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Effects of rapid tryptophan depletion on mood and urge to drink in patients with co-morbid major depression and alcohol dependence

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Abstract

Rationale

Rapid tryptophan depletion (RTD) has been used to study central serotonin function and may therefore be useful in understanding co-morbid alcohol dependence (AD) and major depressive disorder (MDD).

Objectives

To examine (1) the effect of RTD on mood and urge to drink among patients with AD and MDD and (2) the association of RTD effects with alleles of a functional polymorphism in the gene encoding the serotonin transporter protein.

Methods

Double-blind, placebo-controlled study, in which 14 treatment responders recruited from one of two placebo-controlled trials of serotonergic antidepressants were enrolled. Patients underwent two day-long sessions, which were either a tryptophan depletion session or a sham session. During each session, mood and urge for alcohol were measured at regular intervals.

Results

Five hours after RTD, plasma TRP concentrations decreased by 73.1%. There was a significant effect of session on both mood and the urge to drink. Genotype moderated the effect of session on mood, such that, during RTD, individuals homozygous for the long allele reported greater depression than did subjects with one or two copies of the S allele.

Conclusions

This study provides support for the role of serotonergic neurotransmission in modulating mood and alcohol urges, and underscores the utility of these effects as a phenotype for genetic analysis. These findings may also help to identify alcoholics who are at greatest risk for MDD.

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Acknowledgements

This study was supported by NIH grants AA13736, AA07290, AA03510 and RR06192 and by grants from Pfizer, Inc. and Bristol-Myers Squibb Co. Plasma tryptophan concentrations were measured in the laboratory of George Anderson, M.D., at the Yale Child Study Center in New Haven, CT, and in the Department of Psychiatry at Rhode Island Hospital, Providence, RI.

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Authors and Affiliations

  1. Department of Psychiatry, Alcohol Research Center, MC2103, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA

    Amira Pierucci-Lagha, Richard Feinn, Vania Modesto-Lowe, Maggie Nellissery, Jonathan Covault & Henry R. Kranzler

  2. Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA

    Robert Swift

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  1. Amira Pierucci-Lagha
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  2. Richard Feinn
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  3. Vania Modesto-Lowe
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  4. Robert Swift
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  5. Maggie Nellissery
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  6. Jonathan Covault
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  7. Henry R. Kranzler
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Correspondence to Henry R. Kranzler.

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Pierucci-Lagha, A., Feinn, R., Modesto-Lowe, V. et al. Effects of rapid tryptophan depletion on mood and urge to drink in patients with co-morbid major depression and alcohol dependence. Psychopharmacology 171, 340–348 (2004). https://doi.org/10.1007/s00213-003-1588-6

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  • DOI: https://doi.org/10.1007/s00213-003-1588-6

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