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Effects of Rapid Tryptophan Depletion in Patients With Seasonal Affective Disorder in Remission After Light Therapy

Effects of Rapid Tryptophan Depletion in Patients With Seasonal Affective Disorder in Remission... Abstract Background: Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic, but not noradrenergic, antidepressant drugs in patients with remitted nonseasonal depression. The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder (SAD) that was in clinical remission after light therapy. Methods: Patients who met DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern (equivalent to SAD), were treated with a standard course of light therapy. Ten patients with SAD in clinical remission after light therapy underwent rapid tryptophan depletion in a placebo-controlled, double-blind crossover study. Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion. Results: Plasma total and free tryptophan levels were significantly reduced to 20% of normal levels by the rapid tryptophan depletion. The depletion session resulted in significant increases in depression scores compared with the sham control session. Six of 10 patients had a clinically significant relapse of their depression following the tryptophan depletion session. Conclusions: Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD. This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism. References 1. Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Davenport Y, Mueller PS, Newsome DA, Wehr TA. Seasonal affective disorder . Arch Gen Psychiatry . 1984;41:72-80.Crossref 2. Rosenthal NE, Sack DA, Carpenter CJ, Parry BL, Mendelson WB, Wehr TA. Antidepressant effects of light in seasonal affective disorder . Am J Psychiatry . 1985;142:163-170. 3. Terman M, Terman JS, Quitkin FM, McGrath PJ, Stewart JW, Rafferty B. Light therapy for seasonal affective disorder . Neuropsychopharmacology . 1989;2:1-22.Crossref 4. Wehr TA, Rosenthal NE. Seasonality and affective illness . Am J Psychiatry . 1989;146:829-839. 5. Blehar MC, Lewy AJ. Seasonal mood disorders: consensus and controversy . Psychopharmacol Bull . 1990;26:465-494. 6. Jacobsen FM, Murphy DL, Rosenthal NE. The role of serotonin in seasonal affective disorder and the antidepressant response to phototherapy . In: Rosenthal NE, Blehar MC, eds. Seasonal Affective Disorders and Phototherapy . New York, NY: Guilford Press; 1989:333-341. 7. Carlsson A, Svennerhom L, Winblad B. Seasonal and circadian monoamine variations in human brain examined post mortem . Acta Psychiatr Scand (Suppl) . 1980;280:75-83. 8. Brewerton TD, Berrettini WH, Nurnberger JI Jr, Linnoila M. Analysis of seasonal fluctuations of CSF monoamine metabolites and neuropeptides in normal controls . Psychiatry Res . 1988;23:257-265.Crossref 9. Lacoste V, Wirz-Justice A. Seasonal variation in normal subjects . In: Rosenthal NE, Blehar MC, eds. Seasonal Affective Disorders and Phototherapy . New York, NY: Guilford Press; 1989:167-229. 10. Asberg M, Bertlisson L, Rydin E. Monoamine metabolites in cerebrospinal fluid in relation to depressive illness, suicidal behaviour and personality . In: Angrist B, Burrows GD, Lader M, eds. Recent Advances in Neuropsychopharmacology: Selected Papers from the 12th Congress of the Collegium Internationale Neuro Psychopharmacologicum . Oxford, England: Pergamon Press; 1981:257-271. 11. Joseph-Vanderpool JR, Jacobsen FM, Murphy DL, Hill JL, Rosenthal NE. Seasonal variation in behavioral responses to m-CPP in patients with seasonal affective disorder and controls . Biol Psychiatry . 1993;33:496-504.Crossref 12. Garcia-Borreguero D, Jacobsen FM, Murphy DL, Joseph-Vanderpool JR, Chiara A, Rosenthal NE. Hormonal responses to the administration of m-chlorophenylpiperazine in patients with seasonal affective disorder and controls . Biol Psychiatry . 1995;37:740-749.Crossref 13. O'Rourke DA, Wurtman JJ, Brzezinski A, Nader TA, Chew B. Serotonin implicated in etiology of seasonal affective disorder . Psychopharmacol Bull . 1987;23:358-359. 14. O'Rourke D, Wurtman JJ, Wurtman RJ, Chebli R, Gleason R. Treatment of seasonal depression with D-fenfluramine . J Clin Psychiatry . 1989;50:343-347. 15. McGrath RE, Buckwald B, Resnick EV. The effect of L-tryptophan on seasonal affective disorder . J Clin Psychiatry . 1990;51:162-163. 16. Lam RW, Gorman CP, Michalon M, Steiner M, Levitt AJ, Corral MR, Watson GD, Morehouse RL, Tam W, Joff RT. A multi-center, placebo-controlled study of fluoxetine in seasonal affective disorder . Am J Psychiatry . In press. 17. Ruhrmann S, Kasper S, Hawellek B, Martinez B, Hoflich G, Nickelsen T, Moller H-J. Fluoxetine vs light therapy in the treatment of SAD . Biol Psychiatry . 1993;33:83A. 18. Fernstrom JD. Effects of the diet on brain neurotransmitters . Metabolism . 1977;26:207-223.Crossref 19. Curzon G. Relationships between plasma, CSF and brain tryptophan . J Neural Transm . 1979;15:93-105. 20. Young SN, Ervin FR, Pihl RO, Finn P. Biochemical aspects of tryptophan depletion in primates . Psychopharmacology . 1989;98:508-511.Crossref 21. Harper AE, Benevenga NJ, Wohlhueter RM. Effects of ingestion of disproportionate amounts of amino acids . Physiol Rev . 1970;50:428-548. 22. Young SN, Smith SE, Pihl R, Ervin FR. Tryptophan depletion causes a rapid lowering of mood in normal males . Psychopharmacology . 1985;87:173-177.Crossref 23. Moja EA, Cipolla P, Castoda D, Tofanetti O. Dose-responsive decrease in plasma tryptophan and in brain tryptophan and serotonin after tryptophan-free amino acid mixtures in rats . Life Sci . 1989;44:971-976.Crossref 24. Delgado PL, Charney DS, Price LH, Landis H, Heninger GR. Neuroendocrine and behavioral effects of dietary tryptophan restriction in healthy subjects . Life Sci . 1989;45:2323-2332.Crossref 25. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR. Serotonin function and the mechanism of antidepressant action . Arch Gen Psychiatry . 1990;47:411-418.Crossref 26. Delgado PL, Price LH, Miller HL, Licinio J, Krystal JH, Heninger GR, Charney DS. Rapid serotonin depletion as a provocative challenge test for patients with major depression . Psychopharmacol Bull . 1991;27:321-330. 27. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Revised Third Edition . Washington, DC: American Psychiatric Association; 1987. 28. Williams JBW, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID), I: history, rationale, and description . Arch Gen Psychiatry . 1992;49:624-629.Crossref 29. Williams JBW, Link MJ, Rosenthal NE, Terman M. Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders Version (SIGH-SAD) . New York, NY: New York Psychiatric Institute; 1988. 30. Hamilton M. Development of a rating scale for primary depressive illness . Br J Soc Clin Psychol . 1967;6:278-296.Crossref 31. Anderson GM, Young JG, Cohen DJ, Schlicht KR, Patel N. Liquid-chromatographic determination of serotonin and tryptophan in whole blood and plasma . Clin Chem . 1981;27:775-776. 32. SPSS Inc. SPSS for Windows, v.6.01. Chicago, Ill: SPSS Inc; 1994. 33. Jacobsen FM, Mueller EA, Rosenthal NE, Rogers S, Hill JL, Murphy DL. Behavioral responses to intravenous meta-chlorophenylpiperazine in patients with seasonal affective disorder and control subjects before and after phototherapy . Psychiatry Res . 1994;52:181-197.Crossref 34. Mason R. The effect of light on neuronal sensitivity to noradrenaline and serotonin (5-HT) . In: Thompson C, Silverstone T, eds. Seasonal Affective Disorder . London, England: CNS (Clinical Neuroscience); 1989:243-258. 35. Lewy AJ, Sack RL, Singer CM, White DM. The phase shift hypothesis for bright light's therapeutic mechanism of action: theoretical considerations and experimental evidence . Psychopharmacol Bull . 1987;23:349-353. 36. Sack RL, Lewy AJ, White DM, Singer CM, Fireman MJ, Vandiver R. Morning vs evening light treatment for winter depression.1992;49:650] . Arch Gen Psychiatry . 1990;47:343-351.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Effects of Rapid Tryptophan Depletion in Patients With Seasonal Affective Disorder in Remission After Light Therapy

