The relationship between intolerance of uncertainty and anxiety in autism: A systematic literature review and meta-analysis

“Higgins et al. (2003) suggested that I2 percentages of 25%, 50% and 75% can be interpreted as representing low, moderate and high heterogeneity, respectively.”

“Fail-safe analysis (Rosenthal, 1979) was conducted to aid this assessment by quantifying the number of studies that would be required to invalidate the effect (Borenstein et al.”

“Maisel et al. (2016) used structural equation modelling to investigate this relationship, with scores from the autism spectrum quotient (Baron-Cohen et al., 2001) representing autism severity.”

“The second most popular tool was the Screen for Child Anxiety Related Emotional Disorders (SCARED; Birmaher et al., 1997).”

“Additional measures included the Dimensional Anxiety Scales (DAS; American Psychiatric Association, 2013) and the State-Trait Anxiety Inventory (STAI; Spielberger, 2010).”

“To measure anxiety, half of the studies used the Spence Children’s Anxiety Scale (SCAS; Spence, 1998).”

“…on prevalence of co-occurring anxiety disorder in children and in adults identified that 40% of children with ASD had at least one comorbid anxiety disorder (van Steensel et al., 2011), and reported a lifetime prevalence of an anxiety disorder in 42% of autistic adults (Hollocks et al., 2019).”

“Therefore, as White et al. (2009) argued, a more thorough understanding of the mechanism(s) underpinning anxiety in this population is required to inform targeted treatments.”

“There were 10 studies that used a variant of the Intolerance of Uncertainty Scale (Buhr & Dugas, 2002), with the majority of researchers opting to use the 12-item shortened version.”

“…on prevalence of co-occurring anxiety disorder in children and in adults identified that 40% of children with ASD had at least one comorbid anxiety disorder (van Steensel et al., 2011), and reported a lifetime prevalence of an anxiety disorder in 42% of autistic adults (Hollocks et al., 2019).”

“…a substantial role in social anxiety (Boelen & Reijntjes, 2009; Teale Sapach et al., 2015), obsessivecompulsive disorder (Holaway et al., 2006; Lind & Boschen, 2009; Tolin et al., 2003) and depression (Carleton et al., 2012; de Jong-Meyer et al., 2009; McEvoy & Mahoney, 2012; Nelson et al., 2014).”

“Intolerance of uncertainty (IoU) is a trait characterised by the overvaluation of predictability and the tendency to become overwhelmed by the unexpected or the unknown (Birrell et al., 2011; Carleton, 2016; Koerner & Dugas, 2006).”

“, 2015), obsessivecompulsive disorder (Holaway et al., 2006; Lind & Boschen, 2009; Tolin et al., 2003) and depression (Carleton et al.”

“…a substantial role in social anxiety (Boelen & Reijntjes, 2009; Teale Sapach et al., 2015), obsessivecompulsive disorder (Holaway et al., 2006; Lind & Boschen, 2009; Tolin et al., 2003) and depression (Carleton et al., 2012; de Jong-Meyer et al., 2009; McEvoy & Mahoney, 2012; Nelson et al., 2014).”

“Intolerance of uncertainty (IoU) is a trait characterised by the overvaluation of predictability and the tendency to become overwhelmed by the unexpected or the unknown (Birrell et al., 2011; Carleton, 2016; Koerner & Dugas, 2006).”

“Increased understanding of the association has led to interventions that have aimed to increase tolerance of uncertainty and these have demonstrated effectiveness in the treatment of anxiety (e.g. Dugas et al., 2003; Ladouceur et al., 2000).”

“…in the development of generalised anxiety disorder (Carleton et al., 2012; Freeston et al., 1994) and plays a substantial role in social anxiety (Boelen & Reijntjes, 2009; Teale Sapach et al., 2015), obsessivecompulsive disorder (Holaway et al., 2006; Lind & Boschen, 2009; Tolin et al., 2003)…”

“Boulter et al. (2014) found evidence that suggested IoU may mediate the relationship between autism and anxiety and that the relationship between IoU and anxiety is similar in neurotypical and autistic individuals.”

“, 2015), obsessivecompulsive disorder (Holaway et al., 2006; Lind & Boschen, 2009; Tolin et al., 2003) and depression (Carleton et al.”

“…studies (e.g. Maisel et al., 2016) that suggested IoU partially mediated the association between the core features of autism and anxiety, and one study (Wigham et al., 2015) found a significant, serial, indirect effect from sensory-responsiveness through IoU and anxiety to insistence on sameness.”

“A notable exception was Rodgers et al. (2016).”

“Furthermore, research into the effectiveness of treatments for anxiety has shown high nonresponse rates in autistic individuals (e.g. Storch et al., 2013, 2015; Wood et al., 2015).”

“This finding is relevant in the context of a recent meta-analysis by van Steensel and Heeman (2017), as this study found that anxiety levels were elevated in autistic children (compared with neurotypical children) and that this difference widened as IQ increased.”

“Furthermore, research into the effectiveness of treatments for anxiety has shown high nonresponse rates in autistic individuals (e.g. Storch et al., 2013, 2015; Wood et al., 2015).”

“All four of the studies in which the correlation was based on at least one measure that was parent reported (Damiano, 2015; Glod, 2017; Neil et al., 2016; Wigham et al., 2015) found a significant association between IoU and anxiety of a large effect size.”

“and reflect upon uncertainty are likely to mature with age (Osmanağaoğlu et al., 2018), and because previous metaanalyses (e.”

“One study (Joyce et al., 2017) used a screening tool but did not exclude participants with subthreshold scores.”

“Furthermore, research into the effectiveness of treatments for anxiety has shown high nonresponse rates in autistic individuals (e.g. Storch et al., 2013, 2015; Wood et al., 2015).”

“Anxiety amplifies difficulties with social functioning in this population and is predictive of poorer quality of life (van Steensel et al., 2012; White et al., 2009).”

“Maisel et al. (2016) used structural equation modelling to investigate this relationship, with scores from the autism spectrum quotient (Baron-Cohen et al., 2001) representing autism severity.”

“For many autistic individuals, even slight uncertainty is reported to lead to distress and anxiety, which exacerbates difficulties with social interaction (Ashburner et al., 2013; Bogdashina & Casanova, 2016; Trembath et al., 2012).”

“As there is little consensus in regard to behavioural or physiological measures that are valid for assessing anxiety in this population (Lydon et al., 2016; Vasa et al., 2016), this review will parallel meta-analyses conducted with neurotypical populations (e.”

“As there is little consensus in regard to behavioural or physiological measures that are valid for assessing anxiety in this population (Lydon et al., 2016; Vasa et al., 2016), this review will parallel meta-analyses conducted with neurotypical populations (e.”

“This is because there is often a discrepancy between self-reported and proxy-reported data in relation to autistic individuals (e.g. Vasa et al., 2018) and that individuals are often better-informants of their IoU (Comer et al., 2009).”

“For example, Ivey et al. (2004) found that autistic children showed increased participation in novel social events when they knew what to expect beforehand, and Ferrara and Hill (1980) demonstrated that autistic children were more likely to interact with toys if they could predict when the toys…”

“This is in line with theories that suggest sameness behaviours may function to reduce short-term anxiety by avoidance of uncertain situations that provoke distress (Joosten et al., 2009).”

“Five studies (Boulter et al., 2014; Cai et al., 2018; Joyce et al., 2017; Rodgers et al., 2016; Vasa et al., 2018) reported finding a large, significant association between self-reported anxiety and selfreported IoU.”

“It is encouraging that IoU interventions are currently being developed for autistic people and that preliminary data are promising (e.g. Rodgers et al., 2017).”

“A random-effects model was selected due to anticipated heterogeneity between studies and because it permits results to more readily be generalised (Chen & Peace, 2013).”

“For many autistic individuals, even slight uncertainty is reported to lead to distress and anxiety, which exacerbates difficulties with social interaction (Ashburner et al., 2013; Bogdashina & Casanova, 2016; Trembath et al., 2012).”

