Untitled

130 EFFECTS OF EARLY MALTREATMENT AND STRESSThe emotion part of the stress-emotion system is highly complex and not fullyunderstood (see Davidson et al., 2002; Heinrichs & Koob, 2004; LeDoux & Phelps,2000). It seems, however, to center on the amygdala, a bilateral structure (one inthe left and one in the right hemisphere), that plays critical roles in emotion processingand in orchestrating responses to threat. The amygdala is itself a highlycomplex structure, with its different components serving different functions inemotion processing (Pitkanen, Savander, & LeDoux, 1997). However, the centralamygdala serves as an output station, relaying information that then triggersmany of the behaviors associated with fear (e.g., freezing, the prickling sense ofone’s hair standing on edge, vigilance), and it connects with the brainstem andhypothalamic regions that produce the outflow of adrenaline by the SAM systemand glucocorticoids by the HPA system.Interestingly, CRH, the neuropeptide that coordinates the HPA system, is alsoproduced in the central nucleus of the amygdala, and infusing CRH into this regionof the brain triggers both the behavioral and physiological components ofthe stress-emotion response (Heinrichs, Menzaghi, Pich, Britton, & Koob, 1995).On the other hand, there are NE pathways from the brainstem LC region to theamygdala, and stimulating this pathway also results in activation of the stressemotionsystem (Van Bockstaele, Bajic, Proudfit, & Valentino, 2001). Thus oneway of conceptualizing the emotion component of the stress-emotion system isas a reverberating bidirectional system in which information about threat stimulatesthe central nucleus of the amygdala to orchestrate fear/defensive responsesincreasing the tone of stimulation from the LC to the amygdala. This increasedLC input lowers the threshold for subsequent amygdala activation. Without mechanismsto counteract this reverberation, threatened individuals might remain in aconstant state of fear and hyperstress responding. Input from the parasymetheticsystem, as well as from regions in the prefrontal cortex, appear to provide inputsto the amygdale and LC that disrupt this reverberation and return the individualto a calm state (Phillips, Drevets, Rauch, & Lane, 2003; Porges, 1995b).Glucocorticoids play multiple roles in physiology, some critical to stress andsome critical to survival under nonstressful conditions. Glucocorticoids producetheir effects primarily through regulating gene expression (see review, deKloet,Vreugdenhil, Oitzl, & Joels, 1998). Once glucocorticoids dock with their receptors,they get carried into the nucleus of the cell, where they connect with glucocorticoidsreceptive elements (GREs) that typically lie in promoter regions ofgenes. These GREs, once activated, interact with other gene regulatory signals toincrease or decrease gene transcription. There are two types of glucocorticoidreceptors in the brain, mineralocorticoid receptors (MR) and glucocorticoid receptors(GR). The effects of these two types of receptors, as described below, arequite different. Notably, however, because it takes time (many minutes to hours)for these kinds of gene-mediated events to have any effect on brain or body, it hasbeen a challenge to understand just what role glucocorticoids play in stress.