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Serotonin and the Neurobiology of Depression: Effects of Tryptophan Depletion in Drug-Free Depressed Patients

Serotonin and the Neurobiology of Depression: Effects of Tryptophan Depletion in Drug-Free... Abstract Objective: To investigate the effects of tryptophan depletion in untreated depressed patients. Rapid dietary depletion of the precursor of serotonin synthesis, tryptophan, causes a transient return of depression in 67% of patients who have had a therapeutic antidepressant response. Method: Forty-three untreated depressed patients underwent tryptophan depletion in a double-blind, placebocontrolled cross-over study. After testing, they received open sequential antidepressant treatment. Results: Mood did not change when tryptophan was depleted but did change on the day after the depletion test. Relative to the control test, 37% of the patients had 10-point or greater decrease in Hamilton Depression Rating Scale (Ham-D) score, while 23% had a 10-point or greater increase in Ham-D score on the day after the tryptophan depletion test. Change in mood was correlated to treatment response after testing. Patients whose condition worsened proved to be highly refractory to treatment while those who showed improvment were more likely to respond. Conclusions: That tryptophan depletion did not rapidly worsen depression argues that serotonin function is not linearly related to the level of depression and if reduced serotonin function does cause depression, then it is either as predisposing factor or due to a postsynaptic deficit in the utilization of serotonin. References 1. Heninger GR, Charney DS. Mechanism of action of antidepressant treatments: implications for the etiology and treatment of depressive disorders . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987:535-544. 2. Meltzer HY, Lowy MT. The serotonin hypothesis of depression . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987:513-526. 3. Coppen A. The biochemistry of affective disorders . Br J Psychiatry . 1967;113:1237-1264.Crossref 4. Lapin IP, Oxenkrug GF. Intensification of the central serotonergic processes as a possible determinant of the thymoleptic effect . Lancet . 1969;1:132-136.Crossref 5. Murphy DL, Cambell I, Costa JL. Current status of the indoleamine hypothesis of the affective disorders . In: Lipton MA, DiMascio A, Killam KF, eds. Psychopharmacology: A Generation of Progress . New York, NY: Raven Press; 1978:1235-1247. 6. Charney DS, Menekes DB, Heninger GR. Receptor sensitivity and the mechanism of action of antidepressant treatment . Arch Gen Psychiatry . 1981;38:1160-1180.Crossref 7. Delgado PL, Charney DS. Neuroendocrine challenge studies in affective disorders . In: Horton RW, Katona C, eds. Biological Aspects of Affective Disorders . Orlando, Fla: Academic Press Inc; 1991:146-190. 8. Delgado PL, Charney DS. Neurochemistry of affective disorders . In: Paykel ES, ed. Handbook of Affective Disorders . 2nd ed. New York, NY: Churchill Livingstone Inc; 1992:219-253. 9. Coppen A, Eccleston EG, Peet M. Total and free tryptophan concentration in the plasma of depressed patients . Lancet . 1973;2:60-63.Crossref 10. Cowen PJ, Parry-Billings M, Newsholme EA. Decreased plasma tryptophan levels in major depression . J Affect Disord . 1989;16:27-31.Crossref 11. Åsberg M, Schalling D, Traskman-Bendz L, Wagner A. Psychobiology of suicide, impulsivity, and related phenomena . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987:655-668. 12. Roy A, Virkkunen M, Linnoila M. Serotonin in suicide, violence, and alcoholism . In: Coccaro EF, Murphy DL, eds. Serotonin in Major Psychiatric Disorders . Washington, DC: American Psychiatric Press; 1990:187-208. 13. Pare CMB, Trenchard A, Turner P. 5-Hydroxytryptamine in depression . Adv Biochem Psychopharmacol . 1974;11:275-279. 14. Healy D, Leonard BE. Monoamine transport in depression: kinetics and dynamics . J Affect Disord . 