Striatal Activity to Reward Anticipation as a Moderator of the Association Between Early Behavioral Inhibition and Changes in Anxiety and Depressive Symptoms From Adolescence to Adulthood.

Importance: The early childhood temperament of behavioral inhibition (BI), characterized by inhibited and fearful behaviors, has been associated with heightened risk for anxiety and depression across the lifespan. Although several neurocognitive correlates underlying vulnerability to the development of anxiety among inhibited children have been identified, little is known about the neurocognitive correlates underlying vulnerability to the development of depression. Objective: To examine whether blunted striatal activation to reward anticipation, a well-documented neurocognitive vulnerability marker of depression, moderates the association between early BI and the developmental changes in depression and anxiety from adolescence to adulthood. Design, Setting, and Participants: Participants in this prospective longitudinal study were recruited at age 4 months between 1989 and 1993 in the US. Follow-up assessments extended into 2018 (age 26 years). Data were analyzed between September 2021 to March 2022. Main Outcomes and Measures: BI was measured through an observation paradigm in infancy (ages 14 and 24 months). Neural activity to anticipated rewards during a monetary incentive delay task was measured using functional magnetic resonance imaging in adolescence (between ages 15-18 years; 83 individuals had usable data). Anxiety and depressive symptoms were self-reported across adolescence to young adulthood (ages 15 and 26 years; n = 108). A latent change score model, accounting for the interdependence between anxiety and depression, tested the moderating role of striatal activity to reward anticipation in the association between early BI and changes in anxiety and depressive symptoms. A region of interest approach limited statistical tests to regions within the striatum (ie, nucleus accumbens, caudate head, caudate body, putamen). Results: Of 165 participants, 84 (50.1%) were female and 162 (98%) were White. Preliminary analyses revealed significant increases in anxiety and depressive symptoms across ages 15 to 26 years, as well as individual variation in the magnitude of changes. Main analyses showed that reduced activity in the nucleus accumbens to reward anticipation moderated the association between early BI and increases in depressive (ß = -0.32; b = -4.23; 95% CI, -7.70 to -0.76; P = .02), and more depressive symptoms at age 26 years (ß = -0.47; b = -5.09; 95% CI, -7.74 to -2.43; P < .001). However, there were no significant interactions associated with latent changes in anxiety across age nor anxiety at age 26 years. Activity in the caudate and putamen did not moderate these associations. Conclusions and Relevance: Blunted reward sensitivity in the ventral striatum may be a developmental risk factor connecting an inhibited childhood temperament and depression over the transition to adulthood. Future studies should examine the efficacy of prevention programs, which target maladaptive reward processing and motivational deficits among anxious youths, in reducing risks for later depression.

Spectral parameterization for studying neurodevelopment: How and why.

A growing body of literature suggests that the explicit parameterization of neural power spectra is important for the appropriate physiological interpretation of periodic and aperiodic electroencephalogram (EEG) activity. In this paper, we discuss why parameterization is an imperative step for developmental cognitive neuroscientists interested in cognition and behavior across the lifespan, as well as how parameterization can be readily accomplished with an automated spectral parameterization ("specparam") algorithm (Donoghue et al., 2020a). We provide annotated code for power spectral parameterization, via specparam, in Jupyter Notebook and R Studio. We then apply this algorithm to EEG data in childhood (N = 60; Mage = 9.97, SD = 0.95) to illustrate its utility for developmental cognitive neuroscientists. Ultimately, the explicit parameterization of EEG power spectra may help us refine our understanding of how dynamic neural communication contributes to normative and aberrant cognition across the lifespan. Data and annotated analysis code for this manuscript are available on GitHub as a supplement to the open-access specparam toolbox.

The centrality of temperament to the research domain criteria (RDoC): The earliest building blocks of psychopathology.

The research domain criteria (RDoC) is an innovative approach designed to explore dimensions of human behavior. The aim of this approach is to move beyond the limits of psychiatric categories in the hope of aligning the identification of psychological health and dysfunction with clinical neuroscience. Despite its contributions to adult psychopathology research, RDoC undervalues ontogenetic development, which circumscribes our understanding of the etiologies, trajectories, and maintaining mechanisms of psychopathology risk. In this paper, we argue that integrating temperament research into the RDoC framework will advance our understanding of the mechanistic origins of psychopathology beginning in infancy. In illustrating this approach, we propose the incorporation of core principles of temperament theories into a new "life span considerations" subsection as one option for infusing development into the RDoC matrix. In doing so, researchers and clinicians may ultimately have the tools necessary to support emotional development and reduce a young child's likelihood of psychological dysfunction beginning in the first years of life.

