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Brunet_pdf
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
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JOURNAL INTERNATIONAL DE VICTIMOLOGIE 20037 5(2) :
PRIMER SIMPOSIO VIRTUAL DE DOLOR, MEDICINA PALIATIVA Y AVANCES EN FARMACOLOGÍA DEL DOLOR FÁRMACOS COADYUVANTES EN EL TRATAMIENTO DEL DOLOR Su utilización Introducción Se denominan fármacos coadyuvantes en el tratamiento del dolor o coanalgésicos, a las drogas cuya acción farmacológica principal no es la analgesia pero que, debido a su mecanismo de acción partic
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