1987;12:91-103.Crossref 15. Stanley M, Mann JJ. Increased serotonin-2 binding sites in frontal cortex of suicide victims . Lancet . 1983;1:214-216.Crossref 16. Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN. 5-HT-2 receptor changes in major depression . Biol Psychiatry . 1990;27:489-496.Crossref 17. Arora RC, Meltzer HY. Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects . Am J Psychiatry . 1989;146:730-736. 18. Arango V, Ernsberger P, Marzuk PM, et al. Autoradiographic demonstration of increased serotonin 5-HT2 and β-adrenergic receptor binding sites in the brain of suicide victims . Arch Gen Psychiatry . 1990;47:1038-1047.Crossref 19. Heninger GR, Charney DS, Sternberg DE. Serotonergic function in depression: prolactin response to intravenous tryptophan in depressed patients and healthy subjects . Arch Gen Psychiatry . 1984;41:398-402.Crossref 20. Cowen PJ, Charig EM. Neuroendocrine responses to tryptophan in major depression . Arch Gen Psychiatry . 1987;44:958-966.Crossref 21. Deakin JFW, Pennell I, Upadhyaya AJ, Lofthouse R. A neuroendocrine study of 5HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation . Psychopharmacology . 1990;101:85-92.Crossref 22. Price LH, Charney DS, Delgado PL, Heninger GR. Serotonin function and depression: neuroendocrine and mood responses to intravenous L-tryptophan in DSM-III-R depressive subtypes and healthy controls . Am J Psychiatry . 1991;148:1518-1525. 23. Siever LJ, Murphy DL, Slater S, de la Vega E, Lipper S. Plasma prolactin changes following fenfluramine in depressed patients compared to controls: an evaluation of central serotonergic responsivity in depression . Life Sci . 1984;34:1029-1039.Crossref 24. Mitchell P, Smythe G. Hormonal responses to fenfluramine in depressed and control subjects . J Affect Disord . 1990;19:43-51.Crossref 25. Golden RN, Hsiao JK, Lane E, et al. Abnormal neuroendocrine responsivity to acute IV clomipramine challenge in depressed patients . Psychiatry Res . 1990;31:39-47.Crossref 26. Lesch KP, Mayer S, Disselkamp-Tietze J, Hoh A, Schoelnhammer G, Schulte HM. Subsensitivity of the 5-hydroxytryptamine 1A (5-HT1A) receptor medicated hypothermic response to ipsapirone in unipolar depression . Life Sci . 1990;46:1271-1277.Crossref 27. Lesch KP, Disselkamp-Tietze J, Schmidtke A. 5-HT1a receptor function in depression: effect of chronic amitriptyline treatment . J Neural Transm . 1990;80:157-161.Crossref 28. Fernstrom JD. Effects of the diet on brain neurotransmitters . Metabolism . 1977;26:207-223.Crossref 29. Curzon G. Relationships between plasma, CSF and brain tryptophan . J Neural Transm . 1979;15( (suppl) ):93-105. 30. Curzon G. Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity . In: Haber B, Gabay S, eds. Serotonin: Current Aspects of Neurochemistry and Function . New York, NY: Plenum Press; 1981:207-219. 31. Young SN, Ervin FR, Pihl RO, Finn P. Biochemical aspects of tryptophan depletion in primates . Psychopharmacology . 1989;98:508-511.Crossref 32. Moja EA, Cipollo P, Castoldi D, Tofanetti O. 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.Crossref 33. Rose WC, Haines WJ, Warner DT. The amino acid requirements of man . J Biol Chem . 1954;206:421-430. 34. Young VR, Hussein MA, Murray E, Scrimshaw NS. Tryptophan intake, spacing of meals, and diurnal fluctuations of plasma tryptophan in men . Am J Clin Nutr . 1969;22:1563-1567. 35. Young VR, Hussein MA, Murray E, Scrimshaw NS. Plasma tryptophan response curve and its relation to tryptophan requirements in young adult men . J Nutr . 1971;101:45-60. 36. 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 37. 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 38. Smith SE, Pihl RO, Young SW, Ervin FR. A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males . Psychopharmacology . 1987;91:451-457.Crossref 39. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR. Serotonin function and the mechanism of antidepressant action: reversal of antidepressant induced remission by rapid depletion of plasma tryptophan . Arch Gen Psychiatry . 1990;47:411-418.Crossref 40. Delgado PL, Price LH, Miller HL, Salomon RM, Licinio J, Krystal JH, Heninger GR, Charney DS. Rapid serotonin depletion as a provocative challenge test for patients with major depression: relevance to antidepressant action and the neurobiology of depression . Psychopharmacol Bull . 1991;27:321-330. 41. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition . Washington, DC: American Psychiatric Association; 1987. 42. Mazure CM, Nelson JC, Price LH. Reliability and validity of the symptoms of major depressive illness . Arch Gen Psychiatry . 1986;43:451-456.Crossref 43. Task Force on the Use of Laboratory Tests in Psychiatry. Tricyclic antidepressants: blood level measurements and clinical outcome: an APA Task Force report . Am J Psychiatry . 1985;142:155-162. 44. Delgado PL, Price LH, Charney DS, Heninger GR. Efficacy of fluvoxamine in treatment-refractory depression . J Affect Disord . 1988;15:55-60.Crossref 45. Hamilton M. The assessment of anxiety states by rating . Br J Med Psychol . 1959;32:51-53.Crossref 46. Woods SW, Charney DS, Goodman WK, Heninger GR. Carbon dioxideinduced anxiety . Arch Gen Psychiatry . 1988;45:43-52.Crossref 47. Anderson GM, Young JG, Cohen DJ, Schlicht KR, Patel N. Liquidchromatographic determination of serotonin and tryptophan in whole blood and plasma . Clin Chem . 1981;27:775-776. 48. Conover WJ. Practical Nonparametric Statistics . 2nd ed. New York, NY: John Wiley & Sons Inc; 1980. 49. SAS User's Guide: Statistics, 1982 Edition. Cary, NC: SAS Institute Inc; 1982. 50. Dixon WJ, Brown MB, Engelman L, Frane JW, Hill MA, Jennvick RI, Toporek JD. BMDP Statistical Software . Berkley, Calif: University of California Press; 1983. 51. Brain Power, Inc. Statview 521+. 1986. 24009 Ventura Blvd, Calabasas, CA 91302. 52. Super ANOVA User's Guide. 1989. Abacus Concepts, Inc, 1984 Bonita Ave, Berkley, CA 94704. 53. Cricket Software. Cricket Graph Users Guide. 1986. 40 Valley Stream Parkway, Malvern, PA 19355. 54. Lytle LD, Messing RB, Fisher L, Phebus L. Effects of long-term corn consumption on brain serotonin and the response to electric shock . Science . 1975;190:692-694.Crossref 55. Messing RB, Fisher LA, Phebus L, Lytle LD. Interaction of diet and drugs in the regulation of brain 5-hydroxyindoles and the response to painful electric shock . Life Sci . 1976;18:707-714.Crossref 56. Walters JK, Davis M, Sheard MH. Tryptophan-free diet: effects on the acoustic startle reflex in rats . Psychopharmacology . 1979;62:103-109.Crossref 57. Gibbons JL, Barr GA, Bridger WH, Leibowitz SF. Manipulations of dietary tryptophan: effects on mouse killing and brain serotonin in the rat . Brain Res . 1979;169:139-153.Crossref 58. Vergnes M, Kempf E. Tryptophan deprivation: effects on mouse-killing and reactivity in the rat . Psychopharmacol Aggression Soc Behav . 1981;14:19-23. 59. Moja EA, Mendelson WB, Stoff DM, Gillin JC, Wyatt RJ. Reduction of REM sleep by a tryptophan-free amino acid diet . Life Sci . 1979;24:1467-1470.Crossref 60. Clemens JA, Bennett DR, Fuller RW. The effect of a tryptophan-free diet on prolactin and corticosterone release by serotonergic stimuli . Horm Metab Res . 1980;12:35-38.Crossref 61. Badawy AA-B. Minireview: the functions and regulation of tryptophan pyrrolase . Life Sci . 1977;21:755-768.Crossref 62. Badawy AA-B, Evans M. Inhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by acute administration of small doses of antidepressants . Br J Pharmacol . 1982;77:59-67.Crossref 63. Blier P, de Montigny, Chaput Y. A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence . J Clin Psychiatry . 1990;51( (suppl) ):14-20. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Serotonin and the Neurobiology of Depression: Effects of Tryptophan Depletion in Drug-Free Depressed Patients

