A pharmacological challenge paradigm to assess neural signatures of script-elicited acute dissociation in women with post-traumatic stress disorder

Abstract

Background There is limited experimentally controlled neuroimaging research available that could explain how dissociative states occur and which neurobiological changes are involved in acute post-traumatic dissociation. Aims To test the causal hypothesis that acute dissociation is triggered bottom-up by a selective noradrenergic-mediated increase in amygdala activation during the processing of autobiographical trauma memories. Method Women with post-traumatic stress disorder (n = 47) and a history of interpersonal childhood trauma underwent a within-participant, placebo-controlled pharmacological challenge paradigm (4.0 mg reboxetine versus placebo) employing script-driven imagery (traumatic versus neutral autobiographical memory recall). Script-elicited brain activation patterns (measured via functional magnetic resonance imagery) were analysed by means of whole-brain analyses and a pre-registered region of interest (i.e. amygdala). Results Self-reported acute dissociation increased significantly during trauma (versus neutral) recall but did not differ between pharmacological conditions. The pharmacological manipulation was also unsuccessful in eliciting increased amygdala activation following script-driven imagery in the reboxetine (versus placebo) condition. In the reboxetine condition, trauma retrieval resulted in similar activation patterns as in the placebo condition (e.g. elevated brain activation in the middle occipital gyrus and supramarginal gyrus), albeit with different peaks. Conclusions Current (null) findings cast doubt on the suggested role of the amygdala in subserving dissociative processing of trauma memories. Alternative pharmacological manipulation approaches (e.g. ketamine) and analysis techniques (e.g. event-related independent component analysis) might provide better insight into the spatiotemporal dynamics and network shifts involved in dissociative experiences and autobiographical trauma memory recall.

Keywords

• PTSD
• dissociation
• biomarkers
• reboxetine
• imaging