There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study has actually demonstrated that this modality of administration increases concentrations of the peptide in the brain as well as blood in humans. Here using combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving either 24 IU of oxytocin (n = 11) or placebo (n = 4) we have shown that oxytocin levels significantly increased in both plasma and CSF. However, whereas oxytocin plasma concentrations peaked at 15 min after intranasal administration and decreased after 75 min, CSF concentrations took up to 75 min to reach a significant level. Moreover, there was no correlation (r = <0.10) between oxytocin plasma and CSF concentrations. Together, these data provide crucial insights into the plasma and CSF kinetics of intranasally administered oxytocin.

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...

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The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

In humans, interpersonal romantic attraction and the subsequent development of monogamous pair-bonds is substantially predicted by influential impressions formed during first encounters. The prosocial neuropeptide oxytocin (OXT) has been identified as a key facilitator of both interpersonal attraction and the formation of parental attachment. However, whether OXT contributes to the maintenance of monogamous bonds after they have been formed is unclear. In this randomized placebo-controlled trial, we provide the first behavioral evidence that the intranasal administration of OXT stimulates men in a monogamous relationship, but not single ones, to keep a much greater distance (ϳ10 -15 cm) between themselves and an attractive woman during a first encounter. This avoidance of close personal proximity occurred in the physical presence of female but not male experimenters and was independent of gaze direction and whether the female experimenter or the subject was moving. We further confirmed this unexpected finding using a photograph-based approach/ avoidance task that showed again that OXT only stimulated men in a monogamous relationship to approach pictures of attractive women more slowly. Importantly, these changes cannot be attributed to OXT altering the attitude of monogamous men toward attractive women or their judgments of and arousal by pictures of them. Together, our results suggest that where OXT release is stimulated during a monogamous relationship, it may additionally promote its maintenance by making men avoid signaling romantic interest to other women through close-approach behavior during social encounters. In this way, OXT may help to promote fidelity within monogamous human relationships.