Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

Abstract

Post-traumatic stress disorder (PTSD) is a disabling psychiatric disorder. As a substantial part of PTSD patients responds poorly to currently available psychotherapies, pharmacological interventions boosting treatment response are needed. Because of its anxiolytic and pro-social properties, the neuropeptide oxytocin (OT) has been proposed as promising strategy for treatment augmentation in PTSD. As a first step to investigate the therapeutic potential of OT in PTSD, we conducted a double-blind, placebo-controlled, cross-over functional MRI study examining OT administration effects (40 IU) on amygdala reactivity toward emotional faces in unmedicated male and female police officers with (n=37, 21 males) and without (n=40, 20 males) PTSD. Trauma-exposed controls were matched to PTSD patients based on age, sex, years of service and educational level. Under placebo, the expected valence-dependent amygdala reactivity (ie, greater activity toward fearful-angry faces compared with happy-neutral faces) was absent in PTSD patients. OT administration dampened amygdala reactivity toward all emotional faces in male and female PTSD patients, but enhanced amygdala reactivity in healthy male and female trauma-exposed controls, independent of sex and stimulus valence. In PTSD patients, greater anxiety prior to scanning and amygdala reactivity during the placebo session were associated with greater reduction of amygdala reactivity after OT administration. Taken together, our results indicate presumably beneficial neurobiological effects of OT administration in male and female PTSD patients. Future studies should investigate OT administration in clinical settings to fully appreciate its therapeutic potential.

Figures

Figure 1

Difference in amygdala reactivity between PTSD patients and trauma-exposed controls. (a) Mean contrast estimates (± standard errors) in arbitrary units (a.u.) of the left amygdala cluster (peak xyz =−26 −2 −22) during the processing of fearful-angry and happy-neutral faces (versus the visuomotor control condition) in PTSD patients and trauma-exposed controls (males and females combined). Under placebo, trauma-exposed controls showed differential activation toward fearful-angry faces compared with happy-neutral faces, whereas this effect was absent in PTSD patients. (b) Statistical map of the positive group by emotion interaction effect under placebo, overlaid on single-subject template using a statistical threshold of p<0.01 (uncorrected) (unmasked) for display purposes. **p<0.001.

Figure 2

Effect of OT on amygdala reactivity. (a) Mean contrast estimates (± standard errors) in arbitrary units (a.u.) of the left amygdala cluster (peak xyz=−30 −4 −24) during the processing of emotional faces (all emotional faces combined versus the visuomotor control condition) in PTSD patients and trauma-exposed controls (males and females combined) after placebo and oxytocin (OT) administration. OT administration resulted in dampened amygdala reactivity in PTSD patients and in enhanced amygdala reactivity in trauma-exposed controls. (b) Statistical map of the medication by group interaction effect, overlaid on single-subject template using a statistical threshold of p<0.01 (uncorrected) (unmasked) for display purposes. *p<0.05.

Figure 3

Relationship between state anxiety and amygdala reactivity in PTSD patients. Scatterplots of correlations between: (a) state anxiety before placebo and oxytocin administration and left amygdala reactivity toward all emotional faces (compared with the visuomotor control condition) after placebo and OT administration: (b) state anxiety before placebo administration and difference in left amygdala reactivity (placebo—OT). Contrast estimates of left amygdala reactivity in arbitrary units (a.u.) were extracted using a 5-mm sphere surrounding the peak voxel (xyz=−30 −4 −24) of the OT administration effect in PTSD patients. STAI-state=State-Trait Anxiety Inventory (state-version).