“A random-effects model was selected due to anticipated heterogeneity between studies and because it permits results to more readily be generalised (Chen & Peace, 2013).”

“…a substantial role in social anxiety (Boelen & Reijntjes, 2009; Teale Sapach et al., 2015), obsessivecompulsive disorder (Holaway et al., 2006; Lind & Boschen, 2009; Tolin et al., 2003) and depression (Carleton et al., 2012; de Jong-Meyer et al., 2009; McEvoy & Mahoney, 2012; Nelson et al.,…”

“Keefer et al. (2017) reported finding a moderate, significant association.”

“There was also a high percentage of males in the included studies, although this proportion was consistent with prevalence estimates (Whiteley et al., 2010).”

“In neurotypical populations, IoU is recognised as a dispositional risk factor in the development of generalised anxiety disorder (Carleton et al., 2012; Freeston et al., 1994) and plays a substantial role in social anxiety (Boelen & Reijntjes, 2009; Teale Sapach et al., 2015), obsessivecompulsive disorder (Holaway et…”

“…a substantial role in social anxiety (Boelen & Reijntjes, 2009; Teale Sapach et al., 2015), obsessivecompulsive disorder (Holaway et al., 2006; Lind & Boschen, 2009; Tolin et al., 2003) and depression (Carleton et al., 2012; de Jong-Meyer et al., 2009; McEvoy & Mahoney, 2012; Nelson et al., 2014).”

“Autistic people are also often uncomfortable with swift, unexpected change (American Psychiatric Association [APA], 2013), can struggle to deal with uncertainty (Jenkinson et al., 2020), and can be heavily reliant on health, social care and related services that have proven hard to maintain during the pandemic.”

“…useful to reduce anxiety, which is elevated in autistic individuals (Hollocks et al., 2019; van Steensel et al., 2011), has been persistently linked to a dislike or intolerance of uncertainty (Jenkinson et al., 2020), and represents a major priority of the autism community (Autistica, 2016).”

“More specifically, the intolerance of uncertainty, finding it difficult to cope with the unexpected, is associated with anxiety in autistic people (Jenkinson et al., 2020).”

“Difficulties to deal with uncertainty are particularly frequent in people who have an Autism Spectrum Condition (ASC) and are often related to anxiety issues (Jenkinson et al., 2020; Joyce et al., 2017).”

“Indeed, suboptimal predictive abilities might, for instance, explain the higher uncertainty intolerance in autistic individuals 17 or their dif fi culties to rapidly build up an internal representation to categorize stimuli 18 .”

“Girls with autism in late adolescence may particularly benefit from interventions focused on anxiety, intolerance of uncertainty and sensory hypersensitivity (Jenkinson et al., 2020; Wigham et al., 2015).”

“In addition, it has been well-determined that autism is associated with anxiety and memory disturbance [68, 69].”

“…of uncertainty (IU, assessed with the short IU scale; Carleton et al., 2007), as these two aspects explained about half the variance in autistic children’s sensory sensitivities (Neil et al., 2016) and were closely related in autistic adults (Jenkinson et al., 2020; Normansell-Mossa et al., 2021).”

“Cross-sectional data indicate that levels of intolerance of uncertainty in autism are elevated and strongly correlated with anxiety [55, 56], and that intolerance of uncertainty may mediate the anxiety-IS relation [56–58].”

“In addition, differences in emotion regulation, intolerance of uncertainty, and sensory processing have been implicated in vulnerabilities to mood and anxiety conditions for autistic people (Conner et al., 2022; Glod et al., 2015; Jenkinson et al., 2020).”

“In line with these claims, several studies consider ER as a transdiagnostic factor for internalized problems (Aldao et al., 2016; Cai et al., 2018; Jenkinson et al., 2020; White et al., 2014).”

“In terms of dispositional, transdiagnostic risk factors for psychopathology, intolerance of uncertainty is associated with anxiety, emotion dysregulation, phenotypic presentations of autism (Jenkinson et al., 2020), and psychiatric disorders (McEvoy et al., 2019).”

