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Purpose of the Review: This review describes approaches to research on anxiety that attempt to link neural correlates to treatment response and novel therapies. The review emphasizes pediatric anxiety disorders since most anxiety disorders begin before adulthood. Recent Findings: Recent literature illustrates how current treatments for anxiety manifest diverse relations with a range of neural markers. While some studies demonstrate post-treatment normalization of markers in anxious individuals, others find persistence of group differences. For other markers, which show no pretreatment association with anxiety, the markers nevertheless distinguish treatment-responders from non-responders. Heightened error related negativity represents the risk marker discussed in the most depth; however, limitations in measures related to error responding necessitate multimodal and big-data approaches. Summary: Single risk markers show limits as correlates of treatment response. Large-scale, multimodal data analyzed with predictive models may illuminate additional risk markers related to anxiety disorder treatment outcomes. Such work may identify novel targets and eventually guide improvements in treatment response/outcomes. [ABSTRACT FROM AUTHOR]

Anxiety has been associated with reliance on reactive (stimulus-driven/reflexive) control strategies in response to conflict. However, this conclusion rests primarily on indirect evidence. Few studies utilize tasks that dissociate the use of reactive ('just in time') vs. proactive (anticipatory/preparatory) cognitive control strategies in response to conflict, and none examine children diagnosed with anxiety. The current study utilizes the AX-CPT, which dissociates these two types of cognitive control, to examine cognitive control in youth (ages 8–18) with and without an anxiety diagnosis (n = 56). Results illustrate that planful behavior, consistent with using a proactive strategy, varies by both age and anxiety symptoms. Young children (ages 8–12 years) with high anxiety exhibit significantly less planful behavior than similarly-aged children with low anxiety. These findings highlight the importance of considering how maturation influences relations between anxiety and performance on cognitive-control tasks and have implications for understanding the pathophysiology of anxiety in children. [ABSTRACT FROM AUTHOR]

Anxiety disorders are characterized by maladaptive defensive responses to distal or uncertain threats. Elucidating neural mechanisms of anxiety is essential to understand the development and maintenance of anxiety disorders. In fMRI, patients with pathological anxiety (ANX, n = 23) and healthy controls (HC, n = 28) completed a contextual threat learning paradigm in which they picked flowers in a virtual environment comprising a danger zone in which flowers were paired with shock and a safe zone (no shock). ANX compared with HC showed 1) decreased ventromedial prefrontal cortex and anterior hippocampus activation during the task, particularly in the safe zone, 2) increased insula and dorsomedial prefrontal cortex activation during the task, particularly in the danger zone, and 3) increased amygdala and midbrain/periaqueductal gray activation in the danger zone prior to potential shock delivery. Findings suggest that ANX engage brain areas differently to modulate context-appropriate emotional responses when learning to discriminate cues within an environment. Suarez-Jimenez and colleagues use a shock and safe zone experiment with fMRI imaging to examine how pathological anxiety disorders are manifested in the brain. Their findings suggest that safe and dangerous zones within the experiment alter activation in different brain regions. [ABSTRACT FROM AUTHOR]

Childhood exposure to traumatic violence may shape how children respond to threatening faces and increase risk for psychopathology. Maltreated children may exhibit altered processing of threatening faces; however, the effects of witnessing intimate partner violence (IPV) on children's discrimination of facial expressions is under-studied. Emotional face processing differentially relates to psychopathology, with some evidence suggesting improved detection of angry faces in children with fear-related anxiety symptoms, whereas externalizing symptoms are associated with poorer detection of fearful faces and perhaps emotional faces broadly. In this cross-sectional study, we examined discrimination of threatening emotional faces (angry, fearful) in relation to experiences of probable abuse and witnessing of physical IPV, as well as psychopathology. Children (N = 137, mean age = 5.01 years, SD = 0.81) completed a "face in the crowd task" designed to examine discrimination of angry and fearful faces. Children either searched for an angry face among fearful distractor faces or a fearful face among angry distractors. Probable child abuse, witnessed IPV, and symptoms were assessed in semi-structured maternal interviews. Children who witnessed violence showed poorer accuracy when fearful faces were the target; however, effects for probable abuse were non-significant. Greater fear-related anxiety symptoms were associated with poorer accuracy for fearful faces. Externalizing symptoms were associated with poorer overall accuracy. Findings suggest that IPV and fear-related anxiety symptoms were associated with difficulty detecting fearful faces when angry distractors were present, consistent with prior research. Implications of violence- and symptom-associated deficits in emotional face processing are discussed. [ABSTRACT FROM AUTHOR]

