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1.
Artigo em Inglês | MEDLINE | ID: mdl-32167803

RESUMO

Objective: Despite the advances in the field of neuroscience, many questions remain regarding the mechanisms of anxiety, as well as moderators of treatment outcome. Long-term adverse outcomes for anxious youth may relate to pathophysiologically based information processing patterns and self-referential beliefs, such as self-efficacy. In fact, there are no studies highlighting the relationship between self-efficacy and neurocircuitry in youth. The purpose of this study was to explore the relationships between self-efficacy, brain morphometry, and youth anxiety. Methods: Parent, child, and clinician ratings of anxiety symptoms and child-reported self-efficacy were analyzed in a sample of 8- to 17-year-old youth (n = 51). Measures were collected from all youth at baseline and during and after treatment for the patients. Anxious patients (n = 26) received 12 sessions of cognitive behavioral therapy (CBT). Moreover, imaging data obtained from all participants before treatment were utilized in analyses. Results: Patients reported lower self-efficacy than healthy volunteers. Across the entire sample, anxiety was negatively related to total, social, and emotional efficacy. Both social and emotional efficacy predicted anxiety posttreatment. In addition, social efficacy predicted social anxiety symptoms posttreatment and social efficacy increased across treatment. There were no significant relations between self-efficacy and neurocircuitry. Conclusions: Self-efficacy is an important treatment target for anxious youth. Although self-efficacy was not related to brain morphometry, self-efficacy beliefs may constitute an important mechanism through which CBT and psychopharmacological interventions decrease fear and anxiety symptoms in youth.

2.
Neuropsychologia ; : 107416, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173623

RESUMO

Children at risk for anxiety display elevated threat sensitivity and may inaccurately classify safe stimuli as threatening, a process known as overgeneralization. Little is known about whether such overgeneralization might stem from altered sensory representations of stimuli resembling threat, especially in youth. Here we implement representational similarity analysis of fMRI data to examine the similarity of neural representations of threat versus ambiguous or safe stimuli in threat and perceptual neurocircuitry among children at varying levels of anxiety traits. Three weeks after completing threat conditioning and extinction, children underwent a fMRI extinction recall task, during which they viewed the extinguished threat cue (CS+), safety cue (CS-) and generalization stimuli (GS) consisting of CS-/CS + blends. Multivoxel BOLD signal patterns were measured in seven regions of interest: four emotional areas (ventromedial prefrontal cortex (vmPFC), anterior insular cortex (AIC), dorsomedial prefrontal cortex (dmPFC), and amygdala) and three perceptual areas (inferior temporal cortex (ITC) and visual areas V1 and V4). Compared to low anxious children, children with high trait anxiety evidenced less neural pattern differentiation between the CS+ and similar GS, particularly in the vmPFC. Together, these results demonstrate the utility of multivariate neuroimaging approaches in arbitrating the relative contributions of perceptual versus emotional sources to threat generalization.

3.
Behav Ther ; 51(2): 283-293, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32138938

RESUMO

Irritability is impairing in youth and is the core feature of disruptive mood dysregulation disorder (DMDD). Currently, there are no established clinician-rated instruments to assess irritability in pediatric research and clinical settings. Clinician-rated measures ensure consistency of assessment across patients and are important specifically for treatment research. Here, we present data on the psychometric properties of the Clinician Affective Reactivity Index (CL-ARI), the first semistructured interview focused on pediatric irritability. The CL-ARI was administered to a transdiagnostic sample of 98 youth (M age = 12.66, SD = 2.47; 41% female). With respect to convergent validity, CL-ARI scores were (a) significantly higher for youth with DMDD than for any other diagnostic group, and (b) showed uniquely strong associations with other clinician-, parent-, and youth-report measures of irritability compared to measures of related constructs, such as anxiety. The three subscales of the CL-ARI (temper outbursts, irritable mood, impairment) showed excellent internal consistency. Test-retest reliability of the CL-ARI was adequate. These data support that irritability can be feasibly, validly, and reliably assessed by clinicians using the CL-ARI. A validated, gold-standard assessment of pediatric irritability is critical in advancing research and treatment efforts.

