Tryptophan depletion and serotonin loss in selective serotonin reuptake inhibitor-treated depression: an [(18)F] MPPF positron emission tomography study.
BACKGROUND
Recurrence of depressive symptoms after tryptophan depletion (TD) in selective serotonin reuptake inhibitor (SSRI)-treated depression is an important, unexplained phenomenon. With [(18)F] MPPF positron emission tomography (PET), serotonin (5-hydroxytryptamine, 5-HT) 1A receptor binding potential (5-HT(1A)BP) was measured after TD in various brain regions in citalopram-treated depression. This 5-HT(1A)BP measurement is sensitive to changes in extracellular 5-HT in animal models.


METHODS
Eight remitted patients with major depressive disorder received [(18)F] MPPF PET scans twice: once after TD and once after sham depletion. Behavioral measures were evaluated with the Hamilton Depression Rating Scale and visual analog scales.


RESULTS
No effect on regional 5-HT(1A)BP was observed after TD, despite an 86% decrease in total plasma tryptophan and transient depressive relapse in six of eight patients.


CONCLUSIONS
Large-magnitude changes in extracellular 5-HT are not crucial for the mood effects observed in SSRI-treated subjects after TD. Therefore, greater consideration must be given to other mechanisms that involve vulnerability to small perturbations in extracellular 5-HT, such as impairment of signal transduction.
Vivian M. Rakoff PET Imaging Centre and the Mood and Anxiety Disorders Division, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Nicole
N
Praschak-Rieder
Douglas
D
Hussey
Alan A
AA
Wilson
Anna
A
Carella
Maggie
M
Lee
Edward
E
Dunn
Matthäus
M
Willeit
R Michael
RM
Bagby
Sylvain
S
Houle
Jeffrey H
JH
Meyer
D000328:Adult; D000631:Aminopyridines; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D004311:Double-Blind Method; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry / Q000379:methods; D012701:Serotonin / Q000172:deficiency*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014364:Tryptophan / Q000172:deficiency*
D000631:Aminopyridines; D005462:Fluorine Radioisotopes; D010879:Piperazines; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan; C099463:4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine