Effects of tryptophan depletion on the serotonin transporter in healthy humans.
BACKGROUND
Lowering of brain serotonin by acute tryptophan depletion (TD) frequently leads to transient symptoms of depression in vulnerable individuals but not in euthymic healthy subjects with a negative family history of depression. The effects of TD on regional serotonin transporter binding potential (5-HTT BP), an index of 5-HTT density and affinity, were studied in healthy individuals using 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile ([11C]DASB) positron emission tomography (PET). Adaptive decreases in 5-HTT density and/or affinity during TD would be a possible compensatory mechanism to maintain sufficient extracellular serotonin levels during TD, thereby preventing a depressive relapse.


METHODS
Regional noninvasive 5-HTT BP was found in 25 healthy subjects using [11C]DASB PET. Fourteen subjects were scanned twice, once after TD and once after sham depletion, and 11 other healthy subjects were scanned twice to measure test-retest reliability of the method.


RESULTS
None of the healthy subjects experienced depressive symptoms during TD and there was no difference in regional 5-HTT BP during TD as compared with sham depletion.


CONCLUSIONS
Acute changes in 5-HTT density or affinity are unlikely to play a role in protecting healthy subjects against mood symptoms during TD. Other mechanisms that may be associated with greater resilience against acute lowering of extracellular serotonin should be explored to gain further insight into the neurochemical basis of different vulnerabilities to short-term depressive relapse.
Praschak-Rieder
Nicole
N
Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, Canada.
Wilson
Alan A
AA
Hussey
Douglas
D
Carella
Anna
A
Wei
Corie
C
Ginovart
Nathalie
N
Schwarz
Markus J
MJ
Zach
Johanna
J
Houle
Sylvain
S
Meyer
Jeffrey H
JH
D000328:Adult; D001596:Benzylamines; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003866:Depressive Disorder / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D055502:Secondary Prevention; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism* / Q000502:physiology; D014364:Tryptophan / Q000172:deficiency* / Q000378:metabolism*
D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014364:Tryptophan