The effects of oxytocin on trust and aggression

Converging evidence reveals that oxytocin has an important role in a wide
variety of behaviours. Although originally known for it*s effects on uterine
contractions and lactation, oxytocin also appeared to have an effect on social
behaviour like affiliation, social recognition, stress coping and aggression.
Affiliative behaviours (attachment, cooperation, empathy) are critical for the
psychophysiological wellbeing and normal development of individuals. Deficits
in these behaviours are associated with maladaptive interpersonal and
antisocial patterns and psychiatric disorders. There is substantial evidence
that within the realm of aggression a disorganisation in the neural circuitry
between the locus coeruleus, the amygdala and the prefrontal cortex exists, and
hormonal influences and transmitters play an essential role in starting an
aggressive act as a reaction to stress. Furthermore, the amygdala has an
important role in recognizing expressions and, therefore, in the fear response
on social cues. Oxytocin tends to down regulate the activation of the amygdala.
In different animal studies, these reduced fear reactions seem to be linked to
aggression. Much animal research has been done to determine the effect of
oxytocin on maternal aggression. Oxytocin has an important role in the binding
and protection of the newborn, thereby reducing offensive aggression, but
altering defensive aggression against intruders. But also in humans,
cerebrospinal fluid levels of oxytocin seem to be correlated with life history
of aggression. As expected from animal studies, administering oxytocin in
humans, resulted in a *tend to defend* behavior: it promoted in-group trust,
cooperation and defensive behavior and a more aggressive response to competing
out-groups.
In animal studies, oxytocin has been shown to diminish the natural behaviour of
avoidance and promote proximity. Oxytocin down regulates the cortisol release
in the HPA axis and, therefore, dampens the stress reaction. It contributes to
more trust in social interactions and less fear for social betrayal.

In a forensic setting, aggression and a lack of trust of patients are essential
daily problems. Patients often distrust their clinicians and are suspicious
with every new part of their treatment. As a result of this, patients can
react, sometimes unexpectedly, aggressive and distrustful towards their
clinicians. Improved understanding of the neurobiology of aggression and trust
in relation to oxytocin administration may provide challenging options for
future therapeutic interventions. To clarify the extent to which oxytocin
affects these measures, our first goal will be assess the behavioral and
hormonal effects of oxytocin on trust and aggression in a healthy population.
Research so far has mainly focused on the effects of aggression in animal
studies. In this study, we want to make the first step to human research. In a
double-blind placebo-controlled study, the effects of intranasal oxytocin
administration will be studied during performance of a social cooperation task
(Trust game) and an aggression task (Point Subtraction Aggression Paradigm) in
a group of healthy males volunteers.

- to assess the effects of intranasal administration of oxytocin in comparison
to placebo on trust, as measured by the behavioural response to the Trust game
- to assess the effects of intranasal administration of oxytocin in comparison
to placebo on aggression, as measured by the behavioural response to the PSAP.
- to study the relationships between serum and urine levels of oxytocin
- to study the relationships between hormonal and behavioural measures after
intranasal administration of oxytocin.

This study has a randomized double-blind placebo-controlled design. According
to earlier research in which oxytocin was administered to evaluate behavioural
differences, we expect to need 30 participants in each group (placebo,
oxytocin). We will employ a between-subject rather than within-subject design,
due to the uncertainty of the learning effects of the tasks (PSAP and Trust
game).
An independent statistician will provide a computer-generalised randomisation
list, using block randomisation of ten participants per block. The
study-pharmacist is the only one in possession of the randomisation list.

There will be oxytocin 32IU administered or normal saline, using a nasal spray.

before the experiment, participants are asked to fill in the NEO-FFI, TriPM,
TI, AVL RQ and ECR. This will take about 3 hours to complete. On the day of
testing, participants will be asked to collect morning urine. In the
laboratory, blood will be drawn. After this, participants will get a nasal
spray with oxytocin or placebo. Oxytocin is a endogenous substance and used
safely for many years under the name 'syntocinon' in woman. In men, the only
reported side effects are allergic skin reactions, nausea and headache. All
side effects are temporarily and are rare (in 0,01 - 0,1% of the cases
according to the 'farmacologisch kompas').