¹University Department of Psychiatry, Warneford Hospital, Oxford, UK

Correspondence: Dr PJ Cowen, University Department of Psychiatry, Neurosciences Building, Warneford Hospital, Oxford, OX3 7JX, UK. Tel: +44 1865 226394; Fax: +44 1865 251076; E-mail: phil.cowen@psych.ox.ac.uk

Received 15 September 2004; Revised 4 November 2004; Accepted 2 December 2004; Published online 9 February 2005.

Abstract

The role of dopamine (DA) pathways in the pathophysiology of depressive disorder is poorly understood. However, because DA plays a key role in motivational behavior, it is important to study in a disorder characterized by anhedonia, lack of energy and psychomotor retardation. A recently developed dietary manipulation ('tyrosine (TYR) depletion') offers a novel method to assess the role of DA in major depression. We studied 15 euthymic women with a past history of recurrent depression, who received a 74 g amino-acid drink lacking TYR and phenylalanine (PHE) (TYR-free) and a balanced (BAL) amino acid drink on two separate occasions in a double-blind, random-order, crossover design. Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, while performance on a spatial recognition memory task was impaired. However, relative to the BAL drink, the TYR-free drink did not lower objective or subjective measures of mood. We conclude that as in healthy volunteers, TYR depletion in euthymic subjects, with a past history of major depression, attenuated DA function, as reflected in increased plasma prolactin levels and decreased spatial memory performance. However ratings of depression were unaffected, suggesting that disruption of dopaminergic function by this manipulation does not induce a lowering of mood in individuals vulnerable to depression.