You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Oxytocin increases trust in humans
Abstract 1:
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


Title 2:
Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment
Abstract 2:
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


Title 3:
Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans
Abstract 3:
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


Title 4:
Oxytocin Increases Gaze to the Eye Region of Human Faces
Abstract 4:
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


Title 5:
Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial
Abstract 5:
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


Title 6:
Oxytocin Attenuates Amygdala Responses to Emotional Faces Regardless of Valence
Abstract 6:
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
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