Serotonin and Cognitive Flexibility: Neuroimaging Studies into the Effect of Acute Tryptophan Depletion in Healthy Volunteers

Authors: Evers, E. A.T.; van der Veen, F. M.; Fekkes, D.; Jolles, J.

Source: Current Medicinal Chemistry, Volume 14, Number 28, December 2007 , pp. 2989-2995(7)

Publisher: Bentham Science Publishers

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Abstract:

Cognitive flexibility is the ability to adjust behavior to changes in the environment or task conditions. Previous research suggested that serotonin (5-HT) is involved in cognitive flexibility. Disturbed 5-HT functioning in animals, psychiatric patients and healthy volunteers leads to more rigid behavior. A well recognized method to manipulate levels of brain 5-HT is acute tryptophan depletion (ATD). This method induces a transient and reversible lowering of plasma tryptophan that has been shown to result in decreased brain 5- HT. Only recently has ATD research been combined with functional Magnetic Resonance Imaging (fMRI). In this review, we discuss recent investigations into the effect of ATD on the Blood Oxygen Level Dependent (BOLD) response during tasks that require cognitive flexibility, in healthy volunteers.

Functional MRI studies have shown that ATD changes brain activation during tasks that require cognitive flexibility. It is hypothesized that ATD changes the processing of negative feedback, rather than impairing response inhibition, impairing the response to an error or the loss of cognitive control during response interference. Although the results of these studies are intriguing, they are sometimes contradictory. This could be the result of the different paradigms that have been used. Importantly, these studies strongly suggest that future multidisciplinary research should evaluate the mechanisms underlying individual differences and control for variables that have been shown to interact with the effect of ATD on cognitive flexibility and the related brain activation.

Keywords: Serotonin; acute tryptophan depletion; cognitive flexibility; functional neuroimaging

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707782794032

Affiliations: Department of Psychiatry and Neuropsychology (DRT 10), Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.

Publication date: December 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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