Intolerance of Uncertainty and Parental Accommodation: Promising Targets for Personalized Intervention for Youth Anxiety

Abstract

Purpose of Review

After reviewing predictors of differential outcomes of cognitive behavioral therapy (CBT) for pediatric anxiety, we identify and discuss recent evidence for the role of (a) intolerance of uncertainty (IU) and (b) parental accommodation as meaningful targets for personalized intervention.

Recent Findings

Few studies to date have identified promising, theory-driven predictors of differential CBT outcomes. Recent findings suggest that increased IU and high levels of parental accommodation are associated with a poorer response to CBT. Several adaptations of CBT and new interventions targeting either IU or parental accommodation have been developed and found to be efficacious in preliminary studies.

Summary

IU and parental accommodation are promising constructs for personalizing intervention, both in the identification of who will respond to treatment and in the development of targeted intervention. We recommend that future work test if individuals high in IU and/or parental accommodation will respond more optimally to treatments that specifically target these constructs. The results of this future work may help to move the field closer to personalized intervention.

Introduction

Anxiety disorders are the most common form of psychopathology in children and adolescents (referred throughout as youth), with 6.5% pooled prevalence rates worldwide [1]. Left untreated, these disorders are associated with considerable cross-sectional and longitudinal functional impairment (i.e., decreased life satisfaction; increased academic, family, and social dysfunction) [2], along with increased risk for ongoing psychiatric difficulty into adulthood (i.e., suicidality [3], substance use problems [4], and additional psychopathology [5, 6]). On a broader scale, anxiety disorders in youth confer sizable economic burden commensurate with or higher than the cost associated with other common forms of youth psychopathology, particularly as anxiety symptom severity increases [7]. Thus, there is consensus that the efficacious treatment of youth anxiety disorders is critical at both the micro- and macro-level.

Several empirically supported treatments (ESTs) exist for youth anxiety. Among them, cognitive behavioral therapy (CBT) is a well-established treatment that has been designated as a first-line intervention [8•]. Following decades of randomized clinical trials (RCTs) examining CBT efficacy, e.g. [9–13], reviews, suggest that approximately 60% of youth respond to a full course of CBT [14, 15]. Such findings are encouraging but identify a need to better tailor treatment to the individual. Several strategies have been offered for developing such personalized interventions, the most common of which is the adaptation of CBT for specific subgroups [16••]. In this approach, subgroups of youth not expected to fully respond to typical CBT protocols are identified using baseline predictors of differential response. Treatments can then be adapted to better fit the needs of these individuals through updated content or additional treatment components. In the current review, we consider how best to apply this strategy to youth anxiety treatment. Specifically, we (a) briefly review studies of CBT predictors to identify potential variables for categorizing subgroups, (b) identify two variables—intolerance of uncertainty (IU) and parental accommodation—that have promise, and (c) discuss efforts to personalize treatment to better target these variables.

Predictors of Differential Response

A small percentage (28.6%) [17] of RCTs for youth anxiety treatments have reported formal predictor analyses, although emphasis on identification of predictors is increasing [18]. To date, these analyses have primarily examined routinely collected pretreatment youth demographic and clinical characteristics. Few statistically significant and no consistent predictors have been identified across studies [17–19]. In one review of 32 peer-reviewed studies examining youth anxiety CBT treatments of varying formats and protocols, authors concluded that no baseline youth demographic (i.e., biological sex, age, ethnicity, intellectual functioning) or clinical factors (i.e., primary anxiety diagnosis, anxiety severity, general comorbidity, co-occurring externalizing or other internalizing disorders) consistently predicted differential outcome across a majority of reviewed studies [18]. A second review of 51 peer-reviewed and dissertation studies of CBT efficacy similarly reported that the same set of youth demographic (including socioeconomic status/income) and clinical pretreatment variables were not consistently associated with either endpoint symptoms or rate of symptom change [19]. Pretreatment parental psychopathology (i.e., anxiety, depression, psychopathology more broadly) was also not a consistent predictor of post-treatment response. Findings from both studies were in contrast with results from a third review of psychotherapy and medication treatments for youth anxiety, which pointed to increased baseline symptom severity and family dysfunction as predictors of poorer outcome [17]. However, taken together, these reviews highlight a clear conclusion: consistent predictors of CBT response have yet to be identified. Thus, knowledge regarding how best to make empirically guided decisions on stratifying youth into meaningful subgroups for treatment personalization is in its infancy. Current non-significant findings may be due, in part, to the preponderance of analyses that are not grounded in a strong theory of youth anxiety development, maintenance, and treatment.

