GENETIC-LINKAGE STUDY OF BIPOLAR DISORDER AND THE SEROTONIN TRANSPORTER

The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serot onin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism fo r possible linkage to bipolar disorder, Eighteen families were examine d from three populations: the Old Order Amish, Iceland, and the genera l North American population. In addition to HTT, three other microsate llite markers were examined, which span an interval known to contain H TT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + rec urrent unipolar) diagnostic models. Linkage could be excluded to HTT u nder all models examined. Linkage to the interval spanned by the micro satellites was similarly excluded under the dominant models, In two in dividual families, maximum led scores of 1.02 and 0.84 were obtained a t D17S798 and HTT, respectively. However, these data overall do not su pport the presence of a susceptibility locus for bipolar disorder near the serotonin transporter. (C) 1996 Wiley-Liss, Inc.