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


METHODS
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.
Benedetti
F
F
Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University of Milan, School of Medicine, Italy. centro.affettivi@hsr.it
Serretti
A
A
Colombo
C
C
Campori
E
E
Barbini
B
B
di Bella
D
D
Smeraldi
E
E
D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000235:genetics / Q000628:therapy*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D005809:Genes, Regulator / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D006760:Hospitalization; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012701:Serotonin / Q000235:genetics / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins; D012892:Sleep Deprivation / Q000502:physiology*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin