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 ß-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.
Subject(s)
Combat Disorders/drug therapy , Mifepristone/therapeutic use , Propranolol/therapeutic use , Stress Disorders, Post-Traumatic/drug therapy , Veterans/psychology , Adrenergic beta-Antagonists/pharmacology , Adrenergic beta-Antagonists/therapeutic use , Adult , Arousal/drug effects , Combat Disorders/psychology , Double-Blind Method , Emotions/drug effects , Female , Heart Rate/drug effects , Humans , Imagination/drug effects , Male , Mental Recall/drug effects , Middle Aged , Propranolol/pharmacology , Receptors, Glucocorticoid/drug effects , Stress Disorders, Post-Traumatic/psychology , Young AdultABSTRACT
Detecting unexpected environmental change causes modulation of autonomic activity essential for survival. Understanding the neural mechanisms associated with responses to loud sounds may provide insights into the pathophysiology of posttraumatic stress disorder (PTSD), since individuals with PTSD exhibit heightened autonomic responses to unexpected loud sounds. We combined fMRI with autonomic psychophysiological assessment to investigate central and peripheral reactivity to loud tones in 20 healthy participants. Activity in anterior insula, pregenual anterior cingulate cortex, anterior midcingulate cortex, supplementary motor area, supramarginal gyrus, and cerebellar lobules VIII-IX was associated with both tones and concomitant skin conductance responses. Since regions signaling unexpected external events modulate autonomic activity, heightened loud tone autonomic responses in PTSD may reflect sensitization of this "salience" network.