Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder.

Abstract

Aversive conditioning to explicit and contextual cues was examined in Gulf War veterans with and without posttraumatic stress disorder (PTSD) by use of the startle reflex methodology. Veterans participated in a differential aversive conditioning experiment consisting of 2 sessions separated by 4 or 5 days. Each session comprised two startle habituation periods, a preconditioning phase, a conditioning phase, and a postconditioning extinction test. In contrast to the non-PTSD group, the PTSD group showed a lack of differential startle response in the presence of a conditioned stimulus with or without an unconditioned stimulus in Session 1 and an increase in the baseline startle response during Session 2. The PTSD group also exhibited normal differential conditioning following reconditioning in Session 2. These data suggest that individuals with PTSD tend to generalize fear across stimuli and are sensitized by stress.

Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance

“…Though the shape of the generalization gradient in healthy humans resembles that of animals, the elevated tendency of anxiety patients to transfer conditioned fear to a CS-with strong resemblance to the CS+ (Grillon and Morgan, 1999;Lissek et al, 2005) supports the prediction of less steep generalization gradients among those with clinical anxiety, whereby startle magnitudes would remain elevated during presentation of Classes 3, 2, and perhaps 1 before dropping to CS-levels. Additionally, given that anxious individuals are characterized by a heightened tendency to appraise ambiguous stimuli as threatening (for a review, see Richards, 2004), those with clinical anxiety relative to healthy controls would be expected to display elevated risk ratings for shock when presented with classes of rings containing ambiguous threat information (i.e., Classes 4, 3, and 2), but would display approximately equal risk ratings for rings with more certain signal-value (i.e., CS+, CS-).…”

“…Because of these advantages, FPS is increasingly used to measure psychophysiological correlates of pathologic anxiety and to test the anxiolytic properties of pharmaceutical compounds (for a review, see Grillon, in press). Given the strong relevance of conditioned fear generalization to anxiety disorders (e.g., Foa, Steketee, & Rothbaum, 1989;Grillon & Morgan, 1999;Keane, Zimmering, & Caddell, 1985;Lissek et al, 2005;Mineka, 1992), conditioned startle-potentiated paradigms capable of eliciting continuous gradients of fear generalization may be a particularly powerful translational tool. The current study tests a novel conditioned startle-potentiation paradigm designed for this purpose in 20 healthy participants.…”

Downregulation of BDNF mRNA in the Hippocampal Dentate Gyrus after Re-exposure to Cues Previously Associated with Footshock,

“…However, such a phenomenon also may be relevant to human psychopathology as suggested by studies of patients with PTSD. In PTSD, facilitation of classical conditioning (Grillon and Morgan 1999;Orr et al 2000) and deficits in hippocampal volume and hippocampus-dependent tasks such as declarative memory (Bremner et al 1995;Stein et al 1997;Gurvits et al 1996;Bremner et al 1997) appear to co-occur, at least in males.…”

GABA-A and 5-HT1A Receptor Agonists Block Expression of Fear-Potentiated Startle in Mice

“…Interestingly, patients with post-traumatic stress disorder and panic disorder exhibit increased startle response magnitudes during baseline or stressful conditions (Butler et al, 1990;Grillon et al, 1994;Morgan et al, 1996;Grillon and Morgan, 1999). Furthermore, adolescents with a familial history of anxiety disorders exhibit increased expression of FPS (Grillon et al, 1998).…”