Citation

Underwood MD, Kassir SA, Bakalian MJ, Galfalvy H, Mann JJ, Arango V. Int. J. Neuropsychopharmacol. 2012; 15(4): 435-447.

Copyright

(Copyright © 2012, Cambridge University Press)

DOI

10.1017/S1461145711000691

PMID

21733245

PMCID

PMC4167642

Abstract

Although serotonin receptor and cytoarchitectonic alterations are reported in prefrontal cortex (PFC) in suicide and depression, no study has considered binding relative to neuron density. Therefore, we measured neuron density and serotonin transporter (SERT), 5-HT1A and 5-HT2A binding in matched suicides and controls. Suicides and normal controls (n=15 matched pairs) were psychiatrically characterized. Neuron density and binding were determined in dorsal [Brodmann area (BA) 9] and ventral (BA 47) PFC by stereology and quantitative autoradiography in near-adjacent sections. Binding index was defined as the ratio of receptor binding to neuron density. Suicides had lower neuron density in the gyrus of both areas. The binding index was lower for SERT in BA 47 but not in BA9; the 5-HT1A binding index was higher in BA 9 but not in BA 47, while the 5-HT2A binding index was not different between groups. SERT binding was lower in suicides in BA 47 but not BA 9, while 5-HT1A binding was higher in BA 9 but not BA 47. SERT binding negatively correlated with 5-HT1A binding in BA 47 in suicides. Neuron density decreased with age. The 5-HT1A binding index was higher in females than males. We found lower neuron density and lower SERT binding index in both PFC regions in suicides. More 5-HT1A binding with less SERT binding and the negative correlation in depressed suicides suggests post-synaptic receptor up-regulation, and it is independent of the difference in neuron density. Thus, abnormalities in both cortical neurons and in their serotonergic innervation are present in suicides and future studies will need to determine whether cortical changes reflect the trophic effect of altered serotonin innervation.

Language: en

Keywords

Humans; Adult; Aged; Female; Male; Middle Aged; Adolescent; Suicide; Young Adult; Postmortem Changes; Case-Control Studies; Neurons; Depressive Disorder, Major; Prefrontal Cortex; Imipramine; Up-Regulation; Receptors, Serotonin; Tritium; Autoradiography; Protein Binding; Ketanserin; Serotonin Agents; 8-Hydroxy-2-(di-n-propylamino)tetralin