Prenatal substance exposure and maternal hostility from pregnancy to toddlerhood: Associations with temperament profiles at 16 months of age.

We investigated whether infant temperament was predicted by level of and change in maternal hostility, a putative transdiagnostic vulnerability for psychopathology, substance use, and insensitive parenting. A sample of women (N = 247) who were primarily young, low-income, and had varying levels of substance use prenatally (69 nonsmokers, 81 tobacco-only smokers, and 97 tobacco and marijuana smokers) reported their hostility in the third trimester of pregnancy and at 2, 9, and 16 months postpartum, and their toddler's temperament and behavior problems at 16 months. Maternal hostility decreased from late pregnancy to 16 months postpartum. Relative to pregnant women who did not use substances, women who used both marijuana and tobacco prenatally reported higher levels of hostility while pregnant and exhibited less change in hostility over time. Toddlers who were exposed to higher levels of prenatal maternal hostility were more likely to be classified in temperament profiles that resemble either irritability or inhibition, identified via latent profile analysis. These two profiles were each associated with more behavior problems concurrently, though differed in their association with competence. Our results underscore the utility of transdiagnostic vulnerabilities in understanding the intergenerational transmission of psychopathology risk and are discussed in regards to the Research Domain Criteria (RDoC) framework.

A Disruption in the Balance of Attentional Systems Plays a Role in Trait Anxiety.

Elevated levels of anxiety are associated with attentional threat biases and inefficient attentional control, with the latter requiring sustained cognitive effort. The current study assessed self-reported and behavioral evidence of attentional functioning, along with electrodermal activity (EDA; measured via changes in skin conductance level [SCL reactivity]) as an index of sympathetic arousal, to examine whether these vulnerabilities are evident among individuals with elevated trait anxiety (non-clinical). Fifty-nine participants completed a working memory span task measuring attentional control under high cognitive load. A visual change detection task assessed stimulus-driven attention as an indicator of vigilance to non-threatening visual information. Trait anxiety was self-reported. SCL was captured at rest and during the working memory task. Results revealed that trait anxiety was positively related to speed of visual change detection, without accuracy costs, suggesting enhanced vigilance for neutral visual information among those higher in trait anxiety. Trait anxiety also moderated the relation between change detection speed and attentional control, such that attentional vigilance was not associated with variation in attentional control for individuals higher in trait anxiety. However, for individuals lower in trait anxiety, vigilance was negatively associated with attention control. The relationship between vigilance and attentional control was also moderated by SCL reactivity such that the association was only significant at lower SCL reactivity levels. Taken together, results suggest that individuals higher in trait anxiety demonstrate greater attentional control in the service of visual detection, but greater attentional control may come at the cost of increased sympathetic arousal.

Behavioral inhibition and EEG delta-beta correlation in early childhood: Comparing a between-subjects and within-subjects approach.

Heightened delta-beta correlation has been conceptualized as reflecting exaggerated neural regulation and has been implicated in anxiety. Behavioral inhibition (BI) is a temperament characterized by wariness to novelty and is a robust predictor of anxiety, but delta-beta correlation has not been investigated in relation to childhood BI. We examined the relation between BI and between-subjects (i.e., across participants) and within-subjects (i.e., across data epochs) measures of baseline EEG delta-beta correlation in 118 children. Using a between-subjects measure, children scoring high on BI had higher delta-beta correlation relative to low BI children at frontal and central, and marginally higher in parietal, brain regions. Using a within-subjects measure, continuous BI scores were positively correlated with central and parietal delta-beta correlation. Delta-beta correlation may be a neural correlate of BI in childhood that displays differences in region specificity, correlation strength, and variability of correlation values when comparing between- and within-subjects measures.

Limbic and prefrontal neural volume modulate social anxiety in children at temperamental risk.

