Daniel S Pine

National Institutes of Health | NIH · Intramural Research Program (IRP)

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare pat...

Background Threat anticipation engages neural circuitry evolved to promote defensive behaviors; perturbations in this circuitry could generate excessive threat-anticipation responding, a key characteristic of pathological anxiety. Research on such mechanisms in youth faces ethical and practical limitations. Here, we use thermal stimulation to elici...

This report examines the relationship between pediatric anxiety disorders and implicit bias evoked by threats. To do so, the report uses two tasks that assess implicit bias to negative-valence faces, the first by eye-gaze and the second by measuring body-movement parameters. The report contrasts task performance in 51 treatment-seeking, medication-...

Objective: To evaluate the reliability and predictive utility of a time-efficient cognitive development chart that seeks to identify children and adolescents with high-risk for multiple outcomes such as mental health problems, substance use, and educational difficulties. Method: We analyzed data from the Brazilian High-Risk Cohort for Psychiatric D...

Previous studies have reported altered fear circuitry function during fear conditioning in highly anxious individuals and in adults with a history of severe childhood adversity; less is known regarding younger populations and more common forms of adversity. We investigated fear circuitry functioning in healthy youths with histories of high (HH) or...

Objective: Children with the temperament of Behavioral Inhibition (BI) face increased risk for developing an anxiety disorder later in life. However, not all children with BI manifest anxiety symptoms, and cognitive-control-strategy use may moderate the pathway between BI and anxiety. Individuals vary widely in the strategy used to instantiate cont...

Objective Irritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study used a developmental approach to test the hypothesis that there are several forms of irritability, includi...

Background: Children with Behavioral Inhibition (BI) temperament face increased social anxiety risk. However, not all children with BI develop anxiety symptoms. Inhibitory control (IC) has been suggested as a moderator of the pathway between BI and social anxiety. The current study uses longitudinal data to characterize development of IC and tests...

The chapter starts with an overview of the treatment of anxiety disorders in the fields of child and adolescent clinical psychology and psychiatry. Before reviewing what is known about the treatment of anxiety disorders in adolescence, the chapter first provides a brief overview of the history and rationale for cognitive behavioral therapy, pharmac...

This chapter begins by stating the importance of considering the concept of anxiety and its heterogeneity. It defines anxiety to set the scene for the rest of the discussion in this chapter. The chapter then makes a distinction between anxiety and anxiety disorders. The chapter looks at research in the areas of anxiety and anxiety disorders. Recent...

The chapter starts by outlining what is already known about the ecology of adolescent development and culture and how it relates to the development of anxiety disorders in individuals. Identifying which young people are most at risk to develop anxiety disorders after experiencing negative life events, the chapter argues, is an important next step t...

This chapter begins by introducing current thinking on the rationale for preventing anxiety disorders in youth. It explains risk and protective factors in youth and examines symptoms exhibited. An important set of impediments to developing successful prevention intervention is the lack of knowledge about the complex interrelations among the various...

Background: Irritability, a frequent complaint in children with psychiatric disorders, reflects increased predisposition to anger. Preliminary work in pediatric clinical samples links irritability to attention bias to threat, and the current study examines this association in a large population-based sample. Methods: We studied 1,872 children (a...

Altered Neural Habituation to Emotional Faces in Pediatric and Adult Bipolar Disorder

Perturbations in the prefrontal cortex (PFC), hippocampus, and amygdala are implicated in the development of anxiety disorders. However, most structural neuroimaging studies of patients with anxiety disorders utilize adult samples, and the few studies in youths examine small samples, primarily with volume-based measures. This study tested the hypot...

Objective: In the treatment of anxiety disorders, attention bias modification therapy (ABMT) and cognitive-behavioral therapy (CBT) may have complementary effects by targeting different aspects of perturbed threat responses and behaviors. ABMT may target rapid, implicit threat reactions, whereas CBT may target slowly deployed threat responses. The...

Background Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder. Method Unmedicated individuals with GAD ( n = 18) an...

Callous-unemotional (CU) traits comprise the core symptoms of psychopathy, yet no study has estimated the heritability of CU traits in a community sample of children using an instrument designed solely to assess CU traits. The current study uses data from 339 twin pairs aged 9–14 to examine the reliability and heritability of the parent-report Inve...

Objective: Disruptive mood dysregulation disorder (DMDD), characterized by severe irritability, and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid. This is the first study to characterize neural and behavioral similarities and differences in attentional functioning across these disorders. Method: Twenty-seven healthy volunte...

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 substantia...

Although irritability is among the most common reasons that children and adolescents are brought for psychiatric care, there are few effective treatments. Developmentally sensitive pathophysiological models are needed to guide treatment development. In this review, the authors present a mechanistic model of irritability that integrates clinical and...

Objective: Patients with social anxiety disorder exhibit increased attentional dwelling on social threats, providing a viable target for therapeutics. This randomized controlled trial examined the efficacy of a novel gaze-contingent music reward therapy for social anxiety disorder designed to reduce attention dwelling on threats. Method: Forty p...

