Serotonin transporter gene (HTTLPR) is not in linkage disequilibrium with prepubertal and early adolescent bipolarity

Background: As part of an ongoing, larger study, "Phenomenology" and Course of Pediatric Bipolarity", a subset of prepubertal and early adolescent ons et bipolar (PEA-BP) probands, on whom trio blood collection was complete,,w ere used to study genetic transmission of the serotonin transporter linked promoter region (HTTLPR) short and long alleles using the transmission dise quilibrium test(TDT). The HTTLPR alleles were selected based on postulated serotonergic mechanisms for PEA-BP and on the burgeoning number of HTTLPR a llele studies in bipolar (BP) adults. Methods: There were 46 complete trios of PEA-BP probands and both biologica l parents. Probands had a mean age of 11.1 +/- 3.0 years and a mean age of onset of PEA-BP of 8.1 +/- 4.0 years. Comprehensive diagnostic assessments included a semi-structured research interview: the WASH-U-KSADS, administer ed separately to mothers and to children by blind raters. Probands manifest ed severe impairment (CGAS 43.9 +/- 8.9), elated mood (84.8%), grandiosity (78.3%), rapid cycling (78.3%) and psychosis (63.0%). The HTTLPR length var iant was genotyped using fluorescently labeled primers and automated capill ary electrophoresis using laser-induced fluorescence. Results: The TDT was not significant (TDT chi square = .020 df = 1, p =.89) . Conclusions:;This negative result is consistent,with the one negative TDT a nd two negative linkage studies of HTTLPR alleles in bipolar adults in the literature. (C) 1999 Society of Biological Psychiatry.