Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression

Am J Psychiatry. 1999 Sep;156(9):1450-2. doi: 10.1176/ajp.156.9.1450.


Objective: A functional polymorphism in the transcriptional control region upstream of the coding sequence of the 5-hydroxytryptamine transporter (5-HTT) has been reported. This polymorphism has been shown to influence the antidepressant response to fluvoxamine and paroxetine. The authors tested the hypothesis that the allelic variation of the 5-HTT-linked polymorphic region (5-HTTLPR) could influence the response of depressed patients to total sleep deprivation.

Method: Sixty-eight drug-free inpatients with bipolar depression underwent a night of total sleep deprivation. 5-HTTLPR was genotyped in these patients. Changes in perceived mood were rated on a visual analogue scale and analyzed by using repeated measures analysis of covariance.

Results: Patients who were homozygotic for the long variant of 5-HTTLPR showed a significantly better mood amelioration after total sleep deprivation than those who were heterozygotic and homozygotic for the short variant.

Conclusions: The influence of 5-HTTLPR on response to total sleep deprivation is similar to its observed influence on response to serotonergic drug treatments. This finding supports the hypothesis of a major role for serotonin in the mechanism of action of total sleep deprivation in depression.

MeSH terms

  • Adult
  • Analysis of Variance
  • Bipolar Disorder / genetics
  • Bipolar Disorder / therapy*
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology
  • Female
  • Genes, Regulator / physiology
  • Heterozygote
  • Homozygote
  • Hospitalization
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins*
  • Polymorphism, Genetic / physiology*
  • Promoter Regions, Genetic / genetics
  • Serotonin / genetics
  • Serotonin / physiology
  • Serotonin Plasma Membrane Transport Proteins
  • Sleep Deprivation / physiology*


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin