Abstract
Background: Rapid and transient depletion of tryptophan (TRP) causes a brief depressive
relapse in most patients successfully treated with and taking selective serotonin
reuptake inhibitors, but little change in drug-free, symptomatic depressed patients.
This study investigates the effects of TRP depletion in drug-free subjects in clinical
remission from a prior major depressive episode (MDE).
Methods: Twelve subjects with a prior MDE, currently in clinical remission and drug-free
for at least 3 months (patients), and 12 healthy subjects without personal or family
history of Axis I disorder (controls), received TRP depletion. The study was conducted
in a double-blind, controlled [full (102-g) and quarter-strength (25 g) 15-amino acid
drinks], crossover fashion. Behavioral ratings and plasma TRP levels were obtained
prior to, during, and after testing.
Results: All subjects experienced significant depletion of plasma TRP on both test-drinks,
showing a significant dose–response relation. Healthy control subjects had minimal
mood changes, but patients had a depressive response of greater magnitude.
Conclusions: In the context of prior TRP depletion studies with antidepressant-treated,
and drug-free symptomatic depressed patients, these results suggest that depression
may be caused not by an abnormality of 5-HT function, but by dysfunction of other
systems or brain regions modulated by 5-HT.
Keywords
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References
- Diagnostic and Statistical Manual of Mental Disorders. 3rd ed., rev. American Psychiatric Association, Washington, DC1987
- Liquid-chromatographic determination of serotonin and tryptophan in whole blood and plasma.Clin Chem. 1981; 27: 775-776
- Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors.Arch Gen Psychiatry. 1994; 51: 309-317
- The serotonin hypothesis of obsessive-compulsive disorder.J Clin Psychiatry. 1992; 53: 17-28
- Reduction of serotonin function in rat brain by tryptophan depletion.J Neurochem. 1996; 67: 669-676
- Mood-lowering effects of tryptophan depletion.Arch Gen Psychiatry. 1994; 51: 687-697
- Rapid depletion of serum tryptophan, brain tryptophan, serotonin, and 5-hydroxyindoleacetic acid by a tryptophan-free diet.Life Sci. 1974; 14: 1321-1329
- A role for the serotonin system in the mechanism of action of antidepressant treatments.J Clin Psychiatry. 1990; 51: 14-20
- Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse.Arch Gen Psychiatry. 1997; 54: 364-374
- Tryptophan depletion during continuous CSF sampling in healthy human subjects.Neuropsychopharmacology. 1998; 19: 26-35
- Relationships between plasma, CSF and brain tryptophan.J Neural Transm Suppl. 1979; 15: 93-105
- Influence of plasma tryptophan on brain 5-HT synthesis and serotonergic activity.in: Haber B Gabay S Serotonin Current Aspects of Neurochemistry and Function. Plenum Press, New York, London1981: 207-219
- Serotonin function and the mechanism of antidepressant action.Arch Gen Psychiatry. 1990; 47: 411-418
Delgado PL, Gelenberg AJ, Bologna L (1994): Serotonin depletion in paroxetine treated panic disordered patients. Presented at the 147th Annual Meeting of the American Psychiatric Association, New research abstract #616, May.
Delgado PL, Moreno FM, Miller HM, Salomon RM, Licinio J, Krystal JH, et al (1999): Tryptophan depletion challenge in depressed patients treated with desipramine or fluoxetine: Implications for the role of serotonin in the mechanism of antidepressant action. Biol Psychiatry, in press.
- Serotonin and the neurobiology of depression.Arch Gen Psychiatry. 1994; 51: 865-874
- Rapid serotonin depletion as a provocative challenge test for patients with major depression.Psychopharmacol Bull. 1991; 27: 321-330
- Mood response to tryptophan depletion in healthy volunteers.Neuropsychopharmacology. 1996; 15: 465-474
- Effects of the diet on brain neurotransmitters.Metabolism. 1977; 26: 207-223
- Effects of oral administration of tryptophan-free amino acid mixtures on serum tryptophan, brain tryptophan and serotonin metabolism.J Neurochem. 1974; 22: 869-870
- Effects of tryptophan depletion in panic disorder.Biol Psychiatry. 1994; 36: 775-777
- The assessment of anxiety states by rating.Br J Med Psychol. 1959; 32: 51-53
- Examining serotonin function.Neuropsychopharmacology. 1996; 15: 325-328
- Effects of rapid tryptophan depletion in patients with seasonal affective disorder in remission after light therapy.Arch Gen Psychiatry. 1996; 53;1: 41-44
- The effect of tryptophan depletion on mood in medication-free, former patients with major affective disorder.Neuropsychopharmacology. 1997; 16: 292-297
- Reliability and validity of the symptoms of major depressive illness.Arch Gen Psychiatry. 1986; 43: 451-456
- Manual for the Profile of Mood States. Educational and Industrial Testing Service, San Diego1988
- Dose-response decrease in plasma tryptophan and in brain tryptophan and serotonin after tryptophan-free amino acid mixtures in rats.Life Sci. 1989; 44: 971-976
- Cycloheximide blocks the fall of plasma and tissue tryptophan levels after tryptophan-free amino acid mixtures.Life Sci. 1991; 49: 1121-1128
Moreno FA, McGavin C, Malan P, Gelenberg AJ, Heninger GR, Mathe AA, et al (1997): CSF monoamine metabolites during tryptophan depletion in healthy males. American College of Neuropsychopharmacology Annual Meeting. Scientific abstracts page #253.
- Current status of the indoleamine hypothesis of the affective disorders.in: Lipton M.A DiMascio A Killan F Psychopharmacology A Generation of Progress. Raven Press, New York1978: 1235-1247
- Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy.Arch Gen Psychiatry. 1997; 54: 133-138
- Differences between males and females in rates of serotonin synthesis in human brain.Proc Natl Acad Sci U S A. 1997; 94: 5308-5313
- The amino acid requirements of man.J Biol Chem. 1954; 206: 421-430
- The inventory for depressive symptomatology (IDS).Psychiatry Res. 1986; 18: 65-87
- Tryptophan depletion and attenuation of cue-induced craving for cocaine.Am J Psychiatry. 1995; 152: 778-783
- Relapse of depression after rapid tryptophan depletion.Lancet. 1997; 349: 915-919
- Structured Clinical Interview for DSM III-R. Biometrics Research Department, New York State Psychiatric Institute, New York1987
- The functioning and well-being of depressed patients.JAMA. 1989; 262: 914-919
Williams WA, Hommer DW, Shoaf S, Goldman DS, Geyer C, Linnoila MI (1997): Behavioral and biochemical effects of acute depletion of plasma tryptophan in patients with alcoholism and in normal volunteers. Annual Meeting of the American Psychiatric Association, New Research Abstract #165, San Diego, CA: May 17–22.
- Carbon dioxide induced anxiety.Arch Gen Psychiatry. 1988; 45: 43-52
- Biochemical aspects of tryptophan depletion in primates.Psychopharmacology. 1989; 98: 508-511
- Tryptophan depletion causes a rapid lowering of mood in normal males.Psychopharmacology. 1985; 87: 173-177
Article info
Publication history
Accepted:
April 6,
1999
Received in revised form:
March 30,
1999
Received:
December 7,
1998
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
