Tryptophan depletion

Petrakis IL, Trevisan L, Boutros NN, et al Effect of tryptophan depletion on alcohol cue-induced craving in abstinent alcoholic patients. Alcohol Clin Exp Res 23 1151-1155, 2001... 

Petrakis IL, Buonopane A, O Malley S, et al The effect of tryptophan depletion on alcohol self-administration in non-treatment-seeking alcoholic individuals. Alcohol Clin Exp Res 26 969-975, 2002... 

Salomon, RM, Miller, HL, Delgado, PL and Charney, D (1993) The use of tryptophan depletion to evaluate central serotonin function in depression and other neuropsychiatric disorders. Int. J. Clin. Psychopharmacol. 8 41-46. 

Satel S., Krystal J., Delgado R, Kosten T., Chamey D. Tryptophan depletion and attenuation of cue-induced craving for cocaine. Am. J. Psychiatry. 152 778, 1995. 

Figure 7. A serotonergic synapse including a depiction of the acute tryptophan depletion method discussed in the text. All large neutral amino acids (SLNAAs) share a common blood-brain barrier transporter. The serotonergic precursor, tryptophan, essentially competes with the other LNAAs for transport. Thus tryptophan is uniquely susceptible to acute dietary manipulation. Numerous serotonergic receptor types exist, including presynaptic S-HTm and (somatodendritic) 5-HTia autoreceptors and postsynaptic 5-HTia, 5-HTid, 5-HT2a 5-HT2c 5-HT3 and 5-HT4 receptors. Additional modulation of serotonin activity can occur via the action of selective serotonin re-uptake inhibitors (SSRls) including fluoxetine, fluvoxamine, and citalopram.

Tryptophan depletion in healthy volunteers impairs the retrieval of learnt material (Park et al., 1994), an effect probably mediated through a selective impairment of episodic memory consolidation (Riedel et al., 1999 Schmitt et al., 2000). However, tryptophan depletion appears to have no effect on working memory (Riedel et al., 1999) and either no effect or an enhancement of tests of executive function (Park et al., 1994 Schmitt et al., 2000). Thus the abnormality in episodic memory in mood disorders could conceivably be related to an impairment in the 5-HT system, but such an impairment is unlikely to account for the abnormalities in working memory and executive function. Clearly then, changes in consciousness occurring in affective disorders are unlikely to be explainable on the basis of an abnormality in a single neurochemical system. 

Studies in which the availability of serotonin is manipulated in combination with a laboratory panic challenge has considerably increased insight into the relationship between serotonin and panic disorder. Tryptophan depletion caused an increased panic response to a 5% or 35% CO2 challenge in panic disorder patients (Miller et al. 2000 Schruers et al. 2000). Conversely, panic anxiety and symptoms, as well as the number of panic attacks following 35% CO2 inhalation, were significantly reduced by pretreatment with the serotonin precursor L-hydroxytryptophan, suggesting that under certain circumstances serotonin may act to inhibit panic (Schruers et al. 2002). 

Goddard AW, Sholomskas DE, Augeri PM (1994) Effects of tryptophan depletion in panic disorders. Biol Psychiatry 36 775-777... 

Miller HE, Deakin JF, Anderson IM (2000) Effect of acute tryptophan depletion on C02-induced anxiety in patients with panic disorder and normal volunteers. Br J Psychiatry 176 182-188... 

Schruers K, Klaassen T, Pols H, Overbeek T, Deutz NE, Griez E (2000) Effects of tryptophan depletion on carbon dioxide provoked panic in panic disorder patients. Psychiatry Res 93 179-187... 

Bjork, J.M., Dougherty, D.M., Moeller, F.G., Cherek, D.R., and Swann, A.C. (1999) The effects of tryptophan depletion and loading on laboratory aggression in men time course and a food-restricted control. Psychopharmacology 142 24-30. 

Coull, J.T, Sahakian, B.J., Middleton, H.C., Young, A.H., Park, S.B., McShane, R.H., Cowen, P.J., and Robbins, T.W. (1995) Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion on focused attention and attentional search. Psychopharmacology 121 222-230. 

