Impact of Experimentally Induced Serotonin Deficiency by Tryptophan Depletion on Saliva Cortisol Concentrations

Background: Tryptophan depletion (TD) has been shown to induce a transient mood-lowering effect in psychiatric patients and susceptible healthy subjects. We investigated the effects of TD on cortisol secretion in psychiatric patients and healthy subjects based on the hypothesis that the potential mood-lowering effects may be associated with increased activity of the hypothalamic-pituitary-adrenal axis, thus leading to a rise of cortisol secretion. Methods: After TD at 18.00 h, salivary cortisol was sampled in the evening and on the following morning. The first study was a randomized, placebo-controlled, crossover study in healthy subjects. Two further open trials in patients with obsessive-compulsive disorder (OCD) and primary insomnia compared the effects of TD on cortisol with baseline conditions. Results: In healthy subjects, TD significantly diminished cortisol the next morning compared with placebo. In OCD patients and primary insomniacs, cortisol the morning after TD was lowered compared with baseline. Evening cortisol was not affected by TD in any of the groups. Conclusions: Contrary to expectation, TD led to a comparable decrease of morning cortisol in all groups investigated. However, these findings are consistent with former studies analyzing the impact of antiserotonergic drugs on cortisol secretion. The results underline that the antiserotonergic effects caused by TD may influence cortisol secretion.

References

• 1 Aperia B, Thorén M, Zettergren M, Wetterberg L. Plasma pattern of adrenocorticotropin and cortisol during electroconvulsive therapy in patients with major depressive illness.  Acta Psychiatr Scand. 1984;  70 361-369
• 2 Asnis G M, Halbreich U, Rabinovich H, Ryan N D, Sachar E J, Nelson B. et al . The cortisol response to desipramine in endogenous depressives and normal controls: preliminary findings.  Psychiatry Res. 1985;  14 225-233
• 3 Attenburrow M J, Mitter P R, Whale R, Terao T, Cowen P J. Low-dose citalopram as a 5-HT neuroendocrine probe.  Psychopharmacology. 2001;  155 323-326
• 4 Barr L C, Heninger G R, Goodman W, Charney D S, Price L H. Effects of fluoxetine administration on mood response to tryptophan depletion in healthy subjects.  Biol Psychiatry. 1997;  41 949-954
• 5 Bell C, Abrams J, Nutt D. Tryptophan depletion and its implications for psychiatry.  Br J Psychiatry. 2001;  178 399-405
• 6 Benkelfat C, Ellenbogen M, Dean P, Palmour R, Young S. Mood lowering effect of tryptophan depletion.  Arch Gen Psychiatry. 1994;  51 687-697
• 7 Bjork J M, Dougherty D M, Moeller G, Swann A C. Differential behavioral effects of plasma tryptophan depletion and loading in aggressive and nonaggressive men.  Neuropsychopharmacology. 2000;  22 357-369
• 8 Booij L, Van der Does W, Benkelfat C, Bremner J D, Cowen P J, Fava M. et al . Predictors of mood response to acute tryptophan depletion. A reanalysis.  Neuropsychopharmacology. 2002;  27 852-861
• 9 Bschor T, Lewitzka U, Sasse J, Adli M, Köberle U, Bauer M. Lithium augmentation in treatment-resistant depression: clinical evidence, serotonergic and endocrine mechanisms.  Pharmacopsychiatry. 2003;  S3 230-234
• 10 Büttner-Westphal H, Hand I. Yale-Brown Obsessive Compulsive Scale, Deutsche Übersetzung und Bearbeitung.  Verhaltenstherapie. 1991;  1 226-233
• 11 Chihara K, Kato Y, Maeda K, Matsukura S, Imura H. Suppression by cyproheptadine of human growth hormone and cortisol secretion during sleep.  J Clin Invest. 1976;  57 1393-1402
• 12 Cowen P J, Charig E M. Neuroendocrine responses to intravenous tryptophan in major depression.  Arch Gen Psychiatry. 1987;  44 958-966
• 13 DeBattista C, Posener J A, Kalehzan B M, Schatzberg A F. Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: a double-blind, placebo-controlled study.  Am J Psychiatry. 2000;  157 1334-1337
• 14 Delgado P, Charney D, Price L, Aghajanian G, Landis H, Heninger G. Serotonin and the mechanism of antidepressant action.  Arch Gen Psychiatry. 1990;  47 411-418
