in the United States instead of Vietnam, being in regular clothes instead of battle fatigues, and being back with loved ones.
Thus, although a great deal is known about brain systems involved in fear generation, much less is known about brain systems involved in fear inhibition (extinction and safety signals). The need to understand the biologic mechanisms of fear inhibition is just beginning to be appreciated (Myers and Davis 2007).
Exaggerated startle reflex is commonly associated with PTSD. Metzger et al. (1999) in a meta-analysis of the eye-blink component of the startle reflex in PTSD, concluded that the weighted effect sizes across all 11 studies provide support for exaggerated startle as a symptom of PTSD. Eight of 11 of the studies found medium to large-sized effects for eye-blink electromyogram startle-response magnitude to acoustic stimuli. Studies included Vietnam and Gulf War combat veterans and victims of sexual assault and mixed trauma.
In a comprehensive review of the startle reflex in PTSD, Grillon and Baas (2003) concluded that abnormalities of both a tonic and a phasic nature may exist in PTSD. They suggest that exposure to a traumatic event probably prompts a sensitization process that leads to an initial exaggerated startle. As the trauma becomes more distant in time, the enhanced startle response may gradually subside. The exaggerated startle response in patients with chronic PTSD may be a phasic symptom that is elicited by later trauma-related stimuli or by stressful environments and may involve different brain circuits over time. The amygdala may be involved in the early sensitization and in conditioned emotional responses (Hitchcock and Davis 1986; Hitchcock et al. 1989), whereas in chronic PTSD sufferers the exaggeration of startle in stressful contexts suggests that excessive release of CRH leads to involvement of the bed nucleus of the stria terminal (see Chapter 4). The most robust findings of exaggerated startle in PTSD are seen in patients with recent onset (within the preceding 5 years). The results in patients with chronic PTSD (onset more than 10 years earlier) are less clear. Vietnam veterans with chronic PTSD showed exaggerated startle response when assessed under stressful experimental conditions, but only one of the five studies that assessed the veterans with PTSD under nonstressful conditions found exaggerated startle response (Grillon and Baas 2003).
PTSD is characterized by trauma-related nightmares and sleep disturbance, which are often refractory to treatment (Friedman 2002; Ross et al. 1989; Taylor et al. 2007; Van Liempt et al. 2006). It has been hypothesized that increased noradrenergic function in the brain might contribute to PTSD-associated sleep symptoms (Mellman et al. 1995a). For example, increased noradrenergic activity could account for the abnormalities in rapid-eye-movement (REM) sleep in people with PTSD. The abnormalities include increased phasic motor activity, stage shifts, and arousal (Ross et al. 1994; Breslau et al. 2004), and REM fragmentation during early PTSD development (Mellman et al. 1995b). Furthermore, disruption in REM sleep could be related to nightmares (Mellman et al. 1995b, 2002) and the cognitive processing of traumatic events (Stickgold 2007). It is consistent with those findings that prazosin, an alpha-1 adrenergic antagonist, has been demonstrated to be an effective treatment for trauma nightmares and sleep disturbance in PTSD (Raskind et al. 2003, 2007; Taylor and Raskind 2002) by increasing total