Abstract
This work studies association between relapse during acute tryptophan depletion (ATD) and CSF level of tryptophan (TRP) in remitted depressives treated with sertraline or bupropion. Eight medication-responding depressives ingested an ATD amino acid mixture during 48-h continuous CSF sampling before and after treatment. Mood rating scores were compared with nadir levels of TRP in CSF. CSF TRP nadirs averaged 8.7% of am baselines in remitted patients. Mood relapsed whenever the CSF nadir was below 40 nmol/l TRP in remitted patients, and never when above (Fisher's exact test, P=0.029). Relapsing medication responders also showed very low preantidepressant ATD-induced nadirs. ATD-induced relapses were associated with low CSF TRP levels. Individual susceptibility to depletion may be independent of antidepressant treatment, mood state, or treatment status. Resistance to relapse may invoke an undefined, protective CNS mechanism against extremely low CSF levels of TRP during ATD.
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Acknowledgements
We gratefully acknowledge assistance and comments from Sidney Spector, PhD, Fridolin Sulser, MD, and Pedro L Delgado, MD in early planning and execution of this work; support of the Vanderbilt General Clinical Research Center through a grant from NIH/HCRR (MO1RR00095) awarded to Vanderbilt University Medical Center, Nashville, TN; and for investigator-initiated funding from Pfizer, Inc. Statistical assistance from Daniel Byrne, MS at the Vanderbilt GCRC is greatly appreciated. Support from the Stanley Foundation and a NARSAD young investigator's award to RMS for parallel, closely related studies are also acknowledged and appreciated.
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Presented, in part, in meeting abstracts at APA, Toronto, May 1998, and American College of Neuropsychopharmacology, Puerto Rico, December 1998.
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Salomon, R., Kennedy, J., Johnson, B. et al. Association of a Critical CSF Tryptophan Threshold Level with Depressive Relapse. Neuropsychopharmacol 28, 956–960 (2003). https://doi.org/10.1038/sj.npp.1300098
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DOI: https://doi.org/10.1038/sj.npp.1300098
