***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Trust pervades human societies . Trust is indispensable in friendship , love , families and organizations , and plays a key role in economic exchange and politics . In the absence of trust among trading partners , market transactions break down . In the absence of trust in a country 's institutions and leaders , political legitimacy breaks down . Much recent evidence indicates that trust contributes to economic , political and social success . Little is known , however , about the biological basis of trust among humans . Here we show that intranasal administration of oxytocin , a neuropeptide that plays a key role in social attachment and affiliation in non-human mammals , causes a substantial increase in  trust among humans , thereby greatly increasing the benefits from social interactions . We also show that the effect of oxytocin on trust is not due to a general increase in the readiness to bear risks . On the contrary , oxytocin specifically affects an individual 's willingness to accept social risks arising through interpersonal interactions . These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour Despite the promise of intranasal oxytocin ( OT ) for modulating social behavior , recent work has provided mixed results . This may relate to suboptimal drug deposition achieved with conventional nasal sprays , inter-individual differences in nasal physiology and a poor underst and ing of how intranasal OT is delivered to the brain in humans . Delivering OT using a novel ‘ Breath Powered ’ nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport , we evaluated dose-dependent effects on social cognition , compared response with intravenous ( IV ) administration of OT , and assessed nasal cavity dimensions using acoustic rhinometry . We adopted a r and omized , double-blind , double-dummy , crossover design , with 16 healthy male adults completing four single-dose treatments ( intranasal 8 IU ( international units ) or 24 IU OT , 1 IU OT IV and placebo ) . The primary outcome was social cognition measured by emotional ratings of facial images . Secondary outcomes included the pharmacokinetics of OT , vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings . Despite the fact that all the treatments produced similar plasma OT increases compared with placebo , there was a main effect of treatment on anger ratings of emotionally ambiguous faces . Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT . In addition , there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment . These findings provide support for a direct nose-to-brain effect , independent of blood absorption , of low-dose OT delivered from a Breath Powered device 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 BACKGROUND In nonhuman mammals , oxytocin has a critical role in peer recognition and social approach behavior . In humans , oxytocin has been found to enhance trust and the ability to interpret the emotions of others . It has been suggested that oxytocin may enhance facial processing by increasing focus on the eye region of human faces . METHODS In a double-blind , r and omized , placebo-controlled , between-subject design , we tracked the eye movements of 52 healthy male volunteers who were presented with 24 neutral human faces after intranasal administration of 24 IU oxytocin or placebo .  RESULTS Participants given oxytocin showed an increased number of fixations and total gaze time toward the eye region compared with placebo participants . CONCLUSIONS Oxytocin increases gaze specifically toward the eye region of human faces . This may be one mechanism by which oxytocin enhances emotion recognition , interpersonal communication , and social approach behavior in humans . Findings suggest a possible role for oxytocin in the treatment of disorders characterized by eye-gaze avoidance and facial processing deficits UNLABELLED It is unclear if and how exogenous oxytocin ( OT ) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response . To better underst and the delivery routes of intranasal OT administration to the brain and the dose-response , we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging ( fMRI ) in four treatment conditions , including two different doses of intranasal OT using a novel Breath Powered device , intravenous ( IV ) OT , which provided similar concentrations of blood plasma OT , and placebo . We adopted a r and omized , double-blind , double-dummy , crossover design , with 16 healthy male adults administering a single-dose of these four treatments . We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli , with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo . These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT . TRIAL REGISTRATION This trial is registered at the U.S. National Institutes of Health clinical trial registry ( www . clinical trials.gov ; NCT01983514 ) and as EudraCT no. 2013 - 001608 - 12 BACKGROUND Oxytocin is known to reduce  anxiety  and  stress in social interactions as well as to modulate approach behavior . Recent studies suggest that the amygdala might be the primary neuronal basis for these effects . METHODS In a functional magnetic resonance imaging study using a double-blind , placebo-controlled within-subject design , we measured neural responses to fearful , angry , and happy facial expressions  after intranasal application of 24 IU oxytocin compared with placebo . RESULTS Oxytocin reduced right-sided amygdala responses to all three face categories even when the emotional content of the presented face was not evaluated explicitly . Exploratory whole brain analysis revealed modulatory effects in prefrontal and temporal areas as well as in the brainstem . CONCLUSIONS Results suggest a modulatory role of oxytocin on amygdala responses to facial expressions irrespective of their valence . Reduction of amygdala activity to positive and negative stimuli might reflect reduced uncertainty about the predictive value of a social stimulus and thereby facilitates social approach behavior 
    Output:
    
HighlightsThere was a positive association between central and peripheral oxytocin concentrations .
Significant associations were observed after intranasal oxytocin administration and after a stressor .
These results indicate a coordination of central and peripheral oxytocin release after stress and after intranasal administration .
Although popular , the approach of using peripheral oxytocin levels to approximate central levels under basal conditions is not supported by the present results