Other Neurochemical Pathways

Other neurotransmitter systems may or may not be modified in suicide. Cholinergic receptor binding (ligand: 3H-ZNB) appears unaltered (Stanley, 1984). μ-Opioid receptor binding appears increased in prefrontal cortex and caudate but not thalamus (Gabilondo et al., 1995). CRH binding to prefrontal cortex is reduced (Nemeroff et al., 1988). GABAB sites in the prefrontal cortex, temporal cortex, and hippocampus are reported to be unchanged (Cross et al., 1988), whereas benzodiazepine binding is increased in suicides (Manchon et al., 1987). Palmer et al. (1994) report no change in the NMDA receptor, but Nowak et al. (1995) found altered NMDA binding in the prefrontal cortex as indicated by a decrease in high affinity binding of the ligand 3H-CGP-39653.

Several studies have found changes in postsynaptic signal transduction pathways in suicide. The phosphoinositide and protein kinase C signaling systems are second messenger systems for serotonin as well as other neurotransmitters. Cowburn et al. (1994) reported low basal, GTPγS and forskolin-stimulated adenylyl cyclase activity in the cortex of suicide victims. Levels of one isoform of the α-subunit of the G-protein (Gsα-s) were reduced in suicides. Pacheco et al. (1996) reported that GTPγS stimulation of phosphoinositide hydrolysis was reduced by 30 percent in suicides. Pandey et al. (1997) found reduced protein kinase C binding of 3H-phorbol dibutyrate in prefrontal cortex of teen suicides. Furthermore, the phosphoinositide-specific enzyme phospholipase C (PLC) was found to be abnormal in adolescent suicide victims (Pandey et al., 1999) but not in adults (Pandey, 2001). The contribution of these biological pathways deserved further analysis for their contribution to the pathophysiology of suicide.


Similar to most complex conditions, such as obesity (Boutin and Froguel, 2001), hypertension (Higaki et al., 2001), and coronary artery disease (Winkelmann and Hager, 2000), there is growing evidence that genetic factors are related to liability for suicidal behavior. A clinical phenotype of suicide and suicidal behavior shows genetic liability from two sources. One is a genetic liability to mental illness, and the second to impulsive aggression. When both liabilities converge, the risk for suicidal behavior is particularly high. Candidate gene studies suggest that polymorphisms in serotonergic genes may be related to both alterations in serotonin function and to suicidal behavior, although the effects of individual candidate genes are small and may vary depending on psychiatric disorder, sex, and ethnicity. Since the heritability of liability to suicidal

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