Oxytocin facilitates protective responses to aversive social stimuli in males

Abstract

The neuropeptide oxytocin (OXT) can enhance the impact of positive social cues but may reduce that of negative ones by inhibiting amygdala activation, although it is unclear whether the latter causes blunted emotional and mnemonic responses. In two independent double-blind placebo-controlled experiments, each involving over 70 healthy male subjects, we investigated whether OXT affects modulation of startle reactivity by aversive social stimuli as well as subsequent memory for them. Intranasal OXT potentiated acoustic startle responses to negative stimuli, without affecting behavioral valence or arousal judgments, and biased subsequent memory toward negative rather than neutral items. A functional MRI analysis of this mnemonic effect revealed that, whereas OXT inhibited amygdala responses to negative stimuli, it facilitated left insula responses for subsequently remembered items and increased functional coupling between the left amygdala, left anterior insula, and left inferior frontal gyrus. Our results therefore show that OXT can potentiate the protective and mnemonic impact of aversive social information despite reducing amygdala activity, and suggest that the insula may play a role in emotional modulation of memory. (5), social recognition (6-8) and related memory (9-11), social reinforcement learning and emotional empathy (12), and social judgments (13)(14)(15).This prosocial perspective on OXT is challenged, however, by evidence that OXT also enhances envy and schadenfreude (gloating) (16), ethno-centrism (including prejudice, xenophobia, and racial bias) (4), and outgroup derogation (17). Moreover, OXT hinders trust and cooperation when social information about interaction partners is lacking (18). Furthermore, OXT appears to negatively bias recollections of maternal care and closeness and to diminish trust and cooperation in insecurely or anxiously attached individuals (19,20).In an attempt to reconcile this controversial evidence, it has been proposed that the social effects of OXT could be mediated by reduced anxiety or by an increased perceptual salience of social cues (21). The anxiolytic action of OXT has been confirmed by showing reduced amygdala responses to aversive social stimuli in healthy people (22-25; but see also refs. 26 and 27), and subjects with social phobia (28). It is compatible with decreased endocrine and subjective responses to social stress (29), as well as reduced negative cognitive self-appraisal in individuals scoring high in traitanxiety (30). In contrast, the social salience hypothesis has gained substantial support from studies demonstrating increased eye contact (31) and improved mind-reading from facial expressions (32) as a result of OXT treatment. Whether these mechanisms quintessentially yield positive or negative social outcomes may vary depending on contextual or person-specific characteristics (21). An alternative view holds that emotional valence may be the key in guiding the social effects of OXT, with it facilitating social approach to positive cues and inhibiting...

Oxytocin Facilitates Pavlovian Fear Learning in Males

“…In the present study, OXT enhanced pMCC responses to social stimuli during fear conditioning, which is consistent with findings in mice suggesting that OXT specifically facilitates social fear conditioning (Zoicas et al, 2014). Taken together with previous research (Eckstein et al, 2014a;Striepens et al, 2012), this study presents a model of OXT as an enhancer of adaptation in social contexts. This heightened ability to adapt could, however, simultaneously be the groundwork for debilitating hypersensitivity to cues if extinction is not successful.…”

“…Indeed, we observed strengthened activity in the sACC for all fear-associated stimuli (CS+) and in the pMCC for the social fear-associated stimulus (face CS+). This specific profile suggests that OXT facilitates Pavlovian fear conditioning by potentiating neural responses to fearassociated stimuli in regions other than the amygdala, highlighting their importance in the acquisition of fear (Eckstein et al, 2014a;Striepens et al, 2012). Furthermore, in accordance with previous findings (Rash et al, 2014), OXT attenuated both neural and psychophysiological responses to the aversive electric shock.…”

“…Our previous findings also indicate a potential benefit via accelerated fear extinction, thus implicating OXT as a potential augmentation strategy in medication-enhanced cognitive-behavioral therapy of anxiety disorders (Eckstein et al, 2014b). The present results, however, together with findings of heightened alertness to threat (Eckstein et al, 2014a;Striepens et al, 2012) and enhanced social-emotional learning following OXT treatment (Eckstein et al, 2014b;Hurlemann et al, 2010), indicate that the peptide demands rigorous control of the therapeutic context in order to avoid suboptimal clinical outcomes. Secondary prevention intervention targeting the 'golden hours' (or early consolidation phase) immediately following a traumatic event might even yield contra-therapeutic effects if OXT enhances the acquisition of conditioned fear responses more efficiently than their extinction (see also Eskandarian et al, 2013).…”

Oxytocin promotes group-serving dishonesty

“…Indeed, and consistent with evolutionary theory predicting that trust and cooperation are geared primarily at those considered relevant to survival and prosperity (29), intranasal administration of oxytocin (compared with placebo) promotes trust and cooperation in humans (30), especially with familiar individuals and in-group members (27,(31)(32)(33)(34)(35). Thus, next to its well-known role in reproduction and social bond formation (36,37), oxytocin also functions to "tend-and-defend" the in-group by motivating parochial altruism: self-sacrificing to benefit one's own group and, if needed, to aggress against competing out-groups (32,38).…”

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

“…Indeed, experimenter-administered OT augments behavioral performance in emotion recognition, relieves some social deficits observed in individuals with ASD; and increases insular activity and connectivity to frontal cortex [43][44][45] . Furthermore, mutations in the OTR gene predict ASD symptoms 46 , insular activation 47 and social cognition 48,49 .…”