4.
Behav Ther ; 51(2): 211-222, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32138933

RESUMO

Children with anxiety disorders often present with other co-occurring symptom clusters, of which irritability is among the most highly co-occurring. Despite compelling clinical and pathophysiological evidence linking anxiety and irritability, little is known regarding the clinical presentation and associated impairment of children with both anxiety and irritability. In this study, our aims were to confirm the preponderance of irritability in clinically anxious children and compare clinically anxious children with irritability to those without irritability across sociodemographic, clinical, psychosocial, and family domains. Participants were 230 children with anxiety disorders (ages 6-14 years) and their mothers, and 91 healthy controls (ages 6-17 years) and their mothers. Of the clinically anxious children, 121 were anxious and irritable; 109 were anxious but not irritable. Irritability levels were significantly higher in the clinically anxious children compared with the healthy controls. Children with anxiety disorders and irritability presented with greater severity and impairment across clinical phenomenology, psychosocial, and family domains relative to anxious children without irritability. Regression analysis findings were convergent in that greater severity and impairment across these same domains predicted higher irritability levels in the children with anxiety disorders. Results support the meaningful distinction between anxious children with and without irritability. Implications of the findings are discussed particularly in regard to assessment and treatment and future research directions are delineated.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32004697

RESUMO

OBJECTIVE: The aim of this study is to identify the most appropriate threshold for Disruptive Mood Dysregulation Disorder (DMDD) diagnosis and the impact of potential changes in diagnostic rules on prevalence levels in the community. METHOD: Trained psychologists evaluated 3,562 pre-adolescents/early adolescents from the 2004 Pelotas Birth Cohort with the Development and Well-Being Behavior Assessment (DAWBA). The clinical threshold was assessed in three stages: symptomatic, syndromic and clinical operationalization. The symptomatic threshold identified the response category in each DAWBA item which separates normative misbehavior from a clinical indicator. The syndromic threshold identified the number of irritable mood and outbursts needed to capture pre-adolescents/early adolescents with high symptom levels. Clinical operationalization compared the impact of AND/OR rules for combining irritable mood and outbursts on impairment and levels of psychopathology. RESULTS: At the symptomatic threshold, most irritable mood items were normative in their lowest response categories and clinically significant in their highest response categories. For outbursts some indicated a symptom even when present at only a mild level, while others did not indicate symptoms at any level. At the syndromic level, a combination of 2 out of 7 irritable mood and 3 out of 8 outburst indicators accurately captured a cluster of individuals with high level of symptoms. Analysis combining irritable mood and outbursts delineated non-overlapping aspects of DMDD, providing support for the OR rule in clinical operationalization. The best DMDD criteria resulted in a prevalence of 3%. CONCLUSION: Results provide information for initiatives aiming to provide data-driven and clinically oriented operationalized criteria for DMDD.

8.
Pain ; 161(3): 630-640, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31764389

RESUMO

Approximately 1.7 million youth suffer from debilitating chronic pain in the US alone, conferring risk of continued pain in adulthood. Aberrations in threat-safety (T-S) discrimination are proposed to contribute to pain chronicity in adults and youth by interacting with pain-related distress. Yet, few studies have examined the neural circuitry underlying T-S discrimination in patients with chronic pain or how T-S discrimination relates to pain-related distress. In this study, 91 adolescents (10-24 years; 78 females) including 30 chronic pain patients with high pain-related distress, 29 chronic pain patients with low pain-related distress, and 32 healthy peers without chronic pain completed a developmentally appropriate T-S learning paradigm. We measured self-reported fear, psychophysiology (skin conductance response), and functional magnetic resonance imaging responses (N = 72 after functional magnetic resonance imaging exclusions). After controlling for age and anxiety symptoms, patients with high pain-related distress showed altered self-reported fear and frontolimbic activity in response to learned threat and safety cues compared with both patients with low pain-related distress and healthy controls. Specifically, adolescent patients with high pain-related distress reported elevated fear and showed elevated limbic (hippocampus and amygdala) activation in response to a learned threat cue (CS+). In addition, they showed decreased frontal (vmPFC) activation and aberrant frontolimbic connectivity in response to a learned safety cue (CS-). Patients with low pain-related distress and healthy controls appeared strikingly similar across brain and behavior. These findings indicate that altered T-S discrimination, mediated by frontolimbic activation and connectivity, may be one mechanism maintaining pain chronicity in adolescents with high levels of pain-related distress.

