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Presenting unpaired unconditional stimuli (US) during extinction training reduces the renewal of conditional fear due to context change and slows re-acquisition. The present study investigated whether this reduced return of fear is mediated by Pavlovian inhibitory conditioning to the conditional stimulus paired with the US during acquisition (CS+) that is acquired when this stimulus is presented without the US in an excitatory extinction context. Using an ABA renewal paradigm that trained extinction in a context different from acquisition and renewal test, participants either received no USs (Standard), five unsignalled US presentations (Unsignalled) or five presentations of the US preceded by a novel, third CS (Signalled) during extinction training. Extinction was followed by tests for renewal and re-acquisition. Replicating previous results, renewal of electrodermal conditional responses was observed in group Standard, but not in group Unsignalled. Signalling the additional USs, and thus reducing context conditioning and the potential for inhibitory conditioning, did not reduce their effect in that renewal was absent in group Signalled. These results are inconsistent with an inhibitory conditioning account of the effects of unpaired US presentations during extinction. A trial sequence learning account or an arousal account may explain the effects of unpaired presentations of the US during extinction., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Extinction, the repeated presentation of a conditional stimulus (CS) without the unconditional stimulus (US), is the standard paradigm to reduce conditional responding acquired by the repeated pairing of CS and US in acquisition. However, this reduction of conditional responding is prone to relapse. In rodent fear-conditioning, gradual extinction, the fading out of CS-US pairings during extinction, has been shown to reduce the return of fear. The current study replicated the gradual extinction procedure in human fear conditioning and assessed whether it reduced the return of fear due to ABA renewal and reacquisition. During extinction, one group received standard extinction, a second received gradual extinction (increasing the spacing of USs presented after the 1st, 3rd, 6th, 10th, and 15th CS+ trials), and a third received reversed extinction training (decreasing the spacing of USs presented after the 1st, 6th, 10th, 13th, and 15th CS+ trials). Larger renewal and faster reacquisition of differential electrodermal responses to CS+ and CS- were expected after standard and reversed extinction than after gradual extinction training. The results were inconclusive due to the failure to find extinction of differential electrodermal responses and US expectancy ratings in both gradual and reversed extinction groups. Despite successful extinction in group standard, renewal was only observed in US expectancy. Visualization of US expectancy ratings during extinction suggested that potential identification of the US presentation patterns during extinction in the gradual and reversed groups delayed extinction learning., (© 2024 The Author(s). Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Fear conditioning is a common experimental paradigm for modelling the development, and exposure-based treatment, of anxiety disorders. Measures of fear such as threat-expectancy, physiological arousal, and fear ratings typically extinguish, however feared stimuli may still be evaluated negatively (i.e. retain negative valence). This systematic review provides the first investigation of the relationship between fear conditioning methodology and extinction of negative stimulus valence. Principal findings were that type of CS (conditioned stimulus) and the CS-US pairing (i.e. specific combination of CS and unconditioned stimulus) predicted extinction outcome. Extinction of absolute negative CS valence was always achieved with shape CSs; often achieved with low fear-relevant animals as CSs, and less frequently achieved with faces as CSs - particularly neutral faces paired with a shock US. Modified extinction procedures typically achieved the same outcome as standard extinction procedures, except for partially-reinforced extinction, which was less effective than standard extinction, and positive imagery training, which was more effective than standard extinction. Further studies are warranted to evaluate the influence of fear conditioning methodology on extinction of absolute negative CS valence., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We further confirm that any aspect of the work covered in this manuscript that has involved human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). They are responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author and which has been configured to accept email from jamiah.hyde@griffithuni.edu.au., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The association between anxious mood and aberrant fear learning mechanisms has not been fully elucidated. Studying how fear conditioning and extinction constructs relate to anxiety symptoms and reactivity to stressful and benign moments in everyday life provides a powerful addition to experimental paradigms., Method: Fifty-one young adults completed laboratory-based differential conditioning and extinction tasks with (CS + ) and without (CS-) an aversive unconditional stimulus (US). Electrodermal skin conductance responses were measured during each phase, followed by ecological momentary assessment (EMA) tapping anxiety and stressors six times daily for seven days (2, 142 moments)., Results: Conditioned electrodermal reactivity to the CS + and overgeneralisation to the CS- were associated with greater change in anxiety (measured via EMA), across non-stressful situations, remaining the same across stressful situations. Likewise, during extinction when the CS + is now safe, more electrodermal reactivity to the CS + was associated with more anxiety change across non-stressful situations and remained the same across stressful situations. Also, during extinction when threat is absent, more electrodermal reactivity at the late stage of the CS- was associated with less momentary anxiety change in response to stressful situations; more electrodermal activity at the late stage of the CS + was associated with more anxiety change across non-stressful situations and remained the same across stressful situations., Conclusions: Sampling 'in vivo' emotion and stress experiences, study findings revealed links between conditioned electrodermal reactivity and overgeneralisation to safe stimuli and heightened anxious reactivity during non-stressful (i.e. safe) moments in daily life, coupled with less change in response to actual stressors.