Importance: Psychiatric comorbidity complicates clinical care and confounds efforts to elucidate the pathophysiology of commonly occurring symptoms in youths. To our knowledge, few studies have simultaneously assessed the effect of 2 continuously distributed traits on brain-behavior relationships in children with psychopathology. Objective: To d...

Background: Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared with nonabused adolescents, although most prior research is based on adults and...

Background: By conceptualizing domains of behavior transdiagnostically, the National Institute of Mental Health Research Domain Criteria (NIMH RDoC) initiative facilitates new ways of studying psychiatric symptoms. In this study, latent profile analysis (LPA) was used to empirically derive classes or patterns of psychiatric symptoms in youth that...

The Twin Study of Negative Valence Emotional Constructs is a multi-site study designed to examine the relationship between a broad selection of potential measures designed to assess putative endophenotypes for negative valence systems (NVS) and early symptoms of internalizing disorders (IDs). In this article, we describe the sample characteristics,...

Background: Efficacy of pre-trauma prevention for post-traumatic stress disorder (PTSD) has not yet been established in a randomized controlled trial. Attention bias modification training (ABMT), a computerized intervention, is thought to mitigate stress-related symptoms by targeting disruptions in threat monitoring. We examined the efficacy of AB...

Cognitive bias modification (CBM) procedures follow from the view that interpretive biases play an important role in the development and maintenance of anxiety. As such, understanding the link between interpretive biases and anxiety in youth at risk for anxiety (e.g., behaviorally inhibited children) could elucidate the mechanisms involved in the d...

Social anxiety disorder (SAD) is associated with threat-related attention and interpretation biases. Recent research suggests that attention control abilities moderate these associations. The current study examines threat-related attentional engagement and disengagement biases, negative interpretation bias, and attention control among youth with SA...

Previous studies suggested that threat biases underlie familial risk for emotional disorders in children. However, major questions remain concerning the moderating role of the offspring gender and the type of parental emotional disorder on this association. This study addresses these questions in a large sample of boys and girls. Participants were...

Background: Threat-related attention bias relates to anxiety and posttraumatic stress symptoms in adults and adolescents, but few longitudinal studies examine such associations in young children. This study examines prospective relations among attention bias, trauma exposure, and anxiety and trauma symptoms in a sample previously reported to manif...

The current study aimed to extend the results of White et al. (2015) by examining the moderating role of attention biases at age 5 on the relations between Behavioral Inhibition (BI) during toddlerhood and anxiety symptoms at age 10. Children's BI at 2 and 3 years of age was measured using laboratory assessments, and attention bias towards threat w...

Many children with anxiety disorders live in communities with limited access to treatment. Attention bias modification training, a promising computer-based treatment for anxiety disorders, may provide a readily accessible treatment. Recent evidence suggests that a form of ABMT combining visual-search for positive stimuli with features to enhance le...

Social reticence is expressed as shy, anxiously avoidant behavior in early childhood. With development, overt signs of social reticence may diminish but could still manifest themselves in neural responses to peers. We obtained measures of social reticence across 2 to 7 years of age. At age 11, preadolescents previously characterized as high (n = 30...

Considerable translational research on anxiety examines attention bias to threat and the efficacy of attention training in reducing symptoms. Imaging research on the stability of brain functions engaged by attention bias tasks could inform such research. Perturbed fronto-amygdala function consistently arises in attention bias research on adolescent...

Social Anxiety Disorder (SAD) is characterized by a tendency to interpret ambiguous social cues as negative. Here we tested whether interpretation of ambiguous faces differs between participants with SAD and non-anxious controls. Twenty-seven individuals with SAD and 21 non-anxious control participants completed an emotion recognition task in which...

Anxiety disorders are among the most common psychiatric disorders of adolescence. Behavioral and task-based imaging studies implicate altered reward system function, including striatal dysfunction, in adolescent anxiety. However, no study has yet examined alterations of the striatal intrinsic functional connectivity in adolescent anxiety disorders....

Objective: Bipolar disorder and disruptive mood dysregulation disorder (DMDD) are clinically and pathophysiologically distinct, yet irritability can be a clinical feature of both illnesses. The authors examine whether the neural mechanisms mediating irritability differ between bipolar disorder and DMDD, using a face emotion labeling paradigm becau...

Background: Extinction is a key theoretical model of exposure-based treatments, such as cognitive behavioural therapy (CBT). This study examined whether individual differences in physiological responses and subjective stimulus evaluations as indices of fear extinction predicted response to CBT. Methods: Thirty-two nonanxious comparisons and 44 a...

Background Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic, and striatal areas. Methods We collected resting-state fMRI images from youths a...

Background: Development of cortico-amygdala circuitry underlies the maturation of emotion processing and regulation, and age-related changes in amygdala connectivity with anterior cingulate cortex (ACC) have been shown to mediate normative developmental decreases in anxiety. It remains unclear whether developmental changes in this circuitry relate...

