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Individual differences in threat sensitivity predict serotonergic modulation of amygdala response to fearful faces

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Abstract

Rationale

In this study we used functional magnetic resonance imaging (fMRI) to examine the effects of acute tryptophan depletion (ATD), a well-recognised method for inducing transient cerebral serotonin depletion, on brain activation to fearful faces.

Objectives

We predicted that ATD would increase the responsiveness of the amygdala to fearful faces as a function of individual variation in threat sensitivity.

Methods

Twelve healthy male volunteers received a tryptophan depleting drink or a tryptophan balancing amino acid drink (placebo) in a double-blind crossover design. Five hours after drink ingestion participants were scanned whilst viewing fearful, happy and neutral faces.

Results

Consistent with previous findings, fearful faces induced significant signal change in the bilateral amygdala/hippocampus as well as the fusiform face area and the right dorsolateral prefrontal cortex. Furthermore, ATD modulated amygdala/hippocampus activation in response to fearful relative to happy faces as a function of self-reported threat sensitivity (as measured with the Behavioral Inhibition Scale; Carver CS, White TL (1994) Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J Pers Soc Psychol 67:319–333).

Conclusion

The data support the hypothesis that individual variation in threat sensitivity interacts with manipulation of 5-HT function to bias the processing of amygdala-dependent threat-relevant stimuli.

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Notes

  1. In reply to a Reviewer’s question, we performed an additional, post-hoc correlation analysis between neuroticism scores obtained from the short Eysenck Personality Questionnaire (Eysenck and Eysenck 1991) and found that these did not correlate with ATD-induced changes in the amygdala response to fearful faces relative to happy faces (R 12=−0.23, P=0.24). Thus, the effect seems specific to anxiety sensitivity as measured by the BIS, rather than to neuroticism/negative emotionality per se, and this latter null result is in keeping with previous research (Canli et al. 2001).

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Acknowledgements

We thank Wim Riedel, GlaxoSmithKline (Cambridge, UK), for helpful suggestions and Ruth Bisbrown-Chippendale and Claire Sleator from the Wolfson Brain Imaging Centre (Cambridge, UK) for radiographic assistance. We are also grateful to nursing staff in the Wellcome Trust Clinical Research Facility at Addenbrooke’s hospital, Cambridge UK. This study was funded by a Wellcome Trust programme grant to T.W. Robbins, B.J. Everitt, A.C. Roberts and B.J. Sahakian (L.C.), and completed within the MRC Behavioural and Clinical Neuroscience Centre. R.C. holds a Royal Society Dorothy Hodgkin Fellowship and a Junior Research Fellowship from St John’s College, Cambridge, UK.

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Correspondence to Roshan Cools.

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Cools, R., Calder, A.J., Lawrence, A.D. et al. Individual differences in threat sensitivity predict serotonergic modulation of amygdala response to fearful faces. Psychopharmacology 180, 670–679 (2005). https://doi.org/10.1007/s00213-005-2215-5

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