other ADHD symptoms.

BackgroundResearch on the neural correlates of risk-related behaviors and personality traits has provided insight into mechanisms underlying both normal and pathological decision-making. Task-based neuroimaging studies implicate a distributed network of brain regions in risky decision-making. What remains to be understood are the interactions between these regions and their relation to individual differences in personality variables associated with real-world risk-taking.Methodology/principal findingsWe employed resting state functional magnetic resonance imaging (R-fMRI) and resting state functional connectivity (RSFC) methods to investigate differences in the brain's intrinsic functional architecture associated with beliefs about the consequences of risky behavior. We obtained an individual measure of expected benefit from engaging in risky behavior, indicating a risk seeking or risk-averse personality, for each of 21 participants from whom we also collected a series of R-fMRI scans. The expected benefit scores were entered in statistical models assessing the RSFC of brain regions consistently implicated in both the evaluation of risk and reward, and cognitive control (i.e., orbitofrontal cortex, nucleus accumbens, lateral prefrontal cortex, dorsal anterior cingulate). We specifically focused on significant brain-behavior relationships that were stable across R-fMRI scans collected one year apart. Two stable expected benefit-RSFC relationships were observed: decreased expected benefit (increased risk-aversion) was associated with 1) stronger positive functional connectivity between right inferior frontal gyrus (IFG) and right insula, and 2) weaker negative functional connectivity between left nucleus accumbens and right parieto-occipital cortex.Conclusions/significanceTask-based activation in the IFG and insula has been associated with risk-aversion, while activation in the nucleus accumbens and parietal cortex has been associated with both risk seeking and risk-averse tendencies. Our results suggest that individual differences in attitudes toward risk-taking are reflected in the brain's functional architecture and may have implications for engaging in real-world risky behaviors.

Intolerance of uncertainty (IU) has contributed to our understanding of excessive worry and adult anxiety disorders, but there is a paucity of research on IU in child samples. This gap is due to the absence of a psychometrically sound measure of IU in youth. The present study adapted parallel child- and parent-report forms of the Intolerance of Uncertainty Scale (IUS) and examined the internal consistency, convergent validity, and classification properties of these forms in youth aged 7-17 (M = 11.6 years, SD = 2.6). Participating youth (N = 197; 100 girls, 97 boys) either met diagnostic criteria for an anxiety disorder (n = 73) or were nonreferred community participants (n = 124). The child-report form (i.e., IUS for Children, or IUSC), and to a lesser extent the parent-report form, demonstrated strong internal consistency and convergent validity, evidenced by significant associations with anxiety and worry (and reassurance-seeking in the case of the child-report form). Children diagnosed with anxiety disorders scored higher than nonreferred community youth on both forms. Receiver operating characteristic (ROC) analysis demonstrated acceptable overall utility in distinguishing the 2 groups of youth. Findings provide preliminary support for use of the IUSC for continuous measurement of children's ability to tolerate uncertainty.

Electrophysiological studies have long demonstrated a high degree of correlated activity between the left and right hemispheres, however little is known about regional variation in this interhemispheric coordination. Whereas cognitive models and neuroanatomical evidence suggest differences in coordination across primary sensory-motor cortices versus higher-order association areas, these have not been characterized. Here, we used resting-state functional magnetic resonance imaging data acquired from 62 healthy volunteers to examine interregional correlation in spontaneous low-frequency hemodynamic fluctuations. Using a probabilistic atlas, we correlated probability-weighted time series from 112 regions comprising the entire cerebrum. We then examined regional variation in correlated activity between homotopic regions, contrasting primary sensory-motor cortices, unimodal association areas, and heteromodal association areas. Consistent with previous studies, robustly correlated spontaneous activity was noted between all homotopic regions, which was significantly higher than that between nonhomotopic (heterotopic and intrahemispheric) regions. We further demonstrated substantial regional variation in homotopic interhemispheric correlations that was highly consistent across subjects. Specifically, there was a gradient of interhemispheric correlation, with highest correlations across primary sensory-motor cortices (0.758, SD = 0.152), significantly lower correlations across unimodal association areas (0.597, SD = 0.230) and still lower correlations across heteromodal association areas (0.517, SD = 0.226). These results demonstrate functional differences in interhemispheric coordination related to the brain's hierarchical subdivisions. Synchrony across primary cortices may reflect networks engaged in bilateral sensory integration and motor coordination, whereas lower coordination across heteromodal association areas is consistent with functional lateralization of these regions. This novel method of examining interhemispheric coordination may yield insights regarding diverse disease processes as well as healthy development.

