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Brain mechanisms associated with depressive relapse and associated cognitive impairment following acute tryptophan depletion

  • Katharine A. Smith (a1), John S. Morris (a2), Karl J. Fristdn (a2), Philip J. Cowen (a3) and Raymond J. Dolan (a4)...

Acute tryptophan depletion lowers brain serotonin synthesis and results in a transient, but striking, clinical relapse in recovered depressed patients.


To identify brain regions which change their activity as an acute depressive relapse evolves and to determine how pathological mood might modulate neural activity during a cognitive task.


We used H2 15O positron-emission tomography (PET) to study eight recovered depressed men after tryptophan depletion and after a control procedure. During both PET scan sessions, subjects performed a paced verbal fluency task which alternated with a control verbal repetition task.


Increasing levels of depression after tryptophan depletion were associated with diminished neural activity in the ventral anterior cingulate, orbitofrontal cortex and caudate nucleus regions. In addition, depressive relapse attenuated cognitive task-related activation in the anterior cingulate cortex.


Our data indicate that changes in neural activity in distinct brain regions mediate the clinical phenomena of depression and depression-related cognitive impairment following acute tryptophan depletion. These changes could be associated with the widespread distribution of serotonin neurons in brain pathways associated with the expression of affect and cognitive performance.

Corresponding author
Professor R. J. Dolan, Wellcome Department of Cognitive Neurology, Queen Square, London WCIN 3BG
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Declaration of interest

This study was supported by the Wellcome Trust.

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The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
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Brain mechanisms associated with depressive relapse and associated cognitive impairment following acute tryptophan depletion

  • Katharine A. Smith (a1), John S. Morris (a2), Karl J. Fristdn (a2), Philip J. Cowen (a3) and Raymond J. Dolan (a4)...
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