One of the most encouraging, but also the most challenging, aspects of current research on psychopathology is the diversity of measures used to assess constructs across research studies and programs. Clearly, this diversity reflects the creativity and generativity of our field and the continual growth of our science. At the same time, however, this...

Background: Fear acquisition and extinction are central constructs in the cognitive-behavioral model of obsessive-compulsive disorder (OCD), which underlies exposure-based cognitive-behavioral therapy (CBT). Youth with OCD may have impairments in fear acquisition and extinction that carry treatment implications. We examined these processes using a...

Objective: Disruption of executive function is present in many neuropsychiatric disorders. However, determining the specificity of executive dysfunction across these disorders is challenging given high comorbidity of conditions. Here the authors investigate executive system deficits in association with dimensions of psychiatric symptoms in youth u...

There is preliminary data indicating that patients with generalized anxiety disorder (GAD) show impairment on decision-making tasks requiring the appropriate representation of reinforcement value. The current study aimed to extend this literature using the passive avoidance (PA) learning task, where the participant has to learn to respond to stimul...

Objective: This study examined the effects of pediatric anxiety and its interaction with gender on reward processes. Based on the purported greater sensitivity to risk in females than males and the propensity for risk aversion in anxiety, clinical anxiety and female gender were hypothesized to act synergistically in reducing reward sensitivity and...

Combat deployment enhances risk for posttraumatic stress symptoms. We assessed whether attention bias modification training (ABMT), delivered immediately prior to combat, attenuates the association between combat exposure and stress-related symptoms. 99 male soldiers preparing for combat were randomized to receive either an ABMT condition designed...

Objective: Irritability in disruptive mood dysregulation disorder (DMDD) may be associated with a biased tendency to judge ambiguous facial expressions as angry. We conducted three experiments to explore this bias as a treatment target. We tested: 1) whether youth with DMDD express this bias; 2) whether judgment of ambiguous faces can be altered i...

Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6-18 years, 40.4% (n=38) with exposur...

Although risk-taking has been studied from a developmental perspective, no study has examined how anxiety, age, risk-valence and social context interact to modulate decision-making in youths. This study probes this question using a risk-taking task, the Stunt Task, in clinically anxious children (n = 17, 10 F, age = 8.3-12.1 years), healthy childre...

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and, reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working me...

Objective: Perturbations in emotional conflict adaptation, an implicit regulatory process, have been observed in adult anxiety disorders. However, findings remain inconsistent and restricted to adults. The current study compares conflict adaptation in youth and adults, with and without anxiety disorders. We predicted conflict adaptation would be p...

Objective: Behavioral inhibition (BI) during early childhood predicts risk for anxiety disorders and altered cognitive control in adolescence. Although BI has been linked to variation in brain function through adulthood, few studies have examined relations between early childhood BI and adult brain structure. Method: The relation between early c...

Increasing efforts have been made to investigate the underlying pathophysiology of generalized anxiety disorder (GAD), but only limited consistent information is available on gray (GM) and white matter (WM) volume changes in affected adults. Additionally, few studies employed dimensional approaches to GAD pathology. This study compares structural b...

Purpose: Studies suggest anxiety symptoms have increased in children over past years, indicating changes in perceived stress or modern life as possible causes. This study investigated global changes in prevalence of anxiety symptoms in childhood from 1998 to 2013. Methods: Four meta-regression analyses tested the association between year of publica...

Objective: Youths with disruptive behavior disorders (DBD) (conduct disorder and oppositional defiant disorder) have an elevated risk for maladaptive reactive aggression. Theory suggests that this is due to an elevated sensitivity of basic threat circuitry implicated in retaliation (amygdala/periaqueductal gray) in youths with DBD and low levels o...

Attention to faces is a fundamental psychological process in humans, with atypical attention to faces noted across several clinical disorders. Although many clinical disorders onset in adolescence, there is a lack of well-validated stimulus sets containing adolescent faces available for experimental use. Further, the images comprising most availabl...

This chapter defines relevant terms and reviews available literature on classification of childhood anxiety disorders. Specifically, it examines data regarding commonalities and differences among the anxiety disorders as they present in juveniles and in adults. The chapter further reviews the data on one specific childhood anxiety disorder: Social...

Behavioral inhibition (BI), a temperament characterized in early childhood by wariness and avoidance of novelty, is a risk factor for anxiety disorders. An enhanced startle response has been observed in adolescents characterized with BI in childhood, particularly when they also manifest concurrent symptoms of anxiety. However, no prior study has ex...

We examined two groups of combat veterans, one with post-traumatic stress disorder (PTSD) (n = 27) and another without PTSD (n = 16), using an emotional Stroop task (EST) with word lists matched across a series of lexical variables (e.g. length, frequency, neighbourhood size, etc.). Participants with PTSD exhibited a strong EST effect (longer colou...

Attention bias modification training (ABMT) is a promising treatment for anxiety disorders. Recent evidence suggests that attention training towards positive stimuli, using visual-search based ABMT, has beneficial effects on anxiety and attention biases in children. The present study extends this prior research using distinctive techniques designed...