Past research has shown that Intolerance of Uncertainty (IU) affects Pavlovian fear conditioning processes. In particular, extinction of learned fear is delayed in those reporting high IU. Reports of differences during acquisition are less consistent with most of the studies reporting no evidence for effects of IU. This may be due to past studies' focus on first interval electrodermal responses or fear potentiated startle, rather than on indices that may better capture uncertainty - like the response to the absence of a probabilistic unconditional stimulus. The current analysis combined data across three experiments that employed a 50 % reinforcement schedule and assessed electrodermal responses and (in two experiments) ratings of conditional stimulus pleasantness. Participants scoring high on IU showed overall larger electrodermal first interval responses during habituation and acquisition but did not differ from those scoring low on IU in differential conditioning (the difference between CS+ and CS-), as indicated by electrodermal first or second interval responses or ratings of CS pleasantness. However, participants high in IU showed larger differential third interval electrodermal responses to the omission of the electro-tactile unconditional stimulus during acquisition. Some evidence for this difference emerged in each experiment, supporting the reliability of the result. The current results suggest that effects of IU emerge in conditions of high uncertainty in Pavlovian fear learning tasks, such as during the omission of probabilistic unconditional stimuli., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Relapse and return of fear are common following exposure-based treatments which aim to decrease anxiety by reducing danger expectancies and negative stimulus evaluations. Using Pavlovian conditioning and extinction procedures, recent studies found that verbalising catchphrases to prompt attention to, and memory of, stimulus contingencies during extinction prevented US expectancy generalisation to safe stimuli and reduced anxiety ratings. Verbalizations did not improve negative evaluations of conditional stimuli. Given that negative evaluations predict return of fear, the current study examined whether verbalisation strategies combined with listening to liked, non-lyrical background music enhanced expectancy learning and positively changed stimulus evaluations. A differential Pavlovian conditioning procedure was used involving fear acquisition, extinction, and extinction retest phases. Participants were assigned to a verbalisation condition (N = 21), a verbalisation plus liked, non-lyrical music condition (N = 21) or a control condition (N = 21) during extinction. The verbalisation strategies, with and without music, prevented the generalisation of US expectancies to safe stimuli at retest. Verbalisation strategies plus music increased positive evaluations of conditional stimuli during extinction and retest. Further research on the role of verbalising attention regulation strategies and liked, non-lyrical background music during extinction is warranted with clinical samples., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Past research has shown that presenting unconditional stimuli (US) during extinction training, either paired with the conditional stimulus (CS) or explicitly unpaired, can reduce spontaneous recovery and slow the re-acquisition of conditional fear. Whether contextual renewal of conditioned fear as indexed by electrodermal responses and self-report measures of anxiety and CS evaluations is also reduced after presentation of paired or unpaired USs during extinction training is currently unclear. Three groups of participants (Paired, Unpaired, Standard Extinction) completed a sequence of habituation, acquisition, extinction, renewal, and re-acquisition phases. During extinction, five CS-US pairings were presented in group Paired, whereas five US were presented alone in group Unpaired. No US were presented during standard extinction. For all groups, extinction was conducted in a context that was different from that of the other phases. Extinction of differential electrodermal responding was evident in groups Unpaired and Standard, but not in group Paired. Contextual renewal and fast re-acquisition, as indexed by differential electrodermal responding, were evident in group Standard, but not in group Unpaired and differential electrodermal responding persisted in group Paired. After extinction, self-reported anxiety was higher in groups Paired and Unpaired, but differential CS evaluations were evident in group Paired only. The current results suggest that presenting additional unpaired USs during extinction training strengthens extinction and protects against the renewal of differential electrodermal responding., (© 2021 Society for Psychophysiological Research.)

