The Effect of Rapamycin Paired with Traumatic Memory Activation on Cognitive Performance in Veterans Diagnosed with PTSD

Abstract

Many individuals with posttraumatic stress disorder (PTSD) experience cognitive impairment in addition to the characteristic psychological symptoms. Animal studies have shown that rapamycin, a protein synthesis inhibitor that targets the protein kinase mTOR, can prevent the reconsolidation of a reactivated fear memory, thereby reducing its emotional strength at a neurochemical level. The aim of the current study was to determine if pairing rapamycin with traumatic memory reactivation in male veterans with combat-related PTSD would lead to an improvement in cognitive performance, based on scores from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline and 1-month follow-up. In a double-blind, placebo-controlled study, male veterans with combat-related PTSD were administered either a single dose of rapamycin or placebo, followed by a script-driven memory reactivation task. Measures included the RBANS, Clinician Administered PTSD Scale (CAPS), and the Quick Inventory of Depressive Symptomatology (QIDS). A repeated measures ANOVA was conducted to assess the impact of two different interventions (rapamycin, placebo) on participantsÕ scores on the RBANS, across two time periods (baseline, one-month follow-up). The main effect comparing the two type of interventions revealed no significant differences in the effectiveness of the two interventions in the entire sample; F (1,48) = .01, p = .921, partial eta squared < .001. When the sample was limited to participants who demonstrated a clinically significant reduction (³ 20 points) in their CAPS score, a repeated measures ANOVA revealed a significant interaction between time and treatment intervention; Wilks Lambda = .44, F (1, 13) = 16.74, p = .001, partial eta squared = .563. Pairwise comparisons showed a significant improvement between baseline and one-month follow-up on the RBANS for participants in the placebo group, mean difference = 10.00, p = .002. Based on these results, a single rapamycin treatment does not appear to be detrimental or beneficial to cognitive performance. Furthermore, a clinically significant reduction in PTSD symptoms due to rapamycin is not associated with an improvement in cognitive performance.