Lack of linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and bipolar disorder

The serotonin transporter (5HTT) gene appears to be of particular interest as 5HTT is the selective site of action of selective serotonin reuptake inh ibitors (SSRIs) that successfully treat bipolar depression (BP). The 5HTT g ene is located on chromosome 17q11.1-q12 and has a 44 bp deletion/insertion functional polymorphism in the promoter region (SLC6A4). Results from asso ciation studies on SLC6A4 and BP disorder are conflicting, The aim of the p resent study was to investigate for the presence of linkage disequilibrium between SLC6A4 and BP disorder. One hundred thirty-three Bipolar I or Bipol ar II probands with their living parents were recruited. Diagnoses were ass essed by the structured interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition [DSM-IV, American Psychiatric Associat ion, 1994] (SCID-I). Genotyping was performed with standard procedures and data were analyzed using the Transmission Disequilibrium Test [TDT, Spielma n et al., 1993: Am J Hum Genet 52: 506-516]. One hundred two triads were in formative for the analysis. Each of the two alleles of the SLC6A4 was trans mitted at the same rate to bipolar probands (chi(2) = 0.692, df = 1, P = NS ). Thus, it appears unlikely that the SLC6A4 plays a fundamental role in th e pathogenesis of BP disorder, However, further studies focusing on the rol e of the 5HTT gene in predicting the response to SSRIs in BP patients might be worthwhile. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:379-383, 200 0. (C) 2000 Wiley-Liss, Inc.