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-free pediatric patients with anxiety disorders and 36 healthy peers. Among these youth, 53 completed an eye-gaze task, 74 completed a body-movement task, and 40 completed both tasks. On the eye-gaze task, patients displayed longer gaze duration on negative relative to non-negative valence faces than healthy peers, F(1, 174) = 8.27, p =.005. In contrast, on the body-movement task, patients displayed a greater tendency to behaviorally avoid negative-valence faces than healthy peers, F(1, 72) = 4.68, p =.033. Finally, implicit bias measures on the two tasks were correlated, r(38) =.31, p =.049. In sum, we found an association between pediatric anxiety disorders and implicit threat bias on two tasks, one measuring eye-gaze and the other measuring whole-body movements. Converging evidence for implicit threat bias encourages future research using multiple tasks in anxiety. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Wariness in early childhood manifests as shy, inhibited behavior in novel social situations and is associated with increased risk for developing social anxiety. In youth with childhood wariness, exposure to a potent social stressor, such as peer victimization, may potentiate brain-based sensitivity to unpredictable social contexts, thereby increasing risk for developing social anxiety. To test brain-based associations between early childhood wariness, self-reported peer victimization, and current social anxiety symptoms, we quantified neural responses to different social contexts in low- and high-victimized pre-adolescents with varying levels of early childhood wariness. Measures of early childhood wariness were obtained annually from ages 2-to-7-years. At age 11, participants were characterized as having low (N = 20) or high (N = 27) peer victimization. To index their neural responses to peer evaluation, participants completed an fMRI-based Virtual School paradigm (Jarcho et al. Developmental Cognitive Neuroscience, 13, 21-31, 2013a). In highly victimized, relative to low-victimized participants, wariness was differentially related to right amygdala response based on the valence and predictability of peer evaluation. More specifically, in highly victimized participants, wariness was associated with greater right amygdala response to unpredictably positive peer evaluation. Effects of wariness were not observed in participants who reported low levels of victimization. Moreover, in victimized participants, high wariness and right amygdala response to unpredictably positive peer evaluation was associated with more severe social anxiety symptoms. Results can be interpreted using a diathesis-stress model, which suggests that neural response to unexpectedly positive social feedback is a mechanism by which exposure to peer victimization potentiates the risk for developing social anxiety in individuals exhibiting high levels of early childhood wariness. [ABSTRACT FROM AUTHOR]

The Screen for Child Anxiety Related Emotional Disorders (SCARED) is a measure widely used to assess childhood anxiety based on parent and child report. However, while the SCARED is a reliable, valid, and sensitive measure to screen for pediatric anxiety disorders, informant discrepancy can pose clinical and research challenges. The present study assesses informant discrepancy, measurement invariance, test-retest reliability, and external validity of the SCARED in 1092 anxious and healthy parent-child dyads. Our findings indicate that discrepancy does not vary systematically by the various clinical, demographic, and familial variables examined. There was support for strict measurement invariance, strong test-retest reliability, and adequate external validity with a clinician-rated measure of anxiety. These findings further support the utility of the SCARED in clinical and research settings, but low parent-child agreement highlights the need for further investigation of factors contributing to SCARED informant discrepancy. [ABSTRACT FROM AUTHOR]

Attention bias modification treatment (ABMT) aims to reduce anxiety symptoms via practice on computerized attention training tasks. Despite evidence of efficacy, clinical effects appear heterogeneous. More research on ABMT mechanisms and moderators of treatment response is needed. Age is one potentially important moderator, as developmental differences in training effects may impact response. We examined developmental links between ABMT training effects and response in social anxiety disorder (SAD). We pooled data from two randomized controlled trials in treatment-seeking youths and adults with SAD (N = 99) that used identical ABMT methods. We first characterized learning effects associated with the eight-session ABMT training protocol. We then tested whether learning magnitude predicted the clinical (change in SAD symptoms) and cognitive (change in attention bias) responses to treatment. Finally, we tested whether age moderated the association between ABMT learning and treatment response. Results indicate that ABMT was associated with an incremental learning curve during the protocol, and that learning improved with age. Age further moderated the association between learning gains during the ABMT protocol and subsequent reduction in self-reported SAD symptoms, such that this association was stronger with age. These effects were not evident in bias scores or clinician ratings. Finally, pre-treatment SAD symptoms and bias scores predicted ABMT learning gains. This study highlights the links among age, learning processes, and clinical response to ABMT. These insights may inform attempts to increase the clinical efficacy of ABMT for anxiety. [ABSTRACT FROM AUTHOR]