9.
J Am Acad Child Adolesc Psychiatry ; 59(3): 350-361, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31128268

RESUMO

OBJECTIVE: Despite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design. METHOD: After a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. A total of 49 participants, 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria, were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the week 8 of the trial. RESULTS: At the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTP+MPH compared to PBO+MPH (35% CTP+MPH versus 6% PBO+MPH; odds ratio = 11.70, 95% CI = 2.00-68.16, p = 0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms. CONCLUSION: Adjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone. CLINICAL TRIAL REGISTRATION INFORMATION: A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation; https://clinicaltrials.gov; NCT00794040.

10.
J Am Acad Child Adolesc Psychiatry ; 59(1): 157-165, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30877049

RESUMO

OBJECTIVE: Randomized clinical trials of augmentation strategies for youth with treatment-resistant anxiety disorders do not exist. This report presents findings from an efficacy trial of attention bias modification treatment (ABMT) as an augment for this population compared with attention control training (ACT). METHOD: Sixty-four youths (34 boys; mean age 11.7 years) who continued to meet for anxiety diagnoses after completing cognitive-behavioral therapy were randomized to ABMT or ACT. ABMT and ACT consisted of dot-probe attention training trials presenting angry and neutral faces; probes appeared in the location of neutral faces on 100% of trials in ABMT and 50% of trials in ACT. Independent evaluators, youths, and parents completed ratings of youth anxiety severity, and youths completed measures of attention bias to threat and attention control at pretreatment, post-treatment, and 2-month follow-up. RESULTS: The 2 arms showed significant decreases in anxiety severity, with no differences between arms. Specifically, across informants, anxiety severity was significantly decreased at post-treatment and decreases were maintained at follow-up. Primary anxiety disorder diagnostic recovery combined across arms was 50% at post-treatment and 58% at follow-up. Attention control, but not attention bias to threat, was significantly improved at post-treatment in the 2 arms. CONCLUSION: This is the first study to show anxiety can be decreased in youth who did not respond to cognitive-behaviorial therapy, and that the anxiety-decreasing effect is found using these 2 attention training contingency schedules. These findings and increases in attention control in the 2 arms raise intriguing questions about mechanisms of decreasing anxiety in treatment-resistant youth with attention training that require further research. CLINICAL TRIAL REGISTRATION INFORMATION: Attention Bias Modification Training for Child Anxiety CBT Nonresponders; https://clinicaltrials.gov/; NCT01819311.

11.
Psychol Med ; 50(1): 96-106, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30616705

RESUMO

BACKGROUND: Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala-prefrontal cortex (PFC) circuitry function. However, no study has characterized these associations longitudinally. Here, we tested whether level of early-childhood BI predicts distinct evolving associations between amygdala-PFC function and anxiety symptoms across development. METHODS: Eighty-seven children previously assessed for BI level in early childhood provided data at ages 10 and/or 13 years, consisting of assessments of anxiety and an fMRI-based dot-probe task (including threat, happy, and neutral stimuli). Using linear-mixed-effects models, we investigated longitudinal changes in associations between anxiety symptoms and threat-related amygdala-PFC connectivity, as a function of early-childhood BI. RESULTS: In children with a history of high early-childhood BI, anxiety symptoms became, with age, more negatively associated with right amygdala-left dorsolateral-PFC connectivity when attention was to be maintained on threat. In contrast, with age, low-BI children showed an increasingly positive anxiety-connectivity association during the same task condition. Behaviorally, at age 10, anxiety symptoms did not relate to fluctuations in attention bias (attention bias variability, ABV) in either group; by age 13, low-BI children showed a negative anxiety-ABV association, whereas high-BI children showed a positive anxiety-ABV association. CONCLUSIONS: Early-childhood BI levels predict distinct neurodevelopmental pathways to pediatric anxiety symptoms. These pathways involve distinct relations among brain function, behavior, and anxiety symptoms, which may inform diagnosis and treatment.

12.
Neuroimage ; 205: 116301, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31639510

RESUMO

Neuroimaging studies typically focus on either resting state or task-based fMRI data. Prior research has shown that similarity in functional connectivity between rest and cognitive tasks, interpreted as reconfiguration efficiency, is related to task performance and IQ. Here, we extend this approach from adults to children, and from cognitive tasks to a threat-based attention task. The goal of the current study was to examine whether similarity in functional connectivity during rest and an attention bias task relates to threat bias, IQ, anxiety symptoms, and social reticence. fMRI was measured during resting state and during the dot-probe task in 41 children (M = 13.44, SD = 0.70). Functional connectivity during rest and dot-probe was positively correlated, suggesting that functional hierarchies in the brain are stable. Similarity in functional connectivity between rest and the dot-probe task only related to threat bias (puncorr < .03). This effect did not survive correction for multiple testing. Overall, children who allocate more attention towards threat also may possess greater reconfiguration efficiency in switching from intrinsic to threat-related attention states. Finally, functional connectivity correlated negatively across the two conditions of the dot-probe task. Opposing patterns of modulation of functional connectivity by threat-congruent and threat-incongruent trials may reflect task-specific network changes during two different attentional processes.

