However, stress exposure and the concomitant neurophysiological response it elicits can also exert detrimental effects on brain regions that facilitate the control and regulation of behavior. These effects are especially relevant for the regulation of fear expression, where top-down regulatory mechanisms are engaged to control emotional responses to

threatening stimuli. This process—broadly referred to as ‘emotion regulation’—allows an individual to tailor emotional responses and behavior to a dynamic environment (Gross and Thompson, 2007). The capacity to regulate fear responses to threatening cues once the value or significance of such cues change is critical to emotional resilience and health, while deficits in fear regulation capacity strongly predict vulnerability to an array of affective psychopathology,

such as anxiety disorders Selumetinib chemical structure and depression (Cisler et al., 2010 and Johnstone et al., 2007). Fear responses can be flexibly changed through a broad range of processes that include learning that an aversive stimulus no longer poses a threat, or adopting a strategy to deliberately change the nature of an emotional response. These techniques have been repeatedly shown to inhibit or alter fear expression in the service of generating more adaptive responses that are better aligned with the current state of the environment. Importantly, the adaptive benefits afforded by fear regulation are widely known to rely on intact functioning of the prefrontal cortex (PFC), which supports the inhibition and flexible control of GS-7340 fear (see Hartley and Phelps, 2009 for review). The PFC, however, is also a major target of stress hormones that a growing body of research else suggests can markedly impair

its function (see Arnsten, 2009 or Holmes and Wellman, 2009; for reviews). This suggests that the flexible control of fear responses to aversive stimuli may be compromised when accompanied or preceded by exposure to stress. Despite the significance of this possibility, stress has remained largely unexplored within the fear regulation literature. In this review, we examine research investigating the effects of stress and stress hormones on regulatory techniques used to flexibly control fear responses in humans. Before doing so, it is important to recognize that constructs of fear and stress are often conflated in the literature due to their behavioral, neural and neurochemical similarities. To clearly differentiate fear expression from that of stress response in the context of this review, we refer to fear responses as discrete emotional or behavioral responses that occur when an organism detects a threat in its environment, or when it encounters a cue that has predicted danger in the past.