title: Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies.
abstract: Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-d-aspartate (NMDA) partial agonist d-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the β-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (n=15); Study Three: reactivation mifepristone plus d-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD.
authors.affiliation: Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Nellie E
authors.initials: NE
authors.lastname: Wood
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Rosasco
authors.affiliation: VA North Texas Health Care System, and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Alina M
authors.initials: AM
authors.lastname: Suris
authors.affiliation: Columbia University College of Physicians and Surgeons, USA.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Spring
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 120 Second Ave, Charlestown, Boston, MA 02129, USA.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Marin
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 120 Second Ave, Charlestown, Boston, MA 02129, USA.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Lasko
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 120 Second Ave, Charlestown, Boston, MA 02129, USA.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Goetz
authors.affiliation: Boston University School of Medicine, Boston, MA, USA.
authors.forename: Avital M
authors.initials: AM
authors.lastname: Fischer
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 120 Second Ave, Charlestown, Boston, MA 02129, USA.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Orr
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 120 Second Ave, Charlestown, Boston, MA 02129, USA. Electronic address: roger_pitman@hms.harvard.edu.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Pitman
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D001143:Arousal / Q000187:drug effects; D003130:Combat Disorders / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007092:Imagination / Q000187:drug effects; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D015735:Mifepristone / Q000627:therapeutic use*; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000523:psychology; D014728:Veterans / Q000523:psychology*; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D011433:Propranolol
keywords: Cycloserine; Imagery; Mifepristone; Post-traumatic; Propranolol; Psychophysiology (all MeSH terms); Stress disorders