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Effect of Tryptophan Depletion on Conditioned Threat Memory Expression: Role of Intolerance of Uncertainty

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journal contribution
posted on 18.06.2021, 11:02 by JW Kanen, FE Arntz, R Yellowlees, DM Christmas, A Price, AM Apergis-Schoute, BJ Sahakian, RN Cardinal, TW Robbins
Background: Responding emotionally to danger is critical for survival. Normal functioning also requires flexible alteration of emotional responses when a threat becomes safe. Aberrant threat and safety learning occur in many psychiatric disorders, including posttraumatic stress disorder, obsessive-compulsive disorder, and schizophrenia, in which emotional responses can persist pathologically. While there is evidence that threat and safety learning can be modulated by the serotonin systems, there have been few studies in humans. We addressed a critical clinically relevant question: How does lowering serotonin affect memory retention of conditioned threat and safety memory? Methods: Forty-seven healthy participants underwent conditioning to two stimuli predictive of threat on day 1. One stimulus but not the other was subsequently presented in an extinction session. Emotional responding was assessed by the skin conductance response. On day 2, we employed acute dietary tryptophan depletion to lower serotonin temporarily, in a double-blind, placebo-controlled, randomized between-groups design. We then tested for the retention of conditioned threat and extinction memory. We also measured self-reported intolerance of uncertainty, known to modulate threat memory expression. Results: The expression of emotional memory was attenuated in participants who had undergone tryptophan depletion. Individuals who were more intolerant of uncertainty showed even greater attenuation of emotion following depletion. Conclusions: These results support the view that serotonin is involved in predicting aversive outcomes and refine our understanding of the role of serotonin in the persistence of emotional responsivity, with implications for individual differences in vulnerability to psychopathology.

Funding

This work was supported by a Wellcome Trust Senior Investigator Award (Grant No. 104631/Z/14/Z [to TWR]), the National Institute for Health Research Cambridge Biomedical Research Centre (Mental Health Theme) (to BJS), the UK Medical Research Council (Grant No. MC_PC_17213 [to RNC]), a Gates Cambridge Scholarship (to JWK), and an Angharad Dodds John Bursary in Mental Health and Neuropsychiatry (to JWK).

History

Citation

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging May 2021; 6:590–598

Author affiliation

Department of Neuroscience, Psychology and Behaviour

Version

VoR (Version of Record)

Published in

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Volume

6

Issue

5

Pagination

590-598

Publisher

Elsevier

issn

2451-9022

eissn

2451-9030

Acceptance date

16/12/2020

Copyright date

2021

Available date

18/06/2021

Spatial coverage

United States

Language

eng