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Antagonist but not agonist labeling of serotonin-1A receptors is decreased in major depressive disorder.
- Source :
-
Journal of psychiatric research [J Psychiatr Res] 2009 Jul; Vol. 43 (10), pp. 887-94. Date of Electronic Publication: 2009 Feb 12. - Publication Year :
- 2009
-
Abstract
- Serotonin-1A receptors may play a role in the pathophysiology of depression and suicide. In postmortem brain tissue, agonist binding to serotonin-1A receptors is reportedly increased or unchanged in depression or suicide, while neuroimaging studies report a decrease in antagonist binding to these receptors in subjects with depression. In this study, both agonist and antagonist radioligand binding to serotonin-1A receptors were examined in postmortem orbitofrontal cortex from subjects with major depressive disorder (MDD). Brain tissue was collected at autopsy from 11 subjects with MDD and 11 age- and gender-matched normal control subjects. Two depressed subjects had a recent psychoactive substance use disorder. Six subjects with MDD had a prescription for an antidepressant drug in the last month of life, and, of these six, postmortem bloods from only two subjects tested positive for an antidepressant drug. There was no significant difference between cohorts for age, postmortem interval or tissue pH. The receptor agonist [3H]8-OH-DPAT or the antagonist [3H]MPPF were used to autoradiographically label serotonin-1A receptors in frozen sections from cytoarchitectonically-defined left rostral orbitofrontal cortex (area 47). There was no significant difference between depressed and control subjects in agonist binding to serotonin-1A receptors. However, antagonist binding was significantly decreased in outer layers of orbitofrontal cortex in MDD. This observation in postmortem tissue confirms reports using an antagonist radioligand in living subjects with depression. Decreased antagonist binding to serotonin-1A receptors in outer layers of orbitofrontal cortex suggests diminished receptor signaling and may be linked to corresponding neuronal changes detected previously in these depressed subjects.
- Subjects :
- Adult
Aged
Analysis of Variance
Autoradiography methods
Case-Control Studies
Depressive Disorder, Major pathology
Female
Frontal Lobe drug effects
Frontal Lobe metabolism
Frontal Lobe pathology
Humans
Male
Middle Aged
Piperazines metabolism
Postmortem Changes
Protein Binding drug effects
Tritium metabolism
Young Adult
Depressive Disorder, Major diagnosis
Depressive Disorder, Major metabolism
Receptor, Serotonin, 5-HT1A metabolism
Serotonin Antagonists
Serotonin Receptor Agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1379
- Volume :
- 43
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of psychiatric research
- Publication Type :
- Academic Journal
- Accession number :
- 19215942
- Full Text :
- https://doi.org/10.1016/j.jpsychires.2009.01.001