E. Mundo et al., The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder - Preliminary findings, ARCH G PSYC, 58(6), 2001, pp. 539-544
Background: II-he occurrence of mania during antidepressant treatment is a
key issue in the clinical management of bipolar disorder (BP). The serotoni
n transporter (5-HTT) is the selective site of action of most proserotonerg
ic compounds used to treat bipolar depression. The 5-HTT gene (SLC6A4) has
2 known polymorphisms. The aim of this study was to investigate the role of
the SLC6A4 variants in the pathogenesis of antidepressant-induced mania in
BP.
Methods: Twenty-seven patients with a DSM-IV diagnosis of BP I or II, with
at least 1 manic or hypomanic episode induced by treatment with proserotone
rgic antidepressants (IM+ group), were compared with 29 unrelated, matched
patients with a diagnosis of BP I or II, who had been exposed to proseroton
ergic antidepressants without development of manic or hypomanic symptoms (I
M- group). The 2 known polymorphisms of the SLC6A4 were genotyped, and alle
lic and genotypic association analyses were performed.
Results: With respect to the polymorphism in the promoter region (5HTTLPR),
IM+ patients had an excess of the short allele (n=34 [63%]) compared with
IM- patients (n=17 [29%]) (chi (2)(1), 12.77; P < .001). The genotypic asso
ciation analysis showed a higher rate of homozygosity for the short variant
in the IM+ group (n=10 [37%]) than in the IM- group (n=2 [7%]) and a lower
rate of homozygosity for the long variant in the IM+ group (n = 3 [11%]) c
ompared with the IM- group (n=14 [48%]) (chi (2)(2), 12.43; P=.002). No ass
ociations were found for the polymorphism involving a variable number of ta
ndem repeats.
Conclusion: If these results are replicated, the 5HTTLPR polymorphism may b
ecome an important predictor of abnormal response to medication in patients
with BP.