Recent studies have shown that extinction training including the conditional stimulus (CS+) and stimuli similar to the CS + enhances extinction retention and generalisation to novel stimuli. The aim of the present study was to confirm that these effects are specific to presenting stimuli similar to the CS+ during extinction and not merely an effect of additional trials or additional stimuli unrelated to the CS+. In an experiment conducted in a single session on the same day, participants (134 adults; 70.7% female; 17-40 years of age, M = 20.04, SD = 4.36) completed a habituation phase followed by an acquisition phase using dog images presented with (CS+) and without (CS-) a dog growl paired with a scream unconditional stimulus (US). Participants were randomly allocated to four extinction conditions: Multiple exemplar extinction comprising the CSs and two novel dog images similar to the CS+; Standard extinction control matched for the number of CS+ and CS- presentations; Extended extinction control matched for the total number extinction trials, and Other stimuli extinction control comprising the CSs and two novel stimuli unrelated to the CS+. All participants completed an extinction test with the original CSs followed by a generalisation test with two novel dog images. Multiple, Standard and Other stimuli extinction groups exhibited larger skin conductance responses (SCRs) during extinction to the CSs compared to the Extended extinction group. SCRs to the additional dog images in the Multiple group were larger than SCRs to the additional CSs in the Extended group and the novel images in the Other stimuli group. There were no group differences in responses to the CSs during extinction test. Unlike the other groups, SCRs to the first presentation of the novel generalisation dogs did not differ from those to the last CS trials in extinction in the Multiple group. However, this group difference did not persist beyond the initial generalisation trial. Finally, the Multiple, Extended, and Other stimuli groups exhibited more negative CS evaluations after extinction, extinction test, and generalisation test than the Standard extinction group. The results suggest that extinction with the original CSs and additional stimuli resembling the CS + elevated physiological responses during extinction and reduced physiological responses to novel stimuli similar to the CSs. Further studies are needed including clinical samples and trial-by-trial evaluations of the stimuli presented., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The type and number of dependent measures assessed have varied between fear conditioning and extinction experiments and it remains unclear whether methodological differences influence results. Measuring skin conductance responses (SCRs) and between-phase subjective ratings between four conditions; Con condition had no within-phase ratings; US Exp condition included within-phase US expectancy ratings only; CS Eval condition included within-phase CS evaluations only and All Meas condition included both. All Meas condition exhibited larger SCRs compared to other conditions during acquisition, extinction, and return of differential responding at test. Differential SCRs did not extinguish in CS Eval and Con conditions, and CS Eval condition exhibited smaller CS- SCRs than other conditions throughout phases. US Exp condition revealed differential conditioning, successful extinction, and no return of differential SCRs. Between-phase ratings were not affected by within-phase ratings. Researchers should consider assessing different combinations of within-phase subjective ratings depending on the aims of their research., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The mechanisms by which exposure to adversity contributes to psychopathology development are poorly understood. Recent models link experiences of threat of harm and deprivation to psychopathology via disruptions in learning mechanisms underlying fear acquisition and extinction. We empirically tested dimensional elements of this model, by examining whether exposure to images of community violence or neglect differentially influenced fear learning and extinction relative to exposure to neutral images. Participants were randomly allocated to one of three exposure conditions: viewing images depicting neglect (n = 25), violence (n = 25) or control images (n = 24). All participants then completed a fear conditioning and extinction task in which the CS+ was paired with an aversive tone, and the CS- was presented alone during conditioning. Both CSs were presented alone during extinction and extinction retest. Skin conductance responses (SCR) and subjective