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Journal International De Victimologie International Journal Of Victimology Psychophysiologic effect of post-retrieval Propanolol on traumatic memories in post- BRUNET, A. PHD (1), ORR, S. P. PHD (2), TREMBLAY, J. M.D. (3), NADER, K. PHD (4), PITMAN, R. K. M.D. (5) [CANADA, QC & USA] Authors
(1) (3) Department of Psychiatry, McGill University and Douglas Hospital Research Center, Montréal (2) Research Service, U.S. Veterans Affairs Medical Center, Manchester, NH 03104 (2)(5) Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (4) Department of Psychology, McGill University Keywords
Post-traumatic ; memory ; effect ; medication the emergency department within six hours the pathogenesis of post-traumatic stress of a psychologically traumatic event reduced modulation of Pavlovian conditioning (1), a during mental imagery (CS) of the event (3). terrifying event (unconditioned stimulus, UCS) overstimulates endogenous stress hormones as part of an unconditioned fear consolidation of conditioned learning is strengthen the consolidation of conditioned typically no more than a few hours after the fear, which is later manifest in durable fear learning has occurred. After this, ?-blockers responses (conditioned responses, CRs) to reminders of the event (conditioned stimuli, conditioning (4). PTSD cannot be diagnosed CSs). Animal and human data indicate that traumatic event (three months for chronic PTSD), which presumably is long after this noradrenergic activity and can be opposed previously conditioned animals, however, (reviewed in (2). In a previous study, we found that administration of propranolol in presentation of the CS has been found to JOURNAL INTERNATIONAL DE VICTIMOLOGIE 20037 5(2) : reduce subsequent conditioned inhibitory avoidance (5) and cue-elicited freezing (6). sexual abuse (3), motor vehicle accident (3), rape, being taken hostage, and witnessing a subjects’ memories of their traumatic events physical assault; placebo group: rape (2), physical assault (2), childhood sexual abuse threats, house fire, and witnessing a physical assault. Subjects gave written informed consent after the procedures had technique (7) used in the acute, post-trauma psychophysiologic PTSD study cited above (3). Physiologic responses during traumatic systolic blood pressure (SBP) <100 mm Hg; arrhythmias, or insulin-requiring diabetes; c.) previous adverse reaction to a ?-blocker; d.) use of another ?-blocker; e.) use of medication that could involve potentially with chronic PTSD resulting from various dangerous interactions with propranolol; f.) psychologically traumatic events described pregnant or breast feeding; g.) “recovered” Dissociative Experiences Scale (10) score > subject received either randomized, double-blind oral 40 mg short-acting propranolol followed two hours later by oral 60 mg long- placebo capsules (n=10). A trained research assistant composed scripts portraying the agoraphobia (2), social phobia (1), bulimia (1); placebo group: MDD (1), PD without recorded them for playback. A week later, in agoraphobia (2), bulimia (1), generalized the psychophysiology laboratory, the subject listened to the audio recording of their personal traumatic scripts and imagined the event as if it were happening to them again, preparation of two personal traumatic scripts for each subject, each addressing an aspect who had received propranolol a week earlier of the traumatic experience that caused the would show smaller physiologic responses during script-driven traumatic imagery than experience in writing on a standard script preparation form. The investigator reviewed the descriptions and requested additional details. Later, the investigator composed an approximate 30-second “script” portraying PTSD according to the Structured Interview neutral “filler” scripts. Each subject then received 40 mg short-acting propranolol or propranolol (n=9, 5M/4F) or placebo (n=10, placebo. Two hours later, if the participant’s systolic blood pressure had not fallen by (SDs) included: age 34.8 (10.1) vs. 35.1 (10.5), t(17)=0.1, p=0.95; years elapsed the short-acting dose was otherwise well since traumatic event 10.9 (12.5) vs. 10.1 tolerated, the subject received 60 mg of (10.8), t(17)=0.2 p=0.88; Impact of Event Scale-Revised 56.3 (10.8) vs. 55.0 (10.7), participants received both the short- and t(17)=0.3, p=0.79. Etiologic traumatic events JOURNAL INTERNATIONAL DE VICTIMOLOGIE 20037 5(2) : 104 PSYCHOPHYSIOLOGIC EFFECT OF POST-RETRIEVAL PROPANOLOL imagery procedure (7) took place one week later. After a 30-second baseline period, the normative PTSD cut-off. The observed effect subject listened during the playing of each sizes (Cohen’s d, shown in Figure 1) were all in the predicted direction. By conventional portrayed, as if it were happening again, for standards (11), these effect sizes were very large for SC, large for HR, but small for conductance (SC), and left corrugator (facial frowning muscle) electromyogram (EMG) were recorded. Responses (change scores) were calculated by subtracting the preceding baseline period mean for each physiologic measure from the mean for the imagery Discussion
period that followed it. Responses to the subject’s present study with those of a previously administered in the emergency room setting (3) reveals that propranolol given after the subjected to MANOVA with HR1⁄2, SC1⁄2, propranolol given after retrieval of the memory of a past traumatic event similarly dependent variables, as well as univariate t- tests. The criterion for statistical significance was p<0.05. Additionally, data from 152 compared to placebo. In the present study, individuals with (n=79) or without (n=72) the subjects who received post-retrieval technique employed here (8) were entered retrieval propranolol showed physiologic responses typical of trauma victims without EMG1⁄2 responses separately. These cut- offs are shown as dashed lines in Fig. 1.
blockade of reconsolidation (5,12). Such an physiologic responding during script-driven imagery is an index of the strength of the memory of the traumatic event; b.) retrieval during mental imagery of the traumatic event returned the traumatic memory to a labile (reconsolidated) to persist (13); and c.) propranolol blocked this restabilization (5,6). received placebo (multivariate p=0.007, Fig. 1). Drug condition accounted for 49% of the controls such an explanation is premature. variance in overall physiologic responding. The present study did not include a group The univariate analyses indicated that HR that received propranolol in the absence of traumatic memory reactivation (retrieval). To significantly smaller in the propranolol infer blockade of reconsolidation, it should compared to the placebo subjects (Fig. 1). be shown that the physiologic responses of placebo subjects were above the normative lower than those of a reactivated propranolol cut-offs for PTSD (dashed lines), whereas group, in order to rule out nonspecific effects reconsolidation is putatively a permanent JOURNAL INTERNATIONAL DE VICTIMOLOGIE 20037 5(2) : effect, in that the memory is presumed to have been lost (15). Additional research is needed to test the duration of the traumatic Figure 1. Physiologic responses of participants with post-traumatic stress disorder (PTSD)
during mental imagery of personal traumatic events, measured one week after memory
retrieval that was followed by propranolol or placebo. Gray bars (left)-placebo; black bars
(right)-propranolol. Error bars represent SEM. Dashed lines represent empirical cut-offs for PTSD
based upon prior research. Abbreviations: EMG-electromyogram, BPM-beats per minute, ?S-
?Siemens, ?V-?Volts.
JOURNAL INTERNATIONAL DE VICTIMOLOGIE 20037 5(2) : 106 PSYCHOPHYSIOLOGIC EFFECT OF POST-RETRIEVAL PROPANOLOL References
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