Objective To examine attention bias toward threat faces in a large sample of anxiety-disordered youths using a well-established visual probe task. Method Study participants included 101 children and adolescents (ages 7–18 years) with generalized anxiety disorder, social phobia, and/or separation anxiety disorder enrolled in a multisite anxiety treatment study. Nonanxious youths ( n = 51; ages 9–18 years) were recruited separately. Participants were administered a computerized visual probe task that presents pairs of faces portraying threat (angry), positive (happy), and neutral expressions. They pressed a response key to indicate the spatial location of a probe that replaced one of the faces on each trial. Attention bias scores were calculated from response times to probes for each emotional face type. Results Compared to healthy youths, anxious participants demonstrated a greater attention bias toward threat faces. This threat bias in anxious patients did not significantly vary across the anxiety disorders. There was no group difference in attention bias toward happy faces. Conclusions These results suggest that pediatric anxiety disorders are associated with an attention bias toward threat. Future research may examine the manner in which cognitive bias in anxious youths changes with treatment. J. Am. Acad. Child Adolesc. Psychiatry , 2008;47(10):1189–1196.

The amygdala is composed of structurally and functionally distinct nuclei that contribute to the processing of emotion through interactions with other subcortical and cortical structures. While these circuits have been studied extensively in animals, human neuroimaging investigations of amygdala-based networks have typically considered the amygdala as a single structure, which likely masks contributions of individual amygdala subdivisions. The present study uses resting state functional magnetic resonance imaging (fMRI) to test whether distinct functional connectivity patterns, like those observed in animal studies, can be detected across three amygdala subdivisions: laterobasal, centromedial, and superficial. In a sample of 65 healthy adults, voxelwise regression analyses demonstrated positively-predicted ventral and negatively-predicted dorsal networks associated with the total amygdala, consistent with previous animal and human studies. Investigation of individual amygdala subdivisions revealed distinct differences in connectivity patterns within the amygdala and throughout the brain. Spontaneous activity in the laterobasal subdivision predicted activity in temporal and frontal regions, while activity in the centromedial nuclei predicted activity primarily in striatum. Activity in the superficial subdivision positively predicted activity throughout the limbic lobe. These findings suggest that resting state fMRI can be used to investigate human amygdala networks at a greater level of detail than previously appreciated, allowing for the further advancement of translational models.

Objective Generalized anxiety disorder (GAD) typically begins during adolescence and can persist into adulthood. The pathophysiological mechanisms underlying this disorder remain unclear. Recent evidence from resting state functional magnetic resonance imaging (R-fMRI) studies in adults suggests disruptions in amygdala-based circuitry; the present study examines this issue in adolescents with GAD. Method Resting state fMRI scans were obtained from 15 adolescents with GAD and 20 adolescents without anxiety who were group matched on age, sex, scanner, and intelligence. Functional connectivity of the centromedial, basolateral, and superficial amygdala subdivisions was compared between groups. We also assessed the relationship between amygdala network dysfunction and anxiety severity. Results Adolescents with GAD exhibited disruptions in amygdala-based intrinsic functional connectivity networks that included regions in medial prefrontal cortex, insula, and cerebellum. Positive correlations between anxiety severity scores and amygdala functional connectivity with insula and superior temporal gyrus were also observed within the GAD group. There was some evidence of greater overlap (less differentiation of connectivity patterns) of the right basolateral and centromedial amygdala networks in the adolescents with, relative to those without, GAD. Conclusions These findings suggest that adolescents with GAD manifest alterations in amygdala circuits involved in emotion processing, similar to findings in adults. In addition, disruptions were observed in amygdala-based networks involved in fear processing and the coding of interoceptive states.