Association of Serotonin 5-HT_2A receptor binding and the T102C polymorphism in depressed and healthy caucasian subjects

Serotonin S-HT_2A receptor (5-HT_2A) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT_2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts, All were Caucasian. Platelet 5-HT_2A binding kinetics (B_max and K_D) were assayed and adjusted for seasonal variation, All subjects were genotyped forthe T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher B_max in all subjects (F =3.53, df=2,211; p = 0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F = 7.56, df = 2,60, p = 0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. B_max was not related to a diagnosis of mood disorders. The TT genotype appears associated with higher platelet 5-HT_2A B_max in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.