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Acute tryptophan depletion in healthy subjects increases preferences for negative reciprocity.

ABSTRACT: Reciprocity motivates to reward those who are kind (= positive reciprocity) and to punish those who are unkind (= negative reciprocity). The neurotransmitter serotonin (5-HT) modulates human behavior in numerous social situations, such as retaliation in response to perceived unfairness. In a placebo-controlled study, we used acute tryptophan depletion (ATD) to investigate the influence of available serotonin on choice behavior and reciprocity in the Hawk-Dove game. This game illustrates a conflict situation and incorporates two potential strategies: the cooperative Dove strategy and the uncooperative, more aggressive Hawk strategy. After strategic choices, we elicited the subjects' expectations (= beliefs) regarding the opponent's choices and controlled for risk preferences and current mood. We defined strategy choices as negative reciprocity when the participants opted for Hawk in response to an expected Hawk. We hypothesized that the ATD-induced reduction of 5-HT availability would increase participants' preferences for negative reciprocity. Generalized estimating equations reveal no significant main effect of ATD on assessed belief, mood, or risk attitude. But assessment of ATD's marginal effects over beliefs suggests that ATD significantly increases the tendency for negative reciprocity, whereas positive reciprocity (Dove in response to an expected Dove) is unaffected. We could therefore demonstrate that 5-HT availability mediates (negative) reciprocal behavior in social decision-making.

SUBMITTER: Bengart P

PROVIDER: S-EPMC8009398 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD.12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm?Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years).In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C.The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.

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Acute tryptophan depletion in healthy subjects increases preferences for negative reciprocity.

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