The goal of the present investigation was to clarify and compare the structure of genetic and environmental influences on different types (e.g., physical, verbal) of peer victimization experienced by youth in pre-/early adolescence and mid-/late adolescence. Physical, verbal, social, and property-related peer victimization experiences were assessed in two twin samples (306 pairs, ages 9-14 and 294 pairs, ages 15-20). Cholesky decompositions of individual differences in victimization were conducted, and independent pathway (IP) and common pathway (CP) twin models were tested in each sample. In the younger sample, a Cholesky decomposition best described the structure of genetic and environmental contributors to peer victimization, with no evidence that common additive genetic or environmental factors influence different types of peer victimization. In the older sample, common environmental factors influenced peer victimization types via a general latent liability for peer victimization (i.e., a CP model). Whereas the pre-/early adolescent sample demonstrated no evidence of a shared genetic and environmental structure for different types of peer victimization, the mid-/late adolescent sample demonstrates the emergence of an environmentally-driven latent liability for peer victimization across peer victimization types. [ABSTRACT FROM AUTHOR]

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 children (n = 13, 4 F, age = 9.3-12.2 years), clinically anxious adolescents (n = 18, 6 F, age = 12.3-17.7 years), and healthy adolescents (n =14, 10 F, age = 12.5-17.3 years). Social context was manipulated: in one condition, participants were led to believe that a group of peers were observing and judging their performance (peer-judge), while, in the other condition, they were led to believe that peers were not observing them (control). Only anxious children showed an influence of social context on their risk-taking behavior. Specifically, anxious children bet significantly less and had slower reaction times (RT) during the peer-judge than control condition. However, across social conditions, risk-valence modulated RT differently in function of age and diagnosis. Anxious children were slower on the positive-valence risky trial, whereas anxious adolescents were slower on the negative-valence risky trials relative to their respective healthy peers. In conclusion, clinically anxious children were the only group that was sensitive (risk-averse) to the effect of a negative peer-judge context. The negative peer-judge context did not affect risky decision-making in adolescents, whether they were anxious or healthy. Future work using a stronger aversive social context might be more effective at influencing risky behavior in this age group. [ABSTRACT FROM AUTHOR]

Children with anxiety disorders (ADs) experience persistent fear and worries that are highly debilitating, conferring risk for lifelong psychopathology. Anticipatory anxiety is a core clinical feature of childhood ADs, often leading to avoidance of uncertain and novel situations. Extensive studies in non-human animals implicate amygdala dysfunction as a critical substrate for early life anxiety. To test specific amygdala-focused hypotheses in preadolescent children with ADs, we used fMRI to characterize amygdala activation during uncertain anticipation and in response to unexpected stimuli. Forty preadolescent (age 8-12 years) children, 20 unmedicated AD patients and 20 matched controls completed an anticipation task during an fMRI scan. In the task, symbolic cues preceded fear or neutral faces, such that 'certain' cues always predicted the presentation of fear or neutral faces, whereas 'uncertain' cues were equally likely to be followed by fear or neutral faces. Both AD children and controls showed robust amygdala response to faces. In response to the uncertain cues, AD children had increased amygdala activation relative to controls. Moreover, in the AD children, faces preceded by an 'uncertain' cue elicited increased amygdala activation, as compared with the same faces following a 'certain' cue. Children with ADs experience distress both in anticipation of and during novel and surprising events. Our findings suggest that increased amygdala activation may have an important role in the generation of uncertainty-related anxiety. These findings may guide the development of neuroscientifically informed treatments aimed at relieving the suffering and preventing the lifelong disability associated with pediatric ADs. [ABSTRACT FROM AUTHOR]

Fear to predictable threat and anxiety to unpredictable threat reflect distinct processes mediated by different brain structures, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), respectively. This study tested the hypothesis that the corticotropin-releasing factor (CRF1) antagonist GSK561679 differentially reduces anxiety but increases fear in humans. A total of 31 healthy females received each of four treatments: placebo, 50 mg GSK561679 (low-GSK), 400 mg GSK561679 (high-GSK), and 1 mg alprazolam in a crossover design. Participants were exposed to three conditions during each of the four treatments. The three conditions included one in which predictable aversive shocks were signaled by a cue, a second during which shocks were administered unpredictably, and a third condition without shock. Fear and anxiety were assessed using the acoustic startle reflex. High-GSK had no effect on startle potentiation during unpredictable threat (anxiety) but increased startle potentiation during the predictable condition (fear). Low-GSK did not affect startle potentiation across conditions. Consistent with previous findings, alprazolam reduced startle potentiation during unpredictable threat but not during predictable threat. The increased fear by high-GSK replicates animal findings and suggests a lift of the inhibitory effect of the BNST on the amygdala by the CRF1 antagonist. [ABSTRACT FROM AUTHOR]