• 15 Delgado P, Price S, Miller H, Salomon R, Aghajanian G, Heninger F. et al . Serotonin and the neurobiology of depression. Effects of tryptophan depletion in drug free depressed patients.  Arch Gen Psychiatry. 1994;  51 865-874
• 16 Delgado P, Moreno F. Antidepressants and the brain.  Int Clin Psychopharmacol.. 1999;  14 suppl. 1 9-16
• 17 Delgado P L, Moreno F A. Role of norepinephrine in depression.  J Clin Psychiatry. 2000;  61 suppl. 1 5-12
• 18 Ellenbogen M A, Young S N, Dean P, Palmour R M, Benkelfat C. Mood response to acute tryptophan depletion in healthy volunteers: sex differences and temporal stability.  Neuropsychopharmacology. 1996;  15 465-474
• 19 Feuchtl A, Bagli M, Stephan R, Frahnert C, Kölsch H, Kühn K U. et al . Pharmacokinetics of m-chlorophenylpiperazine after intravenous and oral administration in healthy male volunteers: implication for the pharmacodynamic profile.  Pharmacopsychiatry. 2004;  4 180-188
• 20 Franklin M, Cowen P J. Effect of a low tryptophan diet on the prolactin responses to the 5-HT_2A agonist DOI in the rat.  Pharmacopsychiatry. 2001;  34 147-149
• 21 Gessa G L, Biggio G, Fadda F, Corsini G V, Tagliamonte A. Effect of oral administration of tryptophan-free amino acid mixtures on serum tryptophan, brain tryptophan and serotonin metabolism.  J Neurochem. 1974;  22 869-870
• 22 Goddard A W, Charney D S, Germine M, Woods S W, Heninger G R, Krystal J H. et al . Effects of tryptophan depletion on responses to yohimbine in healthy subjects.  Biological Psychiatry. 1995;  38 74-85
• 23 Golden R N, Ekstrom D, Brown T M, Ruegg R, Dwight L E, Haggerty JJ J r. et al . Neuroendocrine effects of intravenous clomipramine in depressed patients and healthy subjects.  Am J Psychiatry. 1992;  149 1168-1175
• 24 Goodman W K, Price L H, Rasmussen S A, Mazure C, Fleischmann R L, Hill C L. et al . The Yale-Brown Obsessive Compulsive Scale: I. Development, use and reliability.  Arch Gen Psychiatry. 1989a;  46 1012-1016
• 25 Goodman W K, Price L H, Rasmussen S A, Mazure C, Delgado P, Heninger G R. et al . The Yale-Brown Obsessive Compulsive Scale: II. Validity.  Arch Gen Psychiatry. 1989b;  46 1006-1011
• 26 Goodwin G M, Muir W J, Seckl J R, Bennie J, Carroll S, Dick H. et al . The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls.  J Affective Disord. 1992;  26 73-83
• 27 Harmer C J, Bhagwagar Z, Shelley N, Cowen P J. Contrasting effects of citalopram and reboxetine on waking salivary cortisol.  Psychopharmacology. 2003;  167 112-114
• 28 Heim C, Ehlert U, Hellhammer D H. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders.  Psychoneuroendocrinology. 2000;  25 1-35
• 29 Heninger G R, Delgado P L, Charney D S. The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans.  Pharmacopsychiatry. 1996;  29 2-11
• 30 Holsboer F, Barden N. Antidepressants and hypothalamic-pituitary-adrenocortical regulation.  Endocrine Rev. 1996;  17 187-205
• 31 Huwig-Poppe C, Voderholzer U, Backhaus J, Riemann D, König A, Hohagen F. The tryptophan depletion test. Impact on sleep in healthy subjects and patients with obsessive-compulsive disorder.  Advan Exp Med Biol. 1999;  467 35-42
• 32 Kirschbaum C, Hellhammer D H. Salivary cortisol in psychoneuroendocrine research: recent developments and applications.  Psychoneuroendocrinol. 1994;  19 313-333
• 33 Kling M A, Geracioti T D, Licinio J, Michelson D, Oldfield E H, Gold P W. Effects of electroconvulsive therapy on the CRH-ACTH-Cortisol system in melancholic depression: preliminary findings.  Psychopharmacol Bulletin. 1994;  30 489-494
• 34 Kojima H, Terao T, Iwakawa M, Soya A, Inoue N, Shiraishi Y. et al . Paroxetine as a 5-HT neuroendocrine probe.  Psychopharmacology. 2003;  167 97-102
• 35 Leproult R, Copinschi G, Buxton O, van Cauter E. Sleep loss results in an elevation of cortisol levels the next evening.  Sleep. 1997;  20 865-870
• 36 Matza L S, Revicki D A, Davidson J R, Stewart J W. Depression with atypical features in the National Comorbidity Survey: classification, description and consequences.  Arch Gen Psychiatry. 2003;  60 817-826
• 37 Moja E A, Cipolla P, Castoldi D, Tofanetti O. 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
• 38 Moreno F A, Gelenberg A J, Heninger G R, Potter R L, McKnight K M, Allen J. et al . Tryptophan depletion and depressive vulnerability.  Biol Psychiatry. 1999;  46 498-505