BACKGROUND: Clinical levels of a social anxiety disorder (SAD) often appear during childhood and rise to a peak during late adolescence. The temperament trait behavioral inhibition (BI), evident early in childhood, has been linked to increased risk for SAD. Functional and structural variations in brain regions associated with the identification of, and response to, fear may support the BI-SAD relation. Whereas relevant functional studies are emerging, the few extant structural studies have focused on adult samples with mixed findings. METHODS: A moderated-mediation model was used to examine the relations between BI, SAD symptoms, and brain-volume individual differences in a sample of children at risk for anxiety (ages 9-12; N = 130, 52 BI). RESULTS: Our findings indicate that at higher levels of BI, children with smaller anterior insula volumes showed stronger correlations between BI and SAD. In addition, larger ventrolateral prefrontal cortex (vlPFC) volumes were associated with fewer SAD symptoms. CONCLUSIONS: These findings support previous reports linking SAD levels with variations in volume and reactivity in both limbic (insula) and prefrontal (vlPFC) regions. These findings set the foundation for further examination of networks of neural structures that influence the transition from BI to SAD across development, helping further clarify mechanisms of risk and resilience.

Perinatal complications are associated with social anxiety: Indirect effects through temperament.

The current investigation examines the relation between perinatal complications and social anxiety incorporating the potential indirect effect of child temperament. Participants were 149 children 9 to 12 years of age (Mage=9.97, SDage=1.00) screened for behavioral inhibition (BI) and assessed for social anxiety symptoms using parent- and child-report. Participating families also reported on the presence of perinatal complications. Results indicated that children who experienced perinatal complications were higher in BI and social anxiety, compared to children who did not experience complications. Furthermore, there was an indirect effect between perinatal complications and social anxiety via BI. These findings provide further support for the established relation between perinatal complications and anxiety and demonstrate, for the first time, that this relation may be mediated by temperament, setting the stage for longitudinal analyses.

Integrating high-density ERP and fMRI measures of face-elicited brain activity in 9-12-year-old children: An ERP source localization study.

Social information processing is a critical mechanism underlying children's socio-emotional development. Central to this process are patterns of activation associated with one of our most salient socioemotional cues, the face. In this study, we obtained fMRI activation and high-density ERP source data evoked by parallel face dot-probe tasks from 9-to-12-year-old children. We then integrated the two modalities of data to explore the neural spatial-temporal dynamics of children's face processing. Our results showed that the tomography of the ERP sources broadly corresponded with the fMRI activation evoked by the same facial stimuli. Further, we combined complementary information from fMRI and ERP by defining fMRI activation as functional ROIs and applying them to the ERP source data. Indices of ERP source activity were extracted from these ROIs at three a priori ERP peak latencies critical for face processing. We found distinct temporal patterns among the three time points across ROIs. The observed spatial-temporal profiles converge with a dual-system neural network model for face processing: a core system (including the occipito-temporal and parietal ROIs) supports the early visual analysis of facial features, and an extended system (including the paracentral, limbic, and prefrontal ROIs) processes the socio-emotional meaning gleaned and relayed by the core system. Our results for the first time illustrate the spatial validity of high-density source localization of ERP dot-probe data in children. By directly combining the two modalities of data, our findings provide a novel approach to understanding the spatial-temporal dynamics of face processing. This approach can be applied in future research to investigate different research questions in various study populations.

Young children's neural processing of their mother's voice: An fMRI study.

In addition to semantic content, human speech carries paralinguistic information that conveys important social cues such as a speaker's identity. For young children, their own mothers' voice is one of the most salient vocal inputs in their daily environment. Indeed, qualities of mothers' voices are shown to contribute to children's social development. Our knowledge of how the mother's voice is processed at the neural level, however, is limited. This study investigated whether the voice of a mother modulates activation in the network of regions activated by the human voice in young children differently than the voice of an unfamiliar mother. We collected fMRI data from 32 typically developing 7- and 8-year-olds as they listened to natural speech produced by their mother and another child's mother. We used emotionally-varied natural speech stimuli to approximate the range of children's day-to-day experience. We individually-defined functional ROIs in children's voice-sensitive neural network and then independently investigated the extent to which activation in these regions is modulated by speaker identity. The bilateral posterior auditory cortex, superior temporal gyrus (STG), and inferior frontal gyrus (IFG) exhibit enhanced activation in response to the voice of one's own mother versus that of an unfamiliar mother. The findings indicate that children process the voice of their own mother uniquely, and pave the way for future studies of how social information processing contributes to the trajectory of child social development.

Developmental patterns of anger from infancy to middle childhood predict problem behaviors at age 8.

