Measurement of 5-HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY-100635.
OBJECTIVE
To assess effects of chronic antidepressant drug treatment on serotonin type-1A receptor (5-HT(1A)R) binding potential (BP) in major depressive disorder.


METHODS
Depressed subjects (n = 27) were imaged using PET and [(11)C]WAY-100635 at baseline and following a median of 9.4 weeks of treatment with selective serotonin reuptake inhibitor or dual reuptake inhibitor antidepressant agents. Fifteen subjects had complete pre- and post-treatment scan data. The 5-HT(1A)R BP was derived from the tissue time-radioactivity concentrations from regions-of-interest defined a priori, using a simplified reference tissue model (SRTM), and in a subset of subjects, compartmental modeling (CMOD).


RESULTS
Chronic treatment had no effect on pre- or post-synaptic 5-HT(1A)R BP, as confirmed by both the SRTM and CMOD analyses. These results were unaffected by treatment response status and were consistent across brain regions. Among the 22 subjects for whom the clinical response-to-treatment was established, the treatment nonresponders (n = 7) had higher baseline BP values in the left (P = 0.01) and right orbital cortex (P = 0.02) than the responders (n = 15).


CONCLUSIONS
Chronic antidepressant drug treatment did not significantly change cerebral 5-HT(1A)R binding, consistent with preclinical evidence that the alterations in serotonergic function associated with antidepressant drug administration are not accompanied by changes in 5-HT(1A)R density. Higher baseline 5-HT(1A)R binding was associated with poorer response to treatment.
Moses-Kolko
Eydie L
EL
Departments of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. MosesEL@upmc.edu
Price
Julie C
JC
Thase
Michael E
ME
Meltzer
Carolyn Cidis
CC
Kupfer
David J
DJ
Mathis
Chester A
CA
Bogers
Wendy D
WD
Berman
Susan R
SR
Houck
Patricia R
PR
Schneider
Trisha N
TN
Drevets
Wayne C
WC
D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000493:pharmacokinetics*; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D012189:Retrospective Studies; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*
D000928:Antidepressive Agents; D010879:Piperazines; D011725:Pyridines; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide