Effects of a Tryptophan-Free Amino Acid Drink Challenge on Normal Human Sleep Electroencephalogram and Mood

Bhatti, Tahir; Gillin, J. Christian; Seifritz, Erich; Moore, Polly; Clark, Camellia P.; Golshan, Shahrokh; Stahl, Stephen M.; Rapaport, Mark Hyman; Kelsoe, John R.

doi:10.1016/s0006-3223(97)80252-1

Cited by 77 publications

(63 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another study showed that 5-HT release in brain slices decreases when the slice preparation is superfused with a solution of large neutral amino acids minus tryptophan (Schaechter and Wurtman 1990). Overall, the effects of the TFD here are very similar to those reported by our laboratory in Bhatti et al (1998) with normal adult males and in Moore et al (1998) with SSRI treated patients: facilitation of REM sleep without significant effects on depressive symptoms. Bupropion's mode of action as an antidepressant is possibly unaffected by manipulations in the 5-HT system.…”

Section: Discussionsupporting

confidence: 86%

“…Consistent with the hypothesis that 5-HT inhibits REM sleep, Bhatti et al (1998) found that a TFD decreased REM latency and increased REM% in normal male subjects. Voderholzer et al (1998) found a significant increase in RD in 12 healthy subjects after TFD administration but saw no other significant REM changes.…”

Section: Serotonin Has Been Implicated In Both Sleep and Mood Regulatsupporting

confidence: 80%

“…Rapid depletion of plasma tryptophan levels by administration of a tryptophan-free amino acid drink (TFD) depletes central 5-HT levels (Biggio et al 1974;Moja et al 1988). See Moore et al (2000) for a recent review of the TFD literature.Consistent with the hypothesis that 5-HT inhibits REM sleep, Bhatti et al (1998) found that a TFD decreased REM latency and increased REM% in normal male subjects. Voderholzer et al (1998) found a significant increase in RD in 12 healthy subjects after TFD administration but saw no other significant REM changes.…”

supporting

confidence: 80%

“…Quintin et al (2001) showed a decline in mood as measured by the Hamilton Rating Scale for Depression (HRSD) and the Depressive Mood Scale in unaffected subjects with at least two bipolar relatives but no change in health controls without a family history of affective disorders. Along the same lines, normal males given a TFD in the Bhatti et al (1998) study showed no significant change on the depression subscale of the POMS. These subjects did, however, show significant decreases in the POMS elation, friendliness, and vigor subscales and significant increases in the confusion and tension subscales .…”

Section: Serotonin Has Been Implicated In Both Sleep and Mood Regulatmentioning

confidence: 61%

See 3 more Smart Citations

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Evans

Golshan

Kelsoe

et al. 2002

Neuropsychopharmacology

View full text Add to dashboard Cite

Serotonin has been implicated in both sleep and mood regulation. When central serotonin was depleted with a tryptophan-free amino acid drink (TFD),Serotonin (5-hydroxytryptamine; 5-HT) has long been implicated in the pathophysiology of depression as well as in the sleep and mood abnormalities associated with depression (Maes and Meltzer 1995). Specifically, deficiencies in 5-HT levels or in cellular responses to 5-HT neurotransmission are thought to be involved in depression. In support of this idea, deficiencies in 5-HT neurotransmission in various projections from the raphe nucleus can at least partially explain many of the common abnormalities seen in depression such as a depressed mood, decreased interest and pleasure, decreased appetite, and insomnia (Stahl 2000). Also commonly seen in depression are reduced rapid eye -Colin 1982;McCarley 1982;Jones 1991;Luebke et al. 1992).The rate of 5-HT synthesis is limited by the availability of its amino acid precursor, tryptophan. Rapid depletion of plasma tryptophan levels by administration of a tryptophan-free amino acid drink (TFD) depletes central 5-HT levels (Biggio et al. 1974;Moja et al. 1988). See Moore et al. (2000) for a recent review of the TFD literature.Consistent with the hypothesis that 5-HT inhibits REM sleep, Bhatti et al. (1998) found that a TFD decreased REM latency and increased REM% in normal male subjects. Voderholzer et al. (1998) found a significant increase in RD in 12 healthy subjects after TFD administration but saw no other significant REM changes. A study by Moore et al. (1998) found reduced RL and stage 2 percent (S2%) and increased REM% and RD after TFD administration in fully remitted depression patients on selective serotonin reuptake inhibitors (SSRIs). Additionally, in four patients treated with the monoamine oxidase inhibitor (MAOI), phenelzine, Landolt et al. (2000) showed increased REM time and REM% after TFD administration.With regard to mood, TFD studies have had mixed results when tested in normal subjects. One TFD study showed normal males having significantly increased scores on a depression scale, the Multiple Affect Adjective Checklist (MAACL), after TFD administration (Young et al. 1985). Benkelfat et al. (1994) also found decreased mood on the Profile of Mood States (POMS) in six out of 20 of his healthy male subjects with a multigenerational history of affective disorder. Additionally, Klaassen et al. (1999) found that TFD administration lowered mood in both subjects with and without a family history of affective disorders with the mood changes being significantly more evident in those with a family history. Ellenbogen et al. (1996) showed that healthy female subjects had significantly lower scores after a TFD on four of six scales on the bipolar form of the POMS including the depression scale. However, Ellenbogen et al. (1999) showed that normal females with a multi-generational family history of major affective disorders had no lowering of mood in response to a TFD. Quintin et al. (2001) showed a decline in mood as m...

