Lower 3H-paroxetine binding in cerebral cortex of suicide victims is partly due to fewer high affinity, non-transporter sites.
Suicide has been associated with decreased serotonin transmission. Measurement of concentrations of serotonin, its precursors tryptophan (TRY) and 5-hydroxytryptophan (5-HTP) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), have been used as indices of serotonin activity, and with serotonin transporter binding, are indices of the integrity of serotonin nerve terminals. Most previous studies have not distinguished high affinity transporter binding from a very similar nontransporter binding site, where binding is not dependent on Na+ or Cl- and that does not have a known functional role. We therefore, assayed binding kinetics in prefrontal (PFC) and temporal cortex (TC) in matched pairs of suicide victims and controls using the selective ligand 3H-paroxetine, and employing 1 microM sertraline to define specific binding to the transporter and 10 microM sertraline which also displaces binding to the high affinity, nontransporter site. In addition, we measured concentrations of TRY, 5-HTP, serotonin and 5-HIAA in the same brain areas. The total number of 3H-paroxetine transporter and nontransporter binding sites (Bmax), was lower in the suicide group compared to controls in both Brodmann area 9 (prefrontal cortex; p = 0.02) and in Brodmann area 38 (temporal cortex, p = 0.01). In contrast, no differences were found in the number of high affinity transporter binding sites and concentrations of serotonin, 5-HIAA, 5-HTP or TRY (p > 0.05). We conclude that the number of serotonin transporter sites is not altered in Brodmann area 9 in suicide, and that fewer 3H-paroxetine and 3H-imipramine binding sites found in this region of cerebral cortex of suicides may be explained by a reduction in the nontransporter binding sites.
Mann
J J
JJ
Department of Neuroscience, New York State Psychiatric Institute, NY, USA.
Henteleff
R A
RA
Lagattuta
T F
TF
Perper
J A
JA
Li
S
S
Arango
V
V
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013405:Suicide; D014364:Tryptophan / Q000378:metabolism
D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D017374:Paroxetine; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D006916:5-Hydroxytryptophan