Abstract
Background: Serotonin has been implicated in the regulation of sleep and mood. In
animals a tryptophan-free amino acid drink (TFD) challenge has been found to reduce
brain serotonin. We hypothesized this TFD would produce alterations in electroencephalographic
(EEG) sleep commonly associated with depression, i.e., an enhancement of rapid eye
movement (REM) sleep, and adversely affect mood ratings in humans.
Methods: We investigated the effects of a TFD challenge in 11 healthy male subjects
on EEG sleep and mood (assessed by Profile of Mood States). All subjects received
on separate occasions an experimental drink containing approximately 100 g of an amino
acid mixture (100% TFD) and a control drink containing one fourth strength (25% TFD)
of the experimental drink 5 hours prior to sleep (6:00 pm).
Results: Both drinks significantly decreased plasma tryptophan levels 5 hours postchallenge
(11:00 pm). Both drinks significantly decreased REM latency, and the 25% TFD also increased
REM time and REM% compared to baseline. No significant changes were found in subjective
ratings of depression; however, subjects reported confusion and tension and a decrease
in elation, vigor, and friendliness compared with baseline.
Conclusions: These TFD findings further support the involvement of serotonin deficiency
in EEG sleep findings commonly seen in depression.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans.Psychopharmacology. 1992; 108: 60-66
- Characterological depressions.Arch Gen Psychiatry. 1980; 37: 777-783
- Dietary tryptophan effects on the sleep of normal subjects.Waking Sleeping. 1977; 1: 163-164
- An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use.N Engl J Med. 1990; 323: 357-365
- Sleep and psychiatric disorders.Arch Gen Psychiatry. 1992; 49: 651-668
- Mood-lowering effect of tryptophan depletion.Arch Gen Psychiatry. 1994; 51: 687-697
- Rapid depletion of serum tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet.Life Sci. 1974; 14: 1321-1329
- Effect of a chronic tryptophan dietary deficiency on the rat’s sleep-wake cycle.Brain Res Bull. 1978; 3: 83-87
- Psychomotor, subjective, and neuroendocrine effects of acute tryptophan depletion in the healthy volunteer.Psychiatr Psychobiol. 1990; 5: 31-38
- Neuroendocrine and behavioral effects of dietary tryptophan restriction in healthy subjects.Life Sci. 1989; 45: 2323-2332
- Serotonin function and the mechanism of antidepressant action.Arch Gen Psychiatry. 1990; 47: 411-418
- Rapid serotonin depletion as a provocative challenge test for patients with major depression.Psychopharmacol Bull. 1991; 27: 321-330
- Serotonin and the neurobiology of depression.Arch Gen Psychiatry. 1994; 51: 865-874
- Some parallel findings in schizophrenic patients and serotonin-depleted cats.in: Sankar DV Schizophrenia—Current Concepts and Research. PJD Publications, Hicksville, NY1969: 775-811
- Sleep changes during chronic administration of parachlorophenylalanine.Rev Can Biol. 1972; 31: 239-246
- The determination of tryptophan in plasma, liver, and urine.J Lab Clin Med. 1967; 69: 160-169
- Functional role of 5-HT2 receptors in the regulation of sleep and wakefulness in the rat.Psychopharmacology. 1989; 97: 436-442
- Platelet serotonin content and free and total plasma tryptophan in healthy volunteers during 24 hours.Clin Chem. 1993; 39: 2337-2340
- Neurotransmitter systems.in: Kryger MH Roth T Dement WC Principles and Practice of Sleep Medicine. 2nd ed. W.B. Saunders Co, Philadelphia1994: 338-348
- Muscarinic supersensitivity.Psychiatry Res. 1979; 1: 17-22
- Inhibition of REM sleep by ipsapirone, a 5-HT1A agonist in normal volunteers.Psychopharmacology. 1994; 116: 433-436
- Increased pressure for rapid eye movement sleep at time of hospital admission predicts relapse in nondepressed patients with primary alcoholism at 3-month follow-up.Arch Gen Psychiatry. 1994; 51: 189-197
- Ipsapirone, a 5-HT1A agonist, suppresses REMsleep equally in unmedicated depressed patients and normal controls.Neuropsychopharmacology. 1996; 15: 109-115
- Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome.Arch Environ Contam Toxicol. 1993; 25: 134-142
- The Dreaming Brain. Basic Books, New York1988
- Sleep cycle oscillation.Science. 1975; 189: 55-58
- Biogenic amines and states of sleep.Science. 1969; 163: 32-41
- The role of monoamines and acetylcholine-containing neurons in the regulation of sleep-waking cycle.Ergeb Physiol. 1972; 64: 166-308
- Effect of chronic tryptophan depletion on the circadian rhythm of wheel-running activity in rats.Physiol Behav. 1994; 55: 1005-1013
- Long-term effects of a tryptophan-free diet on serotonin metabolism and sleep-waking balance in rats.Exp Brain Res. 1981; 41: 346-357
- A preliminary study of the effects of nighttime administration of the serotonin agonist, m-CPP, on sleep architecture and behavior in healthy volunteers.Biol Psychiatry. 1991; 29: 281-286
- The effects of buspirone on sleep in the rat.Neurosci Lett. 1986; 72: 64-68
- Serotonin hyperpolarizes cholinergic low-threshold burst neurons in the rat laterodorsal tegmental nucleus in vitro.Proc Natl Acad Sci USA. 1992; 89: 743-747
- The serotonin hypothesis of major depression.in: Bloom FE Kupfer DJ Psychopharmacology The Fourth Generation of Progress. Raven Press, New York1995: 933-944
- REM sleep and depression.Am J Psychiatry. 1982; 139: 565-570
- Neuronal excitability modulation over the sleep cycle.Science. 1975; 189: 58-60
- Sleep mechanisms.Int Rev Neurobiol. 1982; 23: 392-436
- Dorsal raphe neurons.Brain Res. 1976; 101: 569-575
- Neurochemically defined neurons.in: Phillips MI 5-HT Containing Neurons Unit Activity in Behaving Cats. Academic Press, New York1973: 244-267
- Manual for the Profile of Mood States. Educational Testing Services, San Diego, CA1988
- Reduction of REM sleep by a tryptophan-free amino acid diet.Life Sci. 1979; 24: 1467-1470
- Increase in stage 4 sleep after ingestion of a tryptophan-free diet in humans.Pharmacol Res Comm. 1984; 16: 909-914
- Decrease in plasma tryptophan after tryptophan-free amino acid mixtures in man.Life Sci. 1988; 42: 1551-1556
- 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 a tryptophan-free amino acid mixtures.Life Sci. 1991; 49: 1121-1128
- Effect of acute tryptophan depletion on mood and appetite in healthy female volunteers.J Psychopharmacol. 1994; 8: 8-13
- Dose-related suppression of REM sleep and PGO waves by the serotonin-1 agonist eltoprazine.Neuropsychopharmacology. 1993; 8: 7-13
- A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Public Health Services, Washington, DC1968
- The use of tryptophan depletion to evaluate central serotonin function in depression and other neuropsychiatric disorders.Int Clin Psychopharmacol. 1993; 8: 41-46
- Central administration of two 5-HT receptor agonists.Pharmacol Biochem Behav. 1994; 49: 93-100
- Buspirone.Psychopharmacology. 1985; 87: 371-373
- Effect of pharmacologic treatments on the sleep of depressed patients.Biol Psychiatry. 1995; 37: 85-89
- Brainstem mechanisms generating REM sleep.in: Kryger MH Roth T Dement WC Principles and Practice of Sleep Medicine. 2nd ed. W.B. Saunders Co, Philadelphia1994: 125-144
- A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males.Psychopharmacology. 1987; 91: 451-457
- Brainstem Control of Wakefulness and Sleep. Plenum Press, New York1990
- The serotonin-catecholamine-dream bicycle.Biol Psychiatry. 1972; 5: 33-64
- Tryptophandepletion causes a rapid lowering of mood in normal males.Psychopharmacology. 1985; 87: 173-177
- The effect of lowering plasma tryptophan on food selection in normal males.Pharmacol Biochem Behav. 1988; 31: 149-152
- Biochemical aspects of tryptophan depletion in primates.Psychopharmacology. 1989; 98: 508-511
- Effects of acute tryptophan depletion on nocturnal melatonin secretion in humans.J Clin Endocrinol Metab. 1993; 76: 1160-1164
Article info
Publication history
Accepted:
February 24,
1997
Received in revised form:
January 30,
1997
Received:
October 24,
1996
Identification
Copyright
© 1998 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.