Article

Interfering with the reconsolidation of traumatic memory: Sirolimus as a novel agent for treating veterans with posttraumatic stress disorder.

VA North Texas Health Care System, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA. E-mail: .
Annals of Clinical Psychiatry (Impact Factor: 2.53). 02/2013; 25(1):33-40.
Source: PubMed

ABSTRACT Development of novel treatment approaches for combat-related posttraumatic stress disorder (PTSD) is critical, given the increasing prevalence of PTSD in veterans returning from war zone deployment. Established preclinical research using protein synthesis inhibitors (such as sirolimus) to interfere with fear memory reconsolidation provides a compelling rationale for investigation in humans.
This double-blind, placebo-controlled translational pilot study examined the effects of pairing reactivation of a trauma memory with a single administration of sirolimus on the frequency and intensity of PTSD symptoms in male combat veterans.
Primary analyses found no significant differences between treatment groups on any of the clinical or physiologic outcome measures. In an exploratory analysis of a subsample of post-Vietnam-era veterans who had more recent combat trauma, PTSD symptom scores fell significantly more in these veterans than in controls.
The post-Vietnam-era veteran findings suggest that further investigation of this pairing of sirolimus with traumatic memory reactivation may be warranted. Theoretically, interference with the reconsolidation of fear memories could ameliorate military-related psychological trauma symptoms. Future research should focus on veterans of more recent eras whose traumatic memories may be less entrenched and more amenable to pharmacologic modification within this procedure.

0 Followers
 · 
75 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study utilized psychophysiologic techniques to assess emotional arousal during imagery of psychologically traumatic experiences. All subjects were medication-free Vietnam combat veterans, classified on the basis of DSM-III-R criteria into groups with posttraumatic stress disorder (PTSD, n = 18) and no mental disorder (control, n = 15), which did not differ in extent of combat or in the judged severity of the traumatic experiences reported. "Scripts" describing each subject's combat experiences as well as other experiences were read to them in the laboratory, and they were instructed to imagine the events the scripts portrayed, while heart rate, skin conductance, and frontalis electromyogram were recorded. The PTSD subjects' physiologic responses to their combat scripts were markedly higher than the controls'. The combined physiologic variables identified PTSD subjects with a specificity of 100% and a sensitivity of 61%. The results demonstrate exaggerated physiologic arousal during recollection of traumatic experiences in PTSD.
    Archives of General Psychiatry 12/1987; 44(11):970-5. · 13.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The psychometric properties of the PTSD Checklist (PCL), a new, brief, self-report instrument, were determined on a population of 40 motor vehicle accident victims and sexual assault victims using diagnoses and scores from the CAPS (Clinician Administered PTSD Scale) as the criteria. For the PCL as a whole, the correlation with the CAPS was 0.929 and diagnostic efficiency was 0.900 versus CAPS. Examination of the individual items showed wide ranging values of individual item correlations ranging from 0.386 to 0.788, and with diagnostic efficiencies of 0.700 or better for symptoms. We support the value of the PCL as a brief screening instrument for PTSD.
    Behaviour Research and Therapy 09/1996; 34(8):669-73. · 3.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 'New' memories are initially labile and sensitive to disruption before being consolidated into stable long-term memories. Much evidence indicates that this consolidation involves the synthesis of new proteins in neurons. The lateral and basal nuclei of the amygdala (LBA) are believed to be a site of memory storage in fear learning. Infusion of the protein synthesis inhibitor anisomycin into the LBA shortly after training prevents consolidation of fear memories. Here we show that consolidated fear memories, when reactivated during retrieval, return to a labile state in which infusion of anisomycin shortly after memory reactivation produces amnesia on later tests, regardless of whether reactivation was performed 1 or 14 days after conditioning. The same treatment with anisomycin, in the absence of memory reactivation, left memory intact. Consistent with a time-limited role for protein synthesis production in consolidation, delay of the infusion until six hours after memory reactivation produced no amnesia. Our data show that consolidated fear memories, when reactivated, return to a labile state that requires de novo protein synthesis for reconsolidation. These findings are not predicted by traditional theories of memory consolidation.
    Nature 09/2000; 406(6797):722-6. DOI:10.1038/35021052 · 42.35 Impact Factor