Fear of Uncertain Future Linked To Brain Region Associated With OCD

MedicalResearch.com Interview with:
Justin M. Kim, Ph.D

Dartmouth College
Advisor: Paul J. Whalen

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Anxiety (and its co-conspirator ‘worry’) is an active, energy consuming process. You haven’t given up – you are still fighting back, trying to anticipate what might happen tomorrow. The problem of course is that there are an infinite number of ‘what if…’ scenarios you can come up with. For some individuals, the uncertainty of what ‘might happen’ tomorrow, is actually worse than the negative event itself actually happening. These individuals are intolerant of uncertainty.

We were interested in how uncertainty and ambiguity of potential future threat contribute to the generation of anxiety and how they might be represented in our brain. In the psychology literature, how we deal with an uncertain future can be quantified as intolerance of uncertainty (IU). As is the case with any other personality characteristic, we all have varying degrees of IU. For example, individuals high in IU display difficulty accepting the possibility of potential negative events in the future. Importantly, psychiatric disorders such as generalized anxiety disorder (GAD) or obsessive-compulsive disorder (OCD), whose symptoms are marked with worrying/obsessing, are commonly associated elevated IU. We noticed that while much of the neuroimaging research on IU has been primarily focused on brain function, brain structural correlates of IU have received little attention so far. As such, we believed that it was an important endeavor to assess the relationship between IU and the structural properties of the brain, which can be done through the use of magnetic resonance imaging (MRI) techniques.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In the present study, we used each person’s structural MRI data to quantify the volume of gray matter tissue. Then, data were analyzed to identify brain regions whose size correlated with self-reported levels of IU. We found that individual differences in IU were positively correlated with only the volume of the striatum. To put it another way, people who had difficulty tolerating an uncertain future had a relatively enlarged striatum, particularly a portion of the striatum called the putamen.

MedicalResearch.com: What should readers take away from your report?

Response: Our data argue that structural alterations of the striatum are linked with normal variations in a dimensional personality characteristic (i.e., IU) that has ties with GAD or OCD, rather than the pathophysiology of these disorders per se. Previous studies have observed enlarged striatum in patients with GAD or OCD. What is new here is that we observed this relationship in psychiatrically healthy individuals – meaning that the relationship between the size of the striatum and IU is relevant to all of us, not just individuals with these disorders. Having a relatively enlarged volume of the striatum may be associated with how intolerant you are when facing an uncertain future, but it does not mean you have GAD or OCD. Whether or not this IU-striatum relationship will be helpful in predicting future onset of the disorders, since all our study participants were relatively young (aged 18-26), remains to be seen.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Since we focused on psychiatrically healthy individuals and IU within the normal range, the outcomes of the present study contribute to a clearer understanding of the relationship between IU – a dimensional personality characteristic – and the structural characteristics of the brain in healthy individuals. The IU-striatum relationship was independent of self-reported levels of trait anxiety, a general feeling of anxiousness that is commonly elevated in all anxiety disorders.

These findings would be able to serve as a starting point for treating symptoms specific to GAD or OCD (excessive worrying or obsessing about uncertainty, which is linked with extreme levels of IU) by targeting the striatum and tracking its volume over the course of treatment. As we learn more about the specific neurochemistry of the striatum, perhaps this will offer a clue for pharmacological interventions that might modulate striatal activity. Finally, in tracking healthy individuals with an enlarged striatum, we might find that measuring the volume of the striatum in young adults could predict those at risk for developing GAD or OCD, which could collectively contribute to a data-driven, brain-based approach on the diagnosis of these psychiatric disorders.

MedicalResearch.com: Is there anything else you would like to add?

Response: There is still more work to be done to understand the exact mechanisms that would explain how more gray matter in the striatum reflects our behavior. That being said, a promising possibility is hinted at by neurophysiological studies, which have demonstrated that the striatum is sensitive to the predictability of reward outcomes during learning tasks and rather than to the reward itself. Given that an important component of IU is a desire for predictability, our findings offer a neuroanatomical link related to our need for predictability – when we feel we know what will happen next, this decreases our baseline levels of anxiety, allowing us to focus and get our work done with less distraction.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.


Kim, M.J., Shin, J., Taylor, J.M., Mattek, A.M., Chavez, S.J. & Whalen, P.J. (In Press). Intolerance of uncertainty predicts increased striatal volume. Emotion.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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