Second, intolerance of uncertainty (IU, Table 2) may also be involved in the OCD phenotype. IU is the tendency to perceive and interpret uncertain situations as negative or threatening; it is associated with reduced ability to cope and impulsive or avoidant responses to uncertainty, and an excessive need to establish certainty [43]. Many patients with OCD report IU when describing their symptoms. For example, the patient in Case vignette 2 (Table 1) reports being afraid of uncertainty, which drives a need for control related to his somatic obsessions. Studies investigating the content of patients’ experiences of symptoms have also identified that “a need for certainty” is a key theme involved in reassurance-seeking symptoms of OCD [44] and other studies have shown that that higher IU trait scores predict more severe OCD symptoms [43, 45]. Importantly, neuroimaging studies have reported atypically increased vmPFC and amygdala activity during the anticipation of uncertain threat [46] and during uncertainty in decision-making [47] in OCD patients, suggestive of fronto-limbic hyper-responsivity to uncertainty in OCD. Interestingly, IU has been shown to predict impaired fear extinction in non-psychiatric volunteers [48], suggesting these fronto-limbic dysfunctions may be related to one another.
