Antidepressant-induced mania, rapid cycling and the serotonin transporter gene polymorphism.
The genes involved in the serotonin system are major candidates in association studies on affective disorders and responses to antidepressants. We studied a functional polymorphism of the serotonin transporter (5-HTT) gene (a 44 bp insertion/deletion in the 5-HTT-linked polymorphic region (5-HTTLPR)) and lifetime history of antidepressant-induced mania (AIM) in a population of 305 patients with bipolar affective disorder. AIM was defined using a broad definition and a restrictive definition. No association was found between the "s" allele of the 5-HTTLPR and AIM for either definition. However, we found an association between the 5-HTTLPR and lifetime history of rapid cycling in a subsample of patients (for allele and genotype distributions: exact probability, p=0.0009 and chi(2)=9.4; df=1; p=0.002, respectively). These results may help to explain the conflicting association results obtained with the 5-HTT gene polymorphism, in particular with AIM. Indeed, the precise phenotype associated with the 5-HTT gene is unclear. The association between the "s" allele and rapid cycling may provide further evidence for an association between the 5-HTTLPR "s" allele and a pattern of affective instability.
Service de Psychiatrie, Hôpital Henri Mondor et Albert Chenevier, Assistance Publique-Hôpitaux de Paris, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Créteil, France.
A
A
Rousseva
C
C
Henry
D
D
van den Bulke
G
G
Fournier
J-L
JL
Laplanche
M
M
Leboyer
F
F
Bellivier
J-M
JM
Aubry
P
P
Baud
M
M
Boucherie
C
C
Buresi
F
F
Ferrero
A
A
Malafosse
D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000235:genetics* / Q000523:psychology*; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050486:Serotonin Plasma Membrane Transport Proteins
D000928:Antidepressive Agents; D002352:Carrier Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA