Oxytocin effects on amygdala reactivity to angry faces in males and females with antisocial personality disorder

Abstract

The amygdala is a key region in current neurocircuitry models of reactive aggression as it is crucially involved in detecting social threat and provocation. An increased amygdala reactivity to angry faces has been reported in aggression-prone individuals and the neuropeptide oxytocin (OT) could dampen anger-related amygdala reactivity in a number of mental disorders. One example is the antisocial personality disorder (ASPD) which has so far only been studied in limited numbers. To address the question whether OT can normalize amygdala hyperreactivity to emotional faces, we conducted a functional magnetic resonance imaging experiment with 20 men and 18 women with ASPD and 20 male and 20 female healthy control (HC) participants in a double-blind, randomized, placebo (PLC)-controlled within-subject design. Participants were exposed to an emotion classification task (fearful, angry, and happy faces) after receiving an intranasal dose (24 IU) of synthetic OT or PLC. We found OT to attenuate right amygdala hyperactivity to angry faces in participants with ASPD to such an extent that the intensity of amygdala activity in the ASPD group in the OT condition decreased to the level of amygdala activity in the PLC condition in the HC group. There was also a trend that OT effects were generally larger in women than in men. These findings suggest that OT differentially modulates the amygdala following social threatening or provoking cues in dependence of psychopathology (ASPD vs. HC) and sex (male vs. female). Particularly female ASPD patients could benefit from OT in the treatment of reactive aggression.

Fig. 1. Comparison of reaction times and right amygdala activation after placebo (PLC) and oxytocin (OT) administration in individuals with antisocial personality disorder (ASPD, N = 38)) compared to healthy control (HC, N = 40) participants.

1.1. Comparison of reaction times between individuals with ASPD and HC participants as a function of sex (female, male), facial expression (fearful, angry, happy) and initial presentation of facial region (eyes, mouth) in the PLC) and OT condition. Under PLC, there was a significant group by emotion interaction (F(2, 140) = 5.58, p = 0.005, η² = 0.005). Post-hoc tests revealed that, in each group, participants were faster in classifying happy than fearful and angry faces (all p’s < 0.010). More interestingly, individuals with ASPD responded faster to angry faces than HC (p < 0.010). Error bars indicate standard error of the mean. Abbreviations: ms, milliseconds. **p < 0.010. 2 Comparison of right amygdala activation between individuals with ASPD and HC participants as a function of sex (female, male), facial expression (fearful, angry, happy) and initial presentation of facial region (eyes, mouth) in the PLC and OT condition. There was a significant threefold interaction effect of group by condition by emotion by hemisphere (F(2, 146) = 4.27, p = 0.016, η² = 0.055). In post-hoc tests for the right amygdala, the ASPD group showed a higher activation than the HC group when angry faces were shown under PLC (p < 0.010). Under OT, the ASPD group had a lower activation than the HC group at presentation of fearful, angry, and happy faces (all p’s < 0.010). This group differences could be accounted by a lower right amygdala activation for angry and happy faces in the ASPD group under OT compared to PLC and a higher right amygdala activation for fearful faces in the HC group under OT compared to PLC (all p’s < 0.010). Essentially, the group difference in right amygdala activation for angry faces could be reversed under OT: The ASPD group under OT showed a similarly low right amygdala activation like the HC group under PLC (p > 0.050) and the HC group under OT showed a similarly high right amygdala activation like the ASPD group under PLC (p > 0.050). Error bars indicate standard error of the mean. Abbreviations: ** p < 0.010. 1.2 A Right amygdala activation in women with and without ASPD. 1.2 B Right amygdala activation in men with and without ASPD. There was a statistically not significant trend for the interaction effect of group by sex by condition by emotion by hemisphere (F(2, 146) = 2.48, p = 0.087, η² = 0.033). Descriptively, OT affected women of the ASPD and HC groups more than men of the ASPD and HC groups.

Fig. 2. Correlation between right amygdala activation for angry faces and reaction time to angry faces after placebo (PLC) and oxytocin (OT) administration in women and men with antisocial personality disorder (ASPD, N = 38).

A The scatterplot depicts the correlation of right amygdala activation for angry faces and reaction time to angry faces in women with ASPD (N = 18) under PLC under PLC (R² = 0.309) and OT (R² = 0.028). B The scatterplot depicts the correlation of right amygdala activation for angry faces and reaction time to angry faces in men with ASPD (N = 20) under PLC (R² = 0.017) and OT (R² = 0.051).