The subjective and cognitive effects of acute phenylalanine and tyrosine depletion in patients recovered from depression

Abstract

Although there is evidence for the involvement of dopamine (DA) in unipolar depression, no published study has yet used the technique of acute phenylalanine and tyrosine depletion (APTD), a dietary intervention that selectively lowers DA synthesis, in order to investigate the role of DA in mood disturbance. Tyrosine and phenylalanine depleted and placebo amino acid drinks were administered to 20 patients recovered from depression in a double-blind, placebo-controlled, crossover design. Measures included subjective effects, Hamilton Depression Rating Scale scores, and a comprehensive battery of well-validated computerized cognitive tests. APTD induced a substantial reduction in the ratio of plasma tyrosine and phenylalanine to large neutral amino acids. However, relapse of depressive symptoms was not seen. Although performance on most cognitive tests was unaffected, there was a selective effect on decision-making, with APTD causing participants to bet significantly less. In conclusion, These results suggest a specific role for the involvement of DA in reward/punishment processing in humans. While APTD did not induce relapse in any participant, it did cause patients recovered from depression to show lowered sensitivity to reward in a gambling game. It is hypothesized that tests involving reward/punishment processing are preferentially affected by DA depletion, and that a more complete account of depression is likely to result from considering the roles played by serotonin, noradrenaline, and DA in mediating the various cognitive and clinical symptoms, including anhedonia.

Figure 1

Tyrosine availability to the brain (the ratio of tyrosine and phenylalanine concentrations combined, to those of the other large neutral amino acids) fell from T₀ (baseline) to T₅ (immediately prior to testing) to a significantly greater extent when TYR (tyrosine/phenylalanine-depleted drink) was administered compared to when BAL (placebo drink) was administered. Bars represent the mean, error bars 1 SED.

Figure 2

(a) Rapid Visual Information Processing A′ (sensitivity). Participants improved A′ from T₀ (baseline) to T₅ (immediately prior to testing) when administered BAL (placebo drink) to a significantly greater extent than when administered TYR (tyrosine/phenylalanine-depleted drink). Bars represent the mean, error bars 1 SED. (b) Rapid Visual Information Processing Latency. Participants were quicker at T₅ (immediately prior to testing) compared to T₀ (baseline) when administered BAL (placebo drink), but not when administered TYR (tyrosine/phenylalanine-depleted drink). Bars represent the mean, error bars 1 SED.

Figure 3

Decision-making task percentage bet. Participants bet less when administered TYR (tyrosine/phenylalanine-depleted drink) compared to BAL (placebo drink). Symbols represent the mean, error bars 1 SED.