Focus ArticleThe role of intolerance of uncertainty in current and remitted internalizing and externalizing psychopathology
Introduction
Psychopathologies involving anxiety and depression (i.e. internalizing psychopathologies; Kendler, Prescott, Myers, & Neale, 2003; Krueger, Caspi, Moffitt, & Silva, 1998; Vollebergh et al., 2001) are serious, prevalent, and costly public health burdens. Internalizing psychopathologies are among the top 10 leading disabilities in the United States and carry an economic burden of hundreds of billions of dollars (Baxter, Vos, Scott, Ferrari, & Whiteford, 2014; Greenberg, Fournier, Sisitsky, Pike, & Kessler, 2015). Identifying underlying etiological mechanisms of internalizing psychopathologies could reduce this burden by providing novel clinical targets for early identification and preventative treatments. The personality trait, intolerance of uncertainty (IU), may be an important etiological mechanism of internalizing psychopathology (Carleton, 2016a, 2016b).
Carleton (2016a, p. 31)Carleton, 2016aCarleton (2016a, p. 31) recently defined IU 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” and argued that individuals high in IU experience fear in response to such absence of information (see also Carleton, Norton, & Asmundson, 2007; Freeston, Rheaume, Letarte, Dugas, & Ladouceur, 1994). Early research on IU focused on its role in the maintenance of generalized anxiety disorder (GAD; Dugas, Gagnon, Ladouceur, & Freeston, 1998). More recent evidence has shown that IU, as measured by the Intolerance of Uncertainty Scale and its short form (IUS and IUS-12; Carleton, Norton et al., 2007; Freeston et al., 1994), is not specific to GAD and may relate to anxiety-related disorders more broadly. In fact, scores on the IUS have been found to be positively associated with symptoms of obsessive-compulsive disorder (OCD; Holaway, Heimberg, & Coles, 2006; Tolin, Abramowitz, Brigidi, & Foa, 2003) Panic Disorder (Carleton, Fetzner, Hackl, & McEvoy, 2013, 2014), social anxiety disorder (SAD; Boelen & Reijntjes, 2009; Carleton, Collimore, & Asmundson, 2010; Whiting et al., 2014), and posttraumatic stress disorder (PTSD; Bardeen, Fergus, & Wu, 2013; Fetzner, Horswill, Boelen, & Carleton, 2013). IUS scores are also positively correlated with symptoms of major depressive disorder (MDD; Yook, Kim, Suh, & Lee, 2010) at rates comparable to that of other internalizing disorders (Carleton et al., 2012; Gentes & Ruscio, 2011), even when controlling for neuroticism or negative affectivity (N/NA; McEvoy & Mahoney, 2011, 2012). However, it should be noted that not all studies have found an association between IU and depression after accounting for other internalizing symptoms (Jensen, Cohen, Mennin, Fresco, & Heimberg, 2016; Khawaja & McMahon, 2011). Therefore, IU, as measured by the IUS, not only relates to anxiety disorders, but may be a transdiagnostic trait within internalizing psychopathologies in general.
IU appears to play a particularly important and central role among factors contributing to the etiology and maintenance of internalizing psychopathologies and is generally considered to be a vulnerability factor for internalizing psychopathologies. A meta-analysis of cognitive vulnerabilities related to anxiety or depression showed that IU accounted for the most variance among a wide range of cognitive vulnerabilities (Hong & Cheung, 2015). However, it is unclear whether elevated levels of IU in current internalizing psychopathology (Carleton et al., 2010, 2012; Holaway et al., 2006; Nelson, Shankman, & Proudfit, 2014; Nelson, Liu, Sarapas, & Shankman, 2016; Tolin et al., 2003; Whiting et al., 2014) persist into remission, a key criteria for markers of vulnerability (Zubin & Spring, 1977). In their classic study, Zubin and Spring (1977) proposed that a vulnerability marker should exist (a) before, (b) during, and (c) after an episode of psychopathology and (d) that the vulnerability marker must also be familial (i.e., correlated within families). The presence of the trait before the onset of psychopathology ensures that elevation of the trait is not merely a “scar” or byproduct of psychopathology caused by the onset of psychopathology (elevations in the trait did not lead to the onset of psychopathology). The vulnerability marker must also be present during an acute period or episode of psychopathology to ensure that the marker is, in fact, related to the disorder or disorders of interest. The marker’s presence after an episode of psychopathology further demonstrates that the vulnerability marker is an enduring and stable trait and not just a characteristic of those with acute symptoms of the disorder. Lastly, establishing that a vulnerability marker is familial suggests that the trait is endogenous and perhaps heritable. Elevated levels of IU in individuals with a past, and not current, history of psychopathology (i.e., the disorder is in remission) would demonstrate that high IU is an enduring and stable trait, although IU could also represent a “scar” of psychopathology (Lewinsohn, Steinmetz, Larson, & Franklin, 1981). Moreover, the elevation of IU in remission from internalizing psychopathologies would provide strong preliminary evidence towards examining whether IU is a premorbid and familial vulnerability factor.