Anger is a central characteristic of negative affect and is relatively stable from infancy onward. Absolute levels of anger typically peak in early childhood and diminish as children become socialized and better able to regulate emotions. From infancy to school age, however, there are also individual differences in rank-order levels of anger. For example, although decreasing in absolute levels, some children may stay the same and others may increase in rank order relative to their peers. Although change in rank order of anger over time may provide unique insight into children's social development, little is known concerning variations in developmental patterns of anger from a rank-order perspective and how these patterns are related to children's behavioral adjustment. The current study (N = 361) used group-based trajectory analysis and identified 6 distinct patterns of parent-reported child anger by rank across 9 months to 7 years: low-stable rank, average-stable rank, average-decreasing rank, average-increasing rank, high-decreasing rank, and high-stable rank. Most children (65.1%) were in low- to average-rank groups. However, 28.2% and 6.7% of the children were in average-increasing and high-stable groups, respectively. Children in the high-stable group showed elevated levels of externalizing and internalizing problems at age 8 compared to children in the average-stable, average-decreasing, and high-decreasing groups. These findings help to clarify different patterns of anger development across childhood and how they may relate to later problem behaviors. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Neural correlates of attention bias to masked facial threat cues: Examining children at-risk for social anxiety disorder.

Background: Behavioral inhibition (BI) is an early-appearing temperament trait and a robust predictor of social anxiety disorder (SAD). Both BI and anxiety may have distinct patterns of emotion processing marked by heightened neural responses to threat cues. BI and anxious children display similar frontolimbic patterns when completing an emotion-face attention bias task with supraliminal presentation. Anxious children also show a distinct neural response to the same task with subliminal face presentations, probing stimulus-driven attention networks. We do not have parallel data available for BI children, limiting our understanding of underlying affective mechanisms potentially linking early BI to the later emergence of anxiety. Method: We examined the neural response to subliminal threat presentation during an emotion-face masked dot-probe task in children oversampled for BI (N = 67; 30 BI, 9-12 yrs). Results: Non-BI children displayed greater activation versus BI children in several regions in response to threat faces versus neutral faces, including striatum, prefrontal and temporal lobes. When comparing congruent and incongruent trials, which require attention disengagement, BI children showed greater activation than non-BI children in the cerebellum, which is implicated in rapidly coordinating information processing, aversive conditioning, and learning the precise timing of anticipatory responses. Conclusions: Non-BI children may more readily engage rapid coordinated frontolimbic circuitry to salient stimuli, whereas BI children may preferentially engage subcortical circuitry, in response to limbic "alarms" triggered by subliminal threat cues. These data help reveal the extent to which temperamental risk shares similar neurocircuitry previously documented in anxious adolescents and young adults in response to masked threat.

Biobehavioral Markers of Attention Bias Modification in Temperamental Risk for Anxiety: A Randomized Control Trial.

OBJECTIVE: Children with behavioral inhibition, a temperament characterized by biologically based hypervigilance to novelty and social withdrawal, are at high risk for developing anxiety. This study examined the effect of a novel attention training protocol, attention bias modification (ABM), on symptomatic, behavioral, and neural risk markers in children with behavioral inhibition. METHOD: Nine- to 12-year-old typically developing children identified as having behavioral inhibition (N = 84) were assigned to a 4-session active ABM training (n = 43) or placebo protocol (n = 41) using a double-blinded, randomized, controlled trial approach. Anxiety symptoms (Diagnostic Interview Schedule for Children-Fourth Edition), attention bias (AB; measured by a dot-probe task; AB = incongruent reaction time - congruent reaction time), and AB-related neural activation (measured by functional magnetic resonance imaging activation for the incongruent > congruent contrast in the dot-probe task) were assessed before and after the training sessions. RESULTS: Results showed that active ABM (n = 40) significantly alleviated participants' symptoms of separation anxiety, but not social anxiety, compared with the placebo task (n = 40); ABM did not modify behavioral AB scores in the dot-probe task; and at the neural level, active ABM (n = 15) significantly decreased amygdala and insula activation and increased activation in the ventrolateral prefrontal cortex compared with placebo (n = 19). CONCLUSION: These findings provide important evidence for ABM as a potentially effective protective tool for temperamentally at-risk children in a developmental window before the emergence of clinical disorder and open to prevention and intervention. Clinical trial registration information-Attention and Social Behavior in Children (BRAINS); http://clinicaltrials.gov/; NCT02401282.