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Serotonin Has Been Implicated In Both Sleep and Mood Regulatsupporting

confidence: 80%

supporting

confidence: 80%

Section: Serotonin Has Been Implicated In Both Sleep and Mood Regulatmentioning

confidence: 61%

See 2 more Smart Citations

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Evans

Golshan

Kelsoe

et al. 2002

Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…Here, after an 85% RTD, REM latency was 69 Ϯ 5 (mean Ϯ s.e.m. ), whereas in the Bhatti et al (1998) study after the 100% RTD, mean REM-latencies were 40 Ϯ 11, and 48 Ϯ 12 after the 25% RTD. Baseline REM latencies did not differ significantly between the studies, nor did subject age.…”

Section: Discussionmentioning

confidence: 72%

Rapid Tryptophan Depletion Plus a Serotonin 1A Agonist Competing Effects on Sleep in Healthy Men

Moore¹,

Seifritz

Schlosser

et al. 2001

Neuropsychopharmacology

View full text Add to dashboard Cite

In the present study, we hypothesized that the REMsuppressing effects of 5-HT 1A receptor stimulation would counteract the REM-disinhibiting effects of rapid tryptophan depletion (RTD), and vice versa. We administered RTD plus ipsapirone (10 mg, p.o.) The rapid tryptophan depletion (RTD) paradigm (Young et al. 1985;Delgado et al. 1990) allows researchers to study the consequences of 5-HT system deactivation. In humans and animals, RTD has been shown to cause significant (but transient) reductions in the levels of tryptophan (TRP) in the blood, and to reduce the amount of 5-HT in the brain (for review, see Moore et al. 2000). RTD typically consists of a day's worth of a low-TRP diet, followed by ingestion of a TRP-free amino acid load, and RTD, but not the control TRP-containing condition, has been associated with myriad clinical and physiological effects. Relapse of depressive mood following RTD in recently remitted depressed patients has been reported (Delgado et al. 1990). In healthy subjects, mood responses as well as other behavioral measures have been somewhat inconsistent (Young et al. 1985;Barr et al. 1997).The sleep abnormalities often associated with depression are consistent with the notion of a pathophysiologic deficiency in serotonergic function in depression (Maes and Meltzer 1995). There is strong preclinical and clinical evidence that serotonin plays a role in suppressing REM sleep (McGinty and Harper 1976;Honda and Semba 1994;Luebke et al. 1992;Portas et al. 1996).RTD apparently disinhibits REM sleep measures in serotonin reuptake inhibitor (SRI)-treated patients in full remission ) and in healthy male control subjects ), using two different The Effects of REM Sleep of RTD plus Ipsapirone S41 strengths of RTD (100% and 25%). In SRI-treated patients, both RTD doses also reversed the reduced total sleep time and prolonged sleep latency observed at baseline. In normal males, both RTD doses significantly decreased REM latency compared with baseline, as well as significantly reduced total and free plasma TRP concentrations.Agonists at the 5-HT 1A receptor, such as ipsapirone, have been shown to inhibit REM sleep both in healthy subjects and in depressed patients (Gillin et al. 1994;Gillin et al. 1996;, and this effect presumably reflects predominantly post-synaptic receptor activity. In the present study, we examined the competing effects of 5-HT depletion and 5-HT stimulation on sleep. We predicted REM sleep measures with RTD plus placebo would be significantly enhanced compared with baseline as shown in previous studies with RTD alone, and that the combination of RTD and ipsapirone would produce REM measures with values intermediate between those obtained with either 5-HT manipulation alone. METHODS SubjectsTen healthy male subjects between the ages of 20 to 39 years (28.7 Ϯ 1.9, mean Ϯ SD) were recruited from the general public in the San Diego region through the UCSD Mental Health Clinical Research Center (MH-CRC). Eight Caucasian-Americans and two AfricanAmericans completed the study after givin...

show abstract

Rapid Tryptophan Depletion, Sleep Electroencephalogram, and Mood in Men With Remitted Depression on Serotonin Reuptake Inhibitors

Moore¹,

Gillin²,

Bhatti³

et al. 1998

Arch Gen Psychiatry

Self Cite

View full text Add to dashboard Cite

Background:In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs.

show abstract

Effects of a Tryptophan-Free Amino Acid Drink Challenge on Normal Human Sleep Electroencephalogram and Mood

Cited by 77 publications

References 42 publications

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Rapid Tryptophan Depletion Plus a Serotonin 1A Agonist Competing Effects on Sleep in Healthy Men

Rapid Tryptophan Depletion, Sleep Electroencephalogram, and Mood in Men With Remitted Depression on Serotonin Reuptake Inhibitors

Contact Info

Product

Resources

About