ratings were assessed. Relative to control images, viewing scenes of neglect attenuated SCRs to the CSs during conditioning, extinction and extinction retest. Exposure to images of community violence accentuated SCRs during US anticipation on CS+ trials and impaired the retention of safety learning (larger SCRs to the CS+ compared to the CS- at retest and the CS+ at the end of extinction). No significant group differences emerged in subjective ratings. Findings lend preliminary support for suggestions that adverse experiences may be linked to impairments in fear and safety learning and provide key evidence suggesting that the expression of these impairments may differ as a function of the type of adversity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Since Watson and Rayner's (1920) initial demonstration that human fear can be learned by means of Pavlovian conditioning, neuroscientific and behavioral studies have provided a thorough understanding of fear acquisition. Less is known about the manner in which we can harness insights from Pavlovian conditioning research to reduce fears and, most importantly, make the reduction of fear lasting and resistant against relapse. The current paper reviews three manipulations that have shown promise in achieving a reduction of conditional fear that is more resistant to relapse than is the reduction of conditional fear after standard extinction: novelty-facilitated extinction training, presentation of conditional-unconditional stimulus pairings or of unpaired unconditional stimuli during extinction, and extinction with additional stimuli that are similar to the original conditional stimuli. It summarizes past research involving human and non-human animal subjects and highlights knowledge gaps in the current literature. Moreover, it discusses potential mechanisms that mediate the reduction of fear seen as a result of these manipulations in an attempt to enhance our understanding of what renders fear extinction less vulnerable to the known pathways to fear relapse. It is hoped that this review will contribute to the achievement of the goal that was denied to Watson and Rayner, the development of experimental techniques that can be utilized to remove conditioned emotional responses permanently., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Fear extinction studies in youth have yielded mixed results due to developmental processes and variations in design, methodology and dependent measures. This systematic review focused on studies with healthy youth between 2 and 17 years of age to identify experimental parameters of studies documenting extinction effects. Thirty-five studies met inclusion criteria and the following themes emerged (a) some studies employed parameters and task demands that are complex and require active participant involvement whereas others involved simple stimulus configurations and passive participant involvement, and (b) variation exists among dependent measures in units of measurement, timing and type of measurement. The review identified that studies using geometric shape conditioned stimuli (CS) paired with a tone unconditioned stimulus (US) (e.g., metal scraping on slate), as well as face CSs with a scream US produced the most reliable extinction effects, although the latter combination may be associated with higher drop-out than shape CSs and a tone US. The most commonly used and effective dependent measures for revealing extinction effects were skin conductance responses (SCR) and subjective ratings (SR) of CS valence, fearfulness and arousal. Fear potentiated startle (FPS) blink reflexes were also an effective but less commonly used measure. It is recommended that future studies use shape CSs and the metal scraping on slate US in studies involving children and either shape CSs and the metal scraping on slate US or face CSs paired with a scream US with adolescents. It is also recommended that US expectancy ratings and CS evaluations are assessed trial-by-trial and between-phase, and that startle-eliciting stimuli to measure startle blink reflexes are delivered on every second trial per CS so that SCR and FPS can be examined. However, further research is required to determine whether increased participant involvement due to providing trial-by-trial and between-phase ratings of the CSs and US differentially influences responding, particularly in children relative to adolescents and adults., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Exposure therapy is a key component of efficacious treatment for anxiety. Biases in the allocation of attention towards versus away from threat assessed prior to exposure-based treatments such as