• 39 Murck H. Atypical depression spectrum disorder - neurobiology and treatment.  Acta Neuropsychiatrica. 2003;  15 227-241
• 40 Neumeister A, Praschak-Rieder N, Heßelmann B, Vitouch O, Rauh M, Barocka A. et al . Effects of tryptophan depletion in drug-free depressed patients who responded to total sleep deprivation.  Arch Gen Psychiatry. 1998;  55 167-172
• 41 Parker K J, Schatzberg A F, Lyons D M. Neuroendocrine aspects of hypercortisolism in major depression.  Horm Behav. 2003;  43 60-66
• 42 Pigott T A, L’Heureux F, Dubbert B, Bernstein S, Murphy D L. Obsessive compulsive disorder: comorbid conditions.  J Clin Psychiatry. 1994;  55 suppl 15 - 27, discussion 28 - 32
• 43 Plonk J, Feldman J. Modification of adrenal function by the anti-serotonin agent cyproheptadine.  J Clin Endocrinol Metab. 1976;  42 291-295
• 44 Porter R J, Marshall E F, O’Brien J T. Effects of rapid tryptophan depletion on salivary and plasma cortisol in Alzheimer’s disease and the healthy elderly.  Journal of Psychopharmacology. 2002;  16 73-78
• 45 Price L H, Malison R T, McDougle C J, McCance-Katz E F, Owen K R, Heninger G R. Neurobiology of tryptophan depletion in depression: effects of m-chlorophenylpiperazine (mCPP).  Neuropsychopharmacology. 1997;  17 342-350
• 46 Price L H, Malison R T, McDougle C J, Pelton G H, Heninger G R. The neurobiology of tryptophan depletion in depression: effects of intravenous tryptophan infusion.  Biological Psychiatry. 1998;  43 339-347
• 47 Riedel W J, Klaassen T, Schmitt J A. Tryptophan, mood, and cognitive function.  Brain Behav Immun. 2002;  16 581-589
• 48 Riemann D, Hornyak M, Koch S, Hohagen F, Voderholzer U. The tryptophan-depletion test: Impact on sleep in primary insomnia - a pilot study.  Psychiat Res. 2002;  109 129-135
• 49 Schüle C, Baghai T, Ferrera A, Laakmann G. Neuroendocrine effects of Hypericum extract WS 5570 in 12 healthy male volunteers.  Pharmacopsychiatry. 2001;  34 suppl. 1 127-133
• 50 Sobczak S, Honig A, Nicolson N A, Riedel W J. Effects of acute tryptophan depletion on mood and cortisol release in first-degree relatives of type I and type II bipolar patients and healthy matched controls.  Neuropsychopharmacology. 2002;  27 834-842
• 51 Spiegel K, Leproult R, Cauter van E. Impact of sleep debt on metabolic and endocrine function.  Lancet. 1999;  354 1435-1439
• 52 Spitzer R L, Williams J B, Gibbons M. The structured clinical interview for DSM-III-R. Biometrics Research Department. New York State Psychiatric Institute New York; 1984
• 53 Ströhle A, Holsboer F. Stress Responsive Neurohormones in Depression and Anxiety.  Pharmacopsychiatry. 2003;  S3 207-214
• 54 Tsigos C, Chrousos G P. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.  J Psychosom Res. 2002;  53 865-871
• 55 Voderholzer U, Hohagen F, Klein T, Jungnickel J, Kirschbaum C, Berger M. et al . Impact of Sleep Deprivation and Subsequent Recovery Sleep on Cortisol in Unmedicated Depressed Patients.  Am J Psychiatry. 2004;  161 1404-1410
• 56 Voderholzer U, Hornyak M, Thiel B, Huwig-Poppe C, Kiemen A, König A. et al . Impact of experimentally induced serotonin deficiency by tryptophan depletion on sleep EEG in healthy subjects.  Neuropsychopharmacology. 1998;  18 112-124
• 57 Weitzman E D, Zimmerman J C, Czeisler C A, Ronda J. Cortisol secretion is inhibited during sleep in normal man.  J Clin Endocrinol Metab. 1983;  56 352-358
• 58 Wittchen H U, Zaudig M, Schramm E, Spengler P, Mombour B, Kleig J. et al .Strukturiertes klinisches Interview für DSM-III-R (SKID-P). Beltz-Test Weinheim; 1988
• 59 Wüst S, Federenko I, Hellhammer D H, Kirschbaum C. Genetic factors, perceived chronic stress, and the free cortisol response to awakening.  Psychoneuroendocrinology. 2000;  25 707-720
• 60 Young S N, Smith S E, Pihl R O, Ervin F R. Tryptophan depletion causes a rapid lowering of mood in normal males.  Psychopharmacology. 1985;  87 173-177
• 61 Zerssen von D. Clinical Self-Rating Scales (CSRS) of the Munich Psychiatry Information System (PSYCHIS München). In Sartorius N, Ban TA, editors Assessment of Depression. Berlin Heidelberg New York Tokyo; Springer 1986: pp 270-303