13.
J Abnorm Child Psychol ; 48(4): 561-571, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31853719

RESUMO

Social anxiety typically emerges by adolescence and is one of the most common anxiety disorders. Many clinicians and researchers utilize the Screen for Child Anxiety Related Disorders (SCARED) to quantify anxiety symptoms, including social anxiety, throughout childhood and adolescence. The SCARED can be administered to both children and their parents, though reports from each informant tend to only moderately correlate. Here, we investigated parent-child concordance on the SCARED in a sample of adolescents (N = 360, Mage = 13.2) using a multi-trait multi-method (MTMM) model. Next, in a selected sample of the adolescents, we explored relations among child report, parent report, and latent social anxiety scores with two laboratory tasks known to elicit signs of social anxiety in the presence of unfamiliar peers: a speech task and a "Get to Know You" task. Findings reveal differences in variance of the SCARED accounted for by parent and child report. Parent report of social anxiety is a better predictor of anxiety signs elicited by a structured speech task, whereas child report of social anxiety is a better predictor of anxiety signs during the naturalistic conversation with unfamiliar peers. Moreover, while latent social anxiety scores predict both observed anxiety measures, parent report more closely resembles latent scores in relation to the speech task, whereas child report functions more similarly to latent scores in relation to the peer conversation. Thus, while latent scores relate to either observed anxiety measure, parent and child report on the SCARED each provide valuable information that differentially relate to naturalistic social anxiety-related behaviors.

15.
Behav Res Ther ; 123: 103484, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31734549

RESUMO

Bridging advances in neurodevelopmental assessment and the established onset of common psychopathologies in early childhood with epidemiological data science and computational methods holds much promise for identifying risk for mental disorders as early as infancy. In particular, we propose the development of a mental health risk algorithm for the early detection of mental disorders with the potential for high public health impact that applies and adapts methods innovated in and successfully applied to early detection of cardiovascular risk. Specifically, we propose methods to advance risk prediction of early developmental psychopathology by creating synthetic cohorts that contain complete behavioral and neural data in the first years of life, as the basis for a robust and generalizable risk algorithm. The application of computational approaches within synthetic cohorts, an approach increasingly applied in psychiatry, may be particularly well suited to advancing risk prediction in early childhood mental health. We propose new research directions using these methods to generate an early childhood mental health risk calculator that could significantly advance early mental health risk detection to direct preventive intervention and/or need for more intensive assessment within a pragmatic framework for maximal clinical utility. The availability of such a tool in early childhood, a period of high neuroplasticity, holds promise to reduce the burden of mental disorder by identifying risk early in the clinical sequence and delivering prevention that targets the neurodevelopmental vulnerability phase.

16.
Dev Psychopathol ; : 1-11, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31656217

RESUMO

Early behaviors that differentiate later biomarkers for psychopathology can guide preventive efforts while also facilitating pathophysiological research. We tested whether error-related negativity (ERN) moderates the link between early behavior and later psychopathology in two early childhood phenotypes: behavioral inhibition and irritability. From ages 2 to 7 years, children (n = 291) were assessed longitudinally for behavioral inhibition (BI) and irritability. Behavioral inhibition was assessed via maternal report and behavioral responses to novelty. Childhood irritability was assessed using the Child Behavior Checklist. At age 12, an electroencephalogram (EEG) was recorded while children performed a flanker task to measure ERN, a neural indicator of error monitoring. Clinical assessments of anxiety and irritability were conducted using questionnaires (i.e., Screen for Child Anxiety Related Disorders and Affective Reactivity Index) and clinical interviews. Error monitoring interacted with early BI and early irritability to predict later psychopathology. Among children with high BI, an enhanced ERN predicted greater social anxiety at age 12. In contrast, children with high childhood irritability and blunted ERN predicted greater irritability at age 12. This converges with previous work and provides novel insight into the specificity of pathways associated with psychopathology.