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Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1994.03950110025005
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Abstract

Abstract Objective: To investigate the effects of tryptophan depletion in untreated depressed patients. Rapid dietary depletion of the precursor of serotonin synthesis, tryptophan, causes a transient return of depression in 67% of patients who have had a therapeutic antidepressant response. Method: Forty-three untreated depressed patients underwent tryptophan depletion in a double-blind, placebocontrolled cross-over study. After testing, they received open sequential antidepressant treatment. Results: Mood did not change when tryptophan was depleted but did change on the day after the depletion test. Relative to the control test, 37% of the patients had 10-point or greater decrease in Hamilton Depression Rating Scale (Ham-D) score, while 23% had a 10-point or greater increase in Ham-D score on the day after the tryptophan depletion test. Change in mood was correlated to treatment response after testing. Patients whose condition worsened proved to be highly refractory to treatment while those who showed improvment were more likely to respond. Conclusions: That tryptophan depletion did not rapidly worsen depression argues that serotonin function is not linearly related to the level of depression and if reduced serotonin function does cause depression, then it is either as predisposing factor or due to a postsynaptic deficit in the utilization of serotonin. References 1. Heninger GR, Charney DS. Mechanism of action of antidepressant treatments: implications for the etiology and treatment of depressive disorders . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987:535-544. 2. Meltzer HY, Lowy MT. The serotonin hypothesis of depression . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987:513-526. 3. Coppen A. The biochemistry of affective disorders . Br J Psychiatry . 1967;113:1237-1264.Crossref 4. Lapin IP, Oxenkrug GF. Intensification of the central serotonergic processes as a possible determinant of the thymoleptic effect . Lancet . 1969;1:132-136.Crossref 5. Murphy DL, Cambell I, Costa JL. Current status of the indoleamine hypothesis of the affective disorders . In: Lipton MA, DiMascio A, Killam KF, eds. Psychopharmacology: A Generation of Progress . New York, NY: Raven Press; 1978:1235-1247. 6. Charney DS, Menekes DB, Heninger GR. Receptor sensitivity and the mechanism of action of antidepressant treatment . Arch Gen Psychiatry . 1981;38:1160-1180.Crossref 7. Delgado PL, Charney DS. Neuroendocrine challenge studies in affective disorders . In: Horton RW, Katona C, eds. Biological Aspects of Affective Disorders . Orlando, Fla: Academic Press Inc; 1991:146-190. 8. Delgado PL, Charney DS. Neurochemistry of affective disorders . In: Paykel ES, ed. Handbook of Affective Disorders . 2nd ed. New York, NY: Churchill Livingstone Inc; 1992:219-253. 9. Coppen A, Eccleston EG, Peet M. Total and free tryptophan concentration in the plasma of depressed patients . Lancet . 1973;2:60-63.Crossref 10. Cowen PJ, Parry-Billings M, Newsholme EA. Decreased plasma tryptophan levels in major depression . J Affect Disord . 1989;16:27-31.Crossref 11. Åsberg M, Schalling D, Traskman-Bendz L, Wagner A. Psychobiology of suicide, impulsivity, and related phenomena . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987:655-668. 12. Roy A, Virkkunen M, Linnoila M. Serotonin in suicide, violence, and alcoholism . In: Coccaro EF, Murphy DL, eds. Serotonin in Major Psychiatric Disorders . Washington, DC: American Psychiatric Press; 1990:187-208. 13. Pare CMB, Trenchard A, Turner P. 5-Hydroxytryptamine in depression . Adv Biochem Psychopharmacol . 1974;11:275-279. 