Behavioral inhibition (BI) is an early-appearing temperament characterized by strong reactions to novelty. BI shows a good deal of stability over childhood and significantly increases the risk for later diagnosis of social anxiety disorder (SAD). Despite these general patterns, many children with high BI do not go on to develop clinical, or even subclinical, anxiety problems. Therefore, understanding the cognitive and neural bases of individual differences in developmental risk and resilience is of great importance. The present review is focused on the relation of BI to two types of information processing: automatic (novelty detection, attention biases to threat, and incentive processing) and controlled (attention shifting and inhibitory control). We propose three hypothetical models (Top-Down Model of Control; Risk Potentiation Model of Control; and Overgeneralized Control Model) linking these processes to variability in developmental outcomes for BI children. We argue that early BI is associated with an early bias to quickly and preferentially process information associated with motivationally salient cues. When this bias is strong and stable across development, the risk for SAD is increased. Later in development, children with a history of BI tend to display normative levels of performance on controlled attention tasks, but they demonstrate exaggerated neural responses in order to do so, which may further potentiate risk for anxiety-related problems. We conclude by discussing the reviewed studies with reference to the hypothetical models and make suggestions regarding future research and implications for treatment. [ABSTRACT FROM AUTHOR]

Whereas classical Critical Theory has tended to view phenomenology as inherently uncritical, the recent upsurge of what has become known as critical phenomenology has attempted to show that phenomenological concepts and methods can be used in critical analyses of social and political issues. A recent landmark publication, 50 Concepts for Critical Phenomenology, contains no reference to psychiatry and psychopathology, however. This is an unfortunate omission, since the tradition of phenomenological psychiatry—as we will demonstrate in the present article by surveying and discussing the contribution of Jaspers, Minkowski, Laing, Basaglia, and Fanon—from the outset has practiced critical thinking, be it at the theoretical, interpersonal, institutional, or political level. Fanon is today a recognized figure in critical phenomenology, even if his role in psychiatry might not yet have been appreciated as thoroughly as his anticolonial and antiracist contributions. But as we show, he is part of a long history of critical approaches in psychopathology and psychiatry, which has firm roots in the phenomenological tradition, and which keeps up its critical work today. [ABSTRACT FROM AUTHOR]

Since the turn of the twenty-first century, biomedical psychiatry around the globe has embraced the so-called precision medicine paradigm, a model for medical research that uses innovative techniques for data collection and analysis to reevaluate traditional theories of disease. The goal of precision medicine is to improve diagnostics by restratifying the patient population on the basis of a deeper understanding of disease processes. This paper argues that precision is ill-fitting for psychiatry for two reasons. First, in psychiatry, unlike in fields like oncology, precision medicine has been understood as an attempt to improve medicine by casting out, rather than merely revising, traditional taxonomic tools. Second, in psychiatry the term "biomarker" is often used in reference to signs or symptoms that allow patients to be classified and then matched with treatments; however, in oncology "biomarker" usually refers to a disease mechanism that is useful not only for diagnostics, but also for discovering causal pathways that drug therapies can target. Given these differences between how the precision medicine paradigm operates in psychiatry and in other medical fields like oncology, while precision psychiatry may offer successful rhetoric, it is not a promising paradigm. [ABSTRACT FROM AUTHOR]

Rationale: Excessive fear and anxiety, coupled with corticolimbic dysfunction, are core features of stress- and trauma-related psychopathology, such as posttraumatic stress disorder (PTSD). Interestingly, low doses of ∆9-tetrahydrocannabinol (THC) can produce anxiolytic effects, reduce threat-related amygdala activation, and enhance functional coupling between the amygdala and medial prefrontal cortex and adjacent rostral cingulate cortex (mPFC/rACC) during threat processing in healthy adults. Together, these findings suggest the cannabinoid system as a potential pharmacological target in the treatment of excess fear and anxiety. However, the effects of THC on corticolimbic functioning in response to threat have not be investigated in adults with trauma-related psychopathology. Objective: To address this gap, the present study tests the effects of an acute low dose of THC on corticolimbic responses to threat in three groups of adults: (1) non-trauma-exposed healthy controls (HC; n = 25), (2) trauma-exposed adults without PTSD (TEC; n = 27), and (3) trauma-exposed adults with PTSD (n = 19). Methods: Using a randomized, double-blind, placebo-controlled, between-subjects design, 71 participants were randomly assigned to receive either THC or placebo (PBO) and subsequently completed a well-established threat processing paradigm during functional magnetic resonance imaging. Results: In adults with PTSD, THC lowered threat-related amygdala reactivity, increased mPFC activation during threat, and increased mPFC-amygdala functional coupling. Conclusions: These preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology. [ABSTRACT FROM AUTHOR]