cognitive-behavioural therapy differentially predict treatment outcomes. However, it is unclear whether monitoring versus avoiding threat stimuli influences learning during exposure. Extinction paradigms are the experimental analogue of exposure therapy. Therefore, manipulating attention towards versus away from threat during extinction trials may shed light on the role of attention during exposure therapy. This study utilised a Pavlovian fear conditioning and extinction paradigm to examine whether directing attention towards versus away from the threat conditioned stimulus (CS+) related to differences in extinction, as indexed by skin conductance responses (SCR), CS evaluations and subjective measures of anxiety. Following a fear conditioning phase in which a dog image (CS+) was paired with an aversive tone unconditioned stimulus (US) and another dog image (CS-) was presented alone, 57 participants were randomly assigned to one of three conditions during extinction in which both CSs were presented alone: monitor the CS+ (N = 19), avoid the CS+ and attend to another stimulus (N = 18), no attention manipulation control (N = 20). Eye movements were monitored for visual adherence to assigned location using horizontal electro-oculogram. In the context of the acquisition of differential conditioning and visual adherence during extinction, both active groups exhibited larger SCRs to the CS + relative to the CS- during the first extinction block compared to the control group, and the avoid group exhibited significantly larger SCRs on CS+ and CS- trials throughout the extinction phase compared to the other groups. The avoid group also exhibited less decline in SCRs to the CS+ during the extinction retest phase relative to the control group. No significant group differences were observed in between-phase CS evaluations and subjective anxiety ratings. Avoidance of threat conditioned stimuli may impair extinction learning and increase physiological arousal generalisation to safe stimuli., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study investigated developmental differences in aversive conditioning, extinction, and reinstatement (i.e., the recovery of conditioned aversive associations following reexposure to the unconditioned stimulus [US] post-extinction). This study examined these mechanisms in children (M age =8.8years), adolescents (M age =16.1years), and adults (M age =32.3years) using differential aversive conditioning with a geometric shape conditional stimulus (CS+) paired with an aversive sound US and another shape (CS-) presented alone. Following an extinction phase in which both CSs were presented alone, half of the participants in each age group received three US exposures (reinstatement condition) and the other half did not (control condition), followed by all participants completing an extinction retest phase on the same day. Findings indicated (a) significant differences in generalizing aversive expectancies to safe stimuli during conditioning and extinction that persisted during retest in children relative to adults and adolescents, (b) significantly less positive CS reevaluations during extinction that persisted during retest in adolescents relative to adults and children, and (c) reinstatement of US expectancies to the CS+ relative to the CS- in all age groups. Results suggest important differences in stimulus safety learning in children and stimulus valence reevaluation in adolescents relative to adults., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 anxious, 7-to-13-year-old children completed a Pavlovian conditioning and extinction task. Anxious children then completed group-based CBT. Skin conductance responses (SCRs) as well as subjective arousal and valence evaluations were measured in response to a conditioned stimulus paired with an aversive tone (CS+) and another conditioned stimulus presented alone (CS-). Both stimuli were presented alone during extinction. Diagnostic and symptom measures were completed before and after treatment., Results: Like nonanxious comparisons, treatment responders did not acquire conditioned negative stimulus evaluations and displayed elevated SCRs that declined significantly across extinction trials. Nonresponders, by contrast, showed elevated negative stimulus evaluations of both CSs that were sensitive to extinction trials but showed no change in SCRs during extinction. Change in physiological but not evaluative indices of fear extinction predicted better treatment outcomes., Conclusions: Individual differences in evaluative and physiological indices of fear extinction might moderate response to CBT., (© 2016 Association for Child and Adolescent Mental Health.)

