The role of 5-HTTLPR polymorphism in antidepressant-associated mania in bipolar disorder.
BACKGROUND
The occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BD). The serotonin transporter gene is a candidate to be associated with antidepressant-associated mania (AAM) in some patients. This gene has a polymorphism within the promoter region (5-HTTLPR) with two allelic forms, the long (L) and the short (S) variants.


METHODS
We performed a case-control study to compare 5-HTTLPR genotype and allelic frequencies between 43 patients with a DSM-IV diagnosis of BD, with at least one manic/hypomanic episode associated with treatment with proserotonergic antidepressants (AAM+) and 69 unrelated, matched bipolar patients, who had been exposed to proserotonergic antidepressants without development of manic symptoms (AAM-(*)). Furthermore, we performed this comparison between a subgroup of 23 AAM+ patients that, when they presented AAM, were not using mood stabilizer (AAM+(*)) and 25 AAM- patients who used antidepressant without the concomitant use of a mood stabilizer (AAM-(*)). 5-HTTLPR genotyping was performed using PCR.


RESULTS
No significant differences were found between AAM+ and AAM-. Within the subgroups, our results show that S-carriers (LS+SS Genotypes) are more prone to make a manic/hypomanic episode associated with antidepressant (P=0.017).


CONCLUSIONS
Our study is retrospective.


CONCLUSIONS
The 5-HTTLPR polymorphism may be considered a predictor of abnormal response to antidepressant in patients with BP, but this action is influenced by the presence of a mood stabilizer. Such observations reinforce that a correct diagnosis of bipolarity before the beginning of the treatment is essential, mainly for S-carriers patients.
Ferreira
Alexandre de Aguiar
Ade A
Neuroscience Program, UFMG, Brazil. alex.aferreira@yahoo.com.br
Neves
Fernando Silva
FS
da Rocha
Felipe Filardi
FF
Silva
Gustavo Silveira E
GS
Romano-Silva
Marco Aurélio
MA
Miranda
Débora Marques
DM
De Marco
Luiz
L
Correa
Humberto
H
D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use; D008297:Male; D010597:Pharmacogenetics / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D000927:Anticonvulsants; D000928:Antidepressive Agents; D018020:Lithium Compounds; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin