Cognition following acute tryptophan depletion: difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers

Psychol Med. 2002 Apr;32(3):503-15. doi: 10.1017/s0033291702005342.


Background: Serotonergic circuits have been proposed to mediate cognitive processes, particularly learning and memory. Cognitive impairment is often seen in bipolar disorders in relation to a possible lowered serotonergic turnover.

Methods: We investigated the effects of acute tryptophan depletion (ATD) on cognitive performance in healthy first-degree relatives of bipolar patients (FH) (N= 30) and matched controls (N= 15) in a placebo-controlled, double-blind cross-over design. Performance on planning, memory and attention tasks were assessed at baseline and 5 h after ATD.

Results: Following ATD, speed of information processing on the planning task was impaired in the FH group but not in the control group. FH subjects with a bipolar disorder type I relative (FH I) showed impairments in planning and memory, independent of ATD. In all subjects, ATD impaired long-term memory performance and speed of information processing. ATD did not affect short-term memory and focused and divided attention.

Conclusions: The results suggest serotonergic vulnerability affecting frontal lobe areas in FH subjects, indicated by impaired planning. Biological vulnerability in FH I subjects is reflected in impaired planning and memory performance. In conclusion, the cognitive dysfunctions in FH subjects indicate an endophenotype constituting a possible biological marker in bipolar psychopathology. Serotonin appears to be involved in speed of information processing, verbal and visual memory and learning processes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Amino Acids / administration & dosage
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / physiopathology
  • Cognition Disorders / diagnosis
  • Cognition Disorders / genetics*
  • Cognition Disorders / physiopathology
  • Double-Blind Method
  • Female
  • Frontal Lobe / physiopathology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests*
  • Risk
  • Serotonin / physiology*
  • Tryptophan / deficiency*


  • Amino Acids
  • Serotonin
  • Tryptophan