“…anxiety in the general population (Dugas et al., 1998) and a considerable literature now demonstrates that IU is significantly elevated in autism where it consistently predicts higher levels of anxiety (Boulter et al., 2014; Hwang et al., 2019; Jenkinson et al., 2020; Maisel et al., 2016).”

“…thresholds for the perception of ambiguity and enhanced discomfort with ambigu-ity” (Dugas et al. 2001), “negative beliefs about uncertainty and its implications” (Carleton et al. 2012), or as an “increased tendency to become overwhelmed by the unexpected and the unknown” (Jenkinson et al. 2020).”

“Existing research highlights associations between anxiety and intolerance of uncertainty in autistic individuals, which is consistent with unpredictable situations/feelings in the current study (Boulter et al., 2014; Jenkinson et al., 2020).”

“Research shows that IU is a feature of both autism and anxiety and may be an independent risk marker for anxiety (Jenkinson et al., 2020; Vasa et al., 2018).”

“However, this scale although widely used in studies of autistic people, has not yet been validated in this group [37].”

“Research also identified Intolerance of Uncertainty (IU) (Carleton, 2016) as a transdiagnostic factor in anxiety experienced by autistic people (Jenkinson et al., 2020).”

“Autism-related anxiety often results from sensory sensitivities, idiosyncratic phobias and worries related to uncertainty (Jenkinson et al., 2020; Lau et al., 2020).”

“This latter finding agrees with previous research, which has found robust evidence for elevated intolerance of uncertainty in autism and a strong link with anxiety (Jenkinson et al., 2020).”

“Intolerance to uncertainty is commonly observed in autistic individuals and a link between anxiety and intolerance to uncertainty in autism has been established (Jenkinson et al., 2020).”

“A tendency to find it difficult to cope with unexpected or unknown situations can be considered a core characteristic of autism, and elevated levels of intolerance of uncertainty in autism are documented by a large body of literature (see Jenkinson et al. 64 for a systematic review).”

“Not only are high levels of intolerance of uncertainty more common among autistic individuals compared to their non-autistic peers, the robust association with anxiety has also been confirmed (for a meta-analysis, see Jenkinson et al., 2020).”

“Particularly, static exploration could support participants with high levels of intolerance of uncertainty, a strong correlate of anxiety in autistic populations [32], as they can be reassured that the robot will not do or say anything.”

“Intolerance of uncertainty is often a common experience for autistic people (Jenkinson et al., 2020; Kerns et al., 2014), and this aspect of their experience has been linked to clinically significant anxiety levels (Boulter et al., 2014).”

“Intolerance of uncertainty is a psychological characteristic often found to be heightened in autism, and a driver of anxiety (Jenkinson et al., 2020).”

“IU is a transdiagnostic cognitive vulnerability that has been shown to explain significant variance in anxiety experienced by autistic people (Jenkinson et al., 2020 ).”

“Finally, management strategies aimed at reducing unpre-dictability were commonly reported in this study, adding to a growing body of literature suggesting that coping with uncertainty may be an effective target for RRB interventions (Rodgers et al., 2023; Jenkinson et al., 2020).”

“Previous systematic reviews have largely centered on individuals with formal ASD diagnoses (Hollocks et al., 2013; Lugo-Marin et al., 2019; Jenkinson et al., 2020), and have often examined broader domains such as executive functioning (Demetriou et al., 2018; Velikonja et al., 2019) or general…”

“Uncertainty can be problematic for autistic individuals; Intolerance of Uncertainty (Boulter et al., 2014; Jenkinson, Milne, and Thompson 2020) and Predictive Processing (Bervoets, Milton, and Van de Cruys 2021) are two theories that seek to explain why this may be the case.”

“Studies have shown that autistic individuals score significantly higher on IU Scales compared to non-autistic individuals (see Jenkinson et al., 2020).”

“Third, intolerance to uncertainty has been suggested as a causal model for why emotional symptoms like anxiety are heightened among autistic individuals (Boulter et al., 2014; Jenkinson et al., 2020).”