The effects of a short-term tryptophan depletion were examined in 15 patients with OCD who had responded to treatment with various SRIs such as CMI, fluvoxamine, and fluoxetine. These patients underwent tryptophan depletion under double-blind, placebo-controlled conditions. Reduction of tryptophan had no significant effects on either obsessions or compulsions, but mean depression ratings were significantly increased during tryptophan depletion [Barr et al. 1994]. 

Barr LC, Goodman WK, Price LH, et al The serotonin hypothesis of OCD implications of pharmacologic challenge studies. J Chn Psychiatry 4 17-28s, 1992 Barr LC, Goodman WK, Price LH The serotonin hypothesis of obsessive compulsive disorder. Int Clin Psychopharmacol 8 (suppl 2 79-82, 1993 Barr LC, Goodman WK, McDougle CJ, et al Tryptophan depletion in patients with OCD who respond to serotonin reuptake inhibitors. Arch Gen Psychiatry 51 309-17, 1994... 

Riddle WJR, Scott AIF, Bennie J, et al Current intensity and oxytocin release after electroconvulsive therapy. Biol Psychiatry 33 839-841, 1993 Riedel WJ, Klaassem T, Deutz NE, et al Tryptophan depletion in normal volunteers produces selective impairment in memory consolidation. Psychopharmacology 141 362-369, 1999... 

Bell, C, Forshall, S, Adrover, M., et aI Does 5-HT restrain panic A tryptophan depletion study in panic disorder patients recovered on paroxetine. J. Psychopharmacol. 16(1), 5-14, 2002. 

Patients with SAD have been found to be resistant to exacerbation of depressive symptoms following acute tryptophan depletion ( 32), suggesting that dysfunction of central serotonin mechanisms may be less relevant to the pathophysiology of SAD than other forms of major depression. 

Neumeister A, Praschak-Rieder N, Hebelmann B, et al. Rapid tryptophan depletion in drug-free depressed patients with seasonal affective disorder. Am J Psychiatry 1997 154 1153-1155. 

Serotonin potentiation has also been postulated as a possible mechanism, given that tryptophan depletion may reverse the antidepressant effects of light therapy... 

Moore P, Gillin C, Bhatti T, DeModena A, Seifritz E, Clark C, Stahl S, Rapaport M, Kelsoe J (1998) Rapid tryptophan depletion, sleep electroencephalogram, and mood in men with remitted depression on serotonin reuptake inhibitors. Arch Gen Psychiatry 55 534-539... 

Evans L, Golshan S, Kelsoe J, Rapaport M, Resovsky K, Sutton L, Gillin JC (2002) Effects of rapid tryptophan depletion on sleep electroencephalogram and mood in subjects with partially remitted depression on bupropion. Neuropsychopharmacology 27 1016-1026... 

Landolt HP, Kelsoe JR, Rapaport MH, Gillin JC (2003) Rapid tryptophan depletion reverses phenelzine-induced suppression ofREM sleep. J Sleep Res 12 13-18... 

Haynes PL, McQuaid JR, Kelsoe J, Rapaport M, Gillin JC (2004) Affective state and EEG sleep profile in response to rapid tryptophan depletion in recently recovered non-medicated depressed individuals. J Affect Disord 83 253-262... 

Voderholzer U, Homyak M, Thiel B, Huwig-Poppe C, KiemenA, Konig A, Backhaus J, Riemann D, Berger M, Hohagen F (1998) Impact of experimentally induced serotonin deficiency by tryptophan depletion on sleep EEG in healthy subjects. Neuropsychopharmacology 18 112-124... 

Delgado, P. L., Miller, H. L., Salomon, R. M., Licinio, J., Krystal, J. H., Moreno, F. A., Heninger, G. R., Chamey, D. S. 1999, Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine implications for the role of serotonin in the mechanism of antidepressant action, Biol.Psychiatry, vol. 46, no. 2, pp. 212-220. 

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