14. Healy D, Leonard BE. Monoamine transport in depression: kinetics and dynamics . J Affect Disord . 1987;12:91-103.Crossref 15. Stanley M, Mann JJ. Increased serotonin-2 binding sites in frontal cortex of suicide victims . Lancet . 1983;1:214-216.Crossref 16. Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN. 5-HT-2 receptor changes in major depression . Biol Psychiatry . 1990;27:489-496.Crossref 17. Arora RC, Meltzer HY. Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects . Am J Psychiatry . 1989;146:730-736. 18. Arango V, Ernsberger P, Marzuk PM, et al. Autoradiographic demonstration of increased serotonin 5-HT2 and β-adrenergic receptor binding sites in the brain of suicide victims . Arch Gen Psychiatry . 1990;47:1038-1047.Crossref 19. Heninger GR, Charney DS, Sternberg DE. Serotonergic function in depression: prolactin response to intravenous tryptophan in depressed patients and healthy subjects . Arch Gen Psychiatry . 1984;41:398-402.Crossref 20. Cowen PJ, Charig EM. Neuroendocrine responses to tryptophan in major depression . Arch Gen Psychiatry . 1987;44:958-966.Crossref 21. Deakin JFW, Pennell I, Upadhyaya AJ, Lofthouse R. A neuroendocrine study of 5HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation . Psychopharmacology . 1990;101:85-92.Crossref 22. Price LH, Charney DS, Delgado PL, Heninger GR. Serotonin function and depression: neuroendocrine and mood responses to intravenous L-tryptophan in DSM-III-R depressive subtypes and healthy controls . Am J Psychiatry . 1991;148:1518-1525. 23. Siever LJ, Murphy DL, Slater S, de la Vega E, Lipper S. Plasma prolactin changes following fenfluramine in depressed patients compared to controls: an evaluation of central serotonergic responsivity in depression . Life Sci . 1984;34:1029-1039.Crossref 24. Mitchell P, Smythe G. Hormonal responses to fenfluramine in depressed and control subjects . J Affect Disord . 1990;19:43-51.Crossref 25. Golden RN, Hsiao JK, Lane E, et al. Abnormal neuroendocrine responsivity to acute IV clomipramine challenge in depressed patients . Psychiatry Res . 1990;31:39-47.Crossref 26. Lesch KP, Mayer S, Disselkamp-Tietze J, Hoh A, Schoelnhammer G, Schulte HM. Subsensitivity of the 5-hydroxytryptamine 1A (5-HT1A) receptor medicated hypothermic response to ipsapirone in unipolar depression . Life Sci . 1990;46:1271-1277.Crossref 27. Lesch KP, Disselkamp-Tietze J, Schmidtke A. 5-HT1a receptor function in depression: effect of chronic amitriptyline treatment . J Neural Transm . 1990;80:157-161.Crossref 28. Fernstrom JD. Effects of the diet on brain neurotransmitters . Metabolism . 1977;26:207-223.Crossref 29. Curzon G. Relationships between plasma, CSF and brain tryptophan . J Neural Transm . 1979;15( (suppl) ):93-105. 30. Curzon G. Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity . In: Haber B, Gabay S, eds. Serotonin: Current Aspects of Neurochemistry and Function . New York, NY: Plenum Press; 1981:207-219. 31. Young SN, Ervin FR, Pihl RO, Finn P. Biochemical aspects of tryptophan depletion in primates . Psychopharmacology . 1989;98:508-511.Crossref 32. Moja EA, Cipollo P, Castoldi D, Tofanetti O. 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.Crossref 33. Rose WC, Haines WJ, Warner DT. The amino acid requirements of man . J Biol Chem . 1954;206:421-430. 34. Young VR, Hussein MA, Murray E, Scrimshaw NS. Tryptophan intake, spacing of meals, and diurnal fluctuations of plasma tryptophan in men . Am J Clin Nutr . 1969;22:1563-1567. 35. Young VR, Hussein MA, Murray E, Scrimshaw NS. Plasma tryptophan response curve and its relation to tryptophan requirements in young adult men . J Nutr . 1971;101:45-60. 36. 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 37. 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 38. Smith SE, Pihl RO, Young SW, Ervin FR. A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males . Psychopharmacology . 1987;91:451-457.Crossref 39. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR. Serotonin function and the mechanism of antidepressant action: reversal of antidepressant induced remission by rapid depletion of plasma tryptophan . Arch Gen Psychiatry . 1990;47:411-418.Crossref 40. Delgado PL, Price LH, Miller HL, Salomon RM, Licinio J, Krystal JH, Heninger GR, Charney DS. Rapid serotonin depletion as a provocative challenge test for patients with major depression: relevance to antidepressant action and the neurobiology of depression . Psychopharmacol Bull . 1991;27:321-330. 41. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition . Washington, DC: American Psychiatric Association; 1987. 42. Mazure CM, Nelson JC, Price LH. Reliability and validity of the symptoms of major depressive illness . Arch Gen Psychiatry . 1986;43:451-456.Crossref 43. Task Force on the Use of Laboratory Tests in Psychiatry. Tricyclic antidepressants: blood level measurements and clinical outcome: an APA Task Force report . Am J Psychiatry . 1985;142:155-162. 44. Delgado PL, Price LH, Charney DS, Heninger GR. Efficacy of fluvoxamine in treatment-refractory depression . J Affect Disord . 1988;15:55-60.Crossref 45. Hamilton M. The assessment of anxiety states by rating . Br J Med Psychol . 1959;32:51-53.Crossref 46. Woods SW, Charney DS, Goodman WK, Heninger GR. Carbon dioxideinduced anxiety . Arch Gen Psychiatry . 1988;45:43-52.Crossref 47. Anderson GM, Young JG, Cohen DJ, Schlicht KR, Patel N. Liquidchromatographic determination of serotonin and tryptophan in whole blood and plasma . Clin Chem . 1981;27:775-776. 48. Conover WJ. Practical Nonparametric Statistics . 2nd ed. New York, NY: John Wiley & Sons Inc; 1980. 49. SAS User's Guide: Statistics, 1982 Edition. Cary, NC: SAS Institute Inc; 1982. 50. Dixon WJ, Brown MB, Engelman L, Frane JW, Hill MA, Jennvick RI, Toporek JD. BMDP Statistical Software . Berkley, Calif: University of California Press; 1983. 51. Brain Power, Inc. Statview 521+. 1986. 24009 Ventura Blvd, Calabasas, CA 91302. 52. Super ANOVA User's Guide. 1989. Abacus Concepts, Inc, 1984 Bonita Ave, Berkley, CA 94704. 53. Cricket Software. Cricket Graph Users Guide. 1986. 40 Valley Stream Parkway, Malvern, PA 19355. 54. Lytle LD, Messing RB, Fisher L, Phebus L. Effects of long-term corn consumption on brain serotonin and the response to electric shock . Science . 1975;190:692-694.Crossref 55. Messing RB, Fisher LA, Phebus L, Lytle LD. Interaction of diet and drugs in the regulation of brain 5-hydroxyindoles and the response to painful electric shock . Life Sci . 1976;18:707-714.Crossref 56. Walters JK, Davis M, Sheard MH. Tryptophan-free diet: effects on the acoustic startle reflex in rats . Psychopharmacology . 1979;62:103-109.Crossref 57. Gibbons JL, Barr GA, Bridger WH, Leibowitz SF. Manipulations of dietary tryptophan: effects on mouse killing and brain serotonin in the rat . Brain Res . 1979;169:139-153.Crossref 58. Vergnes M, Kempf E. Tryptophan deprivation: effects on mouse-killing and reactivity in the rat . Psychopharmacol Aggression Soc Behav . 1981;14:19-23. 59. Moja EA, Mendelson WB, Stoff DM, Gillin JC, Wyatt RJ. Reduction of REM sleep by a tryptophan-free amino acid diet . Life Sci . 1979;24:1467-1470.Crossref 60. Clemens JA, Bennett DR, Fuller RW. The effect of a tryptophan-free diet on prolactin and corticosterone release by serotonergic stimuli . Horm Metab Res . 1980;12:35-38.Crossref 61. Badawy AA-B. Minireview: the functions and regulation of tryptophan pyrrolase . Life Sci . 1977;21:755-768.Crossref 62. Badawy AA-B, Evans M. Inhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by acute administration of small doses of antidepressants . Br J Pharmacol . 1982;77:59-67.Crossref 63. Blier P, de Montigny, Chaput Y. A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence . J Clin Psychiatry . 1990;51( (suppl) ):14-20.

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Nov 1, 1994

References