Authors:

Cools, R., CALDER, A.J., LAWRENCE, A.D., Clark, L., Bullmore, E. & Robbins, T.W.

Reference:

Year of publication:

2004

CBU number:

5913

Abstract:

Individual differences in threat sensitivity have been associated with altered serotonergic (5-HT) activity as well as differential response to fear-related stimuli. Neurobiological data suggest that modulation by 5-HT of the amygdala is key to the adaptive processing of harmful stimuli. Acute reduction of central 5-HT function in human subjects can be achieved through dietary depletion of tryptophan, a 5-HT precursor, allowing a test of the link between 5-HT function, amygdala response to fear, and threat sensitivity. We examined the effects of acute tryptophan depletion (ATD) on the BOLD response in the amygdala/hippocampal complex whilst participants (12 young healthy males) viewed fearful, happy and neutral faces. Results from this within-subjects, placebo-controlled design revealed that ATD potentiated the BOLD response in the amygdala/hippocampal complex to fearful relative to happy faces, but only in individuals with high scores on the Behavioral Inhibition Scale [BIS; Carver and White,1994]. This correlation between trait threat sensitivity and the ATD-induced increase in the amygdala fear response was significant as revealed by analysis of a region of interest defined from the orthogonal contrast comparing fearful faces with fixation (r12 = 0.64; P = 0.04). These data concur with existing data and theorizing (Hariri et al., 2002; McNaughton and Gray, 2000) and support the hypothesis that decreased 5-HT functioning potentiates the impact of aversive sensory signals on amygdala/hippocampal processing, particularly in high threat-sensitive individuals.