Serotonin depletion amplifies distinct human social emotions as a function of individual differences in personality

Barbara J Sahakian,Jonathan W Kanen,Trevor W Robbins,Rudolf N Cardinal,Annemieke M Apergis-Schoute,Fréderique E Arntz,Annabel Price,Robyn Yellowlees,David M Christmas

doi:10.1038/s41398-020-00880-9

Abstract

Serotonin is involved in a wide range of mental capacities essential for navigating the social world, including emotion and impulse control. Much recent work on serotonin and social functioning has focused on decision-making. Here we investigated the influence of serotonin on human emotional reactions to social conflict. We used a novel computerised task that required mentally simulating social situations involving unjust harm and found that depleting the serotonin precursor tryptophan—in a double-blind randomised placebo-controlled design—enhanced emotional responses to the scenarios in a large sample of healthy volunteers (n = 73), and interacted with individual differences in trait personality to produce distinctive human emotions. Whereas guilt was preferentially elevated in highly empathic participants, annoyance was potentiated in those high in trait psychopathy, with medium to large effect sizes. Our findings show how individual differences in personality, when combined with fluctuations of serotonin, may produce diverse emotional phenotypes. This has implications for understanding vulnerability to psychopathology, determining who may be more sensitive to serotonin-modulating treatments, and casts new light on the functions of serotonin in emotional processing.

Highlights

A unified function for serotonin (5-hydroxytryptamine; 5-HT) has, perhaps unsurprisingly, proven to be elusive
There were highly significant main effects for emotion (F(2,155) = 171.744, p = 7.4 × 10−42, ηp2 = 0.708), agency (F(1,71) = 630.212, p = 4.9 × 10−37, ηp2 = 0.899) and intentionality (F(1,71) = 11.799, p = 0.001, ηp2 = 0.143), regardless of serotonergic status, which supports task validity and suggests individuals were attuned to the social context of the scenarios
This was driven by guilt when the agent of an unintentional harm

Summary

Introduction

A unified function for serotonin (5-hydroxytryptamine; 5-HT) has, perhaps unsurprisingly, proven to be elusive. It is hypothesised to have a role in many psychiatric disorders[1], and is implicated in a wide range of mental functions including aversive processing, impulse control and social behaviour[2]. These domains can be viewed under a unified framework by considering how serotonin impacts Pavlovian (stimulus-outcome, including emotional) and instrumental (stimulus-response-outcome; operant) processes that underlie both social and nonsocial functions[3]. Studies of healthy volunteers have primarily employed two techniques to investigate serotonin function: acute tryptophan depletion (ATD), a dietary technique that temporarily lowers brain serotonin levels by depleting its biosynthetic precursor, tryptophan[7,8,9,10,11] and treatment with single doses of selective serotonin reuptake inhibitors (SSRIs). ATD studies have revealed disinhibition of retaliatory behaviour in the face of perceived injustice[4], modelled using the Ultimatum

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Discussion

Conclusion