High affinity [3H]imipramine and [3H]paroxetine binding sites in suicide brains

Abstract

Specific binding of [3H]imipramine and [3H]paroxetine was simultaneously examined in human brains (frontal cortex, temporal cortex, cingulate cortex, hypothalamus, hippocampus and amygdala) from 11 controls and 11 depressed suicide victims. A single saturable high affinity site was obtained for both radioligands. Age was not related to significant changes in [3H]imipramine and [3H]paroxetine binding parameters, which indicates the stability of the brain serotonergic system with increasing age. A major finding of the present study concerns the existence of a significant decrease in the maximum number (Bmax) of [3H]imipramine binding sites in hippocampus from depressed suicides as compared with the control group, without changes in the binding affinity (Kd). In contrast, when [3H]paroxetine was used as radioligand, no changes in either Bmax or Kd were detected in any of the brain regions studied. These findings suggest that [3H]imipramine may be a better marker than [3H]paroxetine when alterations in the presynaptic serotonergic uptake site are to be detected.

Serotonin Transporter: A Potential Substrate in the Biology of Suicide

“…Some of these studies reported a reduction in frontal cortex SERT binding (Stanley et al, 1982;Arato et al, 1991;Laruelle et al, 1993;Arango et al, 1995), one an increase (Meyerson et al, 1982), and the remainder no difference when compared to controls (Arato et al, 1987;Arora and Meltzer, 1989;Lawrence et al, 1990aLawrence et al, , b, 1998Mann et al, 1996;Rosel et al, 1997Rosel et al, , 1998Bligh-Glover et al, 2000). One group failed to find SERT density alterations in the frontal cortex of violent suicides but did find a decrease in the hippocampus using [ 3 H]-imipramine, which was not confirmed using [ 3 H]-paroxetine in the same tissue samples (Rosel et al, 1997(Rosel et al, , 1998. Lawrence et al (1998) demonstrated a decrease in SERT binding in the putamen of nonviolent suicides with no differences in the binding of violent suicides.…”

“…Although many of the studies of SERT binding in postmortem brain tissue from suicide completers have examined both violent and nonviolent suicides, several have used violent completers exclusively or have subdivided the suicide group based on the use of violent means (Meyerson et al, 1982;Stanley et al, 1982;Arato et al, 1987Arato et al, , 1991Arora and Meltzer, 1989;Lawrence et al, 1990aLawrence et al, , b, 1998Rosel et al, 1997Rosel et al, , 1998Bligh-Glover et al, 2000). Other studies included only one or two suicide victims who had died by nonviolent methods, while the majority of subjects used violent means (Laruelle et al, 1993;Arango et al, 1995;Mann et al, 1996).…”

“…Within the frontal cortex, researchers have found decreases (Stanley et al, 1982;Crow et al, 1984;Arato et al, 1991;Laruelle et al, 1993;Arango et al, 1995;Mann et al, 2000), increases (Meyerson et al, 1982), and no alterations in the SERT binding of suicides Meltzer, 1989, 1991;GrossIsseroff et al, 1989;Lawrence et al, 1990aLawrence et al, , b, 1997Lawrence et al, , 1998Hrdina et al, 1993;Little et al, 1997;Rosel et al, 1997Rosel et al, , 1998Du et al, 1999;Bligh-Glover et al, 2000). Studies in which SERT binding was measured in various other brain regions of suicide victims have produced similar discordant results (Paul et al, 1984;Owen et al, 1986;Gross-Isseroff et al, 1989;Hrdina et al, 1993;Laruelle et al, 1993;Dean et al, 1996;Mann et al, 1996;Lawrence et al, 1997;Little et al, 1997;Rosel et al, 1997Rosel et al, , 1998. Interestingly, relatively few studies have scrutinized the midbrain, the major site of the raphe 5-HT perikarya (Gross-Isseroff et al, 1989;Lawrence et al, 1990aLawrence et al, , b, 1997Lawrence et al, , 1998Little et al, 1997;Bligh-Glover et al, 2000;Arango et al, 2001).…”

Toward a Biosignature for Suicide

“…Most studies report a decrease (95-98) or no change (99) in 5-HTT binding affinity in the hippocampus and prefrontal cortex, although an increase has also been reported (100). Fewer neurons express the serotonin transporter in the raphe nuclei of suicide victims.…”

Postmortem serotonin (5-HT) concentrations in the cerebrospinal fluid of medicolegal cases

“…Decreased activity in the serotonergic pathways from midbrain raphe to forebrain regions has been associated with a high risk of suicide and with impulsive, aggressive behaviour [4][5][6][7]. Studies in postmortem brain tissue from suicide victims showed a presynaptic serotonergic deficit [8][9][10][11][12] resulting in compensatory upregulation of postsynaptic 5-HT receptors (5-HT 1A and 5-HT 2A ) in the prefrontal cortex [13][14][15][16][17][18][19][20]. In psychiatric patients with affective disorders and mood disorders decreased 5-HT concentrations in the cerebrospinal fluid (CSF) or specific brain sections were reported, especially in acute depressive phases.…”