Objectives: Socially anxious adolescents often display fears of negative evaluation (FNE) and fears of positive evaluation (FPE). The Bivalent Fear of Evaluation model posits that FNE and FPE represent two poles of socio-evaluative fears, and that individuals may simultaneously display high levels of FNE and FPE (high FNE/FPE). To what degree do adolescents who display high FNE/FPE differ in psychosocial functioning from adolescents who display high concerns on one domain and not the other (either high FNE/low FPE, or low FNE/high FPE), or low concerns on both domains (i.e., low FNE/FPE)? We tested this broader question (a) across multiple psychosocial domains, (b) using multiple informants' reports to identify adolescents' patterns of socio-evaluative fears, and (c) in relation to adolescents' reactions to anxiety-provoking social situations with unfamiliar peers. Methods: One-hundred twenty-seven 14–15-year-old adolescents and their parents completed measures of adolescents' FNE, FPE, and domains of psychosocial functioning (i.e., social anxiety, safety behaviors, depressive symptoms, psychosocial impairments). Adolescents participated in several social interaction tasks with unfamiliar peers. Adolescents self-reported on their arousal during these tasks and the unfamiliar peers with whom they interacted completed measures of social anxiety about the adolescent. Results: High FNE/FPE adolescents tended to display poorer psychosocial functioning relative to adolescents who displayed other patterns of socio-evaluative fears. Based on adolescent-classified groups, high FNE/FPE adolescents displayed greater self-reported arousal during social interactions, relative to the other groups. Conclusions: Identifying adolescents' patterns of socio-evaluative fears may inform interpretations of the individual differences among adolescents' clinical presentations of social anxiety. [ABSTRACT FROM AUTHOR]

After obtaining a sample of published, peer-reviewed articles from journals with high and low impact factors in social, cognitive, neuro-, developmental, and clinical psychology, we used a priori equations recently derived by Trafimow (Educational and Psychological Measurement, 77, 831–854, 2017; Trafimow & MacDonald in Educational and Psychological Measurement, 77, 204–219, 2017) to compute the articles' median levels of precision. Our findings indicate that developmental research performs best with respect to precision, whereas cognitive research performs the worst; however, none of the psychology subfields excelled. In addition, we found important differences in precision between journals in the upper versus lower echelons with respect to impact factors in cognitive, neuro-, and clinical psychology, whereas the difference was dramatically attenuated for social and developmental psychology. Implications are discussed. [ABSTRACT FROM AUTHOR]

We examined one-month reliability, internal consistency, and validity of ostracism distress (Need Threat Scale) to simulated social exclusion during Cyberball. Thirty adolescents (13–18 yrs.) completed the Cyberball task, ostracism distress ratings, and measures of related clinical symptoms, repeated over one month. Need Threat Scale ratings of ostracism distress showed adequate test-retest reliability and internal consistency at both occasions. Construct validity was demonstrated via relationships with closely related constructs of anxiety, anxiety sensitivity, and emotion dysregulation, and weaker associations with more distal constructs of state paranoia and subclinical psychosis-like experiences. While ratings of ostracism distress and anxiety were significantly attenuated at retest, most participants continued to experience post-Cyberball ostracism distress at one-month follow-up, which indicates that the social exclusion induction of Cyberball persisted despite participants' familiarity with the paradigm. Overall, results suggest that the primary construct of ostracism distress is preserved over repeated administration of Cyberball, with reliability sufficient for usage in longitudinal research. These findings have important implications for translating this laboratory simulation of social distress into developmental and clinical intervention studies. [ABSTRACT FROM AUTHOR]

The Multidimensional Peer Victimization Scale (MPVS; Mynard and Joseph, British Journal of Educational Psychology, 67, 51-54 2000) is a 16-item self-report scale that captures peer victimization across four dimensions: physical victimization, verbal victimization, social manipulation, and attacks on property. Performance of the scale has not been evaluated among older adolescents. We examined the factor structure, internal consistency reliability, and performance of the scale in two separate epidemiological U.S. samples representing different age groups: 9-14 year olds (N = 610) and 15-17 year olds (N = 524). The four-factor structure of the scale was affirmed in both samples, however; there was not metric invariance by gender in the younger age group. The scale and its subscales were found to have good internal consistency. Expected relationships between the MPVS and measures of irritability, anxiety, and depression were affirmed. Results support continued use of the MPVS among child and adolescent samples. [ABSTRACT FROM AUTHOR]

An author index for the December 2015 issue of "Neuropsychopharmacology" is presented.