As the field moves toward personalized intervention research, predictor selection based on theoretical models may yield more favorable results. Across most studies, the predictors examined were routine pretreatment measures leveraged to conduct secondary predictor analyses [17–19]. Such analyses are an important part of the first phase of research focused on establishing CBT efficacy [20]. However, as the field moves toward personalized intervention research, analyses grounded in a strong theory of youth anxiety development, maintenance, and treatment will be required. For example, the most recent review of CBT efficacy studies reported that a comparatively large number of studies (N = 22) examined age as a predictor [19]. Although results were not significant across the majority of studies, if findings had pointed to age as a meaningful predictor, the next steps for treatment personalization would be unclear without an articulated theory as to why age might differentiate predictors and non-predictors. If age consistently predicted outcome, this could be attributed to any number of unassessed third variables for which age is a proxy. For example, the development of meta-cognitive strategies might enable adolescents to better engage with cognitive restructuring exercises, or perhaps decreased dependence on parents during adolescence may render maladaptive parenting behaviors less influential in the maintenance of anxiety symptoms over time. In the next phase of CBT research, theories behind predictor variables will need to be articulated and assessed via appropriate measures of theoretically relevant constructs.

Constructs of Interest

IU and parental accommodation, both of which are central to the etiology and maintenance of youth anxiety disorders, are promising targets for the identification of meaningful subgroups and development of personalized intervention. We define IU and parental accommodation and present theoretical models discussing their role in the development and maintenance of youth anxiety as an argument for their consideration as stratification variables. We then review recent studies of the association between constructs of interest and treatment response, with a focus on predictor analyses when available, and discuss work on leveraging these findings into more targeted treatments.

Intolerance of Uncertainty

Definition

IU has most recently been defined as “an individual’s dispositional incapacity to endure the aversive response triggered by the perceived absence of salient, key, or sufficient information, and sustained by the associated perception of uncertainty.” [21] Thus, an individual’s experience of a feared stimulus (i.e., the unknown) triggers a fear response that is experienced as aversive and maintained by the individual’s perceptions of uncertainty (i.e., IU). Although IU was originally presented as underlying generalized anxiety disorder (GAD), there is strong support not only for the association between IU and symptoms or a diagnosis of GAD [22, 23] but also for the association between IU and social anxiety disorder, separation anxiety disorder (SAD), panic disorder, obsessive compulsive disorder, and health anxiety [24–28]. As a result, IU can be viewed as a transdiagnostic construct underlying a diverse range of anxiety disorders [29]. In support of IU as a transdiagnostic construct, several studies have found that IU is associated with global anxiety severity, but not with GAD symptom severity specifically [30, 31].

Theoretical Model

The first theory proposed to explain the role of IU in anxiety was the intolerance of uncertainty model (IUM), which has formed the theoretical foundation of several subsequent treatments developed targeting IU [32]. In the first of four main model features, it was proposed that individuals with GAD have a lower threshold for tolerating uncertain or ambiguous situations (i.e., high IU), which leads to either the increase in or onset of reassurance-seeking “what if?” questions. Worries are then further exacerbated by three cognitive processes (i.e., positive beliefs about worry, negative problem orientation, and cognitive avoidance of feared mental imagery). Research has offered some support for IUM in both adult samples [32–37] and samples of youth as young as 7 years old [14, 38–42]. Interestingly, although some findings suggest that IUM is more applicable to adolescents than children, IU remains the strongest predictor of worry frequency in both age groups when compared with both cognitive avoidance and positive beliefs about worry [43]. This finding may be surprising, as meta-cognitive ability is likely necessary for youth to experience and report on IU, and meta-cognitive ability continues to progress through late adolescence and only stabilizes in adulthood [44]. However, studies report that youth begin to consider multiple outcomes within a single situation as young as 7 years of age [45] and that 8-year-old children exhibit meta-cognitive processes when experiencing uncertainty and modulate their responses in the face of uncertainty at comparable rates with adults [46]. Thus, IU may be a relevant construct for youth as young as 7 years of age.