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Publisher
American Medical Association
Copyright
Copyright © 1996 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1996.01830010043007
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Abstract

Abstract Background: Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic, but not noradrenergic, antidepressant drugs in patients with remitted nonseasonal depression. The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder (SAD) that was in clinical remission after light therapy. Methods: Patients who met DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern (equivalent to SAD), were treated with a standard course of light therapy. Ten patients with SAD in clinical remission after light therapy underwent rapid tryptophan depletion in a placebo-controlled, double-blind crossover study. Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion. Results: Plasma total and free tryptophan levels were significantly reduced to 20% of normal levels by the rapid tryptophan depletion. The depletion session resulted in significant increases in depression scores compared with the sham control session. Six of 10 patients had a clinically significant relapse of their depression following the tryptophan depletion session. Conclusions: Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD. This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism. References 1. Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Davenport Y, Mueller PS, Newsome DA, Wehr TA. Seasonal affective disorder . Arch Gen Psychiatry . 1984;41:72-80.Crossref 2. Rosenthal NE, Sack DA, Carpenter CJ, Parry BL, Mendelson WB, Wehr TA. Antidepressant effects of light in seasonal affective disorder . Am J Psychiatry . 1985;142:163-170. 3. Terman M, Terman JS, Quitkin FM, McGrath PJ, Stewart JW, Rafferty B. Light therapy for seasonal affective disorder . Neuropsychopharmacology . 1989;2:1-22.Crossref 4. Wehr TA, Rosenthal NE. Seasonality and affective illness . Am J Psychiatry . 1989;146:829-839. 5. Blehar MC, Lewy AJ. Seasonal mood disorders: consensus and controversy . Psychopharmacol Bull . 1990;26:465-494. 6. Jacobsen FM, Murphy DL, Rosenthal NE. The role of serotonin in seasonal affective disorder and the antidepressant response to phototherapy . In: Rosenthal NE, Blehar MC, eds. Seasonal Affective Disorders and Phototherapy . New York, NY: Guilford Press; 1989:333-341. 7. Carlsson A, Svennerhom L, Winblad B. Seasonal and circadian monoamine variations in human brain examined post mortem . Acta Psychiatr Scand (Suppl) . 1980;280:75-83. 8. Brewerton TD, Berrettini WH, Nurnberger JI Jr, Linnoila M. Analysis of seasonal fluctuations of CSF monoamine metabolites and neuropeptides in normal controls . Psychiatry Res . 1988;23:257-265.Crossref 9. Lacoste V, Wirz-Justice A. Seasonal variation in normal subjects . In: Rosenthal NE, Blehar MC, eds. Seasonal Affective Disorders and Phototherapy . New York, NY: Guilford Press; 1989:167-229. 10. Asberg M, Bertlisson L, Rydin E. Monoamine metabolites in cerebrospinal fluid in relation to depressive illness, suicidal behaviour and personality . In: Angrist B, Burrows GD, Lader M, eds. Recent Advances in Neuropsychopharmacology: Selected Papers from the 12th Congress of the Collegium Internationale Neuro Psychopharmacologicum . Oxford, England: Pergamon Press; 1981:257-271. 11. Joseph-Vanderpool JR, Jacobsen FM, Murphy DL, Hill JL, Rosenthal NE. Seasonal variation in behavioral responses to m-CPP in patients with seasonal affective disorder and controls . Biol Psychiatry . 1993;33:496-504.Crossref 12. Garcia-Borreguero D, Jacobsen FM, Murphy DL, Joseph-Vanderpool JR, Chiara A, Rosenthal NE. Hormonal responses to the administration of m-chlorophenylpiperazine in patients with seasonal affective disorder and controls . Biol Psychiatry . 1995;37:740-749.Crossref 13. O'Rourke DA, Wurtman JJ, Brzezinski A, Nader TA, Chew B. Serotonin implicated in etiology of seasonal affective disorder . Psychopharmacol Bull . 