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Reducing Suicide: A National Imperative
attempts, and twice the level of hopelessness. Other factors may impact these findings: O’Keane et al. (1992) found blunted prolactin responses compared to placebo in antisocial personality disorder.
Serotonin Receptors: SERT
The most studied serotonin receptor in suicidal behavior is the serotonin transporter (SERT). Many studies have suggested that the number of serotonin transporter binding sites is low in suicide victims. Methodological complexities such as the ligand used in the experiments have created some uncertainty about the interpretation of the data.
Furthermore, the changes in binding may be specific to certain brain regions. Gross-Isseroff et al. (1989) found strong regional differences in the binding of the 5-HT receptor ligand 3H-imipramine in suicide victims. Suicide-related decreases in SERT binding may be localized to the ventrolateral prefrontal cortex (Arango et al., 1995; Mann et al., 2000) as evidenced by studies on the binding of 3H-cyanoimipramine, another 5-HT receptor ligand. Earlier studies (Arató et al., 1987; Arató et al., 1991; Crow et al., 1984; Stanley et al., 1982) found low 3H-imipramine binding in the dorsal prefrontal cortex of suicide victims that may reflect fewer SERT sites. Studies of other brain regions are limited, but one preliminary report indicates low brainstem SERT binding (Lloyd et al., 1974).
Serotonin Receptors: 5-HT2A
Binding to the 5-HT2A receptor, a major postsynaptic receptor for serotonin may be greater in suicide victims. Several studies (Arango et al., 1990; Arora and Meltzer, 1989; Hrdina et al., 1993; Laruelle et al., 1993; Mann et al., 1986; Stanley and Mann, 1983) have demonstrated high ligand (either 3H-spiroperidol or 3H-ketanserin) binding to the 5-HT2A receptor in prefrontal cortex of suicide victims. Pandey and colleagues (2002) reported that there was greater 5-HT2A receptor protein and mRNA gene expression in the brains of teenage suicide victims than in matched normal controls. It should be noted, however, that the field is not in consensus on these findings; seven published studies have found no alteration in 5-HT2A binding (Arranz et al., 1994; Cheetham et al., 1988; Crow et al., 1984; Gross-Isseroff et al., 1990a; Lowther et al., 1994; Owen et al., 1983; 1986).
The changes in binding to the 5-HT2A receptor are found to be greater in prefrontal cortex than in temporal cortex (Arango et al., 1990). Like SERT, regional differences are evident for this postsynaptic receptor’s change with suicide. Further work is needed to map the distribution of change in 5-HT2A receptors in suicide victims throughout the prefrontal