Given the observed importance of IU, a new model has been proposed to clarify the unique role of IU in the development and maintenance of anxiety and to provide a framework for targeting IU within CBT [47•]. This model posits that contextual attributes (i.e., ambiguity, novelty, unpredictability) trigger a state of uncertainty that, when misinterpreted as catastrophic, results in excessive anxiety, worry, and engagement in safety behaviors; each phase of this cycle is compounded by dispositional IU, along with emotional state and life circumstances. For example, individuals high in IU may be more likely to detect ambiguity in neutral situations and experience increased anxiety as a consequence.

Predictor Studies

The majority of studies conducted to date examining the role of IU in treatment outcome have been conducted in adult samples and have focused primarily on within-treatment IU change, rather than looking at the association between baseline IU and post-treatment response in line with convention for defining predictors [20, 48]. Results of multiple studies in adults have found that IU decreased over the course of typical CBT and that greater changes in IU were associated with greater reduction in symptom severity from pre- to post-treatment [49–51]. Additionally, one study in adults examining the association between change in IU and the rate of symptom change found that higher pretreatment IU was associated with higher symptom severity during treatment and post-treatment, although IU did not moderate the rate of change in symptoms throughout CBT [52].

To date, no studies have examined whether baseline IU predicts differential response in youth, although one study extending findings within adult samples to examine whether change in IU predicts CBT response warrants review [53••]. In this study of anxious youth ages 7–17 (N = 73) who completed 16 weeks of child-focused CBT, greater reductions in IU from pre- to post-treatment were significantly associated with the three outcome variables examined, including increased coping efficacy, decreased symptom severity, and decreased functional impairment. Findings remained significant after controlling for demographics (i.e., age, sex) and other variables hypothesized to impact the relationship between IU and outcome (i.e., pretreatment levels of IU, pretreatment levels of the outcome variables), and results were consistent across both child and parent reports. Thus, preliminary results examining the association between change in IU and CBT response in youth and adult samples are promising and additional predictor analyses are needed. Of note, additional mediation analyses may also be warranted, as one study found that reductions in IU mediated (and preceded) reductions in worry, but the reverse pattern was not found, highlighting the role of IU as a target of treatment and its effect on worry [54].

Intervention

The majority of research on interventions designed to directly target IU has been conducted in adults. Ladouceur and colleagues trialed the Intolerance of Uncertainty Treatment (IUT) that included awareness training, targeting positive beliefs about worry, problem-orientation training, and cognitive exposure [55]. Following treatment, 77% of participants no longer met diagnostic criteria for GAD and significant reductions in IU and GAD symptoms were reported. Similar efficacy and reductions in IU were found in a group format of the same treatment [56], although an RCT comparing IUT with meta-cognitive therapy and a waitlist control reported larger effect sizes for meta-cognitive therapy than for IUT [57]. Elements targeting IU have also been incorporated into group CBT for social anxiety disorder [58] and via behavioral experiments in adults [33], with promising preliminary findings for both approaches.

Several interventions have been designed to target IU directly in treatment for youth with GAD, although the majority have only been examined in pilot studies. In a preliminary examination of a treatment designed to target the four cognitive components outlined in the IUM, three of seven participants showed large decreases in GAD symptoms across outcome measures, which were maintained at 6- and 12-month follow-up [59]. However, the remaining participants who did not withdraw showed no change (n = 1) or more moderate symptom decreases (n = 2). In a second set of cases (N = 16), the same treatment with minor modifications was associated with an 81% remission rate for GAD, although it is notable that diagnoses were not blindly assessed [60]. Alternative treatments have also been examined in samples of youth with GAD, including use of behavioral experiments (i.e., psychoeducation, awareness training, and experiments designed to facilitate neutral or positive beliefs about uncertainty) [47•] and an IU-CBT [61] protocol adapted from IUT for adults (i.e., worry awareness training, connecting IU and worry, and using exposure to increase tolerance for uncertain situations) [55]. Both studies reported significant reductions in GAD symptom severity across most outcome measures; however, consistent with other trials, sample sizes were small (N = 16 and 12, respectively) and studies did not include a control condition for comparison.

