PRIMARY STRUCTURE OF THE SEROTONIN TRANSPORTER IN UNIPOLAR DEPRESSIONAND BIPOLAR DISORDER

Genetic factors have been implicated in the etiology of affective diso rders but due to the complex inheritance patterns of these disorders, identification of the responsible gene(s) has so far been unsuccessful . Decreased platelet serotonin (5-HT) transport and reduced binding of imipramine or paroxetine to brain and platelet 5-HT uptake sites/tran sporters in patients with depression and suicide victims define the 5- HT transporter (5-HTT) as a candidate gene. The primary structure of t he 5-HTT was analyzed in 17 patients meeting DSM-III-R diagnostic crit eria for major depressive or bipolar disorder and in 4 healthy control s using polymerase chain reaction (PCR-) amplification and sequencing of complementary deoxyribose- nucleic acid (cDNA) synthesized from pla telet 5-HTT messenger ribose nucleic acid (mRNA). Direct PCR sequencin g of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT (40,000 base pairs se quence screened), although a conservative single-base substitution rep resenting a silent polymorphism was found. The results provide prelimi nary evidence that alterations in the primary structure of 5-HTT are n ot generally involved in the pathogenesis of unipolar depression and m anic-depressive illness.