Maternal anxiety predicts attentional bias towards threat in infancy.

Although cognitive theories of psychopathology suggest that attention bias toward threat plays a role in the etiology and maintenance of anxiety, there is relatively little evidence regarding individual differences in the earliest development of attention bias toward threat. The current study examines attention bias toward threat during its potential first emergence by evaluating the relations between attention bias and known risk factors of anxiety (i.e., temperamental negative affect and maternal anxiety). We measured attention bias to emotional faces in infants (N = 98; 57 male) ages 4 to 24 months during an attention disengagement eye-tracking paradigm. We hypothesized that (a) there would be an attentional bias toward threat in the full sample of infants, replicating previous studies; (b) attentional bias toward threat would be positively related to maternal anxiety; and (c) attention bias toward threat would be positively related to temperamental negative affect. Finally, (d) we explored the potential interaction between temperament and maternal anxiety in predicting attention bias toward threat. We found that attention bias to the affective faces did not change with age, and that bias was not related to temperament. However, attention bias to threat, but not attention bias to happy faces, was positively related to maternal anxiety, such that higher maternal anxiety predicted a larger attention bias for all infants. These findings provide support for attention bias as a putative early mechanism by which early markers of risk are associated with socioemotional development. (PsycINFO Database Record

Patterns of attention to threat across tasks in behaviorally inhibited children at risk for anxiety.

Although attention bias towards threat has been causally implicated in the development and maintenance of fear and anxiety, the expected associations do not appear consistently. Reliance on a single task to capture attention bias, in this case overwhelmingly the dot-probe task, may contribute to this inconsistency. Comparing across attentional bias measures could help capture patterns of behavior that have implications for anxiety. This study examines the patterns of attentional bias across two related measures in a sample of children at temperamental risk for anxiety. Children (Meanage = 10.19 ± 0.96) characterized as behaviorally inhibited (N = 50) or non-inhibited (N = 64) via parent-report completed the dot-probe and affective Posner tasks to measure attentional bias to threat. Parent-report diagnostic interviews assessed children's social anxiety. Behavioral inhibition was not associated with performance in the dot-probe task, but was associated with increased attentional bias to threat in the affective Posner task. Cross-task convergence was dependent on temperament, such that attention bias across the two tasks was only related in behaviorally inhibited children. Finally, children who were consistently biased across tasks (showing high or low attentional bias scores in both tasks, rather than high in one but low in the other) had higher levels of anxiety. Convergence across attention bias measures may be dependent on individuals' predispositions (e.g. temperament). Moreover, convergence of attention bias across measures may be a stronger marker of information processing patterns that shape socioemotional outcomes than performance in a single task.

A developmental neuroscience perspective on affect-biased attention.

There is growing interest regarding the impact of affect-biased attention on psychopathology. However, most of the research to date lacks a developmental approach. In the present review, we examine the role affect-biased attention plays in shaping socioemotional trajectories within a developmental neuroscience framework. We propose that affect-biased attention, particularly if stable and entrenched, acts as a developmental tether that helps sustain early socioemotional and behavioral profiles over time, placing some individuals on maladaptive developmental trajectories. Although most of the evidence is found in the anxiety literature, we suggest that these relations may operate across multiple domains of interest, including positive affect, externalizing behaviors, drug use, and eating behaviors. We also review the general mechanisms and neural correlates of affect-biased attention, as well as the current evidence for the co-development of attention and affect. Based on the reviewed literature, we propose a model that may help us better understand the nuances of affect-biased attention across development. The model may serve as a strong foundation for ongoing attempts to identify neurocognitive mechanisms and intervene with individuals at risk. Finally, we discuss open issues for future research that may help bridge existing gaps in the literature.

Neural correlates of attention biases, behavioral inhibition, and social anxiety in children: An ERP study.

