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.
Praschak-Rieder
Nicole
N
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.
Hussey
Douglas
D
Wilson
Alan A
AA
Carella
Anna
A
Lee
Maggie
M
Dunn
Edward
E
Willeit
Matthäus
M
Bagby
R Michael
RM
Houle
Sylvain
S
Meyer
Jeffrey H
JH
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