title: Is the 5-HTTLPR polymorphism associated with bipolar disorder or with suicidal behavior of bipolar disorder patients?
abstract: The serotonin transporter gene has a 44 bp insertion/deletion polymorphism within the promoter region (5-HTTLPR) with two allelic forms, the long (L) and the short (S) variants. Association between the low-activity S variant and bipolar disorder (BPD) has been shown but its replication has not been consistent. It has also been described as an association between the S allele and suicidal behavior. Since suicidal behavior is a rather frequent event in BPD, an important question is whether suicidality, instead of bipolarity itself, could be related to S allele. We assessed 351 subjects (167 bipolar inpatients and 184 healthy controls). Diagnosis was conducted by a psychiatrist using a structured interview (MINI-PLUS), according to DSM-IV criteria. Suicidal behavior was assessed using a semi-structured instrument and a review of medical records. Genotyping of the 5-HTTLPR was performed using PCR. There were 77 patients with a history of previous suicide attempts. Bipolar patients and healthy controls showed comparable genotypic and allelic frequencies. Patients carrying the S allele made violent suicide attempts more frequently (chi(2) = 20.2; P = 0.0001) and made more suicide attempts (t = 2.6; P = 0.01). We were able to show an association between the S allele and suicidal behavior but not with BPD. Our data suggest that a phenotypic stratification, taking into account the suicidal behavior history, is of pivotal importance when performing association studies between BPD and 5-HTTLPR genotypes, which could explain previous contradictory results.
authors.affiliation: IPSEMG, Belo Horizonte, Brazil.
authors.forename: F S
authors.initials: FS
authors.lastname: Neves
authors.forename: G
authors.initials: G
authors.lastname: Silveira
authors.forename: M A
authors.initials: MA
authors.lastname: Romano-Silva
authors.forename: L
authors.initials: L
authors.lastname: Malloy-Diniz
authors.forename: A A
authors.initials: AA
authors.lastname: Ferreira
authors.forename: L
authors.initials: L
authors.lastname: De Marco
authors.forename: H
authors.initials: H
authors.lastname: Correa
mesh_terms: D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013406:Suicide, Attempted
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins