Effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients symptomatically stable on lithium

BackgroundPrevious studies suggest that brain serotonin neurotransmission may mediate the actions of lithium carbonate. Acute tryptophan depletion reduces brain serotonin and allows the study of this neurotransmitter in patient groups.AimsTo examine the effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients who were symptomatically stable on lithium.MethodNineteen subjects satisfying DSM–IV criteria for bipolar I disorder participated in a within-subject, double-blind, placebo-controlled random-order crossover study. Symptoms were evaluated following acute tryptophan depletion, which was induced by a 100 g amino acid drink following an overnight fast.ResultsPlasma tryptophan fell significantly after the depleting drink, but not after the control drink (P < 0.05, paired t-test, mean reduction 83%). No significant changes in mood or suicidality scores were recorded after acute tryptophan depletion.ConclusionsAcute tryptophan depletion does not reverse lithium's effects on mood and suicidality in bipolar disorder.

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Effects of rapid tryptophan depletion in patients with seasonal affective disorder in natural summer remission

Psychological Medicine ◽

10.1017/s003329179900152x ◽

2000 ◽

Vol 30 (1) ◽

pp. 79-87 ◽

Cited By ~ 26

Author(s):

R. W. LAM ◽

T. A. BOWERING ◽

E. M. TAM ◽

A. GREWAL ◽

L. N. YATHAM ◽

...

Keyword(s):

Affective Disorder ◽

Repeated Measures ◽

Seasonal Affective Disorder ◽

Bright Light ◽

Light Therapy ◽

Brain Serotonin ◽

Tryptophan Depletion ◽

Control Session ◽

Double Blind ◽

Plasma Tryptophan

Background. Serotonergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder (SAD) and the therapeutic effect of bright-light treatment. Previously, we showed that SAD patients, in clinical remission with light therapy during the winter, experienced transient depressive relapses after a rapid tryptophan depletion (RTD) technique, which results in decreased brain serotonin levels. The objective of this study was to investigate the effect of RTD in SAD patients who were in natural summer remission.Methods. Twelve drug-free patients with SAD by DSM-IV criteria and 10 normal subjects participated in this double-blind, placebo-controlled, crossover study. SAD patients were in natural summer remission for at least 8 weeks. Behavioural ratings and plasma tryptophan levels were obtained before, and 5 h after, ingesting an amino acid (AA) mixture±tryptophan. Experimental RTD and control sessions were scheduled 1 week apart.Results. The RTD session resulted in significant reduction in total and free plasma tryptophan levels compared to the control session. The behavioural data were analysed using repeated measures analysis of variance. This analysis found significant main effects of time (higher scores after AA ingestion) and diagnosis (higher scores in SAD patients), but no main effect of session or significant interaction effects between the three factors. Thus, there were no significant behavioural effects of RTD compared to the sham depletion control session.Conclusions. The summer remission experienced by SAD patients is not dependent on plasma tryptophan levels (and presumably brain serotonin function) in the same manner as that of remission after light therapy. These results conflict with those of other laboratories, perhaps because of differences in study samples.

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Brain 5-HT function in bipolar affective disorder

Acta Neuropsychiatrica ◽

10.1017/s0924270800035481 ◽

2000 ◽

Vol 12 (3) ◽

pp. 91-95

Author(s):

A.H. Young ◽

J.H. Hughes ◽

C.H. Ashton

Keyword(s):

Bipolar Disorder ◽

Power Spectrum ◽

Evoked Potentials ◽

Auditory Evoked Potentials ◽

Auditory Evoked Potential ◽

Brain Serotonin ◽

Acute Tryptophan Depletion ◽

Tryptophan Depletion ◽

Eeg Activity ◽

Bipolar Patients

ABSTRACTBackground: Previous studies suggest that brain serotonin neurotransmission may mediate the actions of lithium carbonate. Acute tryptophan depletion (ATD) reduces brain serotonin and allows the study of this neurotransmitter in patient groups. Serotonin modulates electroencephalographic (EEG) activity, which is abnormal in bipolar disorder, and EEG abnormalities persist in euthymic bipolar patients. The EEG may therefore be a sensitive marker of 5-HT function in bipolar disorder.Aims: This study examined the effects of ATD on mood, suicidal ideation and EEG activity in bipolar patients who were symptomatically stable on lithium.Methods: 19 subjects satisfying DSM-IV criteria for bipolar I disorder participated in a within-subject, double-blind, placebo-controlled random-order crossover study. Following acute tryptophan depletion (induced by a 100g amino acid drink following an overnight fast) symptoms were evaluated, quantitative power spectrum brain mapping and measurement of auditory evoked potentials were carried out.Results: ATD produced a significant fall in the amplitude of N1P2 and P300 components of the auditory evoked potential, but no significant changes in the power spectrum. There was an 83% reduction in plasma tryptophan (p<0.05, paired t-test) after the depleting but not the control drink. No significant changes in mood or suicidally scores were recorded after ATD.Conclusions: ATD attenuates auditory evoked potentials in bipolar disorder but does not reverse lithium's effects on mood and suicidally in bipolar disorder.

