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 onset bipolar (PEA–BP) probands, on whom trio blood collection was complete, were used to study genetic transmission of the serotonin transporter linked promoter region (HTTLPR) short and long alleles using the transmission disequilibrium test(TDT). The HTTLPR alleles were selected based on postulated serotonergic mechanisms for PEA–BP and on the burgeoning number of HTTLPR allele studies in bipolar (BP) adults. Methods: There were 46 complete trios of PEA-BP probands and both biological 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, administered separately to mothers and to children by blind raters. Probands manifested 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 variant was genotyped using fluorescently labeled primers and automated capillary 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 and two negative linkage studies of HTTLPR alleles in bipolar adults in the literature.