1987;23:358-359. 14. O'Rourke D, Wurtman JJ, Wurtman RJ, Chebli R, Gleason R. Treatment of seasonal depression with D-fenfluramine . J Clin Psychiatry . 1989;50:343-347. 15. McGrath RE, Buckwald B, Resnick EV. The effect of L-tryptophan on seasonal affective disorder . J Clin Psychiatry . 1990;51:162-163. 16. Lam RW, Gorman CP, Michalon M, Steiner M, Levitt AJ, Corral MR, Watson GD, Morehouse RL, Tam W, Joff RT. A multi-center, placebo-controlled study of fluoxetine in seasonal affective disorder . Am J Psychiatry . In press. 17. Ruhrmann S, Kasper S, Hawellek B, Martinez B, Hoflich G, Nickelsen T, Moller H-J. Fluoxetine vs light therapy in the treatment of SAD . Biol Psychiatry . 1993;33:83A. 18. Fernstrom JD. Effects of the diet on brain neurotransmitters . Metabolism . 1977;26:207-223.Crossref 19. Curzon G. Relationships between plasma, CSF and brain tryptophan . J Neural Transm . 1979;15:93-105. 20. Young SN, Ervin FR, Pihl RO, Finn P. Biochemical aspects of tryptophan depletion in primates . Psychopharmacology . 1989;98:508-511.Crossref 21. Harper AE, Benevenga NJ, Wohlhueter RM. Effects of ingestion of disproportionate amounts of amino acids . Physiol Rev . 1970;50:428-548. 22. Young SN, Smith SE, Pihl R, Ervin FR. Tryptophan depletion causes a rapid lowering of mood in normal males . Psychopharmacology . 1985;87:173-177.Crossref 23. Moja EA, Cipolla P, Castoda D, Tofanetti O. Dose-responsive decrease in plasma tryptophan and in brain tryptophan and serotonin after tryptophan-free amino acid mixtures in rats . Life Sci . 1989;44:971-976.Crossref 24. Delgado PL, Charney DS, Price LH, Landis H, Heninger GR. Neuroendocrine and behavioral effects of dietary tryptophan restriction in healthy subjects . Life Sci . 1989;45:2323-2332.Crossref 25. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR. Serotonin function and the mechanism of antidepressant action . Arch Gen Psychiatry . 1990;47:411-418.Crossref 26. Delgado PL, Price LH, Miller HL, Licinio J, Krystal JH, Heninger GR, Charney DS. Rapid serotonin depletion as a provocative challenge test for patients with major depression . Psychopharmacol Bull . 1991;27:321-330. 27. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Revised Third Edition . Washington, DC: American Psychiatric Association; 1987. 28. Williams JBW, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID), I: history, rationale, and description . Arch Gen Psychiatry . 1992;49:624-629.Crossref 29. Williams JBW, Link MJ, Rosenthal NE, Terman M. Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders Version (SIGH-SAD) . New York, NY: New York Psychiatric Institute; 1988. 30. Hamilton M. Development of a rating scale for primary depressive illness . Br J Soc Clin Psychol . 1967;6:278-296.Crossref 31. Anderson GM, Young JG, Cohen DJ, Schlicht KR, Patel N. Liquid-chromatographic determination of serotonin and tryptophan in whole blood and plasma . Clin Chem . 1981;27:775-776. 32. SPSS Inc. SPSS for Windows, v.6.01. Chicago, Ill: SPSS Inc; 1994. 33. Jacobsen FM, Mueller EA, Rosenthal NE, Rogers S, Hill JL, Murphy DL. Behavioral responses to intravenous meta-chlorophenylpiperazine in patients with seasonal affective disorder and control subjects before and after phototherapy . Psychiatry Res . 1994;52:181-197.Crossref 34. Mason R. The effect of light on neuronal sensitivity to noradrenaline and serotonin (5-HT) . In: Thompson C, Silverstone T, eds. Seasonal Affective Disorder . London, England: CNS (Clinical Neuroscience); 1989:243-258. 35. Lewy AJ, Sack RL, Singer CM, White DM. The phase shift hypothesis for bright light's therapeutic mechanism of action: theoretical considerations and experimental evidence . Psychopharmacol Bull . 1987;23:349-353. 36. Sack RL, Lewy AJ, White DM, Singer CM, Fireman MJ, Vandiver R. Morning vs evening light treatment for winter depression.1992;49:650] . Arch Gen Psychiatry . 1990;47:343-351.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Jan 1, 1996

References