coids (Chaouloff, 1995). The link between the two systems is supported in part by the observation that chronic administration of antidepressants can reverse the overactivity of the HPA axis in animal pre-clinical models (Lopez et al., 1997). Van Praag (1996; 2001) proposes that a subtype of depression, anxiety/aggression-driven depression, is correlated with a sustained overproduction of cortisol, resulting in impaired 5-HT synthesis, and reduced 5-HT1a receptor sensitivity leading to susceptibility to stress induction of depression. He proposed that CRH antagonists would be helpful in such cases. On the other hand, Duval et al. (2001) found that the effectiveness of d-fenfluramine, a specific serotonin reuptake inhibitor, did not correlate with the basal or post-DST cortisol levels, suggesting limited functional links between the two systems in suicidal patients. Evidence does suggest that chronic stress of adverse rearing can lead to both low central serotonin responsivity in primates and in humans (Pine et al., 1997) and to HPA axis dysregulation (see Chapter 5) (Higley and Linnoila, 1997).

NEUROCHEMISTRY

The monoamines, particularly dopamine, norepinephrine, and serotonin, have been the focus of much of the research on mental disorders. Changes in these neurotransmitters appear to mediate the effect of the currently utilized psychotropic medications. These neurochemicals show significant changes in various neuropsychiatric disorders. While observable changes in these systems do not necessarily imply causality, they can offer opportunities for developing or improving interventions. A recently developed class of anti-depressants and anti-anxiety drugs, namely, selective serotonin reuptake inhibitors or SSRIs, work through the serotonin system. A wealth of evidence points to reduced serotonergic and altered noradrenergic function in the brains of suicide victims (both attempters and completers). This section summarizes studies on the serotonergic and noradrenergic systems associated with suicide and touches on the limited data on opiate, GABA, and other systems. Although for clarity, this chapter describes these neurochemical systems separately, the reader is reminded that the various systems are interactive and specific changes must be integrated to understand the comprehensive neurobiological effects.

The Serotonergic System

The serotonergic system is complex. Serotonergic pathways are profuse with major projections arising in the median and dorsal raphe nuclei and contacting thousands of cortical neurons. There are more than one



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