Biochemical correlates of the heightened sympathetic nervous system activation in veterans and civilians with PTSD include increased excretion of epinephrine and norepinephrine (Davidson and Baum 1986; Kosten et al. 1987; Yehuda et al. 1992a) and decreased numbers of alpha-2 adrenergic receptors on the surface of platelets (Perry 1994; Perry et al. 1987). As noted in Chapter 4, chronic increases in circulating epinephrine and norepinephrine may lead to a decrease in the number of adrenergic receptors.
These increases in epinephrine and norepinephrine may not be present during resting states. However, it appears that PTSD subjects respond to a variety of stressors with greater increases in catecholamines than do healthy controls (McFall et al. 1990; Murburg et al. 1994; Southwick et al. 1995). Greater increases in epinephrine have been observed in veterans with war-related PTSD than in controls during and after viewing of a combat film but not in response to a film of an automobile accident (McFall et al. 1990). Auditory reminders of trauma have also been used as in vivo probes of noradrenergic responsivity in combat veterans with PTSD. In a study of 15 combat veterans with PTSD and 6 combat veterans without a mental disorder, Blanchard et al. (1991) sampled plasma norepinephrine before and after exposure to combat-related auditory stimuli. The PTSD group showed a 30% increase in plasma norepinephrine and heart rate in contrast with no change in the combat control group.
Pharmacologic provocation studies have also revealed exaggerated catecholamine responses in patients with PTSD. To assess adrenergic responsivity of the peripheral and central nervous system more directly, yohimbine was administered to 20 Vietnam combat veterans with PTSD and 18 healthy controls (Southwick et al. 1993a). Yohimbine is an alpha-2 adrenergic receptor antagonist that activates noradrenergic neurons by blocking the alpha-2 adrenergic auto receptor, thereby increasing the release of endogenous norepinephrine. Yohimbine caused a marked increase in anxiety and PTSD-specific symptoms: 70% of combat veterans with PTSD experienced yohimbine-induced panic attacks, and 40% had flashbacks, but there were no panic attacks and only one flashback in the placebo group. Subjects with PTSD also had significantly greater increases in heart rate and more than twice the plasma 3-methoxy-4-hydroxy phenylglycol, which is a breakdown product of norepinephrine. In the Southwick et al. (1993a) study, the yohimbine-induced increase in catecholamine activity may have produced a biologic response that resembled the biologic state at the time when the traumatic memory was encoded, which then facilitated the retrieval of traumatic memories, a phenomenon known as “state-dependent recall.” Those findings suggest a dysfunction of the locus coeruleus-norepinephrine function in patients with PTSD.
Interventions designed to suppress noradrenergic hyperreactivity directly in trauma survivors with PTSD have been limited to trials with the antiadrenergic agents clonidine (Kinzie and Leung 1989), guanfacine (Horrigan 1996), prazosin (Raskind et al. 2002), and propranolol (Pitman et al. 2002). Pitman et al. (2002), in a pilot study, administered propranolol to survivors of car accidents within 6 hours of the accidents. Although PTSD symptom scores 1 and 3 months after the trauma did not differ significantly between the two groups, the propranolol group at 3 months demonstrated significantly less psychophysiologic reactivity (in heart rate, skin conductance, and corrugator electromyography) to mental imagery that symbolized or resembled the index trauma. Positive results with propanolol have also been reported in accident victims who presented at an emergency room with tachycardia (Vaiva et al. 2003). Those preliminary studies with propranolol need replication, however, to determine whether it will be an effective treatment after trauma exposure to prevent PTSD. The propranolol results are consistent with data on healthy people. Southwick et al. (1993a) found a positive association between enhanced