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254 EFFECTS OF STRESSThompson et al., 2004). Our studies have shown that the prefrontal cortex playsan important modulatory role over the reactivity of the amygdala to stress. Moreover,studies by others have shown that stress can lead to an exacerbation of schizophreniasymptoms, and that of the children at risk for developing schizophrenia,those that eventually convert to schizophrenia are the individuals showing a higherreactivity to stress in the premorbid state (Johnstone et al., 2005). Furthermore,the prodromal symptoms of schizophrenia are reported to include deficits in executivefunction (Parnas & Jorgensen, 1989; Parnas et al., 1982), which are indicativeof prefrontal cortical pathology (Goldman-Rakic, 1998). Finally, studieshave provided evidence that the prefrontal cortex of schizophrenia subjects exhibitspathological changes such as decreased GABAergic markers (Lewis et al.,1999) and decreased dopamine innervation (Akil et al., 1999) that may be presentbefore the onset of symptoms. Indeed, dopamine is known to activate prefrontalcortical neuronal activity (Yang & Seamans, 1996), and stress has been shown toincrease prefrontal cortical dopamine levels (Finlay & Zigmond, 1997; Finlayet al., 1995), potentially facilitating prefrontal cortical neuron modulation of subcorticalstress responses. A deficit in prefrontal cortical dopamine function wouldtherefore limit the ability of this region to properly react to acute stressors, andthereby leave subcortical systems unregulated.This would potentially be of significant importance when one considers thesubdivisions of the amygdala and their effect on target structures. The basolateralamygdala is known to innervate structures that are typically considered to beinvolved in cognitive or affective responses, including the striatum, prefrontalcortex, and cingulate cortex (Gray, 1999). In contrast, the central amygdalanucleus preferentially innervates regions that are more involved in autonomicresponse to stressors, such as the bed nucleus of the stria terminalis, the nucleustractus solitarius, the dorsal motor nucleus of the vagus, the hypothalamus, theparabrachial nucleus, and the locus coeruleus (figure 11-1; Veening et al., 1984).Our studies show that the prefrontal cortex, potentially acting via the intercalatedcell mass, limits the response of the central amygdala to stressors. Thiswould be consistent with what one would expect for a normally functioningsystem. Thus, it would be beneficial for the cognitive component of the stressresponse to be maintained. In this way, the individual can maintain a heightenedstate of vigilance in a threatening environment. In contrast, it would notbe beneficial to maintain a constant, heightened level of activity within the centralamygdala-autonomic outflow pathway. If such a heightened level of activity isalso maintained, it is likely to result in a number of pathological consequencessecondary to the increase in catecholamine output, glucocorticoid levels, andso on. This attenuation of autonomic function would be dependent on the abilityof the prefrontal cortex to regulate the central medial nucleus via the intercalatedcell masses. However, in an individual with disrupted prefrontal corticalfunction, this attenuation may not be optimally functional.