Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder

Laura Nawijn, Mirjam van Zuiden, Saskia B J Koch, Jessie L Frijling, Dick J Veltman, Miranda Olff, Laura Nawijn, Mirjam van Zuiden, Saskia B J Koch, Jessie L Frijling, Dick J Veltman, Miranda Olff

Abstract

Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin.

Keywords: PTSD; insula; medication-enhanced psychotherapy (MEP); oxytocin; reward; social.

© The Author (2016). Published by Oxford University Press.

Figures

Fig. 1.
Fig. 1.
SID task. (A) Stimulus order per trial. Each trial started with presentation of an anticipation cue [green square for reward trials, blue for neutral trials, red for loss trials, see (B)]. Cue duration was jittered between 1000 and 3000 ms. Cues were followed by the target stimulus, for which duration was tailored to individual mean RT based on ten practice trials, to result in feasible target duration (individual aRT + 400 ms) or unfeasible target duration (individual aRT—150 ms). After a delay period with a duration of 1000 ms minus target duration, trial feedback was presented for 1500 ms, followed by a blank screen inter-trial interval, duration jittered between 1000 and 3000 ms. (B) Anticipation cues and feedback stimuli per trial type. Reward trials were signaled by a green square (reward anticipation), neutral trials by a blue square (neutral anticipation) and punishment trials by a red square (punishment anticipation). Reward feedback (i.e. happy faces) was shown in response to hits on reward trials, punishment feedback (i.e. angry faces) was shown in response to misses on punishment trials.
Fig. 2.
Fig. 2.
Main effect of group during feedback of social reward (vs neutral) under placebo in the AI ROI. (A) Left AI [xyz = −36,4,10, F(1,68) = 18.11, PFWE = 0.024, k = 44]; Cluster is overlaid on a single-subject anatomical scan (SPM template), whole brain threshold set at P < 0.01 uncorrected for display purposes. (B) Extracted beta-weights (arbitrary units, a.u.) from 5 mm sphere around peak voxel (xyz = −36,4,10) showing a main effect of group. PTSD patients had significantly lower AI responses to social reward feedback (vs neutral) compared with controls. Error bars indicate standard error of the mean. *P < 0.05.
Fig. 3.
Fig. 3.
Oxytocin effects on neural responses in the right putamen and left AI during social reward feedback (group by drug interaction effect) (A) Right putamen [xyz = 26,10,8, F(1,68) = 19.18, Z = 3.93, PFWE = 0.047, k = 29]; (B) Extracted beta-weights (a.u.) from 5 mm sphere around peak voxel (xyz = 26,10,8) of the right putamen showing a group by drug interaction in controls and PTSD patients; (C) Left AI [xyz = −38,10,14, F(1,68) = 15.37, z = 3.53, PFWE = 0.067, k = 9]; (D) Extracted beta-weights (a.u.) from 5 mm sphere around peak voxel (xyz = −38,10,14) of the left AI showing a group by drug interaction in controls and PTSD patients. For AI group differences under placebo, see Figure 2. Clusters are overlaid on a single-subject anatomical scan (SPM template), whole brain threshold set at P < 0.01 uncorrected for display purposes. Error bars indicate standard error of the mean. *P < 0.05, **P < 0.01. All significant results survived FDR correction.

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