To date, only one RCT has been conducted to evaluate an IU-focused intervention in youth. In this RCT, youth (N = 42) ages 7–12 with a principal diagnosis of GAD and high comorbidity were randomized to a waitlist control or to the No Worries! Program, which was designed to directly target IU [62••]. The No Worries! Program takes a developmentally sensitive approach to present meta-cognitive processes to youth using specific examples. It uses a narrative therapy approach to label worry as the youth’s “Worry Beast” and sessions focus on understanding its demands, how it impacts their life, and ways youth can “tame their Worry Beast.” Results of the initial RCT showed that 52.9% of participants randomized to the active treatment condition no longer met diagnostic for GAD at post-treatment, compared with 0% in the waitlist control group. Interestingly, there were no significant differences in change on a measure of IU. At 3-month follow-up, 100% of participants who completed treatment no longer met criteria for GAD and 50% no longer met criteria for any diagnoses. These results suggest that programs designed to target IU can be efficacious for treating youth with GAD. Because IU has been proposed as transdiagnostic, additional work is needed to examine whether programs, such as the No Worries! Program, are efficacious in the treatment of anxiety more broadly. Importantly, will stratification of participants on the basis of IU enhance treatment benefits? Direct comparisons of CBT protocols with and without IU-tailored content are warranted.

Accommodation

Definition

Family accommodation “refers to the ways in which parents or other family members act to alleviate the accompanying symptoms,” [63••] such that youth distress is minimized in the short-term but maintained in the long-term (discussed below). Common examples of accommodating behaviors include providing reassurance and facilitating youth avoidance of feared stimuli [64], although a range of examples have been documented [64–66]. Studies have shown that accommodation is very common in samples of anxious youth, with as many as 95–97% of caregivers engaging in some form of accommodation [63, 64, 66, 67], and that these behaviors are associated with a range of negative sequela, including increased anxiety severity [68] and sleep disturbances [69]. Thus, although originally examined in the context of obsessive compulsive disorder (OCD) [70, 71], researchers have increasingly recognized the importance of accommodation in the maintenance of separation anxiety disorder (SAD) [64, 72, 73] and youth anxiety disorders more broadly [63, 74], although differences in accommodation rates across anxiety disorders have been noted. For example, several studies suggest that accommodation may be more prevalent among youth with a primary diagnosis of SAD [64, 72, 73].

Theoretical Model

The role of accommodation in youth anxiety disorders can be understood through the two-stage theory of fear development and maintenance [75]. According to this theory, interfering anxiety is acquired when a neutral stimulus is paired with a fear response and generalized via classical conditioning; anxiety is then maintained over time by the negative reinforcement of avoidance behaviors that decrease anxiety in the short-term but interfere with natural extinction of the conditioned fear [76, 77]. Accommodation can be conceptualized as one of several avoidance behaviors that facilitate youth avoidance of the feared stimuli during the maintenance phase, temporarily reducing youth distress but ultimately maintaining the anxiety cycle over time. Importantly, accommodation also may be experienced as negatively reinforcing by the parent due to an immediate decrease in both parental distress [78] and aversive youth behaviors [63••], further facilitating the maintenance of youth anxiety symptoms. Research has provided mixed support for this model. Some studies have shown that parents accommodate more during times of increased child distress [79] and that maternal anxiety and distress are associated with increased accommodation [66, 80]. Other studies, however, have not found a meaningful relationship between parental distress and accommodation [81, 82].

Predictor Studies

Higher levels of parental accommodation consistently predict poor treatment response among samples of youth with OCD [83], and an emerging body of literature has expanded these findings to samples of anxious youth. One study found that baseline levels of parental accommodation were significantly associated with post-treatment anxiety following 16 weeks of CBT; marginally significant associations with responder status also were reported [74]. Another study examining the impact of CBT on sleep-related problems similarly found that absolute levels of accommodation were positively associated with post-treatment sleep-related problems, controlling for pretreatment anxiety severity [84]. Finally, each additional point on an accommodation frequency subscale and an accommodation impact subscale was associated with a 12% and 26% decrease in the odds of remission, respectively, following computer-assisted CBT, although these results did not reach statistical significance [85]. Thus, studies suggest that baseline levels of accommodation may be a promising predictor for future study.

