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 inhibitors (SSRIs) that successfully treat bipolar depression (BP). The 5HTT gene is located on chromosome 17q11.1-q12 and has a 44 bp deletion/insertion functional polymorphism in the promoter region (SLC6A4). Results from association studies on SLC6A4 and BP disorder are conflicting. The aim of the present study was to investigate for the presence of linkage disequilibrium between SLC6A4 and BP disorder. One hundred thirty-three Bipolar I or Bipolar II probands with their living parents were recruited. Diagnoses were assessed by the structured interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition [DSM-IV, American Psychiatric Association, 1994] (SCID-I). Genotyping was performed with standard procedures and data were analyzed using the Transmission Disequilibrium Test [TDT, Spielman et al., 1993: Am J Hum Genet 52: 506-516]. One hundred two triads were informative for the analysis. Each of the two alleles of the SLC6A4 was transmitted 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 the pathogenesis of BP disorder. However, further studies focusing on the role of the 5HTT gene in predicting the response to SSRIs in BP patients might be worthwhile.