“A meta-analysis of 10 studies found that IU was significantly associated with anxiety (with large effect size) in autistic individuals aged 4–70 years (Jenkinson et al., 2020 ).”

“The loss of spontaneity this introduced was outweighed by the benefit of mitigating uncertainty-induced anxiety around the inter-view, which is particularly common in autistic people (Jenkinson et al., 2020).”

“Thus, many studies have sought to understand the relationship between IU and clinical features of autism (Vasa et al., 2018), as well as its role in anxiety in autism (Boulter & Freeston, 2014; Hodgson et al., 2017; Jenkinson et al., 2020; Keefer et al., 2017).”

“Due to intolerance of uncertainty, which is commonly reported by autistic people, this sensory ambiguity, over both internal and external stimuli, may repeatedly be interpreted as threatening and intensify anxiety [44–47].”

“This finding is not novel as other meta-analyses (e.g., Hollocks et al., 2019; Jenkinson et al., 2020; Uljarevi c & Hamilton, 2013) have reported males representing the bulk of the participants in the studies reviewed.”

“This is not surprising, since both anxiety and intolerance of uncertainty are known to be elevated in people with ASD and related to avoidance of demands, leading to refusal to attend (Jenkinson et al., 2020; Stuart et al., 2020).”

“Both are elevated in autistic individuals and show relations to (severity of) core features of ASD (Jenkinson et al., 2020; Kinnaird et al., 2019; Vasa et al., 2018).”

“These differences in data collection periods may be especially important because intolerance of uncertainty is elevated in autistic youth (Jenkinson et al., 2020) and is a core feature of anxiety disorders, but the largest disruptions in routine likely occurred during initial confinements in March…”

“Lastly, a growing body of evidence is highlighting alexithymia and intolerance of uncertainty as predictors not only of the severity of autistic symptomatology [3,48,49] but also of the presence of somatic symptoms among subjects with ASD and the non-clinical population [41].”

“Because autism is strongly related to IU (Jenkinson et al., 2020) and the present study reports a positive relationship between IU and schizotypal personality, more research should investigate if IU mediates the relationship between autism and schizotypal personality.”

“Pearson’s correlation is a statistical method used to measure the strength and direction of a linear relationship between two continuous variables (Jenkinson, Milne, and Thompson 2020).”

“These include difficulties in dealing with uncertainty 70–73 and the generation of rigid, repetitive behaviors that could restore predictability to perceptual experiences 67 .”

“The first possible factor refers to the intolerance of uncertainty, in that it has been shown that anxiety and intolerance of uncertainty are consistently elevated in individuals with ASD [21].”

“This finding is in line with previous studies (for meta-analysis, see Jenkinson et al., 2020) showing increased Intolerance of uncertainty in ASD.”

“…[11], such pathological levels of worry are maintained by intolerance of uncertainty (i.e., a tendency to react negatively to uncertain situations [12]), emotion dysregulation, and maladaptive beliefs, which if not treated can result in significant mental health problems, absence from school,…”

“…and related disorders, depression, PTSD and eating disorders in adults (Brown et al. 2017; Gentes and Ruscio 2011; Gu et al. 2020; McEvoy et al. 2019) and moderate to large associations with worry and anxiety in youth, including those with autism (Jenkinson et al. 2020; Osmanağaoğlu et al. 2018).”

“…significant impact of IU on other disorders such as autism spectrum disorder (ASD) mediating the relationship between ASD and anxiety (Boulter et al. 2014), via its link to restricted and repetitive behaviour (Joyce et al. 2017), and via heightened anxiety (for review, see Jenkinson et al. 2020).”

“InformantratingsofIUarealsohigherinschool - aged children on the autism spectrum compared to non - autistic children (Jenkinson et al., 2020).”

“The development of the interview protocol was informed by theoretical frameworks related to intolerance of uncertainty, a key transdiagnostic mechanism associated with anxiety in autistic individuals (Jenkinson et al. 2020).”