Investigating the Effect of Oxytocin and the Neurochemistry of Antisocial Personality Disorder and Psychopathy Using Neuroimaging
Phase: NA
Conditions: Antisocial Personality Disorder
Sponsor: King's College London

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
OXYASP STUDY PROTOCOL 
 
HRA APPROVAL NUMBER: ID: 15/LO/1086 
 
FINAL VERSION COMPLETED MAY 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
Study Design and Procedures  
 
In a double-blind, placebo controlled, randomised crossover design, participants self-administered, 
under instruction from the researcher, 40 IU of IN-OT (Syntocinon; Novartis, Basel, Switzerland) or 
placebo (identical composition to Syntocinon except for the omission of oxytocin). Participants 
began the morphed faces task within 25-30 minutes of administration. The oxytocin dose employed 
was the highest clinically applicable safe dose administered to human volunteers, in keeping with a 
protocol which demonstrated significant neural activation over a period of 25–78 minutes with this 
dose (Paloyelis, Doyle et al. 2016). At a second session (occurring between three and twenty-eight 
days later), participants completed the fMRI task again under the alternative treatment condition. 
Participants were instructed to avoid food, drinks (except water), and nicotine two hours before 
starting the experiment. Participants completed the Morphed Faces task (see Figure 1). During the 
task, participants were asked to indicate the sex of each face with a left-right button press using the 
index and middle finger of their right hand during a single run, which lasted 9 minutes 56 seconds..  
 
General linear model analysis of behavioural data  
For the Morphed Faces task, means were first calculated across the whole sample for both accuracy 
and reaction time in rating the gender of the faces displayed. To investigate the effect of oxytocin 
and its interaction with other variables, for both accuracy and response latency data, a three group 
(NO, ASPD-P, ASPD+P) by two condition (oxytocin, placebo) by four intensity (40%, 60%, 80%, 100% 
of fearful facial expression) repeated-measures analysis of variance was conducted. Post-hoc  

repeated-measures analysis of variance was performed for ASPD-P vs ASPD+P. SPSS version 25.0 was 
used. A threshold for significance of p <0.05 (corrected) was set for all tests.  

 
Primary outcome measure and MRI processing  
Whole-brain blood oxygen level dependent (BOLD) fMRI data were acquired using a 3.0 Tesla 
General Electric Magnetic Resonance Scanner. The principle outcome measure was a regressor for 
modulation of neural activity (BOLD responsivity) by intensity of fearful expression. Specific MRI 
parameters, and full details of preprocessing and individual level analyses are available in 
supplementary materials.  
 
MRI Data group analysis  
Following preprocessing steps, modulated emotion data were entered into a 3 Group (NO, ASPD-P, 
ASPD+P) by 2 Condition (placebo, oxytocin) 3dMVM (ANOVA style computations) model. Within this 
framework, general linear tests were coded to assess differential effects of drug between the 
groups. Post hoc t-tests were conducted to decompose these interactions by examining between- 
and within- group effects. Correction for multiple comparisons was performed using a spatial 
clustering operation in AFNI’s 3dClustSim, using the autocorrelation function (-acf) with 10,000 
Monte Carlo simulations for the whole-brain analysis. Spatial autocorrelation was estimated from 
residuals from the individual-level GLMs. The initial threshold was set at p = 0.005. As outlined 
above, bilateral amygdala, anterior insula and midcingulate cortex, were selected a priori for ROI 
analysis. Small-volume corrections, calculated using an anatomically defined mask (TTN27, a 
Talaraich atlas from AFNI), yielded thresholds of k = 13 for anterior/mid-cingulate cortex, k = 8 for 
anterior insula, and k = 2 for amygdala at an initial significance threshold of 0.005 (multiple 
comparison corrected p<0.05).