Consistent with IU findings, changes in accommodation throughout treatment have been examined in association to post-treatment response, although these changes are not baseline measures and thus cannot be termed predictor variables. Overall, accommodation has been found to decrease following CBT treatment for anxiety, even when not specifically targeted in treatment [61, 74, 84–86]. Results from one study suggest that decreases in accommodation are positively associated with parent-reported youth post-treatment anxiety, controlling for pretreatment differences in youth anxiety severity [84]; however, this finding did not hold across all outcome variables that were examined [84] and results were not replicated in another study examining sleep outcomes in CBT [84]. Interestingly, results from one study of a family-based prevention program found that reduction in accommodation was a mediator of outcome [87]. Future studies should continue to examine change in accommodation and treatment outcome.

Intervention

Three treatments have been developed to target accommodation: Supportive Parenting for Anxious Childhood Emotions (SPACE) [88, 89], the Accommodation Reduction Intervention (ARI) [86••], and a parent-led exposure therapy program [82]. In these programs, the therapist works with parents to provide psychoeducation of parental accommodation, to identify instances of accommodation, and to help the parent reduce accommodation. In the completely parent-based SPACE program, non-inferiority was established between SPACE and CBT [88••]. Interestingly, there was greater reduction in family accommodation within the SPACE condition compared with the CBT condition. Furthermore, the majority of reduction in accommodation occurred in the first half of SPACE and the second half of CBT. Unlike SPACE, which is a parent-only intervention, ARI is a modification of the Coping Cat program [90] and includes parent and child components. Results from a comparison of ARI using Coping Cat as a benchmark suggested that both treatments resulted in significant reductions in youth symptoms and parental accommodation, with no differences reported between treatments [86••]. Finally, initial results of a pilot study (N = 23) examining a parent-led exposure therapy program for youth ages 4 to 7 suggested that accommodation decreased more in the parent-led exposure therapy program relative to treatment as usual (i.e., prior interventions recommended by their providers) [82]. Together, these findings suggest that treatment reduces accommodation. For youth whose parents engage in high levels of accommodation, treatment that attends to accommodation may enhance benefits of CBT.

Conclusions

Recent research findings on IU and accommodation indicate that these constructs are involved in the development and maintenance of youth anxiety symptoms, and thus represent potential theory-driven constructs for identifying subgroups of youth who may benefit from targeted intervention. Recent studies examining the associations between these constructs and treatment response in adult and youth samples are promising, with results suggesting that high IU and increased parental accommodation are each associated with poorer CBT outcomes. Research has also adapted treatments to better target both constructs. Results suggest that IU- and accommodation-specific treatments can be efficacious for anxious youth, although additional work is needed.

Importantly, to date, the findings from both bodies of work have not been merged to inform personalized intervention. For example, several studies found that CBT and accommodation-focused treatments are comparably efficacious, but is this the case for youth whose parents engage in comparatively higher rates of accommodation? In one of several studies to examine the unique role between SAD and accommodation, an application of a person-centered analytic approach to identify meaningful subgroups of anxious youth found three latent profile of symptom presentations, with the interfering symptom group reporting significantly higher accommodation than other groups [73••]. It is reasonable to hypothesize that the subgroup of youth experiencing excessive accommodation may benefit more from an accommodation-specific intervention than other profiles. Future work should evaluate whether this kind of person-centered analytic approach may be helpful in making personalized treatment decisions.

The well-established efficacy for CBT for youth anxiety is encouraging, but there is need for research designed to address new questions: most pressingly, which treatments work for whom and why? It is possible that theory-driven predictors, such as IU and accommodation, will help to answer these questions and inform the development of targeted interventions. Such targeted interventions can then be leveraged to enhance efficacy for meaningful subgroups of anxious youth, in the hopes of increasing response rates above the reported 60%.