Acute tryptophan depletion attenuates auditory event related potentials in bipolar disorder: a preliminary study

J Affect Disord. 2002 May;69(1-3):83-92. doi: 10.1016/s0165-0327(00)00382-7.


Background: 5-HT modulates electroencephalographic (EEG) activity, which is abnormal in bipolar disorder and EEG abnormalities persist in euthymic bipolar patients. The EEG may therefore be a sensitive marker of 5-HT function in bipolar disorder. We examined the effects of acute tryptophan depletion (ATD) on EEG activity in bipolar patients.

Methods: Fourteen patients with DSM IV Bipolar 1 disorder participated in a within-subject, double-blind, placebo-controlled, random-order crossover study. Following ATD quantitative power spectrum brain mapping and measurement of auditory evoked potentials were carried out.

Results: ATD produced a significant fall in the amplitude of N1P2 and P300 components of the auditory evoked potential, but no significant changes in the power spectrum. There was an 83% reduction in plasma tryptophan after the depleting but not the control drink.

Limitations: The effect of ATD on brain 5-HT levels was not directly measured. The number of patients is relatively small. The control condition may alter these electrophysiological measures.

Conclusions: ATD attenuates auditory evoked potentials in bipolar disorder with the distribution of this effect being towards the front of the brain. These changes are not related to any change in mood. This is a potential trait marker of bipolar disorder, however there needs to be further exploration of this paradigm in controls and other patient groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / physiopathology*
  • Electroencephalography
  • Evoked Potentials, Auditory / physiology*
  • Female
  • Humans
  • Lithium / blood
  • Lithium / therapeutic use
  • Male
  • Middle Aged
  • Tryptophan / blood
  • Tryptophan / deficiency*


  • Tryptophan
  • Lithium