17.
Dev Psychobiol ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31631345

RESUMO

Facilitated attention toward angry stimuli (attention bias) may contribute to anger proneness and temper outbursts exhibited by children with high irritability. However, most studies linking attention bias and irritability rely on behavioral measures with limited precision and no studies have explored these associations in young children. The present study explores irritability-related attention biases toward anger in young children (N = 128; ages 4-7 years) engaged in a dot-probe task with emotional faces, as assessed with event-related brain potential (ERP) indices of early selective attention and multi-method assessment of irritability. Irritability assessed via semi-structured clinical interview predicted larger anterior N1 amplitudes to all faces. In contrast, irritability assessed via a laboratory observation paradigm predicted reduced P1 amplitudes to angry relative to neutral faces. These findings suggest that altered early attentional processing occurs in young children with high irritability; however, the nature of these patterns may vary with methodological features of the irritability assessments. Future investigations using different assessment tools may provide greater clarity regarding the underlying neurocognitive correlates of irritability. Such studies may also contribute to the ongoing debates about how to best define and measure irritability across the developmental spectrum in a manner that is most informative for linkage to neural processes.

18.
Depress Anxiety ; 36(9): 788-789, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31503393
19.
BMC Psychiatry ; 19(1): 246, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391027

RESUMO

BACKGROUND: Attention bias modification training (ABMT) and cognitive behavioral therapy (CBT) likely target different aspects of aberrant threat responses in anxiety disorders and may be combined to maximize therapeutic benefit. However, studies investigating the effect of ABMT in the context of CBT have yielded mixed results. Here, we propose an enhanced ABMT to target the attentional bias towards threat, in addition to classic CBT for anxiety disorders in youth. This enhanced ABMT integrates the modified dot-probe task used in previous studies, where a target is always presented at the previous location of the neutral and not the simultaneously presented threatening stimulus, with a visual search, where the targets are always presented distally of threatening distractors. These two training elements (modified dot-probe and visual search) are embedded in an engaging game to foster motivation and adherence. Our goal is to determine the efficacy of the enhanced ABMT in the context of CBT. Further, we aim to replicate two previous findings: (a) aberrant amygdala connectivity being the neurobiological correlate of the attentional bias towards threat at baseline; and (b) amygdala connectivity being a mediator of the ABMT effect. We will also explore moderators of treatment response (age, sex, depressive symptoms and irritability) on a behavioral and neuronal level. METHODS: One hundred and twenty youth (8-17 years old) with a primary anxiety disorder diagnosis all receive CBT and are randomized to nine weeks of either active or control ABMT and symptom improvement will be compared between the two study arms. We will also recruit 60 healthy comparison youth, who along with eligible anxious youth, will be assessed with the dot-probe task during fMRI (anxious youth: before and after training; healthy volunteers: second measurement twelve weeks after initial assessment). DISCUSSION: The present study will contribute to the literature by (1) potentially replicating that aberrant amygdala connectivity mediates the attentional bias towards threat in anxious youth; (2) determining the efficacy of enhanced ABMT; and (3) advancing our understanding of the mechanisms underlying ABMT. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03283930 Trial registration date: September 14th 2017. The trial registration took place retrospectively. Data acquisition started February 1st 2017.

20.
Neurobiol Aging ; 82: 10-17, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31376729

RESUMO

Research suggested accumulation of tau proteins might lead to the degeneration of functional networks. Studies investigating the impact of genetic risk for Alzheimer's disease (AD) on early brain connections might shed light on mechanisms leading to AD development later in life. Here, we aim to investigate whether the polygenic risk score for Alzheimer's disease (AD-PRS) influences the connectivity among regions susceptible to tau pathology during childhood and adolescence. Participants were youth, aged 6-14 years, and recruited in Porto Alegre (discovery sample, n = 332) and São Paulo (replication sample, n = 304), Brazil. Subjects underwent genotyping and 6-min resting state funcional magnetic resonance imaging. Connections between the local maxima of tau pathology networks were used as dependent variables. The AD-PRS was associated with the connectivity between the right precuneus and the right superior temporal gyrus (discovery sample: ß = 0.180, padjusted = 0.036; replication sample: ß = 0.202, p = 0.031). This connectivity was also associated with inhibitory control (ß = 0.157, padjusted = 0.035) and moderated the association between the AD-PRS and both immediate and delayed recall. These findings suggest the AD-PRS may affect brain connectivity in youth, which might impact memory performance and inhibitory control in early life.

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