Behavioral inhibition (BI) is a biologically-based temperament characterized by vigilance toward threat. Over time, many children with BI increasingly fear social circumstances and display maladaptive social behavior. BI is also one of the strongest individual risk factors for developing social anxiety disorder. Although research has established a link between BI and anxiety, its causal mechanism remains unclear. Attention biases may underlie this relation. The current study examined neural markers of the BI-attention-anxiety link in children ages 9-12 years (N=99, Mean=9.97, SD=0.97). ERP measures were collected as children completed an attention-bias (dot-probe) task with neutral and angry faces. P2 and N2 amplitudes were associated with social anxiety and attention bias, respectively. Specifically, augmented P2 was related to decreased symptoms of social anxiety and moderated the relation between BI and social anxiety, suggesting that increasing attention mobilization may serve as a compensatory mechanism that attenuates social anxiety in individuals with high BI. The BI by N2 interaction found that larger N2 related to threat avoidance with increasing levels of BI, consistent with over-controlled socio-emotional functioning. Lastly, children without BI (BN) showed an augmented P1 to probes replacing angry faces, suggesting maintenance of attentional resources in threat-related contexts.

ALTERED TOPOGRAPHY OF INTRINSIC FUNCTIONAL CONNECTIVITY IN CHILDHOOD RISK FOR SOCIAL ANXIETY.

BACKGROUND: Extreme shyness in childhood arising from behavioral inhibition (BI) is among the strongest risk factors for developing social anxiety. Although no imaging studies of intrinsic brain networks in children with BI have been reported, adults with a history of BI exhibit altered functioning of frontolimbic circuits and enhanced processing of salient, personally relevant information. BI in childhood may be marked by increased coupling of salience (insula) and default (ventromedial prefrontal cortex [vmPFC]) network hubs. METHODS: We tested this potential relation in 42 children ages 9-12, oversampled for high BI. Participants provided resting-state functional magnetic resonance imaging. A novel topographical pattern analysis of salience network intrinsic functional connectivity was conducted, and the impact of salience-default coupling on the relation between BI and social anxiety symptoms was assessed via moderation analysis. RESULTS: Children with high BI exhibit altered salience network topography, marked by reduced insula connectivity to dorsal anterior cingulate and increased insula connectivity to vmPFC. Whole-brain analyses revealed increased connectivity of salience, executive, and sensory networks with default network hubs in children higher in BI. Finally, the relation between insula-ventromedial prefrontal connectivity and social anxiety symptoms was strongest among the children highest in BI. CONCLUSIONS: BI is associated with an increase in connectivity to default network hubs that may bias processing toward personally relevant information during development. These altered patterns of connectivity point to potential biomarkers of the neural profile of risk for anxiety in childhood.

Attention Biases Towards and Away from Threat Mark the Relation between Early Dysregulated Fear and the Later Emergence of Social Withdrawal.

Fearful temperament, mostly studied as behavioral inhibition (BI), has been extensively associated with social withdrawal in childhood and the later emergence of anxiety disorders, especially social anxiety disorder (SAD). Recent studies have characterized a distinct type of fearful temperament marked by high levels of fear in low threat situations - labeled dysregulated fear. Dysregulated fear has been related to SAD over and above risks associated with BI. However, the mechanism by which dysregulated fear is related to SAD has not been studied. Cognitive mechanisms, such as attentional bias towards threat, may be a possible conduit. We examined differences in attentional bias towards threat in six-year-olds who displayed a pattern of dysregulated fear at age two (N = 23) compared with children who did not display dysregulated fear (N = 33). Moreover, we examined the concurrent relation between attentional bias and social withdrawal. Results indicated that children characterized by dysregulated fear showed a significant bias away from threat, and that this bias was significantly different from the children without dysregulated fear, who showed no significant bias. Moreover, attentional bias towards threat was positively related to social withdrawal only for the dysregulated fear group. These results are discussed in consideration of the existing knowledge of attentional bias to threat in the developmental and pediatric anxiety literatures, as well as recent studies that find important heterogeneity in attentional bias.

Behavioral Inhibition: Temperament or Prodrome?

Individual differences in temperament emerge in the first months of life. Some infants display a heightened sensitivity to novelty and uncertainty in the world around them, leading a subset to fearfully withdraw from the social environment. Extreme forms of this temperament, Behavioral Inhibition (BI), are associated with increased risk for social anxiety disorder. Indeed, the link is so strong that some suggest that BI is not simply a risk factor for anxiety, but rather a milder form of the disorder. The current overview describes the literature linking BI and anxiety, highlighting the unique biobehavioral profiles evident in each construct. It then highlights specific evidence that may help distinguish the form and function of BI and anxiety. Finally, we briefly discuss unresolved issues that may help inform future work aimed at improving our understanding of individual development and shape therapeutic interventions directed at specific mechanisms of disorder.