Few studies have examined IU in remission. Treatment studies have found that psychotherapy can reduce the severity of IU in those with GAD, OCD, SAD, and Panic Disorder (Boswell, Thompson-Hollands, Farchione, & Barlow, 2013; Dugas & Ladouceur, 2000; Ladouceur et al., 2000), but have not evaluated whether those in remission still report elevated levels of IU in comparison to those without a history of an internalizing psychopathology.
When examining whether IU is elevated in current and remitted internalizing psychopathology it is also important to examine these relationships while controlling for trait N/NA. N/NA reflects individual differences in negative emotional responding (e.g. anxiety, irritability, sadness, anger, etc.) as well as instability in such responses (Kendler, Neale, Kessler, Heath, & Eaves, 1993; Lahey, 2009). N/NA is also elevated in internalizing psychopathology and may be a vulnerability factor as well (Farmer et al., 2002; Griffith et al., 2010; Kendler et al., 1993; Lahey, 2009; Ormel, Oldehinkel, & Vollebergh, 2004). Additionally, the high correlation between IU and N/NA as well as the conceptual overlap between the two constructs bring into question the independence and specificity of these possible etiological mechanisms (McEvoy & Mahoney, 2012; Sexton, Norton, Walker, & Norton, 2003).
The elevation of IU in both current and remitted internalizing psychopathology may also differ across different aspects of IU. While results have been mixed, factor analytic, latent class analysis, and factor mixture modeling studies have demonstrated that IU is made up of two separate, but related factors - prospective IU and inhibitory IU (Boelen & Lenferink, 2018; Carleton, Norton et al., 2007; Hale et al., 2016; McEvoy & Mahoney, 2011; Oglesby, Allan, Short, Raines, & Schmidt, 2017; Shihata, McEvoy, & Mullan, 2018). Prospective IU is characterized by future-oriented cognitive and emotional distress to uncertainty whereas inhibitory IU is described as behavioral inhibition in response to uncertainty. These subfactors of IU are correlated with each other and have also been shown to have discriminant validity such that prospective IU is associated with symptoms of GAD and OCD whereas inhibitory IU is related to symptoms of SAD, Panic Disorder, and MDD (Carleton et al., 2010; McEvoy & Mahoney, 2011, 2012). It is therefore possible that internalizing psychopathologies may more closely relate to certain subfactors of IU more than others.
In addition to the heterogeneity within IU, internalizing psychopathologies are also heterogeneous. Factor analytic studies have demonstrated that internalizing psychopathologies bifurcate into two distinct, but related, subfactors (Kendler et al., 2003; Krueger, 1999; Slade & Watson, 2006; Vollebergh et al., 2001; Watson, 2005). The first subfactor of disorders is characterized by fear (e.g., specific phobia, SAD, Panic Disorder) and the second is typified by distress and misery (e.g. MDD, GAD). Prospective and inhibitory IU may show different relationships with fear disorders as compared to distress/misery disorders.
