dozen types of serotonin receptors, including at least two auto receptor1 populations. This section will review the evidence concerning changes in brain and cerebrospinal fluid levels of serotonin and its metabolites, and changes in a few of the serotonin receptors.

Brain Levels

Initial studies of the serotonergic system in suicide victims reported modestly low levels of brainstem serotonin and/or its metabolite 5-hydroxyindoleacetic acid (5-HIAA). The original assessments were methodologically limited. First, postmortem assays do not distinguish where the neurotransmitter was localized at the time of death and consequently, its functional importance. Second, serotonin and 5-HIAA levels drop rapidly after death. About a 70 percent loss of serotonin occurs after death and removal of the brain to the freezer prior to assay. This means that group differences must be detected in the residual 30 percent of the serotonin or metabolite. Nevertheless, most studies found low serotonin or 5-HIAA in the brainstem of suicides (Table 4-1). Only three of nine studies found low 5-HIAA levels, and no studies found low 5-HT in the prefrontal cortex (Table 4-1). Four of six studies of other brain regions also reported low serotonin or 5-HIAA (not shown). Postmortem interval differences do not appear to explain discrepancies in the literature (Arango and Mann, 1992), probably because most of the decline in indolamine levels occurs in the first 2 hours postmortem and all published studies of suicide victims have a longer postmortem delay.

Low serotonin or serotonin turnover in suicide appears to be confined to some brain regions. This may reflect the limitations of the assay methodology, which might not be sufficiently sensitive to measure the lower concentrations of serotonin and 5-HIAA in areas that contain less than the brainstem. Alternatively, there may be a regional localization of changes in serotonin levels or turnover, such that serotonin and 5-HIAA in the terminal fields are altered in some areas and not others. That conclusion is consistent with receptor mapping studies by Arango et al. (1995) and Mann et al. (2000).

The reduction in serotonin or 5-HIAA in the brainstem of suicide victims is independent of diagnostic category (Mann et al., 1989),with a similar degree of reduction seen in patients with depression, schizophre-

1  

Auto receptors are found on the cells releasing the chemical, and are involved in regulating further release.



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