Anxious children show attention biases towards and away from threat stimuli. Moreover, threat avoidance compared to vigilance predicts a poorer outcome from exposure-based treatments, such as cognitive-behavioural therapy (CBT), yet the mechanisms underlying this differential response are unclear. Pavlovian fear conditioning is a widely accepted theory to explain the acquisition and extinction of fear, including exposure-based treatments, such as CBT. In typical fear conditioning experiments, anxious children have shown larger physiological responses to an aversive unconditional stimulus (i.e., US on CS+ trials) and to non-reinforced stimuli (CS-) during fear acquisition and to both CSs during fear extinction compared to non-anxious peers. This study examined whether threat avoidance compared to threat vigilance was related to differences in fear acquisition and extinction in anxious children. Thirty-four clinically-anxious children completed a visual probe task including angry-neutral face pairs to determine the direction of threat attention bias as well as a discriminant conditioning and extinction task in which a geometric shape CS+ was paired with an aversive tone US, while the CS- geometric shape was always presented alone during acquisition trials. Both CSs were presented alone during extinction trials. Fear acquisition and extinction were indexed by skin conductance responses (SCR) and subjective measures. Children were classified as threat vigilant (N = 18) and threat avoidant (n = 16) based on the direction of threat attention bias on the visual probe task. During acquisition, threat avoidant relative to threat vigilant anxious children displayed larger orienting SCRs to both CSs during the first block of trials and larger third interval SCRs to the US on CS+ trials as well as on CS- trials. During extinction, threat avoidant anxious children showed delayed extinction of SCRs to both the CS+ and CS- and reported higher subjective anxiety ratings after extinction compared to threat vigilant anxious children. Threat avoidant anxious children may be more reactive physiologically to novel cues and to stimuli that become associated with threat and this may interfere with extinction learning. These findings could help explain previous evidence that threat avoidant anxious children do not respond as well as threat vigilant anxious children to exposure-based CBT., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Maternal anxiety and depression are significant risk factors for the development of these disorders in offspring. The pathways through which risk is conferred remain unclear. This study examined fear acquisition and extinction in 26 children at high risk for emotional disorders by virtue of maternal psychopathology (n=14 with a mother with a principal anxiety disorder and n=12 with a mother with a principal unipolar depressive disorder) and 31 low risk controls using a discriminative Pavlovian conditioning procedure. Participants, aged between 7 and 14 years, completed 16 trials of discriminative conditioning of two geometric figures, with (CS+) and without (CS-) an aversive tone (US), followed by 8 extinction trials (4×CS+, 4×CS-). In the context of comparable discriminative conditioning, children of anxious mothers showed larger skin conductance responses during extinction to the CS+ compared to the CS-, and to both CSs from the first to the second block of extinction trials, in comparison with low risk controls. Compared to low risk controls, children of depressed mothers showed smaller skin conductance responses to the CS+ than the CS- during acquisition. These findings suggest distinct psychophysiological premorbid risk markers in offspring of anxious and depressed mothers., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Learning-based models of anxiety disorders emphasize the role of aversive conditioning and retarded extinction in the etiology and maintenance of anxiety disorders. Yet few studies have examined these underlying processes in children, despite that some anxiety disorders typically onset during childhood. The authors examined the acquisition and extinction of conditioned responses in 17 anxious children and 18 nonanxious control children between 8 and 12 years old using a discriminative Pavlovian conditioning procedure. One geometric shape conditional stimulus was paired with an unpleasant loud tone unconditional stimulus (CS+) whereas another geometric shape was presented alone (CS-). In the context of similar levels of discriminative conditioning in both groups, anxious children showed larger skin conductance responses to the CS+ and the CS- during acquisition and evaluated the CS+ as more arousing than the CS- compared with control children. They also showed greater resistance to extinction in skin conductance responses but not in arousal ratings to the CS+ vs. the CS- relative to control children. Results suggest that deficits in response inhibition to safety cues and retarded extinction may underlie learning processes involved in the pathogenesis of childhood anxiety disorders.