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Effect of acute tryptophan depletion on CO2-induced anxiety in patients with panic disorder and normal volunteers

The British Journal of Psychiatry ◽

10.1192/bjp.176.2.182 ◽

2000 ◽

Vol 176 (2) ◽

pp. 182-188 ◽

Cited By ~ 62

Author(s):

H. E. J. Miller ◽

J. F. W. Deakin ◽

I. M. Anderson

Keyword(s):

Panic Disorder ◽

Panic Attacks ◽

Acute Tryptophan Depletion ◽

Tryptophan Depletion ◽

Double Blind ◽

Normal Volunteers ◽

Plasma Tryptophan ◽

Drug Free ◽

Normal Controls

BackgroundUncertainties remain about the role of serotonin in the aetiology and treatment of panic disorder.AimsTo investigate the effect of reducing brain serotonin function on anxiety at rest, and following 5% CO2 provocation in normal controls and patients with panic disorder.MethodTwenty drug-free patients with DSM–III–R panic disorder and 19 controls received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind, balanced protocol. 5% CO2 was given as a panic challenge after 270 minutes.ResultsPlasma tryptophan fell by more than 80% both patients and controls after the tryptophan-free drink. Tryptophan depletion did not alter resting anxiety. In patients alone, tryptophan depletion caused a greater anxiogenic response and an increased rate of panic attacks (9 v. 2, P<0.05) after 5% CO2 challenge. No normal volunteers panicked.ConclusionsSerotonin may directly modulate panic anxiety in patients with panic disorder. This may underlie the efficacy of serotonergic antidepressants in treating panic disorder.

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Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers

Psychopharmacology ◽

10.1007/s00213-004-2141-y ◽

2004 ◽

Vol 178 (1) ◽

pp. 92-99 ◽

Cited By ~ 49

Author(s):

E. A. T. Evers ◽

D. E. Tillie ◽

F. M. van der Veen ◽

C. K. Lieben ◽

J. Jolles ◽

...

Keyword(s):

Healthy Volunteers ◽

Cognitive Performance ◽

Acute Tryptophan Depletion ◽

Tryptophan Depletion ◽

Plasma Tryptophan ◽

Novel Method

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Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers

Psychopharmacology ◽

10.1007/s00213-004-2043-z ◽

2004 ◽

Vol 177 (1-2) ◽

pp. 238-238

Author(s):

E. A. T. Evers ◽

D. E. Tillie ◽

F. M. van der Veen ◽

C. K. Lieben ◽

J. Jolles ◽

...

Keyword(s):

Healthy Volunteers ◽

Cognitive Performance ◽

Acute Tryptophan Depletion ◽

Tryptophan Depletion ◽

Plasma Tryptophan ◽

Novel Method

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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 ◽

10.1016/s0893-133x(02)00345-7 ◽

2002 ◽

Vol 27 (5) ◽

pp. 834-842 ◽

Cited By ~ 44

Author(s):

S Sobczak

Keyword(s):

Acute Tryptophan Depletion ◽

Tryptophan Depletion ◽

Type I ◽

Type Ii ◽

First Degree Relatives ◽

Bipolar Patients ◽

Cortisol Release

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Acute tryptophan depletion in bipolar disorders; literature review and directives for further research

Acta Neuropsychiatrica ◽

10.1017/s0924270800035432 ◽

2000 ◽

Vol 12 (3) ◽

pp. 69-72 ◽

Cited By ~ 6

Author(s):

S. Sobczak ◽

A. Honig ◽

W.J. Riedel

Keyword(s):

Bipolar Disorder ◽

Literature Review ◽

Affective Disorders ◽

Bipolar Disorders ◽

Acute Tryptophan Depletion ◽

Tryptophan Depletion ◽

Research Protocol ◽

Methodological Procedures ◽

Bipolar Patients ◽

Methodological Aspects

ABSTRACTSerotonin (5-HT) has been implicated in the pathophysiology of bipolar disorders. Acute tryptophan depletion (ATD), which decreases serotonergic turnover, is an established paradigm to study serotonergic vulnerability in affective disorders. Literature on the application of ATD as a research tool in bipolar patients is limited to three studies, which revealed inconsistent results on mood modification. These inconsistencies may be attributed to differences in methodological procedures and / or characteristics of included patients. Patient selection, methodological aspects and procedures of these studies are critically considered and recommendations given. A research protocol to test the 5-HT vulnerability in bipolar disorder is proposed.

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Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly

Psychological Medicine ◽

10.1017/s0033291702006906 ◽

2002 ◽

Vol 33 (1) ◽

pp. 41-49 ◽

Cited By ~ 46

Author(s):

R. J. PORTER ◽

B. S. LUNN ◽

J. T. O'BRIEN

Keyword(s):

Cognitive Function ◽

Rating Scales ◽

Senile Dementia ◽

Specific Effect ◽

Acute Tryptophan Depletion ◽

Elderly Subjects ◽

Tryptophan Depletion ◽

Emotional Symptoms ◽

Double Blind ◽

Healthy Elderly

Background. The cholinergic system is profoundly impaired in senile dementia of Alzheimer type (SDAT) and replacement therapy produces only modest clinical benefits. The serotonergic system is also impaired and may contribute both to cognitive and non-cognitive symptoms in SDAT. To investigate this further we assessed the effects of lowering brain serotonin using the technique of acute tryptophan depletion on cognitive function in patients with SDAT and in age matched control subjects.Method. Sixteen patients with probable SDAT and 17 healthy elderly subjects received two amino acid drinks in a within subject, double-blind, placebo-controlled, counterbalanced, crossover design. One of the drinks was nutritionally balanced and contained tryptophan (placebo), the other was identical but contained no tryptophan. A battery of detailed neuropsychological tests was performed between 4 and 6 h after the drink. Mood rating scales and other ratings of behavioural and emotional symptoms were also performed on both occasions.Results. Acute tryptophan depletion resulted in impairment on tasks of working memory in both groups. There was no group specific effect. Female SDAT subjects performed better on a task of pattern recognition during acute tryptophan depletion compared with placebo. There were no changes in behavioural symptoms during acute tryptophan depletion in either group.Conclusion. Compromised serotonergic function may be an important contributor to cognitive decline in SDAT and in ageing. Strategies targeting specific 5HT receptors may be helpful in SDAT.

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