It is also possible that IU may not be specific to internalizing psychopathologies and could be characteristic of a wider range of psychopathologies than previously thought. Kraemer, Mcleish, and Bryan (2015) examined the relationship between self-reported alcohol use motives and IU in a college sample and found that those who endorsed drinking-to-cope as well as drinking-to-conform reported greater levels of IU above and beyond the effects of gender, smoking status, marijuana use status, alcohol consumption, negative affectivity, and anxiety sensitivity. Thus, those high in IU may be more motivated to drink to avoid distress and social rejection, which could subsequently lead to greater alcohol use. Psychophysiological research has also provided further evidence that IU may not be specific to internalizing psychopathologies. Alcohol dependence (which is typically characterized as an externalizing, not internalizing, disorder; (Kendler et al., 2003; Krueger et al., 1998; Vollebergh et al., 2001)) has been shown to be related to increased startle to uncertain threat (Gorka & Shankman, 2017; Gorka, Nelson, & Shankman, 2013; Gorka, Lieberman, Phan, & Shankman, 2016). Moreover, startle potentiation to uncertain, but not predictable, threat is positively correlated with a family history of alcohol use disorder (AUD; Gorka, Hee et al., 2016). The increased reactivity to uncertain threat evidenced in individuals with AUD may be a behavioral correlate of IU (Nelson et al., 2016). If so, IU may also play a key role in AUD – and perhaps other externalizing psychopathologies as well.
Therefore, the aims of the current study are to assess whether IU is (1) elevated in current internalizing psychopathology and (2) elevated in remitted internalizing psychopathology. In order to examine whether IU is a separate etiological mechanism from N/NA, analyses will control for individuals’ levels of N/NA. It is hypothesized that IU will be elevated in current and remitted internalizing psychopathology given its putative role as a vulnerability factor. Additional exploratory analyses will examine whether 1) N/NA is elevated in current and remitted internalizing psychopathology when adjusting for individuals’ levels of IU, 2) prospective and inhibitory IU are elevated in current and remitted fear disorders and/or distress/misery disorders and 3) IU is specific to internalizing psychopathologies or if IU is also a key factor in externalizing psychopathologies such as AUD.
Section snippets
Participants
A total of 517 participants were drawn from a NIMH-funded family study (see Gorka, Hee et al., 2016; Katz, Hee, Hooker, & Shankman, 2017 for additional details). Participants were nested within 274 families and included 243 sibling pairs. Advertisements (fliers, internet postings, etc.) were used to recruit participants from the community and from mental health clinics. Participants were 18 to 30 years old (M = 22.39, SD = 3.17) with a wide range of psychopathologies, as well as healthy
Identification of covariates
Table 2 displays results for zero-order correlations between total IU, prospective IU, inhibitory IU, and N/NA as well as standardized beta estimates for the associations between each of these variables and current and remitted psychopathology. Individuals that were currently taking psychiatric medications (β = 5.292, p < .001) and were high in N/NA (β = 0.631, p < .001) displayed elevated total IU scores. Age (β = .742, p = .080) and gender (β = −.914, p = .296) did not have significant
Discussion
Intolerance of uncertainty may be a key, transdiagnostic, factor in internalizing psychopathologies. It is unknown whether IU continues to be elevated in remission from internalizing psychopathologies and if IU does so independently of N/NA. It is also unclear whether IU is characteristic of fear and/or distress/misery disorders or if IU is even specific to internalizing psychopathologies (vs. externalizing psychopathologies). Results indicated that total, prospective, and inhibitory IU scores
Author note
This work was supported by a grant from the National Institute of Mental Health (R01MH098093 [PI: Shankman]).
References (93)
Comorbidity and severity of anxiety and depressive disorders in a clinic sample
Journal of the American Academy of Child and Adolescent Psychiatry
(1991)- et al.
Intolerance of uncertainty and social anxiety
Journal of Anxiety Disorders
(2009) Into the unknown: A review and synthesis of contemporary models involving uncertainty
Journal of Anxiety Disorders
(2016)Fear of the unknown: One fear to rule them all?
Journal of Anxiety Disorders
(2016)- et al.
It’s not just the judgements-It’s that I don’t know’’’: Intolerance of uncertainty as a predictor of social anxiety
Journal of Anxiety Disorders
(2010) - et al.
But it might be a heart attack’’’: Intolerance of uncertainty and panic disorder symptoms
Journal of Anxiety Disorders
(2014) - et al.
Increasingly certain about uncertainty: Intolerance of uncertainty across anxiety and depression
Journal of Anxiety Disorders
(2012) - et al.
Fearing the unknown: A short version of the Intolerance of Uncertainty Scale
Journal of Anxiety Disorders
(2007) - et al.
Generalized anxiety disorder: A preliminary test of a conceptual model
Behaviour Research and Therapy
(1998) - et al.
An examination of the structure of posttraumatic stress disorder in relation to the anxiety and depressive disorders
Journal of Affective Disorders
(2011)